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{ "abstract": "It is not easy to diagnose lumbar disc herniation during pregnancy due to the limitation of the examinations and it is also difficult to control the severe pain during this time. A pregnant woman with lumbar disc herniation was transferred to our hospital at the 23rd week of gestation. The pain was successfully controlled with opioids and epidural anesthesia. At the 35th week of gestation, she delivered a girl weighing 2316 g smoothly with an Apgar score of 8/9 without neonatal abstinence syndrome from morphine. In this case, opioid administration was found to be useful for perinatal care with lumbar disc herniation.", "affiliations": "Department of Obstetrics and Gynecology, University of Occupational and Environmental Health, Fukuoka, Japan.", "authors": "Matsumoto|Emi|E|;Yoshimura|Kazuaki|K|;Nakamura|Eiichiro|E|;Hachisuga|Toru|T|;Kashimura|Masamichi|M|", "chemical_list": "D000701:Analgesics, Opioid; D009020:Morphine; D005283:Fentanyl", "country": "United States", "delete": false, "doi": "10.5055/jom.2009.0038", "fulltext": null, "fulltext_license": null, "issn_linking": "1551-7489", "issue": "5(6)", "journal": "Journal of opioid management", "keywords": null, "medline_ta": "J Opioid Manag", "mesh_terms": "D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D015360:Analgesia, Epidural; D000701:Analgesics, Opioid; D003131:Combined Modality Therapy; D005260:Female; D005283:Fentanyl; D005865:Gestational Age; D006801:Humans; D007405:Intervertebral Disc Displacement; D050498:Live Birth; D008159:Lumbar Vertebrae; D009020:Morphine; D010146:Pain; D010147:Pain Measurement; D011247:Pregnancy; D011248:Pregnancy Complications; D012720:Severity of Illness Index; D016896:Treatment Outcome", "nlm_unique_id": "101234523", "other_id": null, "pages": "379-82", "pmc": null, "pmid": "20073412", "pubdate": "2009", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "The use of opioids in a pregnant woman with lumbar disc herniation: a case report.", "title_normalized": "the use of opioids in a pregnant woman with lumbar disc herniation a case report" }

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null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "8 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "INTERVERTEBRAL DISC DISORDER", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "8", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MEPIVACAINE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, 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"drugstructuredosagenumb": "240", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MORPHINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MEPIVACAINE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.05 MG, TID", "drugenddate": null, "drugenddateformat": null, "drugindication": "INTERVERTEBRAL DISC DISORDER", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".15", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MEPIVACAINE HYDROCHLORIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMITRIPTYLINE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMITRIPTYLINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FENTANYL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UP TO 100 MCG/H", "drugenddate": null, "drugenddateformat": null, "drugindication": "PAIN MANAGEMENT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FENTANYL." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Low birth weight baby", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Maternal exposure during pregnancy", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "EMI MATSUMOTO.. THE USE OF OPIOIDS IN A PREGNANT WOMAN WITH LUMBAR DISC HERNIATION: A CASE REPORT.. JOURNAL OF OPIOID MANAGEMENT. 2009?5(6):379?82", "literaturereference_normalized": "the use of opioids in a pregnant woman with lumbar disc herniation a case report", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20210402", "receivedate": "20210402", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19086030, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210717" }, { "companynumb": "NVSC2021JP083070", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "MORPHINE" }, "drugadditional": null, "drugadministrationroute": "064", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "MATERNAL DOSE: 90 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MORPHINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "MORPHINE" }, "drugadditional": null, "drugadministrationroute": "064", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, 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"patientweight": "2.32", "reaction": [ { "reactionmeddrapt": "Premature baby", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Foetal exposure during pregnancy", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MATSUMOTO E, YOSHIMURA K, NAKAMURA E, HACHISUGA T, KASHIMURA M. THE USE OF OPIOIDS IN A PREGNANT WOMAN WITH LUMBAR DISC HERNIATION: A CASE REPORT. JOURNAL OF OPIOD MANAGEMENT. 2009?5(6):379?82", "literaturereference_normalized": "the use of opioids in a pregnant woman with lumbar disc herniation a case report", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20210415", "receivedate": "20210415", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19141893, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210717" } ]

{ "abstract": "Ketamine is being prescribed with greater frequency due to an emphasis on multimodal analgesia. With increasing use, uncommon adverse effects associated with ketamine are likely to surface. Limited reports of transient central diabetes insipidus (DI) occurring early after initiation (ie, within 10 hours) of ketamine have been reported. We present 2 cases of delayed onset (32 hours or more after initiation), ketamine-induced, transient central DI in patients cannulated for venovenous extracorporeal membranous oxygenation. No other causes of central DI were determined based upon physical examination or laboratory data, and both patients responded to treatment with desmopressin/vasopressin. The Naranjo adverse drug reaction probability scale noted a probable causation for each case. These cases demonstrate the possibility of a rare but serious complication of ketamine. Improvement after discontinuation of ketamine and administration of desmopressin/vasopressin appear to support a drug-effect association.", "affiliations": "6887Virginia Commonwealth University Health System, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.;Cardiac Surgery, 6887Virginia Commonwealth University Health System, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.;Department of Anesthesiology, 6887Virginia Commonwealth University Health System, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.;Drug Information Services, 6887Virginia Commonwealth University Health System, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.;Cardiology, 6887Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.", "authors": "Herity|Leah B|LB|;Baker|Cassandra|C|;Kim|Christin|C|;Lowe|Denise K|DK|;Cahoon|William D|WD|https://orcid.org/0000-0002-9976-6596", "chemical_list": "D007649:Ketamine", "country": "United States", "delete": false, "doi": "10.1177/0897190019882266", "fulltext": null, "fulltext_license": null, "issn_linking": "0897-1900", "issue": "34(2)", "journal": "Journal of pharmacy practice", "keywords": "diabetes insipidus; ketamine; polyuria; sedation", "medline_ta": "J Pharm Pract", "mesh_terms": "D000758:Anesthesia; D020790:Diabetes Insipidus, Neurogenic; D003920:Diabetes Mellitus; D015199:Extracorporeal Membrane Oxygenation; D006801:Humans; D007649:Ketamine", "nlm_unique_id": "8900945", "other_id": null, "pages": "314-318", "pmc": null, "pmid": "31648586", "pubdate": "2021-04", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Delayed Onset of Central Diabetes Insipidus With Ketamine Sedation: A Report of 2 Cases.", "title_normalized": "delayed onset of central diabetes insipidus with ketamine sedation a report of 2 cases" }

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DELAYED ONSET OF CENTRAL DIABETES INSIPIDUS WITH KETAMINE SEDATION: A REPORT OF 2 CASES. JOURNAL OF PHARMACY PRACTICE. 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null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISATRACURIUM." } ], "patientagegroup": null, "patientonsetage": "59", "patientonsetageunit": "801", "patientsex": "2", "patientweight": "71.7", "reaction": [ { "reactionmeddrapt": "Diabetes insipidus", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "HERITY LB, BAKER C, KIM C, LOWE DK, CAHOON WD JR.. DELAYED ONSET OF CENTRAL DIABETES INSIPIDUS WITH KETAMINE SEDATION: A REPORT OF 2 CASES. 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"drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALBUTEROL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ALBUTEROL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "74072", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, 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"drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOMIDATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "EPINEPHRINE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HYPERCAPNIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EPINEPHRINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IPRATROPIUM" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "NEBULISED", "drugenddate": null, "drugenddateformat": null, "drugindication": "HYPERCAPNIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IPRATROPIUM" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BIVALIRUDIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BIVALIRUDIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NOREPINEPHRINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NOREPINEPHRINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SODIUM PHOSPHATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SODIUM PHOSPHATE" } ], "patientagegroup": "5", "patientonsetage": "59", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Diabetes insipidus", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "HERITY LB, BAKER C, KIM C, LOWE DK, CAHOON WD JR. DELAYED ONSET OF CENTRAL DIABETES INSIPIDUS WITH KETAMINE SEDATION: A REPORT OF 2 CASES. 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"drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "POTASSIUM CHLORIDE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "KETAMINE HYDROCHLORIDE" }, "drugadditional": "1", "drugadministrationroute": "040", "drugauthorizationnumb": "074549", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "200 MG, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEDATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "KETAMINE HCL" } ], "patientagegroup": null, "patientonsetage": "23", "patientonsetageunit": "801", "patientsex": "1", "patientweight": "86.2", "reaction": [ { "reactionmeddrapt": "Diabetes insipidus", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "HERITY, L.. DELAYED ONSET OF CENTRAL DIABETES INSIPIDUS WITH KETAMINE SEDATION: A REPORT OF 2 CASES. JOURNAL OF PHARMACY PRACTICE. 2021?34 (2):314?318", "literaturereference_normalized": "delayed onset of central diabetes insipidus with ketamine sedation a report of 2 cases", "qualification": "2", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210412", "receivedate": "20191106", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17000760, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210716" }, { "companynumb": "US-TEVA-2021-US-1931390", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "VANCOMYCIN" }, "drugadditional": "3", 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DELAYED ONSET OF CENTRAL DIABETES INSIPIDUS WITH KETAMINE SEDATION: A REPORT OF 2 CASES.. JOURNAL OF PHARMACY PRACTICE. 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{ "abstract": "Interscalene brachial plexus blockade is regularly used for postoperative pain management following shoulder surgery. A known but generally benign side effect of this technique is Horner syndrome. Another syndrome known as harlequin syndrome exists but does not appear to be as common. This syndrome consists of contralateral facial flushing and sweating secondary to ipsilateral sympathetic chain inhibition. Despite the alarming presentation in the perioperative setting, this syndrome appears to be benign and self-limiting when precipitated by regional anesthetic technique. This article describes an occurrence of harlequin syndrome without observed ptosis or miosis following a postoperative interscalene nerve block.", "affiliations": "was a student registered nurse anesthetist at the Geisinger Health System/Bloomsburg University of Pennsylvania Nurse Anesthesia Program, Danville, Pennsylvania, at the time he wrote this article. He is now a Certified Registered Nurse Anesthetist in Spokane, Washington.;is the program director at the Geisinger Health System/Bloomsburg University of Pennsylvania Nurse Anesthesia Program.", "authors": "Adams|Joshua S|JS|;Minzola|Debra J|DJ|", "chemical_list": null, "country": "United States", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "0094-6354", "issue": "86(1)", "journal": "AANA journal", "keywords": "Brachial plexus; harlequin syndrome; interscalene; regional anesthesia; sympathetic chain", "medline_ta": "AANA J", "mesh_terms": null, "nlm_unique_id": "0431420", "other_id": null, "pages": "56-58", "pmc": null, "pmid": "31573494", "pubdate": "2018-02", "publication_types": "D016428:Journal Article", "references": null, "title": "Isolated Harlequin Syndrome Following Brachial Plexus Nerve Block via Interscalene Approach: A Case Report.", "title_normalized": "isolated harlequin syndrome following brachial plexus nerve block via interscalene approach a case report" }

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ISOLATED HARLEQUIN SYNDROME FOLLOWING BRACHIAL PLEXUS NERVE BLOCK VIA INTERSCALENE APPROACH: A CASE REPORT. AANA?J. 2018?86(1):56?58.", "literaturereference_normalized": "isolated harlequin syndrome following brachial plexus nerve block via interscalene approach a case report", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20180712", "receivedate": "20180712", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15137378, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20181010" } ]

{ "abstract": "The case of acute lymphoblastic leukemia developing shortly after the diagnosis and treatment of a mediastinal germ cell tumor, is reported. The close temporal relationship of these two rare diseases and the presence of a population of mononuclear cells with features of lymphoblasts in the resected germ cell tumor, suggest that the leukemic process originated from the mediastinal tumor.", "affiliations": null, "authors": "Larsen|M|M|;Evans|W K|WK|;Shepherd|F A|FA|;Phillips|M J|MJ|;Bailey|D|D|;Messner|H|H|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1002/1097-0142(19840201)53:3<441::aid-cncr2820530312>3.0.co;2-s", "fulltext": null, "fulltext_license": null, "issn_linking": "0008-543X", "issue": "53(3)", "journal": "Cancer", "keywords": null, "medline_ta": "Cancer", "mesh_terms": "D000293:Adolescent; D006801:Humans; D007945:Leukemia, Lymphoid; D008297:Male; D008479:Mediastinal Neoplasms; D009373:Neoplasms, Germ Cell and Embryonal; D009378:Neoplasms, Multiple Primary", "nlm_unique_id": "0374236", "other_id": null, "pages": "441-4", "pmc": null, "pmid": "6318949", "pubdate": "1984-02-01", "publication_types": "D002363:Case Reports; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't", "references": null, "title": "Acute lymphoblastic leukemia. Possible origin from a mediastinal germ cell tumor.", "title_normalized": "acute lymphoblastic leukemia possible origin from a mediastinal germ cell tumor" }

[ { "companynumb": "CA-PFIZER INC-2019058788", "fulfillexpeditecriteria": "1", "occurcountry": "CA", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, CYCLIC", "drugenddate": null, "drugenddateformat": null, "drugindication": "TERATOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "1979", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DACTINOMYCIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, CYCLIC", "drugenddate": null, "drugenddateformat": null, "drugindication": "TERATOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "1979", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACTINOMYCIN D" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BLEOMYCIN SULFATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "065031", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, CYCLIC", "drugenddate": null, "drugenddateformat": null, "drugindication": "TERATOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "1979", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BLEOMYCIN SULFATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINBLASTINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, CYCLIC", "drugenddate": null, "drugenddateformat": null, "drugindication": "TERATOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "1979", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINBLASTINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, CYCLIC", "drugenddate": null, "drugenddateformat": null, "drugindication": "TERATOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "1979", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." } ], "patientagegroup": null, "patientonsetage": "16", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Second primary malignancy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute lymphocytic leukaemia", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bone marrow failure", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 1980" } }, "primarysource": { "literaturereference": "LARSEN, M.. ACUTE LYMPHOBLASTIC LEUKEMIA POSSIBLE ORIGIN FROM A MEDIASTINAL GERM CELL TUMOR. CANCER. 1984?53 (3):441-444", "literaturereference_normalized": "acute lymphoblastic leukemia possible origin from a mediastinal germ cell tumor", "qualification": "1", "reportercountry": "CA" }, "primarysourcecountry": "CA", "receiptdate": "20191009", "receivedate": "20190212", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15953786, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200122" } ]

{ "abstract": "To evaluate the safety of live attenuated influenza vaccine (LAIV) in children 2 through 17 years of age.\n\n\n\nThe study was conducted in 6 large integrated health care organizations participating in the Vaccine Safety Datalink (VSD). Trivalent LAIV safety was assessed in children who received LAIV between September 1, 2003 and March 31, 2013. Eighteen pre-specified adverse event groups were studied, including allergic, autoimmune, neurologic, respiratory, and infectious conditions. Incident rate ratios (IRRs) were calculated for each adverse event, using self-controlled case series analyses. For adverse events with a statistically significant increase in risk, or an IRR > 2.0 regardless of statistical significance, manual medical record review was performed to confirm case status.\n\n\n\nDuring the study period, 396 173 children received 590 018 doses of LAIV. For 13 adverse event groups, there was no significant increased risk of adverse events following LAIV. Five adverse event groups (anaphylaxis, syncope, Stevens-Johnson syndrome, adverse effect of drug, and respiratory failure) met criteria for manual medical record review. After review to confirm cases, 2 adverse event groups remained significantly associated with LAIV: anaphylaxis and syncope. One confirmed case of anaphylaxis was observed following LAIV, a rate of 1.7 per million LAIV doses. Five confirmed cases of syncope were observed, a rate of 8.5 per million doses.\n\n\n\nIn a study of trivalent LAIV safety in a large cohort of children, few serious adverse events were detected. Anaphylaxis and syncope occurred following LAIV, although rarely. These data provide reassurance regarding continued LAIV use.", "affiliations": "Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA.;Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA.;Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA.;Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA.;Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA.;Marshfield Clinic Research Foundation, Marshfield, WI, USA.;HealthPartners Institute, Minneapolis, MN, USA.;Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.;Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA.;Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA.;Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.;Department of Population Medicine, Harvard Medical School, Boston, MA, USA.;Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, GA, USA.;Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, GA, USA.", "authors": "Daley|Matthew F|MF|0000-0003-1309-4096;Clarke|Christina L|CL|;Glanz|Jason M|JM|;Xu|Stanley|S|;Hambidge|Simon J|SJ|;Donahue|James G|JG|;Nordin|James D|JD|;Klein|Nicola P|NP|;Jacobsen|Steven J|SJ|;Naleway|Allison L|AL|;Jackson|Michael L|ML|;Lee|Grace|G|;Duffy|Jonathan|J|;Weintraub|Eric|E|", "chemical_list": "D007252:Influenza Vaccines; D014613:Vaccines, Attenuated", "country": "England", "delete": false, "doi": "10.1002/pds.4349", "fulltext": null, "fulltext_license": null, "issn_linking": "1053-8569", "issue": "27(1)", "journal": "Pharmacoepidemiology and drug safety", "keywords": "anaphylaxis; child; live attenuated influenza vaccine; pharmacoepidemiology; syncope; vaccine safety", "medline_ta": "Pharmacoepidemiol Drug Saf", "mesh_terms": "D000293:Adolescent; D016907:Adverse Drug Reaction Reporting Systems; D000707:Anaphylaxis; D002648:Child; D002675:Child, Preschool; D004342:Drug Hypersensitivity; D005260:Female; D006801:Humans; D015994:Incidence; D007252:Influenza Vaccines; D007251:Influenza, Human; D008297:Male; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D012621:Seasons; D013575:Syncope; D014481:United States; D014611:Vaccination; D014613:Vaccines, Attenuated", "nlm_unique_id": "9208369", "other_id": null, "pages": "59-68", "pmc": null, "pmid": "29148124", "pubdate": "2018-01", "publication_types": "D016428:Journal Article; D016448:Multicenter Study; D013487:Research Support, U.S. Gov't, P.H.S.", "references": "27560619;28390584;16275804;21293327;25108215;22386746;16333007;14872180;16804427;23395734;9080932;26407428;24699471;22895385;21855747;26209838;15121324;21502240;20375998;24962036;26738884;27684447;21907257;26452420;17006278;23292957;12359778;11061799;24048214;19616500;17006279;17301299;25684279;24819580;16828674;27684603;22507656;21849099;28404355;26209836;7766778;18690366;26645895;26589519;21810637;18451756;19153164;17142512;15472840;26743842", "title": "The safety of live attenuated influenza vaccine in children and adolescents 2 through 17 years of age: A Vaccine Safety Datalink study.", "title_normalized": "the safety of live attenuated influenza vaccine in children and adolescents 2 through 17 years of age a vaccine safety datalink study" }

[ { "companynumb": "US-NOVAST LABORATORIES, LTD-US-2017NOV000088", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ACETAMINOPHEN\\BUTALBITAL\\CAFFEINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "040864", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUTALBITAL, ACETAMINOPHEN, AND CAFFEINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "INFLUENZA VIRUS VACCINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INFLUENZA VIRUS VACCINE" } ], "patientagegroup": "3", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Stevens-Johnson syndrome", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "DALEY MF, CLARKE CL, GLANZ JM, XU S, HAMBIDGE SJ, DONAHUE JG, ET AL. THE SAFETY OF LIVE ATTENUATED INFLUENZA VACCINE IN CHILDREN AND ADOLESCENTS 2 THROUGH 17 YEARS OF AGE: A VACCINE SAFETY DATALINK STUDY. PHARMACOEPIDEMIOL-DRUG-SAF. 2017", "literaturereference_normalized": "the safety of live attenuated influenza vaccine in children and adolescents 2 through 17 years of age a vaccine safety datalink study", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20171222", "receivedate": "20171222", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14319552, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" } ]

{ "abstract": "Cystoid macular edema (CME) is a rare adverse event induced by taxane-based chemotherapy. Here, we describe the case of a 71-year-old man who developed bilateral CME during treatment with nab-paclitaxel (nab-PTX) for unresectable pancreatic cancer. Two months after drug discontinuation, his vision improved, and there was significant reduction in the CME on optical coherence tomography. CME is an adverse event that can be treated with the early withdrawal of nab-PTX. Oncologists who use nab-PTX should be aware of this adverse event for timely patient referral to an ophthalmologist and appropriate treatment that would enable the preservation of the patient's visual acuity.", "affiliations": "Department of Gastroenterology and Hepatology, Kobe City Nishi-kobe Medical Center.;Department of Gastroenterology and Hepatology, Kobe City Nishi-kobe Medical Center.;Department of Gastroenterology and Hepatology, Kobe City Nishi-kobe Medical Center.;Department of Gastroenterology and Hepatology, Kobe City Nishi-kobe Medical Center.;Department of Gastroenterology and Hepatology, Kobe City Nishi-kobe Medical Center.;Department of Gastroenterology and Hepatology, Kobe City Nishi-kobe Medical Center.;Department of Gastroenterology and Hepatology, Kobe City Nishi-kobe Medical Center.;Department of Gastroenterology and Hepatology, Kobe City Nishi-kobe Medical Center.", "authors": "Ota|Shogo|S|;Tanke|Gensho|G|;Ito|Ryo|R|;Hara|Kazuya|K|;Takada|Yutaka|Y|;Adachi|Kanna|K|;Shimada|Yukari|Y|;Itani|Toshinao|T|", "chemical_list": "C520255:130-nm albumin-bound paclitaxel; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel", "country": "Japan", "delete": false, "doi": "10.11405/nisshoshi.118.272", "fulltext": null, "fulltext_license": null, "issn_linking": "0446-6586", "issue": "118(3)", "journal": "Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology", "keywords": null, "medline_ta": "Nihon Shokakibyo Gakkai Zasshi", "mesh_terms": "D000368:Aged; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D006801:Humans; D008269:Macular Edema; D008297:Male; D017239:Paclitaxel; D010190:Pancreatic Neoplasms", "nlm_unique_id": "2984683R", "other_id": null, "pages": "272-278", "pmc": null, "pmid": "33692262", "pubdate": "2021", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Cystoid macular edema secondary to albumin-bound paclitaxel therapy for pancreatic cancer.", "title_normalized": "cystoid macular edema secondary to albumin bound paclitaxel therapy for pancreatic cancer" }

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"drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION FOR INFUSION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREATIC CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "85", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LEUCOVORIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION FOR INFUSION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREATIC CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FOLINIC ACID" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "GEMCITABINE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREATIC CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5000", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "IRINOTECAN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION FOR INFUSION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREATIC CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "150", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IRINOTECAN" } ], "patientagegroup": null, "patientonsetage": "71", "patientonsetageunit": "801", "patientsex": "1", "patientweight": "53", "reaction": [ { "reactionmeddrapt": "Cystoid macular oedema", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "OTA S. CYSTOID MACULAR EDEMA SECONDARY TO ALBUMIN?BOUND PACLITAXEL THERAPY FOR PANCREATIC CANCER. THE JAPANESE JOURNAL OF GASTRO?ENTEROLOGY.", "literaturereference_normalized": "cystoid macular edema secondary to albumin bound paclitaxel therapy for pancreatic cancer", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20210520", "receivedate": "20210520", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19279003, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210717" } ]

{ "abstract": "BACKGROUND\nOutcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), often treated with immunosuppressive therapies, are still unknown.\n\n\nMETHODS\nWe conducted a multicenter, retrospective, observational cohort study among all French expert centers for neuromyelitis optica and related disorders. Patients with NMOSD or MOGAD included in the study received a confirmed or highly suspected diagnosis of COVID-19 between 1 March 2020 and 30 June 2020. Main outcome was COVID-19 severity score assessed on a seven-point ordinal scale ranging from 1 (not hospitalized with no limitations on activities) to 7 (death).\n\n\nRESULTS\nFifteen cases (mean [SD] age: 39.3 [14.3] years, 11 female) were included. Five patients (33.3%) were hospitalized, all receiving rituximab. A 24-year-old patient with positive aquaporine-4 antibody, with obesity as comorbidity, needed mechanical ventilation. Outpatients were receiving anti-CD20 (5), mycophenolate mofetil (3) or azathioprine (3). They were younger (mean [SD] age: 37.0 [13.4] years), with a longer disease duration (mean [SD]: 8.3 [6.3] years) and had a lower expanded disability severity score (EDSS) score (median [range] EDSS: 2.5 [0-4]) relative to patients requiring hospitalization (mean [SD] age: 44.0 [16.4] years, mean [SD] disease duration: 5.8 [5.5] years, median [range] EDSS: 4 [0-6.5]).\n\n\nCONCLUSIONS\nCOVID-19 outcome was overall favorable in this cohort. Larger international studies are needed to identify risk factors of severe COVID-19; however, we recommend personal protective measures to reduce risk of SARS-CoV-2 infection in this immunocompromised population.", "affiliations": "Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Institut du Cerveau, CIC Neuroscience, ICM, Hôpital de la Pitié Salpêtrière, Sorbonne Université, Paris, France.;Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Institut du Cerveau, CIC Neuroscience, ICM, Hôpital de la Pitié Salpêtrière, Sorbonne Université, Paris, France.;Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Institut du Cerveau, CIC Neuroscience, ICM, Hôpital de la Pitié Salpêtrière, Sorbonne Université, Paris, France.;Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Institut du Cerveau, CIC Neuroscience, ICM, Hôpital de la Pitié Salpêtrière, Sorbonne Université, Paris, France.;Pole des Neurosciences, B4 Neurology Unit, Centre de ressources et de compétences Sclérose en plaques, CHU Purpan, Toulouse, France.;Pole des Neurosciences, B4 Neurology Unit, Centre de ressources et de compétences Sclérose en plaques, CHU Purpan, Toulouse, France.;Service de Neurologie et CRC SEP, Groupe Hospitalier Henri Mondor, APHP, UPEC Université, Créteil, France.;Unité de neurologie inflammatoire, Département de Neurologie, Hôpital Roger Salengro, Chu de Lille, Lille, France.;Département de neurologie, CHU de Montpellier, Montpellier, France.;Equipe impact, Service de Neurocognition et Neuro-ophtalmologie, Groupe Hospitalier Est, Centre de Recherche en Neurosciences de Lyon, Hospices Civils de Lyon, Université de Lyon, Lyon, France.;Centre de référence des maladies inflammatoires rares du cerveau et de la moelle (MIRCEM), Service de neurologie, sclérose en plaques, Pathologies de la myéline et neuro-inflammation, Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, Lyon, France.;Service de Neurologie, Hôpital Raymond Poincaré, UFR Simone Veil UVSQ, Université Paris Saclay, Garches, France.;Service de neurologie, Centre Régional Hospitalo-Universitaire de Nancy, Hôpital Central, Nancy, France.;Service de neurologie, CHU Bicêtre, Le Kremlin Bicêtre, France.;Service de Neurologie, CHU de Caen Normandie, Caen, France.;Service de Neurologie and CIC INSERM 1434, CHU de Strasbourg, Strasbourg, France.;Centre de référence des maladies inflammatoires rares du cerveau et de la moelle (MIRCEM), Service de neurologie, sclérose en plaques, Pathologies de la myéline et neuro-inflammation, Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, Lyon, France.;Service de Neurologie and CIC INSERM 1434, CHU de Strasbourg, Strasbourg, France.;Service de Neurologie and CIC INSERM 1434, CHU de Strasbourg, Strasbourg, France.", "authors": "Louapre|Céline|C|https://orcid.org/0000-0002-4987-1531;Maillart|Elisabeth|E|https://orcid.org/0000-0001-7699-0328;Papeix|Caroline|C|https://orcid.org/0000-0003-4074-6125;Zeidan|Sinead|S|;Biotti|Damien|D|;Lepine|Zoé|Z|;Wahab|Abir|A|;Zedet|Mickael|M|;Labauge|Pierre|P|;Tilikete|Caroline|C|;Pique|Julie|J|;Tourbah|Ayman|A|;Mathey|Guillaume|G|https://orcid.org/0000-0002-5747-9169;Dimitri Boulos|Dalia|D|;Branger|Pierre|P|;Kremer|Laurent Daniel|LD|;Marignier|Romain|R|;Collongues|Nicolas|N|https://orcid.org/0000-0002-3683-5582;De Seze|Jérôme|J|", "chemical_list": "D051401:Aquaporin 4; D000069283:Rituximab", "country": "England", "delete": false, "doi": "10.1111/ene.14612", "fulltext": null, "fulltext_license": null, "issn_linking": "1351-5101", "issue": "28(10)", "journal": "European journal of neurology", "keywords": "COVID-19; MOGAD; NMOSD; immunosuppressant", "medline_ta": "Eur J Neurol", "mesh_terms": "D000328:Adult; D051401:Aquaporin 4; D000086382:COVID-19; D005260:Female; D006801:Humans; D009471:Neuromyelitis Optica; D012189:Retrospective Studies; D000069283:Rituximab; D000086402:SARS-CoV-2; D055815:Young Adult", "nlm_unique_id": "9506311", "other_id": null, "pages": "3461-3466", "pmc": null, "pmid": "33103295", "pubdate": "2021-10", "publication_types": "D016428:Journal Article; D016448:Multicenter Study; D064888:Observational Study", "references": null, "title": "Outcomes of coronavirus disease 2019 in patients with neuromyelitis optica and associated disorders.", "title_normalized": "outcomes of coronavirus disease 2019 in patients with neuromyelitis optica and associated disorders" }

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AL.. OUTCOMES OF CORONAVIRUS DISEASE 2019 IN PATIENTS WITH NEUROMYELITIS OPTICA AND ASSOCIATED DISORDERS. 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{ "abstract": "Metastatic vulvar melanoma is a rare and aggressive disease and survival is usually poor. Vulvar melanomas harbor BRAF V600 mutations only infrequently; consequently, target therapy is a rare therapeutic option and immunotherapy usually has only a weak effect. On the other hand, KIT mutations are rare in cutaneous melanomas, but relatively frequent in mucosal melanomas, particularly in vulvar-vaginal melanomas, and can be a therapeutic target. Herein, we report a clinical case of a patient with metastatic vulvar melanoma, harboring an exon 17 c-KIT mutation, treated with avapritinib (BLU-285) - a highly potent and selective oral kinase inhibitor designed to treat imatinib-resistant gastro-intestinal stromal tumors (GIST) by targeting KIT/PDGFRα activation loop mutants (exons 17/18). After failure of the combination of ipilimumab + nivolumab first and then nivolumab alone, the patient received avapritinib 300 mg/daily for central nervous system (CNS), lymph-nodal, right adrenal gland, lung, and subcutaneous metastases. Best response was partial remission, according to RECIST 1.1 criteria. Time to treatment progression was 11 months. Main toxicities were grade 2 cutaneous vasculitis that required avapritinib discontinuation, and grade 2 uveitis of unknown origin, treated by vitrectomy and empiric antibiotic and antiviral therapy due to negative cultural tests. Uveitis was detected at the time of progression and therapy was definitively discontinued. In conclusion, avapritinib proved to be effective even in the presence of a pretreated disease, a high tumor burden, and brain metastases. In our experience, treatment was feasible and toxicity manageable. Considering the lack of effective therapies and the poor outcome of the disease, determination of c-KIT mutations should be performed routinely in cases of metastatic mucosal melanoma.", "affiliations": "Division of Medical Oncology of Melanoma, Soft Tissue Sarcoma and Rare Tumors, Istituto Europeo di Oncologia IRCCS, Via Giuseppe Ripamonti 435, Milano, 20141, Italy.;Division of Medical Oncology of Melanoma, Soft Tissue Sarcoma and Rare Tumors, Istituto Europeo di Oncologia IRCCS, Milan, Italy.;Division of Medical Oncology of Melanoma, Soft Tissue Sarcoma and Rare Tumors, Istituto Europeo di Oncologia IRCCS, Milan, Italy.;Pathology and Laboratory Medicine Department, Istituto Europeo di Oncologia IRCCS, Milan, Italy.;Division of Medical Oncology of Melanoma, Soft Tissue Sarcoma and Rare Tumors, Istituto Europeo di Oncologia IRCCS, Milan, Italy.;Department of Experimental Oncology, Istituto Europeo di Oncologia IRCCS, Milan, Italy.", "authors": "Cocorocchio|Emilia|E|https://orcid.org/0000-0003-1184-6426;Pala|Laura|L|;Conforti|Fabio|F|;Guerini-Rocco|Elena|E|;De Pas|Tommaso|T|;Ferrucci|Pier Francesco|PF|", "chemical_list": null, "country": "England", "delete": false, "doi": "10.1177/1758835920946158", "fulltext": "\n==== Front\nTher Adv Med Oncol\nTher Adv Med Oncol\nTAM\nsptam\nTherapeutic Advances in Medical Oncology\n1758-8340 1758-8359 SAGE Publications Sage UK: London, England \n\n10.1177/1758835920946158\n10.1177_1758835920946158\nCase Report\nSuccessful treatment with avapritinib in patient with mucosal metastatic melanoma\nhttps://orcid.org/0000-0003-1184-6426Cocorocchio Emilia Division of Medical Oncology of Melanoma, Soft Tissue Sarcoma and Rare Tumors, Istituto Europeo di Oncologia IRCCS, Via Giuseppe Ripamonti 435, Milano, 20141, Italy\n Pala Laura Division of Medical Oncology of Melanoma, Soft Tissue Sarcoma and Rare Tumors, Istituto Europeo di Oncologia IRCCS, Milan, Italy\n Conforti Fabio Division of Medical Oncology of Melanoma, Soft Tissue Sarcoma and Rare Tumors, Istituto Europeo di Oncologia IRCCS, Milan, Italy\n Guerini-Rocco Elena Pathology and Laboratory Medicine Department, Istituto Europeo di Oncologia IRCCS, Milan, Italy\n De Pas Tommaso Division of Medical Oncology of Melanoma, Soft Tissue Sarcoma and Rare Tumors, Istituto Europeo di Oncologia IRCCS, Milan, Italy\n Ferrucci Pier Francesco Department of Experimental Oncology, Istituto Europeo di Oncologia IRCCS, Milan, Italy\n [email protected]\n31 7 2020 \n2020 \n12 175883592094615828 1 2020 7 7 2020 © The Author(s), 20202020SAGE Publications Ltd unless otherwise noted. Manuscript content on this site is licensed under Creative Commons LicensesThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Metastatic vulvar melanoma is a rare and aggressive disease and survival is usually poor. Vulvar melanomas harbor BRAF V600 mutations only infrequently; consequently, target therapy is a rare therapeutic option and immunotherapy usually has only a weak effect. On the other hand, KIT mutations are rare in cutaneous melanomas, but relatively frequent in mucosal melanomas, particularly in vulvar-vaginal melanomas, and can be a therapeutic target. Herein, we report a clinical case of a patient with metastatic vulvar melanoma, harboring an exon 17 c-KIT mutation, treated with avapritinib (BLU-285) – a highly potent and selective oral kinase inhibitor designed to treat imatinib-resistant gastro-intestinal stromal tumors (GIST) by targeting KIT/PDGFRα activation loop mutants (exons 17/18). After failure of the combination of ipilimumab + nivolumab first and then nivolumab alone, the patient received avapritinib 300 mg/daily for central nervous system (CNS), lymph-nodal, right adrenal gland, lung, and subcutaneous metastases. Best response was partial remission, according to RECIST 1.1 criteria. Time to treatment progression was 11 months. Main toxicities were grade 2 cutaneous vasculitis that required avapritinib discontinuation, and grade 2 uveitis of unknown origin, treated by vitrectomy and empiric antibiotic and antiviral therapy due to negative cultural tests. Uveitis was detected at the time of progression and therapy was definitively discontinued. In conclusion, avapritinib proved to be effective even in the presence of a pretreated disease, a high tumor burden, and brain metastases. In our experience, treatment was feasible and toxicity manageable. Considering the lack of effective therapies and the poor outcome of the disease, determination of c-KIT mutations should be performed routinely in cases of metastatic mucosal melanoma.\n\navapritinibKIT inhibitormucosal melanomatargeted therapyvulvar melanomacover-dateJanuary-December 2020typesetterts1\n==== Body\nIntroduction\nVulvar melanoma is a rare disease, with an incidence of 1.3/1,000,000 persons per year,1 and is the most frequent mucosal melanoma in the Swedish and Dutch populations.2,3\n\nVulvar melanoma can arise from the hairy or from the glabrous part of the vulva. The significance of tumor location, although controversial,4 could account for the particular behavior and the molecular characteristics of this disease that make it a distinct entity from cutaneous and other mucosal melanomas.5\n\nIn the metastatic disease, survival is usually poor, due either to the aggressive biological behavior or to the lack of efficacy of novel therapeutic strategies. Vulvar melanoma only seldomly presents BRAF V600 mutations (3–26% of cases),4,5 and, consequently, target therapy with BRAF and MEK inhibitors is a rare therapeutic option. Immunotherapy with anti-PD1 antibodies seems to have a weak effect on mucosal melanoma, with a median progression-free survival (PFS) and overall survival (OS) of 3.9 and 12.4 months, respectively.6 A combination of anti PD-1 and anti CTLA4 antibodies seems to be more effective, with a median PFS of 5.9 months and an overall response rate (ORR) of 37.1%, despite the high rate of grade 3–4 toxicity (40%).7 Interestingly, there is another possible pathway to target mucosal melanoma through mutations occurring in the c-KIT gene.\n\nKIT is a class III receptor tyrosine kinase (RTK) that has a crucial role in sustaining growth and maintenance of cells and tissues. KIT is expressed by hematopoietic progenitor and stem cells,8,9 mast cells,10 melanocytes,11 and primordial germ cells.12 KIT-activating mutations are involved in the pathogenesis of several cancers, such as most of the mastocytoses,13 mast cell leukemias,14 gastro-intestinal stromal tumors (GISTs),15 and melanomas.16 c-KIT activation is followed by receptor auto-phosphorylation and binding of substrate and adaptor proteins. Downstream molecules then drive the transcription of genes involved in influencing the tumor mechanisms of proliferation, survival, adhesion, invasion, metastasis, and angiogenesis. The most frequent c-KIT mutations involve the juxta-membrane (JM) zone of the receptor (exons 9–11) and are usually point mutations.\n\nIn GISTs, the presence of exons 9–11 c-KIT mutations is usually associated with the response to imatinib, an inhibitor of tyrosine-kinases like KIT, PDGFRA, ABL, and Fms-like tyrosine kinase-3 (FLT3), and of colony stimulating factor-1 receptor (CSF1R).17 On the other hand, some acquired KIT mutations are responsible for imatinib resistance, such as exon 17–18 mutations, which activate the loop domain of the receptor.18\n\nKIT alterations, such as mutations or amplifications, are rare in cutaneous melanoma, but relatively frequent in mucosal melanoma, particularly in vulvar–vaginal melanoma, where they are present in 20–44% of analyzed specimens.16,19\n\nIn several phase II trials, imatinib proved effective in patients with metastatic melanoma mostly harboring JM KIT point mutations, with an ORR (complete + partial remission) ranging from 5 to 29%.20,21 The benefit of imatinib seems to be limited in the presence of only KIT amplifications,20,21 or mutations of the loop domain of the receptor. Both alterations represent mechanisms of resistance to treatment and occur very rarely in melanoma.5\n\nAvapritinib (BLU-285) is a highly potent and selective oral kinase inhibitor, designed to treat imatinib-resistant GISTs by targeting KIT/PDGFRα activation loop mutants (exons 17/18). Avapritinib was demonstrated to be effective in GIST and in systemic mastocytosis with a good toxicity profile.22,23 There are several phase II–III clinical trials currently going on with avapritinib on GISTs and myeloid malignancies. The United States Food and Drug Administration (FDA) recently approved avapritinib for the treatment of unresectable or metastatic PDGFRA exon 18 mutant GISTs.\n\nCase description\nHere, we report the clinical case of a patient with metastatic vulvar melanoma, harboring an exon 17 c-KIT mutation, treated with avapritinib, following disease progression after two lines of treatment. The patient’s consent for publication was obtained in accordance with local regulations and laws, and is archived in the patient’s hospital record.\n\nThis 47-years-old patient came to our attention with stage pT4bN2b vulvar melanoma arising from the mucosa of the right labium minor, after wedge resection of the vulva and right inguinal-iliac-obturator lymph-nodes dissection, performed in December 2015. In September 2016, the patient presented with vulvar recurrence, with lymph-nodal and lung metastases.17 A p.N822K c-KIT mutation was detected by next-generation sequencing (NGS) on vulvar recurrence. KIT was not amplified, while NRAS and BRAF were wild type. In November 2016, the patient started ipilimumab and nivolumab combination immunotherapy and discontinued it after four cycles due to severe toxicity (G4 hyperglycemia with development of type I diabetes mellitus). Best response was stable disease, lasting about 10 months. Progression was observed in November 2017, because of the onset of central nervous system (CNS), lymph nodal, right adrenal gland, lung, and subcutaneous metastases. The patient received nivolumab in combination with cyber-knife radiotherapy on three brain metastases. After radiotherapy, she experienced hemiparesis with seizures due to hemorrhage and radio-necrosis of the irradiated lesions. All symptoms regressed after steroid administration. Despite treatment, after 4 months of therapy, the patient had a further progression due to CNS, right breast, lymph nodal, right adrenal gland, lung, gastric, gallbladder, and subcutaneous metastases. At that time performance status (PS) was 1 [Eastern Cooperative Oncology Group (ECOG)] and lactate dehydrogenase (LDH) 635 international units (IU)/L (UPN 220 IU/L).\n\nIn June 2018, the patient started avapritinib 300 mg/daily. Assessment of response was performed by means of computed tomography (CT) scan, every 8 weeks of therapy, according to RECIST criteria 1.1. Best response was partial remission at the 16th week, which was already evident at the 8th week (Figure 1). LDH normalized after 8 weeks. Site by site responses according to RECIST 1.1 criteria are reported in Table 1. Reduction in tumor burden was evident in all metastases, including CNS metastasis, where the patient only achieved stable disease. She maintained her partial response for 11 months. Afterwards, CT scan showed CNS, liver, and adrenal gland disease progression.\n\nFigure 1. CT scan at baseline, after 8 and 16 weeks focused on right adrenal gland (A), subcutaneous/lymphnodal (B) and CNS (C) metastases.\n\nCNS, central nervous system; CT, computed tomography.\n\nTable 1. Pattern of response according to RECIST 1.1 criteria after 12 weeks of therapy.\n\nSite\t+ 12 weeks\t\nCNS\tSD\t\nLymph-nodes\tPR\t\nBreast\tCR\t\nRight adrenal grand\tPR\t\nStomach\tCR\t\nSubcutaneous\tPR\t\nLung\tPR\t\nPeritoneum\tCR\t\nGallbladder\tPR\t\nCNS, central nervous system; CR, complete response; PR, partial response; SD, stable disease.\n\nMajor adverse events were grade 2 cutaneous vasculitis that required avapritinib discontinuation for 3 weeks and high dose steroid administration, and grade 2 uveitis of unknown origin, treated by vitrectomy and empiric antibiotic and antiviral therapy due to negative cultural tests. Uveitis was detected at the time of progression and therapy was definitively discontinued. The patient died after 4 months from further melanoma progression.\n\nDiscussion\nThe role of KIT as an oncogene and the role of its driven mutations is well known.\n\nGISTs were the first solid tumor in which KIT was targeted by imatinib, which is the standard therapy in both adjuvant and advanced settings. In GISTs, imatinib is usually effective in the presence of exon 9–11 c-KIT mutations, while imatinib resistance is often associated with acquired gene mutations, such as V654A, D820Y, N822K, and A829P.18,24\n\nImatinib showed activity also in patients with melanoma harboring c-KIT mutations, while c-KIT amplifications seem to select imatinib-refractory patients.21\n\nc-KIT N822K mutation is infrequent in melanoma, is often a primary mutation and may predict imatinib resistance. Few data are available on the activity of imatinib in this subgroup of patients. Carvajal et al. described a phase II study in which one patient with metastatic melanoma harboring the c-KIT N822K mutation achieved stable disease during imatinib treatment.25 Thus, the presence of exon 17 mutations activating the loop domain of the receptor provides a strong rationale in giving avapritinib also in metastatic melanoma in the presence of these uncommon mutations.\n\nTo our knowledge, this is the first patient who received avapritinib for metastatic melanoma. The clinical benefit was evident in terms of disease control, in terms of the quality and duration of the response obtained. Time to treatment progression was 11 months, which is reminiscent of the median PFS observed for BRAF and MEK inhibitor combinations in patients with metastatic melanoma harboring BRAFV600 mutation.\n\nThe main toxicities recorded were cutaneous vasculitis and uveitis, which should be very rare with avapritinib,26 and more frequent with immunotherapy.27 Thus, we speculate on the role of previous immunotherapies in the appearance of these more commonly considered immune-related adverse events. Avapritinib proved effective even in the presence of a pretreated disease, a high tumor burden, and CNS metastases. In our experience, treatment was feasible and toxicity manageable. The activity of avapritinib should be evaluated prospectively in patients with metastatic melanoma harboring exon 17–18 KIT mutations. Considering the lack of effective therapies and the poor prognosis of the disease, the determination of c-KIT mutations should be performed routinely in the presence of metastatic mucosal melanoma to explore all therapeutic options in this subgroup of patients.\n\nThanks go to Lucia Stavolone for English language support.\n\nConflict of interest statement: Cocorocchio E.: paid consultant for Roche, Novartis, BMS Ferrucci PF: paid consultant for Roche, Novartis, BMS, Amgen, MSD.\n\nFunding: The authors received no financial support for the research, authorship, and/or publication of this article.\n\nORCID iD: Emilia Cocorocchio \nhttps://orcid.org/0000-0003-1184-6426\n==== Refs\nReferences\n1 \nPleunis N Schuurman MS Van Rossum MM , et al\nRare vulvar malignancies; incidence, treatment and survival in the Netherlands\n. Gynecol Oncol \n2016 ; 142 : 440 –445\n.27126004 \n2 \nThe National Board of Health and Welfare . The Swedish Cancer Registry: cancer incidence in Sweden . Stockholm : Annual Publications \n1960 –2004\n.\n3 \nKoomen ER de Vries E van Kempen LC , et al\nEpidemiology of extracutaneous melanoma in the Netherlands\n. Cancer Epidemiol Biomarkers Prev \n2010 ; 6 : 1453 –1459\n.\n4 \nZarei S Jesse S Voss JS , et al\nMutational profile in vulvar, vaginal, and urethral melanomas: review of 37 cases with focus on primary tumor site\n. Int J Gynecol Pathol . Epub ahead of print 20 \n9 \n2019 DOI: 10.1097/PGP.0000000000000636. \n5 \nHou JY Baptiste C Hombalegowda RB , et al\nVulvar and vaginal melanoma: a unique subclass of mucosal melanoma based on a comprehensive molecular analysis of 51 cases compared with 2253 cases of nongynecologic melanoma\n. Cancer \n2017 ; 123 : 1333 –1344\n.28026870 \n6 \nShoushtari AN Munhoz RR Kuk D , et al\nEfficacy of anti-PD-1 agents in acral and mucosal melanoma\n. Cancer \n2016 ; 122 : 3354 –3362\n.27533633 \n7 \nD’Angelo SP Larkin J Sosman JA , et al\nEfficacy and safety of nivolumab alone or in combination with ipilimumab in patients with mucosal melanoma: a pooled analysis\n . J Clin Oncol \n2017 ; 35 : 226 –235\n.28056206 \n8 \nMatthews W Jordan CT Wiegand GW , et al\nA receptor tyrosine kinase specific to hematopoietic stem and progenitor cell-enriched populations\n. Cell \n1991 ; 65 : 1143 –1152\n.1648448 \n9 \nOkada S Nakauchi H Nagayoshi K , et al\nEnrichment and characterization of murine hematopoietic stem cells that express c-kit molecule\n. Blood \n1991 ; 78 : 1706 –1712\n.1717068 \n10 \nNocka K Buck J Levi E , et al\nCandidate ligand for the c-kit transmembrane kinase receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors\n. Embo J \n1990 : 9 : 3287 –3294\n.1698611 \n11 \nNatali PG Nicotra MR Sures I , et al\nExpression of c-kit receptor in normal and transformed human nonlymphoid tissues\n. Cancer Res \n1992 ; 52 : 6139 –6143\n.1384954 \n12 \nDolci S Williams DE Ernst MK , et al\nRequirement for mast cell growth factor for primordial germ cell survival in culture\n. Nature \n1991 ; 352 : 809 –811\n.1715518 \n13 \nValent P Akin C Hartmann K , et al\nAdvances in the classification and treatment of mastocytosis: current status and outlook toward the future\n. Cancer Res \n2017 ; 77 : 1261 –1270\n.28254862 \n14 \nVerstovsek S. \nAdvanced systemic mastocytosis: the impact of KIT mutations in diagnosis, treatment, and progression\n. Eur J Haematol \n2013 ; 90 : 89 –98\n.23181448 \n15 \nBannon AE Klug LR Corless CL , et al\nUsing molecular diagnostic testing to personalize the treatment of patients with gastrointestinal stromal tumors\n. Expert Rev Mol Diagn \n2017 : 1 –13\n.\n16 \nBeadling C Jacobson-Dunlop E Hodi FS , et al\nKIT gene mutations and copy number in melanoma subtypes\n. Clin Cancer Res \n2008 ; 14 : 6821 –6828\n.18980976 \n17 \nDemetri GD von Mehren M Blanke CD , et al\nEfficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors\n. N Engl J Med \n2002 ; 347 : 472 –480\n.12181401 \n18 \nAntonescu CR Besmer P Guo T , et al\nAcquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation\n. Clin Cancer Res \n2005 ; 11 : 4182 –4190\n.15930355 \n19 \nCurtin JA Busam K Pinkel D , et al\nSomatic activation of KIT in distinct subtypes of melanoma\n. J Clin Oncol \n2006 ; 24 : 4340 –4346\n.16908931 \n20 \nKim KB Eton O Davis DW , et al\nPhase II trial of imatinib mesylate in patients with metastatic melanoma\n. Br J Cancer \n2008 ; 99 : 734 –740\n.18728664 \n21 \nHodi FS Corless CL Giobbie-Hurder A , et al\nImatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin\n. J Clin Oncol \n2013 ; 31 : 3182 –3190\n.23775962 \n22 \nHeinrich MC Jones RL von Mehren M , et al\nClinical activity of BLU-285 in advanced gastrointestinal stromal tumor (GIST)\n. J Clin Oncol \n2017 ; 35 : 11011 .\n23 \nDe Angelo DJ Quiery AT Radia D , et al\nClinical activity in a phase 1 study of Blu-285, a potent, highly-selective inhibitor of KIT D816V in Advanced Systemic Mastocytosis (AdvSM)\n. Blood \n2017 ; 130 : 2 .28684445 \n24 \nHeinrich MC Corless CL Blanke CD , et al\nMolecular correlates of imatinib resistance in gastrointestinal stromal tumors\n. J Clin Oncol \n2006 ; 24 : 4764 –4774\n.16954519 \n25 \nCarvajal RD Antonescu CR Wolchok JD , et al\nKIT as a therapeutic target in metastatic melanoma\n. JAMA \n2011 ; 305 : 2327 –2334\n.21642685 \n26 \nHeinrich M von Mehren M Jones RL , et al\nAvapritinib is highly active and well tolerated in patients with advanced GIST driven by a diverse variety of oncogenic mutations in KIT and PDGFRA\n. In: CTOS annual meeting , Rome, Italy \nhttps://www.blueprintmedicines.com/wp-content/uploads/2019/01/CTOS-Avapritinib-Update-Nov-2018.pdf. (2018 , accessed 12 February 2019 ).\n27 \nBrahmer JT Lacchetti C Schneider BJ , et al\nManagement of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline\n. J Clin Oncol \n2018 ; 36 : 1714 –1768\n.29442540\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "1758-8340", "issue": "12()", "journal": "Therapeutic advances in medical oncology", "keywords": "KIT inhibitor; avapritinib; mucosal melanoma; targeted therapy; vulvar melanoma", "medline_ta": "Ther Adv Med Oncol", "mesh_terms": null, "nlm_unique_id": "101510808", "other_id": null, "pages": "1758835920946158", "pmc": null, "pmid": "32821296", "pubdate": "2020", "publication_types": "D002363:Case Reports", "references": "18980976;29442540;16908931;28026870;28056206;28317407;1717068;15930355;28254862;23181448;1698611;1648448;16954519;1715518;31567539;27533633;27126004;1384954;18728664;20501769;21642685;23775962;12181401", "title": "Successful treatment with avapritinib in patient with mucosal metastatic melanoma.", "title_normalized": "successful treatment with avapritinib in patient with mucosal metastatic melanoma" }

[ { "companynumb": "IT-BRISTOL-MYERS SQUIBB COMPANY-BMS-2020-068090", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "IPILIMUMAB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "125377", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "METASTATIC MALIGNANT MELANOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201611", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IPILIMUMAB" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "NIVOLUMAB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "METASTATIC MALIGNANT MELANOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201611", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NIVOLUMAB" } ], "patientagegroup": null, "patientonsetage": "47", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Type 1 diabetes mellitus", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "COCOROCCHIO E, PALA L, CONFORTI F, GUERINI?ROCCO E, DE PAS T, FERRUCCI PF. SUCCESSFUL TREATMENT WITH AVAPRITINIB IN PATIENT WITH MUCOSAL METASTATIC MELANOMA. THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY. 2020?12:1?5", "literaturereference_normalized": "successful treatment with avapritinib in patient with mucosal metastatic melanoma", "qualification": "3", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20200824", "receivedate": "20200824", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18190413, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" } ]

{ "abstract": "Research is moving towards a more personalized management of immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI). Our objective was to evaluate the efficacy and safety of tocilizumab in the treatment of these clinical manifestations.\n\n\n\nA systematic literature review was performed to retrieve data about the use of tocilizumab in the treatment of irAEs. Additionally, data from cancer patients referred to our Immune-related Adverse Event Clinic and treated with tocilizumab were collected.\n\n\n\nOur literature review identified 20 articles and 11 meeting abstracts. Data about 91 cancer patients who received tocilizumab for the treatment of irAEs were collected. In 85% of cases, this therapy was associated with clinical benefit and no case of disease progression was reported. ICI therapy was continued following irAE onset and biologic therapy initiation in only three patients. Five patients developed irAEs upon ICI initiation and were subsequently treated with tocilizumab at our Centre. At a median follow-up of eight months, tocilizumab was safely continued along with ICI in three out of five patients, and an adequate control of irAE was obtained in all cases. No significant adverse reactions to tocilizumab were reported. Only one patient experienced a disease progression 18 months after ICI discontinuation.\n\n\n\nBoth our systematic literature review and case series highlight the efficacy and safety of tocilizumab in the treatment of irAEs. Furthermore, they both support the possibility of a combined approach with tocilizumab and ICI, to guarantee an effective irAEs management without losing the oncologic response.", "affiliations": "Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele, via Olgettina 60, Milan, Italy; Vita-Salute San Raffaele University, via Olgettina 60, Milan, Italy. Electronic address: [email protected].;Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele, via Olgettina 60, Milan, Italy; Vita-Salute San Raffaele University, via Olgettina 60, Milan, Italy.;Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele, via Olgettina 60, Milan, Italy; Vita-Salute San Raffaele University, via Olgettina 60, Milan, Italy.;Thoracic Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian 1, Milan, Italy.;Department of Oncology, IRCCS San Raffaele, via Olgettina 60, Milan, Italy.;Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele, via Olgettina 60, Milan, Italy; Vita-Salute San Raffaele University, via Olgettina 60, Milan, Italy.;Department of Oncology, IRCCS San Raffaele, via Olgettina 60, Milan, Italy.;Thoracic Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian 1, Milan, Italy.;Department of Radiology, IRCCS San Raffaele Hospital, via Olgettina 60, Milan, Italy.;Department of Radiology, IRCCS San Raffaele Hospital, via Olgettina 60, Milan, Italy.;Department of Arrhythmology, IRCCS San Raffaele Hospital, via Olgettina 60, Milan, Italy.;Department of Arrhythmology, IRCCS San Raffaele Hospital, via Olgettina 60, Milan, Italy.;Department of Radiology, IRCCS San Raffaele Hospital, via Olgettina 60, Milan, Italy.;Thoracic Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian 1, Milan, Italy.;Department of Oncology, IRCCS San Raffaele, via Olgettina 60, Milan, Italy.;Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele, via Olgettina 60, Milan, Italy; Vita-Salute San Raffaele University, via Olgettina 60, Milan, Italy.", "authors": "Campochiaro|Corrado|C|;Farina|Nicola|N|;Tomelleri|Alessandro|A|;Ferrara|Roberto|R|;Lazzari|Chiara|C|;De Luca|Giacomo|G|;Bulotta|Alessandra|A|;Signorelli|Diego|D|;Palmisano|Anna|A|;Vignale|Davide|D|;Peretto|Giovanni|G|;Sala|Simone|S|;Esposito|Antonio|A|;Garassino|Marina|M|;Gregorc|Vanesa|V|;Dagna|Lorenzo|L|", "chemical_list": null, "country": "Netherlands", "delete": false, "doi": "10.1016/j.ejim.2021.07.016", "fulltext": null, "fulltext_license": null, "issn_linking": "0953-6205", "issue": "93()", "journal": "European journal of internal medicine", "keywords": "Arthritis; Immune checkpoint inhibition; Immune-related adverse events; Myocarditis; Tocilizumab; Vasculitis", "medline_ta": "Eur J Intern Med", "mesh_terms": null, "nlm_unique_id": "9003220", "other_id": null, "pages": "87-94", "pmc": null, "pmid": "34391591", "pubdate": "2021-11", "publication_types": "D016428:Journal Article", "references": null, "title": "Tocilizumab for the treatment of immune-related adverse events: a systematic literature review and a multicentre case series.", "title_normalized": "tocilizumab for the treatment of immune related adverse events a systematic literature review and a multicentre case series" }

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TOCILIZUMAB FOR THE TREATMENT OF IMMUNE?RELATED ADVERSE EVENTS: A SYSTEMATIC LITERATURE REVIEW AND A MULTICENTRE CASE SERIES. EUROPEAN JOURNAL OF INTERNAL MEDICINE. 2021", "literaturereference_normalized": "tocilizumab for the treatment of immune related adverse events a systematic literature review and a multicentre case series", "qualification": "3", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20210825", "receivedate": "20210825", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19746034, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20211014" }, { "companynumb": "IT-009507513-2108ITA006279", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "PEMBROLIZUMAB" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "125514", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "UNK", "drugenddate": "2020", "drugenddateformat": "602", "drugindication": "NEOPLASM MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202001", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEMBROLIZUMAB." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PEMBROLIZUMAB" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "125514", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEMBROLIZUMAB." } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Immune-mediated arthritis", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 202002" } }, "primarysource": { "literaturereference": "CAMPOCHIARO C, FARINA N, TOMELLERI A, FERRARA R, LAZZARI C, DE LUCA G, ET AL.. TOCILIZUMAB FOR THE TREATMENT OF IMMUNE?RELATED ADVERSE EVENTS: A SYSTEMATIC LITERATURE REVIEW AND A MULTICENTRE CASE SERIES. EUROPEAN JOURNAL OF INTERNAL MEDICINE. 2021", "literaturereference_normalized": "tocilizumab for the treatment of immune related adverse events a systematic literature review and a multicentre case series", "qualification": "3", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20210825", "receivedate": "20210825", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19746058, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20211014" } ]

{ "abstract": "Anncaliia algerae myositis is a life-threatening, emerging microsporidiosis among immunocompromised hosts. We report a case of disseminated A algerae infection in a man previously treated with alemtuzumab. Due to failure of albendazole-based therapy, fumagillin was added as a novel approach to management, with a good clinical response and patient survival.", "affiliations": "Departments of Hematology-Oncology.;Pathology.;Departments of Hematology-Oncology.;Infectious Diseases and Medical Microbiology , Hôpital Maisonneuve-Rosemont, Université de Montréal , Canada.;Division of Parasitic Diseases and Malaria , Centers for Disease Control and Prevention , Atlanta, Georgia.;Infectious Diseases and Medical Microbiology , Hôpital Maisonneuve-Rosemont, Université de Montréal , Canada.", "authors": "Boileau|Mélissa|M|;Ferreira|José|J|;Ahmad|Imran|I|;Lavallée|Christian|C|;Qvarnstrom|Yvonne|Y|;Dufresne|Simon F|SF|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1093/ofid/ofw158", "fulltext": "\n==== Front\nOpen Forum Infect DisOpen Forum Infect DisofidofidsOpen Forum Infectious Diseases2328-8957Oxford University Press 10.1093/ofid/ofw158ofw158Brief ReportsSuccessful Treatment of Disseminated Anncaliia algerae Microsporidial Infection With Combination Fumagillin and Albendazole Boileau Mélissa 1Ferreira José 2Ahmad Imran 1Lavallée Christian 3Qvarnstrom Yvonne 4Dufresne Simon F. 31 Departments of Hematology-Oncology2 Pathology3 Infectious Diseases and Medical Microbiology, Hôpital Maisonneuve-Rosemont, Université de Montréal, Canada4 Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GeorgiaCorrespondence: S. F. Dufresne, Department of Infectious Diseases and Medical Microbiology, Hôpital Maisonneuve-Rosemont, 5415 Boul. de l'Assomption Montréal, QC H1T 2M4, Canada ([email protected]).9 2016 29 7 2016 3 3 ofw15827 4 2016 19 7 2016 © The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.2016This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact [email protected] algerae myositis is a life-threatening, emerging microsporidiosis among immunocompromised hosts. We report a case of disseminated A algerae infection in a man previously treated with alemtuzumab. Due to failure of albendazole-based therapy, fumagillin was added as a novel approach to management, with a good clinical response and patient survival.\n\nAnncaliia algeraefumagillinimmunocompromisedmicrosporidiosismyositis cover-dateSummer 2016\n==== Body\nA 49-year-old-man was referred to our center for refractory chronic lymphocytic leukemia (CLL) with TP53 deletion. He was treated for concurrent diabetes mellitus. Over the past years, he had received several chemotherapy regimens including chlorambucil, fludarabine, cyclophosphamide, and rituximab. He was treated with alemtuzumab and high-dose dexamethasone for 2 months. This regimen also failed; hence, ibrutinib was initiated as a bridge to allogeneic hematopoietic stem cell transplantation. Trimethoprim-sulfamethoxazole (TMP-SMX), posaconazole, and valacyclovir were given as primary prophylaxis from the introduction of alemtuzumab onwards.\n\nOne month after ibrutinib initiation, the patient was admitted at our hospital for febrile neutropenia. No infection was identified upon initial investigation. However, the patient complained of upper and lower limb pain that had started 2 months earlier. Creatine kinase (CK) was elevated over 3 times the upper limit of normal value (625 U/L). A lower extremity electromyogram was done and suggested diffuse acute myopathy. Magnetic resonance imaging (MRI) of the 4 limbs identified stigmata of polymyositis involving deltoids, triceps, and quadriceps. Myocardial involvement was also suspected because of elevated high-sensitivity cardiac troponin T (hs-cTnT). However, initial electrocardiogram and transthoracic echocardiogram were both normal. A biopsy of the vastus lateralis was performed, and light microscopy demonstrated a necrotizing myositis with numerous minute (2 micrometers), poorly stained intramuscular microorganisms. Immunohistochemistry with anti-Toxoplasma gondii antibodies was negative, as was T gondii polymerase chain reaction (PCR) on whole blood. Electron microscopy was consistent with microsporidial myositis [1, 2]. A fresh frozen muscle tissue sample was sent to the Centers for Disease Control Prevention ([CDC] Atlanta, GA), where species-level identification was performed by PCR and sequence analysis, which revealed Anncaliia algerae. Primers specific to that species (NALGF1-TCA CCA GAG CCT ATG TGC AGG; NALGR2- CTT CAT AAA AAC ATC CAT CTC) were used and amplified from 405-base pair segment of the small ribosomal subunit ribonucleic acid gene, which showed 100% identity with previous GenBank entries (accession numbers AY963290 and AF024656). Because toxoplasmosis was initially suspected, cerebral MRI was performed and revealed multiple parenchymal lesions with fine contrast enhancement and slight oedema. The A algerae-specific PCR was performed on the patient's cerebrospinal fluid (CSF) at the CDC and was positive. Urine and stools were negative for microsporidia by light microscopy (modified trichrome stain).\n\nThe patient was initially treated with a combination of albendazole (400 mg twice daily), pyrimethamine (50 mg once daily), and TMP-SMX (160–800 mg twice daily). Access to sulfadiazine was denied by Health Canada for this indication. After a few days without fever and diminished myalgia, the patient was discharged from the hospital with presumed effective therapy. The clinical and biological response to therapy is shown in Figure 1.\nFigure 1. Clinical and biological response to therapy and CD4 cell count. Creatine kinase (CK), high-sensitivity cardiac troponin T (hs-cTnT), body temperature (highest measure of each day, any body site) and CD4 cell count are shown according to time after diagnosis. Dashed lines represent the upper normal limit value for each parameter. Fumagillin treatment (20 mg 3 times daily) and maintenance (20 mg once daily) therapy periods are shown in full dark gray and checkered light gray, respectively. Albendazole was given concomitantly with fumagillin.\n\n\n\nAfter 25 days of the initial regimen, the patient was readmitted because of recurring fever and myalgia, with peripheral oedema and progressive weakness involving all limbs (Medical Research Council Scale for Muscle Strength grade 4 proximally and grade 3 distally). Levels of CK (>1000 U/L) and hs-cTnT (>1500 ng/L) had risen significantly. Worsened signs of polymyositis were observed on control MRI while a second muscular biopsy showed a higher parasitic burden. A second cardiac MRI was still normal. Because fumagillin is known to be effective against certain microsporidia species [3], a 2-week trial was attempted at full therapeutic dose (20 mg 3 times daily). Albendazole (400 mg twice daily) was maintained whereas pyrimethamine was discontinued. Prophylactic TMP-SMX was continued (80–400 mg once daily). Upon fumagillin initiation, significant improvement occurred: fever ceased, and the patient's muscular endurance and balance improved. Prompt CK normalization and a 60% reduction in hs-cTnT were also observed.\n\nUnfortunately, after a week of fumagillin discontinuation, fever recurred, muscular strength declined, and CK and hs-cTnT bounced back. In addition, the patient developed symptomatic congestive heart failure, and a cardiac MRI confirmed moderate biventricular dysfunction with a reduced left ventricular ejection fraction (LVEF) of 30%. A second 2-week trial of full dose fumagillin was initiated and again led to significant clinical and biological improvement. At that time, CD4+ T lymphocyte count was still extremely low (19 × 109/L); therefore, we decided to provide reduced-intensity fumagillin as maintenance therapy (20 mg twice daily for 4 days, then 20 mg once daily) until immune recovery. Hospitalization was complicated by central venous catheter infection (Pseudomonas aeruginosa) and nosocomial pneumonia that accounted for 2 additional episodes of fever (Figure 1).\n\nFumagillin and albendazole maintenance therapy was stopped after 290 days, because the patient's condition had improved significantly and the CD4+ T lymphocyte count had reached 200. Before fumagillin introduction, the patient was bedridden because of severe generalized myopathy; by the end of therapy, he was in a rehabilitation center and able to walk over 30 meters. A lower limb MRI confirmed an almost complete resolution of polymyositis stigmata. Creatine kinase normalized and hs-cTnT improved for approximately 8 months and stabilized approximately 90 ng/L. The LVEF remained at approximately 30%. Follow-up cerebral MRIs showed reduction in parenchymal lesions, with minimal residual abnormalities consistent with scars. To this date, 6 months after therapy was ended, the patient has shown no sign of relapse.\n\nDISCUSSION\nThe microsporidia A algerae, formerly called Nosema and Brachiola, was long known as an insect parasite, but it is now recognized as an emerging human pathogen. Anncaliia algerae has been reported to cause severe myositis in 5 patients under immunosuppressive treatment for rheumatoid arthritis and solid-organ transplantation [2, 4, 5]. Acquisition mode is not known, but the current lead hypothesis is that the infection could be transmitted through contact with spore-contaminated water inhabited by infected mosquitoes [6]. The optimal therapy of this infection is yet to be determined, and A algerae myositis was fatal in all but 1 case [2].\n\nWe described a case in a man heavily immunosuppressed due to treatment for CLL. The patient was from a rural area of Québec, Canada, and reported living in an area where bodies of water and mosquitoes are abundant. Of note, this is the first case of A algerae infection where central nervous system (CNS) and cardiac involvement could be substantiated along with skeletal muscles, although it was not proven by histopathology. Central nervous system infection was supported by positive PCR on CSF and cerebral MRI lesions, whereas cardiac infection was suggested by progressive congestive heart failure, cardiac MRI abnormalities, and high hs-cTnT, all of which subsided with antiparasitic therapy. It is interesting to note that both cardiac and CNS disorders had been suspected to be associated with A algerae infection in previous cases [2]. Immunosuppression of our patient was multifactorial, but it was mainly driven by a profound alemtuzumab-induced CD4+ T-cell lymphopenia. Unfortunately, this effect is not readily reversible, and yet reducing immunosuppression was thought to be a key factor in the management of the only surviving patient with A algerae microsporidial myositis [2]. Therefore, it was paramount to optimize antimicrobial therapy.\n\nAlbendazole is an antitubulin polymerization drug whose efficacy against A algerae is supported by genomic, in vitro, and clinical data. Anncaliia algerae β-tubulin gene sequence exhibits conserved regions associated with sensitivity to this drug among other microsporidia [7]. In cell culture, albendazole can attenuate A algerae infection and inhibit new spore production [7]. Moreover, the survival of the case described by Watts et al [2] may have been attributable to this drug. However, in other cases and this one, albendazole appeared to slow disease progression, but it seemed insufficient to control the infection.\n\nFumagillin, an antibiotic derived from Aspergillus fumigatus, has traditionally been used to treat microsporidiosis in honeybees [8]. In vitro and animal studies suggest that fumagillin and its derivative (TNP-470, ovalicin) are active against several microsporidia [9–11], probably through their irreversible inhibition of methionine aminopeptidase type 2 (MetAP2) [12]. In a randomized placebo-control trial, fumagillin was identified as an effective treatment for Enterocytozoon bieneusi in immunocompromised patients [3]. Direct data supporting fumagillin activity against A algerae is lacking, although this species was shown to harbor a MetAP2 gene homologous to that of various other microsporidia [13]. Based on these previous reports and the failure of initial therapy in our patient, we decided to attempt fumagillin, which was obtained from Sanofi (Paris, France) through Health Canada Special Access Program. Manifest improvement was observed, albeit a 14-day course was not long enough to control the disease. A second intensive phase followed by maintenance therapy until immune recovery and disease resolution was successful in this case. It is unlikely that immune reconstitution contributed significantly to control of infection during intensive fumagillin courses, because CD4 cell count was still extremely low at that point.\n\nThe chief undesirable effect of fumagillin is hematotoxicity, namely thrombocytopenia and granulocytopenia. To the best of our knowledge, this is the first patient treated with fumagillin for longer than 14 days. Our patient has received a cumulative dose of 7560 mg (378 tablets) over an 11-month period. While receiving a therapeutic dose (20 mg 3 times daily) and then a maintenance dose (20 mg one daily), the patient's lowest platelet count was 14 × 109/L and 50 × 109/L, respectively. However, because the patient was treated with low molecular weight heparin for a recent pulmonary embolism, he received platelet transfusions to keep his platelet count above 50 × 109/L. No clinically significant bleeding occurred, and, more importantly, after the first therapeutic attempt, the patient's platelet count normalized spontaneously. Transient neutropenia was observed concomitantly to P aeruginosa bacteremia. Aspartate transaminase and alanine transaminase increased up to twice the upper limit of normal value during treatment. Hematotoxicity remains an issue and requires careful follow up. For our patient, the benefit of fumagillin outweighed the risk, although we cannot accurately evaluate long-term adverse effects.\n\nCONCLUSIONS\nIn immunocompromised hosts, A algerae has emerged as a new human pathogen. The hallmark of systemic infection is diffuse myositis, which can be accompanied by myocardial and CNS involvement. This infection is characterized by a high fatality rate. This case indicates that fumagillin may be an effective addition to albendazole, particularly where there is significant host immunosuppression. A prolonged course may be necessary with careful surveillance of adverse events and meticulous weighing of risks and benefits.\n\nAcknowledgments\nWe thank Jean-Michel Molina and Matthew R. Watts for their valuable advice on the clinical management of this case. We are also grateful to Dr. Watts for his critical review of this manuscript.\n\nPotential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.\n==== Refs\nReferences\n1 Ramanan P , Pritt BS \nExtraintestinal microsporidiosis . J Clin Microbiol \n2014 ; 52 :3839 –44 .24829239 \n2 Watts MR , Chan RC , Cheong EY et al \nAnncaliia algerae microsporidial myositis . Emerg Infect Dis \n2014 ; 20 :185 –91 .24447398 \n3 Molina JM , Tourneur M , Sarfati C et al \nFumagillin treatment of intestinal microsporidiosis . N Engl J Med \n2002 ; 346 :1963 –9 .12075057 \n4 Coyle CM , Weiss LM , Rhodes LV IIIet al \nFatal myositis due to the microsporidian Brachiola algerae, a mosquito pathogen . N Engl J Med \n2004 ; 351 :42 –7 .15229306 \n5 Field AS , Paik JY , Stark D et al \nMyositis due to the microsporidian Anncaliia (Brachiola) algerae in a lung transplant recipient . Transpl Infect Dis \n2012 ; 14 :169 –76 .22385431 \n6 Cali A , Weiss LM , Takvorian PM \nA review of the development of two types of human skeletal muscle infections from microsporidia associated with pathology in invertebrates and cold-blooded vertebrates . Folia Parasitol (Praha) \n2005 ; 52 :51 –61 .16004364 \n7 Santiana M , Pau C , Takvorian PM , Cali A \nAnalysis of the beta-tubulin gene and morphological changes of the microsporidium Anncaliia algerae both suggest albendazole sensitivity . J Eukaryot Microbiol \n2015 ; 62 :60 –8 .25105446 \n8 Katznelson H , Jamieson CA \nControl of nosema disease of honeybees with fumagillin . Science \n1952 ; 115 :70 –1 .14913168 \n9 Didier PJ , Phillips JN , Kuebler DJ et al \nAntimicrosporidial activities of fumagillin, TNP-470, ovalicin, and ovalicin derivatives in vitro and in vivo . Antimicrob Agents Chemother \n2006 ; 50 :2146 –55 .16723577 \n10 Coyle C , Kent M , Tanowitz HB et al \nTNP-470 is an effective antimicrosporidial agent . J Infect Dis \n1998 ; 177 :515 –8 .9466552 \n11 Beauvais B , Sarfati C , Challier S , Derouin F \nIn vitro model to assess effect of antimicrobial agents on Encephalitozoon cuniculi . Antimicrob Agents Chemother \n1994 ; 38 :2440 –8 .7840584 \n12 Alvarado JJ , Nemkal A , Sauder JM et al \nStructure of a microsporidian methionine aminopeptidase type 2 complexed with fumagillin and TNP-470 . Mol Biochem Parasitol \n2009 ; 168 :158 –67 .19660503 \n13 Zhang H , Huang H , Cali A et al \nInvestigations into microsporidian methionine aminopeptidase type 2: a therapeutic target for microsporidiosis . Folia Parasitol (Praha) \n2005 ; 52 :182 –92 .16004378\n\n", "fulltext_license": "CC BY-NC-ND", "issn_linking": "2328-8957", "issue": "3(3)", "journal": "Open forum infectious diseases", "keywords": "Anncaliia algerae; fumagillin; immunocompromised; microsporidiosis; myositis", "medline_ta": "Open Forum Infect Dis", "mesh_terms": null, "nlm_unique_id": "101637045", "other_id": null, "pages": "ofw158", "pmc": null, "pmid": "27704013", "pubdate": "2016-09", "publication_types": "D016428:Journal Article", "references": "22385431;7840584;16723577;19660503;25105446;12075057;15229306;16004364;24829239;16004378;14913168;24447398;9466552", "title": "Successful Treatment of Disseminated Anncaliia algerae Microsporidial Infection With Combination Fumagillin and Albendazole.", "title_normalized": "successful treatment of disseminated anncaliia algerae microsporidial infection with combination fumagillin and albendazole" }

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SUCCESSFUL TREATMENT OF DISSEMINATED ANNCALIIA ALGERAE MICROSPORIDIAL INFECTION WITH COMBINATION FUMAGILLIN AND ALBENDAZOLE.. OPEN FORUM INFECTIOUS DISEASES. 2016?3(3)", "literaturereference_normalized": "successful treatment of disseminated anncaliia algerae microsporidial infection with combination fumagillin and albendazole", "qualification": "3", "reportercountry": "CA" }, "primarysourcecountry": "CA", "receiptdate": "20180611", "receivedate": "20180610", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14993304, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "CA-PFIZER INC-2017162130", "fulfillexpeditecriteria": "1", "occurcountry": "CA", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA REFRACTORY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IBRUTINIB" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", 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SUCCESSFUL TREATMENT OF DISSEMINATED ANNCALIIA ALGERAE MICROSPORIDIAL INFECTION WITH COMBINATION FUMAGILLIN AND ALBENDAZOLE. OPEN FORUM INFECTIOUS DISEASES. 2016?3(3):10.1093/OFID/OFW158", "literaturereference_normalized": "successful treatment of disseminated anncaliia algerae microsporidial infection with combination fumagillin and albendazole", "qualification": "1", "reportercountry": "CA" }, "primarysourcecountry": "CA", "receiptdate": "20200609", "receivedate": "20170419", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13457658, "safetyreportversion": 6, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20200713" }, { "companynumb": "CA-JNJFOC-20190209832", "fulfillexpeditecriteria": "1", "occurcountry": "CA", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "FUMAGILLIN" 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"drugtreatmentdurationunit": null, "medicinalproduct": "PYRIMETHAMINE" } ], "patientagegroup": "5", "patientonsetage": "49", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Febrile neutropenia", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pneumonia", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Polymyositis", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MELISSA B, JOSE F, IMRAN A, CHRISTIAN L, YVONNE Q, SIMON FD. SUCCESSFUL TREATMENT OF DISSEMINATED ANNCALIIA ALGERAE MICROSPORIDIAL INFECTION WITH COMBINATION FUMAGILLIN AND ALBENDAZOLE. OPEN FORUM INFECTIOUS DISEASES 29-JUL-2016?3 (ISSUE 3).", "literaturereference_normalized": "successful treatment of disseminated anncaliia algerae microsporidial infection with combination fumagillin and albendazole", "qualification": "3", "reportercountry": "CA" }, "primarysourcecountry": "CA", "receiptdate": "20190213", "receivedate": "20190213", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15956558, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20190417" }, { "companynumb": "CA-SA-2017SA058442", "fulfillexpeditecriteria": "1", "occurcountry": "CA", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "ALEMTUZUMAB" }, 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"CHLORAMBUCIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK,UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA REFRACTORY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CHLORAMBUCIL" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CHLORAMBUCIL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": 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"drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA REFRACTORY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALEMTUZUMAB" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "RITUXIMAB" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, 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"actiondrug": "6", "activesubstance": { "activesubstancename": "IBRUTINIB" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBRUTINIB" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "HIGH-DOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA REFRACTORY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE SALT NOT SPECIFIED" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "POSACONAZOLE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "POSACONAZOLE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "RITUXIMAB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK,UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA REFRACTORY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITUXIMAB." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VALACYCLOVIR HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VALACICLOVIR" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cardiac failure congestive", "reactionmeddraversionpt": "23.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "23.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Treatment failure", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Lymphopenia", "reactionmeddraversionpt": "23.0", "reactionoutcome": "3" }, { "reactionmeddrapt": "Microsporidia infection", "reactionmeddraversionpt": "23.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Myalgia", "reactionmeddraversionpt": "23.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Device related infection", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Myositis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Muscular weakness", "reactionmeddraversionpt": "23.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pneumonia", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Polymyositis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pseudomonas infection", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "BOILEAU M, FERREIRA J, AHMAD I, LAVALLEE C, QVARNSTROM Y, DUFRESNE SF.. SUCCESSFUL TREATMENT OF DISSEMINATED ANNCALIIA ALGERAE MICROSPORIDIAL INFECTION WITH COMBINATION FUMAGILLIN AND ALBENDAZOLE.. OPEN FORUM INFECTIOUS DISEASES. 2016?3(3):UNK", "literaturereference_normalized": "successful treatment of disseminated anncaliia algerae microsporidial infection with combination fumagillin and albendazole", "qualification": "1", "reportercountry": "CA" }, "primarysourcecountry": "CA", "receiptdate": "20200610", "receivedate": "20170407", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13414116, "safetyreportversion": 4, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20200713" }, { "companynumb": "CA-BAUSCH-BL-2017-009602", "fulfillexpeditecriteria": "1", "occurcountry": "CA", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "VALACYCLOVIR 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"drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "OVER THE PAST YEARS", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA REFRACTORY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUDARABINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ALEMTUZUMAB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, 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SUCCESSFUL TREATMENT OF DISSEMINATED ANNCALIIA ALGERAE MICROSPORIDIAL INFECTION WITH COMBINATION FUMAGILLIN AND ALBENDAZOLE. OPEN FORUM INFECTIOUS DISEASES. 2016?3(3):1-4. 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{ "abstract": "Gemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA).\n\n\n\nThis study evaluated the efficacy of eculizumab, a monoclonal antibody targeting the terminal complement pathway, in patients with gemcitabine-induced TMA (G-TMA). We conducted an observational, retrospective, multicenter study in 5 French centres, between 2011 and 2016.\n\n\n\nTwelve patients with a G-TMA treated by eculizumab were included. The main characteristics were acute renal failure (100%), including stage 3 acute kidney injury (AKI, 58%) and renal replacement therapy (17%), hypertension (92%) and diffuse oedema (83%). Eculizumab was started after a median of 15 days (range 4-44) following TMA diagnosis. A median of 4 injections of eculizumab was performed (range 2-22). Complete hematological remission was achieved in 10 patients (83%) and blood transfusion significantly decreased after only one injection of eculizumab (median of 3 packed red blood cells (range 0-10) before treatment vs 0 (range 0-1) after one injection, P < 0.001). Two patients recovered completely renal function (17%), and 8 achieved a partial remission (67%). Compared to a control group of G-TMA without use of eculizumab, renal outcome was more favourable. At the end of the follow up, median eGFR was 45 vs 33 ml/min/1.73m2 respectively in the eculizumab group and in the control group.\n\n\n\nThese results suggest that eculizumab is efficient on haemolysis and reduces transfusion requirement in G-TMA. Moreover, eculizumab may improve renal function recovery.", "affiliations": "Medical Intensive Care Unit, Rouen University Hospital, 37 boulevard Gambetta, 76031, Rouen Cedex, France.;French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France.;French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France.;French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France.;French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France.;French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France.;French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France.;Department of Nephrology, Georges Pompidou Hospital, APHP, Paris, France.;Department of Nephrology, Rouen University Hospital, Rouen, France.;Department of Pathology, Rouen University Hospital, Rouen, France.;French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France.;French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France.;French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France.;French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France.;Medical Intensive Care Unit, Rouen University Hospital, 37 boulevard Gambetta, 76031, Rouen Cedex, France. [email protected].", "authors": "Grall|Maximilien|M|;Daviet|Florence|F|;Chiche|Noémie Jourde|NJ|;Provot|François|F|;Presne|Claire|C|;Coindre|Jean-Philippe|JP|;Pouteil-Noble|Claire|C|;Karras|Alexandre|A|;Guerrot|Dominique|D|;François|Arnaud|A|;Benhamou|Ygal|Y|;Veyradier|Agnès|A|;Frémeaux-Bacchi|Véronique|V|;Coppo|Paul|P|;Grangé|Steven|S|", "chemical_list": null, "country": "England", "delete": false, "doi": "10.1186/s12882-021-02470-3", "fulltext": "\n==== Front\nBMC Nephrol\nBMC Nephrol\nBMC Nephrology\n1471-2369\nBioMed Central London\n\n2470\n10.1186/s12882-021-02470-3\nResearch\nEculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre\nGrall Maximilien 12\nDaviet Florence 32\nChiche Noémie Jourde 32\nProvot François 42\nPresne Claire 52\nCoindre Jean-Philippe 62\nPouteil-Noble Claire 72\nKarras Alexandre 8\nGuerrot Dominique 9\nFrançois Arnaud 10\nBenhamou Ygal 112\nVeyradier Agnès 122\nFrémeaux-Bacchi Véronique 132\nCoppo Paul 142\nGrangé Steven [email protected]\n\n12\n1 grid.41724.34 Medical Intensive Care Unit, Rouen University Hospital, 37 boulevard Gambetta, 76031 Rouen Cedex, France\n2 grid.412370.3 0000 0004 1937 1100 French TMA Reference Centre, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France\n3 grid.411535.7 0000 0004 0638 9491 Department of Nephrology, Conception University Hospital, APHM, Marseille, France\n4 grid.410463.4 0000 0004 0471 8845 Department of Nephrology, Lille University Hospital, Lille, France\n5 grid.134996.0 0000 0004 0593 702X Department of Nephrology, Amiens University Hospital, Amiens, France\n6 Department of Nephrology, Le Mans General Hospital, Le Mans, France\n7 Department of Nephrology, E. Herriot Hospital, Lyon I university, Lyon, France\n8 grid.50550.35 0000 0001 2175 4109 Department of Nephrology, Georges Pompidou Hospital, APHP, Paris, France\n9 grid.41724.34 Department of Nephrology, Rouen University Hospital, Rouen, France\n10 grid.41724.34 Department of Pathology, Rouen University Hospital, Rouen, France\n11 grid.41724.34 Department of Internal Medicine, Rouen University Hospital, Rouen, France\n12 grid.411296.9 0000 0000 9725 279X Department of Biological Hematology, Lariboisière University Hospital, APHP, Paris, France\n13 grid.50550.35 0000 0001 2175 4109 Department of immunology, Georges Pompidou Hospital, APHP, Paris, France\n14 grid.412370.3 0000 0004 1937 1100 Department of Hematology, Hopital Saint-Antoine, Sorbonne Université, AP-HP, Paris, France\n21 7 2021\n21 7 2021\n2021\n22 2677 2 2021\n1 7 2021\n© The Author(s) 2021\nhttps://creativecommons.org/licenses/by/4.0/ Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.\nBackground\n\nGemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA).\n\nMethods\n\nThis study evaluated the efficacy of eculizumab, a monoclonal antibody targeting the terminal complement pathway, in patients with gemcitabine-induced TMA (G-TMA). We conducted an observational, retrospective, multicenter study in 5 French centres, between 2011 and 2016.\n\nResults\n\nTwelve patients with a G-TMA treated by eculizumab were included. The main characteristics were acute renal failure (100%), including stage 3 acute kidney injury (AKI, 58%) and renal replacement therapy (17%), hypertension (92%) and diffuse oedema (83%). Eculizumab was started after a median of 15 days (range 4–44) following TMA diagnosis. A median of 4 injections of eculizumab was performed (range 2–22). Complete hematological remission was achieved in 10 patients (83%) and blood transfusion significantly decreased after only one injection of eculizumab (median of 3 packed red blood cells (range 0–10) before treatment vs 0 (range 0–1) after one injection, P < 0.001). Two patients recovered completely renal function (17%), and 8 achieved a partial remission (67%). Compared to a control group of G-TMA without use of eculizumab, renal outcome was more favourable. At the end of the follow up, median eGFR was 45 vs 33 ml/min/1.73m2 respectively in the eculizumab group and in the control group.\n\nConclusions\n\nThese results suggest that eculizumab is efficient on haemolysis and reduces transfusion requirement in G-TMA. Moreover, eculizumab may improve renal function recovery.\n\nSupplementary Information\n\nThe online version contains supplementary material available at 10.1186/s12882-021-02470-3.\n\nKeywords\n\nCoagulation, thrombotic disorders and therapies, Cancer and thrombosis\nEculizumab\nGemcitabine-induced thrombotic microangiopathy\nissue-copyright-statement© The Author(s) 2021\n==== Body\nKey points\n\nIn G-TMA, eculizumab is efficient in controlling the hematological disorders and may improve renal function recovery\n\nC5b9 deposits in kidney biopsies suggest the role of complement activation in gemcitabine-induced TMA\n\nBackground\n\nThrombotic microangiopathy (TMA) syndromes are characterized by a microangiopathic hemolytic anemia, peripheral thrombocytopenia, and organ injury of variable severity [1]. The principal subtypes of TMA are thrombotic thrombocytopenic purpura (TTP) mainly due to anti-ADAMTS13 autoantibodies and the hemolytic uremic syndrome (HUS) associated with shigatoxin-related endothelial toxicity (shiga-toxin related HUS) or with complement alternative pathway dysregulation (atypical HUS or aHUS). TMA may also result from drug exposure, the most usual agents being calcineurin inhibitors, quinine, antiplatelet agents as well as antineoplastic agents [2]. Gemcitabine is a pyrimidine antimetabolite used for the treatment of a wide range of malignancies. The reported incidence of gemcitabine-induced TMA (G-TMA) in the literature was initially low (0.015%) [3] but but a rising number of cases have since been documented with the increasing use of gemcitabine [4–7].\n\nBeyond permanent discontinuation of gemcitabine and supportive care, the optimal management of G-TMA is not well codified [5, 8]. As opposed to TTP, G-TMA generally responds poorly to therapeutic plasma exchange (TPE) and prognosis is dismal [9]. Although there is no complement alternative pathway-related abnormalities described, the severe renal injury and normal ADAMTS13 are reminiscent of HUS, in which complement blockade is remarkably efficient [10]. Single reports suggested the efficacy of eculizumab in G-TMA [11], a monoclonal antibody directed against the complement protein C5 that has been approved for treatment of atypical HUS. In this context, the present study evaluated the efficacy of eculizumab in a retrospective series of patients with G-TMA.\n\nMethods\n\nStudy design\n\nWe conducted an observational, retrospective, multicenter study including all patients with G-TMA treated by eculizumab in 5 French centres, between 2011 and 2016.\n\nPatients\n\nPatients who were included in the study met the following criteria: evidence of microangiopathic hemolytic anemia, including schistocytes on peripheral blood smear, thrombocytopenia (< 150 G/L), increased lactate dehydrogenase levels (> Upper limit of normal), low serum haptoglobin < normal and/or renal TMA proven by kidney biopsy. Only one of these criteria could be missing. The diagnosis was retained by the team which took charge of the patient with discontinuation of treatment with gemcitabine. Patients with a TMA attributed to an uncontrolled cancer, as defined by erythroblastosis, metastatic bone marrow infiltration, impaired general condition, and low-cumulative dose gemcitabine (< 5000 mg/m2) were excluded [11–13]. Patients treated with another chemotherapy concomitantly with gemcitabine were excluded. Patients with a positive shiga-toxin or ADAMTS13 activity < 10% were also excluded.\n\nPatients were treated with eculizumab according to the regimen previously reported [14]. It consisted generally in 4 weekly infusions 900 mg IV. In responders, a maintenance treatment was started every 2 weeks at week 5, 1200 mg. The number of infusions was left at the discretion of the practitioner.\n\nHematological and renal responses were evaluated, based on data that were systematically extracted from the clinical record. Hematological response was defined by normalization of hematologic values (a normal platelet count and lactate dehydrogenase level) as previously described [14]. The transfusion needs were calculated over a period going from the admission of the patient to the end of the treatment with eculizumab. Renal response was considered as complete if serum creatinine level returned to baseline and as partial if serum creatinine level decreased by 15% or more.\n\nAcute renal injury (AKI) was assessed according to KDIGO classification 2012. To make possible the comparison between the two groups, we chose to use the CKD-EPI formula for the estimation of the eGFR (glomerular filtration rate), despite we are aware of the limits in the context of AKI. The eGFR of dialysed patients was estimated at 0 ml/min.\n\nWe compared patients with G-TMA treated with eculizumab with a control cohort of patients who did not receive eculizumab treatment. Using the French national network, 14 patients were selected using criteria of G-TMA described above without eculizumab therapy. Patients were matched by age and baseline renal function.\n\nThis study was approved by the institutional review board of Rouen University Hospital in accordance with the Declaration of Helsinki, and the French Data Protection Authority (“Commission Nationale Informatique et Libertés,” CNIL, authorization n°911,539, and “Comité consultatif sur le traitement de l’information en matière de recherche dans le domaine de la santé,” CCTIRS, authorization n°11.537, Paris, France).\n\nStatistical methods\n\nMedian with range and percentage (%) were respectively determined for continuous and categorical variables. Differences between groups were assessed by the chi-square test or Fisher’s exact test for categorical variables and by the Mann–Whitney U test for continuous variables [15].\n\nResults\n\nTwelve patients with a G-TMA treated by eculizumab were included (10 women, 2 men). None had a past history of chronic renal failure. Gemcitabine was prescribed for ovarian (n = 5, 41.7%), pancreatic (n = 4, 33.3%), pulmonary (n = 2, 16.7%) or uterine (n = 1, 8.3%) cancer. TMA occurred after a median of 6 months (range 1.7–16) after initiation of gemcitabine and a median cumulative dose of 31.2 g (range, 9.0–48.0) (Table 1). The main characteristics were microangiopathic hemolytic anemia (100%), thrombocytopenia (92%), acute renal failure (100%), including stage 3 acute kidney injury (AKI, 58%), and renal replacement therapy (17%), hypertension (92%) and diffuse oedema (83%). The median maximum serum creatinine level was 21 mg/l (range, 10–76). Quantitative analysis of the complement alternative pathway (CFH, CFI, C3, C1 inhibitor, CD46/MCP and anti-factor H antibodies) was available in 9 patients (75%), and revealed no factor deficiency (Supplemental data). Screening for genetic mutation was performed for one patient and was negative (Genes assessed were factor H, factor I, factor B, MCP, C3 and thrombomodulin). Bone marrow aspiration was realized in 4 patients with no evidence of metastatic infiltration. Table 1 Clinical features of patients in the eculizumab group\n\nPatient\tAge (years old)\tType of cancer\tCumulative dose of gemcitabine (mg)\tTime to eculizumab initiation (days) after TMA / Number of injection\tStaging of AKI\tHemoglobin level (g/dl)\tPlatelets count (G/l)\tLDH ratio (x normal)\tSerum Creatinine level at diagnosis (mg/l)\tHematological response\tRenal response\tReduction of creatinine level at the end of the follow-up (mg/l)\tOutcome / Time to death or time of last follow-up for still alive patients (months)\t\n1\t36\tOvarian, M+\t23,760\t7 d / 4\t2\t9.3\t76\t1.8\t18.0\tYes\tPartial\t2.9\tDeceased / 9 m\t\n2\t64\tOvarian, M+\t16,300\t7 d / 3\t3, RRT\t6.9\t23\t2.5\t28.0\tNo\tNo\t0\tDeceased / 1 m\t\n3\t54\tPancreatic, M+\t31,000\t44 d / 22\t2\t8.5\t27\t2.2\t14.3\tYes\tPartial\t2.5\tAlive / 47 m\t\n4\t69\tPancreatic, M+\t9040\t27 d / 3\t3, RRT\t7.3\t11\t2.4\t18.0\tNo\tNo\t0\tDeceased / 2 m\t\n5\t64\tOvarian, NA\t48,000\t13 d / 7\t2\t9.7\t130\t2.2\t22.5\tYes\tPartial\t7.1\tDeceased / 13 m\t\n6\t68\tPancreatic, M-\t30,000\t34 d / 14\t3\t7.9\t13\t4.6\t17.1\tYes\tComplete\t10.6\tDeceased / 10 m\t\n7\t59\tPulmonary, M+\t31,200\t6 d / 5\t3\t11.0\t137\t1.5\t31\tYes\tPartial\t6.9\tAlive / 14 m\t\n8\t57\tPulmonary, M+\t42,500\t26 d / 4\t3\t7.6\t150\t1.5\t76\tYes\tPartial\t16\tDeceased / 3 m\t\n9\t52\tUterine, M+\t47,000\t4 d / 2\t3\t8.7\t48\t2.2\t70\tYes\tPartial\t47\tAlive / 5 m\t\n10\t50\tPancreatic, M+\t15,000\t19 d / 2\t1\t8.0\t139\t2.2\t10.2\tYes\tComplete\t3\tAlive / 5 m\t\n11\t56\tOvarian, M+\t38,000\t18 d / 3\t3\t7.3\t144\t3.7\t24\tYes\tPartial\t10\tAlive / 4 m\t\n12\t55\tOvarian, M+\t32,000\t7 d / 4\t3\t8.1\t122\t1.8\t64\tYes\tPartial\t29\tAlive / 6 m\t\nTMA Thrombotic microangiopathy, AKI Acute kidney injury (AKI was assessed according to KDIGO classification 2012), LDH Lactate, dehydrogenase, RRT Renal replacement therapy, M- No metastatic, M+ Metastatic, NA Data not available\n\nRenal TMA was proven by kidney biopsy in 3 cases. We compared our patients with 4 patients who had a kidney biopsy for glomerular diseases (minimal change disease was used as a comparator because in this pathology there are usually no deposits of complement on the renal biopsy). By immunofluorescence, we found deposits of the membrane attack complex C5b9 along the glomerular and tubular membrane and also in the capillary wall in our patients as compared to control patients, suggesting the activation of complement cascade in this form of TMA (Fig. 1). Fig. 1 Kidney biopsy in gemcitabine-induced TMA. By immunofluorescence, kidney biopsy of G-TMA patients (A) showed deposits of membrane attack complex C5b9 in the glomerular and tubular membrane and also in the capillary walls, as compared to control patients with glomerular disease (minimal change disease) (B)\n\nAll patients had their gemcitabine treatment stopped. First-line therapeutic plasma exchange (TPE) was performed in 5 patients (42%), with a median of 7 sessions (range 4–9) without significant benefit on hemolysis or renal function recovery. Eculizumab was started after a median delay of 15 days (range 4–44) following TMA diagnosis. A median of 4 injections (900 mg/injection, total 3600 mg) of eculizumab was administered (range 2–22). Of note, only three patients had received more than four injections of eculizumab. Hematological response was obtained in 10 patients (83%) and blood transfusion significantly decreased after the first infusion of eculizumab (median of 3 packed red blood cells (range 0–10) before treatment vs 0 (range 0–1) after one injection, p < 0.001) (Fig. 2). Two patients recovered renal function completely (17%), and 8 achieved a partial renal response (67%), with a median reduction of 8.5 mg/l of maximum creatinine level (range 2.5–47) (Table 1). After a median follow-up of 13 months, seven patients (58%) had persistent chronic renal failure with an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73m2. No treatment-associated adverse event was reported. Especially, no meningococcal infection was recorded during follow-up. No exacerbation or relapse of TMA were recorded after eculizumab discontinuation. Six patients (50%) died during follow-up, as an indirect complication of TMA with hemorrhagic shock (1 case) despite eculizumab treatment, or to cancer progression after a median of 9 months (range 2–13) following eculizumab initiation (5 cases). Six patients (50%) were in complete hematological response and at least partial renal response of TMA after eculizumab discontinuation allowing a switch to another antineoplastic agent (Table 1). Fig. 2 Comparison of packed red blood cell transfusion before and after eculizumab therapy. Quantitative values are expressed as median with range\n\nWe compared patients with G-TMA treated with eculizumab with a control cohort of 14 patients who didn’t receive eculizumab treatment (Table 2). TPE were performed in 8 of them. Median baseline eGFR was comparable in the 2 groups, 95 (47–147) ml/min/1.73m2 in the control group and 106 (59–132) ml/min/1.73m2 in the eculizumab group. Compared to the control cohort, patients with G-TMA treated by eculizumab had a better renal outcome (Fig. 3). 83% of patients in eculizumab group had improvement of their renal function versus 64% in control group, and median eGFR was 45 (0–119) vs 33 (0–66) ml/min/1.73m2 respectively at the end of the follow up (Table 3). Of note, 2 patients (16%) still had end stage renal failure in the eculizumab group versus 3 patients (21%) in the control group. Table 2 Characteristics of patients in the control group\n\nPatient\tAge (years old)\tType of cancer\tStaging of AKI\tHemoglobin level (g/dl)\tPlatelets count (G/l)\tLDH ratio (x normal)\tSerum Creatinine level at diagnosis (mg/l)\tHematological response\tRenal response\tOutcome / Time to death or time of last follow-up for still alive patients (months)\t\n1\t56\tPancreatic, NA\t3\t12.3\t79\t1.9\t44\tYes\tPartial\tDeceased / 72 m\t\n2\t33\tOvarian, M+\t2\t6.2\t58\t1.4\t18\tYes\tPartial\tDeceased / 10 m\t\n3\t80\tPancreatic, M+\t2\t7.3\t81\t1.7\t10\tYes\tComplete\tDeceased / 14 m\t\n4\t65\tPancreatic, M+\t3\t9.7\t70\t1.2\t35\tYes\tPartial\tDeceased / 18 m\t\n5\t74\tPancreatic, M+\t3, RRT\t9.7\t34\t2.9\t35\tNo\tNo\tAlive / 3 m\t\n6\t66\tPulmonary, NA\t3, RRT\t4\t146\t3.9\t94\tYes\tNo\tDeceased / 1 m\t\n7\t59\tPancreatic, M+\t3\t6.9\t85\t1.5\t41\tYes\tPartial\tAlive / 3 m\t\n8\t55\tPancreatic, M-\t3\t8.7\t100\t3.0\t41\tYes\tNo\tDeceased / 2 m\t\n9\t78\tPancreatic, M-\t3\t7.2\t450\t1.0\t29\tYes\tComplete\tAlive / 24 m\t\n10\t56\tBreast, M+\t2\t7.5\t61\t1.0\t17\tYes\tComplete\tAlive / 2 m\t\n11\t58\tHepatic, NA\t3, RRT\t10.4\t42\t6.5\t32.4\tYes\tNo\tDeceased / 8 m\t\n12\t60\tPancreatic, M+\t3\t8.7\t202\t2.5\t23\tYes\tNo\tDeceased / 7 m\t\n13\t52\tHepatic, M+\t3\t9.1\t96\t5.8\t50\tYes\tPartial\tDeceased / 10 m\t\n14\t73\tPancreatic, NA\t3\t9.9\t430\t3.1\t29\tYes\tPartial\tDeceased / 14 m\t\nTMA Thrombotic microangiopathy, AKI Acute kidney injury (AKI was assessed according to KDIGO classification 2012), LDH Lactate dehydrogenase, RRT Renal replacement therapy, M- No metastatic, M+ Metastatic, NA Data not available\n\nFig. 3 Evolution of renal function as a function of time in the eculizumab group and in the control group. Values expressed as mean and standard deviations\n\nTable 3 Outcome of patients\n\n\tEculizumab group\nN = 12 (%)\tControl group\nN = 14 (%)\t\nRenal response\t10 (83)\t9 (64)\t\nPartial\t8 (66)\t6 (43)\t\ncomplete\t2 (17)\t3 (21)\t\neGFR at onset (ml/min/1.73m2)\t19 (0–76)\t12 (0–31)\t\neGFR at the end of follow up\t45 (0–119)\t33 (0–66)\t\neGFR Estimated glomerular filtration rate. Quantitative values are expressed as median with range\n\nDiscussion\n\nWe report here the largest case series of G-TMA treated by eculizumab. In our patients, we found that the transient use of eculizumab was efficient in controlling the hematologic disorders, by reducing significantly transfusion needs and by correcting thrombocytopenia. Remarkably, hematologic improvement was usually observed just after the two first injections of eculizumab, which strongly suggests a therapeutic action of eculizumab. However, we cannot rule out the hypothesis that the decrease in transfusion requirements was linked to the elimination of gemcitabine after discontinuation of this treatment. As in atypical HUS [14, 16], the use of eculizumab in G-TMA may improve renal function recovery. Indeed, 83% of patients in our study had a complete or partial renal remission within 2 to 4 weeks after complement blockade, suggesting again that eculizumab was efficient in controlling TMA. This two-step response with first a rapid improvement in cytopenias after the initiation of eculizumab followed by a more progressive renal improvement is reminiscent of the schedule of response observed in atypical HUS [14].\n\nThe pathophysiology of G-TMA is not well established. However, our data show C5b9 deposits in kidney biopsies supporting the hypothesis that the pathophysiology of G-TMA is at least partially related to complement activation, which may result from a direct endothelial toxicity of the drug. This transient complement activation seems to have no genetic background. A recent work has not revealed any pathogenic variant involved in the regulation of the alternate pathway of complement [17]. There still remains little evidence for quantitative analyses of complement proteins as valid biomarkers.\n\nReports of patients with G-TMA treated by eculizumab are rare [18–27]. To our knowledge, only 13 cases have been reported in literature, and a similar good outcome was observed. However, these results must be interpreted with caution due to publication bias. As opposed to the hematological response, renal remission is generally observed later and may occur after several weeks because of the process of endothelial healing. One could hypothesize that, similar to atypical HUS, an earlier initiation of eculizumab could allow a greater improvement in renal function recovery [14]. Moreover, there has been no exacerbation or relapse of TMA following eculizumab discontinuation, suggesting that a limited number of infusions may be sufficient to control the TMA process, in association with definitive gemcitabine withdrawal.\n\nAlthough eculizumab raises cost concerns, these considerations should be weighted against a decreased burden of care, including lower transfusion needs, reduced needs for TPE, and possibly less renal replacement therapy with reduced length of hospitalisation in the intensive care unit during the early stages of AKI. As a result, this strategy could allow a significant improvement in patients’ quality of life, particularly when the underlying malignancy has a favourable prognosis.\n\nOur results have the usual limitations of those of a retrospective study, in particular concerning the probable presence of confounding factors; moreover, the number of patients is relatively limited. Therefore, further larger controlled studies are needed to definitely confirm our results, which will be very difficult given the rarity of the disease. These studies should also address whether gemcitabine should be considered contraindicated after resolution of G-TMA. Only one patient had a genetic evaluation of the alternative complement pathway. Nevertheless, in France, a quantitative analysis of the complement is sometimes carried out in this context of TMAs secondary to gemcitabine. If this is abnormal, it is completed by the genetic evaluation. We now know that there is no pathogenic variant found in secondary TMAs in the vast majority of patients [17]. On the other hand, our study rather suggests a transient activation of the alternate pathway of complement. Finally, there were analyzable kidney biopsies in just 3 patients, so it is difficult to draw broad conclusions about the findings in G-TMA.\n\nAknowledgements\n\nThe members of the Reference Centre for Thrombotic Microangiopathies (CNR-MAT) are: Azoulay Elie (Service de Réanimation Médicale, Hôpital Saint-Louis, Paris); Barbay Virginie (Laboratoire d’Hématologie, CHU Charles Nicolle, Rouen); Benhamou Ygal (Service de Médecine Interne, CHU Charles Nicolle, Rouen); Bordessoule Dominique (Service d’Hématologie, Hôpital Dupuytren, Limoges); Charasse Christophe (Service de Néphrologie, Centre Hospitalier de Saint-Brieuc); Chauveau Dominique (Département de Néphrologie et Transplantation d’Organes, CHU Rangueil, Toulouse); Choukroun Gabriel (Service de Néphrologie, Hôpital Sud, Amiens); Coindre Jean-Philippe (Service de Néphrologie, CH Le Mans); Coppo Paul (Service d’Hématologie, Hôpital Saint-Antoine, Paris); Corre Elise (Service d’Hématologie, Hôpital Saint-Antoine, Paris); Delmas Yahsou (Service de Néphrologie, Hôpital Pellegrin, Bordeaux); Deschenes Georges (Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris); Devidas Alain (Service d’Hématologie, Hôpital Sud-Francilien, Corbeil-Essonnes); Fain Olivier (Service de Médecine Interne, Hôpital Saint-Antoine, Paris); Frémeaux-Bacchi Véronique (Laboratoire d’Immunologie, Hôpital Européen Georges Pompidou, Paris); Galicier Lionel (Service d’Immunopathologie, Hôpital Saint-Louis, Paris); Grange Steven (Service de Réanimation, CHU Charles Nicolle, Rouen); Guidet Bertrand (Service de Réanimation Médicale, Hôpital Saint-Antoine, Paris); Halimi Jean-Michel (Service de Néphrologie Pédiatrique, Hôpital Bretonneau, Tours); Hamidou Mohamed (Service de Médecine Interne, Hôtel-Dieu, Nantes); Herbrecht Raoul (service d’Oncologie et d’Hématologie, Hôpital de Hautepierre, Strasbourg); Jacobs Frédéric (Service de Réanimation Médicale, Hôpital Antoine Béclère, Clamart); Joly Bérangère (Service d’Hématologie Biologique, Hôpital Lariboisière, Paris); Kanouni Tarik (Unité d’Hémaphrèse, Service d’Hématologie, CHU de Montpellier); Lautrette Alexandre (Service de Néphrologie Pédiatrique B, Hôpital Hôtel-Dieu, Clermont-Ferrand); Le Guern Véronique (Unité d’Hémaphérèse, Service de Médecine Interne, Hôpital Cochin, Paris); Loirat Chantal (Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris); Mira Jean-Paul (Service de Réanimation Médicale, Hôpital Cochin); Moulin Bruno (Service de Néphrologie, Hôpital Civil, Strasbourg); Mousson Christiane (Service de Néphrologie, CHU de Dijon); Ojeda Uribe Mario (Service d’Hématologie, Hôpital Emile Muller, Mulhouse); Ouchenir Abdelkader (Service de Réanimation, Hôpital Louis Pasteur, Le Coudray); Parquet Nathalie (Unité de Clinique Transfusionnelle, Hôpital Cochin, Paris); Peltier Julie (Urgences Néphrologiques et Transplantation Rénale, Hôpital Tenon, Paris); Perez Pierre (Service de Réanimation polyvalente, CHU de Nancy); Poullin Pascale (Service d’hémaphérèse et d’autotransfusion, Hôpital la Conception, Marseille); Pouteil-Noble Claire (Service de Néphrologie, CHU Lyon-Sud, Lyon); Presne Claire (Service de Néphrologie, Hôpital Nord, Amiens); Provôt François (Service de Néphrologie, Hôpital Albert Calmette, Lille); Ribeil Jean-Antoine (Service de Thérapie Cellulaire, Hôpital Necker-Enfants Malades, Paris); Rondeau Eric (Urgences Néphrologiques et Transplantation Rénale, Hôpital Tenon, Paris); Saheb Samir (Unité d’Hémaphérèse, Hôpital la Pitié-Salpétrière, Paris); Schlemmer Benoît (Service de Réanimation Médicale, Hôpital Saint-Louis, Paris); Seguin Amélie (Service de Réanimation Médicale, CHU de Caen); Stépanian Alain (Service d’Hématologie Biologique, Hôpital Lariboisière, Paris); Vernant Jean-Paul (Service d’Hématologie, Hôpital la Pitié-Salpétrière, Paris); Veyradier Agnès (Service d’Hématologie Biologique, Hôpital Lariboisière, Paris); Vigneau Cécile (Service de Néphrologie, Hôpital Pontchaillou, Rennes); Wynckel Alain (Service de Néphrologie, Hôpital Maison Blanche, Reims); Zunic Patricia (Service d’Hématologie, Groupe Hospitalier Sud-Réunion, la Réunion).\n\nSupplementary Information\n\nAdditional file 1.\n\nAbbreviations\n\nAKI Acute Kidney Injury\n\neGFR Estimated Glomerular Filtration Rate\n\nG-TMA Gemcitabine-induced Thrombotic Microangiopathy\n\nHUS Hemolytic Uremic Syndrome\n\nLDH Lactate Dehydrogenase\n\nRRT Renal Replacement Therapy\n\nTMA Thrombotic Microangiopathy\n\nTPE Therapeutic Plasma Exchange\n\nTTP Thrombocytopenic Thrombotic Purpura\n\nAuthors’ contributions\n\nMG and SG performed and design the research, and analysed the data. MG, SG and PC wrote the paper. All authors provided cases and have read and approved the final version of the manuscript.\n\nFunding\n\nNone.\n\nAvailability of data and materials\n\nThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\n\nDeclarations\n\nEthics approval and consent for participate\n\nAll patients and/or parents/guardians provided written informed consent for entry into the current study. This study was approved by our institutional review board (Rouen University Hospital) in accordance with the Declaration of Helsinki, and the French Data Protection Authority (“Commission Nationale Informatique et Libertés,” CNIL, authorization n°911,539, and “Comité consultatif sur le traitement de l’information en matière de recherche dans le domaine de la santé,” CCTIRS, authorization n°11.537, Paris, France).\n\nConsent for publication\n\nNot applicable.\n\nCompeting interests\n\nPC, SG and VFB are members of the Clinical Advisory Board for Alexion. PC and YG are members of the Clinical Advisory Board for Sanofi and Octapharma. PC received financings from Roche Pharma. SG received grants from Alexion.\n\nPublisher’s Note\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n==== Refs\nReferences\n\n1. Kremer Hovinga JA Coppo P Lämmle B Thrombotic thrombocytopenic purpura Nat Rev Dis Primer 2017 3 17020 10.1038/nrdp.2017.20\n2. Al-Nouri ZL Reese JA Terrell DR Vesely SK George JN Drug-induced thrombotic microangiopathy: a systematic review of published reports Blood. 2015 125 4 616 618 10.1182/blood-2014-11-611335 25414441\n3. Casper ES Green MR Kelsen DP Phase II trial of gemcitabine (2,2′-difluorodeoxycytidine) in patients with adenocarcinoma of the pancreas Investig New Drugs 1994 12 1 29 34 10.1007/BF00873232 7960602\n4. Fung MC Storniolo AM Nguyen B A review of hemolytic uremic syndrome in patients treated with gemcitabine therapy Cancer. 1999 85 9 2023 2032 10.1002/(SICI)1097-0142(19990501)85:9<2023::AID-CNCR21>3.0.CO;2-2 10223245\n5. Flombaum CD Mouradian JA Casper ES Erlandson RA Benedetti F Thrombotic microangiopathy as a complication of long-term therapy with gemcitabine Am J Kidney Dis 1999 33 3 555 562 10.1016/S0272-6386(99)70194-0 10070921\n6. Glezerman I Kris MG Miller V Seshan S Flombaum CD Gemcitabine nephrotoxicity and hemolytic uremic syndrome: report of 29 cases from a single institution Clin Nephrol 2009 71 2 130 139 10.5414/CNP71130 19203505\n7. Izzedine H Isnard-Bagnis C Launay-Vacher V Gemcitabine-induced thrombotic microangiopathy: a systematic review Nephrol Dial Transplant 2006 21 11 3038 3045 10.1093/ndt/gfl507 16968717\n8. Zupancic M Shah PC Shah-Khan F Gemcitabine-associated thrombotic thrombocytopenic purpura Lancet Oncol 2007 8 7 634 641 10.1016/S1470-2045(07)70203-6 17613425\n9. Dasanu CA Gemcitabine: vascular toxicity and prothrombotic potential Expert Opin Drug Saf 2008 7 6 703 716 10.1517/14740330802374262 18983217\n10. Gore EM Jones BS Marques MB Is therapeutic plasma exchange indicated for patients with gemcitabine-induced hemolytic uremic syndrome? J Clin Apher 2009 24 5 209 214 10.1002/jca.20213 19816959\n11. Francis KK Kalyanam N Terrell DR Vesely SK George JN Disseminated malignancy misdiagnosed as thrombotic thrombocytopenic Purpura: a report of 10 patients and a systematic review of published cases Oncologist 2007 12 1 11 19 10.1634/theoncologist.12-1-11\n12. Lechner K Obermeier HL Cancer-related microangiopathic hemolytic anemia: clinical and laboratory features in 168 reported cases Medicine (Baltimore) 2012 91 4 195 205 10.1097/MD.0b013e3182603598 22732949\n13. Oberic L Buffet M Schwarzinger M Cancer awareness in atypical thrombotic microangiopathies Oncologist 2009 14 8 769 779 10.1634/theoncologist.2009-0067 19684072\n14. Legendre CM Licht C Muus P Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome N Engl J Med 2013 368 23 2169 2181 10.1056/NEJMoa1208981 23738544\n15. Grall M Provôt F Coindre JP Efficacy of Eculizumab in gemcitabine-induced thrombotic Microangiopathy: experience of the French thrombotic Microangiopathies reference center Blood. 2016 128 22 136 10.1182/blood.V128.22.136.136\n16. Fakhouri F Zuber J Frémeaux-Bacchi V Loirat C Haemolytic uraemic syndrome Lancet. 2017 390 10095 681 696 10.1016/S0140-6736(17)30062-4 28242109\n17. Le Clech A Simon-Tillaux N Provôt F Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors Kidney Int 2019 95 1443 10.1016/j.kint.2019.01.023 30982675\n18. Al Ustwani O Lohr J Dy G Eculizumab therapy for gemcitabine induced hemolytic uremic syndrome: case series and concise review J Gastrointest Oncol 2014 5 1 E30 E33 24490050\n19. Starck M, Wendtner C-M. Use of eculizumab in refractory gemcitabine-induced thrombotic microangiopathy. Br J Haematol. 2013.\n20. Rogier T Gerfaud-Valentin M Pouteil-Noble C Clinical efficacy of eculizumab as treatment of gemcitabine-induced thrombotic microangiopathy: a case report Rev Med Interne Fondee Par Soc Natl Francaise Med Interne 2016 37 701\n21. Turner JL Reardon J Bekaii-Saab T Cataland SR Arango MJ Gemcitabine-Associated Thrombotic Microangiopathy: Response to Complement Inhibition and Reinitiation of Gemcitabine Clin Colorectal Cancer 2016 1 30178\n22. López Rubio ME Rodado Martínez R Illescas ML Gemcitabine-induced hemolytic-uremic syndrome treated with eculizumab or plasmapheresis: two case reports Clin Nephrol 2017 87 2 100 106 10.5414/CN108838 27879189\n23. Martin K Roberts V Chong G Eculizumab therapy in gemcitabine-induced thrombotic microangiopathy in a renal transplant recipient Oxf Med Case Rep 2019 2019 6 omz048 10.1093/omcr/omz048\n24. Krishnappa V Gupta M Shah H The use of eculizumab in gemcitabine induced thrombotic microangiopathy BMC Nephrol 2018 19 1 9 10.1186/s12882-018-0812-x 29329518\n25. Gosain R Gill A Fuqua J Gemcitabine and carfilzomib induced thrombotic microangiopathy: eculizumab as a life-saving treatment Clin Case Rep 2017 5 12 1926 1930 10.1002/ccr3.1214 29225827\n26. Facchini L Lucchesi M Stival A Role of eculizumab in a pediatric refractory gemcitabine-induced thrombotic microangiopathy: a case report J Med Case Rep 2017 11 1 209 10.1186/s13256-017-1373-5 28747219\n27. Daviet F Rouby F Poullin P Thrombotic microangiopathy associated with gemcitabine use: presentation and outcome in a national French retrospective cohort Br J Clin Pharmacol 2019 85 403 412 10.1111/bcp.13808 30394581\n\n", "fulltext_license": "CC BY", "issn_linking": "1471-2369", "issue": "22(1)", "journal": "BMC nephrology", "keywords": "Coagulation, thrombotic disorders and therapies, Cancer and thrombosis; Eculizumab; Gemcitabine-induced thrombotic microangiopathy", "medline_ta": "BMC Nephrol", "mesh_terms": null, "nlm_unique_id": "100967793", "other_id": null, "pages": "267", "pmc": null, "pmid": "34284729", "pubdate": "2021-07-21", "publication_types": "D016428:Journal Article", "references": "7960602;31214360;19684072;29329518;22732949;28382967;30394581;10223245;10070921;24666021;23738544;16968717;24490050;28242109;17613425;19816959;29225827;28747219;26833144;27879189;18983217;19203505;27743743;17227897;25414441;30982675", "title": "Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre.", "title_normalized": "eculizumab in gemcitabine induced thrombotic microangiopathy experience of the french thrombotic microangiopathies reference centre" }

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Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. BMC Nephrol. 2021;22(1):267 (1-8)", "literaturereference_normalized": "eculizumab in gemcitabine induced thrombotic microangiopathy experience of the french thrombotic microangiopathies reference centre", "qualification": "3", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20220623", "receivedate": "20220623", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 20996648, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220721" }, { "companynumb": "FR-SUN PHARMACEUTICAL INDUSTRIES LTD-2022RR-341749", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "GEMCITABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "78433", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Breast cancer", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE" } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Thrombotic microangiopathy", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Grall M, Daviet F, Chiche NJ, Provot F, Presne C, Coindre J-P, et al. Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. BMC Nephrol. 2021;22(1):267 (1-8)", "literaturereference_normalized": "eculizumab in gemcitabine induced thrombotic microangiopathy experience of the french thrombotic microangiopathies reference centre", "qualification": "3", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20220623", "receivedate": "20220623", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 20996816, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220721" }, { "companynumb": "FR-SUN PHARMACEUTICAL INDUSTRIES LTD-2022RR-341752", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "GEMCITABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "78433", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Hepatic cancer", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE" } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Thrombotic microangiopathy", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Grall M, Daviet F, Chiche NJ, Provot F, Presne C, Coindre J-P, et al. Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. BMC Nephrol. 2021;22(1):267(1-8)", "literaturereference_normalized": "eculizumab in gemcitabine induced thrombotic microangiopathy experience of the french thrombotic microangiopathies reference centre", "qualification": "3", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20220623", "receivedate": "20220623", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 20996636, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220720" }, { "companynumb": "FR-SUN PHARMACEUTICAL INDUSTRIES LTD-2022RR-341728", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "GEMCITABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "78433", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": "23.76", "drugcumulativedosageunit": "003", "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Ovarian cancer", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE" } ], "patientagegroup": null, "patientonsetage": "36", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Thrombotic microangiopathy", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Grall M, Daviet F, Chiche NJ, Provot F, Presne C, Coindre J-P, et al. Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. BMC Nephrol. 2021;22(1):267 (1-8)", "literaturereference_normalized": "eculizumab in gemcitabine induced thrombotic microangiopathy experience of the french thrombotic microangiopathies reference centre", "qualification": "3", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20220623", "receivedate": "20220623", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 20996646, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220720" }, { "companynumb": "FR-SUN PHARMACEUTICAL INDUSTRIES LTD-2022RR-341730", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "GEMCITABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "78433", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": "31", "drugcumulativedosageunit": "003", "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pancreatic carcinoma", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE" } ], "patientagegroup": null, "patientonsetage": "54", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Thrombotic microangiopathy", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Grall M, Daviet F, Chiche NJ, Provot F, Presne C, Coindre J-P, et al. Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. BMC Nephrol. 2021;22(1):267 (1-8)", "literaturereference_normalized": "eculizumab in gemcitabine induced thrombotic microangiopathy experience of the french thrombotic microangiopathies reference centre", "qualification": "3", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20220623", "receivedate": "20220623", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 20996649, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220721" }, { "companynumb": "FR-SUN PHARMACEUTICAL INDUSTRIES LTD-2022RR-341746", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "GEMCITABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "78433", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pancreatic carcinoma", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE" } ], "patientagegroup": null, "patientonsetage": "59", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Thrombotic microangiopathy", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Grall M, Daviet F, Chiche NJ, Provot F, Presne C, Coindre J-P, et al. Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. BMC Nephrol. 2021;22(1):267(1-8)", "literaturereference_normalized": "eculizumab in gemcitabine induced thrombotic microangiopathy experience of the french thrombotic microangiopathies reference centre", "qualification": "3", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20220623", "receivedate": "20220623", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 20996849, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220720" }, { "companynumb": "FR-SUN PHARMACEUTICAL INDUSTRIES LTD-2022RR-341738", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "GEMCITABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "78433", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Ovarian cancer", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE" } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Thrombotic microangiopathy", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Grall M, Daviet F, Chiche NJ, Provot F, Presne C, Coindre J-P, et al. Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. BMC Nephrol. 2021;22(1):267(1-8)", "literaturereference_normalized": "eculizumab in gemcitabine induced thrombotic microangiopathy experience of the french thrombotic microangiopathies reference centre", "qualification": "3", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20220623", "receivedate": "20220623", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 20997022, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220721" }, { "companynumb": "FR-SUN PHARMACEUTICAL INDUSTRIES LTD-2022RR-341751", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "GEMCITABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "78433", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pancreatic carcinoma", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE" } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Thrombotic microangiopathy", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Grall M, Daviet F, Chiche NJ, Provot F, Presne C, Coindre J-P, et al. Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. 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Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. BMC Nephrol. 2021;22 (1):267 (1-8)", "literaturereference_normalized": "eculizumab in gemcitabine induced thrombotic microangiopathy experience of the french thrombotic microangiopathies reference centre", "qualification": "3", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20220623", "receivedate": "20220623", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 20996815, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220720" }, { "companynumb": "FR-SUN PHARMACEUTICAL INDUSTRIES LTD-2022RR-341753", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "GEMCITABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "78433", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pancreatic carcinoma", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE" } ], "patientagegroup": null, "patientonsetage": "73", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Thrombotic microangiopathy", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Grall M, Daviet F, Chiche NJ, Provot F, Presne C, Coindre J-P, et al. Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. BMC Nephrol. 2021;22(1):267 (1-8)", "literaturereference_normalized": "eculizumab in gemcitabine induced thrombotic microangiopathy experience of the french thrombotic microangiopathies reference centre", "qualification": "3", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20220623", "receivedate": "20220623", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 20996631, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220721" }, { "companynumb": "FR-SUN PHARMACEUTICAL INDUSTRIES LTD-2022RR-341739", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "GEMCITABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "78433", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Ovarian cancer", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE" } ], "patientagegroup": null, "patientonsetage": "55", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Thrombotic microangiopathy", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Grall M, Daviet F, Chiche NJ, Provot F, Presne C, Coindre J-P, et al. Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. 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Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. 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Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. 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Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. 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Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre. 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{ "abstract": "Febrile infection-related epilepsy syndrome (FIRES) is a severe epileptic encephalopathy with presumed inflammatory origin and lacking effective treatments. Anakinra is the human recombinant interleukin 1 receptor antagonist clinically used in autoinflammatory or autoimmune conditions. We report a case of FIRES for which the spatial and temporal match between electroencephalography (EEG) and magnetic resonance imaging (MRI) focal alterations provides support for the detrimental synergic interplay between seizures and inflammation that may evolve to permanent focal lesions and progressive brain atrophy in weeks to months. Brain biopsy showed aspects of chronic neuroinflammation with scarce parenchymal lymphocytes. We report the novel evidence that anakinra reduces the relapse of highly recurrent refractory seizures at 1.5 years after FIRES onset. Our evidence, together with previously reported therapeutic effects of anakinra administered since the first days of disease onset, support the hypothesis that interleukin 1β and inflammation-related factors play a crucial role in seizure recurrence in both the acute and chronic stages of the disease.", "affiliations": "Clinical Neurophysiology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy.;Department of Pathophysiology and Transplantation Dino Ferrari Centre University of Milan Milan Italy.;Department of (Neuro) Pathology Amsterdam Neuroscience Amsterdam UMC University of Amsterdam Amsterdam The Netherlands.;Neurology IV - Neuroimmunology and Neuromuscular Diseases Unit Fondazione IRCCS Istituto Neurologico \"Carlo Besta\" Milan Italy.;Clinical Neurophysiology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy.;Neurology IV - Neuroimmunology and Neuromuscular Diseases Unit Fondazione IRCCS Istituto Neurologico \"Carlo Besta\" Milan Italy.;Division of Neurosurgery Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy.;Division of Pathology Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy.;Scientific Institute IRCCS Eugenio Medea Molecular Biology Lab Bosisio Parini Lecco Italy.;Pediatric Unit Department of Pathophysiology and Transplantation University of Milan Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy.;Pediatric Intensive Care Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy.;Neuroradiology Unit Fondazione IRCCS Ca' Granda Osp. Maggiore Policlinico Milan Italy.;Clinical Neurophysiology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy.;Pediatric Intensive Care Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy.;Department of Neuroscience Istituto di Ricerche Farmacologiche Mario Negri IRCCS Milano Italy.", "authors": "Dilena|Robertino|R|;Mauri|Eleonora|E|;Aronica|Eleonora|E|;Bernasconi|Pia|P|;Bana|Cristina|C|;Cappelletti|Cristina|C|;Carrabba|Giorgio|G|;Ferrero|Stefano|S|;Giorda|Roberto|R|;Guez|Sophie|S|;Scalia Catenacci|Stefano|S|;Triulzi|Fabio|F|;Barbieri|Sergio|S|;Calderini|Edoardo|E|;Vezzani|Annamaria|A|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1002/epi4.12317", "fulltext": "\n==== Front\nEpilepsia OpenEpilepsia Open10.1002/(ISSN)2470-9239EPI4Epilepsia Open2470-9239John Wiley and Sons Inc. Hoboken 10.1002/epi4.12317EPI412317Short Research ArticleShort Research ArticleTherapeutic effect of Anakinra in the relapsing chronic phase of febrile infection–related epilepsy syndrome DILENA et al.Dilena Robertino [email protected] \n1\nMauri Eleonora \n2\nAronica Eleonora \n3\n\n4\nBernasconi Pia \n5\nBana Cristina \n1\nCappelletti Cristina \n5\nCarrabba Giorgio \n6\nFerrero Stefano \n7\nGiorda Roberto \n8\nGuez Sophie \n9\nScalia Catenacci Stefano \n10\nTriulzi Fabio \n11\nBarbieri Sergio \n1\nCalderini Edoardo \n10\nVezzani Annamaria \n12\n\n1 \nClinical Neurophysiology Unit\nFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico\nMilan\nItaly\n\n2 \nDepartment of Pathophysiology and Transplantation\nDino Ferrari Centre\nUniversity of Milan\nMilan\nItaly\n\n3 \nDepartment of (Neuro) Pathology\nAmsterdam Neuroscience\nAmsterdam UMC\nUniversity of Amsterdam\nAmsterdam\nThe Netherlands\n\n4 \nStichting Epilepsie Instellingen Nederland (SEIN)\nHeemstede\nThe Netherlands\n\n5 \nNeurology IV ‐ Neuroimmunology and Neuromuscular Diseases Unit\nFondazione IRCCS Istituto Neurologico “Carlo Besta”\nMilan\nItaly\n\n6 \nDivision of Neurosurgery\nFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico\nMilan\nItaly\n\n7 \nDivision of Pathology\nFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico\nMilan\nItaly\n\n8 \nScientific Institute\nIRCCS Eugenio Medea\nMolecular Biology Lab\nBosisio Parini\nLecco\nItaly\n\n9 \nPediatric Unit\nDepartment of Pathophysiology and Transplantation\nUniversity of Milan\nFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico\nMilan\n Italy\n\n10 \nPediatric Intensive Care Unit\nFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico\nMilan\n Italy\n\n11 \nNeuroradiology Unit\nFondazione IRCCS Ca’ Granda Osp. Maggiore Policlinico\nMilan\n Italy\n\n12 \nDepartment of Neuroscience\nIstituto di Ricerche Farmacologiche Mario Negri IRCCS\nMilano\nItaly\n* Correspondence\n\nRobertino Dilena, Clinical Neurophysiology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy.\n\nEmail: [email protected]\n27 3 2019 6 2019 4 2 10.1002/epi4.2019.4.issue-2344 350 03 1 2019 01 3 2019 © 2019 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy.This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.Summary\nFebrile infection–related epilepsy syndrome (FIRES) is a severe epileptic encephalopathy with presumed inflammatory origin and lacking effective treatments. Anakinra is the human recombinant interleukin 1 receptor antagonist clinically used in autoinflammatory or autoimmune conditions. We report a case of FIRES for which the spatial and temporal match between electroencephalography (EEG) and magnetic resonance imaging (MRI) focal alterations provides support for the detrimental synergic interplay between seizures and inflammation that may evolve to permanent focal lesions and progressive brain atrophy in weeks to months. Brain biopsy showed aspects of chronic neuroinflammation with scarce parenchymal lymphocytes. We report the novel evidence that anakinra reduces the relapse of highly recurrent refractory seizures at 1.5 years after FIRES onset. Our evidence, together with previously reported therapeutic effects of anakinra administered since the first days of disease onset, support the hypothesis that interleukin 1β and inflammation‐related factors play a crucial role in seizure recurrence in both the acute and chronic stages of the disease.\n\nepileptic encephalopathyfebrile infection–related epilepsy syndromeIL‐1βneuroinflammation source-schema-version-number2.0component-idepi412317cover-dateJune 2019details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_NLMPMC version:5.6.4 mode:remove_FC converted:03.06.2019\n\n\nDilena \nR \n, \nMauri \nE \n, \nAronica \nE \n, et al. Therapeutic effect of Anakinra in the relapsing chronic phase of febrile infection–related epilepsy syndrome . Epilepsia Open . 2019 ;4 :344 –350 . 10.1002/epi4.12317\n==== Body\n1 INTRODUCTION\nFebrile infection–related epilepsy syndrome (FIRES) is a severe epileptic encephalopathy that occurs in previously healthy subjects. Although it was initially described in children, adults may also be affected.1 The pathogenesis remains unknown, although a presumed immune and inflammatory‐mediated etiology is suspected.1 FIRES is characterized by an explosive superrefractory status epilepticus, a preceding history of fever, and presumable infection without evidence of infective encephalitis. Seizures are extremely difficult to control and the outcome is poor. Interleukin 1β (IL‐1β) is a proinflammatory cytokine chiefly involved in both infections and febrile seizures,2 and recent evidence has shown that the human recombinant interleukin 1 (IL‐1) receptor antagonist (anakinra), which blocks IL‐1β actions, reduces seizures in the acute phase of FIRES.3 Anakinra effectively reduced drug‐resistant seizures also in some cases of inflammatory chronic epilepsy.4, 5\n\n\nWe report the novel evidence of a beneficial use of anakinra in the chronic phase of FIRES when seizure clusters were refractory to multiple antiepileptic drugs. Our data support an underlying pathogenic role of neuroinflammation and the therapeutic potential of a specific antiinflammatory intervention in the chronic phases of FIRES.\n\n2 CASE REPORT\n2.1 History of the acute epileptic phase\nAfter 4 days of fever and upper respiratory tract infection, a previously healthy 10‐year‐old child presented recurrent focal and generalized seizures and developed since the first day a status epilepticus refractory to midazolam and phenytoin. The family belongs to a mixed mulatto‐mestizo ethnicity and the family history was unremarkable for seizures and epilepsy. Status epilepticus was partially controlled, inducing burst‐suppression activity using midazolam, propofol, and then thiopental. Also an antimicrobial empiric treatment with acyclovir and ceftriaxone was started. Each attempt to reduce sedation in the first weeks caused relapse of severe status epilepticus with seizures and hypertension (secondary to seizures). Treatment with phenobarbital, levetiracetam, topiramate, lacosamide, and clobazam was unsuccessful. High‐dose steroids (methylprednisolone, 1 g, i.v., for 5 days, followed by enteral prednisone 2 mg/kg) and i.v. immunoglobulins were administered without efficacy (see therapy and seizure course in Figure 1). Protracted anesthetic coma with propofol caused important systemic complication (hypotension, hypertransaminemia, increase of serum pancreatic enzymes). Consequently, ketamine was introduced, attaining partial control of seizures, which nonetheless relapsed after a short time. Therefore, we introduced ketogenic diet, which was continued for 3 weeks without benefit. After 2 months, the patient was weaned from sedation and tracheal intubation, and was maintained under treatment with phenobarbital, topiramate, and lacosamide. He continued to manifest highly recurring seizures without clear consciousness recovery, but with a trend toward seizure reduction over the following months. Trend of seizures and responses to therapy during the first 3 years after disease onset are shown in Figure 1A.\n\nFigure 1 Evolution of the disease and treatment effect. A, Trend of seizures and treatments during the 3 years after disease onset. Thiopental sedation in the acute phase induces burst‐suppression with status epilepticus rebound at thiopental withdrawal. During the chronic phase, seizure reduction is attained by anakinra. B, Representative electroencephalography (EEG) tracings acquired during the first month from disease onset. a: EEG tracing of the second day during a left temporal‐occipital epileptic activity; b: burst‐suppression EEG pattern induced by high‐dose thiopental used to control the aggressive status epilepticus; c: relapse of epileptic abnormalities upon reduction of thiopental sedation; d: status epilepticus after interruption of continuous pharmacologic burst‐suppression (26 days from disease onset). C, Brain magnetic resonance imaging (MRI) evolution during the first year from disease onset. The first brain MRI performed at 2 days (d) from the onset of status epilepticus was unremarkable. The second and third MRI studies at 9 and 21 days showed a stable cortical hyperintensity in the left temporal‐occipital region, with a slight hyperintensity of both hippocampi. The fourth MRI (41 day) was performed after more than 10 days from burst‐suppression interruption (indicated by dotted vertical line in C) with the patient experiencing rebound of aggressive ongoing multifocal and generalized seizures. A more evident left temporal‐occipital hyperintensity involved not only the cortical region, but also the subcortical white matter. A diffuse hyperintensity of the bilateral hippocampal region and of the pulvinar region of the left thalamus became evident. In the fifth MRI study (78 days) after gradual reduction of epileptic activity, the hippocampal alteration was slightly reduced and the pulvinar alteration was no longer present, whereas the temporal‐occipital lesion was still present and a progressive increase in ventricular size became evident. At 1‐year follow‐up, the MRI showed a global brain atrophy with an increased enlargement of the posterior temporal horn. The left temporal‐occipital hyperintensity as well as the hippocampal hyperintensity were no longer visible, but these structures were deeply atrophic\n\n2.2 Laboratory tests\nEvaluation of cerebrospinal fluid (CSF) showed elevated protein level (60 mg/dL), normal glucose level (83 mg/dL), normal cells (<1/mm3), and negative viral and bacterial polymerase chain reaction (PCR) studies. Extensive blood investigations excluded ongoing infections, autoimmune disease, and antibody‐mediated encephalitis. Serum testing for anti‐basal ganglia antibodies (ABGAs) showed the presence of antibodies against a still unidentified 150 kDa antigen. An immunoblot stain on rat brain section6 showed a positive reaction, particularly in the neocortex and basal ganglia as compared to serum from a healthy control (Figure 2A). The significance of these findings remains unknown; they may represent an autoantibody‐mediated form of the disease or, as the titer of antibodies is low, a nonspecific reaction induced by exposure of the immune system to autoantigens released by injured brain cells. Mitochondrial pathology was considered through screening of POLG mutation and muscle biopsy, both resulting in negative findings. Next‐generation sequencing panel for genetic epilepsy did not show significant variants. Based on evidence of IL1RN haplotype containing RN2 in a group of Japanese patients with FIRES and an association of IL1RN rs4251981 G>A and SCN2A rs1864885 A>G,7 we tested for but we did not find these polymorphisms in the two genes in our patient.\n\nFigure 2 Immunoblots and histopathology. A, Immunohistoblots showing the labeling of horizontal transversal hemisections of rat brain with patient's serum and cerebrospinal fluid (CSF). No labeling was observed in sections incubated with a pool of healthy donor (HD) sera. The principal brain structure identified by patient's serum is neocortex (see Ref. 8). B, Histopathology of biopsy of left posterior temporal lobe. The biopsy consists of small fragments of predominant white matter (Wm) with presence of activated HLA‐DR‐positive cells (a); high magnification photographs of HLA‐DR‐positive reactive microglia within the Wm (arrows in b); few scattered CD8‐positive T lymphocytes (arrows in c). Scale bars: A, 1 mm; B, 25 μm; C, 40 μm. Anti‐human leukocyte antigen (HLA)‐DP, DQ, DR (HLA‐DR; clone CR3/43) anti‐CD8 (mouse monoclonal, clone C8/144B)\n\n2.3 Continuous electroencephalography monitoring\nSeizures were multifocal in both hemispheres, but with two prominent active foci, that is, a left posterior temporal focus and a less‐prominent right frontotemporal focus. Seizures stopped only during deep sedation with anesthetic (thiopental) but returned upon anesthetic drug reduction. The highly recurrent seizures had migrating focal seizure‐like features beyond the above‐described foci (Figure 1B).\n\n2.4 Brain magnetic resonance imaging evolution\nThe first brain magnetic resonance imaging (MRI) was performed 2 days after onset of status epilepticus and did not show remarkable signs (Figure 1C). Subsequent brain MRI studies were performed at 8, 21, 41, and 78 days, marking the topographic anatomic relationship between the evolving MRI alterations and the trend of electroencephalography (EEG) epileptic focal activities. During partial suppression of seizures by anesthetic drugs, brain MRI showed T2‐weighted hyperintensities in the left temporo‐occipital region, in the right insula, and both hippocampi. During aggressive uncontrolled ongoing multifocal seizures, the left temporo‐occipital hyperintensity increased, involving both cortical and subcortical regions. After reduction of epileptic activity, hippocampal and left pulvinar hyperintensities were clearly reduced; the temporo‐occipital lesion was still present. At 1 year, brain MRI showed an increased global atrophy with a temporo‐occipital focal malacia, where previously MRI hyperintensity and epileptic activity were more prominent (Figure 1C).\n\n2.5 Histopathology\nBrain biopsy was performed at 2 months from onset showing reactive astrogliosis (not shown), prominent microglia activation, and a few scattered CD8‐positive T lymphocytes (Figure 2B). No known or novel viruses could be identified based on a nucleotide and protein search (using a random DNA and RNA amplification approach in combination with next‐generation sequencing ‐ not shown).\n\n2.6 History of chronic epilepsy phase and effect of anakinra\nFour months after status epilepticus onset the patient was bedridden and poorly reactive to stimuli with recurrent daily seizures. He was then sent to an intensive rehabilitation unit where he stayed for 5 months. Seizures during both acute and chronic phases had multifocal onset and corresponding variable semiology, occasionally with secondary generalization. During the chronic phase the seizures were focal motor and nonmotor. In particular, the most frequent manifestations were behavioral arrest, ocular deviation, and facial and oral clonic movements. In the following months, seizures gradually decreased in frequency but continued with a tendency to a monthly clustering of seizures. EEG showed recurrent electric focal seizures (multifocal foci, predominantly in the posterior regions of brain). After discharge, during the rehabilitation period, new hospital admissions for cluster of clinical seizures were required for adjustments of the polytherapy (high‐dose phenobarbital and topiramate, oxcarbazepine, and clobazam at therapeutic doses) but without sustained efficacy. At 1 year and a half from the disease onset, during a new admission for frequent clusters of epileptic multifocal and generalized seizures unresponsive to phenobarbital 7 mg/kg, topiramate 11 mg/kg, clobazam 0.5 mg/kg, and oxcarbazepine 30 mg/kg daily, treatment with subcutaneous (s.c.) anakinra was introduced at the dosage of 2.5 mg/kg per day (100 mg) with partial efficacy and 3 days after increased to 2.5 mg/kg twice a day, finally reaching full seizure control. Anakinra is a recombinant of human IL‐1 receptor antagonist, approved for different neonatal and pediatric autoinflammatory acute and chronic conditions. Its safety profile has been established after long‐term administration at a dose from 1 to 10 mg/kg per day (maximum 200 mg/day).8 No adverse effects were reported in our patient. The occurrence of oppositional behavior made it sometimes problematic for caregivers to perform subcutaneous injections, but the drug was always regularly administered. During this treatment no comedication dosage was modified. Two months after introduction, anakinra was reduced to 100 mg per day (2.5 mg/kg per day). During the 7 months of anakinra treatment only two clinical seizures occurred and control EEG studies show no electric seizures, with some improvement of background activity. After anakinra withdrawal, seizures and EEG epileptiform abnormalities increased until a new admission for epileptic status occurred 11 months after anakinra interruption (Figure 1A). Status epilepticus was managed with adjunctive intravenous doses of phenobarbital after which oral perampanel was initiated. Anakinra reintroduction has been considered but not started yet due to insurance issues and patient's increased oppositional behavior toward injections.\n\nAs to the neurofunctional outcome, the patient shows a cognitive disability with frontal behavior, aphasia, and a right spastic gait.\n\n3 DISCUSSION\nClinical, neurophysiologic, and MRI features of the patient were consistent with FIRES.1 In accordance, EEG frequently shows global slowing and multifocal seizures and brain MRI in the initial stages of FIRES is often normal or with minor abnormalities, whereas later evolution typically leads to brain atrophy.9 Whether these changes are due to prolonged intractable seizures and involve brain inflammation remains uncertain.10 A series of brain MRI studies was collected in our patient and matched to continuous EEG monitoring, showing the topographic correspondence of the epileptic multiple focuses with the alterations on brain MRI. MRI lesions may be due to excitotoxic changes, even if the mechanism is not completely understood. The observation of new MRI alterations after stopping drug‐induced burst‐suppression, related to the increased seizure burden (Figure 1A‐C), suggests a vicious cycle between inflammation and seizure.11 This hypothesis suggests that novel therapies should be rapidly applied to efficiently control both inflammation and seizures. FIRES is a condition that may be sustained by brain inflammation, possibly as mirror focus of a systemic inflammatory response to a common infection in predisposed patients. In support, neuroinflammation in animal models is associated with long‐term reduction in seizure threshold together with lasting alterations of brain physiology and gene expression.12, 13 Moreover, specific antiinflammatory drugs reduce ongoing seizures and inhibit epileptogenesis.13 Early brain biopsy is performed rarely, but it could help to clarify FIRES pathogenesis: as in our case, brain biopsy indicated a sustained activation of the innate immune response. Overproduction of proinflammatory cytokines and chemokines by microglia in FIRES could contribute to epileptogenesis.14 In particular, the proinflammatory cytokine IL‐1β released by glial cells promotes neuroinflammation, enhances neuronal excitability, and contributes to seizures in animal models.2 Notably, the balance between brain IL‐1β and IL‐1Ra represents a crucial mechanism to control seizure recurrence and generalization, and anakinra exerts anticonvulsive effects in preclinical models and enhances the therapeutic response to otherwise ineffective drugs.15, 16\n\n\nBased on a recent case report where anakinra was effective in the acute phase of FIRES3 and additional evidence of its therapeutic effects in inflammatory refractory epilepsy,4, 5, 11 we started anakinra treatment in a patient already in the chronic phase of FIRES during a period of intractable seizure relapse with multiple seizures per day. We observed a rapid and significant improvement after anakinra treatment (as seizures became much rarer than before treatment) and then again seizure increase after anakinra interruption. This observation supports the efficacy of anakinra in the chronic phase of FIRES, although the possibility that anakinra is just coincidentally related to seizure frequency reduction cannot be formally ruled out. This observation also might suggest that neuroinflammation could be involved in seizure generation and seizure recurrence in FIRES.11 Our data raise the need to design treatment protocols suitable for interrupting the vicious cycle between neuroinflammation and recurrent seizures to maximize the therapeutic effects and prevent long‐term outcomes.\n\nThe duration of anakinra treatment in FIRES for attaining a therapeutic effect persisting after drug withdrawal is a key aspect that requires further clinical studies. Multicenter studies are urgently needed to clarify the physiopathology and to ascertain efficacy, dose, and tolerance of drugs regulating innate immunity in severe epileptic conditions such as FIRES.\n\nCONFLICT OF INTEREST\nNone of the authors has any conflict of interest to disclose. All co‐authors have been substantially involved in the study and/or the preparation of the manuscript; no undisclosed groups or persons have had a primary role in the study and/or in manuscript preparation. All co‐authors have seen and approved the submitted version of the paper and accept responsibility for its content. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.\n\nSupporting information\n \n\nClick here for additional data file.\n\n ACKNOWLEDGMENTS\nThe authors would like to thank the family members for their cooperation.\n==== Refs\nREFERENCES\n1 \n\nHirsch \nLJ \n, \nGaspard \nN \n, \nvan Baalen \nA \n, \nNabbout \nR \n, \nDemeret \nS \n, \nLoddenkemper \nT \n, et al. Proposed consensus definitions for new‐onset refractory status epilepticus (NORSE), febrile infection‐related epilepsy syndrome (FIRES), and related conditions . Epilepsia \n2018 ;59 :739 –744 .29399791 \n2 \n\nVezzani \nA \n, \nMaroso \nM \n, \nBalosso \nS \n, \nSanchez \nMA \n, \nBartfai \nT \n. IL‐1 receptor/Toll‐like receptor signaling in infection, inflammation, stress and neurodegeneration couples hyperexcitability and seizures . Brain Behav Immun \n2011 ;25 :1281 –1289 .21473909 \n3 \n\nKenney‐Jung \nDL \n, \nVezzani \nA \n, \nKahoud \nRJ \n, \nLaFrance‐Corey \nRG \n, \nHo \nML \n, \nMuskardin \nTW \n, et al. Febrile infection‐related epilepsy syndrome treated with anakinra . Ann Neurol \n2016 ;80 :939 –945 .27770579 \n4 \n\nJyonouchi \nH \n, \nGeng \nL \n. Intractable Epilepsy (IE) and Responses to Anakinra, a Human Recombinant IL‐1 Receptor Antagonist (IL‐1Ra): case Reports . J Clin Cell Immunol \n2016 ;7 :456 –460 .\n5 \n\nDeSena \nAD \n, \nDo \nT \n, \nSchulert \nGS \n. Systemic autoinflammation with intractable epilepsy managed with interleukin‐1 blockade . J Neuroinflammation \n2018 ;15 :38 .29426321 \n6 \n\nBernasconi \nP \n, \nCipelletti \nB \n, \nPasserini \nL \n, \nGranata \nT \n, \nAntozzi \nC \n, \nMantegazza \nR \n, et al. Similar binding to glutamate receptors by Rasmussen and partial epilepsy patients’ sera . Neurology . 2002 ;12 :1998 –2001 .\n7 \n\nSaitoh \nM \n, \nKobayashi \nK \n, \nOhmori \nI \n, \nTanaka \nY \n, \nTanaka \nK \n, \nInoue \nT \n, et al. Cytokine‐related and sodium channel polymorphism as candidate predisposing factors for childhood encephalopathy FIRES/AERRPS . J Neurol Sci \n2016 ;368 :272 –276 .27538648 \n8 \n\nKullenberg \nT \n, \nLöfqvist \nM \n, \nLeinonen \nM \n, \nGoldbach‐Mansky \nR \n, \nOlivecrona \nH \n. Long‐term safety profile of anakinra in patients with severe cryopyrin‐associated periodic syndromes . Rheumatol Oxf Engl \n2016 ;55 :1499 –1506 .\n9 \n\nRivas‐Coppola \nMS \n, \nShah \nN \n, \nChoudhri \nAF \n, \nMorgan \nR \n, \nWheless \nJW \n. Chronological evolution of magnetic resonance imaging findings in children with febrile infection‐related epilepsy syndrome . Pediatr Neurol \n2016 ;55 :22 –29 .26597039 \n10 \n\nLee \nHF \n, \nChi \nCS \n. Febrile infection‐related epilepsy syndrome (FIRES): therapeutic complications, long‐term neurological and neuroimaging follow‐up . Seizure \n2018 ;56 :53 –59 .29453111 \n11 \n\nNabbout \nR \n, \nVezzani \nA \n, \nDulac \nO \n, \nChiron \nC \n. Acute encephalopathy with inflammation‐mediated status epilepticus . Lancet Neurol \n2011 ;10 :99 –108 .21163447 \n12 \n\nVezzani \nA \n, \nAronica \nE \n, \nMazarati \nA \n, \nPittman \nQJ \n. Epilepsy and brain inflammation . Exp Neurol \n2013 ;4 :11 –21 .\n13 \n\nAronica \nE \n, \nBauer \nS \n, \nBozzi \nY \n, \nCaleo \nM \n, \nDingledine \nR \n, \nGorter \nJA \n, et al. Neuroinflammatory targets and treatments for epilpesy validated in experimental models . Epilepsia \n2017 ;58 :27 –28 .\n14 \n\nSakuma \nH \n, \nTanuma \nN \n, \nKuki \nI \n, \nTakahashi \nY \n, \nShiomi \nM \n, \nHayashi \nM \n. Intrathecal overproduction of proinflammatory cytokines and chemokines in febrile infection‐related refractory status epilepticus . J Neurol Neurosurg Psychiatry \n2015 ;86 :820 –822 .25398790 \n15 \n\nVezzani \nA \n, \nDingledine \nR \n, \nRossetti \nAO \n. Immunity and inflammation in status epilepticus and its sequelae: possibilities for therapeutic application . Expert Rev Neurother \n2015 ;15 :1081 –1092 .26312647 \n16 \n\nZheng‐Hao \nX \n, \nWang \nY \n, \nTao \nAF \n, \nYu \nJ \n, \nWang \nXY \n, \nZu \nYY \n, et al. Interleukin‐1 receptor is a target for adjunctive control of diazepam‐refractory status epilepticus in mice . Neuroscience \n2016 ;328 :22 –29 .27133574\n\n", "fulltext_license": "CC BY-NC-ND", "issn_linking": "2470-9239", "issue": "4(2)", "journal": "Epilepsia open", "keywords": "IL‐1β; epileptic encephalopathy; febrile infection–related epilepsy syndrome; neuroinflammation", "medline_ta": "Epilepsia Open", "mesh_terms": null, "nlm_unique_id": "101692036", "other_id": null, "pages": "344-350", "pmc": null, "pmid": "31168503", "pubdate": "2019-06", "publication_types": "D016428:Journal Article", "references": "12499503;21163447;21473909;21985866;25398790;26312647;26597039;27133574;27143789;27538648;27770579;28675563;29399791;29426321;29453111", "title": "Therapeutic effect of Anakinra in the relapsing chronic phase of febrile infection-related epilepsy syndrome.", "title_normalized": "therapeutic effect of anakinra in the relapsing chronic phase of febrile infection related epilepsy syndrome" }

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THERAPEUTIC EFFECT OF ANAKINRA IN THE RELAPSING CHRONIC PHASE OF FEBRILE INFECTION-RELATED EPILEPSY SYNDROME. EPILEPSIA OPEN. 2019?4 (2):344-350", "literaturereference_normalized": "therapeutic effect of anakinra in the relapsing chronic phase of febrile infection related epilepsy syndrome", "qualification": "3", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20191016", "receivedate": "20190627", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16483166, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": 1, "seriousnessother": null, "transmissiondate": "20200122" }, { "companynumb": "IT-MYLANLABS-2019M1062494", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "TOPIRAMATE" }, "drugadditional": "3", 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{ "abstract": "Constituting less than 25% of all renal artery dissections (RAD), isolated spontaneous renal artery dissection (SRAD) is a rare diagnosis that can cause subsequent renal infarction with impairment. The majority of SRAD cases are idiopathic. Management ranges from conservative, medical to endovascular, and surgical repair. We report a case of a young female on multiple medications who presented with SRAD. She presented with acute abdominal pain and was found to have isolated spontaneous renal artery dissection. The etiology of this patient's isolated SRAD could possibly be pinned down to her multiple stimulant medications used after the major known causes were ruled out.", "affiliations": "Internal Medicine, Southern Illinois University School of Medicine, Springfield, USA.;Internal Medicine and Psychiatry, Southern Illinois University School of Medicine, Springfield, USA.;Internal Medicine, Southern Illinois University School of Medicine, Springfield, USA.;Internal Medicine, Southern Illinois University School of Medicine, Springfield, USA.;Internal Medicine, Southern Illinois University School of Medicine, Springfield, USA.", "authors": "Regmi|Manjari R|MR|;Carbrey|Sarah-Grace A|SA|;Parajuli|Priyanka|P|;Lara Garcia|Odalys Estefania|OE|;Bhattarai|Mukul|M|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.7759/cureus.5770", "fulltext": "\n==== Front\nCureusCureus2168-8184Cureus2168-8184Cureus Palo Alto (CA) 10.7759/cureus.5770MiscellaneousNephrologyInternal MedicineA Rare Case of Isolated and Idiopathic Spontaneous Renal Artery Dissection in a Female Patient on Multiple Medications Muacevic Alexander Adler John R Regmi Manjari R 1Carbrey Sarah-Grace A 2Parajuli Priyanka 1Lara Garcia Odalys Estefania 1Bhattarai Mukul 1\n1 \nInternal Medicine, Southern Illinois University School of Medicine, Springfield, USA \n2 \nInternal Medicine and Psychiatry, Southern Illinois University School of Medicine, Springfield, USA \nManjari R. Regmi [email protected] 9 2019 9 2019 11 9 e577018 9 2019 25 9 2019 Copyright © 2019, Regmi et al.2019Regmi et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article is available from https://www.cureus.com/articles/23406-a-rare-case-of-isolated-and-idiopathic-spontaneous-renal-artery-dissection-in-a-female-patient-on-multiple-medicationsConstituting less than 25% of all renal artery dissections (RAD), isolated spontaneous renal artery dissection (SRAD) is a rare diagnosis that can cause subsequent renal infarction with impairment. The majority of SRAD cases are idiopathic. Management ranges from conservative, medical to endovascular, and surgical repair. We report a case of a young female on multiple medications who presented with SRAD. She presented with acute abdominal pain and was found to have isolated spontaneous renal artery dissection. The etiology of this patient’s isolated SRAD could possibly be pinned down to her multiple stimulant medications used after the major known causes were ruled out. \n\nspontaneous renal artery dissectionpoly-pharmacystimulant usemethylphenidatedissectiondextroamphetamineThe content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.\n==== Body\nIntroduction\nAn isolated, spontaneous renal artery dissection (SRAD) is a dissection of the renal artery and is a very rare diagnosis. The first report of isolated, spontaneous renal artery dissection (SRAD) occurred in 1944 [1]. With the increasing use of imaging modalities and advanced endovascular technology, detection rates and incidence rates of RAD are on the rise. However, due to the limited number of cases of isolated RAD, there continues to be limited literature on other possible etiologies. Information on this subject is mostly limited to case series and individual case reports. The known associated conditions include malignant hypertension, atherosclerosis, connective tissue disorders (which include fibromuscular dysplasia, Marfan’s syndrome, and Ehlers-Danlos), blunt trauma, catheter procedures, and idiopathic causes. As mentioned by Jain et al., the leading cause of isolated SRAD is fibromuscular dysplasia, whereas, the second leading cause is still idiopathic contributing to 37% of SRAD [2]. As these cases are uncommon, it is difficult to reach the root cause of SRAD, especially when other signs and symptoms are not present.\n\nCase presentation\nA 48-year-old female prison nurse (history of hypertension, migraine, major depressive disorder, and attention-deficit hyperactive disorder) presented after a sudden onset of severe sharp left lower quadrant abdominal pain and confusion. At that time, she was taking fluoxetine of 20 mg, hydrochlorothiazide of 12.5 mg, topiramate of 100 mg, eletriptan of 40 mg, amphetamine-dextroamphetamine of 30 mg, and methylphenidate of 10 mg. She reported increasing the frequency of her as-needed drug, methylphenidate, recently because of elevated stress at work. She had no personal or family history of vascular disease and connective tissue disorders. The physical exam was significant for mild tenderness in the left flank. Blood pressure (BP) was elevated at 156/97 on arrival with subsequent normalizations. Initial laboratory studies were within normal limits and urine toxicology was positive for amphetamines. Upon further evaluation, a CT scan of the abdomen and pelvis showed left renal artery dissection and left renal cortical infarct. Figure 1 shows the CT findings of the patient. The patient was given morphine for pain relief and her confusion resolved as her pain decreased. Within 48 hours of admission, repeated CT angiogram of chest, abdomen, and pelvis revealed unchanged left renal artery dissection with a thrombosed false lumen and partial infarction of the left kidney with no evidence of fibromuscular dysplasia. Further workup including CT head, ultrasound carotid arteries, and echocardiography was normal. Vascular surgery recommended conservative management and no surgical intervention. The pain was managed with morphine and Tylenol. Dextroamphetamine, methylphenidate, and eletriptan were held and BP remained controlled with hydrochlorothiazide. The patient was discharged on single antiplatelet therapy with a follow-up appointment with vascular surgery for repeat imaging.\n\nFigure 1 CT abdomen and pelvis: left renal artery dissection with a thrombosed false lumen and partial left kidney infarct\nCT, computed tomography\n\nDiscussion\nThe different types of RAD are as follows: 1) isolated (if localized to the renal artery without aortic involvement) or combined (if originating in the aorta with the involvement of renal artery) - static obstruction or dynamic obstruction; 2) primary (if associated with atherosclerosis or FM) or secondary (if associated with blunt trauma or endovascular interventions with wires/catheters); 3) idiopathic (all others without underlying pathology known or identified); unilateral or bilateral (one or both renal arteries involved); 4) spontaneous (SRAD; presenting in otherwise healthy individuals with acute presentation). Our patient herein had SRAD. \n\nWith a male to female prevalence ratio of 4:1, SRAD is commonly found in healthy males in their 40s-60s. Due to the rarity of SRAD, information on a temporal cause-effect relationship is limited to case series and individual reports. Although there are various conditions associated with SRAD, the specific causal relationship and pathologies behind it are still not well understood. Some theories suggest an atherosclerotic alteration of vasa vasorum and its rupture as the underlying mechanism of SRAD [3].\n\nThe peculiar part of our patient was that she was on multiple medications, potentially interacting with each other, which have known sympathomimetic effects. The first drug, dextroamphetamine, an amphetamine salt, is known to exert catecholaminergic effects by stimulating the release of epinephrine and norepinephrine and also by inhibiting monoamine oxidase. Moreover, the second drug, eletriptan, class of abortive migraine drugs, are serotonin agonists on blood vessels and neurons and therefore, lead to vasoconstriction. The third drug, hydrochlorothiazide, and the fourth, topiramate, are urine alkalinizers that increase serum levels and decrease the excretion of dextroamphetamine. The fifth drug, fluoxetine increases serum levels of dextroamphetamine due to CYP2D6. In summary, two of the five drugs were responsible for sympathomimetic effects. The significant interactions of the other three drugs lead to an increased level of dextroamphetamine and therefore, amplified the catecholaminergic effects [4]. Amphetamine derivatives, combined with triptan can lead to intimal hypertrophy due to vasoconstriction or medial vasa-vasorum vascular changes that are highly associated with isolated RAD or RAD with aortic dissections. [5-6]\n\nAmphetamine use leading to spontaneous coronary and aortic dissection has been reported in some cases; however, to the best of the authors’ knowledge, its association with isolated SRAD has not been reported yet. This case presentation provides strong evidence towards the validation of the theory that suggests an atherosclerotic alteration of vasa vasorum and its rupture as the underlying pathology behind SRAD. \n\nConclusions\nSRAD is a rare but also a threatening condition that does not have a significant known temporal cause. While there are some cases reported of spontaneous coronary and aortic dissection in the setting of amphetamine use, there remains a paucity of published literature exploring this specific association. More research in this area is warranted in light of the rising rates of prescription stimulant use in the general population. Also, this case highlights that we have to be very cautious while using multiple, potentially interacting, medications. \n\nThe authors have declared that no competing interests exist.\n\nHuman Ethics\nConsent was obtained by all participants in this study. Not required issued approval Not required. As it was a case-report, no IRB approval was required. Informed consent has been obtained for the case report.\n==== Refs\nReferences\n1 Spontaneous renal artery dissection: treatment with coil embolization J Vasc Interv Radiol Mudrick D Arepally A Geschwind JF Ronsivalle JA Lund GB Scheel P 497 500 14 2003 12682209 \n2 Renal malperfusion: spontaneous renal artery dissection and with aortic dissection Semin Vasc Surg Jain A Tracci MC Coleman DM Cherry KJ Upchurch Jr GR 178 188 26 2013 25220324 \n3 Spontaneous renal artery dissection Rev Urol Kanofsky JA Lepor H 156 160 9 2007 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2002504/. 17934571 \n4 Dextroamphetamine sulfate - drug summary 9 2019 2019 https://www.pdr.net/drug-summary/ProCentra-dextroamphetamine-sulfate-1511 \n5 The cardiac complications of methamphetamines Heart Lung Circ Paratz ED Cunningham NJ MacIsaac AI 325 332 25 2016 Apr 1 26706652 \n6 Isolated spontaneous dissection of the renal artery J Vasc Surg Lacombe M 385 391 33 2001 11174794\n\n", "fulltext_license": "CC BY", "issn_linking": "2168-8184", "issue": "11(9)", "journal": "Cureus", "keywords": "dextroamphetamine; dissection; methylphenidate; poly-pharmacy; spontaneous renal artery dissection; stimulant use", "medline_ta": "Cureus", "mesh_terms": null, "nlm_unique_id": "101596737", "other_id": null, "pages": "e5770", "pmc": null, "pmid": "31723529", "pubdate": "2019-09-26", "publication_types": "D002363:Case Reports", "references": "25220324;12682209;11174794;17934571;26706652", "title": "A Rare Case of Isolated and Idiopathic Spontaneous Renal Artery Dissection in a Female Patient on Multiple Medications.", "title_normalized": "a rare case of isolated and idiopathic spontaneous renal artery dissection in a female patient on multiple medications" }

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FREQ UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TOPIRAMATE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHYLPHENIDATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MILLIGRAM; FREQ UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPHENIDATE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHYLPHENIDATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, INCREASING THE FREQUENCY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPHENIDATE." } ], "patientagegroup": null, "patientonsetage": "48", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Renal artery dissection", "reactionmeddraversionpt": "24.0", "reactionoutcome": "3" }, { "reactionmeddrapt": "Renal infarct", "reactionmeddraversionpt": "24.0", "reactionoutcome": "3" } ], "summary": null }, "primarysource": { "literaturereference": "REGMI M R, CARBREY S, PARAJULI P, GARCIA OEL, BHATTARAI M.. A RARE CASE OF ISOLATED AND IDIOPATHIC SPONTANEOUS RENAL ARTERY DISSECTION IN A FEMALE PATIENT ON MULTIPLE MEDICATIONS. CUREUS. 2019?11(9):E5770", "literaturereference_normalized": "a rare case of isolated and idiopathic spontaneous renal artery dissection in a female patient on multiple medications", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210601", "receivedate": "20210601", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19359625, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210717" } ]

{ "abstract": "BACKGROUND\nEpithelioid hemangio-endothelioma (EHE) is a rare malignant tumor of vascular origin that electively metastasizes to lungs and liver.\n\n\nMETHODS\nWe report the case of a 51-year-old woman with metastatic and progressive EHE of the liver. She was successfully treated with daily administration of sunitinib malate, an oral multi-target tyrosine kinase inhibitor, which particularly targets vascular endothelial growth factor (VEGF) receptors. Stabilization has lasted 6 years. We discuss the rationale for using antiangiogenic treatment for EHE.\n\n\nCONCLUSIONS\nThis case adds to a growing body of evidence that suggests that antiangiogenic agents should be considered in patients who present with advanced EHE.", "affiliations": "Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France.", "authors": "Saada|Esma|E|;Saint Paul|Marie-Christine|MC|;Gugenheim|Jean|J|;Follana|Philippe|P|;François|Eric|E|", "chemical_list": "D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib", "country": "Netherlands", "delete": false, "doi": "10.1159/000360208", "fulltext": null, "fulltext_license": null, "issn_linking": "2296-5270", "issue": "37(3)", "journal": "Oncology research and treatment", "keywords": null, "medline_ta": "Oncol Res Treat", "mesh_terms": "D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D005260:Female; D018323:Hemangioendothelioma, Epithelioid; D006801:Humans; D007211:Indoles; D008113:Liver Neoplasms; D008137:Longitudinal Studies; D008175:Lung Neoplasms; D008297:Male; D009389:Neovascularization, Pathologic; D011758:Pyrroles; D000077210:Sunitinib; D016896:Treatment Outcome", "nlm_unique_id": "101627692", "other_id": null, "pages": "124-6", "pmc": null, "pmid": "24685916", "pubdate": "2014", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Metastatic hepatic epithelioid hemangio-endothelioma: long-term response to sunitinib malate.", "title_normalized": "metastatic hepatic epithelioid hemangio endothelioma long term response to sunitinib malate" }

[ { "companynumb": "FR-MYLANLABS-2015M1017504", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "SUNITINIB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "201275", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/DAY FOR 4WK; 6WK CYCLE", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANGIOSARCOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200611", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SUNITINIB" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Eyelid oedema", "reactionmeddraversionpt": "18.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Cough", "reactionmeddraversionpt": "18.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Headache", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypertension", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Gingival bleeding", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Swelling face", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypothyroidism", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Leukopenia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Asthenia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "2" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 200705" } }, "primarysource": { "literaturereference": "SAADA E, SAINT PAUL M-C, GUGENHEIM J, FOLLANA P, FRANCOIS E. METASTATIC HEPATIC EPITHELIOID HEMANGIO-ENDOTHELIOMA: LONG-TERM RESPONSE TO SUNITINIB MALATE. ONCOL-RES-TREAT 2014; 37(3):124-126.", "literaturereference_normalized": "metastatic hepatic epithelioid hemangio endothelioma long term response to sunitinib malate", "qualification": "3", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20150528", "receivedate": "20150528", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11146531, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150821" } ]

{ "abstract": "Acetaminophen is the most commonly used analgesic-antipyretic medication in the United States. Acetaminophen overdose, a frequent cause of drug toxicity, has been recognized as the leading cause of fatal and non-fatal hepatic necrosis. N-Acetylcysteine is the recommended antidote for acetaminophen poisoning. Despite evidence on the efficacy of N-acetylcysteine for prevention of hepatic injury, controversy persists about the optimal duration of the therapy. Here, we describe the case of a 65-year-old male with acetaminophen overdose and opioid co-ingestion who developed a second peak in acetaminophen serum levels after completing the recommended 21-hour intravenous N-acetylcysteine protocol and when the standard criteria for monitoring drug levels was achieved. Prolongation of N-acetylcysteine infusion beyond the standard protocol, despite a significant gap in treatment, was critical for successful avoidance of hepatotoxicity. Delay in acetaminophen absorption may be associated with a second peak in serum concentration following an initial declining trend, especially in cases of concomitant ingestion of opioids. In patients with acetaminophen toxicity who co-ingest other medications that may potentially delay gastric emptying or in those with risk factors for delayed absorption of acetaminophen, we recommend close monitoring of aminotransferase enzyme levels, as well as trending acetaminophen concentrations until undetectable before discontinuing the antidote therapy.", "affiliations": "Department of Internal Medicine, Montefiore New Rochelle Hospital, Albert Einstein College of Medicine, New Rochelle, NY, USA; [email protected].;Department of Internal Medicine, Montefiore New Rochelle Hospital, Albert Einstein College of Medicine, New Rochelle, NY, USA.;Department of Internal Medicine, Montefiore New Rochelle Hospital, Albert Einstein College of Medicine, New Rochelle, NY, USA.;Department of Internal Medicine, Montefiore New Rochelle Hospital, Albert Einstein College of Medicine, New Rochelle, NY, USA.;Department of Internal Medicine, Montefiore New Rochelle Hospital, Albert Einstein College of Medicine, New Rochelle, NY, USA.", "authors": "Papazoglu|Cristian|C|;Ang|Jonathan R|JR|;Mandel|Michael|M|;Basak|Prasanta|P|;Jesmajian|Stephen|S|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.3402/jchimp.v5.29589", "fulltext": "\n==== Front\nJ Community Hosp Intern Med PerspectJ Community Hosp Intern Med PerspectJCHIMPJournal of Community Hospital Internal Medicine Perspectives2000-9666Co-Action Publishing 2958910.3402/jchimp.v5.29589Case ReportAcetaminophen overdose associated with double serum concentration peaks Papazoglu Cristian MD, PhD*Ang Jonathan R. MDMandel Michael MDBasak Prasanta MD, FACPJesmajian Stephen MD, FACPDepartment of Internal Medicine, Montefiore New Rochelle Hospital, Albert Einstein College of Medicine, New Rochelle, NY, USA* Correspondence to: Cristian Papazoglu, Department of Internal Medicine, Montefiore New Rochelle Hospital, Albert Einstein College of Medicine, 16 Guion Place, New Rochelle, NY 10802, USA, Email: [email protected] 12 2015 2015 5 6 10.3402/jchimp.v5.2958931 8 2015 09 11 2015 12 11 2015 © 2015 Cristian Papazoglu et al.2015This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Acetaminophen is the most commonly used analgesic–antipyretic medication in the United States. Acetaminophen overdose, a frequent cause of drug toxicity, has been recognized as the leading cause of fatal and non-fatal hepatic necrosis. N-Acetylcysteine is the recommended antidote for acetaminophen poisoning. Despite evidence on the efficacy of N-acetylcysteine for prevention of hepatic injury, controversy persists about the optimal duration of the therapy. Here, we describe the case of a 65-year-old male with acetaminophen overdose and opioid co-ingestion who developed a second peak in acetaminophen serum levels after completing the recommended 21-hour intravenous N-acetylcysteine protocol and when the standard criteria for monitoring drug levels was achieved. Prolongation of N-acetylcysteine infusion beyond the standard protocol, despite a significant gap in treatment, was critical for successful avoidance of hepatotoxicity. Delay in acetaminophen absorption may be associated with a second peak in serum concentration following an initial declining trend, especially in cases of concomitant ingestion of opioids. In patients with acetaminophen toxicity who co-ingest other medications that may potentially delay gastric emptying or in those with risk factors for delayed absorption of acetaminophen, we recommend close monitoring of aminotransferase enzyme levels, as well as trending acetaminophen concentrations until undetectable before discontinuing the antidote therapy.\n\nacetaminophen toxicityacetaminophen levelN-acetylcysteine\n==== Body\nAcetaminophen has become the most widely used analgesic–antipyretic in the United States, since its introduction in 1955. It is a component of innumerable over-the-counter and prescription medications that are used worldwide. Although safe when taken at usual therapeutic doses, acetaminophen overdose is a very common cause of drug toxicity and has been recognized as the most common cause of fatal and non-fatal hepatic necrosis (1).\n\n\nN-Acetylcysteine (NAC) is an effective antidote for the prevention and treatment of acetaminophen hepatotoxicity (2). There are two FDA-approved regimens for the treatment of acetaminophen poisoning: a 72-hour oral and a 21-hour IV protocol (2, 3). Current literature suggests that there is no significant difference between the rates of hepatotoxicity for oral and IV NAC administration (4). Both routes of administration are acceptable, but IV protocol is preferred in patients with contraindications to oral administration (e.g., vomiting, bowel ileus, or ingestion of substances that may alter gastric motility). Ideally, NAC treatment should be started within 8 hours of acetaminophen ingestion, or as soon as possible (2, 5). It is recommended that serum acetaminophen levels as well as liver functions be evaluated prior to, during, and at the end of the treatment regimen. If encephalopathy or elevated liver enzymes are present at the end of the 72-hour oral or 21-hour IV protocols, extending the NAC treatment is highly recommended (6, 7). Candidates for extension of NAC therapy include those with massive acetaminophen overdose, concomitant ingestion of other substances, preexisting liver disease, or patients with evidence of hepatic injury at the end of the recommended NAC therapy (7).\n\nCase report\nA 65-year-old male with a history of previous suicide attempts, bipolar disorder, hypertension, and coronary artery disease was found to be drowsy by his family members in the morning of his presentation to the emergency department (ED). He ingested an unknown number of Percocet (oxycodone 5 mg/acetaminophen 325 mg) and Xanax (alprazolam 1 mg) tablets in an attempted suicide. Two empty bottles of Percocet and Xanax were found in the patient's room. The number of ingested pills and the exact time of ingestion were unknown. He filled both prescriptions 7 days prior to the suicide attempt. His home medications consisted of Xanax 1 mg every 6 hours PRN, Percocet 325 mg/5 mg every 6 hours PRN, carvedilol (Coreg) 6.25 mg two times per day, amlodipine (Norvasc) 10 mg daily, Ibuprofen 600 mg daily PRN, tramadol 50 mg every 6 hours PRN, and zolpidem (Ambien) 10 mg daily at bedtime. No known drug allergies were reported.\n\nNaloxone was given in the ambulance with minimal improvement of his mental status. In the emergency room, the patient was found to be drowsy, unable to follow commands but arousable. Vital signs were temperature 98.8°F, heart rate 94 beats/min, blood pressure 112/88 mmHg, respiratory rate 18/min, and an oxygen saturation of 95% on room air. Pupils were 2 mm in diameter, equal, and reactive to light. A nasogastric tube (NGT) was placed and 1 L of bilious material was evacuated with pill fragments. Patient's mental status continued to deteriorate, and soon, he became unresponsive and bradycardic which warranted endotracheal intubation for airway protection. Urine toxicology was positive for benzodiazepines and opioids. Serum salicylate and ethanol levels were undetectable. The initial acetaminophen level was 75 µg/mL. Poison control center was contacted and the case discussed. The patient was subsequently started on NAC therapy, using the 21-hour IV protocol. Other baseline laboratory results included BUN 18 mg/dL, Cr 1.10 mg/dL, AST 8 IU/L, ALT 11 IU/L, total bilirubin 0.7 mg/dL, alkaline phosphatase 62 IU/L, and INR 0.97.\n\nThe patient was admitted to the intensive care unit. Two hours later, acetaminophen level decreased to 72 µg/mL. He continued to remain bradycardic and hypotensive, and was started on dopamine drip. Acetaminophen level measured 4 hours after admission was 67 µg/mL. His LFTs remained within normal limits. He completed the 21-hour NAC IV therapy with 1-hour loading dose (150 mg/kg/hr NAC), followed by a 4-hour (12.5 mg/kg/hr NAC) and then a 16-hour maintenance infusion (6.25 mg/kg/hr). His mental status slowly improved, vital signs stabilized, vasopressors were discontinued, and he was successfully extubated. At 24 hours from admission, the acetaminophen level was 21 µg/mL, and the NAC protocol was completed.\n\nAt 30 hours, patient's NGT was clogged and was removed. Upon inspection of the tube, there appeared to be solid material blocking the lumen which was thought to be medication fragments and a repeat acetaminophen level was immediately done and was found to be 150 µg/mL. After a 6-hour gap from the initial antidote protocol, NAC IV therapy was restarted using the last 16-hour infusion step of the 21-hour protocol. Patient's aminotransferase levels continued to remain normal. By 34 hours, his acetaminophen level was 119 µg/mL, and by 40 hours post-admission, it had trended down to normal/therapeutic level (27 µg/mL). Acetaminophen level became undetectable 90 hours post-admission (Fig. 1). The patient's liver enzymes remained normal throughout his admission. He was later discharged to an inpatient psychiatric facility.\n\nFig. 1 Variability of the acetaminophen serum concentration and levels of transaminases, during patient's hospitalization.\n\nDiscussion\nNAC is the recommended antidote for acetaminophen poisoning and is given to all patients at significant risk for hepatotoxicity. While there are no randomized, placebo-controlled trials evaluating the efficacy of NAC for the prevention of hepatic injury due to acetaminophen poisoning, several studies have described an extremely low incidence of hepatotoxicity following early NAC administration (3, 8). Additionally, NAC administration following acetaminophen ingestion in patients with evidence of hepatic failure decreases mortality and improves hepatic and cerebral function (7, 9). Despite evidence on the efficacy of NAC, controversy persists about the optimal duration of the therapy. While the two FDA-approved protocols for the treatment of acetaminophen poisoning are adequate for the vast majority of patients, there are reports indicating that the 21-hour protocol is not long enough in some cases (10, 11). Many authors recommend that therapy be tailored to each patient, using clinical endpoints rather than time, to determine the duration of treatment (11).\n\nThere were only two case reports of acetaminophen poisoning associated with double concentration peaks (10, 12). In contrast to previous reports, our patient's clinical course was not complicated by hepatotoxicity. Because our patient was asymptomatic and transaminases were within normal levels at the time of detection of the second acetaminophen peak, the antidotal therapy was prolonged by using the low-dose NAC infusion. Therefore, NAC therapy was extended for another 16 hours past the recommended 21-hour IV protocol and hepatic toxicity was successfully avoided.\n\nAberrant acetaminophen absorption and/or delayed gastric emptying potentiated by concurrent ingestion of other substances, like opiates, may cause persistently elevated acetaminophen serum levels. Published literature indicates that poisoning with tricyclic antidepressants, acetaminophen, opioid–acetaminophen mixtures, and carbamazepine causes gastric hypomotility and delayed emptying (13). Although acetaminophen is not known to have any inhibitory effect on the gastrointestinal tract, acetaminophen overdose doubled the individual average gastric emptying times (13).\n\nOther theories as to why some patients demonstrate a second peak of serum levels despite no repeated ingestions include excessive solubility, possible medication bezoar formation, individual variations in gastric emptying time, physiologically or chemically altered gastrointestinal motility, and enterohepatic recycling (14–17). These factors imply that potentially toxic amounts of residual acetaminophen can persist after a 21-hour intravenous NAC course. Discontinuation of NAC prior to complete acetaminophen absorption, metabolism, and elimination may result in significant hepatic injury and death.\n\nBased on current recommendations, NAC is indicated in patients with an unknown time of ingestion and a serum acetaminophen concentration >10 µg/mL. Our patient's initial acetaminophen level upon arrival in the ED was 75 µg/mL and a second peak of acetaminophen serum level was demonstrated 30 hours after admission. Continuous direct observation (one-to-one suicide precautions) made a second ingestion unlikely in our patient. We hypothesized that delayed gastric emptying due to high doses of acetaminophen along with oxycodone was the cause of the double peak of acetaminophen levels in our patient. More frequent interval sampling might have uncovered higher values at slightly different times, and the second peak of potentially hepatotoxic residual acetaminophen metabolite might have been discovered earlier. Fortunately, our patient did not have any significant liver damage despite a gap in continuation of NAC.\n\nIn patients with acetaminophen toxicity who co-ingest other medications that may potentially delay gastric emptying or in those with risk factors for delayed absorption of acetaminophen, we recommend close monitoring of aminotransferase enzyme levels, as well as trending acetaminophen concentrations until undetectable before discontinuing NAC therapy. High acetaminophen level after 21 hours of NAC treatment, elevated transaminases or symptomatic patient (e.g., right upper quadrant pain, hepatic encephalopathy), require prolongation of the standard recommended time for NAC therapy.\n\nConclusions\nWe presented a case of a patient with concomitant acetaminophen and opioid ingestion who developed a rising acetaminophen level after completing IV NAC protocol when the standard ‘stop’ criteria for monitoring drug levels was achieved. Experimental evidence and case reports have documented delayed absorption following ingestion of extended-release acetaminophen, opioid- or anticholinergic- containing acetaminophen products, or co-ingestants (13). Delay in acetaminophen absorption may be associated with a second peak in acetaminophen concentration following an initial declining trend. We recommend checking acetaminophen serum levels several hours after protocol completion to detect post-treatment rising levels, especially in cases of concomitant ingestion of opioids.\n\nAuthors' contributions\nCP, JRA, MM, PB, and SJ contributed to conception and design, and drafting and revising of this article; CP acquired and interpreted the data; JRA interpreted the data. Finally, all authors approved the final version.\n\nConflict of interest and funding\nThe authors declare that they do not have a conflict of interest.\n==== Refs\nReferences\n1 Bronstein AC Spyker DA Cantilena LR Jr Green J Rumack BH Heard SE Annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS) Clin Toxicol 2007 45 815 917 \n2 Smilkstein MJ Knapp GL Kulig KW Rumack BH Efficacy of oral N -acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985) N Engl J Med 1988 319 1557 62 3059186 \n3 Prescott LF Park J Ballantyne A Adriaenssens P Proudfoot AT Treatment of paracetamol (acetaminophen) poisoning with N -acetylcysteine Lancet 1977 2 432 70646 \n4 Green JL Heard KJ Reynolds KM Albert D Oral and intravenous acetylcysteine for treatment of acetaminophen toxicity: A systematic review and meta-analysis West J Emerg Med 2013 14 218 26 23687539 \n5 Prescott LF Treatment of severe acetaminophen poisoning with intravenous acetylcysteine Arch Intern Med 1981 141 386 7469630 \n6 Doyon S Klein-Schwartz W Hepatotoxicity despite early administration of intravenous N -acetylcysteine for acute acetaminophen overdose Acad Emerg Med 2009 16 34 19007345 \n7 Keays R Harrison PM Wendon JA Forbes A Gove C Alexander GJ Intravenous acetylcysteine in paracetamol-induced fulminant hepatic failure: A prospective controlled trial BMJ 1991 303 1026 9 1954453 \n8 Heard K Rumack BH Green JL Bucher-Bartelson B Heard S Bronstein AC A single-arm clinical trial of a 48-hour intravenous N -acetylcysteine protocol for treatment of acetaminophen poisoning Clin Toxicol (Phila) 2014 52 512 24708414 \n9 Harrison PM Keays R Bray GP Alexander GJ Williams R Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine Lancet 1990 335 1572 1972496 \n10 Smith SW Howland MA Hoffman RS Nelson LS Acetaminophen overdose with altered acetaminophen pharmacokinetics and hepatotoxicity associated with premature cessation of intravenous N -acetylcysteine therapy Ann Pharmacother 2008 42 9 1333 9 18628444 \n11 Dart RC Rumack BH Patient-tailored acetylcysteine administration Ann Emerg Med 2007 50 280 17418449 \n12 Burda T Sigg T Double peak and prolonged absorption after large acetaminophen extended release and diphenhydramine ingestion Am J Ther 2012 19 2 e101 4 21403469 \n13 Adams BK Mann MD Aboo A Isaacs S Evans A Prolonged gastric emptying half-time and gastric hypomotility after drug overdose Am J Emerg Med 2004 6 548 54 15666259 \n14 Roberts MS Magnusson BM Burczynski FJ Weiss M Enterohepatic circulation: Physiological, pharmacokinetic and clinical implications Clin Pharmacokinet 2002 41 751 90 12162761 \n15 Young A Inhibition of gastric emptying Adv Pharmacol 2005 52 99 121 16492543 \n16 Clements JA Heading RC Nimmo WS Prescott LF Kinetics of acetaminophen absorption and gastric emptying in man Clin Pharmacol Ther 1978 24 420 31 688732 \n17 Schurizek BA Kraglund K Andreasen F Vinter-Jensen L Juhl B Antroduodenal motility and gastric emptying. Gastroduodenal motility and pH following ingestion of paracetamol Aliment Pharmacol Ther 1989 3 93 101 2491461\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "2000-9666", "issue": "5(6)", "journal": "Journal of community hospital internal medicine perspectives", "keywords": "N-acetylcysteine; acetaminophen level; acetaminophen toxicity", "medline_ta": "J Community Hosp Intern Med Perspect", "mesh_terms": null, "nlm_unique_id": "101601396", "other_id": null, "pages": "29589", "pmc": null, "pmid": "26653695", "pubdate": "2015", "publication_types": "D002363:Case Reports", "references": "24708414;16492543;19007345;688732;12162761;70646;1954453;1972496;18163234;15666259;23687539;7469630;18628444;17418449;3059186;2491461;21403469", "title": "Acetaminophen overdose associated with double serum concentration peaks.", "title_normalized": "acetaminophen overdose associated with double serum concentration peaks" }

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{ "abstract": "We present the case of a 36-year-old woman with diffuse idiopathic skeletal hyperostosis especially at cervical spine since she was 29 years old. The only relevant feature was the use of isotretinoin at regular doses in the past for severe acne.", "affiliations": "Department of Rheumatology, Hospital Son Llàtzer, Palma de Mallorca, Spain. Electronic address: [email protected].;Department of Radiology, Hospital Son Llàtzer, Palma de Mallorca, Spain.;Department of Rheumatology, Hospital Son Llàtzer, Palma de Mallorca, Spain.;Department of Rheumatology, Hospital Son Llàtzer, Palma de Mallorca, Spain.", "authors": "Ibáñez Barceló|Monica|M|;Estremera Rodrigo|Ana|A|;Ros Vilamajó|Inmaculada|I|;Juan Mas|Antonio|A|", "chemical_list": null, "country": "Spain", "delete": false, "doi": "10.1016/j.reuma.2020.09.005", "fulltext": null, "fulltext_license": null, "issn_linking": "2173-5743", "issue": null, "journal": "Reumatologia clinica", "keywords": "Diffuse idiopathic skeletal hyperostosis; Hiperostosis anquilosante vertebral difusa; Isotretinoin; Isotretinoína", "medline_ta": "Reumatol Clin (Engl Ed)", "mesh_terms": null, "nlm_unique_id": "101717526", "other_id": null, "pages": null, "pmc": null, "pmid": "33139176", "pubdate": "2020-10-31", "publication_types": "D002363:Case Reports", "references": null, "title": "Diffuse Idiopathic Skeletal Hyperostosis in a Young Woman Treated With Isotretinoin.", "title_normalized": "diffuse idiopathic skeletal hyperostosis in a young woman treated with isotretinoin" }

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Diffuse idiopathic skeletal hyperostosis in a young woman treated with isotretinoin. Reumatol Clin. 2022;18(3):184-185", "literaturereference_normalized": "diffuse idiopathic skeletal hyperostosis in a young woman treated with isotretinoin", "qualification": "3", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20220607", "receivedate": "20220607", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20928894, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220720" }, { "companynumb": "ES-SUN PHARMACEUTICAL INDUSTRIES LTD-2020R1-268266", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "ISOTRETINOIN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "021951", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MILLIGRAM, DAILY", "drugenddate": "201004", "drugenddateformat": "610", "drugindication": "Acne", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200901", "drugstartdateformat": "610", "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": "464", "drugtreatmentdurationunit": "804", "medicinalproduct": "ISOTRETINOIN" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "ISOTRETINOIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "021951", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "CYCLICAL", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "1995", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ISOTRETINOIN" } ], "patientagegroup": null, "patientonsetage": "36", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Diffuse idiopathic skeletal hyperostosis", "reactionmeddraversionpt": "25.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Enthesopathy", "reactionmeddraversionpt": "25.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Enthesopathy", "reactionmeddraversionpt": "25.0", "reactionoutcome": "2" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20080101" } }, "primarysource": { "literaturereference": "Ibanez Barcelo M, Estremera Rodrigo A, Ros Vilamajo I, Juan Mas A. Diffuse Idiopathic Skeletal Hyperostosis in a Young Woman Treated With Isotretinoin. Reumatol Clin. 2020;18:184-185", "literaturereference_normalized": "diffuse idiopathic skeletal hyperostosis in a young woman treated with isotretinoin", "qualification": "3", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20220606", "receivedate": "20201120", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18524415, "safetyreportversion": 4, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220721" } ]

{ "abstract": "A 15-year-old patient with cystic fibrosis with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung transplantation. Effective lytic phage derivatives that efficiently kill the infectious M. abscessus strain were developed by genome engineering and forward genetics. Intravenous phage treatment was well tolerated and associated with objective clinical improvement, including sternal wound closure, improved liver function, and substantial resolution of infected skin nodules.", "affiliations": "Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.;Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.;Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.;Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.;Great Ormond Street Hospital, London, UK.;Great Ormond Street Hospital, London, UK.;Great Ormond Street Hospital, London, UK.;Great Ormond Street Hospital, London, UK.;Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.;Department of Medicine, University of California, San Diego, La Jolla, CA, USA.;Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA. [email protected].;Great Ormond Street Hospital, London, UK. [email protected].", "authors": "Dedrick|Rebekah M|RM|;Guerrero-Bustamante|Carlos A|CA|;Garlena|Rebecca A|RA|;Russell|Daniel A|DA|;Ford|Katrina|K|;Harris|Kathryn|K|;Gilmour|Kimberly C|KC|;Soothill|James|J|;Jacobs-Sera|Deborah|D|;Schooley|Robert T|RT|;Hatfull|Graham F|GF|http://orcid.org/0000-0002-6705-6821;Spencer|Helen|H|http://orcid.org/0000-0003-2474-3290", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1038/s41591-019-0437-z", "fulltext": null, "fulltext_license": null, "issn_linking": "1078-8956", "issue": "25(5)", "journal": "Nature medicine", "keywords": null, "medline_ta": "Nat Med", "mesh_terms": "D000293:Adolescent; D003550:Cystic Fibrosis; D024881:Drug Resistance, Bacterial; D005260:Female; D005818:Genetic Engineering; D006801:Humans; D009165:Mycobacterium Infections, Nontuberculous; D000073358:Mycobacterium abscessus; D000071059:Phage Therapy", "nlm_unique_id": "9502015", "other_id": null, "pages": "730-733", "pmc": null, "pmid": "31068712", "pubdate": "2019-05", "publication_types": "D002363:Case Reports; D016428:Journal Article; D052061:Research Support, N.I.H., Extramural; D013485:Research Support, Non-U.S. Gov't", "references": "810794;20008865;29588855;26018169;19088849;28881094;23246436;30948168;23638204;7327068;30071553;25580261;29359872;23084079;30214436;16388028;28807909", "title": "Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus.", "title_normalized": "engineered bacteriophages for treatment of a patient with a disseminated drug resistant mycobacterium abscessus" }

[ { "companynumb": "US-VERTEX PHARMACEUTICALS-2019-005166", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "IVACAFTOR\\LUMACAFTOR" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": "206038", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "CYSTIC FIBROSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ORKAMBI" } ], "patientagegroup": null, "patientonsetage": "15", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Forced expiratory volume decreased", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pulmonary artery dilatation", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypercapnia", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Lung transplant", "reactionmeddraversionpt": "22.0", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "DEDRICK RM, GUERRERO-BUSTAMANTE CA, GARLENA RA, RUSSELL DA, FORD K, HARRIS K, ET AL. ENGINEERED BACTERIOPHAGES FOR TREATMENT OF A PATIENT WITH A DISSEMINATED DRUG-RESISTANT MYCOBACTERIUM ABSCESSUS. NAT MED. 2019?25:730-733", "literaturereference_normalized": "engineered bacteriophages for treatment of a patient with a disseminated drug resistant mycobacterium abscessus", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20190607", "receivedate": "20190607", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16406010, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190711" } ]

{ "abstract": "Adverse drug reactions are a major cause of hospital admissions in older individuals, with the majority potentially preventable. Despite the apparent magnitude of this problem, little is known about rates of repeat admission to hospital as a result of adverse drug reactions.\n\n\n\nThe objectives of this study were to investigate the occurrence of repeat adverse drug reaction-related hospital admissions in elderly patients within 12 months of an adverse drug reaction-related admission to a medical ward and whether a validated adverse drug reaction score could be useful in identifying patients at higher risk of a repeat adverse drug reaction-related hospitalisation.\n\n\n\nThis retrospective study followed elderly participants who were hospitalised with an adverse drug reaction from our earlier study [the PADR-EC (Prediction of Hospitalization due to Adverse Drug Reactions in Elderly Community-Dwelling Patients) study] to identify repeat adverse drug reaction-related hospital admissions within 12 months of discharge. The PADR-EC score is the sum of points assigned to five significant predictors of adverse drug reaction-related hospitalisation: antihypertensive use, renal failure, dementia, inappropriate anticholinergic use and drug changes in the preceding 3 months. The causality, preventability and severity of each adverse drug reaction-related repeat admission within the 12-month follow-up were assessed.\n\n\n\nAdverse drug reaction-related repeat admissions occurred after 13.4% (n = 15) of 112 adverse drug reaction-related index admissions. Patients with a repeat adverse drug reaction-related admission had significantly higher PADR-EC scores at discharge of their index admission (median PADR-EC score 7, interquartile range 7-9) than patients who were not readmitted (median PADR-EC score 7, interquartile range 5-7, p = 0.034). Most (73.3%) adverse drug reaction-related repeat admissions were considered 'preventable'. Adverse drug reaction severity was 'moderate' in all cases. Renal disorders (44.4%) represented the most common adverse drug reactions and the most frequently implicated drug classes were diuretics (44.8%). All adverse drug reaction-related repeat admissions were found to be 'probable'.\n\n\n\nOne in eight elderly patients hospitalised because of an adverse drug reaction had a repeat admission for an adverse drug reaction within 12 months of discharge. The PADR-EC score could potentially be used at hospital discharge to prioritise patients for interventions to prevent subsequent adverse drug reaction-related hospital admissions.", "affiliations": "Unit for Medication Outcomes Research and Education, Division of Pharmacy, Faculty of Health, School of Medicine, University of Tasmania, Private Bag 26, Hobart, TAS, 7001, Australia. [email protected].;Unit for Medication Outcomes Research and Education, Division of Pharmacy, Faculty of Health, School of Medicine, University of Tasmania, Private Bag 26, Hobart, TAS, 7001, Australia.;Unit for Medication Outcomes Research and Education, Division of Pharmacy, Faculty of Health, School of Medicine, University of Tasmania, Private Bag 26, Hobart, TAS, 7001, Australia.;Unit for Medication Outcomes Research and Education, Division of Pharmacy, Faculty of Health, School of Medicine, University of Tasmania, Private Bag 26, Hobart, TAS, 7001, Australia.;Unit for Medication Outcomes Research and Education, Division of Pharmacy, Faculty of Health, School of Medicine, University of Tasmania, Private Bag 26, Hobart, TAS, 7001, Australia.", "authors": "Parameswaran Nair|Nibu|N|0000-0002-0202-6453;Chalmers|Leanne|L|;Bereznicki|Bonnie J|BJ|;Curtain|Colin M|CM|;Bereznicki|Luke R|LR|", "chemical_list": "D018680:Cholinergic Antagonists; D004232:Diuretics", "country": "New Zealand", "delete": false, "doi": "10.1007/s40266-017-0490-6", "fulltext": null, "fulltext_license": null, "issn_linking": "1170-229X", "issue": "34(10)", "journal": "Drugs & aging", "keywords": null, "medline_ta": "Drugs Aging", "mesh_terms": "D000368:Aged; D001315:Australia; D018680:Cholinergic Antagonists; D004232:Diuretics; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006760:Hospitalization; D006761:Hospitals; D006801:Humans; D008297:Male; D008875:Middle Aged; D010343:Patient Admission; D010351:Patient Discharge; D012189:Retrospective Studies", "nlm_unique_id": "9102074", "other_id": null, "pages": "777-783", "pmc": null, "pmid": "28952130", "pubdate": "2017-10", "publication_types": "D016428:Journal Article", "references": "15147529;27798708;27913837;16908802;10075613;10118597;27194906;17274789;7843344;25340159;1524068;18245865;19129307;7249508;26884320;27377393;18313773;21039769;23252914;28382494", "title": "Repeat Adverse Drug Reaction-Related Hospital Admissions in Elderly Australians: A Retrospective Study at the Royal Hobart Hospital.", "title_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital" }

[ { "companynumb": "AU-VALIDUS PHARMACEUTICALS LLC-AU-2017VAL001574", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "016273", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL TARTRATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL TARTRATE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bradycardia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR N P., CHALMERS L.,BEREZNICKI B J., CURTAIN C M., BEREZNICKI L R.;. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AGING. 2017;34:777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171122", "receivedate": "20171122", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14216644, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-BAUSCH-BL-2018-025566", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LOSARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOSARTAN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ETHACRYNIC ACID" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "016092", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "INAPPROPRIATE DOSING", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHACRYNIC ACID." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DIGOXIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "INAPPROPRIATE DOSING", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIGOXIN." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Diarrhoea", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR N, CHALMERS L, BEREZNICKI B, CURTAIN C, BEREZNICKI L. REPEAT ADVERSE DRUG REACTION?RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AGING. 2017?34:777?783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20180920", "receivedate": "20180920", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15409064, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20181010" }, { "companynumb": "AU-MYLANLABS-2017M1072471", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PROPRANOLOL HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PROPRANOLOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IRBESARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "200461", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IRBESARTAN." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Syncope", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING 2017;34(10):777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171117", "receivedate": "20171117", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14200464, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-MYLANLABS-2017M1072425", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "040424", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": [ { "drugrecuraction": "Acute kidney injury" } ], "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": [ { "drugrecuraction": "Acute kidney injury" } ], "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CANDESARTAN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": [ { "drugrecuraction": "Acute kidney injury" } ], "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hyponatraemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING 2017;34(10):777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171117", "receivedate": "20171117", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14199947, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-SUN PHARMACEUTICAL INDUSTRIES LTD-2017RR-155693", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "NITROGLYCERIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLYCERYL TRINITRATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXAZEPAM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXAZEPAM." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMLODIPINE BESYLATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "77974", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMLODIPINE" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Dizziness", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Syncope", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171204", "receivedate": "20171204", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14245987, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-MYLANLABS-2017M1072427", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PERINDOPRIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PERINDOPRIL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "040424", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PRAZOSIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PRAZOSIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMITRIPTYLINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMITRIPTYLINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "RECEIVING 2G/DAY DURING 1ST ADMISSION", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Wrong drug administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Orthostatic hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Blood lactic acid increased", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING 2017;34(10):777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171117", "receivedate": "20171117", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14200037, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-MYLANLABS-2017M1072477", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ALLOPURINOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "018659", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALLOPURINOL." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING 2017;34(10):777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171117", "receivedate": "20171117", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14200467, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "PHHY2017AU171982", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PROPRANOLOL HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PROPRANOLOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IRBESARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "77466", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IRBESARTAN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Syncope", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR NP, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AND AGING. 2017;34 (10):777-83", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171122", "receivedate": "20171122", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14216477, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-SUN PHARMACEUTICAL INDUSTRIES LTD-2017RR-155747", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "91258", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171204", "receivedate": "20171204", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14246587, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-VALIDUS PHARMACEUTICALS LLC-AU-2017VAL001576", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "016273", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL TARTRATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL TARTRATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bradycardia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR N P., CHALMERS L., BEREZNICKI B J., CURTAIN C M., BEREZNICKI L R.. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AGING. 2017;34:777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171122", "receivedate": "20171122", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14216687, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-SUN PHARMACEUTICAL INDUSTRIES LTD-2017RR-155736", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DIGOXIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIGOXIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ETHACRYNIC ACID" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHACRYNIC ACID." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LOSARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOSARTAN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "91258", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Diarrhoea", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Rash", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171204", "receivedate": "20171204", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14245988, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-MYLANLABS-2017M1072468", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CLOPIDOGREL BISULFATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "077665", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLOPIDOGREL" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Haemorrhage", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypoglycaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING 2017;34(10):777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171117", "receivedate": "20171117", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14200308, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-VIVIMED-2018SP005471", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NITROGLYCERIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLYCERYL TRINITRATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMLODIPINE BESYLATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "077516", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMLODIPINE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Syncope", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Dizziness", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR.. REPEAT ADVERSE DRUG REACTION?RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL.. DRUGS?AGING. 2017?34(10):777?783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20180709", "receivedate": "20180709", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15118698, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20181010" }, { "companynumb": "AU-SUN PHARMACEUTICAL INDUSTRIES LTD-2017RR-155775", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "089424", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hyponatraemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171204", "receivedate": "20171204", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14246588, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-PFIZER INC-2017470032", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": [ { "drugrecuraction": "Drug interaction" } ], "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "019901", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": [ { "drugrecuraction": "Drug interaction" } ], "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR, N.. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AND AGING. 2017;34 (10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171124", "receivedate": "20171124", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14220406, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-SUN PHARMACEUTICAL INDUSTRIES LTD-2017RR-155742", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "91258", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "THEOPHYLLINE ANHYDROUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THEOPHYLLINE" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Vomiting", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171204", "receivedate": "20171204", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14245986, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-009507513-1711AUS001475", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "SITAGLIPTIN PHOSPHATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "021995", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "FILM-COATED TABLET", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SITAGLIPTIN PHOSPHATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "GLICLAZIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLICLAZIDE" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hypoglycaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR N, CHALMERS L, BEREZNICKI B, CURTAIN C, BEREZNICKI L. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AND AGING. 2017;34(10):777-83", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171109", "receivedate": "20171105", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14157616, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-VALIDUS PHARMACEUTICALS LLC-AU-2017VAL001575", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PERINDOPRIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PERINDOPRIL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PRAZOSIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PRAZOSIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMITRIPTYLINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMITRIPTYLINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "016273", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 G, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Orthostatic hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Blood lactic acid increased", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR N P., CHALMERS L., BEREZNICKI B J., CURTAIN C M., BEREZNICKI L R.;. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AGING. 2017;34:777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171122", "receivedate": "20171122", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14216656, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-SUN PHARMACEUTICAL INDUSTRIES LTD-2017RR-155748", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "74644", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bradycardia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171204", "receivedate": "20171204", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14246586, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-MYLANLABS-2017M1072422", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMIODARONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "076217", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMIODARONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "GLICLAZIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLICLAZIDE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SITAGLIPTIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SITAGLIPTIN" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hypoglycaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypothyroidism", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING 2017;34(10):777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171117", "receivedate": "20171117", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14199946, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-VALIDUS PHARMACEUTICALS LLC-AU-2017VAL001585", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "016273", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ALLOPURINOL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALLOPURINOL." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR NP, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AGING. 2017;34:777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171127", "receivedate": "20171127", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14227436, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-MYLANLABS-2017M1072430", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "THEOPHYLLINE ANHYDROUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THEOPHYLLINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "018487", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Labelled drug-drug interaction medication error", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Vomiting", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING 2017;34(10):777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171117", "receivedate": "20171117", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14199949, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "PHHY2017AU162558", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "77360", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN CILEXETIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN CILEXETIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bradycardia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR NP, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AND AGING. 2017;34:777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171109", "receivedate": "20171109", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14174599, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-DRREDDYS-AUS/AUS/17/0094737", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CLOPIDOGREL BISULFATE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "076273", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLOPIDOGREL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Haemorrhage", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypoglycaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR P, CHALMERS L, BEREZNICKI B, CURTAIN C, BEREZNICKI L. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL.. DRUGS-AGING. 2017;34(10):777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171123", "receivedate": "20171123", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14217939, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-SUN PHARMACEUTICAL INDUSTRIES LTD-2017RR-155743", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "089424", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyponatraemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171204", "receivedate": "20171204", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14245989, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "PHHY2017AU166335", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "GLICLAZIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLICLAZIDE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMIODARONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "75315", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMIODARONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SITAGLIPTIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SITAGLIPTIN" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hypoglycaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypothyroidism", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34 (10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171124", "receivedate": "20171124", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14220429, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-SUN PHARMACEUTICAL INDUSTRIES LTD-2017RR-155746", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "91258", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ALLOPURINOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALLOPURINOL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171204", "receivedate": "20171204", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14246582, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-MYLANLABS-2017M1072432", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN CILEXETIL" }, 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"drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CANDESARTAN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BISOPROLOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BISOPROLOL" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Bradycardia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING 2017;34(10):777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171117", "receivedate": "20171117", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14199952, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "PHHY2017AU162543", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN CILEXETIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN CILEXETIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMLODIPINE BESYLATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMLODIPINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NITROGLYCERIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLYCERYL TRINITRATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "018569", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Syncope", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Dizziness", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR NP, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AND AGING. 2017;34:777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171108", "receivedate": "20171108", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14171562, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-PFIZER INC-2017483620", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "019901", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR, N.. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AND AGING. 2017;34 (10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171129", "receivedate": "20171120", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14206402, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "PHHY2017AU162562", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "75985", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 G, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PRAZOSIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PRAZOSIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED 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"drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMITRIPTYLINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "75985", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Orthostatic hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Blood lactic acid increased", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR NP, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AND AGING. 2017;34:777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171107", "receivedate": "20171107", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14165180, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "PHHY2017AU166361", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ALLOPURINOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "70269", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALLOPURINOL." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR NP, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AND AGING. 2017;34 (10):774-83", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171116", "receivedate": "20171116", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14197190, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-VALIDUS PHARMACEUTICALS LLC-AU-2017VAL001570", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL TARTRATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "017963", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL TARTRATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXAZEPAM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXAZEPAM." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN CILEXETIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN CILEXETIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMLODIPINE BESYLATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMLODIPINE BESILATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NITROGLYCERIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLYCERYL TRINITRATE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Dizziness", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Syncope", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR N P., CHALMERS L., BEREZNICKI B J., CURTAIN C M., BEREZNICKI L R.;. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AGING. 2017;34:777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171122", "receivedate": "20171122", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14216570, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-MYLANLABS-2017M1072421", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "076704", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "RECEIVED INAPPROPRIATE DOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Bradycardia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING 2017;34(10):777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171117", "receivedate": "20171117", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14199960, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "PHHY2017AU162552", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "75985", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CLOPIDOGREL BISULFATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLOPIDOGREL" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Haemorrhage", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypoglycaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR NP, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL.. DRUGS AND AGING. 2017;34:777-83", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171108", "receivedate": "20171108", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14170130, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-NORTHSTAR HEALTHCARE HOLDINGS-AU-2017NSR000249", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PROPRANOLOL HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "078213", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PROPRANOLOL HYDROCHLORIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IRBESARTAN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IRBESARTAN." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Syncope", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171218", "receivedate": "20171218", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14295760, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-SUN PHARMACEUTICAL INDUSTRIES LTD-2017RR-155738", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CLOPIDOGREL BISULFATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "90494", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLOPIDOGREL" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Haemorrhage", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypoglycaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171204", "receivedate": "20171204", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14246585, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-NORTHSTAR HEALTHCARE HOLDINGS-AU-2017NSR000251", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ALLOPURINOL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "078253", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALLOPURINOL." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171218", "receivedate": "20171218", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14298875, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-SUN PHARMACEUTICAL INDUSTRIES LTD-2017RR-155796", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "089424", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BISOPROLOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BISOPROLOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bradycardia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171205", "receivedate": "20171205", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14249545, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-MYLANLABS-2017M1072465", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DIGOXIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIGOXIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LOSARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOSARTAN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ETHACRYNATE SODIUM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETACRYNATE SODIUM" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "018487", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Diarrhoea", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Rash", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING 2017;34(10):777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171117", "receivedate": "20171117", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14200315, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-PFIZER INC-2017483624", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "012151", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMITRIPTYLINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, 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null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PRAZOSIN HCL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PERINDOPRIL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PERINDOPRIL" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Orthostatic hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Wrong drug administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR, N.. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AND AGING. 2017;34 (10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171109", "receivedate": "20171109", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14175695, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-EDENBRIDGE PHARMACEUTICALS, LLC-AU-2017EDE000223", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ETHACRYNIC ACID" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "205609", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHACRYNIC ACID." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR.. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL.. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171221", "receivedate": "20171221", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14315171, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-PFIZER INC-2017483404", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXAZEPAM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXAZEPAM." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NITROGLYCERIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "021134", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NITROGLYCERIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMLODIPINE BESYLATE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "019787", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMLODIPINE BESILATE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CANDESARTAN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Dizziness", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Syncope", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR, N.. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AND AGING. 2017;34 (10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171120", "receivedate": "20171109", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14175401, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-MYLANLABS-2017M1072461", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NITROGLYCERIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "074559", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLYCERYL TRINITRATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXAZEPAM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXAZEPAM." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN MYLAN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN CILEXETIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "RECEIVED INAPPROPRIATE DOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN CILEXETIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMLODIPINE BESYLATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMLODIPINE" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Dizziness", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Syncope", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING 2017;34(10):777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171117", "receivedate": "20171117", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14200311, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-MYLANLABS-2017M1072473", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "018487", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "RECEIVED INAPPROPRIATE DOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "RECEIVED INAPPROPRIATE DOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyponatraemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING 2017;34(10):777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171117", "receivedate": "20171117", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14200463, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-BAUSCH-BL-2018-025998", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMLODIPINE BESYLATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMLODIPINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NITROGLYCERIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "89771", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLYCERYL TRINITRATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXAZEPAM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXAZEPAM." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CANDESARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "INAPPROPRIATE DOSING", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CANDESARTAN." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Syncope", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Dizziness", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAIR N, CHALMERS L, BEREZNICKI B, CURTAIN C, BEREZNICKI L. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS AGING. 2017?34:777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20181024", "receivedate": "20181024", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15546923, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190205" }, { "companynumb": "AU-SUN PHARMACEUTICAL INDUSTRIES LTD-2017RR-155789", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "SPIRONOLACTONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "089424", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SPIRONOLACTONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMITRIPTYLINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMITRIPTYLINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PRAZOSIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PRAZOSIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PERINDOPRIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PERINDOPRIL" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Incorrect dose administered", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug administration error", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperlactacidaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Orthostatic hypotension", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI L. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171205", "receivedate": "20171205", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14249543, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-TEVA-2017-AU-827689", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CLOPIDOGREL BISULFATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "076999", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLOPIDOGREL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Haemorrhage", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypoglycaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING 2017;34(10):777-783.", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171204", "receivedate": "20171201", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14244723, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "AU-SUN PHARMACEUTICAL INDUSTRIES LTD-2017RR-155745", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "91258", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PARAMESWARAN NAIR N, CHALMERS L, BEREZNICKI BJ, CURTAIN CM, BEREZNICKI LR. REPEAT ADVERSE DRUG REACTION-RELATED HOSPITAL ADMISSIONS IN ELDERLY AUSTRALIANS: A RETROSPECTIVE STUDY AT THE ROYAL HOBART HOSPITAL. DRUGS-AGING. 2017;34(10):777-783", "literaturereference_normalized": "repeat adverse drug reaction related hospital admissions in elderly australians a retrospective study at the royal hobart hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171204", "receivedate": "20171204", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14246583, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" } ]

{ "abstract": "Initial presentation of peritoneal dialysis associated infectious peritonitis can be clinically indistinguishable from Clostridioides difficile infection (CDI) and both may demonstrate a cloudy dialysate. Empiric treatment of the former entails use of 3rd-generation cephalosporins, which could worsen CDI. We present a logical management approach of this clinical scenario providing examples of two cases with CDI associated peritonitis of varying severity where the initial picture was concerning for peritonitis and treatment for CDI resulted in successful cure.\n\n\n\nA 73-year-old male with ESRD managed with PD presented with fever, abdominal pain, leukocytosis and significant diarrhea. Cell count of the peritoneal dialysis effluent revealed 1050 WBCs/mm3 with 71% neutrophils. C. difficile PCR on the stool was positive. Patient was started on intra-peritoneal (IP) cefepime and vancomycin for treatment of the peritonitis and intravenous (IV) metronidazole and oral vancomycin for treatment of the C. difficile colitis but worsened. PD fluid culture showed no growth. He responded well to IV tigecycline, oral vancomycin and vancomycin enemas. Similarly, a 55-year-old male with ESRD with PD developed acute diarrhea and on the third day noted a cloudy effluent from his dialysis catheter. PD fluid analysis showed 1450 WBCs/mm3 with 49% neutrophils. IP cefepime and vancomycin were initiated. CT of the abdomen showed rectosigmoid colitis. C. difficile PCR on the stool was positive. IP cefepime and vancomycin were promptly discontinued. Treatment with oral vancomycin 125 mg every six hours and IV Tigecycline was initiated. PD fluid culture produced no growth. PD catheter was retained.\n\n\n\nIn patients presenting with diarrhea with risk factors for CDI, traditional empiric treatment of PD peritonitis may need to be reexamined as they could have detrimental effects on CDI course and patient outcomes.", "affiliations": "Metro Infectious Disease Consultants, 7444 Hannover Pkwy Ste 210, Stockbridge, GA, 30281, USA. [email protected].;Department of Medicine, Division of Infectious Diseases and Global Medicine, University of Florida, Gainesville, FL, USA.;Department of Medicine, Division of Infectious Diseases and Global Medicine, University of Florida, Gainesville, FL, USA.;University of Florida - College of Medicine, Gainesville, FL, USA.;Department of Veteran Affairs, North Florida South Georgia VHS, Gainesville, FL, USA.", "authors": "Shah|Kairav J|KJ|0000-0001-6518-2683;Cherabuddi|Kartikeya|K|;Pressly|Kalynn B|KB|;Wright|Kaitlyn L|KL|;Shukla|Ashutosh|A|", "chemical_list": "D000900:Anti-Bacterial Agents; D014640:Vancomycin; D000078304:Tigecycline", "country": "England", "delete": false, "doi": "10.1186/s12882-020-01734-8", "fulltext": "\n==== Front\nBMC Nephrol\nBMC Nephrol\nBMC Nephrology\n1471-2369 BioMed Central London \n\n1734\n10.1186/s12882-020-01734-8\nCase Report\nClostridioides difficile associated peritonitis in peritoneal dialysis patients – a case series based review of an under-recognized entity with therapeutic challenges\nhttp://orcid.org/0000-0001-6518-2683Shah Kairav J. [email protected] 1 Cherabuddi Kartikeya [email protected] 2 Pressly Kalynn B. [email protected] 2 Wright Kaitlyn L. [email protected] 3 Shukla Ashutosh [email protected] 45 1 Metro Infectious Disease Consultants, 7444 Hannover Pkwy Ste 210, Stockbridge, GA 30281 USA \n2 grid.15276.370000 0004 1936 8091Department of Medicine, Division of Infectious Diseases and Global Medicine, University of Florida, Gainesville, FL USA \n3 grid.15276.370000 0004 1936 8091University of Florida – College of Medicine, Gainesville, FL USA \n4 Department of Veteran Affairs, North Florida South Georgia VHS, Gainesville, FL USA \n5 grid.15276.370000 0004 1936 8091Department of Medicine, Division of Nephrology, Hypertension & Renal Transplantation, University of Florida, Gainesville, FL USA \n4 3 2020 \n4 3 2020 \n2020 \n21 7618 7 2019 19 2 2020 © The Author(s) 2020Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background\nInitial presentation of peritoneal dialysis associated infectious peritonitis can be clinically indistinguishable from Clostridioides difficile infection (CDI) and both may demonstrate a cloudy dialysate. Empiric treatment of the former entails use of 3rd-generation cephalosporins, which could worsen CDI. We present a logical management approach of this clinical scenario providing examples of two cases with CDI associated peritonitis of varying severity where the initial picture was concerning for peritonitis and treatment for CDI resulted in successful cure.\n\nCase presentation\nA 73-year-old male with ESRD managed with PD presented with fever, abdominal pain, leukocytosis and significant diarrhea. Cell count of the peritoneal dialysis effluent revealed 1050 WBCs/mm3 with 71% neutrophils. C. difficile PCR on the stool was positive. Patient was started on intra-peritoneal (IP) cefepime and vancomycin for treatment of the peritonitis and intravenous (IV) metronidazole and oral vancomycin for treatment of the C. difficile colitis but worsened. PD fluid culture showed no growth. He responded well to IV tigecycline, oral vancomycin and vancomycin enemas. Similarly, a 55-year-old male with ESRD with PD developed acute diarrhea and on the third day noted a cloudy effluent from his dialysis catheter. PD fluid analysis showed 1450 WBCs/mm3 with 49% neutrophils. IP cefepime and vancomycin were initiated. CT of the abdomen showed rectosigmoid colitis. C. difficile PCR on the stool was positive. IP cefepime and vancomycin were promptly discontinued. Treatment with oral vancomycin 125 mg every six hours and IV Tigecycline was initiated. PD fluid culture produced no growth. PD catheter was retained.\n\nConclusions\nIn patients presenting with diarrhea with risk factors for CDI, traditional empiric treatment of PD peritonitis may need to be reexamined as they could have detrimental effects on CDI course and patient outcomes.\n\nKeywords\nPeritonitisClostridioides difficilePeritoneal dialysishttp://dx.doi.org/10.13039/100000738U.S. Department of Veterans AffairsI01HX002639I01CX001661Shukla Ashutosh issue-copyright-statement© The Author(s) 2020\n==== Body\nBackground\nPeritoneal dialysis (PD) peritonitis is a dominant cause of PD failure among patients with end stage renal disease (ESRD). These individuals present largely with a gastrointestinal (GI) syndrome with or without accompanying systemic features e.g. fever; and a cloudy PD effluent secondary to elevated white blood cell (WBC) counts with predominance of neutrophils. Current management guidelines recommend early institution of empirical broad-spectrum antibiotic therapy triggered by PD fluid cytology [1]. However, even with the current recommended protocols for microbiology, 15–20% of the PD peritonitis are culture negative [2]. Concerns for atypical infections or non-infectious peritonitis are higher in culture negative peritonitis. Neutrophilic reaction can also occur with peri-peritoneal infection or inflammation as in pancreatitis and colitis [3, 4].\n\nClostridioides difficile (formerly Clostridium difficile) infection (CDI) presents with GI symptoms and has significant adverse outcomes including mortality, for both hospitalized and ambulatory patient populations [5–7]. Chronically ill and immunocompromised individuals, including those with end stage renal disease (ESRD), are at higher risk for developing CDI [8, 9]. These statistics along with the similar presenting syndromes, pose two unique challenges in the routine clinical care of ESRD patients on PD: GI presentation with cloudy PD effluent can detract from the timely diagnosis of CDI and empirical management of PD peritonitis with routinely recommended antimicrobials including cephalosporins negatively impacts CDI. Together, these could lead to inappropriate early management, prolonged disease course, and adverse patient outcomes [10]. A strategy that allows greater vigilance for diagnosing CDI, and appropriate antimicrobial administration without potential for worsening CDI may improve patient care in this population [11]. We present a potentially novel strategy for the empiric management of PD peritonitis through discussion of two such cases who received care in our medical center within a 12-month period.\n\nCase presentation\nCase #1\nA 73-year-old male with Type II diabetes, ESRD managed with PD, and urethral stenosis managed by suprapubic catheter, presented to the Emergency Department (ED) with fever, abdominal pain, leukocytosis and significant diarrhea. Computed tomography (CT) of the abdomen demonstrated pan-colitis. Cell count of the peritoneal dialysis effluent revealed 1050 WBCs/mm3 with 71% neutrophils, 1% lymphocytes, and 28% monocytes. Clostridioides difficile PCR on the stool was positive. Patient was started on intra-peritoneal cefepime and vancomycin for treatment of the peritonitis and intravenous (IV) metronidazole and oral vancomycin for treatment of the C. difficile colitis. On day 3, due to development of ileus and worsening clinical status, oral vancomycin dose was increased to 500 mg every 6 h, vancomycin enemas were initiated along with IV tigecycline, and intra-peritoneal cefepime and vancomycin were discontinued. Peritoneal dialysate effluent culture produced no growth. IV metronidazole and vancomycin enemas were discontinued once the ileus resolved. Serial monitoring of the PD fluid with cell count was performed through day 11 and showed continued improvement in the WBC count. [Table 1] PD catheter was retained. Patient was discharged from the hospital on oral vancomycin taper after receiving 14 days of IV tigecycline.\nTable 1 Serial PD fluid analysis and cell count\n\nCase #1\t\nDay\tWBC/mm3\t%Poly\t%Lymph\t% Mono\t\nAdmission\n\n(Day Zero)\n\n\t1050\t71\t1\t28\t\nDay 1\t545\t91\t4\t5\t\nDay 2\t93\t82\t8\t10\t\nDay 3\t96\t74\t4\t22\t\nDay 4\t69\t88\t4\t8\t\nDay 5\t178\t79\t6\t15\t\nDay 6\t237\t87\t1\t13\t\nDay 7\t6\t89\t0\t10\t\nDay 8\t167\t70\t0\t30\t\nDay 9\t82\t51\t2\t47\t\nDay 10\t40\t69\t5\t26\t\nDay 11\t12\t83\t2\t15\t\nCase #2\t\nDay\tWBC/mm3\t%Poly\t%Lymph\t% Mono\t\nAdmission\n\n(Day Zero)\n\n\t1450\t49\t3\t48\t\nDay 1\t111\t28\t14\t58\t\nDay 2\t58\t12\t10\t78\t\nDay 3\t25\t3\t6\t91\t\nDay 4\t31\t4\t13\t83\t\n\n\nCase #2\nA 55-year-old male with ESRD secondary to polycystic kidney disease managed with PD developed acute diarrhea ranging from ten to twenty watery bowel movements per day. He became febrile on the second day of symptoms, and on the third day he noted a cloudy effluent from his dialysis catheter and presented to the ED. He denied pain at the site of the PD catheter, and no drainage was noted at the catheter exit site. Analysis of the peritoneal dialysate effluent found 1450 WBCs/mm3with 49% neutrophils, 49% monocytes, and 2% lymphocytes. Intra-peritoneal cefepime and vancomycin were initiated. CT of the abdomen identified “inflammatory changes of the rectosigmoid colon compatible with an infectious or inflammatory process.” C. difficile PCR of the stool was positive. Intra-peritoneal cefepime and vancomycin were promptly discontinued. Treatment with oral vancomycin 125 mg every 6 h and IV Tigecycline was initiated. Serial monitoring of the PD fluid with cell count was continued. By day 3, the WBC count in effluent fluid decreased to 25 cells/mm3. [Table 1] PD fluid culture produced no growth. PD catheter was retained. Tigecycline was discontinued after 5 days, and the patient was discharged on oral vancomycin to complete a 14-day course. At his 2-month follow-up clinic appointment, he had fully recovered.\n\nDiscussion and conclusions\nCDI is a growing concern worldwide in both hospitalized and ambulatory patient populations. In the United States, one retrospective analysis found the incidence of CDI among hospitalized adults nearly doubled between 2001 and 2010 [12]. Further, there is worry that community-acquired CDI may be overlooked by the predominance of hospital-based studies. A population-based study in Minnesota found that community-acquired CDI accounted for 41% of all reported cases, which led the group to conclude the reported burden of disease is likely underestimated [13]. Additionally, CDI has a proclivity towards affecting those with chronic illness and immune-compromised state. As such ESRD patients with PD form a high-risk group for CDI [14].\n\nCDI presents several unique diagnostic and therapeutic challenges in ESRD patients on PD. Although diarrhea remains the commonest symptom for CDI, overall clinical presentation of CDI can often be indistinguishable from PD peritonitis as many of these patients also present with sepsis, abdominal pain, tenderness, nausea, vomiting and diarrhea. Laroche et al. described the first case of C. difficile peritonitis in a patient undergoing chronic ambulatory peritoneal dialysis (CAPD) with a fatal outcome. PD fluid culture inoculated in blood culture bottles yielded Candida albicans and C. difficile. Interestingly, 3 weeks prior, the patient had received treatment for Bacteroides fragilis and Streptococcus spp peritonitis. Autopsy revealed no perforation or pseudomembranous colitis [15]. In another instance, Bharti et al. reported successful resolution of polymicrobial peritonitis in a 72-year-old man on CAPD. In this case, the PD fluid cultures using blood culture bottles revealed E. coli, B. fragilis, C. albicans and C. difficile. The identification of organisms was performed using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and treatment included antibiotics and PD catheter removal. As these cases demonstrate, isolation of C. difficile in PD peritonitis is uncommon and these are typically found in polymicrobial infections [16]. In contrast, Arikan et al. reported a 63-year-old male on PD who had previously been treated for pneumonia with piperacillin-tazobactam [17]. He presented with nausea, vomiting, abdominal pain, and cloudy dialysate and was found to have CDI, with positive stool toxin B assay, and peritonitis, with effluent white blood cell count 1160/mm3 with neutrophil predominance and negative fluid culture. Similarly, Ribes-Cruz et al., reported a patient with watery diarrhea, abdominal pain, fever, and cloudy peritoneal effluent that failed to respond to IP ceftazidime and vancomycin [18]. Stool was positive for C. difficile toxin. Peritoneal dialysate was negative for C. difficile toxin or antigen however, clinical improvement was noted only after the initiation of oral vancomycin. Some studies have hypothesized the concerns for transmigration of bacteria as well as bacteremia and secondary peritoneal seeding as the pathophysiology of infectious peritonitis, whereas others have suggested the upregulation of ICAM-1 receptors causing chemoattraction and transmigration of leukocytes through the intestinal epithelium causing non-infectious peritonitis [19, 20]. Fulminant CDI with perforation and peritonitis has also been demonstrated [21, 22].\n\nTaken together, these reports highlight a clinical conundrum when a PD patient presents with cloudy effluent, abdominal pain, and diarrhea likely secondary to CDI (Fig. 1). On one hand these patients may have a non-infectious neutrophilic reaction due to the presence of peri-peritoneal inflammation/colitis while on the other, the possibilities exist for a true bacterial peritonitis either with C. difficile itself or related to the other more conventional bacteria [4, 17, 18, 23]. Findings of cloudy effluent in these situations do not assist in establishing the diagnosis of either, and the current guidelines trigger empiric initiation of broad-spectrum antimicrobials, including third generation cephalosporins for the management of PD peritonitis. Unfortunately, these may worsen CDI. A strategy that allows for appropriate antimicrobial administration without potential for worsening CDI may improve patient care in this population [11].\nFig. 1 *CDI [acute diarrhea with clinical and risk factors concerning for CDI + positive stool test for C. difficile]; Peritonitis [clinical features including cloudy effluent + peritoneal fluid analysis with neutrophilic leukocytosis]\n\n\n\nTigecycline, an intravenously administered glycylcycline, may provide an effective alternative to cephalosporins in this clinical scenario. It has antimicrobial activity covering gram-positive organisms including MRSA and VRE, gram-negative organisms as well as anaerobic bacteria and is an approved treatment of complex intra-abdominal infections including peritonitis [24, 25]. While not standard therapy for CDI, tigecycline has also been shown to have efficacy against C. difficile and has been reported as an effective adjunct for CDI in recent reports [26]. Herpers et al., in a case series demonstrated successful eradication of C. difficile in four severe refractory cases after the addition of IV tigecycline [27]. Duration of tigecycline therapy ranged between 7 to 24 days. Another retrospective cohort evaluating severe complicated, non-operative CDI showed similar outcomes in patients who received tigecycline compared to those who did not. Although, the study had a small sample size and was not powered to adjust for comorbidities and severity of illness [28]. Common side effects include nausea and vomiting while rare adverse effects of tigecycline are pancreatitis [29], hepatic dysfunction, hypersensitivity reactions with potential for low cross-reactivity to tetracyclines, photosensitivity, and pseudotumor cerebri. A black box warning exists for its use. A meta-analysis of Phase 3 and 4 clinical trials demonstrated increased all-cause mortality in tigecycline versus comparator treated patients, but the cause for this has not been determined, and use has been recommended to be reserved for specific indications [30].\n\nIn our report, Case 1 had an admission for pneumonia requiring antibiotics 1 month prior to presentation and Case 2 had a history of CDI. We used IV tigecycline as empiric treatment of possible PD associated infectious peritonitis while also providing adjunctive CDI treatment. We do not believe that tigecycline alone led to a positive treatment response but, our use of tigecycline was primarily to prevent worsening of C. difficile colitis. This enabled the treating physicians to avoid systemic administration of third generation cephalosporins while culture results on the dialysate fluid were awaited. The difference in duration of tigecycline between the two cases (14 days v/s 5 days) was because Case 1 had severe C. difficile disease and the peritoneal fluid cell count responded at a much slower rate as displayed in Table 1. Both our cases were eventually PD culture negative and thus were successfully managed with IV tigecycline and oral vancomycin without evidence for slowly responsive or refractory peritonitis. While we do not recommend combination therapy in every such patient, we feel that the empiric use of tigecycline could be considered in patients presenting with the diagnosis of CDI, or at high risk for CDI until the cause for their cloudy dialysate can be determined. This may allow appropriate coverage for the possible infectious agents without adversely impacting the CDI in those with neutrophilic reaction. In the latter cases, once PD fluid analysis shows improvement, tigecycline may be discontinued (Fig. 1).\n\nIn conclusion, the diagnosis of CDI is challenging and could be delayed or missed in PD patients presenting with diarrhea and cloudy peritoneal effluent with positive fluid cytology suggestive of PD peritonitis. CDI associated peritonitis may be inflammatory and not necessarily infectious. In patients presenting with diarrhea with risk factors for CDI, traditional empiric treatment of PD peritonitis may need to be reexamined as it could have detrimental effects on CDI course and patient outcomes. Prospective studies are needed to evaluate the ideal treatment strategy.\n\nAbbreviations\nCDIClostridioides difficile infection\n\nCTComputed tomography\n\nEDEmergency department\n\nESRDEnd stage renal disease\n\nGIGastrointestinal\n\nIVIntravenous\n\nPDPeritoneal dialysis\n\nWBCWhite blood cell\n\nPublisher’s Note\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n\nAcknowledgements\nNone.\n\nAuthors’ contributions\nKS wrote the initial manuscript, edited and reviewed the manuscript, KC, KBP, KLW and AMS contributed, edited and performed literature review. All authors contributed significantly, have read and approved the final manuscript.\n\nFunding\nAMS reports the following ongoing grant supports: I01HX002639 HSR&D, Department of Veterans Affairs and I01CX001661, CSR&D, Department of Veteran Affairs. The funding agency did not have any role in the design of the study, collection, analysis, interpretation of data or in the writing of the manuscript.\n\nAvailability of data and materials\nAll available data has been shared in the manuscript.\n\nEthics approval and consent to participate\nNo ethical approval was required for this case report. Written informed consent was obtained from the patients.\n\nConsent for publication\nWritten informed consent was obtained from the patients for publication of this case report. A copy of the written consent is available for review.\n\nCompeting interests\nAll authors report no competing interests.\n==== Refs\nReferences\n1. Li PK Szeto CC Piraino B de Arteaga J Fan S Figueiredo AE Fish DN Goffin E Kim YL Salzer W ISPD peritonitis recommendations: 2016 update on prevention and treatment Perit Dial Int : J Int Soc Perit Dial 2016 36 5 481 508 10.3747/pdi.2016.00078 \n2. Port FK Held PJ Nolph KD Turenne MN Wolfe RA Risk of peritonitis and technique failure by CAPD connection technique: a national study Kidney Int 1992 42 4 967 974 10.1038/ki.1992.375 1453589 \n3. Teitelbaum I Cloudy peritoneal dialysate: it's not always infection Contrib Nephrol 2006 150 187 194 10.1159/000093594 16721010 \n4. Rocklin MA Teitelbaum I Noninfectious causes of cloudy peritoneal dialysate Semin Dial 2001 14 1 37 40 10.1046/j.1525-139x.2001.00012.x 11208038 \n5. Cohen SH Gerding DN Johnson S Kelly CP Loo VG McDonald LC Pepin J Wilcox MH Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA) Infect Control Hosp Epidemiol 2010 31 5 431 455 10.1086/651706 20307191 \n6. Frequently asked questions about Clostridium difficile for healthcare providers [https://www.cdc.gov/hai/organisms/cdiff/cdiff_clinicians.html]. Accessed 06/16/2019.\n7. Gupta A Khanna S Community-acquired Clostridium difficile infection: an increasing public health threat Infect Drug Resist 2014 7 63 72 24669194 \n8. Phatharacharukul P Thongprayoon C Cheungpasitporn W Edmonds PJ Mahaparn P Bruminhent J The risks of incident and recurrent Clostridium difficile-associated diarrhea in chronic kidney disease and end-stage kidney disease patients: a systematic review and meta-analysis Dig Dis Sci 2015 60 10 2913 2922 10.1007/s10620-015-3714-9 25986528 \n9. Tirath A Tadros S Coffin SL Kintziger KW Waller JL Baer SL Colombo RE Huber LY Kheda MF Nahman NS Jr Clostridium difficile infection in dialysis patients J Invest Med : Official Publ Am Fed Clini Res 2017 65 2 353 357 10.1136/jim-2016-000183 \n10. Barbut F Surgers L Eckert C Visseaux B Cuingnet M Mesquita C Pradier N Thiriez A Ait-Ammar N Aifaoui A Does a rapid diagnosis of Clostridium difficile infection impact on quality of patient management? Clin Microbiol Infect : Official Publ Eur Soc Clin Microbiol Infect Dis 2014 20 2 136 144 10.1111/1469-0691.12221 \n11. Bharti S Malhotra P Juretschko S Successful treatment of peritoneal Dialysis catheter-related Polymicrobial peritonitis involving <span class=\"named-content genus-species\" id=\"named-content-1\">Clostridium difficile</span> J Clin Microbiol 2015 53 12 3945 3946 10.1128/JCM.02021-15 26378285 \n12. Reveles KR Lee GC Boyd NK Frei CR The rise in Clostridium difficile infection incidence among hospitalized adults in the United States: 2001-2010 Am J Infect Control 2014 42 10 1028 1032 10.1016/j.ajic.2014.06.011 25278388 \n13. Khanna S Pardi DS Aronson SL Kammer PP Orenstein R St Sauver JL Harmsen WS Zinsmeister AR The epidemiology of community-acquired Clostridium difficile infection: a population-based study Am J Gastroenterol 2012 107 1 89 95 10.1038/ajg.2011.398 22108454 \n14. Eddi R Malik MN Shakov R Baddoura WJ Chandran C Debari VA Chronic kidney disease as a risk factor for Clostridium difficile infection Nephrology (Carlton, Vic) 2010 15 4 471 475 10.1111/j.1440-1797.2009.01274.x \n15. Laroche MC Alfa MJ Harding GKM Isolation of toxigenic Clostridium difficile from dialysate fluid in a fatal case of chronic ambulatory peritoneal Dialysis-related peritonitis Clin Infect Dis 1997 25 5 1248 10.1086/516960 9402394 \n16. Brook I Walker RI Pathogenicity of Clostridium species with other bacteria in mixed infections J Infect 1986 13 3 245 253 10.1016/S0163-4453(86)91190-4 2878957 \n17. Arikan T Unal A Kocyigit I Yurci A Oymak O Peritoneal Dialysis-related peritonitis triggered by Clostridium difficile-associated colitis Perit Dial Int : J Int Soc Perit Dial 2014 34 1 139 140 10.3747/pdi.2012.00177 \n18. Ribes-Cruz JJ Gonzalez-Rico M Juan-Garcia I Puchades-Montesa MJ Torregrosa-Maicas I Ramos-Tomas C Solis-Salguero MA Tomas-Simo P Tejedor-Alonso S Zambrano-Esteves P Cloudy peritoneal effluent and diarrhoea due to Clostridium difficile Nefrol : Publ oficial de la Soc Esp Nefrol 2014 34 1 130 131 \n19. Canny G Drudy D Macmathuna P O'Farrelly C Baird AW Toxigenic C. difficile induced inflammatory marker expression by human intestinal epithelial cells is asymmetrical Life Sci 2006 78 9 920 925 10.1016/j.lfs.2005.05.102 16185718 \n20. Liberek T Chmielewski M Lichodziejewska-Niemierko M Lewandowski K Rutkowski B Transmigration of blood leukocytes into the peritoneal cavity is related to the upregulation of ICAM-1 (CD54) and mac-1 (CD11b/CD18) adhesion molecules Perit Dial Int : J Int Soc Perit Dial 2004 24 2 139 146 10.1177/089686080402400204 \n21. Bauer MP Kuijper EJ van Dissel JT European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI) Clin Microbiol Infect : Official Publ Eur Soc Clin Microbiol Infect Dis 2009 15 12 1067 1079 10.1111/j.1469-0691.2009.03099.x \n22. Sartelli M Di Bella S McFarland LV Khanna S Furuya-Kanamori L Abuzeid N Abu-Zidan FM Ansaloni L Augustin G Bala M 2019 update of the WSES guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients World J Emerg Surg 2019 14 1 8 10.1186/s13017-019-0228-3 30858872 \n23. Sakao Y Kato A Sugiura T Fujikura T Misaki T Tsuji T Sakakima M Yasuda H Fujigaki Y Hishida A Cloudy dialysate and pseudomembranous colitis in a patient on CAPD Perit Dial Int : J Int Soc Perit Dial 2008 28 5 562 563 10.1177/089686080802800528 \n24. Eckmann C Montravers P Bassetti M Bodmann KF Heizmann WR Sanchez Garcia M Guirao X Capparella MR Simoneau D Dupont H Efficacy of tigecycline for the treatment of complicated intra-abdominal infections in real-life clinical practice from five European observational studies J Antimicrob Chemother 2013 68 Suppl 2 ii25 ii35 10.1093/jac/dkt142 23772043 \n25. Oliva ME Rekha A Yellin A Pasternak J Campos M Rose GM Babinchak T Ellis-Grosse EJ Loh E A multicenter trial of the efficacy and safety of tigecycline versus imipenem/cilastatin in patients with complicated intra-abdominal infections [Study ID Numbers: 3074A1–301-WW; ClinicalTrials.gov Identifier: NCT00081744] BMC Infect Dis 2005 5 88 10.1186/1471-2334-5-88 16236177 \n26. El-Herte RI Baban TA Kanj SS Recurrent refractory Clostridium difficile colitis treated successfully with rifaximin and tigecycline: a case report and review of the literature Scand J Infect Dis 2012 44 3 228 230 10.3109/00365548.2011.616224 22077098 \n27. Herpers BL Vlaminckx B Burkhardt O Blom H Biemond-Moeniralam HS Hornef M Welte T Kuijper EJ Intravenous tigecycline as adjunctive or alternative therapy for severe refractory Clostridium difficile infection Clin Infect Dis : Official Publ Infect Dis Soc Am 2009 48 12 1732 1735 10.1086/599224 \n28. MT LS Branch-Elliman W Snyder GM Mahoney MV Alonso CD Gold HS Wright SB Does Adjunctive Tigecycline Improve Outcomes in Severe-Complicated, Nonoperative Clostridium difficile Infection? Open Forum Infect Dis 2017 4 1 ofw264 28480257 \n29. Lin J Wang R Chen J Tigecycline-induced acute pancreatitis in a renal transplant patient: a case report and literature review BMC Infect Dis 2018 18 1 201 10.1186/s12879-018-3103-z 29720098 \n30. Tygacil (tigecycline) iv injection label – FDA [https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021821s026s031lbl.pdf]. Accessed 16 June 2019.\n\n", "fulltext_license": "CC BY", "issn_linking": "1471-2369", "issue": "21(1)", "journal": "BMC nephrology", "keywords": "Clostridioides difficile; Peritoneal dialysis; Peritonitis", "medline_ta": "BMC Nephrol", "mesh_terms": "D000368:Aged; D000900:Anti-Bacterial Agents; D016360:Clostridioides difficile; D003015:Clostridium Infections; D003967:Diarrhea; D006801:Humans; D007676:Kidney Failure, Chronic; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D010538:Peritonitis; D012307:Risk Factors; D000078304:Tigecycline; D014640:Vancomycin", "nlm_unique_id": "100967793", "other_id": null, "pages": "76", "pmc": null, "pmid": "32131755", "pubdate": "2020-03-04", "publication_types": "D002363:Case Reports; D016428:Journal Article; D013486:Research Support, U.S. Gov't, Non-P.H.S.", "references": "20609100;30858872;23772043;27282851;26378285;22077098;22108454;20307191;24669194;16721010;2878957;25278388;24525609;16236177;28480257;1453589;15119634;29720098;19929973;16185718;11208038;19435431;18708558;25986528;9402394;27737913;23565919", "title": "Clostridioides difficile associated peritonitis in peritoneal dialysis patients - a case series based review of an under-recognized entity with therapeutic challenges.", "title_normalized": "clostridioides difficile associated peritonitis in peritoneal dialysis patients a case series based review of an under recognized entity with therapeutic challenges" }

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{ "abstract": "Severe intrahepatic cholestasis of pregnancy (ICP), defined as a serum bile acid (SBA) level > 100 μmol/l, remains poorly understood in its mechanism and implications.\nA patient with a missed diagnosis of mild ICP went on to develop clinical jaundice and liver function abnormalities in the setting of newly diagnosed hepatitis C and severe ICP on repeat SBA testing.\nThis case highlights and adds to the growing body of evidence supporting the need for universal screening for hepatitis C in ICP patients and the potential role for repeat SBA testing, which would be a notable change from the traditional care of these individuals.", "affiliations": "Obstetrics and Gynecology Penn State Health Milton S. Hershey Medical Center, USA.;Maternal Fetal Medicine Penn State Health Milton S. Hershey Medical Center, USA.;Maternal Fetal Medicine Penn State Health Milton S. Hershey Medical Center, USA.", "authors": "Birchall|Courtney|C|;Prentice|Danielle|D|;Pauli|Jaimey|J|", "chemical_list": null, "country": "Netherlands", "delete": false, "doi": "10.1016/j.crwh.2020.e00178", "fulltext": "\n==== Front\nCase Rep Womens HealthCase Rep Womens HealthCase Reports in Women's Health2214-9112Elsevier S2214-9112(20)30008-410.1016/j.crwh.2020.e00178e00178ArticleElevated international normalized ratio (INR) and new diagnosis of hepatitis C associated with severe intrahepatic cholestasis of pregnancy (ICP): A case report Birchall Courtney [email protected]⁎Prentice Danielle bPauli Jaimey ba Obstetrics and Gynecology Penn State Health Milton S. Hershey Medical Center, USAb Maternal Fetal Medicine Penn State Health Milton S. Hershey Medical Center, USA⁎ Corresponding author at: Obstetrics and Gynecology, Penn State Health Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA. [email protected] 1 2020 4 2020 30 1 2020 26 e0017813 1 2020 20 1 2020 23 1 2020 © 2020 The Authors2020This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Background\nSevere intrahepatic cholestasis of pregnancy (ICP), defined as a serum bile acid (SBA) level > 100 μmol/l, remains poorly understood in its mechanism and implications.\n\nCase\nA patient with a missed diagnosis of mild ICP went on to develop clinical jaundice and liver function abnormalities in the setting of newly diagnosed hepatitis C and severe ICP on repeat SBA testing.\n\nConclusion\nThis case highlights and adds to the growing body of evidence supporting the need for universal screening for hepatitis C in ICP patients and the potential role for repeat SBA testing, which would be a notable change from the traditional care of these individuals.\n\nHighlights\n• Patient who presented with clinical jaundice and was diagnosed with ICP and previously undiagnosed Hepatitis C.\n\n• Evaluation of hepatic synthetic function is important in patients with severe intrahepatic cholestasis of pregnancy.\n\n• The case presented supports for the role of repeat serum bile acid testing in patients with Intrahepatic Cholestasis of Pregnancy.\n\n\n\nKeywords\nCholestasisHepatitis CBile acidsPregnancyAbbreviations\nICP, Intrahepatic cholestasis of pregnancySBA, Serum bile acidINR, International normalized ratioAST, Aspartate aminotransferaseALT, Alanine aminotransferase\n==== Body\n1 Introduction\nIntrahepatic cholestasis of pregnancy (ICP), known for its distinctive presentation of pruritus of the palms and soles in the third trimester, is a rare and poorly understood condition affecting 0.2–2% of pregnancies. The diagnosis is confirmed with a serum bile acid level and can be further supported with findings of elevated transaminases. For most women diagnosed with ICP, management is targeted towards both symptomatic relief and prevention of stillbirth [1,2].\n\nSevere ICP, classified by serum bile acid levels >100 μmol/l, (normal ≤10 μmol/l) is an exceedingly uncommon finding during pregnancy and can present with more severe hepatobiliary symptoms and complications, including clinical jaundice, elevated serum bilirubin and coagulopathy [1,3].\n\nHepatitis C is another uncommon comorbidity of pregnancy, estimated to affect between 0.1 and 3.6% of pregnancies [4]. We describe the case of a patient who presented with clinical jaundice, emesis and decreased fetal movement and was ultimately diagnosed with severe ICP and previously unknown hepatitis C infection.\n\n2 Case\nA 31-year-old woman (G6 P 3023) presented at 31 weeks and 5 days of gestation for evaluation of new-onset scleral icterus, nausea/emesis and decreased fetal movement. Her medical history was notable for intravenous heroin abuse, for which she was enrolled in a local methadone clinic for maintenance.\n\nThe patient initially presented early in her pregnancy and her routine prenatal laboratory results were within normal limits. This evaluation included HIV and hepatitis B but notably not a hepatitis C assay. However, she did have negative hepatitis C testing documented as recently as two years before this presentation. At approximately 27 weeks of gestation she noted itching on her palms and soles. She had mild elevation of serum bile acid level, to 12 μmol/l (normal ≤10 μmol/l). Her aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were within normal limits at that time. Unfortunately, these results and the diagnosis of cholestasis were not communicated to the patient.\n\nShe continued with her routine prenatal care and had an elevated one-hour glucose tolerance test, ar 202 mg/dL (normal <130 mg/dl), leading to a diagnosis of gestational diabetes. She then presented to clinic at 31 weeks and 5 days of gestation with complaints of new-onset “yellowing” of her skin and eyes over the last week, as well as decreased fetal movement. Given these new findings she was transferred to labor and delivery for further assessment.\n\nOn presentation she had reassuring electronic fetal monitoring. Upon review of her chart she was noted to have had elevated bile acids four weeks prior and was counseled on her diagnosis of cholestasis of pregnancy.\n\nInitial laboratory testing revealed an elevated bilirubin level of 6.6 mg/dl (normal 0.0–1.2 mg/dl) as well as elevated AST level, to 46 units/l (normal 0–32 units/l), and ALT level, to 56 units/l (normal 0–33 units/l). The patient was evaluated for viral hepatitis and had a positive hepatitis C screen; she had a positive viral load of 118,000 I·U./ml (normal <0 I.U/ml). The patient had no knowledge of her hepatitis C status prior to admission. An abdominal ultrasound scan was negative for acute pathology. Repeat tests of serum bile acids were also ordered.\n\nGiven her marked abnormalities on initial evaluation, further work-up was done to evaluate synthetic function of the liver. She was noted to have a mildly low albumin level and an elevated international normalized ratio (INR) of 2.3 (normal 0.9–1.1), for which she was treated with vitamin K.\n\nThe patient remained in hospital and had daily monitoring of her transaminase levels and coagulation panels. Her INR returned to normal with the addition of vitamin K and her AST/ALT trended down to normal. She was treated with ursodeoxycholic acid for symptomatic relief of ICP.\n\nFetal status was monitored daily with non-stress tests followed by biophysical profiles if non-reactive. The patient developed moderate polyhydramnios. She was also treated for preterm labor during her inpatient stay and received a course of betamethasone.\n\nOn day 7 of her admission her serum bile acid level was 104 μmol/l (normal ≤10 μmol/l). The patient was counseled extensively about this finding. In addition to her bile acids, the severity of her disease was discussed, as were the new diagnosis of polyhydramnios and her recent betamethasone course. Together with the patient and the Maternal Fetal Medicine and the Neonatal Intensive Care Unit, the decision was made to move forward with induction of labor at 32 weeks 6 days of gestation. She had a spontaneous vaginal delivery of a male infant with APGAR scores of 8 and 9 at 1 and 5 min respectively. The infant required NICU admission for respiratory support.\n\nThe patient's post-partum course in hospital was uncomplicated. She was counseled that her risk of recurrence of ICP in subsequent pregnancies was 60–70%. For her new diagnosis of hepatitis C she was recommended hepatology follow-up as an outpatient. She was discharged home with a plan for repeat laboratory evaluation at her 6-week post-partum visit.\n\n3 Discussion\nPatients with ICP typically present late in pregnancy, with 80% of women diagnosed after 30 weeks of gestation. By far the most common symptom is the characteristic pruritus of the palms and soles; however, other, rare manifestations include pigmented skin lesions, blisters, and jaundice [1].\n\nElevated serum bile acid levels are the confirmatory test of choice in patients with suspected ICP and are further used to categorize severity of disease as mild (SBA < 40 μmol/l), moderate (SBA > 40 μmol/l < 100 μmol/l) or severe (SBA > 100 μmol/l) [1,5]. Other common laboratory abnormalities include elevated transaminase levels. Less common laboratory abnormalities include elevated serum bilirubin, derangements in glucose metabolism and coagulopathy, all of which were seen in the case reported [1,3].\n\nOnce the diagnosis of ICP has been established, treatment is often initiated for symptomatic management of maternal pruritus. Ursodeoxycholic acid, the most commonly recommended medication for women with ICP, has been well studied and is known to reduce pruritus and decrease transaminase and serum bile acids levels. In the past, studies suggested that this decrease in SBA can lead to decreased risk of complications, including preterm delivery and improve neonatal outcomes. However, a recent large multi-center randomized control trial largely refuted these claims. [6,7]\n\nThe fetal risks of ICP include increased rates of spontaneous and iatrogenic preterm birth, non-reassuring fetal status, meconium stained amniotic fluid, NICU admissions, and stillbirth [1,5]. Due to the increased risk of these complications, most clinicians recommend twice-weekly antenatal testing following diagnosis, including non-stress tests and ultrasound scans to assess fetal status. Despite these recommendations, there is a lack of evidence to show that this increased fetal surveillance predicts or prevents the above-mentioned complications [1,2]. The current recommendation is for delivery at 36 weeks of gestation, as the increased risk of stillbirth rises with each week of gestation after this time. [8]\n\nTraditionally, ICP patients have been treated the same regardless of their serum bile acid levels due to a lack of evidence strongly supporting repeat laboratory evaluation. However, the results of one recent meta-analysis contradict this tendency. Ovadia et al found in their meta-analysis that women with SBA levels in the severe range were at a significantly increased risk of stillbirth. They proposed that repeat SBA testing could be important in distinguishing women who develop severe ICP, as their management could vary significantly from those with only mild to moderate disease [5]. This point is highlighted in the case reported, where the initial SBA level was mild, but with subsequent testing, encouraged by her worsening clinical condition, the findings of SBA levels in the severe range significantly influenced her counseling and ultimately the timing of her delivery. The authors do not specifically mention an ideal interval for re-testing SBAs; however, some experts suggest it could be beneficial as frequently as once a week. [2,9]\n\nA second key point worth discussing in the context of the case presented is the relationship between ICP and hepatitis C [[10], [11], [12]]. ICP has been linked to several hepatobiliary conditions, including hepatitis C, liver cirrhosis, chronic hepatitis, cholangitis and cholelithiasis. Hepatitis C specifically has been noted to worsen symptoms of ICP, including pruritus. Although no direct cause for this association has been found, one suggestion is that a common genetic predisposition may play a role [13]. Given these findings, it becomes important to test for co-existing hepatobiliary disease in this patient population. For the patient described here, the diagnosis of hepatitis C was important as it allowed precautions to be taken for the fetus and the staff during her labor course and also directed her care in the post-partum period. Given the important clinical implications of a hepatitis C diagnosis and that it is now a treatable condition, it is suggested that testing be considered in all patients with ICP [13].\n\nCare for and treatment of women diagnosed with ICP is an evolving field of study. The present case highlights several key points in the care of ICP patients. Most importantly, we see the importance and necessity of following up on laboratory evaluations in the outpatient setting, as missing the initial diagnosis can lead to deficient care and follow-up. Additionally, this case illuminates the role of laboratory evaluation for uncommon but clinically significant sequelae, and the roles of universal hepatitis C screening and repeat SBA testing in patients with ICP.\n\nContributors\nCourtney Birchall drafted and reviewed and revised the manuscript.\n\nDanielle Prentice reviewed and revised the manuscript.\n\nJaimey Pauli reviewed and revised the manuscript.\n\nConflict of interest\nThe authors declare that they have no conflict of interest regarding the publication of this case report.\n\nFunding\nThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\n\nPatient consent\nObtained.\n\nProvenance and peer review\nThis case report was peer reviewed.\n==== Refs\nReferences\n1 Williamson C. Geenes V. Intrahepatic cholestasis of pregnancy Obstet. Gynecol. 124 2014 120 133 24901263 \n2 Lindor K. Lee R. Intrahepatic Cholestasis of Pregnancy, UpToDate 2019 https://www-uptodate-com.medjournal.hmc.psu.edu:2200/contents/intrahepatic-cholestasis-of-pregnancy?search=intrahepaticcholestasisofpregnancy&source=search_result&selectedTitle=1~65&usage_type=default&display_rank=1#H3755223507 (accessed September 9, 2019) \n3 Maldonado M. Alhousseini A. Awadalla M. Idler J. Welch R. Puder K. Patwardhan M. Gonik B. Intrahepatic cholestasis of pregnancy leading to severe vitamin K deficiency and coagulopathy Case Rep. Obstet. Gynecol. 2017 2017 1 3 \n4 Floreani A. Hepatitis C and pregnancy World J. Gastroenterol. 19 2013 6714 6720 24187446 \n5 Ovadia C. Seed P.T. Sklavounos A. Geenes V. Di Illio C. Chambers J. Kohari K. Bacq Y. Bozkurt N. Brun-Furrer R. Bull L. Estiú M.C. Grymowicz M. Gunaydin B. Hague W.M. Haslinger C. Hu Y. Kawakita T. Kebapcilar A.G. Kebapcilar L. Kondrackienė J. Koster M.P.H. Kowalska-Kańka A. Kupčinskas L. Lee R.H. Locatelli A. Macias R.I.R. Marschall H.U. Oudijk M.A. Raz Y. Rimon E. Shan D. Shao Y. Tribe R. Tripodi V. Yayla Abide C. Yenidede I. Thornton J.G. Chappell L.C. Williamson C. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses Lancet. 393 2019 899 909 30773280 \n6 Chappell L.C. Bell J.L. Smith A. Linsell L. Juszczak E. Dixon P.H. Chambers J. Hunter R. Dorling J. Williamson C. Thornton J.G. Ahmed I. Arya R. Beckett V. Bhide A. Brown H. Bugg G. Cameron H. Deole N. Dey M. Dwyer J. Fahel L. Gada R. Girling J. Haestier A. Hughes S. Indusekhar R. Jones B. Khan R. Kirkpatrick A. Knox E. Lincoln K. MacDougall M. Majoko F. McIntyre K. Noori M. Oakley W. Preston J. Ranka P. Rashid M. Salloum M. Samyraju M. Schram C. Sen S. Stone S. Tan B. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial Lancet. 394 2019 849 860 31378395 \n7 Zhang Y. Lu L. Victor D.W. Xin Y. Xuan S. Ursodeoxycholic acid and S-adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy: a meta-analysis Hepat. Mon. 16 2016 \n8 Puljic A. The risk of infant and fetal death by each additional week of expectant management in intrahepatic cholestasis of pregnancy by gestational age Am. J. Obstet. Gynecol. 212 2015 667 e1–667.e5 10.1016/j.ajog.2015.02.012 25687562 \n9 Potashinsky A. Lee T.P. Atypical presentation of intrahepatic cholestasis of pregnancy Am. J. Gastroenterol. 2015 \n10 Locatelli A. Roncaglia N. Arreghini A. Bellini P. Vergani P. Ghidini A. Hepatitis C virus infection is associated with a higher incidence of cholestasis of pregnancy BJOG An Int. J. Obstet. Gynaecol. 106 1999 498 500 \n11 Covach A. Rose W. Intrahepatic cholestasis of pregnancy refractory to multiple medical therapies and plasmapheresis Am. J. Perinatol. Rep. 7 2017 e223 e225 \n12 Paternoster D.M. Fabris F. Palu G. Palu P. Santarossa C. Bracciante R. Snijders D. Floreani A. Acta Obstetricia et Gynecologica Scandinavica intra-hepatic cholestasis of pregnancy in hepatitis C virus infection* Acta Obs. Gynecol. Scand. 81 2002 99 103 \n13 Marschall H.U. Wikström Shemer E. Ludvigsson J.F. Stephansson O. Intrahepatic cholestasis of pregnancy and associated hepatobiliary disease: a population-based cohort study Hepatology. 58 2013 1385 1391 23564560\n\n", "fulltext_license": "CC BY-NC-ND", "issn_linking": "2214-9112", "issue": "26()", "journal": "Case reports in women's health", "keywords": "ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; Bile acids; Cholestasis; Hepatitis C; ICP, Intrahepatic cholestasis of pregnancy; INR, International normalized ratio; Pregnancy; SBA, Serum bile acid", "medline_ta": "Case Rep Womens Health", "mesh_terms": null, "nlm_unique_id": "101682122", "other_id": null, "pages": "e00178", "pmc": null, "pmid": "32055455", "pubdate": "2020-04", "publication_types": "D002363:Case Reports", "references": "30773280;24187446;31378395;29250459;24901263;23564560;10430202;25687562;11942897;27799965;28680707", "title": "Elevated international normalized ratio (INR) and new diagnosis of hepatitis C associated with severe intrahepatic cholestasis of pregnancy (ICP): A case report.", "title_normalized": "elevated international normalized ratio inr and new diagnosis of hepatitis c associated with severe intrahepatic cholestasis of pregnancy icp a case report" }

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{ "abstract": "Merkel cell carcinoma (mcc) is an uncommon malignancy of the skin arising from cells located in the deeper layers of the epidermis called Merkel cells. This malignancy rarely presents as a metastatic disease, and the field is therefore deficient in regards to management. We report the case of a 49-year-old woman who presented with a presumptive diagnosis of osteomyelitis of the left fifth digit that was resistant to treatment with antibiotics; she underwent debridement of the digit that revealed mcc and was later to have metastatic disease to her lungs, liver, and musculoskeletal system. The management of mcc, although simple in the early stage of the disease, can become challenging when it is more advanced. Multiple new modalities for its treatment have emerged over the last few years, and more recently, clinical trials are being conducted for the use of immunotherapy agents in the treatment of this malignancy.", "affiliations": "Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY, USA.;Department of Internal Medicine, Staten Island University Hospital, Staten Island, NY, USA.;Department of Hematology and Oncology, Staten Island University Hospital, Staten Island, NY, USA; and.;Department of Pathology, Staten Island University Hospital, Staten Island, NY, USA.;Department of Hematology and Oncology, Staten Island University Hospital, Staten Island, NY, USA; and.", "authors": "Safa|F|F|;Pant|M|M|;Weerasinghe|C|C|;Felix|R|R|;Terjanian|T|T|", "chemical_list": null, "country": "Switzerland", "delete": false, "doi": "10.3747/co.25.3836", "fulltext": null, "fulltext_license": null, "issn_linking": "1198-0052", "issue": "25(1)", "journal": "Current oncology (Toronto, Ont.)", "keywords": "Merkel cell carcinoma; Merkel cell polyoma virus; metastatic; skin neoplasm", "medline_ta": "Curr Oncol", "mesh_terms": null, "nlm_unique_id": "9502503", "other_id": null, "pages": "e106-e112", "pmc": null, "pmid": "29507504", "pubdate": "2018-02", "publication_types": "D016428:Journal Article", "references": "18280333;25329450;25720654;26922661;25550797;27093365;21043828;20162707;16625069;23431473;28821198;17369567;27592805;10375107;25993218;24406863;24416729;21750118;23922299;21711338;27879975;23304516;19638070", "title": "Merkel cell carcinoma masquerading as cellulitis: a case report and review of the literature.", "title_normalized": "merkel cell carcinoma masquerading as cellulitis a case report and review of the literature" }

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"drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "TENDERNESS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEPHALEXIN /00145501/" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "WARFARIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": 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"summary": null }, "primarysource": { "literaturereference": "SAFA F, PANT M, WEERASINGHE C, FELIX R, TERJANIAN T. MERKEL CELL CARCINOMA MASQUERADING AS CELLULITIS: A CASE REPORT AND REVIEW OF THE LITERATURE.. CURRENT ONCOLOGY. 2018?25(1):E106 TO E112", "literaturereference_normalized": "merkel cell carcinoma masquerading as cellulitis a case report and review of the literature", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20180404", "receivedate": "20180404", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14712307, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "US-ACCORD-065404", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "074513", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NEUROENDOCRINE CARCINOMA OF THE SKIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "CARBOPLATIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "206775", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "METASTASIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBOPLATIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "WARFARIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PULMONARY EMBOLISM", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "WARFARIN" } ], "patientagegroup": null, "patientonsetage": "49", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Escherichia urinary tract infection", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pancytopenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SAFA F, PANT M, WEERASINGHE C, FELIX R, TERJANIAN T. MERKEL CELL CARCINOMA MASQUERADING AS CELLULITIS: A CASE REPORT AND REVIEW OF THE LITERATURE. CURRENT ONCOLOGY. 2018?25(1):E106-E112. DOI: 10.3747/CO.25.3836", "literaturereference_normalized": "merkel cell carcinoma masquerading as cellulitis a case report and review of the literature", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20180409", "receivedate": "20180409", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14733040, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" } ]

{ "abstract": "OBJECTIVE\nThe aim of this study was to review our experience with patients having gynaecological surgeries while on long-term anticoagulation and to postulate a better guide for their perioperative management.\n\n\nMETHODS\nA retrospective review of all women on long-term warfarin who underwent gynaecological surgeries from January 2003 to December 2012. Data from medical records including operation reports and inpatient and outpatient charts were reviewed and analyzed.\n\n\nRESULTS\nSixty-seven cases from 58 patients were identified. Twenty and 38 patients underwent major and minor gynaecological surgeries, respectively. The incidence of postoperative bleeding was higher after major surgery (4 cases, 20%) than after minor surgery (1 case, 2.1%; P = 0.025). All bleeding complications occurred between postoperative day 3 and day 10. Three patients, who had resumption of warfarin at a lower dose and slowly stepped up, had no bleeding complications. None of our patients developed venous thromboembolic complications. There was one mortality due to septic shock.\n\n\nCONCLUSIONS\nPatients on long-term anticoagulation have a trend of increased bleeding complications after major gynaecological surgeries than in minor gynaecological surgeries. We suggest that delaying resumption of warfarin at a lower dose may have a role in reducing the risk of postoperative bleeding without increasing the risk of venous thromboembolism.", "affiliations": "Department of Obstetrics and Gynaecology, Queen Mary Hospital, Hong Kong. Electronic address: [email protected].;Department of Obstetrics and Gynaecology, Queen Mary Hospital, Hong Kong.", "authors": "Cheng|Hiu Yee Heidi Hyh|HYHH|;Cheung|Vincent Y T|VYT|", "chemical_list": "D014859:Warfarin", "country": "Netherlands", "delete": false, "doi": "10.1016/j.jogc.2017.05.037", "fulltext": null, "fulltext_license": null, "issn_linking": "1701-2163", "issue": "40(2)", "journal": "Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC", "keywords": "Warfarin; gynaecologic surgery; haemorrhage; postoperative complications", "medline_ta": "J Obstet Gynaecol Can", "mesh_terms": "D000328:Adult; D000368:Aged; D016063:Blood Loss, Surgical; D005260:Female; D013509:Gynecologic Surgical Procedures; D006801:Humans; D008875:Middle Aged; D059035:Perioperative Period; D019106:Postoperative Hemorrhage; D012189:Retrospective Studies; D015912:Thrombolytic Therapy; D054556:Venous Thromboembolism; D014859:Warfarin", "nlm_unique_id": "101126664", "other_id": null, "pages": "199-204", "pmc": null, "pmid": "28821415", "pubdate": "2018-02", "publication_types": "D016428:Journal Article", "references": null, "title": "Patients on Long-Term Warfarin Undergo Gynecological Surgeries: A 10-Year Review of Perioperative Anticoagulation.", "title_normalized": "patients on long term warfarin undergo gynecological surgeries a 10 year review of perioperative anticoagulation" }

[ { "companynumb": "HK-TEVA-2018-HK-872113", "fulfillexpeditecriteria": "1", "occurcountry": "HK", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "WARFARIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "40145", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTICOAGULANT THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "WARFARIN" } ], "patientagegroup": null, "patientonsetage": "48", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Post procedural haemorrhage", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Abdominal pain", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Haemoglobin decreased", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "CHENG HYHH, CHEUNG VYT. PATIENTS ON LONG-TERM WARFARIN UNDERGO GYNECOLOGICAL SURGERIES: A 10-YEAR REVIEW OF PERIOPERATIVE ANTICOAGULATION. J-OBSTET-GYNAECOL-CAN 2018?40(2):199-204.", "literaturereference_normalized": "patients on long term warfarin undergo gynecological surgeries a 10 year review of perioperative anticoagulation", "qualification": "1", "reportercountry": "HK" }, "primarysourcecountry": "HK", "receiptdate": "20180326", "receivedate": "20180326", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14681266, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180509" }, { "companynumb": "HK-TEVA-2018-HK-872111", "fulfillexpeditecriteria": "1", "occurcountry": "HK", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "WARFARIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "40145", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTICOAGULANT THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "WARFARIN" } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Post procedural haemorrhage", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Haemoglobin decreased", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "CHENG HYHH, CHEUNG VYT. PATIENTS ON LONG-TERM WARFARIN UNDERGO GYNECOLOGICAL SURGERIES: A 10-YEAR REVIEW OF PERIOPERATIVE ANTICOAGULATION. J-OBSTET-GYNAECOL-CAN 2018?40(2):199-204.", "literaturereference_normalized": "patients on long term warfarin undergo gynecological surgeries a 10 year review of perioperative anticoagulation", "qualification": "1", "reportercountry": "HK" }, "primarysourcecountry": "HK", "receiptdate": "20180326", "receivedate": "20180326", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14681269, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180509" }, { "companynumb": "HK-TEVA-2018-HK-872118", "fulfillexpeditecriteria": "1", "occurcountry": "HK", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "WARFARIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "40145", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTICOAGULANT THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "WARFARIN" } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Haemoglobin decreased", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Perineal pain", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Vaginal haemorrhage", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "CHENG HYHH, CHEUNG VYT. PATIENTS ON LONG-TERM WARFARIN UNDERGO GYNECOLOGICAL SURGERIES: A 10-YEAR REVIEW OF PERIOPERATIVE ANTICOAGULATION. J-OBSTET-GYNAECOL-CAN 2018?40(2):199-204.", "literaturereference_normalized": "patients on long term warfarin undergo gynecological surgeries a 10 year review of perioperative anticoagulation", "qualification": "1", "reportercountry": "HK" }, "primarysourcecountry": "HK", "receiptdate": "20180326", "receivedate": "20180326", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14681220, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180509" }, { "companynumb": "HK-TEVA-2018-HK-872128", "fulfillexpeditecriteria": "1", "occurcountry": "HK", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "WARFARIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "40145", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTICOAGULANT THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "WARFARIN" } ], "patientagegroup": null, "patientonsetage": "44", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Vaginal haemorrhage", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Haemoglobin decreased", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "CHENG HYHH, CHEUNG VYT. PATIENTS ON LONG-TERM WARFARIN UNDERGO GYNECOLOGICAL SURGERIES: A 10-YEAR REVIEW OF PERIOPERATIVE ANTICOAGULATION. J-OBSTET-GYNAECOL-CAN 2018?40(2):199-204.", "literaturereference_normalized": "patients on long term warfarin undergo gynecological surgeries a 10 year review of perioperative anticoagulation", "qualification": "1", "reportercountry": "HK" }, "primarysourcecountry": "HK", "receiptdate": "20180326", "receivedate": "20180326", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14681265, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180509" }, { "companynumb": "HK-MYLANLABS-2018M1015349", "fulfillexpeditecriteria": "1", "occurcountry": "HK", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "WARFARIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "040415", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTICOAGULANT THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "WARFARIN" } ], "patientagegroup": null, "patientonsetage": "44", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Vaginal haemorrhage", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Post procedural haemorrhage", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Haemoglobin decreased", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "CHENG HYHH, CHEUNG VYT. PATIENTS ON LONG-TERM WARFARIN UNDERGO GYNECOLOGICAL SURGERIES: A 10-YEAR REVIEW OF PERIOPERATIVE ANTICOAGULATION. J-OBSTET-GYNAECOL-CAN 2018?40(2):199-204.", "literaturereference_normalized": "patients on long term warfarin undergo gynecological surgeries a 10 year review of perioperative anticoagulation", "qualification": "1", "reportercountry": "HK" }, "primarysourcecountry": "HK", "receiptdate": "20180313", "receivedate": "20180313", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14631611, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180509" }, { "companynumb": "HK-TEVA-2018-HK-872116", "fulfillexpeditecriteria": "1", "occurcountry": "HK", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "WARFARIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "40145", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "3 MILLIGRAM DAILY; 3MG DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTICOAGULANT THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "WARFARIN" } ], "patientagegroup": null, "patientonsetage": "47", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Post procedural haemorrhage", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Haemoglobin decreased", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Abdominal pain", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "CHENG HYHH, CHEUNG VYT. PATIENTS ON LONG-TERM WARFARIN UNDERGO GYNECOLOGICAL SURGERIES: A 10-YEAR REVIEW OF PERIOPERATIVE ANTICOAGULATION. J-OBSTET-GYNAECOL-CAN 2018?40(2):199-204.", "literaturereference_normalized": "patients on long term warfarin undergo gynecological surgeries a 10 year review of perioperative anticoagulation", "qualification": "1", "reportercountry": "HK" }, "primarysourcecountry": "HK", "receiptdate": "20180326", "receivedate": "20180326", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14681261, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180509" } ]

{ "abstract": "We herein report the case of a 68-year-old man with a history of allogeneic hematopoietic stem cell transplantation for acute myelocytic leukemia in whom graft-versus-host disease (GVHD) developed in the gastrointestinal tract and liver five months after transplantation. In that same period, chest computed tomography showed infiltration in both upper lungs. We performed bronchoscopy to clarify the GVHD and pulmonary infection. Nocardia nova was identified in the bronchoalveolar lavage fluid, and we diagnosed the patient as having pulmonary nocardiosis. Because the differential diagnosis is important for the medical management of GVHD and pulmonary infection, performing bronchoscopy is essential for making an appropriate and rapid diagnosis.", "affiliations": "Department of Internal Medicine, Division of Respiratory Medicine, Jikei University School of Medicine, Kashiwa Hospital, Japan.", "authors": "Yamakawa|Hideaki|H|;Yoshida|Masahiro|M|;Morikawa|Noriyuki|N|;Fujimoto|Shota|S|;Ishikawa|Takeo|T|;Sano|Koji|K|;Nishiwaki|Kaichi|K|;Takagi|Masamichi|M|;Hayashi|Masahiro|M|;Kuwano|Kazuyoshi|K|;Aiba|Keisuke|K|", "chemical_list": null, "country": "Japan", "delete": false, "doi": "10.2169/internalmedicine.53.1860", "fulltext": null, "fulltext_license": null, "issn_linking": "0918-2918", "issue": "53(12)", "journal": "Internal medicine (Tokyo, Japan)", "keywords": null, "medline_ta": "Intern Med", "mesh_terms": "D000368:Aged; D001999:Bronchoscopy; D003937:Diagnosis, Differential; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute; D008297:Male; D009617:Nocardia Infections", "nlm_unique_id": "9204241", "other_id": null, "pages": "1391-5", "pmc": null, "pmid": "24930664", "pubdate": "2014", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Pulmonary Nocardia nova infection after allogeneic hematopoietic stem cell transplantation.", "title_normalized": "pulmonary nocardia nova infection after allogeneic hematopoietic stem cell transplantation" }

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"drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Formulation Unknown", "drugdosagetext": "UNK UNK, UNKNOWN FREQ.", "drugenddate": null, "drugenddateformat": null, "drugindication": "BONE MARROW CONDITIONING REGIMEN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUSULFAN" } ], "patientagegroup": null, "patientonsetage": "68", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Acute graft versus host disease", "reactionmeddraversionpt": "17.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Nocardiosis", "reactionmeddraversionpt": "17.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Graft versus host disease", "reactionmeddraversionpt": "17.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "17.1", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 2012" } }, "primarysource": { "literaturereference": "YAMAKAWA H, YOSHIDA M, MORIKAWA N, FUJIMOTO S, ISHIKAWA T, SANO K, ET AL.. PULMONARY NOCARDIA NOVA INFECTION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION. INTERNAL MEDICINE. 2014;53 (12):1391-5", "literaturereference_normalized": "pulmonary nocardia nova infection after allogeneic hematopoietic stem cell transplantation", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20140722", "receivedate": "20140722", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10331045, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150326" }, { "companynumb": "JP-SHIONOGI, INC-2014000667", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DORIPENEM MONOHYDRATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "022106", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "POWDER", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NOCARDIOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FINIBAX" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISOLONE\\PREDNISOLONE ACETATE\\PREDNISOLONE SODIUM SUCCINATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDONINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NOCARDIOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BAKTAR" } ], "patientagegroup": null, "patientonsetage": "68", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Renal failure", "reactionmeddraversionpt": "17.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "YAMAKAWA, H., ET AL.. PULMONARY NOCARDIA NOVA INFECTION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION. INTERNAL MEDICINE. 2014;53 (12):1391-1395", "literaturereference_normalized": "pulmonary nocardia nova infection after allogeneic hematopoietic stem cell transplantation", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20140721", "receivedate": "20140721", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10329841, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150326" } ]

{ "abstract": "Over the past decade, subset analyses of retrospective and prospective clinical studies have determined that KRAS-mutated metastatic colorectal cancers do not respond effectively to inhibition of epidermal growth factor receptor (EGFR) with the EGFR-targeting monoclonal antibodies cetuximab or panitumumab. Within the past few years, the scope of tested variants in the KRAS oncogene has expanded significantly, and testing of all RAS family genes has become more widely available in clinical laboratories. Expert consensus guidelines have recommended not using EGFR inhibitors in patients with KRAS-mutated tumors. However, with increasing identification of low-prevalence variants, it is conceivable that some RAS mutations do not provide equivalent resistance to EGFR inhibition compared with the most prevalent mutations at codons 12, 13, and 61. This report describes a case of a patient with metastatic colon cancer harboring the p.A59T variant of KRAS, with objective radiographic response (36% decrease per RECIST 1.1) and carcinoembryonic antigen biomarker response to panitumumab therapy given with FOLFIRI chemotherapy. We propose that A59T represents one potential exception to the guidelines that KRAS mutant tumors fail to respond to therapy with EGFR inhibitors, altering the paradigm of using this generalized approach.", "affiliations": "Departments of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, Minnesota;Departments of Radiology, University of Minnesota, Minneapolis, Minnesota;Departments of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, Minnesota", "authors": "Lou|Emil|E|;D'Souza|Donna|D|;Nelson|Andrew C|AC|", "chemical_list": "D000911:Antibodies, Monoclonal; D000077544:Panitumumab; D066246:ErbB Receptors", "country": "United States", "delete": false, "doi": "10.6004/jnccn.2017.0043", "fulltext": null, "fulltext_license": null, "issn_linking": "1540-1405", "issue": "15(4)", "journal": "Journal of the National Comprehensive Cancer Network : JNCCN", "keywords": null, "medline_ta": "J Natl Compr Canc Netw", "mesh_terms": "D000911:Antibodies, Monoclonal; D000971:Antineoplastic Combined Chemotherapy Protocols; D015179:Colorectal Neoplasms; D004252:DNA Mutational Analysis; D066246:ErbB Receptors; D005260:Female; D011905:Genes, ras; D005820:Genetic Testing; D006801:Humans; D061705:Image-Guided Biopsy; D008875:Middle Aged; D064847:Multimodal Imaging; D020125:Mutation, Missense; D009362:Neoplasm Metastasis; D000077544:Panitumumab; D016896:Treatment Outcome", "nlm_unique_id": "101162515", "other_id": null, "pages": "427-432", "pmc": null, "pmid": "28404754", "pubdate": "2017-04", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": "25355519;21228335;21398618;25741868;19339720;21727090;19282350;27542512;23182985;19097774;19942479;15294875;19188670;27114605;20978259;1553789;23550210;26438111;19679400;24024839", "title": "Therapeutic Response of Metastatic Colorectal Cancer Harboring a KRAS Missense Mutation After Combination Chemotherapy With the EGFR Inhibitor Panitumumab.", "title_normalized": "therapeutic response of metastatic colorectal cancer harboring a kras missense mutation after combination chemotherapy with the egfr inhibitor panitumumab" }

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{ "actiondrug": null, "activesubstance": { "activesubstancename": "BEVACIZUMAB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "ADDED TO THE FOLFIRI REGIMEN", "drugenddate": null, "drugenddateformat": null, "drugindication": "COLORECTAL CANCER METASTATIC", "drugintervaldosagedefinition": "811", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BEVACIZUMAB." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", 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THERAPEUTIC RESPONSE OF METASTATIC COLORECTAL CANCER HARBORING A KRAS MISSENSE MUTATION AFTER COMBINATION CHEMOTHERAPY WITH THE EGFR INHIBITOR PANITUMUMAB. 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"patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Epistaxis", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Rectal haemorrhage", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "LOU E, D^SOUZA D AND NELSON A. THERAPEUTIC RESPONSE OF METASTATIC COLORECTAL CANCER HARBORING A KRAS MISSENSE MUTATION AFTER COMBINATION CHEMOTHERAPY WITH THE EGFR INHIBITOR PANITUMUMAB. JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK 2017 APR 01?15 (4):427-432.", "literaturereference_normalized": "therapeutic response of metastatic colorectal cancer harboring a kras missense mutation after combination chemotherapy with the egfr inhibitor panitumumab", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20180501", "receivedate": "20180501", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14833663, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" } ]

{ "abstract": "BACKGROUND\nPreeclampsia remains a major cause of maternal and neonatal morbidity and mortality. Biologic plausibility, compelling preliminary data, and a pilot clinical trial support the safety and utility of pravastatin for the prevention of preeclampsia.\n\n\nOBJECTIVE\nWe previously reported the results of a phase I clinical trial using a low dose (10 mg) of pravastatin in high-risk pregnant women. Here, we report a follow-up, randomized trial of 20 mg pravastatin versus placebo among pregnant women with previous preeclampsia who required delivery before 34+6 weeks' gestation with the objective of evaluating the safety and pharmacokinetic parameters of pravastatin.\n\n\nMETHODS\nThis was a pilot, multicenter, blinded, placebo-controlled, randomized trial of women with singleton, nonanomalous pregnancies at high risk for preeclampsia. Women between 12+0 and 16+6 weeks of gestation were assigned to receive a daily pravastatin dose of 20 mg or placebo orally until delivery. In addition, steady-state pravastatin pharmacokinetic studies were conducted in the second and third trimesters of pregnancy and at 4 to 6 months postpartum. Primary outcomes included maternal-fetal safety and pharmacokinetic parameters of pravastatin during pregnancy. Secondary outcomes included maternal and umbilical cord blood chemistries and maternal and neonatal outcomes, including rates of preeclampsia and preterm delivery, gestational age at delivery, and birthweight.\n\n\nRESULTS\nOf note, 10 women assigned to receive pravastatin and 10 assigned to receive the placebo completed the trial. No significant differences were observed between the 2 groups in the rates of adverse or serious adverse events, congenital anomalies, or maternal and umbilical cord blood chemistries. Headache followed by heartburn and musculoskeletal pain were the most common side effects. We report the pravastatin pharmacokinetic parameters including pravastatin area under the curve (total drug exposure over a dosing interval), apparent oral clearance, half-life, and others during pregnancy and compare it with those values measured during the postpartum period. In the majority of the umbilical cord and maternal samples at the time of delivery, pravastatin concentrations were below the limit of quantification of the assay. The pregnancy and neonatal outcomes were more favorable in the pravastatin group. All newborns passed their brainstem auditory evoked response potential or similar hearing screening tests. The average maximum concentration and area under the curve values were more than 2-fold higher following a daily 20 mg dose compared with a 10 mg daily pravastatin dose, but the apparent oral clearance, half-life, and time to reach maximum concentration were similar, which is consistent with the previously reported linear, dose-independent pharmacokinetics of pravastatin in nonpregnant subjects.\n\n\nCONCLUSIONS\nThis study confirmed the overall safety and favorable pregnancy outcomes for pravastatin in women at high risk for preeclampsia. This favorable risk-benefit analysis justifies a larger clinical trial to evaluate the efficacy of pravastatin for the prevention of preeclampsia. Until then, pravastatin use during pregnancy remains investigational.", "affiliations": "Department of Obstetrics and Gynecology, the Ohio State University, Columbus, OH; Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, TX. Electronic address: [email protected].;Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, TX.;Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL.;Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, PA.;Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, TX.;Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, PA.;Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL.;Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, TX.;Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, TX.;Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, TX.", "authors": "Costantine|Maged M|MM|;West|Holly|H|;Wisner|Katherine L|KL|;Caritis|Steve|S|;Clark|Shannon|S|;Venkataramanan|Raman|R|;Stika|Catherine S|CS|;Rytting|Erik|E|;Wang|Xiaoming|X|;Ahmed|Mahmoud S|MS|;|||", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1016/j.ajog.2021.05.018", "fulltext": null, "fulltext_license": null, "issn_linking": "0002-9378", "issue": "225(6)", "journal": "American journal of obstetrics and gynecology", "keywords": "angiogenic biomarkers; high-risk pregnancy; investigational new drug; maternal and neonatal morbidity; myopathy; pharmacokinetics; pilot randomized trial; pravastatin; preeclampsia; safety", "medline_ta": "Am J Obstet Gynecol", "mesh_terms": null, "nlm_unique_id": "0370476", "other_id": null, "pages": "666.e1-666.e15", "pmc": null, "pmid": "34033812", "pubdate": "2021-12", "publication_types": "D016428:Journal Article", "references": "2106337;2589440;11192473;27678424;26723196;30217571;9537338;19909254;18997196;25194836;30575675;21592865;27777223;20567176;26360932;15262174;7509433;18792975;9114914;23194157;665563;15546153;12896819;16332646;24070396;31715077;27161513;11001066;32835720;15947178;18640262;12021218;9671773;30920918;15544924;32971013;21187414;33096092;25784688;32818477;15843671;7266377;23344286;17506782;32615618;25200125;17512048;1904355;32946849;23746925;26222708;16639429", "title": "A randomized pilot clinical trial of pravastatin versus placebo in pregnant patients at high risk of preeclampsia.", "title_normalized": "a randomized pilot clinical trial of pravastatin versus placebo in pregnant patients at high risk of preeclampsia" }

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A RANDOMIZED PILOT CLINICAL TRIAL OF PRAVASTATIN VERSUS PLACEBO IN PREGNANT PATIENTS AT HIGH?RISK OF PREECLAMPSIA. AM J OBSTET GYNECOL. 2021", "literaturereference_normalized": "a randomized pilot clinical trial of pravastatin versus placebo in pregnant patients at high risk of preeclampsia", "qualification": null, "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20210621", "receivedate": "20160617", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 12474783, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 1, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210716" }, { "companynumb": "US-CIPLA LTD.-2016US06538", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PRAVASTATIN" }, "drugadditional": null, "drugadministrationroute": "064", "drugauthorizationnumb": "077904", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PRAVASTATIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Foetal exposure during pregnancy", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Premature baby", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "COSTANTINE MM, WEST H, WISNER KL, CARITIS S, CLARK S, VENKATARAMANAN R ET AL. A RANDOMIZED PILOT CLINICAL TRIAL OF PRAVASTATIN VERSUS PLACEBO IN PREGNANT PATIENTS AT HIGH?RISK OF PREECLAMPSIA. AM J OBSTET GYNECOL. 2021", "literaturereference_normalized": "a randomized pilot clinical trial of pravastatin versus placebo in pregnant patients at high risk of preeclampsia", "qualification": null, "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20210618", "receivedate": "20160617", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 12474703, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210716" } ]

{ "abstract": "Breast FA is the most common breast tumor diagnosed in young women. Female renal transplant recipients on CsA have an increased risk of developing FA. However, reports of FA after LDLT have not been described. Our objectives were to determine the incidence of FA, analyze risk factors for FA, and evaluate treatment strategies in adolescent females after LDLT. A total of 18 female patients aged 10-19 years who underwent LDLT and survived at least one year after transplantation were enrolled in our study. The incidence of FA was 11.1%. To determine pre- or post-transplant conditions that are associated with FA after transplantation, the patients were divided into two groups according to the presence or absence of FA: FA group (n=2) and non-FA group (n=16). There were no differences in mean age at LDLT, mean age at breast evaluation, and mean duration between transplantation and breast evaluation between the two groups. However, there was a difference in the immunosuppressive regimen between the two groups. The FA group was maintained on CsA, whereas the non-FA group was maintained on tacrolimus. CsA might be implicated in FA development in adolescent females after LDLT.", "affiliations": "Pediatric Surgery, Hyogo Ika Daigaku, Nishinomiya, Hyogo.;Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka.;Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka.;Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka.;Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka.;Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.;Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka.", "authors": "Tanaka|N|N|http://orcid.org/0000-0002-7019-7748;Ueno|T|T|;Takama|Y|Y|;Yamanaka|H|H|;Tazuke|Y|Y|;Bessho|K|K|;Okuyama|H|H|", "chemical_list": null, "country": "Denmark", "delete": false, "doi": "10.1111/petr.12947", "fulltext": null, "fulltext_license": null, "issn_linking": "1397-3142", "issue": "21(6)", "journal": "Pediatric transplantation", "keywords": "adolescent female; cyclosporine; fibroadenoma; living donor liver transplantation", "medline_ta": "Pediatr Transplant", "mesh_terms": "D000293:Adolescent; D001943:Breast Neoplasms; D002648:Child; D005260:Female; D018226:Fibroadenoma; D006801:Humans; D015994:Incidence; D016031:Liver Transplantation; D019520:Living Donors; D011183:Postoperative Complications; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult", "nlm_unique_id": "9802574", "other_id": null, "pages": null, "pmc": null, "pmid": "28556594", "pubdate": "2017-09", "publication_types": "D016428:Journal Article", "references": null, "title": "Fibroadenoma in adolescent females after living donor liver transplantation.", "title_normalized": "fibroadenoma in adolescent females after living donor liver transplantation" }

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"actiondrug": "1", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "2", "drugadministrationroute": "065", "drugauthorizationnumb": "090596", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "TARGET TROUGH LEVEL WAS 12-15 DURING THE FIRST TWO WEEKS AND 2-4 NG/ML THEREAFTER", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.6 MG/KG/DAY ON POSTOPERATIVE DAY 3", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." } ], "patientagegroup": "3", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Adenoma benign", "reactionmeddraversionpt": "20.1", "reactionoutcome": "3" }, { "reactionmeddrapt": "Neurotoxicity", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "TANAKA N, UENO T, TAKAMA Y, YAMANAKA H, TAZUKE Y, BESSHO K, ET AL.. FIBROADENOMA IN ADOLESCENT FEMALES AFTER LIVING DONOR LIVER TRANSPLANTATION. PEDIATR-TRANSPLANT. 2017;21(6):E12947", "literaturereference_normalized": "fibroadenoma in adolescent females after living donor liver transplantation", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20171016", "receivedate": "20171016", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14095209, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" } ]

{ "abstract": "Increased numbers of adrenaline auto-injectors (AAIs) are in circulation in the UK. The rate of accidental auto-injection injuries has increased during this time. Various treatment strategies are described in the literature. We present the case of a 32-year-old, right-hand-dominant man who sustained an unintentional AAI injury to the volar aspect of his right thumb. On presentation to the emergency department, the thumb was ischaemic. There was no improvement with simple conservative measures (warm soaks). The patient was referred to our tertiary hand surgery service and a digital block using 2% lidocaine promoted reversal of ischaemia within 2 hours with no long-term sequelae. Phentolamine rescue, on standby, was not necessary in this case. In this case report, we highlight the therapeutic challenges associated with managing AAI injury and propose an evidence-based treatment algorithm to prevent risk of severe adverse outcomes such as digital necrosis.", "affiliations": "Plastic Surgery, Saint Thomas' Hospital, London, UK [email protected].;Plastic Surgery, Saint Thomas' Hospital, London, UK.;Plastic Surgery, Saint Thomas' Hospital, London, UK.", "authors": "Rajiah|Elizabeth|E|;McKean|Andrew R|AR|;Bain|Charles|C|", "chemical_list": "D008012:Lidocaine; D004837:Epinephrine; D010646:Phentolamine", "country": "England", "delete": false, "doi": "10.1136/bcr-2020-237016", "fulltext": null, "fulltext_license": null, "issn_linking": "1757-790X", "issue": "14(4)", "journal": "BMJ case reports", "keywords": "accidents; injuries; plastic and reconstructive surgery", "medline_ta": "BMJ Case Rep", "mesh_terms": "D000328:Adult; D000465:Algorithms; D004837:Epinephrine; D006801:Humans; D007511:Ischemia; D008012:Lidocaine; D008297:Male; D010646:Phentolamine", "nlm_unique_id": "101526291", "other_id": null, "pages": null, "pmc": null, "pmid": "33910787", "pubdate": "2021-04-28", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Accidental adrenaline auto-injector-induced digital ischaemia: a proposed treatment algorithm.", "title_normalized": "accidental adrenaline auto injector induced digital ischaemia a proposed treatment algorithm" }

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{ "abstract": "We report here the case of a 51-year-old man presenting to the Emergency Department with a febrile cutaneous eruption with diffuse arthralgia 10 days after the onset of azathioprine therapy. The clinical examination did not reveal any inflammatory syndrome and the results of all bacteriological tests were negative. A skin biopsy was performed, which revealed a granulocytary pustula with superficial dermal oedema and a neutrophil infiltration without sign of vasculitis. A side effect of azathioprine was suspected, and treatment was discontinued. Fortunately, the patient recovered within a few days. Azathioprine hypersensitivity syndrome is a rare side effect of azathioprine. Hypersensitivity syndrome is an idiosyncratic, non-IgE-mediated reaction that appears to be unrelated to thiopurine methyltransferase levels. Diagnosis is mainly clinical and requires an exclusion of other processes. The only treatment option available is to stop azathioprine intake.", "affiliations": "Department of Internal Medicine and Nephrology, Clinique et Maternité Sainte Elisabeth, Namur, Belgium. [email protected]", "authors": "Fenaux|S|S|;Tintillier|M|M|;Cuvelier|Ch|Ch|;Migali|G|G|;Pochet|J M|JM|", "chemical_list": "D007166:Immunosuppressive Agents; D001379:Azathioprine", "country": "England", "delete": false, "doi": "10.2143/ACB.3256", "fulltext": null, "fulltext_license": null, "issn_linking": "1784-3286", "issue": "68(3)", "journal": "Acta clinica Belgica", "keywords": null, "medline_ta": "Acta Clin Belg", "mesh_terms": "D001379:Azathioprine; D001706:Biopsy; D003424:Crohn Disease; D006801:Humans; D007166:Immunosuppressive Agents; D008297:Male; D008875:Middle Aged; D016463:Sweet Syndrome", "nlm_unique_id": "0370306", "other_id": null, "pages": "223-4", "pmc": null, "pmid": "24156226", "pubdate": "2013", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Azathioprine hypersensitivity syndrome: a case report.", "title_normalized": "azathioprine hypersensitivity syndrome a case report" }

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AZATHIOPRINE HYPERSENSITIVITY SYNDROME: A CASE REPORT. ACTA-CLIN-BELG 2013; 68(3) 223-224", "literaturereference_normalized": "azathioprine hypersensitivity syndrome a case report", "qualification": "3", "reportercountry": "BE" }, "primarysourcecountry": "BE", "receiptdate": "20140707", "receivedate": "20140707", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10281907, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150326" }, { "companynumb": "BE-ROXANE LABORATORIES, INC.-2014-RO-01047RO", "fulfillexpeditecriteria": "1", "occurcountry": "BE", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "AZATHIOPRINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "074069", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "CROHN^S DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZATHIOPRINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BUDESONIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "6 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "CROHN^S DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ENTOCORT" } ], "patientagegroup": null, "patientonsetage": "51", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "FENAUX S,TINTILLIER M,CUVELIER C,MIGALI G. AZATHIOPRINE HYPERSENSITIVITY SYNDROME: A CASE REPORT. ACTA CLINICA BELGICA 2013 JUN;68:3:223-224.", "literaturereference_normalized": "azathioprine hypersensitivity syndrome a case report", "qualification": "3", "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "BE", "receiptdate": "20140714", "receivedate": "20140714", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10303221, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150326" } ]

{ "abstract": "Background: To investigate the prognostic value of circulating plasma cells (CPC) and establish novel nomograms to predict individual progression-free survival (PFS) as well as overall survival (OS) of patients with newly diagnosed multiple myeloma (NDMM). Methods: One hundred ninetyone NDMM patients in Wuhan Union Hospital from 2017.10 to 2020.8 were included in the study. The entire cohort was randomly divided into a training (n = 130) and a validation cohort (n = 61). Univariate and multivariate analyses were performed on the training cohort to establish nomograms for the prediction of survival outcomes, and the nomograms were validated by calibration curves. Results: When the cut-off value was 0.038%, CPC could well distinguish patients with higher tumor burden and lower response rates (P < 0.05), and could be used as an independent predictor of PFS and OS. Nomograms predicting PFS and OS were developed according to CPC, lactate dehydrogenase (LDH) and creatinine. The C-index and the area under receiver operating characteristic curves (AUC) of the nomograms showed excellent individually predictive effects in training cohort, validation cohort or entire cohort. Patients with total points of the nomograms ≤ 60.7 for PFS and 75.8 for OS could be defined as low-risk group and the remaining as high-risk group. The 2-year PFS and OS rates of patients in low-risk group was significantly higher than those in high-risk group (p < 0.001). Conclusions: CPC is an independent prognostic factor for NDMM patients. The proposed nomograms could provide individualized PFS and OS prediction and risk stratification.", "affiliations": "Institute of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.;Institute of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.;Institute of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.;Institute of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.;Institute of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.;Institute of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.", "authors": "Cheng|Qianwen|Q|;Cai|Li|L|;Zhang|Yuyang|Y|;Chen|Lei|L|;Hu|Yu|Y|;Sun|Chunyan|C|", "chemical_list": null, "country": "Switzerland", "delete": false, "doi": "10.3389/fonc.2021.639528", "fulltext": "\n==== Front\nFront Oncol\nFront Oncol\nFront. Oncol.\nFrontiers in Oncology\n2234-943X\nFrontiers Media S.A.\n\n10.3389/fonc.2021.639528\nOncology\nOriginal Research\nCirculating Plasma Cells as a Biomarker to Predict Newly Diagnosed Multiple Myeloma Prognosis: Developing Nomogram Prognostic Models\nCheng Qianwen 1\nCai Li 1\n\nZhang Yuyang 1\nChen Lei 1\n\nHu Yu 12*\n\nSun Chunyan 12*\n\n1Institute of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China\n2Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, China\nEdited by: María-Victoria Mateos, University Hospital of Salamanca, Spain\n\nReviewed by: Shaji Kumar, Mayo Clinic, United States; Alessandra Larocca, University Hospital of the City of Health and Science of Turin, Italy\n\n*Correspondence: Yu Hu [email protected]\nChunyan Sun [email protected]\nThis article was submitted to Hematologic Malignancies, a section of the journal Frontiers in Oncology\n\n05 3 2021\n2021\n11 63952809 12 2020\n10 2 2021\nCopyright © 2021 Cheng, Cai, Zhang, Chen, Hu and Sun.\n2021\nCheng, Cai, Zhang, Chen, Hu and Sun\nThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.\nBackground: To investigate the prognostic value of circulating plasma cells (CPC) and establish novel nomograms to predict individual progression-free survival (PFS) as well as overall survival (OS) of patients with newly diagnosed multiple myeloma (NDMM).\n\nMethods: One hundred ninetyone NDMM patients in Wuhan Union Hospital from 2017.10 to 2020.8 were included in the study. The entire cohort was randomly divided into a training (n = 130) and a validation cohort (n = 61). Univariate and multivariate analyses were performed on the training cohort to establish nomograms for the prediction of survival outcomes, and the nomograms were validated by calibration curves.\n\nResults: When the cut-off value was 0.038%, CPC could well distinguish patients with higher tumor burden and lower response rates (P < 0.05), and could be used as an independent predictor of PFS and OS. Nomograms predicting PFS and OS were developed according to CPC, lactate dehydrogenase (LDH) and creatinine. The C-index and the area under receiver operating characteristic curves (AUC) of the nomograms showed excellent individually predictive effects in training cohort, validation cohort or entire cohort. Patients with total points of the nomograms ≤ 60.7 for PFS and 75.8 for OS could be defined as low-risk group and the remaining as high-risk group. The 2-year PFS and OS rates of patients in low-risk group was significantly higher than those in high-risk group (p < 0.001).\n\nConclusions: CPC is an independent prognostic factor for NDMM patients. The proposed nomograms could provide individualized PFS and OS prediction and risk stratification.\n\nnewly diagnosed multiple myeloma\ncirculating plasma cells\nbiomarker\nnomograms\nprognosis\n==== Body\nIntroduction\n\nMultiple myeloma (MM) is a malignant plasma cell disorder with wide variation in clinical progression and prognosis, which would be estimated 32,270 new cases and 12,830 deaths in American in 2020 (1). Results from the Surveillance, Epidemiology, and End Results database showed an increase in 10–20-year relative survival of MM patients between 2002–2006 and 2012–2016 (2). In China, the incidence of MM kept increasing from 2006 to 2016, but the mortality remained stable between 2014 and 2016 after the increase from 2006 to 2014, which might due to the development of new therapeutic approaches such as bortezomib, lenalidomide, and hematopoietic stem cell transplantation (3–5). The prognosis of MM is highly heterogeneous, with some patients surviving for more than 10 years and others for only a few months (6). The prognostic factors and staging systems of MM are changing with the development of detection techniques and treatment strategies. The first widely used staging system of MM was the Durie-Salmon (D-S) staging system in 1975 (7). Later, with the development of new treatment methods, the International Staging System (ISS) was established in 2005 (8). With increasing attention paid to cytogenetic features, Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) 2007, updated mSMART 2013, mSMART 3.0 in 2018 and the International Myeloma Working Group (IMWG) 2016 staging system all recommended using cytogenetic abnormalities (CA) as the risk stratification criteria for MM patients (9–12). The Revised International Staging System (R-ISS) proposed in 2015 have incorporated CA and lactate dehydrogenase (LDH) (13).\n\nCirculating plasma cells (CPC) has been found to have prognostic significance in MM patients for decades (14), and the technology to detect CPC has changed from slide-base immunofluorescence assay to multi-parameter flow cytometry (MFC). Subsequent studies have shown that CPC has prognostic significance both in patients with newly diagnosed MM (NDMM) (15), refractory/relapsed MM (16), smoldering MM (17), and MM patients who have undergone autologous hematopoietic stem cell transplantation (ASCT) (18, 19). But there is no conclusion on the optimal cut-off value of CPC at present, and few studies have reported how we should apply the results of CPC in combination with other predictors to predict survival in MM patients in clinical application.\n\nNomogram is constructed on the basis of multivariate regression models (such as Cox and logistic regression models), which can transform complex regression equations into simple and visual graphics, and making the results of prediction model more readable and valuable for use (20). When predicting the probability of individual events, nomogram is more quickly, intuitively, and accurately, compared with the traditional clinical staging systems (21, 22). Therefore, nomogram has been increasingly used in clinical practice, especially in predicting the recurrence, metastasis or death of cancer patients (22–26). In this retrospective study, we used seven-color MFC to evaluate CPC in peripheral blood of NDMM patients. Then we explored the correlation of CPC with the clinical features and prognosis of NDMM patients, and established nomograms to predict individual progression-free survival (PFS) and overall survival (OS) based on CPC.\n\nPatients and Methods\n\nPatients\n\nWe conducted a retrospective study on 191 consecutive patients with NDMM treated in Wuhan Union hospital of China between 2017.10 and 2020.8. The International Myeloma Working Group (IMWG) criteria was used to assess the diagnosis and treatment response. Patients with diseases such as Waldenström macroglobulinemia, lymphoma, plasma cell leukemia, systemic light chain amyloidosis (AL amyloidosis), and MM patients who previously had received chemotherapy were excluded. The patient's flow diagram was in Figure 1. The clinical information was collected retrospectively by reviewing the patients' medical records. PFS was calculated from the beginning of first-line chemotherapy until the date of disease progression, death, or the last date the patient was known to be free of disease progression. OS was calculated from the beginning of first-line chemotherapy until death or the last date the patient was known to be alive. The degree of myeloma bone disease (MBD) was assessed using radiographic methods. This study has been approved by the Ethics Committee of Tongji Medical College of Huazhong University of Science and Technology and followed the principles of the Declaration of Helsinki.\n\nFigure 1 Patient flow diagram. CPC, circulating plasma cells; MM, multiple myeloma; NDMM, newly diagnosed multiple myeloma; systemic AL amyloidosis, systemic light chain amyloidosis; SMM, smoldering multiple myeloma; WM, Waldenström macroglobulinemia; PCL, plasma cell leukemia; POEMS, POEMS Syndrome; MGUS, monoclonal gammopathy of undetermined significance; MGRS, monoclonal gammopathy of renal significance.\n\nQuantification of CPC\n\nCPC levels at the time of diagnosis were detected and quantified by two-tube, seven-color MFC. Peripheral blood mononuclear cells isolated by Ficoll gradient were analyzed by flow cytometric analyses and stained with antibodies to CD38, CD138, CD45, CD56, CD19, and cytoplasmic kappa and lambda immunoglobulin light chains. Samples were examined on a BD FACS Canto flow cytometer (BD Biosciences) and data were analyzed by BD FACS Diva 8.0 (BD Biosciences). The sensitivity of clonal CPC was more than 0.001% (106 cells were collected per tube), and the results of CPC were reported as a percentage of total mononuclear cells.\n\nConstruction of the Nomograms\n\nThe 191 NDMM patients were randomly divided into a training cohort of 130 patients and a validation cohort of 61 patients with a ratio of 7:3 through a random number list generated by SPSS. The training cohort was used to establish the PFS and OS nomograms. In the training cohort, the following clinical features were assessed to identify predictors of survival: age, sex, D-S stage, ISS stage, R-ISS stage, extramedullary myeloma, first line therapy regimens, ASCT, CA, clonal bone marrow plasma cells (BMPC), LDH, albumin (ALB), β2-microglobulin (β2-MG), hypersensitive C-reactive protein (hs-CRP), CPC, calcium, creatinine, hemoglobin, and monoclonal protein (M-protein). According to the R-ISS in 2015, IMWG in 2016 and mSMART 3.0 in 2018, high-risk CA include t (4; 14), gain (1q), del (17p), t (14; 16) as well as t (14; 20) (11–13). Univariate analysis of potential risk factors for PFS and OS was performed using the Cox proportional hazards regression model. Variables in the univariate analysis with p < 0.10 were chosen for multivariate Cox proportional hazard regression to identify the independent prognostic factors. Based on the results of the multivariate Cox regression analyses, nomogram models to predict PFS and OS for NDMM patients were formulated.\n\nValidation of the Nomograms\n\nThe prognostic performance of the nomogram was validated by measuring discrimination and calibration in training, validation and entire cohort. The predictive power of the nomogram was assessed by C-index (concordance index), and a higher C-index indicates a better ability to discriminate patients among different survival outcomes. The calibration plots generated by 1,000 bootstraps resampling reflect the agreement between observed outcomes and predicted probabilities. The total point of nomogram for PFS and OS was calculated for each patient. In addition, receiver operating characteristic (ROC) curve analysis were conducted to further evaluate the predictive performance of the nomogram total point for PFS and OS, and the discriminative power of different models were evaluated by calculating the area under the ROC curve (AUC).\n\nStatistical Analysis\n\nBaseline continuous variables were presented as mean and standard deviation for normally distributed data or as median and inter-quartile range (IQR) for non-normal data, and categorical variables were presented as counts and percentages. Continuous variables were compared using the independent Student's t-test or Mann-Whitney U-test, and categorical data were compared using χ2-test or Fisher's exact test. ROC curve analysis was performed to determine the optimal cut-off values of continuous variables based on maximum Youden index. PFS and OS rates were estimated by the Kaplan-Meier method and compared between groups by the log-rank test. A 2-sided p < 0.05 was considered statistically significant. Statistical analyses were conducted using SPSS version 23.0 (IBM Corp). Kaplan-Meier survival curves and scatter plots were generated by GraphPad Prism (Version 8.0.2, GraphPad Software Inc.). ROC curves were plotted using MedCalc (Version 18.2.1). The nomograms and calibration curves were formulated with the R software (Version 3.6.1, R Project for Statistical Computing, Vienna, Austria).\n\nResults\n\nClinical Characteristics\n\nThe baseline characteristics of the training and validation cohorts are presented in Table 1. A total of 191 patients were included in the analysis, whose average age was 59.0 ± 9.8 years (range: 30–88 years), with 58 (30.4%) patients of 65 year-old or older. Among these patients, there were 105 (55%) men and 86 (45%) women, with a median CPC of 0.006% (0.000–0.120%), and a median clonal BMPC of 19% (7–40%). In total, 160 (83.8%) patients received proteasome inhibitors (PIs)-containing regimens (bortezomib and carfilzomib), 31 (16.2%) received immunomodulatory drugs (IMiDs)-based regimens (lenalidomide and thalidomide) as first line therapy regimen. The patients were randomly divided into a training cohort of 130 patients and a validation cohort of 61 patients. There were no significant differences between the two groups of patients in age, sex, clonal bone marrow plasma cells, CPC, hemoglobin, albumin, creatinine, β2-MG, LDH, hs-CRP, extramedullary myeloma, MM type, high-risk CA, D-S, ISS, R-ISS, first line therapy regimens, ASCT, or response rates.\n\nTable 1 Patients' baseline characteristics.\n\nCharacteristics\tTraining cohort (n = 130)\tValidation cohort (n = 61)\tP\t\nAge, years, mean (SD)\t59 (9)\t59 (11)\t0.736\t\nSex, n (%)\t\t\t0.884\t\n Male\t71 (54.6)\t34 (55.7)\t\t\n Female\t59 (45.4)\t27 (44.3)\t\t\nClonal bone marrow plasma cells, %, Median (IQR)\t17 (7–41)\t21 (8–39)\t0.333\t\nCPC, %, median (IQR)\t0.005 (0.000–0.122)\t0.009 (0.000–0.135)\t0.718\t\nCPC status, n (%)\t\t\t0.748\t\n  ≤ 0.038%\t82 (63.1)\t37 (60.7)\t\t\n >0.038%\t48 (34.9)\t24 (39.3)\t\t\nHemoglobin, g/L, mean (SD)\t98 (25)\t93 (26)\t0.184\t\nAlbumin, g/L, mean (SD)\t37.0 (6.6)\t36 (5)\t0.104\t\nCreatinine, μmol/L, median (IQR)\t80.0 (61.8–119.2)\t91.9(61.0–223.7)\t0.234\t\nβ2-MG, mg/L, median (IQR)\t4.1 (2.7–7.7)\t5.4 (2.9–10.8)\t0.222\t\nLDH, U/L, median (IQR)\t194 (160–250)\t184 (146–271)\t0.884\t\nhs-CRP, mg/L, median (IQR)\t0.87 (0.00–9.04)\t2.72 (0.21–8.31)\t0.222\t\nExtramedullary myeloma, n (%)\t12 (9.2)\t3 (4.9)\t0.457\t\nType, n (%)\t\t\t0.070\t\n IgG\t60 (46.2)\t34 (55.7)\t\t\n IgA\t35 (26.9)\t7 (11.5)\t\t\n IgD\t9 (6.9)\t8 (13.1)\t\t\n Other\t26 (20.0)\t12 (19.7)\t\t\nHigh-risk CA, n (%)\t58 (44.6)\t34 (55.7)\t0.151\t\nD-S, n (%)\t\t\t0.361\t\n I\t15 (11.5)\t5 (8.2)\t\t\n II\t28 (21.5)\t9 (14.8)\t\t\n III\t87 (66.9)\t47 (77.0)\t\t\nISS, n (%)\t\t\t0.103\t\n I\t37 (28.5)\t13 (21.3)\t\t\n II\t48 (36.9)\t17 (27.9)\t\t\n III\t45 (34.6)\t31 (50.8)\t\t\nR-ISS, n (%)\t\t\t0.466\t\n I\t29 (22.3)\t11 (18.0)\t\t\n II\t71 (54.6)\t31 (50.8)\t\t\n III\t30 (23.1)\t19 (31.1)\t\t\nFirst line therapy regimens, n (%)\t\t\t0.705\t\n PIs-containing regimens\t108 (83.1)\t52 (85.2)\t\t\n IMiDs-based regimens\t22 (16.9)\t9 (14.8)\t\t\nASCT, n (%)\t8 (6.2)\t1 (1.6)\t0.314\t\nResponse rates, n (%)\t\t\t\t\n VGPR or better\t67 (51.5)\t29 (47.5)\t0.606\t\n PR or better\t98 (75.4)\t48 (78.7)\t0.616\t\nCPC, circulating plasma cells; β2-MG, β2-microglobulin; LDH, lactate dehydrogenase; hs-CRP, hypersensitive C-reactive protein; High-risk CA, High-risk Cytogenetic abnormalities, D-S, Durie-Salmon staging system; ISS, International Staging System; R-ISS, Revised-International Staging System; PIs, proteasome inhibitors; IMiDs, immunomodulatory drugs; ASCT, autologous hematopoietic stem cell transplantation; VGPR, very good partial response; PR, partial response.\n\nSurvival of Training and Validation Cohorts\n\nWith a median follow-up duration of 11 months (range: 2–36 months), the 2-year PFS rate was 45.8% and the 2-year OS rate was 77.2% among all patients. The median follow-up duration was 11 months (range: 2–36 months) in training cohort and 12 months (range: 2–36 months) in validation cohort, respectively (P = 0.178). Kaplan-Meier analysis of the NDMM patients showed that the 2-year PFS rate was 42.1 and 50.8% for the training cohort and the validation cohort, respectively (P = 0.539), while the 2-year OS rate was 78.0 and 75.7%, respectively (P = 0.886).\n\nThe Relationship Among CPC, Patient Survival and Clinical Characteristics\n\nCPC were detected in 113 patients (59.2%) with a median of 0.070% (range, 0.001–9.670%). We tested different cut-off values for CPC, and used 0.038% as the cut-off value for subsequent analysis because of the largest Youden index for OS (training cohort and entire cohort: 0.298 and 0.223). We compared patients with undetectable CPC (n = 78) and those with detectable CPC less than 0.038% (n = 41), and found that the baseline features, response rates and survival showed no differences between the two group of patients (p > 0.05) (Supplementary Table 1). So, the grade of CPC was performed as follows: CPC negative group included 119 patients who had <0.038% or undetectable CPC, CPC positive group included patients who had more than 0.038% CPC. Statistically significant differences were found in markers of high disease burden including BMPC, hemoglobin, creatinine, β2-MG, LDH, and MBD between patients of CPC negative and positive group (P < 0.05). CPC positive was significantly associated with D-S (p = 0.046), ISS (p < 0.001), and R-ISS stage (p < 0.001). The response rate of CPC positive group (37.5% ≥ very good partial response and 68.1% ≥ partial response) was lower than of negative group (58.0% ≥ very good partial response and 81.5% ≥ partial response) (P < 0.05) (Table 2; Figures 2A–F). In the training cohort and entire cohort, the PFS and OS rates of CPC negative group were better than those of CPC positive group (2-year PFS rate of training cohort: 55.2 vs. 21.7%, p = 0.007; 2-year OS rate of training cohort: 84.3 vs. 66.9%, p = 0.001; 2-year PFS rate of entire cohort: 60.3 vs. 19.8%, p < 0.001; 2-year OS rate of entire cohort: 82.5 vs. 68.4%, p = 0.002). In the validation cohort, PFS rate of CPC negative group was better than that of CPC positive group (2-year PFS rate: 67.6 vs. 16.4%, p = 0.011), but there was no significant difference in OS rate between the two groups (2-year OS rate: 79.3 vs. 72.5%, p = 0.150) (Figures 2G–L).\n\nTable 2 The relationship between CPC and clinical characteristics.\n\nCharacteristics\tCPC negative (≤0.038%) (n = 119)\tCPC positive (>0.038%) (n = 72)\tP\t\nAge, years, mean (SD)\t58 (9)\t60 (11)\t0.211\t\nSex, n (%)\t\t\t0.439\t\n Male\t68 (57.1)\t37 (51.4)\t\t\n Female\t51 (42.9)\t35 (48.6)\t\t\nClonal bone marrow plasma cells, %, median (IQR)\t15 (5–31)\t31 (12–50)\t<0.001\t\nHemoglobin, g/L, mean (SD)\t101 (26)\t88 (21)\t<0.001\t\nAlbumin, g/L, mean (SD)\t36.8 (6.3)\t36.2 (6.1)\t0.433\t\nCreatinine, μmol/L, median (IQR)\t75.8 (60.2–111.6)\t99.2 (72.1–292.4)\t0.001\t\nβ2-MG, mg/L, median (IQR)\t3.5 (2.6–6.0)\t7.0 (3.7–12.6)\t<0.001\t\nLDH, U/L, median (IQR)\t182 (148–236)\t207 (166–275)\t0.044\t\nhs-CRP, mg/L, median (IQR)\t1.01 (0.00–6.98)\t1.95 (0.00–11.50)\t0.279\t\nCalcium, mmol/L, median (IQR)\t2.26 (2.15–2.38)\t2.34 (2.15–2.54)\t0.058\t\nExtramedullary myeloma, n (%)\t11 (9.2)\t4 (5.6)\t0.358\t\nMyeloma bone disease, n (%)\t\t\t0.032\t\n 0–3\t55 (46.2)\t22 (30.6)\t\t\n >3\t64 (53.8)\t50 (69.4)\t\t\nType, n (%)\t\t\t0.861\t\n IgG\t59 (49.6)\t35 (48.6)\t\t\n IgA\t28 (23.5)\t14 (19.4)\t\t\n IgD\t10 (8.4)\t7 (9.7)\t\t\n Other\t22 (18.5)\t16 (22.2)\t\t\nHigh-risk CA, n (%)\t51 (42.9)\t41 (56.9)\t0.059\t\nD-S, n (%)\t\t\t0.046\t\n I\t17 (14.3)\t3 (4.2)\t\t\n II\t25 (21.0)\t12 (16.7)\t\t\n III\t77 (64.7)\t57 (79.2)\t\t\nISS, n (%)\t\t\t<0.001\t\n I\t42 (35.3)\t8 (11.1)\t\t\n II\t45 (37.8)\t20 (27.8)\t\t\n III\t32 (26.9)\t44 (61.1)\t\t\nR-ISS, n (%)\t\t\t<0.001\t\n I\t33 (27.7)\t7 (9.7)\t\t\n II\t68 (57.1)\t34 (47.2)\t\t\n III\t18 (15.1)\t31 (43.1)\t\t\nFirst line therapy regimens, n (%)\t\t\t0.349\t\n PIs-containing regimens\t102 (85.7)\t58 (80.6)\t\t\n IMiDs-based regimens\t17 (14.3)\t14 (19.4)\t\t\nASCT, n (%)\t7 (5.9)\t2 (2.8)\t0.326\t\nResponse rates, n (%)\t\t\t\t\n VGPR or better\t69 (58.0)\t27 (37.5)\t0.006\t\n PR or better\t97 (81.5)\t49 (68.1)\t0.034\t\nCPC, circulating plasma cells; β2-MG, β2-microglobulin; LDH, lactate dehydrogenase; hs-CRP, hypersensitive C-reactive protein; High-risk CA, High-risk Cytogenetic abnormalities, D-S, Durie-Salmon staging system; ISS, International Staging System; R-ISS, Revised-International Staging System; PIs, proteasome inhibitors; IMiDs, immunomodulatory drugs; ASCT, autologous hematopoietic stem cell transplantation; VGPR, very good partial response; PR, partial response.\n\nFigure 2 Characteristics and Kaplan-Meier curves of CPC negative (≤0.038%) (n = 119) and positive (>0.038%) (n = 72) group. (A–F) Comparison of BMPC, hemoglobin, creatinine, β2-MG, LDH, and calcium between CPC negative and positive group (P < 0.05). The PFS (G–I) and OS (J–L) curves for patients in training cohort (G,J), validation cohort (H,K), and entire cohort (I,L).\n\nNomogram of PFS for NDMM\n\nDevelopment and Validation of a Nomogram of PFS for NDMM\n\nAs shown in Table 3, univariate Cox regression analysis showed that CPC, creatinine, LDH, β2-MG and high-risk CA were correlated with PFS, and multivariate analysis identified CPC, creatinine and LDH as independent predictors of PFS in NDMM patients. The above three independent predictors of PFS were integrated into a PFS rate estimation nomogram (Figure 3A). The method to estimate PFS rates based on nomogram: the value of the creatinine, LDH and CPC is located on each variable axis, and then draw an upward line to the point axis to determine the number of points corresponding to each variable value. The sum of these points is located on the total point axis, and then a downward line is drawn from the total points axis to the survival axis to get the 1-year and 2-year PFS rates. The C-index of the nomogram in discriminating PFS in the training cohort was 0.738 (95% CI: 0.643–0.832), and the calibration plots showed good agreement between the predicted PFS and the observed PFS rate (Figures 3B,E). In the validation cohort and the entire cohort, the C-index of the nomogram were 0.687 (95% CI: 0.549–0.824) and 0.716 (95% CI: 0.637–0.795). The calibration plots also showed good agreement between predictions and actual observations in both validation cohort (Figures 3C,F) and entire cohort (Figures 3D,G).\n\nTable 3 Univariate and multivariate Cox analysis for OS and PFS in patients with NDMM in training cohort.\n\nVariable\tUnivariate\tMultivariate\t\n\tHR (95% CI)\tP\tHR (95% CI)\tP\t\nPFS\t\nβ2-MG\t1.034 (1.004–1.066)\t0.028\t0.949 (0.893–1.009)\t0.094\t\nCPC\t2.157 (1.202–3.871)\t0.010\t2.047 (1.101–3.807)\t0.024\t\nCreatinine\t1.003 (1.002–1.004)\t<0.001\t1.004 (1.002–1.006)\t<0.001\t\nLDH\t1.004 (1.002–1.007)\t0.001\t1.005 (1.002–1.008)\t0.001\t\nHigh-risk CA\t1.720 (0.963–3.075)\t0.067\t1.627 (0.885–2.990)\t0.117\t\nOS\t\nCPC\t4.125 (1.626–10.470)\t0.003\t3.394 (1.253–9.192)\t0.016\t\nCreatinine\t1.004 (1.002–1.005)\t<0.001\t1.004 (1.002–1.006)\t<0.001\t\nLDH\t1.004 (1.001–1.008)\t0.008\t1.005 (1.001–1.009)\t0.022\t\nβ2-MG\t1.041 (1.008–1.076)\t0.015\t0.965 (0.903–1.031)\t0.294\t\nHemoglobin\t0.981 (0.962–1.001)\t0.057\t0.993 (0.971–1.016)\t0.541\t\nHigh-risk CA\t1.968 (0.824–4.696)\t0.127\t\t\t\nPFS, progression-free survival; OS, overall survival; CPC, circulating plasma cells; β2-MG, β2-microglobulin; LDH, lactate dehydrogenase; High-risk CA, High-risk Cytogenetic abnormalities.\n\nFigure 3 (A) Nomogram of PFS for patients with NDMM. Calibration curves for predicting 1-year and 2-year PFS in training cohort (B,E), validation cohort (C,F), and entire cohort (D,G). CPC negative: ≤0.038%; CPC positive: >0.038%.\n\nThe C-Index and AUC of Nomogram and D-S, ISS, and R-ISS Staging System for PFS\n\nThe results showed that the C-index of the nomogram in the training cohort, validation cohort, and entire cohort was 0.738, 0.687, and 0.716, respectively. In the training cohort, validation cohort, and entire cohort, the C-index of D-S was 0.532, 0.604, and 0.553, the C-index of ISS was 0.608, 0.596, and 0.601, and the C-index of R-ISS was 0.621, 0.601, and 0.612. The AUC of the nomogram and the D-S, ISS and R-ISS staging systems was shown in Figures 4A–C.\n\nFigure 4 Area under the ROC curves of nomogram, D-S, ISS, and R-ISS stage of PFS (A–C) and OS (D–F) in training cohort (A,D), validation cohort (B,E), and entire cohort (C,F).\n\nNomogram of OS for NDMM\n\nDevelopment and Validation of a Nomogram of OS for NDMM\n\nThe results of univariate and multivariate Cox regression analysis based on pretreatment data are shown in Table 3. Univariate analysis showed that CPC, creatinine, LDH, β2-MG, and hemoglobin were correlated with OS. Multivariate analysis identified CPC, creatinine and LDH as independent predictors for OS of NDMM patients. Then, the above three independent predictors of OS were integrated into an OS rate estimation nomogram (Figure 5A). The nomogram of OS is used in a similar way to the nomogram of PFS. The C-index of the nomogram in discriminating OS in the training cohort was 0.802 (95% CI: 0.679–0.926), and the calibration plots showed good agreement between the predicted OS and the observed OS rate (Figures 5B,E). In the validation cohort and the entire cohort, the C-index of the nomogram were 0.722 (95% CI: 0.512–0.931) and 0.766 (95% CI: 0.655–0.878). The calibration plots also showed good agreement between predictions and actual observations both in the validation cohort (Figures 5C,F) and the entire cohort (Figures 5D,G).\n\nFigure 5 (A) Nomogram of OS for patients with NDMM. Calibration curves for predicting 1-year and 2-year OS in training cohort (B,E), validation cohort (C,F), and entire cohort (D,G). CPC negative: ≤0.038%; CPC positive: >0.038%.\n\nThe C-Index and AUC of Nomogram and D-S, ISS, and R-ISS Staging System for OS\n\nThe results showed that the C-index of the nomogram in the training cohort, validation cohort, and entire cohort was 0.802, 0.722, and 0.766, respectively. In the training cohort, validation cohort, and entire cohort, the C-index of D-S was 0.514, 0.603, and 0.538, the C-index of ISS was 0.688, 0.650, and 0.681, and the C-index of R-ISS was 0.705, 0.669, and 0.697. The AUC of the nomogram and the D-S, ISS and R-ISS staging system was shown in Figures 4D–F.\n\nDistinguishing High- and Low-Risk Patients Based on the Nomogram Total Points\n\nAs shown in Figure 6, for PFS of patients in entire cohort, all of the three existing staging systems (D-S, ISS, and R-ISS staging system) cannot distinguish well the prognosis of patients among stage I, II, and III (Figures 6A–C). And for OS of them, the D-S cannot well distinguish the prognosis of patients among stage I, II, and III (Figure 6D), the ISS cannot well distinguish the prognosis of patients between stage I and II (Figure 6E), and the R-ISS showed good prognostic stratification for the patients among stages I, II, and III (Figure 6F). Each patient was given a total point for PFS and a total point for OS based on the 2 nomogram models. With the threshold of 60.7 for PFS and 75.8 for OS, the nomogram score respectively stratified patients from the 3 cohorts into high-risk and low-risk groups. For PFS, 45 patients were assigned to the high-risk group (>60.7) and 146 to the low-risk group (≤60.7). Eighty percent (36/45) of patients in the high-risk group and 84.9% (124/146) of patients in the low-risk group received PIs-containing regimens as first line therapy (p = 0.433). The 2-year PFS rate of patients in low-risk group was significantly higher than that in high-risk group (all patients: 56.0 vs 17.2%, p < 0.001; HR: 3.241, 95% CI: 1.992–5.272) (Figures 6G–I). For OS, there were 40 patients in the high-risk group (>75.8) and 151 patients in the low-risk group (≤75.8). 82.5% (33/40) of the high-risk group and 84.1% (127/151) of the low-risk group received PI-containing regimens as first line therapy (p = 0.807). The difference of 2-year OS rate between low-risk group and high-risk group was statistically significant (all patients: 86.6 vs. 44.7%, p < 0.001; HR: 5.651, 95% CI: 2.807–11.379) (Figures 6J–L). According to the survival analysis of PFS and OS, the nomogram showed excellent prediction ability when divided patients into high-risk and low-risk groups (p < 0.05 in training cohort, validation cohort, and entire cohort) (Figures 6G–L).\n\nFigure 6 Kaplan-Meier survival curves of the NDMM patients, categorized by different staging systems. PFS (A–C) and OS (D–F) curve of the D-S (A,D), ISS (B,E) and R-ISS (C,F) stage in entire cohort. PFS (G–I) and OS (J–L) curve of the nomogram stage in training cohort (G,J), validation cohort (H,K), and entire cohort (I,L).\n\nDiscussion\n\nThe prognostic significance of CPC measured by MFC has been well established in MM patients at the time of diagnosis (15, 27–29), and the objective of this analysis was to develop and validate a CPC based individual prognostic nomogram for patients with NDMM. The C-index of the nomogram for PFS were 0.738 (95% CI: 0.643–0.832) in training cohort, 0.687 (95% CI: 0.549–0.824) in validation cohort and 0.716 (95% CI: 0.637–0.795) in entire cohort. The C-index of the nomogram for OS were 0.802 (95% CI: 0.679–0.926) in training cohort, 0.722 (95% CI: 0.512–0.931) in validation cohort and 0.766 (95% CI: 0.655–0.878) in entire cohort. The C-indexes and ROC curves demonstrated that nomograms showed excellent individually predictive effects in predicting PFS and OS of patients with NDMM in training cohort, validation cohort or entire cohort. Patients with total points of the nomograms ≤60.7 for PFS and 75.8 for OS could be defined as low-risk group with a 2-year PFS rate of 56.0% and a 2-year OS rate of 86.6%, while patients with total points of the nomograms >60.7 for PFS and 75.8 for OS could be defined as high-risk group with a 2-year PFS rate of 17.2% and a 2-year OS rate of 44.7. Our results suggest that when predicting the individual PFS and OS rates, nomogram is a quickly, intuitively and accurately tool, and the risk stratification based on nomogram shows excellent performance.\n\nOur nomograms for PFS and OS both included CPC, creatinine, and LDH. All these factors had been found to be associated with advanced myeloma in previous studies. Serum creatinine was a commonly used indicator to evaluate renal function in daily work and had been included in D-S staging system and IMWG updated criteria for the diagnosis of MM (7, 30). Thanks to the advent of new drugs, the survival of patients with renal insufficiency has improved considerably over the past decade. However, patients with severe renal insufficiency, especially the elderly, still have a high risk of early death (31, 32). High serum LDH level have been shown to be a marker of aggressive myeloma and short survival, and have been included in the R-ISS (13, 32, 33). Our results support that serum creatinine and LDH as independent predictors of PFS and OS in patients with NDMM (Table 3).\n\nThe cut-off value of CPC is different among studies, ranged from 10 CPC per 50,000 events (0.02%) to 400 CPC per 150,000 events (0.267%) (15, 27, 34–37). Differences in cut-off values may be attributed to difference of patient populations, detection techniques, and treatment regimens. Since most of the relevant reports are single-center studies, it is not clear whether these cut-off values are applicable to the prognosis of all MM patients, so there is no consensus on the optimal cut-off value of CPC. But in different studies, patients in high CPC group showed highly proliferative disease in terms of higher BMPC, LDH, M-protein, β2-MG and high risk CA, higher D-S, ISS and R-ISS stage, lower hemoglobin and albumin, and shorter survival time (27, 36, 38–40). Our study found that when the cut-off value was 0.038%, CPC could be used as an independent predictor of PFS and OS, and could well distinguish patients with higher tumor burden, more aggressive tumor status and lower response rates as well (Table 2; Figure 2). It is important for its clinical application to determine the optimal cut-off value of CPC, and our research may provide a better choice for the optimal cut-off value of CPC.\n\nAlthough there have been several nomogram prediction models for NDMM patients in previous studies, to our knowledge, this is the first nomogram based on CPC, and the first nomogram to predict PFS in NDMM patients (41–43). The nomograms we developed in this study to predict the PFS and OS rates of NDMM patients showed excellent individually predictive effects. Moreover, the nomograms showed greater predictive ability in PFS and OS than the commonly used MM staging models such as the D-S, ISS and R-ISS staging system. Compared with other studies, our nomogram is simpler, more intuitive and easier to apply in clinical practice.\n\nAlthough our nomogram performed well in predicting PFS and OS in NDMM patients, there were some limitations in this study. First, as with other retrospective studies, data bias exists. Second, our nomograms were developed and validated using single-center data without external validation using data from other research centers. Third, a limited number of subjects were included in this study, and the median follow-up time was only 11 months. Fourth, due to low economic level, low health insurance coverage of the transplant drugs, low educational level, and low acceptance of standardized and holistic treatment of the disease, only 7% of the eligible patients received ASCT in our research. So, the results in our study need to be further corroborated by data from prospective and other institutions, and the verification of the nomograms requires a larger sample size and a longer follow-up time to get more convincing results when implemented in clinical practice.\n\nConclusions\n\nIn conclusion, we developed a nomogram to predict 1-year, 2-year PFS and a nomogram to predict 1-year, 2-year OS as prognostic tools for patients with NDMM. Our results suggest that the nomograms can individually and accurately predict patient prognosis and risk stratification.\n\nData Availability Statement\n\nThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.\n\nEthics Statement\n\nThe studies involving human participants were reviewed and approved by the Ethics Committee of Tongji Medical College of Huazhong University. The patients/participants provided their written informed consent to participate in this study.\n\nAuthor Contributions\n\nQC collected, analyzed the data, and wrote the paper. LCa, YZ, and LCh researched the literature and revised the paper. CS and YH conceived and designed the study, analyzed the data, and wrote the paper. All authors reviewed the paper and approved the final manuscript.\n\nConflict of Interest\n\nThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\n\nThe authors would like to thank all the researchers and study participants for their contributions.\n\nSupplementary Material\n\nThe Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2021.639528/full#supplementary-material\n\nClick here for additional data file.\n\nFunding. This work was supported by grants from the National Natural Science Foundation of China (Nos. 81670197 and 81974007 for CS, No. 31620103909 for YH) and the Clinical Research Physician Program of Tongji Medical College, HUST (for CS).\n==== Refs\nReferences\n\n1. Siegel RL Miller KD Jemal A . Cancer statistics, 2020. CA Cancer J Clin. (2020) 70 :7–30. 10.3322/caac.21590 31912902\n2. Pulte D Jansen L Brenner H . Changes in long term survival after diagnosis with common hematologic malignancies in the early 21st century. Blood Cancer J. (2020) 10 :56. 10.1038/s41408-020-0323-4 32404891\n3. Lu J Lu J Chen W Huo Y Huang X Hou J . Clinical features and treatment outcome in newly diagnosed Chinese patients with multiple myeloma: results of a multicenter analysis. Blood Cancer J. (2014) 4 :e239. 10.1038/bcj.2014.55 25127393\n4. Liu J Liu W Mi L Zeng X Cai C Ma J . Incidence and mortality of multiple myeloma in China, 2006–2016: an analysis of the Global Burden of Disease Study 2016. J Hematol Oncol. (2019) 12 :136. 10.1186/s13045-019-0807-5 31823802\n5. Kim K Lee JH Kim JS Min CK Yoon SS Shimizu K . Clinical profiles of multiple myeloma in Asia-An Asian myeloma network study. Am J Hematol. (2014) 89 :751–6. 10.1002/ajh.23731 24723430\n6. Kumar SK Dispenzieri A Lacy MQ Gertz MA Buadi FK Pandey S . Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. (2014) 28 :1122–8. 10.1038/leu.2013.313 24157580\n7. Durie BG Salmon SE . A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. (1975) 36 :842–54.1182674\n8. Greipp PR San Miguel J Durie BGM Crowley JJ Barlogie B Bladé J . International staging system for multiple myeloma. J Clin Oncol. (2005) 23 :3412–20. 10.1200/JCO.2005.04.242 15809451\n9. Dispenzieri A Rajkumar SV Gertz MA Fonseca R Lacy MQ Bergsagel PL . Treatment of newly diagnosed multiple myeloma based on Mayo stratification of Myeloma and Risk-adapted Therapy (mSMART): consensus statement. Mayo Clin Pro. (2007) 82 :323–41. 10.1016/S0025-6196(11)61029-X 17352369\n10. Mikhael JR Dingli D Roy V Reeder CB Buadi FK Hayman SR . Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Pro. (2013) 88 :360–76. 10.1016/j.mayocp.2013.01.019 23541011\n11. mSMART, 3.0: Classification of Active MM. Available online at: www.msmart.org (accessed November 30, 2020).\n12. Sonneveld P Avet-Loiseau H Lonial S Usmani S Siegel D Anderson KC . Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the international myeloma working group. Blood. (2016) 127 :2955–62. 10.1182/blood-2016-01-631200 27002115\n13. Palumbo A Avet-Loiseau H Oliva S Lokhorst HM Goldschmidt H Rosinol L . Revised international staging system for multiple myeloma: a report from international myeloma working group. J Clin Oncol. (2015) 33 :2863–9. 10.1200/JCO.2015.61.2267 26240224\n14. Witzig TE Dhodapkar MV Kyle RA Greipp PR . Quantitation of circulating peripheral blood plasma cells and their relationship to disease activity in patients with multiple myeloma. Cancer. (1993) 72 :108–13.8508395\n15. Nowakowski GS Witzig TE Dingli D Tracz MJ Gertz MA Lacy MQ . Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. Blood. (2005) 106 :2276–9. 10.1182/blood-2005-05-1858 15961515\n16. Gonsalves WI Morice WG Rajkumar V Gupta V Timm MM Dispenzieri A . Quantification of clonal circulating plasma cells in relapsed multiple myeloma. Br J Haematol. (2014) 167 :500–5. 10.1111/bjh.13067 25113422\n17. Gonsalves WI Rajkumar SV Dispenzieri A Dingli D Timm MM Morice WG . Quantification of circulating clonal plasma cells via multiparametric flow cytometry identifies patients with smoldering multiple myeloma at high risk of progression. Leukemia. (2017) 31 :130–5. 10.1038/leu.2016.205 27457702\n18. Dingli D Nowakowski GS Dispenzieri A Lacy MQ Hayman SR Rajkumar SV . Flow cytometric detection of circulating myeloma cells before transplantation in patients with multiple myeloma: a simple risk stratification system. Blood. (2006) 107 :3384–8. 10.1182/blood-2005-08-3398 16339399\n19. Chakraborty R Muchtar E Kumar SK Jevremovic D Buadi FK Dingli D . Risk stratification in myeloma by detection of circulating plasma cells prior to autologous stem cell transplantation in the novel agent era. Blood Cancer J. (2016) 6 :e512. 10.1038/bcj.2016.117 27983726\n20. Iasonos A Schrag D Raj GV Panageas KS . How to build and interpret a nomogram for cancer prognosis. J Clin Oncol. (2008) 26 :1364–70. 10.1200/JCO.2007.12.9791 18323559\n21. Zhang B Tian J Dong D Gu D Dong Y Zhang L . Radiomics features of multiparametric mri as novel prognostic factors in advanced nasopharyngeal carcinoma. Clin Cancer Res. (2017) 23 :4259–69. 10.1158/1078-0432.CCR-16-2910 28280088\n22. Wang S Yang L Ci B Maclean M Gerber DE Xiao G . Development and validation of a nomogram prognostic model for SCLC patients. J Thorac Oncol. (2018) 13 :1338–48. 10.1016/j.jtho.2018.05.037 29902534\n23. Dong D Fang MJ Tang L Shan XH Gao JB Giganti F . Deep learning radiomic nomogram can predict the number of lymph node metastasis in locally advanced gastric cancer: an international multicenter study. Ann Oncol. (2020) 31 :912–20. 10.1016/j.annonc.2020.04.003 32304748\n24. Vienot A Beinse G Louvet C de Mestier L Meurisse A Fein F . Overall survival prediction and usefulness of second-line chemotherapy in advanced pancreatic adenocarcinoma. J Natl Cancer Inst. (2017) 109 :djx037. 10.1093/jnci/djx037 28383673\n25. Shouval R Labopin M Gorin NC Bomze D Houhou M Blaise D . Individualized prediction of leukemia-free survival after autologous stem cell transplantation in acute myeloid leukemia. Cancer. (2019) 125 :3566–73. 10.1002/cncr.32344 31225904\n26. Tian X-P Xie D Huang W-J Ma S-Y Wang L Liu Y-H . A gene-expression-based signature predicts survival in adults with T-cell lymphoblastic lymphoma: a multicenter study. Leukemia. (2020) 34 :2392–404. 10.1038/s41375-020-0757-5 32080345\n27. Gonsalves WI Rajkumar SV Gupta V Morice WG Timm MM Singh PP . Quantification of clonal circulating plasma cells in newly diagnosed multiple myeloma: implications for redefining high-risk myeloma. Leukemia. (2014) 28 :2060–5. 10.1038/leu.2014.98 24618735\n28. Foulk B Schaffer M Gross S Rao C Smirnov D Connelly MC . Enumeration and characterization of circulating multiple myeloma cells in patients with plasma cell disorders. Br J Haematol. (2018) 180 :71–81. 10.1111/bjh.15003 29105742\n29. Chakraborty R Muchtar E Kumar SK Jevremovic D Buadi FK Dingli D . Serial measurements of circulating plasma cells before and after induction therapy have an independent prognostic impact in patients with multiple myeloma undergoing upfront autologous transplantation. Haematologica. (2017) 102 :1439–45. 10.3324/haematol.2017.166629 28473618\n30. Rajkumar SV Dimopoulos MA Palumbo A Blade J Merlini G Mateos M-V . International Myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. (2014) 15 :e538–48. 10.1016/S1470-2045(14)70442-5 25439696\n31. Dimopoulos MA Delimpasi S Katodritou E Vassou A Kyrtsonis MC Repousis P . Significant improvement in the survival of patients with multiple myeloma presenting with severe renal impairment after the introduction of novel agents. Ann Oncol. (2014) 25 :195–200. 10.1093/annonc/mdt483 24356630\n32. Shouval R Teper O Fein JA Danylesko I Shem Tov N Yerushalmi R . LDH and renal function are prognostic factors for long-term outcomes of multiple myeloma patients undergoing allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. (2020) 55 :1736–43. 10.1038/s41409-020-0829-1 32066863\n33. Terpos E Katodritou E Roussou M Pouli A Michalis E Delimpasi S . High serum lactate dehydrogenase adds prognostic value to the international myeloma staging system even in the era of novel agents. Eur J Haematol. (2010) 85 :114–9. 10.1111/j.1600-0609.2010.01466.x 20477863\n34. Muccio VE Gilestro M Saraci E Capra A Costa A Ruggeri M . Tumor circulating plasma cells detected by flow cytometric single platform method correlate with clinical response to therapy and unfavorable patients' characteristics. Blood. (2019) 134 (Suppl. 1 ):4357. 10.1182/blood-2019-122657\n35. Abe Y Narita K Kobayashi H Kitadate A Miura D Takeuchi M . Pretreatment F-FDG PET/CT combined with quantification of clonal circulating plasma cells as a potential risk model in patients with newly diagnosed multiple myeloma. Eur J Nucl Med Mol Imaging. (2019) 46 :1325–3. 10.1007/s00259-019-4275-5 30687892\n36. Bae MH Park SH Park C-J Kim BH Cho Y-U Jang S . Increased circulating plasma cells predicts poor overall survival in symptomatic plasma cell Myeloma patients. Blood. (2015) 126 :4205. 10.1182/blood.V126.23.4205.4205\n37. Bertamini L Grasso M D'Agostino M Pascarella A Tosi P Monaco F . Poor prognosis of multiple myeloma predicted by high levels of circulating plasma cells is independent from other high-risk features but is modulated by the achievement of minimal residual disease negativity. Blood. (2020) 136 (Suppl. 1 ):12–3. 10.1182/blood-2020-137075\n38. Gonsalves WI Jevremovic D Nandakumar B Dispenzieri A Buadi FK Dingli D . Enhancing the R-ISS classification of newly diagnosed multiple myeloma by quantifying circulating clonal plasma cells. Am J Hematol. (2020) 95 :310–5. 10.1002/ajh.25709 31867775\n39. Vagnoni D Travaglini F Pezzoni V Ruggieri M Bigazzi C Dalsass A . Circulating plasma cells in newly diagnosed symptomatic multiple myeloma as a possible prognostic marker for patients with standard-risk cytogenetics. Br J Haematol. (2015) 170 :523–31. 10.1111/bjh.13484 26010293\n40. Abe Y Narita K Kobayashi H Kitadate A Takeuchi M Matsue K . Prognostic relevance of clonal circulating plasma cells detected by multiparameter flow cytometry in patients with newly diagnosed multiple myeloma treated with novel agents: comparative investigation with the revised international staging system. Blood. (2017) 130 (Suppl. 1 ):4354. 10.1182/blood.V130.Suppl_1.4354.4354\n41. Chen X Chen J Zhang W Sun R Liu T Zheng Y . Prognostic value of diametrically polarized tumor-associated macrophages in multiple myeloma. Oncotarget. (2017) 8 :112685–96. 10.18632/oncotarget.22340 29348856\n42. Zhang Y Chen X-L Chen W-M Zhou H-B . Prognostic nomogram for the overall survival of patients with newly diagnosed multiple myeloma. BioMed Res Int. (2019) 2019 :5652935. 10.1155/2019/5652935 31080823\n43. Lee B-H Park Y Kim JH Kang K-W Lee SJ Kim SJ . PD-L1 expression in bone marrow plasma cells as a biomarker to predict multiple myeloma prognosis: developing a nomogram-based prognostic model. Sci Rep. (2020) 10 :12641. 10.1038/s41598-020-69616-5 32724129\n\n", "fulltext_license": "CC BY", "issn_linking": "2234-943X", "issue": "11()", "journal": "Frontiers in oncology", "keywords": "biomarker; circulating plasma cells; newly diagnosed multiple myeloma; nomograms; prognosis", "medline_ta": "Front Oncol", "mesh_terms": null, "nlm_unique_id": "101568867", "other_id": null, "pages": "639528", "pmc": null, "pmid": "33747963", "pubdate": "2021", "publication_types": "D016428:Journal Article", "references": "31225904;23541011;25113422;20477863;27983726;32404891;1182674;8508395;24356630;15809451;32724129;15961515;24618735;16339399;25439696;32066863;30687892;31912902;29348856;26010293;25127393;31823802;32080345;32304748;29105742;27457702;24723430;28383673;17352369;18323559;28473618;24157580;27002115;29902534;28280088;31080823;31867775;26240224", "title": "Circulating Plasma Cells as a Biomarker to Predict Newly Diagnosed Multiple Myeloma Prognosis: Developing Nomogram Prognostic Models.", "title_normalized": "circulating plasma cells as a biomarker to predict newly diagnosed multiple myeloma prognosis developing nomogram prognostic models" }

[ { "companynumb": "CN-AMGEN-CHNSP2021134503", "fulfillexpeditecriteria": "2", "occurcountry": "CN", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "CARFILZOMIB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "202714", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN FORMULATION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARFILZOMIB" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "BORTEZOMIB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BORTEZOMIB." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "THALIDOMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THALIDOMIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LENALIDOMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LENALIDOMIDE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Therapy partial responder", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Death", "reactionmeddraversionpt": "24.0", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "CAI L.. CIRCULATING PLASMA CELLS AS A BIOMARKER TO PREDICT NEWLY DIAGNOSED MULTIPLE MYELOMA PROGNOSIS: DEVELOPING NOMOGRAM PROGNOSTIC MODELS. FRONTIERS IN ONCOLOGY. 2021?11:639528", "literaturereference_normalized": "circulating plasma cells as a biomarker to predict newly diagnosed multiple myeloma prognosis developing nomogram prognostic models", "qualification": "3", "reportercountry": "CN" }, "primarysourcecountry": "CN", "receiptdate": "20210906", "receivedate": "20210906", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19791454, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20211014" } ]

{ "abstract": "This double-blind, randomized crossover study assessed the effect of acetaminophen (1000 mg every 8 hours) versus indomethacin (50 mg every 8 hours) versus placebo on cyclooxygenase enzymes (COX-1 and COX-2). Urinary excretion of 2,3-dinor-6-keto-PGF1α, (prostacyclin metabolite, PGI-M; COX-2 inhibition) and 11-dehydro thromboxane B2 (thromboxane metabolite, Tx-M; COX-1 inhibition) were measured after 1 dose and 5 days of dosing. Peak inhibition of urinary metabolite excretion across 8 hours following dosing was the primary end point. Mean PGI-M excretion was 33.7%, 55.9%, and 64.6% on day 1 and 49.4%, 65.1%, and 80.3% on day 5 (placebo, acetaminophen, and indomethacin, respectively). Acetaminophen and indomethacin inhibited PGI-M excretion following single and multiple doses (P = .004 vs placebo). PGI-M excretion inhibition after 1 dose was similar for indomethacin and acetaminophen, but significantly greater with indomethacin after multiple doses (P = .006). Mean Tx-M excretion was 16.2%, 45.2%, and 86.6% on day 1 and 46.2%, 58.4%, and 92.6% on day 5 (placebo, acetaminophen, and indomethacin, respectively). Tx-M excretion inhibition following 1 dose was reduced by acetaminophen (P ≤ .003). Indomethacin reduced Tx-M excretion significantly more than acetaminophen and placebo after single and multiple doses (P ≤ .001). Acetaminophen and indomethacin inhibited COX-1 and COX-2 following a single dose, but acetaminophen was a less potent COX-1 inhibitor than indomethacin.", "affiliations": "Merck & Co., Inc., Whitehouse Station, NJ, USA.;Merck & Co., Inc., Whitehouse Station, NJ, USA.;Merck & Co., Inc., Whitehouse Station, NJ, USA.;Merck & Co., Inc., Whitehouse Station, NJ, USA.;Merck & Co., Inc., Whitehouse Station, NJ, USA.;Merck & Co., Inc., Whitehouse Station, NJ, USA.;Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA.", "authors": "Schwartz|Jules I|JI|;Musser|Bret J|BJ|;Tanaka|Wesley K|WK|;Taggart|William V|WV|;Mehta|Anish|A|;Gottesdiener|Keith M|KM|;Greenberg|Howard E|HE|", "chemical_list": "D015415:Biomarkers; D052246:Cyclooxygenase 2 Inhibitors; D000082:Acetaminophen; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; C049235:11-dehydro-thromboxane B2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D007213:Indomethacin", "country": "United States", "delete": false, "doi": "10.1002/cpdd.194", "fulltext": null, "fulltext_license": null, "issn_linking": "2160-763X", "issue": "4(5)", "journal": "Clinical pharmacology in drug development", "keywords": "acetaminophen; clinical trial; cyclooxygenase enzymes; indomethacin; urinary prostanoids", "medline_ta": "Clin Pharmacol Drug Dev", "mesh_terms": "D015121:6-Ketoprostaglandin F1 alpha; D000082:Acetaminophen; D000284:Administration, Oral; D000328:Adult; D015415:Biomarkers; D018592:Cross-Over Studies; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007213:Indomethacin; D008297:Male; D015143:Philadelphia; D011446:Prospective Studies; D065667:Renal Elimination; D013929:Thromboxane B2; D055815:Young Adult", "nlm_unique_id": "101572899", "other_id": null, "pages": "337-45", "pmc": null, "pmid": "27137142", "pubdate": "2015-09", "publication_types": "D003160:Comparative Study; D016428:Journal Article; D016449:Randomized Controlled Trial; D013485:Research Support, Non-U.S. Gov't", "references": null, "title": "Inhibition of prostacyclin and thromboxane biosynthesis in healthy volunteers by single and multiple doses of acetaminophen and indomethacin.", "title_normalized": "inhibition of prostacyclin and thromboxane biosynthesis in healthy volunteers by single and multiple doses of acetaminophen and indomethacin" }

[ { "companynumb": "US-JNJFOC-20151006456", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ACETAMINOPHEN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "019872", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CAPLET", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TYLENOL EXTRA STRENGTH" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ACETAMINOPHEN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "019872", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CAPLET", "drugdosagetext": "2 CAPLETS (1000 MG PARACETAMOL OR MATCHING PLACEBO) ON 8 AM, 4 PM, AND 12 AM.", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TYLENOL EXTRA STRENGTH" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INDOMETHACIN\\INDOMETHACIN SODIUM" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CAPSULE", "drugdosagetext": "1 CAPSULE (INDOMETHACIN OR MATCHING PLACEBO) EVERY 8 HOURS (8 AM, 4 PM, AND 12 AM.", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INDOCIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "UNSPECIFIED INGREDIENT" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNSPECIFIED", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PLACEBO" } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Blood creatinine increased", "reactionmeddraversionpt": "18.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MEHTA A, SCHWARTZ J, MUSSER BJ, TANAKA WK, TAGGART WV, GOTTESDIENER KM, ET AL. INHIBITION OF PROSTACYCLIN AND THROMBOXANE BIOSYNTHESIS IN HEALTHY VOLUNTEERS BY SINGLE AND MULTIPLE DOSES OF ACETAMINOPHEN AND INDOMETHACIN. CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT 2015?4(5) :337-345.", "literaturereference_normalized": "inhibition of prostacyclin and thromboxane biosynthesis in healthy volunteers by single and multiple doses of acetaminophen and indomethacin", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20151126", "receivedate": "20151126", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11780295, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20160305" } ]

{ "abstract": "Pityriasis rubra pilaris (PRP) is a group of uncommon chronic inflammatory skin conditions with unclear pathophysiology and etiology. To date there is limited published literature and no clinical guidelines for the management of PRP. Infliximab, alone or in combination, is the most widely published successful treatment for adults and etanercept for pediatric populations. We present a case series of patients diagnosed with PRP. Retrospective data were collected from a tertiary Australian dermatology department between January 2010 and December 2019 on patients with PRP. Electronic medical records and pathology database were searched. A total of 13 patients were included. Twelve of the 13 patients used topical agents and three patients attempted narrow-band ultraviolet B phototherapy. All patients received acitretin as first line systemic agent with the dose varying from 10 to 50 mg daily. Six patients treated with acitretin reported adverse events, requiring dose reduction or cessation. Of the nine patients who did not receive a biologic agent, complete clearance of PRP was achieved in five cases. At least one biologic agent was used in four cases with two experiencing a marked improvement. Overall, complete clearance was achieved in six patients. PRP continues to be a challenge to treat with many treatment options used with variable efficacy.", "affiliations": "Department of Dermatology, St Vincent's Hospital Melbourne, Fitzroy, Australia.;Department of Dermatology, St Vincent's Hospital Melbourne, Fitzroy, Australia.;Department of Dermatology, St Vincent's Hospital Melbourne, Fitzroy, Australia.;Department of Dermatology, St Vincent's Hospital Melbourne, Fitzroy, Australia.", "authors": "Ringin|Sarah|S|https://orcid.org/0000-0002-8100-1448;Baker|Christopher S|CS|;Foley|Peter|P|https://orcid.org/0000-0001-5891-5607;Daniel|Benjamin S|BS|https://orcid.org/0000-0002-2675-1115", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1111/dth.15128", "fulltext": null, "fulltext_license": null, "issn_linking": "1396-0296", "issue": "34(6)", "journal": "Dermatologic therapy", "keywords": "erythroderma; pharmacology; pityriasis rubra pilaris; therapy-biology; therapy-systemic", "medline_ta": "Dermatol Ther", "mesh_terms": null, "nlm_unique_id": "9700070", "other_id": null, "pages": "e15128", "pmc": null, "pmid": "34505752", "pubdate": "2021-11", "publication_types": "D016428:Journal Article", "references": null, "title": "Pityriasis rubra pilaris treatment options: A retrospective case series from a tertiary hospital.", "title_normalized": "pityriasis rubra pilaris treatment options a retrospective case series from a tertiary hospital" }

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Pityriasis rubra pilaris treatment options: A retrospective case series from a tertiary hospital. 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"drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLYCERIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SECUKINUMAB" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "300 MILLIGRAM, MONTHLY", "drugenddate": "2019", "drugenddateformat": "602", "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": "802", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "2018", "drugstartdateformat": "602", "drugstructuredosagenumb": "300", "drugstructuredosageunit": "003", "drugtreatmentduration": "4", "drugtreatmentdurationunit": "802", "medicinalproduct": "SECUKINUMAB" } ], "patientagegroup": null, "patientonsetage": "65", "patientonsetageunit": "801", "patientsex": "1", "patientweight": "88", "reaction": [ { "reactionmeddrapt": "Therapeutic product effect incomplete", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug ineffective for unapproved indication", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Ringin S, Baker CS, Foley P, Daniel BS. Pityriasis rubra pilaris treatment options: A retrospective case series from a tertiary hospital. Dermatol Ther. 2021;34 (6):e15128", "literaturereference_normalized": "pityriasis rubra pilaris treatment options a retrospective case series from a tertiary hospital", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20220407", "receivedate": "20220323", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 20626509, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220720" }, { "companynumb": "AU-LUPIN PHARMACEUTICALS INC.-2022-02288", "fulfillexpeditecriteria": "2", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "BETAMETHASONE DIPROPIONATE" }, "drugadditional": "4", "drugadministrationroute": "061", "drugauthorizationnumb": "209106", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Ointment", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BETAMETHASONE DIPROPIONATE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "MOMETASONE FUROATE" }, "drugadditional": "4", "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", 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null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MINERAL OIL" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, QD (2.5-25 MILLIGRAM)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE" } ], "patientagegroup": null, "patientonsetage": "70", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Ringin S, Baker CS, Foley P, Daniel BS. Pityriasis rubra pilaris treatment options: A retrospective case series from a tertiary hospital. Dermatologic Therapy. 2021;34(6):e15128:1-5", "literaturereference_normalized": "pityriasis rubra pilaris treatment options a retrospective case series from a tertiary hospital", "qualification": "1", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20220301", "receivedate": "20220301", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20530492, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220423" }, { "companynumb": "AU-LUPIN PHARMACEUTICALS INC.-2022-02253", "fulfillexpeditecriteria": "2", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "BETAMETHASONE" }, "drugadditional": "4", 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"drugtreatmentduration": "4", "drugtreatmentdurationunit": "802", "medicinalproduct": "METHOTREXATE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "MOMETASONE FUROATE" }, "drugadditional": "4", "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MOMETASONE FUROATE" } ], "patientagegroup": null, "patientonsetage": "64", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Ringin S, Baker CS, Foley P, Daniel BS. Pityriasis rubra pilaris treatment options: A retrospective case series from a tertiary hospital. Dermatologic Therapy. 2021;34(6):e15128:1-5", "literaturereference_normalized": "pityriasis rubra pilaris treatment options a retrospective case series from a tertiary hospital", "qualification": "1", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20220223", "receivedate": "20220223", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20508610, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220423" }, { "companynumb": "AU-LUPIN PHARMACEUTICALS INC.-2022-02296", "fulfillexpeditecriteria": "2", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "BETAMETHASONE DIPROPIONATE" }, "drugadditional": "4", "drugadministrationroute": "061", "drugauthorizationnumb": "209106", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Ointment", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BETAMETHASONE DIPROPIONATE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ACITRETIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, QD (25-37.5 MILLIGRAM)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACITRETIN" } ], "patientagegroup": null, "patientonsetage": "57", "patientonsetageunit": "801", "patientsex": "1", "patientweight": "80", "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Ringin S, Baker CS, Foley P, Daniel BS. Pityriasis rubra pilaris treatment options: A retrospective case series from a tertiary hospital. Dermatologic Therapy. 2021;34(6):e15128:1-5", "literaturereference_normalized": "pityriasis rubra pilaris treatment options a retrospective case series from a tertiary hospital", "qualification": "1", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20220228", "receivedate": "20220228", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20527100, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220423" }, { "companynumb": "AU-LUPIN PHARMACEUTICALS INC.-2022-02290", "fulfillexpeditecriteria": "2", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "BETAMETHASONE DIPROPIONATE" }, "drugadditional": "4", "drugadministrationroute": "061", "drugauthorizationnumb": "209106", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Ointment", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BETAMETHASONE DIPROPIONATE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "4", "drugadministrationroute": "061", "drugauthorizationnumb": "209097", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ACITRETIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACITRETIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "MOMETASONE FUROATE" }, "drugadditional": "4", "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK 0.1 PERCENT", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MOMETASONE FUROATE" } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "2", "patientweight": "66", "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Ringin S, Baker CS, Foley P, Daniel BS. Pityriasis rubra pilaris treatment options: A retrospective case series from a tertiary hospital. Dermatologic Therapy. 2021;34(6):e15128:1-5", "literaturereference_normalized": "pityriasis rubra pilaris treatment options a retrospective case series from a tertiary hospital", "qualification": "1", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20220301", "receivedate": "20220301", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20530595, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220423" }, { "companynumb": "AU-LUPIN PHARMACEUTICALS INC.-2022-02295", "fulfillexpeditecriteria": "2", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "BETAMETHASONE DIPROPIONATE" }, "drugadditional": "4", "drugadministrationroute": "061", "drugauthorizationnumb": "209106", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Ointment", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BETAMETHASONE DIPROPIONATE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ACITRETIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MG, QD", "drugenddate": "2016", "drugenddateformat": "602", "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "2016", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": "14", "drugtreatmentdurationunit": "804", "medicinalproduct": "ACITRETIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ACITRETIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG, QD", "drugenddate": "2016", "drugenddateformat": "602", "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "2016", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": "3", "drugtreatmentdurationunit": "802", "medicinalproduct": "ACITRETIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ACITRETIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG, QD RESTARTED WITH METHOTREXATE", "drugenddate": "2017", "drugenddateformat": "602", "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "2016", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACITRETIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MG PER WEEK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2016", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "INCREASED TO 25 MG/W, OVER 1 MONTH", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MG PER WEEK (THEN REDUCING TO 10 MG/W WITH ACETRETIN)", "drugenddate": "2017", "drugenddateformat": "602", "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "USTEKINUMAB" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "90 MG PER 12 WEEKLY", "drugenddate": "2018", "drugenddateformat": "602", "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2017", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": "18", "drugtreatmentdurationunit": "802", "medicinalproduct": "USTEKINUMAB" } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "1", "patientweight": "120", "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Ringin S, Baker CS, Foley P, Daniel BS. Pityriasis rubra pilaris treatment options: A retrospective case series from a tertiary hospital. Dermatologic Therapy. 2021;34(6):e15128:1-5", "literaturereference_normalized": "pityriasis rubra pilaris treatment options a retrospective case series from a tertiary hospital", "qualification": "1", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20220301", "receivedate": "20220301", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20531045, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220424" }, { "companynumb": "AU-LUPIN PHARMACEUTICALS INC.-2022-02292", "fulfillexpeditecriteria": "2", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "BETAMETHASONE DIPROPIONATE" }, "drugadditional": "4", "drugadministrationroute": "061", "drugauthorizationnumb": "209106", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Ointment", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BETAMETHASONE DIPROPIONATE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "HYDROCORTISONE" }, "drugadditional": "4", "drugadministrationroute": "061", "drugauthorizationnumb": "210209", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK APPLY ON THE FACE", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROCORTISONE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ACITRETIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, QD (10-35 MILLIGRAM)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACITRETIN" } ], "patientagegroup": null, "patientonsetage": "76", "patientonsetageunit": "801", "patientsex": "1", "patientweight": "76", "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Ringin S, Baker CS, Foley P, Daniel BS. Pityriasis rubra pilaris treatment options: A retrospective case series from a tertiary hospital. Dermatologic Therapy. 2021;34(6):e15128:1-5", "literaturereference_normalized": "pityriasis rubra pilaris treatment options a retrospective case series from a tertiary hospital", "qualification": "1", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20220301", "receivedate": "20220301", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20531011, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220423" }, { "companynumb": "AU-SUN PHARMACEUTICAL INDUSTRIES LTD-2022R1-328051", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "201749", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MILLIGRAM, WEEKLY", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "7", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MOMETASONE" }, "drugadditional": "3", "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.1%", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MOMETASONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ACITRETIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10-50 MG/DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACITRETIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BETAMETHASONE" }, "drugadditional": "3", "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.02%", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BETAMETHASONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.1%", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE" } ], "patientagegroup": null, "patientonsetage": "64", "patientonsetageunit": "801", "patientsex": "1", "patientweight": "74", "reaction": [ { "reactionmeddrapt": "Therapy partial responder", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Ringin S, Baker CS, Foley P, Daniel BS. Pityriasis rubra pilaris treatment options: A retrospective case series from a tertiary hospital. 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Pityriasis rubra pilaris treatment options: A retrospective case series from a tertiary hospital. Dermatologic Therapy. 2021;34(6):e15128:1-5", "literaturereference_normalized": "pityriasis rubra pilaris treatment options a retrospective case series from a tertiary hospital", "qualification": "1", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20220302", "receivedate": "20220302", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20539621, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220423" }, { "companynumb": "AU-LUPIN PHARMACEUTICALS INC.-2022-02289", "fulfillexpeditecriteria": "2", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "BETAMETHASONE DIPROPIONATE" }, "drugadditional": "4", "drugadministrationroute": "061", "drugauthorizationnumb": "209106", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Ointment", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BETAMETHASONE DIPROPIONATE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "SALICYLIC ACID" }, "drugadditional": "4", "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SALICYLIC ACID" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ACITRETIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, QD (25-35 MILLIGRAM)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pityriasis rubra pilaris", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACITRETIN" } ], "patientagegroup": null, "patientonsetage": "54", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Ringin S, Baker CS, Foley P, Daniel BS. Pityriasis rubra pilaris treatment options: A retrospective case series from a tertiary hospital. Dermatologic Therapy. 2021;34(6):e15128:1-5", "literaturereference_normalized": "pityriasis rubra pilaris treatment options a retrospective case series from a tertiary hospital", "qualification": "1", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20220301", "receivedate": "20220301", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20530571, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220423" } ]

{ "abstract": "Hypersensitivity syndrome is defined as a drug-induced complex of symptoms consisting of fever, rash, and internal organ involvement. The hypersensitivity syndrome is well recognized as being caused by anticonvulsants. Olanzapine is an atypical antipsychotic agent whose side effects include sedation, weight gain, and increased creatinine kinase and transaminase levels. To date, there have been no reports of hypersensitivity syndrome related to this drug. A 34-year-old man developed a severe generalized pruritic skin eruption, fever, eosinophilia, and toxic hepatitis 60 days after ingestion of olanzapine. After termination of olanzapine treatment, the fever resolved, the skin rash was reduced, eosinophil count was reduced to normal, and the transaminase levels were markedly reduced. Clinical features and the results of skin and liver biopsies indicated that the patient developed hypersensitivity syndrome caused by olanzapine.", "affiliations": "Department of Medicine E, Rambam Medical Center, Haifa, Israel.", "authors": "Raz|A|A|;Bergman|R|R|;Eilam|O|O|;Yungerman|T|T|;Hayek|T|T|", "chemical_list": "D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine", "country": "United States", "delete": false, "doi": "10.1097/00000441-200102000-00008", "fulltext": null, "fulltext_license": null, "issn_linking": "0002-9629", "issue": "321(2)", "journal": "The American journal of the medical sciences", "keywords": null, "medline_ta": "Am J Med Sci", "mesh_terms": "D000328:Adult; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D056486:Chemical and Drug Induced Liver Injury; D003951:Diagnostic Errors; D003875:Drug Eruptions; D004342:Drug Hypersensitivity; D004417:Dyspnea; D004802:Eosinophilia; D005334:Fever; D006801:Humans; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine; D011537:Pruritus; D012130:Respiratory Hypersensitivity; D012131:Respiratory Insufficiency; D012563:Schizophrenia, Paranoid; D013577:Syndrome", "nlm_unique_id": "0370506", "other_id": null, "pages": "156-8", "pmc": null, "pmid": "11217818", "pubdate": "2001-02", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "A case report of olanzapine-induced hypersensitivity syndrome.", "title_normalized": "a case report of olanzapine induced hypersensitivity syndrome" }

[ { "companynumb": "IL-MACLEODS PHARMACEUTICALS US LTD-MAC2022035638", "fulfillexpeditecriteria": "1", "occurcountry": "IL", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "OLANZAPINE" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": "202862", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "20 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Schizophrenia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OLANZAPINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Drug hypersensitivity", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CLONAZEPAM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLONAZEPAM" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hepatitis toxic", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Raz A, Eilam O, Hayek T, Bergman R, Yungerman T.. A case report of olanzapine-induced hypersensitivity syndrome. The American Journal of the Medical Sciences. 2001;321(2):156-8", "literaturereference_normalized": "a case report of olanzapine induced hypersensitivity syndrome", "qualification": "1", "reportercountry": "IL" }, "primarysourcecountry": "IL", "receiptdate": "20220521", "receivedate": "20220521", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20858163, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220721" } ]

{ "abstract": "BACKGROUND\nLamotrigine is an antiepileptic medication approved as a mood stabilizer for the prevention of depressive episodes in bipolar disorder. Among its adverse reactions, it may present maniac symptoms, despite being an idiosyncratic adverse effect and low incidence.\n\n\nMETHODS\nWe present the case of a 58-year-old patient, diagnosed with bipolar disorder since her youth and who has required multiple therapeutic schemes. After a pharmacological change from lithium to lamotrigine in progressive ascending doses, she presented a mania decompensation, temporally consistent with the initiation of lamotrigine, and that was accentuated with increasing dose. The symptoms disappear when lamotrigine is withdrawn and a pharmacological approach is carried out. When evaluating the case according to the causality criteria of Naranjo et al, we found a possible result.\n\n\nCONCLUSIONS\nAlthough lamotrigine-induced manifest symptoms have been previously documented, it is important to take this adverse effect into account, given the affective and behavioral repercussions. Further studies are needed to understand the bilateral relationship of this effect from a clinical and neurobiological point of view.", "affiliations": "Hospital Universitari Vall d'Hebron, 08035 Barcelona, España.;Hospital Universitari Vall d'Hebron, 08035 Barcelona, España.;Hospital Universitari Vall d'Hebron, 08035 Barcelona, España.;Hospital Universitari Vall d'Hebron, 08035 Barcelona, España.;Hospital Universitari Vall d'Hebron, 08035 Barcelona, España.", "authors": "Pereira-Pinto|A|A|;Palma-Álvarez|R F|RF|;Ortega-Hernández|G|G|;Grau-López|L|L|;Ramos-Quiroga|J A|JA|", "chemical_list": null, "country": "Spain", "delete": false, "doi": "10.33588/rn.7210.2021082", "fulltext": null, "fulltext_license": null, "issn_linking": "0210-0010", "issue": "72(10)", "journal": "Revista de neurologia", "keywords": null, "medline_ta": "Rev Neurol", "mesh_terms": null, "nlm_unique_id": "7706841", "other_id": null, "pages": "368-370", "pmc": null, "pmid": "33978231", "pubdate": "2021-05-16", "publication_types": "D002363:Case Reports; D004740:English Abstract", "references": null, "title": "Drug-induced mania and hypomania: analysis of a case of lamotrigine-induced mania.", "title_normalized": "drug induced mania and hypomania analysis of a case of lamotrigine induced mania" }

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"activesubstancename": "LEVOTHYROXINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "75 UG, 1D", "drugenddate": null, "drugenddateformat": null, "drugindication": "HYPOTHYROIDISM", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "004", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVOTHYROXINE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "020241", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG, 1D", "drugenddate": null, "drugenddateformat": null, "drugindication": "BIPOLAR DISORDER", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "020241", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MG, 1D", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LORAZEPAM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "3 MG, 1D", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LORAZEPAM." } ], "patientagegroup": null, "patientonsetage": "58", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Tremor", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Mania", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug intolerance", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypomania", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Psychomotor hyperactivity", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "PEREIRA?PINTO A, PALMA?ALVAREZ RF, ORTEGA?HERNANDEZ G, GRAU?LOPEZ L , RAMOS?QUIROGA J A. DRUG?INDUCED MANIA AND HYPOMANIA: ANALYSIS OF A CASE OF LAMOTRIGINE?INDUCED MANIA. REVISTA DE NEUROLOGIA. 2021?72 (10):368?370", "literaturereference_normalized": "drug induced mania and hypomania analysis of a case of lamotrigine induced mania", "qualification": "3", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20210617", "receivedate": "20210617", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19431836, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210717" } ]

{ "abstract": "Technological advances and increasing operator experience have improved the success rate of transvenous lead extraction (TLE). However, in some cases-especially with longer lead dwelling time-TLE can be highly complicated. In this case report, the authors present an unusual case of implantable cardioverter defibrillator (ICD) pocket infection diagnosed by 18F‑fluorodeoxyglucose positron emission tomography/computed tomography (18F‑FDG-PET/CT). Complete lead extraction required a combined transvenous and surgical approach. Contralateral reimplantation failed due to occlusion of the right brachiocephalic vein. Therefore, a subcutaneous ICD was implanted. This case highlights the importance of an interdisciplinary approach to the treatment of cardiac implantable electronic device infection.", "affiliations": "2nd Department of Medicine and Cardiology Center, University of Szeged, Szeged, Hungary.;2nd Department of Medicine and Cardiology Center, University of Szeged, Szeged, Hungary.;Department of Nuclear Medicine, University of Szeged, Szeged, Hungary.;2nd Department of Medicine and Cardiology Center, University of Szeged, Szeged, Hungary.;2nd Department of Medicine and Cardiology Center, University of Szeged, Szeged, Hungary.;2nd Department of Medicine and Cardiology Center, Electrophysiology Division, University of Szeged, Semmelweis u. 8., 6725, Szeged, Hungary. [email protected].", "authors": "Benak|Attila|A|;Kohari|Maria|M|;Besenyi|Zsuzsanna|Z|;Makai|Attila|A|;Saghy|Laszlo|L|;Vamos|Mate|M|", "chemical_list": null, "country": "Germany", "delete": false, "doi": "10.1007/s00399-020-00728-1", "fulltext": null, "fulltext_license": null, "issn_linking": "0938-7412", "issue": "32(1)", "journal": "Herzschrittmachertherapie & Elektrophysiologie", "keywords": "18F‑FDG PET/CT; Cardiac implantable electronic device infection; Implantable cardioverter defibrillator; Subcutaneous ICD; Transvenous lead extraction", "medline_ta": "Herzschrittmacherther Elektrophysiol", "mesh_terms": "D017147:Defibrillators, Implantable; D020878:Device Removal; D004581:Electronics; D006331:Heart Diseases; D006801:Humans; D000072078:Positron Emission Tomography Computed Tomography; D016896:Treatment Outcome", "nlm_unique_id": "9425873", "other_id": null, "pages": "124-127", "pmc": null, "pmid": "33095291", "pubdate": "2021-03", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": "32101604", "title": "Management of cardiac implantable electronic device infection using a complete interdisciplinary approach.", "title_normalized": "management of cardiac implantable electronic device infection using a complete interdisciplinary approach" }

[ { "companynumb": "HU-STRIDES ARCOLAB LIMITED-2021SP004304", "fulfillexpeditecriteria": "1", "occurcountry": "HU", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "VANCOMYCIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "65490", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "VASCULAR DEVICE INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VANCOMYCIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "VANCOMYCIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "65490", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "SPHINGOMONAS PAUCIMOBILIS INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VANCOMYCIN" } ], "patientagegroup": null, "patientonsetage": "69", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "BENAK A, KOHARI M, BESENYI Z, MAKAI A, SAGHY L,. MANAGEMENT OF CARDIAC IMPLANTABLE ELECTRONIC DEVICE INFECTION USING A COMPLETE INTERDISCIPLINARY APPROACH. HERZSCHRITTMACHERTHER?ELEKTROPHYSIOL. 2021?32(1):124?127", "literaturereference_normalized": "management of cardiac implantable electronic device infection using a complete interdisciplinary approach", "qualification": "3", "reportercountry": "HU" }, "primarysourcecountry": "HU", "receiptdate": "20210415", "receivedate": "20210415", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19143777, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210717" }, { "companynumb": "HU-TEVA-2021-HU-1904337", "fulfillexpeditecriteria": "1", "occurcountry": "HU", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "VANCOMYCIN" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "065510", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "MEDICAL DEVICE SITE INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VANCOMYCIN" } ], "patientagegroup": "6", "patientonsetage": "69", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "BENAK A, KOHARI M, BESENYI Z, MAKAI A, SAGHY L, VAMOS M. MANAGEMENT OF CARDIAC IMPLANTABLE ELECTRONIC DEVICE INFECTION USING A COMPLETE INTERDISCIPLINARY APPROACH. HERZSCHRITTMACHERTHER?ELEKTROPHYSIOL 2021?32(1):124?127.", "literaturereference_normalized": "management of cardiac implantable electronic device infection using a complete interdisciplinary approach", "qualification": "1", "reportercountry": "HU" }, "primarysourcecountry": "HU", "receiptdate": "20210422", "receivedate": "20210422", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19167911, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210717" } ]

{ "abstract": "Evidence to support available therapies for pyoderma gangrenosum (PG) is limited. Many patients do not respond to topical therapies such as tacrolimus or topical steroids. Currently favored oral systemic treatments (eg, cyclosporine and steroids) achieve complete remission in only 50% of patients and have unfavorable adverse effect profiles. There is a growing body of evidence to support biologic agents for the treatment of PG, but their exact role remains unclear. Here the authors present a patient with peristomal PG, the first reported case of PG responding to treatment with risankizumab, an anti-interleukin 23 monoclonal antibody. Risankizumab may represent an effective and relatively safe treatment for PG that merits additional exploration in prospective, controlled studies.", "affiliations": "In Miami, Florida, Maximillian A. Weigelt, MD, is Clinical Research Fellow, Dr Phillip Frost Department of Dermatology & Cutaneous Surgery University of Miami Miller School of Medicine; and Robert S. Kirsner, MD, PhD, is Chairman and Harvey Blank Professor, Dr Phillip Frost Department of Dermatology & Cutaneous Surgery, Professor of Public Health Sciences, University of Miami Miller School of Medicine, and Director, University of Miami Hospital and Clinics Wound Center. Acknowledgments: This manuscript describes off-label product use: risankizumab for pyoderma gangrenosum. The authors have disclosed no financial relationships related to this article. Submitted May 6, 2020; accepted in revised form June 19, 2020.", "authors": "Weigelt|Maximillian A|MA|;Kirsner|Robert S|RS|", "chemical_list": "D000911:Antibodies, Monoclonal; C000601773:risankizumab", "country": "United States", "delete": false, "doi": "10.1097/01.ASW.0000744324.59877.df", "fulltext": null, "fulltext_license": null, "issn_linking": "1527-7941", "issue": "34(6)", "journal": "Advances in skin & wound care", "keywords": null, "medline_ta": "Adv Skin Wound Care", "mesh_terms": "D000328:Adult; D000911:Antibodies, Monoclonal; D003424:Crohn Disease; D005260:Female; D006801:Humans; D011446:Prospective Studies; D017511:Pyoderma Gangrenosum; D054047:Surgical Stomas", "nlm_unique_id": "100911021", "other_id": null, "pages": "327-329", "pmc": null, "pmid": "33979822", "pubdate": "2021-06-01", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Peristomal Pyoderma Gangrenosum Responding to Risankizumab.", "title_normalized": "peristomal pyoderma gangrenosum responding to risankizumab" }

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{ "abstract": "To report a diagnostically challenging case of cranial neuropathy due to perineural invasion by a basal cell carcinoma presenting 7.5 years after treatment of the primary tumor with Mohs micrographic surgery.\nA 62-year-old male with a history of Mohs micrographic surgery for basal cell carcinoma (BCC) of the left brow presented with insidious onset of diplopia and paresthesia localizing to the ipsilateral cranial nerves V1, V2, and VI. He had no evidence of recurrent cutaneous BCC. Magnetic resonance imaging of the orbits and skull base identified equivocal, subtle abnormalities in the ipsilateral superior orbital fissure and cavernous sinus, with normal appearance of the clinically involved nerve branches. A radiographically normal branch of cranial nerve V was biopsied and histopathology identified perineural invasion by recurrent basal cell carcinoma.\nThe diagnosis of perineural invasion by BCC can pose several challenges, including subtle to absent imaging findings of clinically involved nerves and a lengthy latent period following primary tumor treatment. This case represents, to our knowledge, the longest reported interval between primary treatment and biopsy-proven recurrence with perineural invasion by BCC.", "affiliations": "Department of Ophthalmology, University of California, San Francisco, 10 Koret Way, San Francisco, CA, 94143, USA.;Department of Ophthalmology, University of California, San Francisco, 10 Koret Way, San Francisco, CA, 94143, USA.;Department of Ophthalmology, Palo Alto Medical Foundation, 795 El Camino Real, Palo Alto, CA, 94301, USA.;Department of Ophthalmology, University of California, San Francisco, 10 Koret Way, San Francisco, CA, 94143, USA.", "authors": "Ashraf|Davin C|DC|;Kalin-Hajdu|Evan|E|;Levin|Marc H|MH|;Kersten|Robert C|RC|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1016/j.ajoc.2018.12.018", "fulltext": "\n==== Front\nAm J Ophthalmol Case RepAm J Ophthalmol Case RepAmerican Journal of Ophthalmology Case Reports2451-9936Elsevier S2451-9936(18)30136-110.1016/j.ajoc.2018.12.018Case reportMixed cranial neuropathies due to occult perineural invasion of basal cell carcinoma Ashraf Davin C. [email protected]∗Kalin-Hajdu Evan aLevin Marc H. bKersten Robert C. aa Department of Ophthalmology, University of California, San Francisco, 10 Koret Way, San Francisco, CA, 94143, USAb Department of Ophthalmology, Palo Alto Medical Foundation, 795 El Camino Real, Palo Alto, CA, 94301, USA∗ Corresponding author. 10 Koret Way, San Francisco, CA, 94143, USA. [email protected] 12 2018 3 2019 19 12 2018 13 136 139 16 4 2018 30 11 2018 17 12 2018 Published by Elsevier Inc.2018This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Purpose\nTo report a diagnostically challenging case of cranial neuropathy due to perineural invasion by a basal cell carcinoma presenting 7.5 years after treatment of the primary tumor with Mohs micrographic surgery.\n\nObservations\nA 62-year-old male with a history of Mohs micrographic surgery for basal cell carcinoma (BCC) of the left brow presented with insidious onset of diplopia and paresthesia localizing to the ipsilateral cranial nerves V1, V2, and VI. He had no evidence of recurrent cutaneous BCC. Magnetic resonance imaging of the orbits and skull base identified equivocal, subtle abnormalities in the ipsilateral superior orbital fissure and cavernous sinus, with normal appearance of the clinically involved nerve branches. A radiographically normal branch of cranial nerve V was biopsied and histopathology identified perineural invasion by recurrent basal cell carcinoma.\n\nConclusions and importance\nThe diagnosis of perineural invasion by BCC can pose several challenges, including subtle to absent imaging findings of clinically involved nerves and a lengthy latent period following primary tumor treatment. This case represents, to our knowledge, the longest reported interval between primary treatment and biopsy-proven recurrence with perineural invasion by BCC.\n\nKeywords\nBasal cell carcinomaPerineural invasionCranial neuropathyBCCPerineural spread\n==== Body\n1 Introduction\nCutaneous malignancies have a well-reported propensity to invade the perineural sheath of adjacent nerve fibers.1, 2, 3, 4 Perineural invasion (PNI) allows the contiguous spread of malignant cells along the course of the involved nerve(s). When a large branch is affected, symptomatic neuropathy may develop. The timely diagnosis of cranial neuropathy due to PNI can prove challenging due to several factors. This report describes the diagnostic challenges encountered for a patient with a remote history of Mohs-excised basal cell carcinoma (BCC) who developed progressive cranial neuropathies due to PNI.\n\n2 Case report\nA 62-year-old male was referred for 18 months of left forehead numbness, 9 months of horizontal binocular diplopia, and 3 months of left cheek numbness. He had a history of Mohs micrographic surgery (MMS) 9 years prior for a left eyebrow BCC. Though he lacked clinical neuropathies at that time, the BCC was infiltrative, ulcerated, and demonstrated histologic PNI. Therefore, Mohs excision extended into the frontalis muscle to obtain 3-mm tumor-free margins. On examination in our office 9 years later, the patient demonstrated a left cranial nerve VI palsy and hypoesthesia along the left V1 and V2 dermatomes. There were no suspicious skin lesions or lymphadenopathy (Fig. 1).Fig. 1 Clinical color photograph.\n\nA color photograph of the patient's face obtained after he had received radiation therapy for his diagnosis of recurrent basal cell carcinoma with perineural invasion. There is esotropia and no sign of a cutaneous malignancy, representative of his pre-treatment appearance. Erythema of the left eyelid and atrophy of the left inferior eyelid fat pad are related to radiation therapy. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)\n\nFig. 1\n\nAn extensive workup had been performed over the preceding 12 months prior to referral. Cholesterol, blood pressure, blood glucose, complete blood count, acetylcholine receptor binding and blocking antibodies, erythrocyte sedimentation rate, and C-reactive protein were unremarkable. Serial MRIs over the preceding seven months identified progressive atrophy of the left lateral rectus muscle without abnormality specific to the ophthalmic (V1) or maxillary (V2) branches of the left trigeminal nerve. Review by multiple neuro-radiologists and clinicians suggested that the left superior orbital fissure and left lateral cavernous sinus had either normal appearance or subtle fullness, lacking a clear consensus (Fig. 2). Imaging also revealed chronic opacification of the left sphenoid sinus. Endonasal biopsies of the sphenoid sinus showed chronic fungal sinusitis without invasive disease or necrosis. Cerebrospinal fluid cytology and whole-body PET/CT were negative for malignancy.Fig. 2 Magnetic resonance imaging.\n\nA T1-weighted, post-gadolinium, axial magnetic resonance imaging section of the brain and orbit showing left lateral rectus atrophy (green arrow), left sphenoid sinus opacification (blue arrow), and equivocal fullness of the superior orbital fissure (white arrow). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)\n\nFig. 2\n\nPNI was suspected based on the patient's history of an ipsilateral BCC, and the patient underwent biopsy of the left supraorbital (V1) and infraorbital (V2) nerves via superior and inferior orbitotomies. Pathologic examination revealed normal infraorbital nerve tissue and PNI of the supraorbital nerve by an epithelial neoplasm with basaloid morphology (Fig. 3). Immunohistochemistry was consistent with BCC (pancytokeratin+, p63+, Ber-EP4+, EMA-). This pattern suggested retrograde spread of BCC along V1 into the cavernous sinus, followed by anterograde spread into cranial nerves V2 and VI, presumably with V2 involvement isolated to the region proximal of the negative biopsy site.Fig. 3 Histopathology.\n\n(A) A 10× magnification view of a pathologic tissue section from the supraorbital nerve biopsy, stained with hematoxylin and eosin. The section demonstrates a nest of invasive, epithelial cells with basaloid morphology including hyperchromatic nuclei without nucleoli and scant cytoplasm (arrow). There is adjacent S-100 positive neural tissue (+, stain not shown) residing within the perineurium (*), confirming tumor presence within the nerve.\n\n(B) A similar section stained with a cytokeratin cocktail to highlight the invasive cells. Further immunohistochemical testing (not shown) included p63 (positive), Ber-EP4 (positive), and EMA (negative), consistent with basal cell carcinoma.\n\nFig. 3\n\nThe patient was initiated on treatment for American Joint Committee on Cancer stage IV BCC, beginning with external beam radiation to the left orbit and cavernous sinus. He was placed on a continual course of vismodegib, a small molecule inhibitor of the hedgehog signaling pathway indicated for advanced basal cell carcinoma. After 6 months of treatment, he unfortunately required temporary cessation of his vismodegib due to adverse effects including weight loss, muscle spasm, loss of taste, and pruritic rash; however, at 10 months of follow-up, repeat magnetic resonance imaging showed no progressive disease. He recovered a small measure of abduction in the left eye, but ultimately required strabismus surgery to achieve orthotropia in primary gaze. His V2 paresthesia evolved into a persistent dysesthesia during treatment, while his V1 paresthesia remained static.\n\n3 Discussion\nThis report describes a challenging case of symptomatic PNI caused by a recurrent BCC lacking specific radiographic or cutaneous abnormalities. PNI by BCC is a rare entity, with histologic evidence present in only 0.18–3.8% of BCCs,5, 6, 7 compared with 3–14% of squamous cell carcinomas.2 The prevalence of histologic PNI is greater for aggressive BCC subtypes, including the infiltrative subtype found in our case.6,7 A large series found that 7.2% of aggressive BCCs had histologic PNI, whereas less aggressive BCCs had PNI in 0.6% of cases.7 It is worth noting that only 30–40% of cases with histologically-confirmed PNI (by SCC or BCC) develop symptomatic cranial neuropathy.1\n\nOur patient sequentially developed mixed cranial neuropathies, with V1, V2, and VI ultimately affected. Although the majority of patients with clinically-detectable PNI have only one cranial neuropathy, multiple nerves may become involved if the neoplasm spreads to a region of neural confluence,3,4 such as the cavernous sinus. Cranial nerve VII and V2 are most commonly affected due to their superficial branches in the mid-face, where most cutaneous malignancies occur, but involvement of every cranial nerve has been reported.3\n\nThis case demonstrates the high index of suspicion necessary to make a timely diagnosis of clinically significant PNI. Several factors can impede arrival at this diagnosis. First, symptoms insidiously develop over a median of six months prior to presentation.4 Second, while dermatologic examination is essential, a skin lesion is absent in nearly 25% of cases.4 Last, symptomatic PNI has been reported following seemingly clear-margin excision, fulguration or cryotherapy of presumed pre-malignant lesions, and uncommonly, in patients without a known history of a skin lesion.3,4 In cases of recurrent skin cancers, a median of 16 months (range 1–86) may separate primary carcinoma treatment and symptom onset.4 The latent period of 7.5 years (90 months) demonstrated in our case represents, to our knowledge, the longest reported interval between the diagnosis of primary BCC and biopsy-proven PNI by recurrent BCC, though for SCCs, the longest reported interval approaches two decades.1\n\nImaging studies are important for the diagnosis of clinically evident PNI, but must be ordered and interpreted with specific attention to the affected nerve(s). A propensity for subtle axial growth, rather than concentric growth, may cause PNI to be missed without careful review of imaging studies.1 Traditional, non-focused CT or MRI studies have sensitivity as low as 50% for symptomatic, histologically-proven PNI.8 Focused MRI should instead be pursued, involving thin slices along the course of the affected cranial nerve(s) with a sequence optimized for the suspected location of pathology. Neuro-radiologists possess several tools to enhance detection of PNI. MRI “neurography”, as originally described, is a protocol emphasizing ultra T2-weighted sequences with thin slices to offer excellent resolution of nerve tissue from cerebrospinal fluid. Notably, some authors and sites use the term more broadly to describe high resolution, focused cranial nerve MRI. Sommerville et al. described a sensitivity of 95–100% using this broader definition of neurography.9 Steady state precession sequences, more commonly known by trade names such as FIESTA (Fast Imaging Employing Steady-state Acquisition) or CISS (Constructive Interference Steady State), are another promising tool, though data is limited.10 These sequences derive signal intensity from the tissue ratio of T2 to T1 signal, again offering improved resolution between cerebrospinal fluid and nerve tissue.\n\nIn this case, neuro-radiology was most suspicious for pathology in the region of the superior orbital fissure, which involves discrimination of nerve from soft tissue. For this reason, they selected protocols emphasizing thinly-sliced T1-weighted sequences, rather than a steady state precession sequence or the ultra T2-weighted sequences of traditional neurography. Given the subtle radiologic signs of PNI, it is important for the clinician to communicate the expected etiology and locus of pathology to assist the neuro-radiologist in optimizing and focusing the protocol. The normal appearance of the histologically-involved V1 on high resolution, focused MRI in the present case is unusual. Subtle fullness of the superior orbital fissure and cavernous sinus was the only suggestive, albeit equivocal imaging finding. Biopsy of the clinically involved nerves should be pursued when PNI is suspected,11 even in the absence of a direct imaging correlate of the biopsy target.\n\nThe patient in this case had local histologic PNI associated with his primary BCC, and developed symptomatic PNI despite MMS with 3-mm tumor-free margins. There is no consensus on the appropriate management and surveillance of such high-risk patients with a primary cutaneous malignancy exhibiting histologic PNI. Measures including adjunctive radiotherapy, an additional stage of MMS, and surveillance imaging have been suggested, but data has been inconclusive.1,5,12 To reduce diagnostic delays, such patients should be counseled regarding symptoms of PNI, and practitioners should carry a high index of suspicion when encountering sequential development of cranial neuropathies or slowly progressive mononeuropathy during subsequent skin surveillance visits for years after treatment.\n\n4 Conclusion\nThis report demonstrates the multitude of challenges faced in establishing a diagnosis of PNI by BCC. Not only is the disease process rare, but negative imaging studies and late presentation after uncomplicated treatment of the primary lesion can provide false reassurance.\n\nPatient consent\nWritten informed consent for publication of this report and all included images was obtained from the patient, and a copy is available for review by the journal editor.\n\nFunding\nOpen access article funding will be pursued from the UCSF Library Open Access Fund if the manuscript is accepted. The UCSF Library played no role in the writing of this manuscript.\n\nConflicts of interest\nThe following authors have no financial disclosures: DCA, EKH, MHL, RCK.\n\nAuthorship\nAll authors attest that they meet the current ICMJE criteria for Authorship.\n\nDisclosures\nAll procedures performed in this study involving a human participant adhered to the 1964 Declaration of Helsinki and its later amendments. Collection of information in this report complied with the Health Insurance Portability and Accountability Act of 1996.\n\nAppendix A Supplementary data\nThe following are the Supplementary data to this article:Multimedia component 1\nMultimedia component 1 Multimedia component 2\nMultimedia component 2 \n\nAcknowledgements\nThe authors would like to thank Michele Bloomer, MD for providing histopathology images.\n\nAppendix A Supplementary data to this article can be found online at https://doi.org/10.1016/j.ajoc.2018.12.018.\n==== Refs\nReferences\n1 Brown T.J. Bogle M.A. Tschen J.A. Nelson B.R. Feasel A.M. Perineural invasion of cutaneous malignancies Dermatol Surg 27 6 2001 531 542 11442588 \n2 Leibovitch I. Huilgol S.C. Selva D. Cutaneous squamous cell carcinoma treated with Mohs micrographic surgery in Australia II. Perineural invasion J Am Acad Dermatol 53 2005 261 266 16021121 \n3 Amdur R.J. Williams L.S. Mancuso A.A. Stringer S.P. Mendenhall N.P. Mendenhall W.M. Carcinoma of the skin of the head and neck with perineural invasion Head Neck 24 1 2002 78 83 11774406 \n4 Warren T.A. Whiteman D.C. Prceddu S.V. Panizza B.J. Insight into the epidemiology of cutaneous squamous cell carcinoma with perineural spread Head Neck 38 9 2016 1416 1420 27043827 \n5 Ratner D. Lowe L. Johnson T.M. Fader D.J. Perineural spread of basal cell carcinomas treated with Mohs micrographic surgery Cancer 88 7 2000 1605 1613 10738219 \n6 Leibovitch I. Huilgol S.C. Selva D. Basal cell carcinoma treated with Mohs surgery in Australia III. Perineural invasion J Am Acad Dermatol 53 2005 458 463 16112353 \n7 Cho M. Lee J. James C.L. Marshman G. Huilgol S.C. Scalp basal cell carcinoma: review of 2,202 cases Dermatol Surg 42 7 2016 834 841 27243131 \n8 Mancusco A.A. Mendenhall W.M. Williams L.S. Perineural spread of cutaneous squamous and basal cell carcinoma: CT and MR detection and its impact on patient management and prognosis Int J Radiat Oncol Biol Phys 49 4 2001 1061 1069 11240248 \n9 Sommerville J. Gandhi M. The imaging of large nerve perineural spread J Neurol Surg B Skull Base 77 2 2016 113 123 27123387 \n10 Yagi A. Sato N. Takahashi A. Added value of contrast-enhanced CISS imaging in relation to conventional MR images for the evaluation of intracavernous cranial nerve lesions Neuroradiology 52 12 2010 1101 1109 20383633 \n11 Esmaeli B. Ahmadi M.A. Gillenwater A.M. Faustina M.M. Amato M. The role of supraorbital nerve biopsy in cutaneous malignancies of the periocular region Ophthalmic Plast Reconstr Surg 19 4 2003 282 286 12878876 \n12 Geist D.E. Garcia-Moliner M. Fitzek M.M. Cho H. Rogers G.S. Perineural invasion of cutaneous squamous cell carcinoma and basal cell carcinoma: raising awareness and optimizing management Dermatol Surg 34 12 2008 1642 1651 19018830\n\n", "fulltext_license": "CC BY", "issn_linking": "2451-9936", "issue": "13()", "journal": "American journal of ophthalmology case reports", "keywords": "BCC; Basal cell carcinoma; Cranial neuropathy; Perineural invasion; Perineural spread", "medline_ta": "Am J Ophthalmol Case Rep", "mesh_terms": null, "nlm_unique_id": "101679941", "other_id": null, "pages": "136-139", "pmc": null, "pmid": "30705997", "pubdate": "2019-03", "publication_types": "D002363:Case Reports", "references": "10738219;11240248;11442588;11774406;12878876;16021121;16112353;19018830;20383633;27043827;27123387;27243131", "title": "Mixed cranial neuropathies due to occult perineural invasion of basal cell carcinoma.", "title_normalized": "mixed cranial neuropathies due to occult perineural invasion of basal cell carcinoma" }

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{ "abstract": "OBJECTIVE\nSuccessful use of a 4-drug oral fixed-dose combination therapy to treat chronic hepatitis C in a patient receiving peritoneal dialysis (PD) is reported.\n\n\nCONCLUSIONS\nNew highly effective treatments for chronic hepatitis C virus (HCV) infection are now available, but safety and efficacy data on the use of anti-HCV therapies in patients with renal failure, particularly those requiring PD, remain limited. A 73-year-old black man with chronic HCV genotype 1a infection and stage 5 chronic renal disease requiring daily automated PD was referred for HCV treatment prior to renal transplantation. HCV treatment was initiated with paritaprevir-ritonavir-ombitasvir- dasabuvir, or \"PrOD\" (a combination tablet containing paritaprevir 75 mg, ritonavir 50 mg, and ombitasvir 12.5 mg to be taken once daily and a dasabuvir sodium 250-mg tablet to be taken twice daily), in conjunction with ribavirin 200 mg once daily. After a 12-week course of PrOD therapy, during which ribavirin therapy was tapered and then discontinued at week 10 and subcutaneous epoetin alfa was administered for anemia control from weeks 4 to 12, the patient's HCV viral load was undetectable; a sustained virologic response at 12 weeks (SVR12) was noted.\n\n\nCONCLUSIONS\nA patient with end-stage renal disease requiring PD was treated successfully for HCV genotype 1a infection with PrOD fixed-dose combination therapy plus ribavirin therapy. The patient achieved an SVR12 despite withdrawal of ribavirin at treatment week 10, with minimal adverse effects reported.", "affiliations": "Department of Pharmacy, Veterans Health Care System of the Ozarks, Fayetteville, AR. [email protected].;Department of Pharmacy, Veterans Health Care System of the Ozarks, Fayetteville, AR.", "authors": "Stark|Jennifer E|JE|;Cole|Jennifer|J|", "chemical_list": "D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D004338:Drug Combinations; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C586094:ombitasvir; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir", "country": "England", "delete": false, "doi": "10.2146/ajhp160729", "fulltext": null, "fulltext_license": null, "issn_linking": "1079-2082", "issue": "74(19)", "journal": "American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists", "keywords": "hepatitis C; kidney disease; peritoneal dialysis", "medline_ta": "Am J Health Syst Pharm", "mesh_terms": "D015081:2-Naphthylamine; D000368:Aged; D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D004338:Drug Combinations; D019698:Hepatitis C, Chronic; D006801:Humans; D007676:Kidney Failure, Chronic; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D008297:Male; D010530:Peritoneal Dialysis; D011392:Proline; D019438:Ritonavir; D013449:Sulfonamides; D016896:Treatment Outcome; D014498:Uracil; D014633:Valine", "nlm_unique_id": "9503023", "other_id": null, "pages": "1541-1544", "pmc": null, "pmid": "28947525", "pubdate": "2017-10-01", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Successful treatment of chronic hepatitis C virus infection in a patient receiving daily peritoneal dialysis.", "title_normalized": "successful treatment of chronic hepatitis c virus infection in a patient receiving daily peritoneal dialysis" }

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"drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALLOPURINOL." } ], "patientagegroup": null, "patientonsetage": "73", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Anaemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "STARK JE, COLE J. SUCCESSFUL TREATMENT OF CHRONIC HEPATITIS C VIRUS INFECTION IN A PATIENT RECEIVING DAILY PERITONEAL DIALYSIS. AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY. 2017;74(19):1541-4", "literaturereference_normalized": "successful treatment of chronic hepatitis c virus infection in a patient receiving daily peritoneal dialysis", "qualification": "2", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20171026", "receivedate": "20171026", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14127555, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" }, { "companynumb": "US-ALLERGAN-1756317US", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "URSODIOL" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "020675", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 DF, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHOLESTASIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "032", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "URSODEOXYCHOLIC ACID UNK" } ], "patientagegroup": null, "patientonsetage": "29", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Angioedema", "reactionmeddraversionpt": "20.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Erythema", "reactionmeddraversionpt": "20.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Atrial fibrillation", "reactionmeddraversionpt": "20.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "STARK JE, COLE J. SUCCESSFUL TREATMENT OF CHRONIC HEPATITIS C VIRUS INFECTION IN A PATIENT RECEIVING DAILY PERITONEAL DIALYSIS.. AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY. 2017;19:1541-1544", "literaturereference_normalized": "successful treatment of chronic hepatitis c virus infection in a patient receiving daily peritoneal dialysis", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20171017", "receivedate": "20171004", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14043691, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20180321" } ]

{ "abstract": "Terbinafine is a drug that can induce acute liver damage. We present the case of a 40-year-old male patient who developed liver dysfunction after 35 days of terbinafine treatment for onychomycosis. The anatomopathological study showed: acute hepatitis in resolution, in addition to ductopenia and cholestasis. These findings, without a history of viral or autoimmune hepatitis, are consistent with the diagnosis of drug-induced liver damage (DILI). In this report we present the first case in our country of a patient who is affected by an acute liver disease: terbinafine-induced liver injury, to which SARS-CoV-2 infection was later associated in the context of a pandemic.", "affiliations": "Servicio de Gastroenterología, Clínica Delgado. Lima, Perú.;Servicio de Anatomía Patológica, Laboratorio Patólogas AS. SAC. Lima, Perú.;Servicio de Anatomía Patológica, Laboratorio Patólogas AS. SAC. Lima, Perú.;Servicio de Gastroenterología, Clínica Delgado. Lima, Perú.", "authors": "Bustios Sanchez|Carla|C|;Sumire Umeres|Julia|J|;Asato Higa|Carmen|C|;Monge Zapata|Victor|V|", "chemical_list": "D000935:Antifungal Agents; D009281:Naphthalenes; D000077291:Terbinafine", "country": "Peru", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "1022-5129", "issue": "41(2)", "journal": "Revista de gastroenterologia del Peru : organo oficial de la Sociedad de Gastroenterologia del Peru", "keywords": null, "medline_ta": "Rev Gastroenterol Peru", "mesh_terms": "D000328:Adult; D000935:Antifungal Agents; D000086382:COVID-19; D056486:Chemical and Drug Induced Liver Injury; D019693:Hepatitis, Autoimmune; D006801:Humans; D008297:Male; D009281:Naphthalenes; D014009:Onychomycosis; D058873:Pandemics; D000086402:SARS-CoV-2; D000077291:Terbinafine", "nlm_unique_id": "9108294", "other_id": null, "pages": "107-111", "pmc": null, "pmid": "34724692", "pubdate": "2021", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Terbinafine-induced liver toxicity in the context of a SARS-CoV-2 pandemic: a case report.", "title_normalized": "terbinafine induced liver toxicity in the context of a sars cov 2 pandemic a case report" }

[ { "companynumb": "PE-GLAXOSMITHKLINE-PECH2021GSK081591", "fulfillexpeditecriteria": "1", "occurcountry": "PE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "TERBINAFINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "020749", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 MG, QD,35 DAYS CONSECUTIVELY", "drugenddate": null, "drugenddateformat": null, "drugindication": "Onychomycosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "202005", "drugstartdateformat": "610", "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TERBINAFINE" } ], "patientagegroup": null, "patientonsetage": "40", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug-induced liver injury", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hepatitis acute", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Vanishing bile duct syndrome", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cholestasis", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pruritus", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Jaundice", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Choluria", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hepatomegaly", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200601" } }, "primarysource": { "literaturereference": "Sanchez CGB, Umeres SJ, Higa CA, Zapata VM. Terbinafine-induced liver toxicity in the context of a SARS-CoV-2 pandemic: a case report. Revista de gastroenterologia del Peru : organo oficial de la Sociedad de Gastroe. 2021;41 (2):107-111", "literaturereference_normalized": "terbinafine induced liver toxicity in the context of a sars cov 2 pandemic a case report", "qualification": "3", "reportercountry": "PE" }, "primarysourcecountry": "PE", "receiptdate": "20211119", "receivedate": "20211119", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20090796, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "PE-NOVARTISPH-NVSC2021PE266812", "fulfillexpeditecriteria": "1", "occurcountry": "PE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "TERBINAFINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "20539", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 MG, QD, 35 DAYS CONSECUTIVELY", "drugenddate": null, "drugenddateformat": null, "drugindication": "Onychomycosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "202005", "drugstartdateformat": "610", "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TERBINAFINE" } ], "patientagegroup": null, "patientonsetage": "40", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug-induced liver injury", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hepatitis acute", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Vanishing bile duct syndrome", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cholestasis", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pruritus", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Jaundice", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Choluria", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hepatomegaly", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200601" } }, "primarysource": { "literaturereference": "Sanchez CGB, Umeres SJ, Higa CA, Zapata VM. Terbinafine-induced liver toxicity in the context of a SARS-CoV-2 pandemic: A case report. REVISTA DE GASTROENTEROLOGIA DEL PERU : ORGANO OFICIAL DE LA SOCIEDAD DE GASTROE. 2021;41(2):107-11", "literaturereference_normalized": "terbinafine induced liver toxicity in the context of a sars cov 2 pandemic a case report", "qualification": "3", "reportercountry": "PE" }, "primarysourcecountry": "PE", "receiptdate": "20211122", "receivedate": "20211122", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20097105, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" } ]

{ "abstract": "Nicolau syndrome is a skin and underlying tissue necrosis resulting from vascular occlusion after various injections of certain drugs. Intramuscular injections are the most common cause but it may occur after other types of parenteral interventions. There are many medications reported as causative factors inducing Nicolau syndrome including penicillin, nonsteroidal anti-inflammatory drugs, corticosteroids, local anesthetics, and several others. We present an observational study of diclofenac induced Nicolau syndrome.", "affiliations": "Faculty of Medicine, Department of Dermatology, Karabuk University, Karabuk, Turkey.;Department of Plastic and Reconstructive Surgery, Izmir Medicalpark Hospital, Izmir, Turkey.;Faculty of Medicine, Department of Plastic and Reconstructive Surgery, Karabuk University, Turkey.;Department of Dermatology, Private Yalova Hospital, Yalova, Turkey.", "authors": "Aktas|Habibullah|H|0000-0001-9239-1659;Yılmaz|Onur Evren|OE|;Ertugrul|Goksen|G|;Terzi|Erdinc|E|0000-0002-0956-1096", "chemical_list": "D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac", "country": "United States", "delete": false, "doi": "10.1111/dth.13392", "fulltext": null, "fulltext_license": null, "issn_linking": "1396-0296", "issue": "33(3)", "journal": "Dermatologic therapy", "keywords": "Nicolau syndrome; diclofenac", "medline_ta": "Dermatol Ther", "mesh_terms": "D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D065148:Nicolau Syndrome; D009765:Obesity", "nlm_unique_id": "9700070", "other_id": null, "pages": "e13392", "pmc": null, "pmid": "32268452", "pubdate": "2020-05", "publication_types": "D016428:Journal Article; D064888:Observational Study", "references": null, "title": "Intramuscular diclofenac is a cause of Nicolau syndrome in obese women: An observational study of consecutive ten patients.", "title_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients" }

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INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. 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INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. 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INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. 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INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. 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INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOL THER. 2020?33(3):E13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200722", "receivedate": "20200722", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 18056584, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "TR-GLAXOSMITHKLINE-TR2020GSK069495", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "022122", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "55", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fat necrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fibrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOLOGIC THERAPY. 2020?DOI: 10.1111/DTH.13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200427", "receivedate": "20200427", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 17712177, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" }, { "companynumb": "TR-SUN PHARMACEUTICAL INDUSTRIES LTD-2020RR-254622", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "075470", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC" } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOL THER. 2020?33(3):E13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200723", "receivedate": "20200723", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 18057747, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "TR-GLAXOSMITHKLINE-TR2020GSK070990", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "022122", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fat necrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fibrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOLOGIC THERAPY. 2020?DOI: 10.1111/DTH.13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200427", "receivedate": "20200427", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 17712527, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" }, { "companynumb": "TR-AMNEAL PHARMACEUTICALS-2020-AMRX-01238", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "208077", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, Y?LMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOL THER. 2020", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200504", "receivedate": "20200504", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17740857, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" }, { "companynumb": "TR-GLAXOSMITHKLINE-TR2020GSK070992", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "022122", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "53", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fat necrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fibrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOLOGIC THERAPY. 2020?DOI: 10.1111/DTH.13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200427", "receivedate": "20200427", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 17713058, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" }, { "companynumb": "NVSC2020TR203022", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "019201", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOLOGIC THERAPY. 2020?33(3):1?3", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200720", "receivedate": "20200720", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18044218, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "TR-GLAXOSMITHKLINE-TR2020GSK070988", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "022122", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fat necrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fibrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOLOGIC THERAPY. 2020?DOI: 10.1111/DTH.13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200427", "receivedate": "20200427", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 17712388, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" }, { "companynumb": "TR-SUN PHARMACEUTICAL INDUSTRIES LTD-2020RR-254623", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "075470", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC" } ], "patientagegroup": null, "patientonsetage": "65", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOL THER. 2020?33(3):E13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200722", "receivedate": "20200722", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 18056588, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "NVSC2020TR203025", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "019201", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK (SITE OF INJECTION LEFT GLUTEUS)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "64", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOLOGIC THERAPY. 2020?33(3):1?3", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200720", "receivedate": "20200720", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18045678, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "TR-ZYLA LIFE SCIENCES-TR-2020EGA000168", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "204592", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC" } ], "patientagegroup": null, "patientonsetage": "51", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E.. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. [TI] DERMATOL THER [INTERNET]. 2020", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "5", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200505", "receivedate": "20200505", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17746256, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200714" }, { "companynumb": "TR-ZYLA LIFE SCIENCES-TR-2020EGA000176", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "204592", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC" } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E.. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. [TI] DERMATOL THER [INTERNET].. 2020", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "5", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200505", "receivedate": "20200505", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17746266, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200714" }, { "companynumb": "TR-GLAXOSMITHKLINE-TR2020GSK070989", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "022122", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "65", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fat necrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fibrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOLOGIC THERAPY. 2020?DOI: 10.1111/DTH.13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200427", "receivedate": "20200427", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 17712526, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" }, { "companynumb": "TR-SUN PHARMACEUTICAL INDUSTRIES LTD-2020RR-254620", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "075470", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC" } ], "patientagegroup": null, "patientonsetage": "51", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOL THER. 2020?33(3):E13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200722", "receivedate": "20200722", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 18056586, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "TR-GLAXOSMITHKLINE-TR2020GSK070986", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "022122", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "51", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fat necrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fibrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOLOGIC THERAPY. 2020?DOI: 10.1111/DTH.13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200427", "receivedate": "20200427", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 17712219, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" }, { "companynumb": "TR-SUN PHARMACEUTICAL INDUSTRIES LTD-2020RR-254624", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "075470", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC" } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOL THER. 2020?33(3):E13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200722", "receivedate": "20200722", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 18056579, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "TR-ZYLA LIFE SCIENCES-TR-2020EGA000174", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "204592", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC" } ], "patientagegroup": null, "patientonsetage": "53", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E.. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. [TI] DERMATOL THER [INTERNET].. 2020", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "5", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200505", "receivedate": "20200505", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17746262, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200714" }, { "companynumb": "TR-SUN PHARMACEUTICAL INDUSTRIES LTD-2020RR-254627", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "075470", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC" } ], "patientagegroup": null, "patientonsetage": "64", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOL THER. 2020?33(3):E13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200723", "receivedate": "20200723", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 18057202, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "NVSC2020TR203019", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "019201", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "62", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOLOGIC THERAPY. 2020?33(3):1?3", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200720", "receivedate": "20200720", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18045052, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "TR-SUN PHARMACEUTICAL INDUSTRIES LTD-2020RR-254628", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "075470", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC" } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOL THER. 2020?33(3):E13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200722", "receivedate": "20200722", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 18056602, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "NVSC2020TR203020", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "019201", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOLOGIC THERAPY. 2020?33(3):1?3", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200720", "receivedate": "20200720", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18045670, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "TR-GLAXOSMITHKLINE-TR2020GSK070994", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "022122", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fat necrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fibrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOLOGIC THERAPY. 2020?DOI: 10.1111/DTH.13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200427", "receivedate": "20200427", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 17714805, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" }, { "companynumb": "TR-GLAXOSMITHKLINE-TR2020GSK070987", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "022122", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "62", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fibrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fat necrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. 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INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. [TI] DERMATOL THER [INTERNET].. 2020", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "5", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200505", "receivedate": "20200505", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17746255, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200714" }, { "companynumb": "TR-ZYLA LIFE SCIENCES-TR-2020EGA000175", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "204592", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC" } ], "patientagegroup": null, "patientonsetage": "64", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E.. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. [TI] DERMATOL THER [INTERNET].. 2020", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "5", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200505", "receivedate": "20200505", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17746265, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200714" }, { "companynumb": "TR-ZYLA LIFE SCIENCES-TR-2020EGA000172", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "204592", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC" } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E.. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. 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INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOLOGIC THERAPY. 2020?33(3):1?3", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200720", "receivedate": "20200720", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18046681, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "TR-SUN PHARMACEUTICAL INDUSTRIES LTD-2020RR-254621", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "075470", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC" } ], "patientagegroup": null, "patientonsetage": "62", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOL THER. 2020?33(3):E13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200722", "receivedate": "20200722", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 18056601, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "NVSC2020TR203026", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "019201", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK (INJECTION SITE WAS LEFT GLUTEUS)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "65", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. 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INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOL THER. 2020?33(3):E13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200722", "receivedate": "20200722", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 18056603, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "NVSC2020TR203015", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "019201", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "55", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOLOGIC THERAPY. 2020?33(3):1?3", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200720", "receivedate": "20200720", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18043663, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "TR-ZYLA LIFE SCIENCES-TR-2020EGA000170", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "204592", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC" } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E.. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. [TI] DERMATOL THER [INTERNET]. 2020", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "5", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200505", "receivedate": "20200505", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17746263, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200714" }, { "companynumb": "TR-GLAXOSMITHKLINE-TR2020GSK070993", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC SODIUM" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "022122", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC SODIUM." } ], "patientagegroup": null, "patientonsetage": "64", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fibrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fat necrosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOLOGIC THERAPY. 2020?DOI: 10.1111/DTH.13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200427", "receivedate": "20200427", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 17714803, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" }, { "companynumb": "TR-SUN PHARMACEUTICAL INDUSTRIES LTD-2020RR-254625", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DICLOFENAC" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": "075470", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DICLOFENAC" } ], "patientagegroup": null, "patientonsetage": "45", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Embolia cutis medicamentosa", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AKTAS H, YILMAZ OE, ERTUGRUL G, TERZI E. INTRAMUSCULAR DICLOFENAC IS A CAUSE OF NICOLAU SYNDROME IN OBESE WOMEN: AN OBSERVATIONAL STUDY OF CONSECUTIVE TEN PATIENTS. DERMATOL THER. 2020?33(3):E13392", "literaturereference_normalized": "intramuscular diclofenac is a cause of nicolau syndrome in obese women an observational study of consecutive ten patients", "qualification": "3", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200722", "receivedate": "20200722", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 18056583, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" } ]

{ "abstract": "OBJECTIVE\nA delayed-onset effect of clofarabine in the treatment of an adult patient with acute myeloid leukemia (AML) is reported.\n\n\nCONCLUSIONS\nA 44-year-old African-American man with pancytopenia was transferred to an academic medical center for evaluation. His medical history included bipolar depression, gynecomastia, and HIV infection (diagnosed 5 years prior) for which he was being treated with atazanavir, emtricitabine-tenofovir, and ritonavir. He was diagnosed with AML with 60% myeloblasts found during bone marrow biopsy. He had primary refractory disease after induction chemotherapy treatment. His disease was refractory to subsequent therapy with high-dose cytarabine and then etoposide and mitoxantrone. The patient then underwent treatment with granulocyte-colony stimulating factor-primed clofarabine and cytarabine (G-CLAC). At blood count recovery, he was diagnosed with refractory disease, with 17% blasts in peripheral blood and was subsequently discharged home on hospice 38 days after G-CLAC and 19 days after the last dose of filgrastim. He arrived at the outpatient clinic 79 days after G-CLAC chemotherapy with significantly improved blood counts. Two weeks later, a bone marrow biopsy confirmed complete remission with incomplete hematologic recovery.\n\n\nCONCLUSIONS\nA patient with relapsed AML achieved a delayed response to clofarabine at least 38 days after treatment.", "affiliations": "Department of Pharmacy, West Virginia University Medicine, Morgantown, WV.;Department of Pharmacy, West Virginia University Medicine, Morgantown, WV.;Department of Pathology, West Virginia University, Morgantown, WV.;Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University, Morgantown, WV.", "authors": "Walchack|Robert|R|;Cumpston|Aaron|A|;Vos|Jeffrey|J|;Kanate|Abraham S|AS|", "chemical_list": "D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D000077866:Clofarabine; D000069585:Filgrastim", "country": "England", "delete": false, "doi": "10.1093/ajhp/zxy055", "fulltext": null, "fulltext_license": null, "issn_linking": "1079-2082", "issue": "76(6)", "journal": "American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists", "keywords": " refractory disease; acute myeloid leukemia; clofarabine; delayed-onset; remission", "medline_ta": "Am J Health Syst Pharm", "mesh_terms": "D000328:Adult; D000964:Antimetabolites, Antineoplastic; D000971:Antineoplastic Combined Chemotherapy Protocols; D001706:Biopsy; D001772:Blood Cell Count; D001853:Bone Marrow; D000077866:Clofarabine; D003561:Cytarabine; D000069585:Filgrastim; D006801:Humans; D015470:Leukemia, Myeloid, Acute; D008297:Male; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome", "nlm_unique_id": "9503023", "other_id": null, "pages": "349-352", "pmc": null, "pmid": "31361841", "pubdate": "2019-02-21", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Delayed-onset effect of clofarabine in the treatment of an adult patient with acute myeloid leukemia.", "title_normalized": "delayed onset effect of clofarabine in the treatment of an adult patient with acute myeloid leukemia" }

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METER, QD (FOR 7 DAYS, 1 CYCLE)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE MYELOID LEUKAEMIA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYTARABINE." } ], "patientagegroup": "5", "patientonsetage": "44", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Acute myeloid leukaemia recurrent", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Death", "reactionmeddraversionpt": "22.0", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "VOS, JEFFREY. DELAYED-ONSET EFFECT OF CLOFARABINE IN THE TREATMENT OF AN ADULT PATIENT WITH ACUTE MYELOID LEUKEMIA. AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY. 2019?76(6):349-352", "literaturereference_normalized": "delayed onset effect of clofarabine in the treatment of an adult patient with acute myeloid leukemia", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20190812", "receivedate": "20190812", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16692952, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20191004" }, { "companynumb": "US-MYLANLABS-2020M1024057", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYTARABINE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "INDUCTION CHEMOTHERAPY WITH 1 CYCLE", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE MYELOID LEUKAEMIA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYTARABINE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "FILGRASTIM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "THE LAST DOSE OF FILGRASTIM WAS ADMINISTERED 20 DAYS...", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FILGRASTIM" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DECITABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PALLIATIVE THERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE MYELOID LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DECITABINE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "MITOXANTRONE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "10 MILLIGRAM/SQ. METER, QD, REINDUCTION CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE MYELOID LEUKAEMIA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MITOXANTRONE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYTARABINE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "REINDUCTION CHEMOTHERAPY CYTARABINE 2 G/M2", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYTARABINE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "RITONAVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "SHE HAD BEEN RECEIVING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY OF UNKNOWN DURATION...", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITONAVIR." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "100 MILLIGRAM/SQ. METER, QD, REINDUCTION CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE MYELOID LEUKAEMIA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYTARABINE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "1 CYCLE OF CONSOLIDATION CHEMOTHERAPY CYTARABINE 1 G/M2", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYTARABINE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ATAZANAVIR" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "SHE HAD BEEN RECEIVING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY OF UNKNOWN DURATION...", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATAZANAVIR." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CLOFARABINE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "REINDUCTION CHEMOTHERAPY WITH GRANULOCYTE-COLONY STIMULATING FACTOR-PRIMED CLOFARABINE", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE MYELOID LEUKAEMIA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "25", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLOFARABINE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "EMTRICITABINE\\TENOFOVIR DISOPROXIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "SHE HAD BEEN RECEIVING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY OF UNKNOWN DURATION...", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EMTRICITABINE W/TENOFOVIR" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYTARABINE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "CONSOLIDATION CHEMOTHERAPY WITH 2 CYCLES OF HIGH-DOSE CYTARABINE...", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYTARABINE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CLOFARABINE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "RECEIVED 1 CYCLE OF CONSOLIDATION CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLOFARABINE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "IDARUBICIN" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "200144", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "INDUCTION CHEMOTHERAPY WITH 1 CYCLE", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE MYELOID LEUKAEMIA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IDARUBICIN" } ], "patientagegroup": null, "patientonsetage": "44", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "WALCHACK R, CUMPSTON A, VOS J, KANATE AS. DELAYED-ONSET EFFECT OF CLOFARABINE IN THE TREATMENT OF AN ADULT PATIENT WITH ACUTE MYELOID LEUKEMIA. AM-J-HEALTH-SYST-PHARM 2019?76(6):349-352.", "literaturereference_normalized": "delayed onset effect of clofarabine in the treatment of an adult patient with acute myeloid leukemia", "qualification": "2", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20200304", "receivedate": "20200304", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17497983, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200409" } ]

{ "abstract": "To increase awareness of unusual inflammatory and other responses including severe insulin resistance (IR) associated with the use of targeted immunotherapies such as brentuximab.\nWe report the case of a man without any previous diagnosis of diabetes who developed diabetic ketoacidosis complicated by severe IR (unresponsive to >600 units of intravenous insulin per hour) after receiving brentuximab for Hodgkin lymphoma.\nAutoantibodies to the insulin receptor were not detected in the patient's serum, thus excluding a diagnosis of type B IR.\nWe hypothesize that brentuximab administration led to a rare reaction leading to systemic cytokine release with extreme IR in our patient.", "affiliations": null, "authors": "Chiang|Janet M|JM|;Lai|Andrew R|AR|;Anderson|Mark|M|;Rushakoff|Robert J|RJ|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.4158/ACCR-2019-0435", "fulltext": null, "fulltext_license": null, "issn_linking": "2376-0605", "issue": "6(2)", "journal": "AACE clinical case reports", "keywords": null, "medline_ta": "AACE Clin Case Rep", "mesh_terms": null, "nlm_unique_id": "101670593", "other_id": null, "pages": "e98-e100", "pmc": null, "pmid": "32524020", "pubdate": "2020", "publication_types": "D002363:Case Reports", "references": "27911591;24981690;10192335;15910639;22424602;17068147;22472351;10754341;24771533;24913471;14722622", "title": "SEVERE INSULIN RESISTANCE WITH DIABETIC KETOACIDOSIS AFTER BRENTUXIMAB TREATMENT.", "title_normalized": "severe insulin resistance with diabetic ketoacidosis after brentuximab treatment" }

[ { "companynumb": "US-SEATTLE GENETICS-2016SGN00668", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "BRENTUXIMAB VEDOTIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "125388", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "180 MG/24H, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HODGKIN^S DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20160415", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ADCETRIS" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINBLASTINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HODGKIN^S DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20160415", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINBLASTINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DACARBAZINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HODGKIN^S DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20160415", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DACARBAZINE." } ], "patientagegroup": null, "patientonsetage": "54", "patientonsetageunit": "801", "patientsex": "1", "patientweight": "110", "reaction": [ { "reactionmeddrapt": "Insulin resistance", "reactionmeddraversionpt": "23.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Pain", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Diabetic ketoacidosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cytokine storm", "reactionmeddraversionpt": "23.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Multiple organ dysfunction syndrome", "reactionmeddraversionpt": "23.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Fatigue", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperglycaemia", "reactionmeddraversionpt": "23.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Distributive shock", "reactionmeddraversionpt": "23.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Polyuria", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Polydipsia", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Myalgia", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20160415" } }, "primarysource": { "literaturereference": "CHIANG JM, LAI AR, ANDERSON M, RUSHAKOFF R. SEVERE INSULIN RESISTANCE WITH DIABETIC KETOACIDOSIS AFTER BRENTUXIMAB TREATMENT. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS. 2020?6 (NO.2):98-100", "literaturereference_normalized": "severe insulin resistance with diabetic ketoacidosis after brentuximab treatment", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20200624", "receivedate": "20160502", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12323575, "safetyreportversion": 6, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20200713" } ]

{ "abstract": "An allergic reaction was occurred in a 17-years old girl who was undergoing local anesthesia before tonsillectomy. Ptosis was observed in right side of patient shortly after injection of lidocaine to right palate. Then the patient feel grasp and cough, accompanied by nausea and vomiting. The patient was placed in supine position. Dexamethasone and epinephrine was administrated intramuscularly, symptoms were relieved 10 minutes later.", "affiliations": null, "authors": "Wang|Yao|Y|;Zhu|Yongwei|Y|;Zhou|Yan|Y|", "chemical_list": "D008012:Lidocaine", "country": "China", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "2096-7993", "issue": "28(11)", "journal": "Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery", "keywords": null, "medline_ta": "Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi", "mesh_terms": "D000293:Adolescent; D000772:Anesthesia, Local; D005143:Eyelids; D005260:Female; D006801:Humans; D008012:Lidocaine; D018908:Muscle Weakness", "nlm_unique_id": "101303164", "other_id": null, "pages": "829-30", "pmc": null, "pmid": "25219215", "pubdate": "2014-06", "publication_types": "D002363:Case Reports; D004740:English Abstract; D016428:Journal Article", "references": null, "title": "Levator muscle gravis following injection of lidocaine: a case report.", "title_normalized": "levator muscle gravis following injection of lidocaine a case report" }

[ { "companynumb": "CN-WATSON-2015-01440", "fulfillexpeditecriteria": "1", "occurcountry": "CN", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": null, "drugadministrationroute": "051", "drugauthorizationnumb": "080377", "drugbatchnumb": "UNCONFIRMED", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNK", "drugdosagetext": "1 ML, SINGLE(2% CONC)", "drugenddate": null, "drugenddateformat": null, "drugindication": "LOCAL ANAESTHESIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE (UNKNOWN)" } ], "patientagegroup": null, "patientonsetage": "17", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Type I hypersensitivity", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WANG Y, ZHU Y, ZHOU Y. [LEVATOR MUSCLE GRAVIS FOLLOWING INJECTION OF LIDOCAINE: A CASE REPORT]. LIN CHUNG ER BI YAN HOU TOU JING WAI KE ZA ZHI. 2014;28(11):829-30.CHINESE", "literaturereference_normalized": "levator muscle gravis following injection of lidocaine a case report", "qualification": "3", "reportercountry": "CN" }, "primarysourcecountry": "CN", "receiptdate": "20150219", "receivedate": "20150209", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10776268, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" } ]

{ "abstract": "BACKGROUND\nHigh-grade (HGG) and diffuse intrinsic pontine gliomas (DIPG) with primary metastatic spread are extremely rare and have a dismal prognosis. Analogous to simultaneous radiochemotherapy in non-metastatic HGG and DIPG, concurrent craniospinal irradiation (CSI) and metronomic temozolomide (metroTMZ) may represent a reasonable therapeutic approach. However, the antitumor efficacy and toxicity of this treatment still have to be investigated.\n\n\nMETHODS\nBetween March 2007 and December 2012, six children with primary metastatic HGG (n = 4) or DIPG (n = 2) received CSI and concurrent metroTMZ based on individual treatment recommendations and, in some cases, within the HIT-HGG 2007 multicenter trial. Outcome and treatment-related toxicities were evaluated.\n\n\nRESULTS\nAll patients received irradiation to the entire craniospinal axis (35.2 Gy, n = 5; 36 Gy, n = 1:) and 5 received a local boost to macroscopic tumor deposits. Simultaneously, metroTMZ (75 mg/m(2)/day, n = 5; 60 mg/m(2)/day, n = 1) was administered. Additionally, 1 patient received nimotuzumab once per week. Within a median follow-up of 10.0 months (range 6.5-18.7 months), all patients experienced disease progression and 5 patients died. Median progression-free survival was 4.0 ± 0.8 months (range 2.4-10.7 months) and median overall survival was 7.6 ± 3.5 months (range 4.0-17.6 months). Acute myelosuppression most severely limited application of this aggressive treatment strategy. Severe hematotoxicities (≥ grade 3) occurred in all patients and metroTMZ had to be interrupted or discontinued in 4 out of 6 cases.\n\n\nCONCLUSIONS\nConcurrent CSI and metroTMZ might represent a feasible treatment approach for primary metastatic HGG and DIPG. On the basis of our experience, severe but manageable acute hematotoxicity has to be expected. An international effort is warranted to reassess the efficacy and toxicity of this approach within a prospective study.", "affiliations": "Department of Radiation Oncology, University Medical Center Leipzig, Stephan-Str. 9a, 04103, Leipzig, Germany, [email protected].", "authors": "Müller|K|K|;Schlamann|A|A|;Guckenberger|M|M|;Warmuth-Metz|M|M|;Glück|A|A|;Pietschmann|S|S|;Wawer|A|A|;Kortmann|R-D|RD|;Kramm|C|C|;von Bueren|A O|AO|", "chemical_list": "D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide", "country": "Germany", "delete": false, "doi": "10.1007/s00066-013-0513-0", "fulltext": null, "fulltext_license": null, "issn_linking": "0179-7158", "issue": "190(4)", "journal": "Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]", "keywords": null, "medline_ta": "Strahlenther Onkol", "mesh_terms": "D000293:Adolescent; D018906:Antineoplastic Agents, Alkylating; D020295:Brain Stem Neoplasms; D059248:Chemoradiotherapy; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine; D005260:Female; D005910:Glioma; D006801:Humans; D008297:Male; D020266:Radiotherapy, Conformal; D015996:Survival Rate; D000077204:Temozolomide; D016896:Treatment Outcome", "nlm_unique_id": "8603469", "other_id": null, "pages": "377-81", "pmc": null, "pmid": "24638239", "pubdate": "2014-04", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": "22037651;16525181;18577561;21171927;23754473;23471572;7799011;21339192;15758009;17094400;2550594;16598416;15925999", "title": "Craniospinal irradiation with concurrent temozolomide for primary metastatic pediatric high-grade or diffuse intrinsic pontine gliomas. A first report from the GPOH-HIT-HGG Study Group.", "title_normalized": "craniospinal irradiation with concurrent temozolomide for primary metastatic pediatric high grade or diffuse intrinsic pontine gliomas a first report from the gpoh hit hgg study group" }

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CRANIOSPINAL IRRADIATION WITH CONCURRENT TEMOZOLOMIDE FOR PRIMARY METASTATIC PEDIATRIC HIGH-GRADE OR DIFFUSE INTRINSIC PONTINE GLIOMAS: A FIRST REPORT FROM THE GPOH-HIT-HGG STUDY GROUP. 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CRANIOSPINAL IRRADIATION WITH CONCURRENT TEMOZOLOMIDE FOR PRIMARY METASTATIC PEDIATRIC HIGH-GRADE OR DIFFUSE INTRINSIC PONTINE GLIOMAS: A FIRST REPORT FROM THE GPOH-HIT-HGG STUDY GROUP. 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CRANIOSPINAL IRRADIATION WITH CONCURRENT TEMOZOLOMIDE FOR PRIMARY METASTATIC PEDIATRIC HIGH-GRADE OR DIFFUSE INTRINSIC PONTINE GLIOMAS: A FIRST REPORT FROM THE GPOH-HIT-HGG STUDY GROUP. 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{ "abstract": "We report a novel phase 2 clinical trial in patients with poor prognosis refractory non-Hodgkin lymphoma (NHL) testing the efficacy of haploidentical donor natural killer (NK) cell therapy (NK dose 0.5-3.27 × 107 NK cells/kg) with rituximab and IL-2 (clinicaltrials.gov NCT01181258). Therapy was tolerated without graft-versus-host disease, cytokine release syndrome, or neurotoxicity. Of 14 evaluable patients, 4 had objective responses (29%; 95% CI 12-55%) at 2 months: 2 had complete response lasting 3 and 9 months. Circulating donor NK cells persisted for at least 7 days after infusion at the level 0.6-16 donor NK cells/µl or 0.35-90% of total CD56 cells. Responding patients had lower levels of circulating host-derived Tregs (17 ± 4 vs. 307 ± 152 cells/µL; p = 0.008) and myeloid-derived suppressor cells at baseline (6.6 ± 1.4% vs. 13.0 ± 2.7%; p = 0.06) than non-responding patients. Lower circulating Tregs correlated with low serum levels of IL-10 (R 2 = 0.64; p < 0.003; n = 11), suggestive of less immunosuppressive milieu. Low expression of PD-1 on recipient T cells before therapy was associated with response. Endogenous IL-15 levels were higher in responders than non-responding patients at the day of NK cell infusion (mean ± SEM: 30 ± 4; n = 4 vs. 19.0 ± 4.0 pg/ml; n = 8; p = 0.02) and correlated with day 14 NK cytotoxicity as measured by expression of CD107a (R 2 = 0.74; p = 0.0009; n = 12). In summary, our observations support development of donor NK cellular therapies for advanced NHL as a strategy to overcome chemoresistance. Therapeutic efficacy may be further improved through disruption of the immunosuppressive environment and infusion of exogenous IL-15.", "affiliations": "Blood and Marrow Transplant Program, University of Minnesota, MMC 480, 420 Delaware Street, Minneapolis, MN, 55455, USA. [email protected].;Blood and Marrow Transplant Program, University of Minnesota, MMC 480, 420 Delaware Street, Minneapolis, MN, 55455, USA.;Blood and Marrow Transplant Program, University of Minnesota, MMC 480, 420 Delaware Street, Minneapolis, MN, 55455, USA.;Blood and Marrow Transplant Program, University of Minnesota, MMC 480, 420 Delaware Street, Minneapolis, MN, 55455, USA.;Blood and Marrow Transplant Program, University of Minnesota, MMC 480, 420 Delaware Street, Minneapolis, MN, 55455, USA.;Blood and Marrow Transplant Program, University of Minnesota, MMC 480, 420 Delaware Street, Minneapolis, MN, 55455, USA.;Blood and Marrow Transplant Program, University of Minnesota, MMC 480, 420 Delaware Street, Minneapolis, MN, 55455, USA.;National Marrow Donor Program, Minnesota, MN, USA.;Blood and Marrow Transplant Program, University of Minnesota, MMC 480, 420 Delaware Street, Minneapolis, MN, 55455, USA.;Blood and Marrow Transplant Program, University of Minnesota, MMC 480, 420 Delaware Street, Minneapolis, MN, 55455, USA.", "authors": "Bachanova|Veronika|V|http://orcid.org/0000-0002-9325-432X;Sarhan|Dhifaf|D|;DeFor|Todd E|TE|;Cooley|Sarah|S|;Panoskaltsis-Mortari|Angela|A|;Blazar|Bruce R|BR|;Curtsinger|Julie M|JM|;Burns|Linda|L|;Weisdorf|Daniel J|DJ|;Miller|Jeffrey S|JS|", "chemical_list": "D014408:Biomarkers, Tumor; D007166:Immunosuppressive Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic; C534712:TIGIT protein, human", "country": "Germany", "delete": false, "doi": "10.1007/s00262-017-2100-1", "fulltext": null, "fulltext_license": null, "issn_linking": "0340-7004", "issue": "67(3)", "journal": "Cancer immunology, immunotherapy : CII", "keywords": "Adoptive transfer NK cells; Cellular therapy; Chemotherapy-refractory non-Hodgkin lymphoma; IL-2; Immunosuppressive environment", "medline_ta": "Cancer Immunol Immunother", "mesh_terms": "D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002648:Child; D046148:Donor Selection; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural; D008228:Lymphoma, Non-Hodgkin; D008297:Male; D008875:Middle Aged; D000072737:Myeloid-Derived Suppressor Cells; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor; D011446:Prospective Studies; D011971:Receptors, Immunologic; D012074:Remission Induction; D014184:Transplantation, Homologous; D055815:Young Adult", "nlm_unique_id": "8605732", "other_id": null, "pages": "483-494", "pmc": null, "pmid": "29218366", "pubdate": "2018-03", "publication_types": "D017427:Clinical Trial, Phase II; D016428:Journal Article; D016449:Randomized Controlled Trial", "references": "19109155;20680271;25651421;24652987;25113753;21199897;24618042;25700246;27643872;24719405;27503932;22323453;23152559;16010652;23775959;27338100;26171588;20460501;24816582;22900959;27192565;26432560;12379638;22226108;22714941;1421393;20085940;16737934;25154820;24907113;27132279;26883990;28295190", "title": "Haploidentical natural killer cells induce remissions in non-Hodgkin lymphoma patients with low levels of immune-suppressor cells.", "title_normalized": "haploidentical natural killer cells induce remissions in non hodgkin lymphoma patients with low levels of immune suppressor cells" }

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"drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IL-2" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, 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"reaction": [ { "reactionmeddrapt": "Sepsis", "reactionmeddraversionpt": "21.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Pneumocystis jirovecii pneumonia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Clostridium difficile colitis", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Tumour lysis syndrome", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Neutropenic sepsis", "reactionmeddraversionpt": "21.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Thrombotic microangiopathy", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Febrile neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": ", SARHAN D, DEFOR T, COOLEY S, PANOSKALTSIS-MORTARI A, BLAZAR B, CURTSINGER J, BURNS L, WEISDORF D AND MILLER J. HAPLOIDENTICAL NATURAL KILLER CELLS INDUCE REMISSIONS IN NON-HODGKIN LYMPHOMA PATIENTS WITH LOW LEVELS OF IMMUNE-SUPPRESSOR CELLS. CANCER IMMUNOLOGY IMMUNOTHERPY 2018?67(3):483-494.", "literaturereference_normalized": "haploidentical natural killer cells induce remissions in non hodgkin lymphoma patients with low levels of immune suppressor cells", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20180423", "receivedate": "20170222", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 13258466, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" } ]

{ "abstract": "Severe irinotecan-induced toxicity is associated with UGT1A1 polymorphisms. However, some patients develop side-effects despite harbouring a normal UGT1A1 genotype. As CYP3A4 is also an irinotecan-metabolizing enzyme, our study aimed to elucidate the influence of the CYP3A4*20 loss-of-function allele in the toxicity profile of these patients. Three-hundred and eight metastatic colorectal cancer patients treated with an irinotecan-containing chemotherapy were studied. The presence of CYP3A4*20, UGT1A1*37 and UGT1A1*28 alleles was tested. Associations between these genetic variants and toxicity were evaluated. UGT1A1*28 was significantly associated with severe diarrhoea, neutropenia and asthenia (P = 0.002, P = 0.037 and P = 0.041, respectively). One patient with the UGT1A1*28/*37 genotype presented with grade IV neutropenia and lethal septic shock. One heterozygous UGT1A1 (*1/*28) patient also carried the CYP3A4*20 allele but did not develop toxicity. We confirm that UGT1A1*37 and UGT1A1*28 are associated with severe toxicity and suggest that the CYP3A4*20 allele does not play a role in irinotecan-induced toxicity.", "affiliations": "Genetics Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.;Genetics Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.;Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.;Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.;Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.;Genetics Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.;Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.;Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.", "authors": "Riera|Pau|P|0000-0002-3074-3927;Salazar|Juliana|J|0000-0002-3581-4499;Virgili|Anna C|AC|;Tobeña|María|M|;Sebio|Ana|A|;Gallano|Pía|P|;Barnadas|Agustí|A|;Páez|David|D|", "chemical_list": "D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C418331:UGT1A1 enzyme; D014453:Glucuronosyltransferase", "country": "England", "delete": false, "doi": "10.1111/bcp.13574", "fulltext": null, "fulltext_license": null, "issn_linking": "0306-5251", "issue": "84(6)", "journal": "British journal of clinical pharmacology", "keywords": "CYP3A4*20; UGT1A1*28; UGT1A1*37; colorectal cancer; irinotecan; toxicity", "medline_ta": "Br J Clin Pharmacol", "mesh_terms": "D000368:Aged; D001247:Asthenia; D015179:Colorectal Neoplasms; D051544:Cytochrome P-450 CYP3A; D003967:Diarrhea; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase; D006579:Heterozygote; D006801:Humans; D000077146:Irinotecan; D008297:Male; D009503:Neutropenia; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D012307:Risk Factors; D012720:Severity of Illness Index; D059004:Topoisomerase I Inhibitors", "nlm_unique_id": "7503323", "other_id": null, "pages": "1389-1392", "pmc": null, "pmid": "29504153", "pubdate": "2018-06", "publication_types": "D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't", "references": "17992531;12610178;28711984;18797458;29149325;11141380;29055034;29504153;20068078;15297419;29054579;12118026;22722682;15523087;25348618;21654688;15007088;15280927", "title": "Relevance of CYP3A4*20, UGT1A1*37 and UGT1A1*28 variants in irinotecan-induced severe toxicity.", "title_normalized": "relevance of cyp3a4 20 ugt1a1 37 and ugt1a1 28 variants in irinotecan induced severe toxicity" }

[ { "companynumb": "ES-ACCORD-064777", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "IRINOTECAN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "079068", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "COLORECTAL CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "150", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IRINOTECAN" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenic colitis", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Septic shock", "reactionmeddraversionpt": "21.0", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "RIERA P, SALAZAR J, VIRGILI A, TOBENA M, SEBIO A, GALLANO P, ET AL. RELEVANCE OF CYP3A4*20, UGT1A1*37 AND UGT1A1*28 VARIANTS IN IRINOTECAN-INDUCED SEVERE TOXICITY. BR J CLIN PHARMACOL. 2018 MAR 5.", "literaturereference_normalized": "relevance of cyp3a4 20 ugt1a1 37 and ugt1a1 28 variants in irinotecan induced severe toxicity", "qualification": "2", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20180326", "receivedate": "20180326", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14678288, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20180509" }, { "companynumb": "ES-PFIZER INC-2018097506", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "IRINOTECAN HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "020571", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "150 MG/M2, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COLORECTAL CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "150", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IRINOTECAN HCL" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Febrile neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Neutropenic colitis", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "RIERA, P.. RELEVANCE OF CYP3A4*20, UGT1A1*37 AND UGT1A1*28 VARIANTS IN IRINOTECAN-INDUCED SEVERE TOXICITY. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY. 2018?84(6):1389-1392", "literaturereference_normalized": "relevance of cyp3a4 20 ugt1a1 37 and ugt1a1 28 variants in irinotecan induced severe toxicity", "qualification": "2", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20180614", "receivedate": "20180313", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14632235, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" } ]

{ "abstract": "Limited pharmacokinetic and safety data exist for MMF in pediatric HTR. Previously targeted MPA-TL are 1.5-3.0 μg/mL. The objective of this study was to assess the outcomes targeting MPA-TL of 0.8-2.0 μg/mL in pediatric HTR. MPA-TL were retrospectively collected 2-12 months post-transplant. Acute rejection, infection, leukopenia, and GI complaints were then correlated with MPA-TL. A total of 355 MPA-TL from 22 HTR were included. Median age was 2.5 yr. Primary indication for transplant was dilated cardiomyopathy (64%). Mean MPA-TL was 1.7 ± 0.9 μg/mL. African American patients received significantly higher doses (702 ± 235 mg/m(2) ) compared with other races (p = 0.035). Leukopenia was less common in patients with SUB MPA vs. others (p = 0.01). MMF was discontinued for GI complaints in one patient and leukopenia in two patients. One SUB patient had acute rejection, and one SUP patient had infection. One-yr survival was 100%. Targeting a lower range for MPA-TL was not associated with significant rejection or infection. Despite lower MPA-TL, MMF was discontinued in 3/22 patients for adverse effects.", "affiliations": "Department of Pharmacy, Children's Hospital at Montefiore, Bronx, NY, USA.;Cardiology Division, Department of Pediatrics, Children's Hospital at Montefiore, Bronx, NY, USA.;Cardiology Division, Department of Pediatrics, Children's Hospital at Montefiore, Bronx, NY, USA.", "authors": "Siddiqi|Nida|N|;Lamour|Jacqueline M|JM|;Hsu|Daphne T|DT|", "chemical_list": "D015415:Biomarkers; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid", "country": "Denmark", "delete": false, "doi": "10.1111/petr.12542", "fulltext": null, "fulltext_license": null, "issn_linking": "1397-3142", "issue": "19(6)", "journal": "Pediatric transplantation", "keywords": "cardiac transplantation; mycophenolate mofetil; pediatric heart transplant; therapeutic drug monitoring", "medline_ta": "Pediatr Transplant", "mesh_terms": "D000293:Adolescent; D015415:Biomarkers; D002311:Cardiomyopathy, Dilated; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006084:Graft Rejection; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents; D007223:Infant; D008297:Male; D009173:Mycophenolic Acid; D011183:Postoperative Complications; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult", "nlm_unique_id": "9802574", "other_id": null, "pages": "618-22", "pmc": null, "pmid": "26082342", "pubdate": "2015-09", "publication_types": "D023362:Evaluation Study; D016428:Journal Article", "references": null, "title": "The effect of MMF dose and trough levels on adverse effects in pediatric heart transplant recipients.", "title_normalized": "the effect of mmf dose and trough levels on adverse effects in pediatric heart transplant recipients" }

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THE EFFECT OF MMF DOSE AND TROUGH LEVELS ON ADVERSE EFFECTS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS. PEDIATR-TRANSPLANT 2015; 19(6):618-622.", "literaturereference_normalized": "the effect of mmf dose and trough levels on adverse effects in pediatric heart transplant recipients", "qualification": "2", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20150831", "receivedate": "20150831", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11437794, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20151125" }, { "companynumb": "US-STRIDES ARCOLAB LIMITED-2016SP013051", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "NYSTATIN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK (SOLUTION)", "drugenddate": null, "drugenddateformat": null, "drugindication": "INFECTION PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NYSTATIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CORTICOSTEROID NOS" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEART TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CORTICOSTEROIDS" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "90055", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEART TRANSPLANT", 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"drugtreatmentdurationunit": null, "medicinalproduct": "ANTITHYMOCYTE IMMUNOGLOBULIN (RABBIT)" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "INFECTION PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SULFAMETHOXAZOLE AND TRIMETHOPRIM" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Leukopenia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SIDDIQI N, LAMOUR JM, HSU DT. THE EFFECT OF MMF DOSE AND TROUGH LEVELS ON ADVERSE EFFECTS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS.. PEDIATR TRANSPLANT. 2015;19(6):618-22", "literaturereference_normalized": "the effect of mmf dose and trough levels on adverse effects in pediatric heart transplant recipients", "qualification": "2", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20170719", "receivedate": "20170719", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13768617, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20171127" }, { "companynumb": "US-STRIDES ARCOLAB LIMITED-2015SP001154", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "90055", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.5 MG/KG, 5 DOSES", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.5", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANTITHYMOCYTE IMMUNOGLOBULIN (RABBIT)" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "NYSTATIN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "ORAL SOLUTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "INFECTION PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, 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"drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SULFAMETHOXAZOLE AND TRIMETHOPRIM" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Gastrointestinal disorder", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "SIDDIQI N, LAMOUR JM, HSU DT. THE EFFECT OF MMF DOSE AND TROUGH LEVELS ON ADVERSE EFFECTS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS. 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LAMOUR, JM? HSU, DT.. THE EFFECT OF MMF DOSE AND TROUGH LEVELS ON ADVERSE EFFECTS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS.. PEDIATR-TRANSPLANT. 2015?19(6):618-622", "literaturereference_normalized": "the effect of mmf dose and trough levels on adverse effects in pediatric heart transplant recipients", "qualification": "2", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20160203", "receivedate": "20160203", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11995833, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20160526" } ]

{ "abstract": "We report the case of a patient who presented with a large pelvic mass, which was biopsy-proven to be Ewing sarcoma. The patient was also found to have 18 pulmonary lesions on a staging CT that were presumed to represent metastatic disease. After induction chemotherapy, a PET/CT scan revealed a marked reduction in his pelvic mass along with improvement in nearly all his pulmonary lesions except 2, which increased in size. The mixed response to chemotherapy was unusual and the decision was made to resect one of the growing lesions. Fungal culture from the excised lesion grew Coccidioides immitis.", "affiliations": "*Department of Pediatric Hematology Oncology, UCSF Benioff Children's Hospital †Department of Anatomic Pathology, Urology and Radiation Oncology, UCSF, San Francisco, CA.", "authors": "Stieglitz|Elliot|E|;Hsiang|Michelle S|MS|;Simko|Jeffry P|JP|;Hirose|Shinjiro|S|;Goldsby|Robert E|RE|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1097/MPH.0b013e318286d4fd", "fulltext": null, "fulltext_license": null, "issn_linking": "1077-4114", "issue": "36(1)", "journal": "Journal of pediatric hematology/oncology", "keywords": null, "medline_ta": "J Pediatr Hematol Oncol", "mesh_terms": "D000328:Adult; D001859:Bone Neoplasms; D003045:Coccidioides; D003047:Coccidioidomycosis; D003937:Diagnosis, Differential; D006801:Humans; D008175:Lung Neoplasms; D008297:Male; D011014:Pneumonia; D012512:Sarcoma, Ewing", "nlm_unique_id": "9505928", "other_id": null, "pages": "e57-60", "pmc": null, "pmid": "23588326", "pubdate": "2014-01", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Pulmonary coccidiomycosis masquerading as refractory metastatic Ewing sarcoma.", "title_normalized": "pulmonary coccidiomycosis masquerading as refractory metastatic ewing sarcoma" }

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{ "abstract": "Inadvertent dural puncture (IDP) is one of the complications of lumbar epidural steroid injections (ESIs). We report a case in which pneumocephalus and chemical meningitis developed at the same time after an IDP during a lumbar interlaminar ESI. A 60-year-old woman presented to the emergency room with thunderclap headache and febrile sensation 3 hours after receiving a lumbar interlaminar ESI. Brain computed tomography (CT) scan showed multiple small foci of air within the subarachnoid space and ventricle. After the admission, the patient was afebrile and reported mild improvement of headache with analgesics. However, 2 days after the admission, headache worsened and fever recurred. Follow-up brain CT scan revealed resolution of the pneumocephalus. A diagnostic lumbar puncture for cerebrospinal fluid (CSF) examination revealed the findings suggestive of aseptic (chemical) meningitis rather than bacterial meningitis. With symptomatic treatment, headache improved and there was no fever after 48 hours. No bacteria, Mycobacterium, or fungi grew in the CSF for 7 days. This case shows an IDP during a lumbar ESI can cause pneumocephalus and chemical meningitis at the same time and efforts should be made to reduce the risk of IDP during lumbar ESIs.", "affiliations": "Department of Neurosurgery, Dongguk University Ilsan Hospital, Goyang, Korea.;Department of Neurosurgery, Dongguk University Ilsan Hospital, Goyang, Korea.", "authors": "Koo|Jinhwan|J|https://orcid.org/0000-0003-1488-193X;Cho|Keun-Tae|KT|https://orcid.org/0000-0002-8372-7250", "chemical_list": null, "country": "Korea (South)", "delete": false, "doi": "10.13004/kjnt.2020.16.e8", "fulltext": "\n==== Front\nKorean J Neurotrauma\nKorean J Neurotrauma\nKJN\nKorean Journal of Neurotrauma\n2234-8999 2288-2243 Korean Neurotraumatology Society \n\n10.13004/kjnt.2020.16.e8\nCase Report\nPneumocephalus and Chemical Meningitis after Inadvertent Dural Puncture during Lumbar Epidural Injection\nhttps://orcid.org/0000-0003-1488-193XKoo Jinhwan https://orcid.org/0000-0002-8372-7250Cho Keun-Tae Department of Neurosurgery, Dongguk University Ilsan Hospital, Goyang, Korea.\nCorrespondence to Keun-Tae Cho. Department of Neurosurgery, Dongguk University Ilsan Hospital, 27 Dongguk-ro, Ilsandong-gu, Goyang 10326, Korea. [email protected]\n4 2020 \n10 4 2020 \n16 1 67 72\n29 2 2020 25 3 2020 27 3 2020 Copyright © 2020 Korean Neurotraumatology Society2020Korean Neurotraumatology SocietyThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Inadvertent dural puncture (IDP) is one of the complications of lumbar epidural steroid injections (ESIs). We report a case in which pneumocephalus and chemical meningitis developed at the same time after an IDP during a lumbar interlaminar ESI. A 60-year-old woman presented to the emergency room with thunderclap headache and febrile sensation 3 hours after receiving a lumbar interlaminar ESI. Brain computed tomography (CT) scan showed multiple small foci of air within the subarachnoid space and ventricle. After the admission, the patient was afebrile and reported mild improvement of headache with analgesics. However, 2 days after the admission, headache worsened and fever recurred. Follow-up brain CT scan revealed resolution of the pneumocephalus. A diagnostic lumbar puncture for cerebrospinal fluid (CSF) examination revealed the findings suggestive of aseptic (chemical) meningitis rather than bacterial meningitis. With symptomatic treatment, headache improved and there was no fever after 48 hours. No bacteria, Mycobacterium, or fungi grew in the CSF for 7 days. This case shows an IDP during a lumbar ESI can cause pneumocephalus and chemical meningitis at the same time and efforts should be made to reduce the risk of IDP during lumbar ESIs.\n\nPneumocephalusMeningitisDura materPuncturesInjections\n==== Body\nINTRODUCTION\nEpidural steroid injections (ESIs) have been used for the symptomatic relief of back pain with a radicular component in patients with herniated disk, foraminal stenosis, and central canal stenosis.213) ESIs are relatively safe, and serious complications are uncommon.21013) Inadvertent dural puncture (IDP) is one of the complications of ESIs and can cause postdural puncture headache (PDPH) or pneumocephalus.121317) Although extremely rare, meningitis is also one of the complications of ESIs.516) Although there were clinical studies and case reports that reported these two complications separately, there were only a few case reports in which both complications occurred at the same time after ESIs.516) We report a case in which pneumocephalus and chemical meningitis developed at the same time after an IDP during a lumbar interlaminar ESI.\n\nCASE REPORT\nA 60-year-old woman presented to the emergency room (ER) with thunderclap headache and febrile sensation 3 hours after receiving a lumbar interlaminar ESI with mepivacaine and dexamethasone at an outpatient pain clinic. The patient reported there was no abnormal symptoms except mild discomfort in the lower back during or immediately after the procedure. When leaving the clinic 30 minutes after the procedure, a mild headache began. Over time, the headache got worse, and a thunderclap headache with febrile sensation began. The headache was global, constant, and throbbing. Changes in the posture and position were not related to the intensity of the headache. On arrival at the ER, the patient's body temperature was 40.1°C, and blood pressure, pulse rate and respiration rate were normal. On examination, no neck stiffness and focal neurologic deficits were found. In the laboratory tests, white blood cell (WBC) count was 9400/uL (normal range: 4,000–10,000/uL) with 83.9% of neutrophils and C-reactive protein (CRP) was 0.11 (normal range: 0–0.5 mg/dL). Although postdural puncture headache (PDPH) was suspected, the patient underwent a non-contrast brain computed tomography (CT) scan to rule out other causes of thunderclap headache. Brain CT scan showed multiple small foci of air within the subarachnoid space and lateral ventricle (FIGURE 1). The patient had a fever on arrival at the ER. Therefore, we suspected a possibility of meningitis and recommended the patient a diagnostic lumbar puncture (LP) for cerebrospinal fluid (CSF) study at the ER. However, the patient refused the LP stubbornly because the patient still had the discomfort in the lower back due to the ESI and appealed fear of the LP. Therefore, while monitoring the body temperature, we decided to do the diagnostic LP when the fever recurred.\n\nFIGURE 1 Brain CT at the emergency room. (A) CT shows multifocal air density in the lateral ventricle and subarachnoid space (arrows). (B) CT shows multifocal air density in the basal cisterns (arrow).\nCT: computed tomography.\n\nThe patient admitted for the symptomatic treatment, monitoring vital signs, and serial neurologic examinations. The following day, the patient was afebrile and reported mild improvement of the headache with analgesics. However, the next day, the headache got worse and there was a fever accompanied by vomiting. In the blood tests, an increase in CRP from 0.11 to 3.72 mg/dL was found. Follow-up brain CT scan revealed resolution of the pneumocephalus (FIGURE 2). A diagnostic LP for CSF study was performed to rule out meningitis. Opening pressure was 26 cmH2O and CSF examination showed WBC 300/mm3 with 59.5% neutrophils, 18% lymphocyte, 22% monocyte, protein 62.1 mg/dL, and glucose 49.1 mg/dL with serum glucose 119 mg/dL. Gram's staining of the CSF showed no organisms. Under the diagnosis of chemical meningitis rather than bacterial meningitis, antibiotic treatment was withheld until the CSF culture results were confirmed. With symptomatic treatment with hydration and analgesics, the headache improved and there was no fever after 48 hours. The patient remained afebrile for the next 5 days and was discharged without headache and fever. No bacteria, Mycobacterium, or fungi grew in the CSF for 7 days.\n\nFIGURE 2 Brain CT (2 days later) shows resolution of pneumocephalus.\nCT: computed tomography.\n\nDISCUSSION\nIDP is one of the complications of epidural anesthesia and ESIs.1231317) Choi et al.3) reported that the incidence of IPD during obstetrical epidural anesthesia was 1.5% in their meta-analysis. Aida et al.1) reported that the incidence of IDP during interlaminar ESI was 2.7% of 3730 patients in the retrospective study. Manchikanti et al.10) reported that the incidence of IDP was 0.8% in a prospective evaluation of 1,450 fluoroscopically directed lumbar interlaminar ESIs.\n\nIDP can cause PDPH.314) PDPH is typically secondary to a CSF leak after an IDP, but can be associated with pneumocephalus after an IDP in rare cases.14) Two main mechanisms have been postulated for the development of pneumocephalus in relation to lumbar anesthesias.714) The ball-valve theory is air movement in one direction from outside into the cranial cavity, which then creates an air trap.714) In the other mechanism, the inverted soda bottle theory, excessive CSF loss leads to a negative intracranial pressure gradient that may be relieved by the influx of air.714) In the present case, the air might have been injected into the subarachnoid space when an unrecognized IDP occurred during the interlaminar ESI.\n\nHeadaches associated with pneumocephalus usually have a rapid onset, are severe, and may not be relieved with recumbency or supine position.14) On the other hand, headache associated with persistent CSF leakage usually has a later onset, and is relieved when the patient lies down, but is provoked or worsens with sitting or standing.14) In the present case, the patient's headache on arrival at the ER might be due to the pneumocephalus, because the headache was a rapid onset, severe, and not relieved when the patient was lying down. It was possible that headache got worse to thunderclap headache as the air in the spinal subarachnoid space moved to cephalad during standing or sitting while returning to home after the procedure.6)\n\nLoss of resistance to air (LORA) technique and loss of resistance to saline (LORS) technique are used for the identification of the epidural space during ESIs or epidural anesthesias.1415) Some authors reported a higher frequency of IDP when using the LORA technique to identify the epidural space, while others report no difference in the frequency of IDP between the 2 techniques.1415) However, even if there is no difference in the frequency of IDP between the two techniques, when an IDP occurs during EISs or epidural anesthesia, the incidence of pneumocephalus and resultant headache is higher when using the LORA technique.115) In the present case, the LORA technique was used for the interlaminar lumbar ESI.\n\nWhen an IDP occurs during ESIs or epidural anesthesias using LORA technique, air can enter the subarachnoid space or subdural space, resulting in pneumocephauls.117) The intracranial air bubbles can behave like a space-occupying lesion, causing meningeal irritation and resultant headache.12) In 2014, Verdun et al.17) reviewed the literature on pneumocephalus after ESIs published from 1919 to 2013. In their review, onset of pneumocephalus-related headache could begin from immediately following the procedure and symptom resolution was variable from 1 to 3 hours to 7 days.17) Time to radiological resolution of pneumocephalus was also variable from 1 day to 2 weeks.17) In the present case, pneumocephalus disappeared within 2 days based on the brain CT findings.\n\nWhen an unrecognized IDP during ESIs or epidural anesthesia, not only air, but drugs can also enter the subdural or subarachnoid space.516) It is a commonly held belief that the instillation of any substance into the CSF may result in chemical irritation and meningitis.11) Steroid or local anesthetic agents such as bupivacaine, lidocaine, or mepivacaine can cause chemical meningitis when entering the thecal sac.5816) Although there were many reports of chemical meningitis due to local anesthetics after spinal anesthesia or due to steroid after intrathecal steroid injections, reported cases of chemical meningitis after lumbar ESIs are extremely rare.516) In addition, reported cases in which chemical meningitis and pneumocepahus occurred at the same time after lumbar ESIs were even rarer.516) Gutknecht5) reported a case of chemical meningitis in which symptoms of meningitis developed 4 hours after the epidural injection of methylprednisolone for the treatment of lumbar radiculopathy. In this case, brain CT scan showed air droplets in the subarachnoid space and probable dural puncture was noted during the injection in the author's opinion.5) Shah et al.16) reported a case of pneumocephalus and chemical meningitis in which symptoms of meningitis developed 1.5 hours after the epidural injection of lidocaine, methylprednisolone and betamethasone. In the present case, mixed solution with dexamethasone and mepivacaine was used for the interlaminar ESI. It is unclear, however, which component of the injected solution induced the chemical meningitis.\n\nIn the present case, the patient had a fever. It is not known whether or not there was chemical meningitis on arrival at the ER because the diagnostic LP for CSF study was not performed at the ER. In addition, intraventricular air itself has been reported to cause fever.9) It was suggested that the hypothalamic temperature regulating center is stimulated by intraventricular air.9) It is also possible that irritation of either the ependyma or the meninges may be responsible for the fever.9) Therefore, it is unclear whether the cause of fever on arrival at the ER was due to chemical meningitis, pneumocephalus, or both. The worsening headache and recurred fever 2 days after the admission might be due to chemical meningitis because the headache and fever developed even after air was lost on the brain CT scan.\n\nIn the present case, pneumocephalus and chemical meningitis were most likely caused by an IDP during an interlaminar ESI. The risk of IDP can be reduced by the use of a blunt needle, the use of the LORS technique rather than the LORA technique, and accurate placement of the needle on live fluoroscopy.1317) Some authors recommend, in case of significant central canal stenosis from a disk herniation, bilateral transforaminal ESIs rather than interlaminar ESIs or positioning the needle 1 interspace cephalad to reduce the risk of IDP in the narrowed epidural space.17)\n\nCONCLUSION\nPneumocephalus and chemical meningitis can occur at the same time after an IDP during ESIs. Best efforts should be made to reduce the risk of IDP during ESIs. This can prevent pneumocephalus or meningitis as well as more serious complications such as paresis, cardiopulmonary arrest, or respiratory depression.\n\nConflict of Interest: The authors have no financial conflicts of interest.\n==== Refs\n1 Aida S Taga K Yamakura T Endoh H Shimoji K Headache after attempted epidural block: the role of intrathecal air Anesthesiology 88 76 81 1998 9447859 \n2 Benyamin RM Manchikanti L Parr AT Diwan S Singh V Falco FJ The effectiveness of lumbar interlaminar epidural injections in managing chronic low back and lower extremity pain Pain Physician 15 E363 E404 2012 22828691 \n3 Choi PT Galinski SE Takeuchi L Lucas S Tamayo C Jadad AR PDPH is a common complication of neuraxial blockade in parturients: a meta-analysis of obstetrical studies Can J Anaesth 50 460 469 2003 12734154 \n4 Evron S Sessler D Sadan O Boaz M Glezerman M Ezri T Identification of the epidural space: loss of resistance with air, lidocaine, or the combination of air and lidocaine Anesth Analg 99 245 250 2004 15281538 \n5 Gutknecht DR Chemical meningitis following epidural injections of corticosteroids Am J Med 82 570 1987 \n6 Kozikowski GP Cohen SP Lumbar puncture associated with pneumocephalus: report of a case Anesth Analg 98 524 526 2004 14742399 \n7 Kwon J Rha HK Park HK Chough CK Joo WI Cho SH Proper management of posttraumatic tension pneumocephalus Korean J Neurotrauma 13 158 161 2017 29201853 \n8 Lee SH Lee MJ Kim WJ Chemical meningitis after spinal or epidural anesthesia J Neurocrit Care 7 40 43 2014 \n9 Lipton MJ Crowther D Fever after air encephalography Br J Radiol 41 672 673 1968 5302838 \n10 Manchikanti L Malla Y Wargo BW Cash KA Pampati V Fellows B A prospective evaluation of complications of 10,000 fluoroscopically directed epidural injections Pain Physician 15 131 140 2012 22430650 \n11 Marinac JS Drug- and chemical-induced aseptic meningitis: a review of the literature Ann Pharmacother 26 813 822 1992 1611165 \n12 Nafiu OO Urquhart JC Pneumocephalus with headache complicating labour epidural analgesia: should we still be using air? Int J Obstet Anesth 15 237 239 2006 16798452 \n13 Pountos I Panteli M Walters G Bush D Giannoudis PV Safety of epidural corticosteroid injections Drugs R D 16 19 34 2016 26715572 \n14 Reddi S Honchar V Robbins MS Pneumocephalus associated with epidural and spinal anesthesia for labor Neurol Clin Pract 5 376 382 2015 29443169 \n15 Schier R Guerra D Aguilar J Pratt GF Hernandez M Boddu K Epidural space identification: a meta-analysis of complications after air versus liquid as the medium for loss of resistance Anesth Analg 109 2012 2021 2009 19923534 \n16 Shah AK Bilko A Takayesu JK Epidural steroid injection complicated by intrathecal entry, pneumocephalus, and chemical meningitis J Emerg Med 51 265 268 2016 27381953 \n17 Verdun AV Cohen SP Williams BS Hurley RW Pneumocephalus after lumbar epidural steroid injection: a case report and review of the literature A A Case Rep 3 9 13 2014 25612267\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "2234-8999", "issue": "16(1)", "journal": "Korean journal of neurotrauma", "keywords": "Dura mater; Injections; Meningitis; Pneumocephalus; Punctures", "medline_ta": "Korean J Neurotrauma", "mesh_terms": null, "nlm_unique_id": "101584658", "other_id": null, "pages": "67-72", "pmc": null, "pmid": "32395453", "pubdate": "2020-04", "publication_types": "D002363:Case Reports", "references": "12734154;14742399;16798452;9447859;29443169;26715572;5302838;22828691;19923534;15281538;1611165;29201853;3826114;22430650;27381953;25612267", "title": "Pneumocephalus and Chemical Meningitis after Inadvertent Dural Puncture during Lumbar Epidural Injection.", "title_normalized": "pneumocephalus and chemical meningitis after inadvertent dural puncture during lumbar epidural injection" }

[ { "companynumb": "KR-FRESENIUS KABI-FK202010027", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "MEPIVACAINE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "008", "drugauthorizationnumb": "089406", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "BACK PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MEPIVACAINE INJECTION (MANUFACTURER UNKNOWN)" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "008", "drugauthorizationnumb": "084916", "drugbatchnumb": "UNKNOWN,UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "BACK PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE INJECTION (MANUFACTURER UNKNOWN)" } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Meningitis chemical", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pneumocephalus", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Anaesthetic complication", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "KOO J, CHO K. PNEUMOCEPHALUS AND CHEMICAL MENINGITIS AFTER INADVERTENT DURAL PUNCTURE DURING LUMBAR EPIDURAL INJECTION. KOREAN JOURNAL OF NEUROTRAUMA. 2020 APR?16 (1):67?72.", "literaturereference_normalized": "pneumocephalus and chemical meningitis after inadvertent dural puncture during lumbar epidural injection", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20200929", "receivedate": "20200929", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18326164, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" } ]

{ "abstract": "OBJECTIVE\nAlthough systemic therapy is recommended for patients with multiple intermediate stage unresectable hepatocellular carcinoma (u-HCC) classified as beyond the up-to-7 criteria (UT-7 out/multiple) as a transcatheter arterial chemoembolization (TACE) unsuitable condition, few reports have examined the therapeutic efficacy of atezolizumab plus bevacizumab combination therapy (Atez/Bev) in such cases. This study aimed to elucidate the therapeutic response of Atez/Bev in u-HCC patients classified as UT-7 out/multiple.\n\n\nMETHODS\nFrom September 2020 to September 2021, 95 u-HCC Japanese patients classified as UT-7 out/multiple/Child-Pugh A were enrolled from 21 institutions (median age 76 years, males 73, Child-Pugh 5:6 = 68:27, TNM stage II:III = 17:78). Therapeutic response was retrospectively evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), ver. 1.1 and modified RECIST (mRECIST).\n\n\nRESULTS\nAtez/Bev was given as first-line treatment to 52 (54.7%). Objective response rate (ORR)/disease control rate (DCR) at six weeks of RECIST and mRECIST were 17.7%/84.7% and 42.5%/86.2%, respectively. Median PFS was 8.0 months (median observation period: 6.0 months). Child-Pugh A/modified Albumin-bilirubin grade (mALBI) 1 and 2a at baseline, 3, 6, and 9 weeks, were 100%/69.4%, 89.8%/57.3%, 94.8%/65.3%, and 91.4%/60.0%, respectively. Among adverse events (any-grade, >10%) during the present observation period, general fatigue was most frequent (23.2%), followed by urine protein (21.1%), appetite loss (20.0%), and hypertension (13.7%).\n\n\nCONCLUSIONS\nAtez/Bev treatment showed favorable therapeutic response with less influence on hepatic function, suggesting it as a useful therapeutic option for patients with such condition.", "affiliations": "Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.;Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan.;Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan.;Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.;Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.;Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan.;Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.;Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.;Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.;Department of Gastroenterology, Osaka Medical College, Osaka, Japan.;Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.;Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.;Department of Gastroenterology, Toyama University Hospital, Toyama, Japan.;Hepato-Biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan.;Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.;Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.;Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu, Japan.;Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan.;Department of Gastroenterology, Saiseikai Maebashi Hospital, Gunma, Japan.;Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.;Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan.;Department of Hepatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.;Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.;Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.;Department of Gastroenterology, Osaka Medical College, Osaka, Japan.;Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.;Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan.;Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.;Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.;Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.;Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.;Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.;Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.;Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.;Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan.;Hepato-Biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan.;Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan.;Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.;Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.", "authors": "Hiraoka|Atsushi|A|https://orcid.org/0000-0003-1989-0480;Kumada|Takashi|T|https://orcid.org/0000-0003-2211-495X;Tada|Toshifumi|T|https://orcid.org/0000-0002-0976-6761;Hirooka|Masashi|M|;Kariyama|Kazuya|K|;Tani|Joji|J|;Atsukawa|Masanori|M|;Takaguchi|Koichi|K|;Itobayashi|Ei|E|;Fukunishi|Shinya|S|;Tsuji|Kunihiko|K|;Ishikawa|Toru|T|;Tajiri|Kazuto|K|https://orcid.org/0000-0002-2373-8601;Ochi|Hironori|H|;Yasuda|Satoshi|S|;Toyoda|Hidenori|H|https://orcid.org/0000-0002-1652-6168;Ogawa|Chikara|C|;Nishimura|Takashi|T|;Hatanaka|Takeshi|T|;Kakizaki|Satoru|S|https://orcid.org/0000-0002-1508-584X;Shimada|Noritomo|N|;Kawata|Kazuhito|K|https://orcid.org/0000-0002-4986-8578;Naganuma|Atsushi|A|;Tanaka|Takaaki|T|;Ohama|Hideko|H|;Nouso|Kazuhiro|K|https://orcid.org/0000-0002-2018-0008;Morishita|Asahiro|A|https://orcid.org/0000-0002-0760-3045;Tsutsui|Akemi|A|;Nagano|Takuya|T|;Itokawa|Norio|N|;Okubo|Tomomi|T|;Arai|Taeang|T|;Imai|Michitaka|M|;Koizumi|Yohei|Y|;Nakamura|Shinichiro|S|;Joko|Kouji|K|https://orcid.org/0000-0001-8111-3266;Iijima|Hiroko|H|;Hiasa|Yoichi|Y|https://orcid.org/0000-0003-4117-339X;Kudo|Masatoshi|M|;|||;|||", "chemical_list": null, "country": "Netherlands", "delete": false, "doi": "10.1111/hepr.13734", "fulltext": null, "fulltext_license": null, "issn_linking": "1386-6346", "issue": null, "journal": "Hepatology research : the official journal of the Japan Society of Hepatology", "keywords": "BCLC-B; TACE unsuitable; atezolizumab plus bevacizumab; hepatocellular carcinoma; modified RECIST", "medline_ta": "Hepatol Res", "mesh_terms": null, "nlm_unique_id": "9711801", "other_id": null, "pages": null, "pmc": null, "pmid": "34799975", "pubdate": "2021-11-19", "publication_types": "D016428:Journal Article", "references": null, "title": "Early experience of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma BCLC-B stage patients classified as beyond up to seven criteria - Multicenter analysis.", "title_normalized": "early experience of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma bclc b stage patients classified as beyond up to seven criteria multicenter analysis" }

[ { "companynumb": "JP-PFIZER INC-202101787707", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "BEVACIZUMAB" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "761099", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Solution for infusion", "drugdosagetext": "5 MG/KG, EVERY 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Hepatocellular carcinoma", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BEVACIZUMAB" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ATEZOLIZUMAB" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1200 MG, EVERY 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Hepatocellular carcinoma", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1200", "drugstructuredosageunit": "003", "drugtreatmentduration": "3", "drugtreatmentdurationunit": "803", "medicinalproduct": "ATEZOLIZUMAB" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hyperthyroidism", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Hiraoka, A.. Early experience of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma BCLC-B stage patients classified as beyond up to seven criteria- Multicenter analysis. Hepatology Research. 2021;10.1111/hepr.13734", "literaturereference_normalized": "early experience of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma bclc b stage patients classified as beyond up to seven criteria multicenter analysis", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20211223", "receivedate": "20211223", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 20222740, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" } ]

{ "abstract": "Immunocompromised patients may be at increased risk to develop COVID-19 during the 2019 β-coronavirus infection. We present the unique opportunity we had to monitor the liver, IL-6 and immune cell course before, during and after COVID-19 in a boy with autoimmune hepatitis (AIH) and type 1 diabetes (T1D). CD4 and CD8 T cells frequencies decreased because of prednisolone, followed by a plateauing increase whereas CD19CD20 B cell increased strongly and was unaffected by COVID-19 infection. Moreover, the percentage of activated CD8 T cells expressing HLA-DR (CD8HLA-DR) increased during COVID-19 and subsided after its clearance. Total regulatory T cells (Tregs: CD4CD25CD127FOXP3) remained stable. Although activated Tregs (CD4CD45RAFOXP3) strongly increased upon prednisolone, it decreased afterwards. Furthermore, regulatory B cells (Bregs: CD19CD20CD24CD38) declined sharply owing to prednisolone. Serum IL-6 remained undetectable at all times. We demonstrated for the first time immune monitoring in a child with AIH and T1D before, during and after COVID-19. We hypothesize that continuing with low level of prednisolone without azathioprine may have abrogated activated Tregs, Bregs and IL-6 production and therefore permitting the activation of CD8 T cells, clearing the virus.", "affiliations": "Paediatric Gastroenterology-Hepatology/Liver Transplantation Centre, Koç University.;Koç University Paediatric infectious diseases.;Paediatric Gastroenterology-Hepatology/Liver Transplantation Centre, Koç University.", "authors": "Yuksel|Muhammed|M|;Akturk|Hacer|H|;Arikan|Cigdem|C|", "chemical_list": null, "country": "England", "delete": false, "doi": "10.1097/MEG.0000000000001804", "fulltext": null, "fulltext_license": null, "issn_linking": "0954-691X", "issue": "32(9)", "journal": "European journal of gastroenterology & hepatology", "keywords": null, "medline_ta": "Eur J Gastroenterol Hepatol", "mesh_terms": "D000073640:Betacoronavirus; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D000086382:COVID-19; D002675:Child, Preschool; D018352:Coronavirus Infections; D003922:Diabetes Mellitus, Type 1; D019693:Hepatitis, Autoimmune; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D015166:Monitoring, Immunologic; D058873:Pandemics; D011024:Pneumonia, Viral; D000086402:SARS-CoV-2", "nlm_unique_id": "9000874", "other_id": null, "pages": "1251-1255", "pmc": null, "pmid": "32541245", "pubdate": "2020-09", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Immune monitoring of a child with autoimmune hepatitis and type 1 diabetes during COVID-19 infection.", "title_normalized": "immune monitoring of a child with autoimmune hepatitis and type 1 diabetes during covid 19 infection" }

[ { "companynumb": "TR-TEVA-2020-TR-1827276", "fulfillexpeditecriteria": "1", "occurcountry": "TR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "TYPE 1 DIABETES MELLITUS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "080354", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "FOR 2?WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "AUTOIMMUNE HEPATITIS", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "20200129", "drugstartdateformat": "102", "drugstructuredosagenumb": "2", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "AZATHIOPRINE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "AUTOIMMUNE HEPATITIS", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": "50", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZATHIOPRINE." } ], "patientagegroup": "3", "patientonsetage": "5", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "COVID-19", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 2020" } }, "primarysource": { "literaturereference": "YUKSEL M, AKTURK H, ARIKAN C. IMMUNE MONITORING OF A CHILD WITH AUTOIMMUNE HEPATITIS AND TYPE 1 DIABETES DURING COVID?19 INFECTION. EUR?J?GASTROENTEROL?HEPATOL 2020?32(9):1251?1255.", "literaturereference_normalized": "immune monitoring of a child with autoimmune hepatitis and type 1 diabetes during covid 19 infection", "qualification": "1", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20200915", "receivedate": "20200915", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18266163, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" } ]

{ "abstract": "Repair of spontaneous cerebrospinal fluid (CSF) fistulas in patients with invasive skull base prolactinomas represents a surgical challenge because of the many sites of potential leak around the tumor and the possibility of developing additional sites of leak as the tumor regresses on dopamine agonist therapy. Little has been published on effective methods for treating this problem. In this case, a vascularized nasoseptal flap was used to repair a spontaneous CSF leak in a 31-year-old male with an invasive prolactinoma who was commenced on dopamine agonist therapy. The patient underwent successful multilayer repair of the fistula with a nasoseptal vascularized flap and abdominal rectus fascia. After 3 months of follow-up, he has had no CSF leak. CSF fistulas caused by skull base prolactinomas can be repaired successfully using a vascularized nasoseptal flap. Long-term follow-up will determine the durability of this repair technique.", "affiliations": "Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, United States.", "authors": "Little|Andrew S|AS|", "chemical_list": null, "country": "Germany", "delete": false, "doi": "10.1055/s-0032-1331386", "fulltext": null, "fulltext_license": null, "issn_linking": "2193-6315", "issue": "74 Suppl 1()", "journal": "Journal of neurological surgery. Part A, Central European neurosurgery", "keywords": null, "medline_ta": "J Neurol Surg A Cent Eur Neurosurg", "mesh_terms": "D000328:Adult; D065634:Cerebrospinal Fluid Leak; D002559:Cerebrospinal Fluid Rhinorrhea; D004724:Endoscopy; D006801:Humans; D009300:Nasal Septum; D015175:Prolactinoma; D019651:Reconstructive Surgical Procedures; D019292:Skull Base Neoplasms; D013524:Surgical Flaps", "nlm_unique_id": "101580767", "other_id": null, "pages": "e50-3", "pmc": null, "pmid": "23315667", "pubdate": "2013-12", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Repair of cerebrospinal fluid fistula from an invasive skull base prolactinoma using a septal mucosal vascularized flap: technical case report.", "title_normalized": "repair of cerebrospinal fluid fistula from an invasive skull base prolactinoma using a septal mucosal vascularized flap technical case report" }

[ { "companynumb": "US-IMPAX LABORATORIES, LLC-2018-IPXL-03984", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CABERGOLINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "077843", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROLACTIN-PRODUCING PITUITARY TUMOUR", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CABERGOLINE." } ], "patientagegroup": null, "patientonsetage": "31", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cerebrospinal fluid leakage", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LITTLE AS.. REPAIR OF CEREBROSPINAL FLUID FISTULA FROM AN INVASIVE SKULL BASE PROLACTINOMA USING A SEPTAL MUCOSAL VASCULARIZED FLAP TECHNICAL CASE REPORT. J NEUROL SURG. 2013?74:1:E50?E53", "literaturereference_normalized": "repair of cerebrospinal fluid fistula from an invasive skull base prolactinoma using a septal mucosal vascularized flap technical case report", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20181206", "receivedate": "20181206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15695689, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190205" } ]

{ "abstract": "OBJECTIVE\nA case of pancytopenia in a patient receiving treatment with fidaxomicin for Clostridium difficile infection (CDI) is described.\n\n\nCONCLUSIONS\nA 33-year-old Caucasian woman was admitted to the hospital with a chief complaint of loose stools occurring approximately 7 times a day; she also reported fever, nausea, diffuse abdominal pain, and fatigue. The patient had a history of recurrent CDI, recurrent urinary tract infections, nephrolithiasis, chronic hepatitis C, and endometriosis. Her previous therapies for CDI included metronidazole, vancomycin, rifaximin, and fecal microbiota transplantation. On admission, she had a platelet count of 172,000 platelets/mm3, hemoglobin concentration of 11.1 g/dL, and white blood cell (WBC) count of 3,100 cells/mm3. Within 24 hours of the first dose of fidaxomicin and before the second dose, the patient's platelet count fell to 156,000 platelets/mm3, her hemoglobin concentration decreased to 9.9 g/dL, and her WBC count fell to 2,600 cells/mm3. Values for all 3 tests continued to decrease during the first few days of fidaxomicin therapy. One dose of filgrastim 300 μg was administered subcutaneously on day 6 in response to the pancytopenia, after which the platelet, hemoglobin, and WBC values stabilized for a day and then generally declined. Platelet, hemoglobin, and WBC values returned to normal within 3 days of the patient's last dose of fidaxomicin. Use of the Naranjo et al. adverse drug reaction probability scale indicated a probable association (score of 6) between fidaxomicin and the patient's pancytopenia.\n\n\nCONCLUSIONS\nA 33-year-old woman developed pancytopenia during a course of fidaxomicin therapy for CDI. Platelet, hemoglobin, and WBC values returned to normal within 3 days of the final fidaxomicin dose.", "affiliations": "Palm Beach Atlantic University, Lloyd L. Gregory School of Pharmacy, West Palm Beach, FL [email protected].;Palm Beach Atlantic University, Lloyd L. Gregory School of Pharmacy, West Palm Beach, FL.;Palm Beach Atlantic University, Lloyd L. Gregory School of Pharmacy, West Palm Beach, FL.", "authors": "Axtell|Samantha|S|;Shokoya|Aisha|A|;Yocum|Christine|C|", "chemical_list": "D000900:Anti-Bacterial Agents; D000077732:Fidaxomicin", "country": "England", "delete": false, "doi": "10.2146/ajhp170239", "fulltext": null, "fulltext_license": null, "issn_linking": "1079-2082", "issue": "75(8)", "journal": "American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists", "keywords": "Clostridium difficile infection; diarrhea; fidaxomicin; pancytopenia", "medline_ta": "Am J Health Syst Pharm", "mesh_terms": "D000328:Adult; D000900:Anti-Bacterial Agents; D003015:Clostridium Infections; D005260:Female; D000077732:Fidaxomicin; D006801:Humans; D007279:Injections, Subcutaneous; D010198:Pancytopenia", "nlm_unique_id": "9503023", "other_id": null, "pages": "532-535", "pmc": null, "pmid": "29626003", "pubdate": "2018-04-15", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Probable fidaxomicin-induced pancytopenia.", "title_normalized": "probable fidaxomicin induced pancytopenia" }

[ { "companynumb": "US-009507513-1805USA000776", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": null, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "4 MG DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "4", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BIFIDOBACTERIUM (UNSPECIFIED)" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "FIDAXOMICIN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "201699", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "200 MG, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": "CLOSTRIDIUM DIFFICILE INFECTION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIFICID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ACETAMINOPHEN\\OXYCODONE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "(5 AND 325 MG, RESPECTIVELY) ORALLY EVERY 6 HOURS AS NEEDED", "drugenddate": null, "drugenddateformat": null, "drugindication": "PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACETAMINOPHEN (+) OXYCODONE HYDROCHLORIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ONDANSETRON" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "ORODISPERSIBLE TABLET", "drugdosagetext": "4 MG EVERY 12 HOURS AS NEEDED", "drugenddate": null, "drugenddateformat": null, "drugindication": "NAUSEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "4", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ONDANSETRON" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "SACCHAROMYCES CEREVISIAE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 MG, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SACCHAROMYCES BOULARDII" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CYANOCOBALAMIN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1,000 ?G ORALLY DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYANOCOBALAMIN." } ], "patientagegroup": null, "patientonsetage": "33", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pancytopenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Inappropriate schedule of drug administration", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "AXTELL S, SHOKOYA A, YOCUM C. PROBABLE FIDAXOMICIN-INDUCED PANCYTOPENIA. AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY. 2018?75 (8):532-5", "literaturereference_normalized": "probable fidaxomicin induced pancytopenia", "qualification": "2", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20180608", "receivedate": "20180508", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14859646, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "PHHY2019US038536", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "FILGRASTIM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "125553", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "300 UG, ONCE/SINGLE", "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCYTOPENIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "300", "drugstructuredosageunit": "004", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FILGRASTIM" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ONDANSETRON" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "4 MG, Q12H", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "12", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "4", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ONDANSETRON" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BIFIDOBACTERIUM ANIMALIS LACTIS" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "4 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", 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"drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FIDAXOMICIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ACETAMINOPHEN\\OXYCODONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MG AND 325 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "PAIN", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "6", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXYCODONE AND ACETAMINOPHEN" } ], "patientagegroup": null, "patientonsetage": "33", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "White blood cell count decreased", "reactionmeddraversionpt": "21.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Platelet count decreased", "reactionmeddraversionpt": "21.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Haemoglobin decreased", "reactionmeddraversionpt": "21.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "AXTELL S, SHOKOYA A, YOCUM C. PROBABLE FIDAXOMICIN-INDUCED PANCYTOPENIA. AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY. 2018?75 (8):532-5", "literaturereference_normalized": "probable fidaxomicin induced pancytopenia", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20190220", "receivedate": "20190220", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15985731, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190418" } ]

{ "abstract": "We present a case of transient lingual papillitis associated with confirmed herpes simplex virus 1 that developed after a child received intravenous immunoglobulin and infliximab for acute Kawasaki disease.", "affiliations": "Department of Pediatrics, Rady Children's Hospital, San Diego and University of California, San Diego, San Diego, California; Department of Dermatology, Rady Children's Hospital, San Diego and University of California, San Diego, San Diego, California.", "authors": "Krakowski|Andrew C|AC|;Kim|Silvia S|SS|;Burns|Jane C|JC|", "chemical_list": "D000914:Antibodies, Viral; D007074:Immunoglobulin G", "country": "United States", "delete": false, "doi": "10.1111/pde.12477", "fulltext": null, "fulltext_license": null, "issn_linking": "0736-8046", "issue": "31(6)", "journal": "Pediatric dermatology", "keywords": null, "medline_ta": "Pediatr Dermatol", "mesh_terms": "D000914:Antibodies, Viral; D005928:Glossitis; D006561:Herpes Simplex; D018259:Herpesvirus 1, Human; D006801:Humans; D007074:Immunoglobulin G; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome", "nlm_unique_id": "8406799", "other_id": null, "pages": "e124-5", "pmc": null, "pmid": "25424222", "pubdate": "2014", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Transient lingual papillitis associated with confirmed herpes simplex virus 1 in a patient with kawasaki disease.", "title_normalized": "transient lingual papillitis associated with confirmed herpes simplex virus 1 in a patient with kawasaki disease" }

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{ "abstract": "The incidence of brain abscess is higher among immunosuppressed patients. We report a case of a brain abscess in the temporal lobe in a patient under treatment with adalimumab and methotrexate, who developed radiological worsening. Clinical remission was essential to suspect Immune Reconstitution Inflammatory Syndrome and to continue empirical antimicrobial therapy due to the low suspicion of worsening of the abscess itself.", "affiliations": "Hospital Universitario de La Princesa, Department of Neurology, Madrid, Spain. Electronic address: [email protected].;Hospital Universitario de La Princesa, Department of Neurology, Madrid, Spain.;Hospital Universitario de La Princesa, Department of Infectious Diseases, Madrid, Spain.;Hospital Universitario de La Princesa, Department of Neurology, Madrid, Spain.", "authors": "Quintas|Sonia|S|;Sánchez|Pedro|P|;López|Manuel|M|;Vivancos|José|J|", "chemical_list": "D007166:Immunosuppressive Agents; D000068879:Adalimumab; D008727:Methotrexate", "country": "Scotland", "delete": false, "doi": "10.1016/j.jocn.2018.12.018", "fulltext": null, "fulltext_license": null, "issn_linking": "0967-5868", "issue": "62()", "journal": "Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia", "keywords": "Abscess; Immune Reconstitution Inflammatory Syndrome; MRI; Methotrexate; TNF-blocker", "medline_ta": "J Clin Neurosci", "mesh_terms": "D000068879:Adalimumab; D001922:Brain Abscess; D003424:Crohn Disease; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents; D008297:Male; D008727:Methotrexate; D008875:Middle Aged", "nlm_unique_id": "9433352", "other_id": null, "pages": "240-242", "pmc": null, "pmid": "30611629", "pubdate": "2019-04", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Neuroradiological worsening of brain abscess after adalimumab and methotrexate withdrawal: Do not forget Immune Reconstitution Inflammatory Syndrome.", "title_normalized": "neuroradiological worsening of brain abscess after adalimumab and methotrexate withdrawal do not forget immune reconstitution inflammatory syndrome" }

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SANCHEZ P.? LOPEZ M.? ET. AL. NEURORADIOLOGICAL WORSENING OF BRAIN ABSCESS AFTER ADALIMUMAB AND METHOTREXATE WITHDRAWAL: DO NOT FORGET IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME. 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SANCHEZ P.? LOPEZ M.? ET. AL. NEURORADIOLOGICAL WORSENING OF BRAIN ABSCESS AFTER ADALIMUMAB AND METHOTREXATE WITHDRAWAL: DO NOT FORGET IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME. 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{ "abstract": "BACKGROUND\nSpontaneous spinal epidural hematoma (SSEH) is a rare spinal cord disorder requiring urgent diagnosis and prompt treatment to prevent irreversible neurological damage. Subarachnoid hemorrhage (SAH), usually presenting with headache and neck stiffness, is also a worldwide neurosurgical emergency. In this case study, a patient on clopidogrel presented with an SSEH mimicking a spontaneous SAH.\n\n\nMETHODS\nA 74-year-old female presented with severe headache and neck pain which ultimately attributed to a cervicothoracic SSEH resulting in cord compression. Notably, there was a long delay in establishing the diagnosis of SSEH as her symptoms mimicked a SAH. Although the patient ultimately underwent spinal surgery followed by intense rehabilitation, the diagnostic delay resulted in a poor neurological outcome.\n\n\nCONCLUSIONS\nPatients with spontaneous cervicothoracic epidural hematomas may occasionally present with symptoms of severe headache and neck pain/stiffness mimicking an SAH. Long diagnostic delays in establishing SSEH may result in irreversible cord damage.", "affiliations": "Neurosurgical Department, Asclepeion General Hospital of Athens, Athens, Greece.;Neurosurgical Department, Asclepeion General Hospital of Athens, Athens, Greece.", "authors": "Aristedis|Rovlias|R|;Dimitrios|Bougioulis|B|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.4103/sni.sni_197_17", "fulltext": "\n==== Front\nSurg Neurol IntSurg Neurol IntSNISurgical Neurology International2229-50972152-7806Medknow Publications & Media Pvt Ltd India SNI-8-18210.4103/sni.sni_197_17Spine: Case ReportSpinal epidural hematoma mimicking subarachnoid hemorrhage: A case study Aristedis Rovlias *[email protected] Bougioulis [email protected] Department, Asclepeion General Hospital of Athens, Athens, Greece* Corresponding author\n2017 10 8 2017 8 18227 5 2017 08 6 2017 Copyright: © 2017 Surgical Neurology International2017This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.Background:\nSpontaneous spinal epidural hematoma (SSEH) is a rare spinal cord disorder requiring urgent diagnosis and prompt treatment to prevent irreversible neurological damage. Subarachnoid hemorrhage (SAH), usually presenting with headache and neck stiffness, is also a worldwide neurosurgical emergency. In this case study, a patient on clopidogrel presented with an SSEH mimicking a spontaneous SAH.\n\nCase Description:\nA 74-year-old female presented with severe headache and neck pain which ultimately attributed to a cervicothoracic SSEH resulting in cord compression. Notably, there was a long delay in establishing the diagnosis of SSEH as her symptoms mimicked a SAH. Although the patient ultimately underwent spinal surgery followed by intense rehabilitation, the diagnostic delay resulted in a poor neurological outcome.\n\nConclusions:\nPatients with spontaneous cervicothoracic epidural hematomas may occasionally present with symptoms of severe headache and neck pain/stiffness mimicking an SAH. Long diagnostic delays in establishing SSEH may result in irreversible cord damage.\n\nClopidogrelmagnetic resonance imagingspinal epidural hematomasubarachnoid hemorrhage\n==== Body\nINTRODUCTION\nSubarachnoid hemorrhage (SAH), usually presenting with headache and neck pain/stiffness, is a worldwide neurosurgical emergency and must be differentiated from spontaneous spinal epidural hematoma (SSEH). SSEH, however, is a rare entity that must be differentiated from SAH early on in the clinical course to avoid irreversible spinal cord injury (0.1 patients per 100,000 individuals per year).[236]\n\nHere, we present a 74-year-old female on clopidogrel whose headache/neck stiffness was originally misdiagnosed as a SAH. This led to delayed treatment of a cervicothoracic SSEH that resulted in an irreversible quadriparesis.\n\nCASE REPORT\nAn obese 74-year-old female patient presented with a 3-day history of spontaneous sudden-onset headache and neck pain, accompanied by nausea, and a worsening occipital headache unresponsive to analgesics. Notably, she was taking clopidogrel 75 mg/d for coronary artery disease.\n\nNeurological examination revealed marked nuchal rigidity, positive Kernig's sign, normal funduscopic examination (e.g., no papilledema), and no other focal neurological deficits. The initial clinical diagnosis was a spontaneous SAH.\n\nDiagnostic studies\nRoutine laboratory and coagulation tests were within normal limits. Chest X-ray showed no abnormalities. Noncontrast cranial computed tomography (CT) was negative for intracranial hemorrhage. Lumbar puncture (LP) yielded clear cerebrospinal fluid (CSF); laboratory analysis of the CSF was normal. Doppler ultrasonography of the carotid revealed no significant stenosis or arterial dissection.\n\nProgressive neurological deterioration\nThirty hours postadmission, the patient developed a rapidly progressive right hemiparesis accompanied by severe pain in the right shoulder. On examination, she exhibited marked hypesthesia with a severe flaccid paresis in both the right upper and right lower extremities (2/5 motor function). On the right side, deep tendon reflexes were decreased and there was no Babinski response. The second emergent brain CT scan was negative.\n\nThe patient was transferred to another institution 8 hours after the onset of hemiparesis at which point she was nearly quadriplegic (e.g., severe bilateral motor and sensory deficits below C5 level, labored respiration, and decreased chest expansion). Following cardiopulmonary resuscitation, magnetic resonance imaging (MRI) scan of the cervical spine demonstrated a large extradural mass, dorsally to the spinal cord extending from C3 through mid-T3. The mass had well-defined contours and contributed to multilevel posterior to anterior spinal cord compression. It was hyperintense on T1 [Figure 1a] and heterogeneously hyperintense on T2-weighted studies [Figure 1b]. It was more right-sided in location and was accompanied by an increased cord signal from C3 all the way down to the T2 level, which was suggestive of severe cord edema/infarction [Figure 1b]. Following gadolinium contrast administration, no enhancement was observed. These radiological findings were compatible with a cervicothoracic spinal epidural hematoma.\n\nFigure 1 An extradural more right -sided mass located dorsal to the spinal cord, extending from C3 through the mid-T3 vertebral level, resulting in marked spinal cord compression and edema/myelomalacia (high intrinsic cord signal). It was hyperintense on T1-weighted images (a), and heterogeneously hyperintense on T2-weighted images (b)\n\nOperational procedure\nThe patient underwent a C3 to T1 laminectomy with lateral masses screws – posterior fixation to prevent instability; the C3–T3 epidural hematoma was completely evacuated. Below the ligamentum flavum, large hard, dark clots were found, but no discrete bleeding points or abnormal vessels could be identified [Figure 2a and b]. At the end of the procedure, routine hemostasis was achieved and dural pulsations were evident. Histopathological examination was consistent with a hematoma; there was no evidence of a neoplasm or vascular malformation. The patient failed to improve following surgery and expired 18 months later.\n\nFigure 2 Following multilevel C3-T1 laminectomy with posterior instrumentation, the intraoperative photographs revealed a large epidural hematoma (a and b)\n\nDISCUSSION\nSSEH rarely causes spinal cord compression. It requires early diagnosis and prompt surgical treatment to prevent irreversible neurological damage or even death if the hematoma extends into the cephalad cervical region.[236] Presenting symptoms typically include sudden onset of pain, local and/or radiculopathy, followed by progressive myelopathy (e.g., weakness, sensory loss, and sphincter disturbances) developing within minutes to hours or days later.[1256] Somewhat confounding, is the overlap of symptoms/presentation between patients with SSEH vs. SAH [Table 1].[15678910]\n\nTable 1 Summary of previously reported cases of spontaneous spinal epidural hematomas mimicking subarachnoid hemorrhage\n\nRisk factors for SSEH include anticoagulant therapy, aspirin, vascular malformation, venous epidural plexus defects, hypertension, pregnancy, thrombolysis, physical exertion, chiropractic spinal manipulation, and hematological disorders.[469] Our patient was receiving clopidogrel that likely contributed to the progression of her hematoma.\n\nDelays in diagnosing SSEH increase the risks of permanent neurological deficits.[14] In the present patient, the first and secondary brain CT scans and LP were negative for SAH. She should have undergone earlier emergent cervical CT scan or MR studies of the cervicothoracic spine to diagnose SSEH.\n\nSSEH requires emergent surgery to avoid rapid neurological deterioration. In our patient, the MR findings documented a subacute C3–T3 epidural hematoma, but the surgical delay of 36 hours resulted in an irreversible neurological injury/quadriparesis.\n\nCONCLUSIONS\nPatients with SSEH rarely present with severe headache and neck pain/stiffness. SSEH must rapidly be differentiated from a SAH, and MR studies of the neuraxis must be performed to localize and then surgically treat the SSEH to avoid permanent neurological injury.\n\nFinancial support and sponsorship\nNil.\n\nConflicts of interest\nThere are no conflicts of interest.\n\nhttp://surgicalneurologyint.com/Spinal-epidural-hematoma-mimicking-subarachnoid-hemorrhage:-A-case-study/\n==== Refs\nREFERENCES\n1 Fukui MB Swarnkar AS Williams RL Acute spontaneous spinal epidural hematomas AJNR Am J Neuroradiol 1999 20 1365 72 10472999 \n2 Groen RJ van Alphen HA Operative treatment of spontaneous spinal epidural hematomas: A study of the factors determining postoperative outcome Neurosurgery 1996 39 494 508 8875479 \n3 Holtas S Heiling M Lonntoft M Spontaneous spinal epidural hematoma: Findings at MR imaging and clinical correlation Radiology 1996 199 409 13 8668786 \n4 Kreppel D Antoniadis G Seeling W Spinal hematoma: A literature survey with meta-analysis of 613 patients Neurosurg Rev 2003 26 1 49 12520314 \n5 Labeodan OA Spinal epidural haematoma mimicking spontaneous subarachnoid haemorrhage Emerg Med J 2005 22 606 7 16046780 \n6 Law EM Smith PJ Fitt G Hennessy OF Non-traumatic spinal extradural haematoma: Magnetic resonance findings Australas Radiol 1999 43 192 6 10901900 \n7 Lucchesi C Ulivi M Kiferle L Baldacci F Cafalli M Puglioli M Dorsal extramedullary hematoma: A rare case presenting as isolated thunderclap headache Headache 2015 55 1263 5 26316097 \n8 Ninomiya K Iwatsuki K Mrasawa A Goto T Naao K Yoshimine T Spontaneous spinal epidural hematoma: Magnetic resonance imaging for diagnosis and patient management in two cases J Neurosci Behav Health 2015 7 26 30 \n9 Sathirapanya P Setthawatcharawanich S Limapichat K Phabphal K Thunderclap headache as a presentation of spontaneous spinal epidural hematoma with spontaneous recovery J Spinal Cord Med 2013 36 707 10 24090118 \n10 Schwartz D Arcot K Grosberg BM Robbins MS Spontaneous cervical epidural hematoma associate with thunderclap headache J Headache Pain 2012 13 331 3 22422346\n\n", "fulltext_license": "CC BY-NC-SA", "issn_linking": "2152-7806", "issue": "8()", "journal": "Surgical neurology international", "keywords": "Clopidogrel; magnetic resonance imaging; spinal epidural hematoma; subarachnoid hemorrhage", "medline_ta": "Surg Neurol Int", "mesh_terms": null, "nlm_unique_id": "101535836", "other_id": null, "pages": "182", "pmc": null, "pmid": "28868194", "pubdate": "2017", "publication_types": "D002363:Case Reports", "references": "16046780;24090118;10901900;12520314;26316097;22422346;8875479;8668786;10472999", "title": "Spinal epidural hematoma mimicking subarachnoid hemorrhage: A case study.", "title_normalized": "spinal epidural hematoma mimicking subarachnoid hemorrhage a case study" }

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SPINAL EPIDURAL HEMATOMA MIMICKING SUBARACHNOID HEMORRHAGE: A CASE STUDY. SURGICAL NEUROLOGY INTERNATIONAL. 2017;8: 182:1-5", "literaturereference_normalized": "spinal epidural hematoma mimicking subarachnoid hemorrhage a case study", "qualification": "3", "reportercountry": "GR" }, "primarysourcecountry": "GR", "receiptdate": "20170922", "receivedate": "20170922", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13999197, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20171128" }, { "companynumb": "GR-TEVA-2018-GR-885329", "fulfillexpeditecriteria": "1", "occurcountry": "GR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "CLOPIDOGREL BISULFATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "076999", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "75 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "CORONARY ARTERY DISEASE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLOPIDOGREL" } ], "patientagegroup": null, "patientonsetage": "74", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Spinal epidural haematoma", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Quadriparesis", "reactionmeddraversionpt": "21.0", "reactionoutcome": "3" } ], "summary": null }, "primarysource": { "literaturereference": "ARISTEDIS R, DIMITRIOS B. SPINAL EPIDURAL HEMATOMA MIMICKING SUBARACHNOID HEMORRHAGE: A CASE STUDY. SURG-NEUROL-INT 2017?8(1):182.", "literaturereference_normalized": "spinal epidural hematoma mimicking subarachnoid hemorrhage a case study", "qualification": "3", "reportercountry": "GR" }, "primarysourcecountry": "GR", "receiptdate": "20180427", "receivedate": "20180427", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14817899, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180711" }, { "companynumb": "GR-MYLANLABS-2018M1025193", "fulfillexpeditecriteria": "1", "occurcountry": "GR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CLOPIDOGREL BISULFATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "077665", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "75 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "CORONARY ARTERY DISEASE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLOPIDOGREL" } ], "patientagegroup": null, "patientonsetage": "74", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Quadriparesis", "reactionmeddraversionpt": "21.0", "reactionoutcome": "3" }, { "reactionmeddrapt": "Spinal epidural haematoma", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "ARISTEDIS R, DIMITRIOS B. SPINAL EPIDURAL HEMATOMA MIMICKING SUBARACHNOID HEMORRHAGE: A CASE STUDY. SURG-NEUROL-INT 2017?8(1):182.", "literaturereference_normalized": "spinal epidural hematoma mimicking subarachnoid hemorrhage a case study", "qualification": "3", "reportercountry": "GR" }, "primarysourcecountry": "GR", "receiptdate": "20180427", "receivedate": "20180420", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14786171, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" } ]

{ "abstract": "Cutaneous adverse reactions to antiepileptic drugs (AEDs) are usually easily recognized in daily clinical practice when they manifest as a morbilliform or maculopapular rash within the first few weeks after introducing an AED. Valproate (VPA)-induced encephalopathy is a rare but serious complication, presenting with impaired consciousness, with or without hyperammonemia, normal liver enzymes, and normal serum level of VPA. A 2-year-old Caucasian boy with severe developmental disability and pharmacoresistant epilepsy presented with fever, generalized erythrodermia, and encephalopathy, which resolved after discontinuation of valproate. Sodium valproate (30 mg/kg/day) was introduced 5 months previously, as the third drug in combination with vigabatrin and levetiracetam, due to frequent daily seizures. The clinical condition of generalized erythrodermia and encephalopathy was recognized by the treating physician as a possible adverse reaction to VPA: with the Naranjo scale it was probably associated with VPA (six points) and possibly associated with vigabatrin and levetiracetam (three and two points, respectively). After valproate withdrawal, the patient recovered completely. This case is of interest because erythrodermia was a clue to the recognition of valproate-related adverse reaction with severe central nervous system involvement without hyperammonemia and with normal liver enzymes--a very rare occurrence.", "affiliations": "Department of Child, Adolescent, and Developmental Neurology, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia. Medical Faculty, University of Ljubljana, Ljubljana, Slovenia. Corresponding author: [email protected].;Department of Dermatology, Novo mesto General Hospital, Novo mesto, Slovenia.", "authors": "Rener-Primec|Zvonka|Z|;Balkovec|Valerija|V|", "chemical_list": "D000927:Anticonvulsants; D014635:Valproic Acid", "country": "Slovenia", "delete": false, "doi": "10.15570/actaapa.2014.9", "fulltext": null, "fulltext_license": null, "issn_linking": "1318-4458", "issue": "23(2)", "journal": "Acta dermatovenerologica Alpina, Pannonica, et Adriatica", "keywords": null, "medline_ta": "Acta Dermatovenerol Alp Pannonica Adriat", "mesh_terms": "D000927:Anticonvulsants; D001927:Brain Diseases; D002675:Child, Preschool; D003873:Dermatitis, Exfoliative; D003875:Drug Eruptions; D006801:Humans; D008297:Male; D012720:Severity of Illness Index; D014635:Valproic Acid", "nlm_unique_id": "9422563", "other_id": null, "pages": "35-8", "pmc": null, "pmid": "24964948", "pubdate": "2014", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Valproate-related erythrodermia with reversible encephalopathy: a rare but serious adverse reaction, case report.", "title_normalized": "valproate related erythrodermia with reversible encephalopathy a rare but serious adverse reaction case report" }

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VALPROATE-RELATED ERYTHRODERMIA WITH REVERSIBLE ENCEPHALOPATHY: A RARE BUT SERIOUS ADVERSE REACTION, CASE REPORT. 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VALPROATE-RELATED ERYTHRODERMIA WITH REVERSIBLE ENCEPHALOPATHY: A RARE BUT SERIOUS ADVERSE REACTION, CASE REPORT. ACTA DERMATOVENEROLOGICA ALPINA, PANNONICA ET ADRIATICA. 2014;23(2):35-37.", "literaturereference_normalized": "valproate related erythrodermia with reversible encephalopathy a rare but serious adverse reaction case report", "qualification": null, "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "SI", "receiptdate": "20141030", "receivedate": "20141030", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "3", "safetyreportid": 10553792, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150529" }, { "companynumb": "SI-ABBVIE-14P-261-1292591-00", "fulfillexpeditecriteria": "1", "occurcountry": "SI", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { 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null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VIGABATRIN" } ], "patientagegroup": null, "patientonsetage": "2", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Encephalopathy", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Erythema", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Dermatitis exfoliative", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Alanine aminotransferase increased", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Somnolence", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Leukocytosis", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Lethargy", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "C-reactive protein increased", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Eosinophilia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Coma", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Thrombocytopenia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Face oedema", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "RENER-PRIMEC Z, BALKOVEC V. VALPROATE-RELATED ERYTHRODERMIA WITH REVERSIBLE ENCEPHALOPATHY: A RARE BUT SERIOUS ADVERSE REACTION, CASE REPORT. ACTA DERMATOVENEROLOGICA ALPINA, PANNONICA ET ADRIATICA. 2014 JAN 01;23 (2):35-37.", "literaturereference_normalized": "valproate related erythrodermia with reversible encephalopathy a rare but serious adverse reaction case report", "qualification": "3", "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "SI", "receiptdate": "20141010", "receivedate": "20141010", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10512192, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150528" }, { "companynumb": "SI-PFIZER INC-2016315416", "fulfillexpeditecriteria": "1", "occurcountry": "SI", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "VALPROATE SODIUM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "30 MG/KG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "30", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SODIUM VALPROATE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "202869", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "40 MG/KG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "VIGABATRIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "40 MG/KG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VIGABATRIN" } ], "patientagegroup": null, "patientonsetage": "2", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "19.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Encephalopathy", "reactionmeddraversionpt": "19.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "RENER-PRIMEC, Z.. VALPROATE-RELATED ERYTHRODERMIA WITH REVERSIBLE ENCEPHALOPATHY: A RARE BUT SERIOUS ADVERSE REACTION, CASE REPORT. ACTA DERMATOVENEROLOGICA ALPINA, PANONICA ET ADRIATICA. 2014;23(2):35-37", "literaturereference_normalized": "valproate related erythrodermia with reversible encephalopathy a rare but serious adverse reaction case report", "qualification": "3", "reportercountry": "SI" }, "primarysourcecountry": "SI", "receiptdate": "20160630", "receivedate": "20160630", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12517075, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20160815" }, { "companynumb": "SI-MYLANLABS-2014M1008293", "fulfillexpeditecriteria": "1", "occurcountry": "SI", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "VALPROATE SODIUM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "30MG/KG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VALPROATE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "VIGABATRIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "40MG/KG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VIGABATRIN" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "202543", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "40MG/KG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." } ], "patientagegroup": null, "patientonsetage": "2", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Somnolence", "reactionmeddraversionpt": "18.0", "reactionoutcome": null }, { "reactionmeddrapt": "Lethargy", "reactionmeddraversionpt": "18.0", "reactionoutcome": null }, { "reactionmeddrapt": "Dermatitis exfoliative", "reactionmeddraversionpt": "18.0", "reactionoutcome": null }, { "reactionmeddrapt": "General physical health deterioration", "reactionmeddraversionpt": "18.0", "reactionoutcome": null }, { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Encephalopathy", "reactionmeddraversionpt": "18.0", "reactionoutcome": null }, { "reactionmeddrapt": "Upper respiratory tract infection", "reactionmeddraversionpt": "18.0", "reactionoutcome": null }, { "reactionmeddrapt": "Coma", "reactionmeddraversionpt": "18.0", "reactionoutcome": null }, { "reactionmeddrapt": "Thrombocytopenia", "reactionmeddraversionpt": "18.0", "reactionoutcome": null } ], "summary": null }, "primarysource": { "literaturereference": "RENER-PRIMEC Z, BALKOVEC V. VALPROATE-RELATED ERYTHRODERMIA WITH REVERSIBLE ENCEPHALOPATHY: A RARE BUT SERIOUS ADVERSE REACTION, CASE REPORT. ACTA-DERMATOVENEROL-A-P-A 2014; 23(2) 35-37", "literaturereference_normalized": "valproate related erythrodermia with reversible encephalopathy a rare but serious adverse reaction case report", "qualification": "3", "reportercountry": "SI" }, "primarysourcecountry": "SI", "receiptdate": "20141027", "receivedate": "20141027", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10543813, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150529" } ]

{ "abstract": "BACKGROUND\nThe risk factors for invasive fungal infection have gradually become evident for pediatric patients with hematological diseases. Here we analyze the efficacy of liposomal amphotericin (L-AMB) for pediatric patients with febrile neutropenia using prophylactic voriconazole (VRCZ).\n\n\nMETHODS\nWe administered L-AMB (2.5 mg/kg/day) in patients with febrile neutropenia who were receiving prophylactic VRCZ (10 mg/kg/day, orally) and were resistant to second-line antibiotics therapy. Thirteen patients (5 males, 8 females) with 19 febrile neutropenia episodes were targeted in this analysis. The median age of the patients was 14 years (range, 1-19 years). Eighteen out of 19 episodes occurred in patients with acute myeloid leukemia, with the remaining episode occurring in a patient with acute unclassified leukemia.\n\n\nRESULTS\nThe median period from start of L-AMB administration to resolution of fever was 4 days (1-27 days). In 15 out of 19 episodes, fever resolved within 5 days from commencement of L-AMB administration. Using criteria proposed by T. J. Walsh et al., the success rate of L-AMB for febrile neutropenia was 89.5% in this study.\n\n\nCONCLUSIONS\nAlthough the sample size of our study was small, the extremely high efficacy of L-AMB warrants its administration in patients with febrile neutropenia who are receiving VRCZ.", "affiliations": "Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, Japan.;Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, Japan.;Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, Japan.;Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, Japan.;Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, Japan.;Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, Japan.;Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, Japan.;Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, Japan.;Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, Japan.;Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, Japan.", "authors": "Kobayashi|Ryoji|R|https://orcid.org/0000-0002-3937-0856;Matsushima|Satoru|S|;Hori|Daiki|D|https://orcid.org/0000-0003-0634-6961;Sano|Hirozumi|H|;Suzuki|Daisuke|D|;Kishimoto|Kenji|K|;Nakano|Takaaki|T|;Yanagi|Masato|M|;Kodama|Kouya|K|;Kobayashi|Kunihiko|K|", "chemical_list": "D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B; D065819:Voriconazole", "country": "Australia", "delete": false, "doi": "10.1111/ped.14450", "fulltext": null, "fulltext_license": null, "issn_linking": "1328-8067", "issue": "63(5)", "journal": "Pediatrics international : official journal of the Japan Pediatric Society", "keywords": "febrile neutropenia; liposomal amphotericin; voriconazole", "medline_ta": "Pediatr Int", "mesh_terms": "D000293:Adolescent; D000328:Adult; D000666:Amphotericin B; D000935:Antifungal Agents; D002648:Child; D002675:Child, Preschool; D064147:Febrile Neutropenia; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute; D008297:Male; D065819:Voriconazole; D055815:Young Adult", "nlm_unique_id": "100886002", "other_id": null, "pages": "550-555", "pmc": null, "pmid": "32869416", "pubdate": "2021-05", "publication_types": "D016428:Journal Article", "references": null, "title": "Efficacy of liposomal amphotericin against febrile neutropenia in pediatric patients receiving prophylactic voriconazole.", "title_normalized": "efficacy of liposomal amphotericin against febrile neutropenia in pediatric patients receiving prophylactic voriconazole" }

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Efficacy of liposomal amphotericin against febrile neutropenia in pediatric patients receiving prophylactic voriconazole. 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Efficacy of liposomal amphotericin against febrile neutropenia in pediatric patients receiving prophylactic voriconazole. 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Efficacy of liposomal amphotericin against febrile neutropenia in pediatric patients receiving prophylactic voriconazole. 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Efficacy of liposomal amphotericin against febrile neutropenia in pediatric patients receiving prophylactic voriconazole. 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Efficacy of liposomal amphotericin against febrile neutropenia in pediatric patients receiving prophylactic voriconazole. 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Efficacy of liposomal amphotericin against febrile neutropenia in pediatric patients receiving prophylactic voriconazole. 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"drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYTARABINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Acute myeloid leukaemia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYTARABINE" }, { "actiondrug": "5", "activesubstance": { 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"24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Kobayashi R, Matsushima S, Hori D, Sano H, Suzuki D, Kishimoto K, et al. Efficacy of liposomal amphotericin against febrile neutropenia in pediatric patients receiving prophylactic voriconazole. Pediatr-Int 2021;63(5):550-555.. 2021;63(5):550-555", "literaturereference_normalized": "efficacy of liposomal amphotericin against febrile neutropenia in pediatric patients receiving prophylactic voriconazole", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20211022", "receivedate": "20211022", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19985903, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220304" } ]

{ "abstract": "OBJECTIVE\nAn enlarged fourth ventricle, otherwise known as fourth ventriculomegaly (4th VM), has been reported previously in the pediatric population, yet literature on adults is scant. We report our experience with 4th VM in adults over an 11-year period and review the literature.\n\n\nMETHODS\nThis was a retrospective chart review of adult patients with the diagnosis of 4th VM admitted to the intensive care unit in a tertiary care center.\n\n\nRESULTS\nNine patients were identified with 4th VM. Most presented with symptoms in the posterior fossa. Five cases were related to previous shunting and the underlying neurosurgical diseases, and average time interval to develop symptoms was 5.3 years. We divided our cases into primary, acquired, and degenerative based on the pathophysiology involved. Treatments included extended subzero cerebrospinal fluid diversion using a frontal external ventricular drain followed by low-pressure shunt revision, endoscopic third ventriculostomy, suboccipital decompression, and fourth ventricular catheter placement. Literature review identified additional published cases, and there were no reports of a formal classification scheme or treatment algorithm.\n\n\nCONCLUSIONS\nThis case series illustrates a narrow spectrum of etiologies associated with 4th VM in adults. We propose a simple classification scheme dividing 4th VM into 3 categories: primary, acquired, and degenerative. We recommend a stepwise treatment approach starting with extended subzero cerebrospinal fluid diversion followed by shunting for symptomatic primary and acquired 4th VM. Lower success rates and greater morbidity are associated with rescue procedures such as fourth ventricle drainage catheters, endoscopic third ventriculostomies, and skull base decompression.", "affiliations": "Department of Neurosurgery, Kaiser Permanente, Sacramento, California, USA. Electronic address: [email protected].;Department of Neurosurgery, Kaiser Permanente, Sacramento, California, USA.;Department of Neurosurgery, Kaiser Permanente, Sacramento, California, USA.;Department of Neurosurgery, Kaiser Permanente, Sacramento, California, USA.;Department of Neurosurgery, Kaiser Permanente, Sacramento, California, USA.", "authors": "Barami|Kaveh|K|;Chakrabarti|Indro|I|;Silverthorn|James|J|;Ciporen|Jeremy|J|;Akins|Paul T|PT|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1016/j.wneu.2018.05.073", "fulltext": null, "fulltext_license": null, "issn_linking": "1878-8750", "issue": "116()", "journal": "World neurosurgery", "keywords": "Arachnoiditis; Cerebellar atrophy; Coccidioidomycosis; Endoscopic third ventriculostomy; Fourth ventriculomegaly; Hydrocephalus; Isolated fourth ventricle; Low-pressure hydrocephalus; Ventricular shunts", "medline_ta": "World Neurosurg", "mesh_terms": "D000293:Adolescent; D000328:Adult; D019468:Disease Management; D005260:Female; D020546:Fourth Ventricle; D006801:Humans; D006849:Hydrocephalus; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D014057:Tomography, X-Ray Computed; D055815:Young Adult", "nlm_unique_id": "101528275", "other_id": null, "pages": "e709-e722", "pmc": null, "pmid": "29778601", "pubdate": "2018-08", "publication_types": "D016428:Journal Article; D016454:Review", "references": null, "title": "Diagnosis, Classification, and Management of Fourth Ventriculomegaly in Adults: Report of 9 Cases and Literature Review.", "title_normalized": "diagnosis classification and management of fourth ventriculomegaly in adults report of 9 cases and literature review" }

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{ "abstract": "Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment that enhances survival and stabilizes neurologic symptoms in X-linked adrenoleukodystrophy (X-ALD) with cerebral involvement, a severe demyelinating disease of childhood. Patients with X-ALD who lack a well-matched HLA donor need a rapid alternative. Haploidentical HSCT using post transplant cyclophosphamide (PT/Cy) has been performed in patients with malignant and nonmalignant diseases showing similar outcomes compared to other alternative sources. We describe the outcomes of transplants performed for nine X-ALD patients using haploidentical donors and PT/Cy. Patients received conditioning regimen with fludarabine 150 mg/m2, cyclophosphamide 29 mg/kg and 2 Gy total body irradiation (TBI) with or without antithymocyte globulin. Graft-vs.-host disease prophylaxis consisted of cyclophosphamide 50 mg/kg/day on days +3 and +4, tacrolimus or cyclosporine A and mycophenolate mofetil. One patient had a primary graft failure and was not eligible for a second transplant. Three patients had secondary graft failure and were successfully rescued with second haploidentical transplants. Trying to improve engraftment, conditioning regimen was changed, substituting 2 Gy TBI for 4 Gy total lymphoid irradiation. Eight patients are alive and engrafted (17-37 months after transplant). Haploidentical HSCT with PT/Cy is a feasible alternative for X-ALD patients lacking a suitable matched donor. Graft failure has to be addressed in further studies.", "affiliations": "Hematology and Bone Marrow Transplantation Program, Hospital Israelita Albert Einstein, São Paulo, Brazil.;Bone Marrow Transplantation Department, Hospital de Clinicas da Universidade Federal do Paraná, Curitiba, Brazil.;Hematology and Bone Marrow Transplantation Program, Hospital Israelita Albert Einstein, São Paulo, Brazil.;Hematology and Bone Marrow Transplantation Program, Hospital Israelita Albert Einstein, São Paulo, Brazil.;Hematology and Bone Marrow Transplantation Program, Hospital Israelita Albert Einstein, São Paulo, Brazil.;Hematology and Bone Marrow Transplantation Program, Hospital Israelita Albert Einstein, São Paulo, Brazil.;Hematology and Bone Marrow Transplantation Program, Hospital Israelita Albert Einstein, São Paulo, Brazil.;Hematology and Bone Marrow Transplantation Program, Hospital Israelita Albert Einstein, São Paulo, Brazil.;Hematology and Bone Marrow Transplantation Program, Hospital Israelita Albert Einstein, São Paulo, Brazil.;Bone Marrow Transplantation Department, Hospital de Clinicas da Universidade Federal do Paraná, Curitiba, Brazil.;Bone Marrow Transplantation Department, Hospital de Clinicas da Universidade Federal do Paraná, Curitiba, Brazil.;Department of Neurology, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.;Hematology and Bone Marrow Transplantation Program, Hospital Israelita Albert Einstein, São Paulo, Brazil.;Hematology and Bone Marrow Transplantation Program, Hospital Israelita Albert Einstein, São Paulo, Brazil.;Department of Neurology, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.;Hematology and Bone Marrow Transplantation Program, Hospital Israelita Albert Einstein, São Paulo, Brazil. [email protected].", "authors": "Fernandes|Juliana Folloni|JF|;Bonfim|Carmem|C|;Kerbauy|Fábio Rodrigues|FR|;Rodrigues|Morgani|M|;Esteves|Iracema|I|;Silva|Nathalia Halley|NH|;Azambuja|Alessandra Prandini|AP|;Mantovani|Luiz Fernando|LF|;Kutner|José Mauro|JM|;Loth|Gisele|G|;Kuwahara|Cilmara Cristina|CC|;Bueno|Clarissa|C|;Kondo|Andrea Tiemi|AT|;Ribeiro|Andreza Alice Feitosa|AAF|;Kok|Fernando|F|;Hamerschlak|Nelson|N|", "chemical_list": "D003520:Cyclophosphamide", "country": "England", "delete": false, "doi": "10.1038/s41409-017-0015-2", "fulltext": null, "fulltext_license": null, "issn_linking": "0268-3369", "issue": "53(4)", "journal": "Bone marrow transplantation", "keywords": null, "medline_ta": "Bone Marrow Transplant", "mesh_terms": "D000293:Adolescent; D000326:Adrenoleukodystrophy; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D003520:Cyclophosphamide; D006085:Graft Survival; D006086:Graft vs Host Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors; D019172:Transplantation Conditioning; D000075442:Transplantation, Haploidentical; D016896:Treatment Outcome; D055815:Young Adult", "nlm_unique_id": "8702459", "other_id": null, "pages": "392-399", "pmc": null, "pmid": "29330393", "pubdate": "2018-04", "publication_types": "D016428:Journal Article", "references": null, "title": "Haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with X-linked adrenoleukodystrophy: a suitable choice in an urgent situation.", "title_normalized": "haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with x linked adrenoleukodystrophy a suitable choice in an urgent situation" }

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"drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ACYCLOVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HERPES SIMPLEX", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACYCLOVIR." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TRIMETHOPRIM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMOCYSTIS JIROVECII PNEUMONIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TRIMETHOPRIM." } ], "patientagegroup": "3", "patientonsetage": "7", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Product used for unknown indication", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cytomegalovirus infection", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute graft versus host disease", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Chronic graft versus host disease", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Transplant failure", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "FERNANDES JF, BONFIM C, KERBAUY FR, RODRIGUES M, ESTEVES I, SILVA NH ET AL. HAPLOIDENTICAL BONE MARROW TRANSPLANTATION WITH POST TRANSPLANT CYCLOPHOSPHAMIDE FOR PATIENTS WITH X-LINKED ADRENOLEUKODYSTROPHY: A SUITABLE CHOICE IN AN URGENT SITUATION. BONE MARROW TRANSPLANT. 2018 APR 53 4 392-399 10.1038/S41409-017-0", "literaturereference_normalized": "haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with x linked adrenoleukodystrophy a suitable choice in an urgent situation", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20190603", "receivedate": "20190603", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16383074, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190711" }, { "companynumb": "BR-PANACEA BIOTEC LIMITED-000011", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "746730000", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "FLUCONAZOLE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIFUNGAL PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUCONAZOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "090802", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "EVERY 8H", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "15", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TRIMETHOPRIM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMOCYSTIS JIROVECII PNEUMONIA", 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"drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MICAFUNGIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ACYCLOVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HERPES SIMPLEX TEST POSITIVE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACYCLOVIR." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "SULFAMETHOXAZOLE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMOCYSTIS JIROVECII PNEUMONIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SULFAMETHOXAZOLE" } ], "patientagegroup": "3", "patientonsetage": "6", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cytomegalovirus infection", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute graft versus host disease", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "FERNANDES JF, BONFIM C, KERBAUY FR, RODRIGUES M, ESTEVES I, SILVA NH ET AL. HAPLOIDENTICAL BONE MARROW TRANSPLANTATION WITH POST TRANSPLANT CYCLOPHOSPHAMIDE FOR PATIENTS WITH X-LINKED ADRENOLEUKODYSTROPHY: A SUITABLE CHOICE IN AN URGENT SITUATION. BONE MARROW TRANSPLANT 2018 APR 53 4 392-399", "literaturereference_normalized": "haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with x linked adrenoleukodystrophy a suitable choice in an urgent situation", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20190603", "receivedate": "20190603", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16383072, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190711" }, { "companynumb": "BR-ACCORD-129227", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "091195", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "STARTED ON DAY +5.", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUDARABINE PHOSPHATE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "30 MG/M2 ON DAYS 6 TO 2", "drugenddate": null, "drugenddateformat": null, "drugindication": "BONE MARROW CONDITIONING REGIMEN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "30", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUDARABINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "14.5 MG/KG ON DAYS 6 AND 5. LATER STARTED ON DAY +5 AT 50 MG/KG.", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "14.5", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE/CYCLOPHOSPHAMIDE MONOHYDRATE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "THYMOCYTE IMMUNE GLOBULIN NOS" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.5 MG/KG ON DAY 9 AND 2 MG/KG ON DAYS 8 AND 7.", "drugenddate": null, "drugenddateformat": null, "drugindication": "BONE MARROW CONDITIONING REGIMEN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANTITHYMOCYTE IMMUNOGLOBULIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MYCOPHENOLIC ACID" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "065416", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "15 MG/KG EVERY 8 H STARTED ON DAY +5.", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "15", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLIC ACID." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Adenovirus infection", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bacterial sepsis", "reactionmeddraversionpt": "22.0", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "FERNANDES JF, BONFIM C, KERBAUY FR, RODRIGUES M, ESTEVES I, SILVA NH,ET AL. HAPLOIDENTICAL BONE MARROW TRANSPLANTATION WITH POST TRANSPLANT CYCLOPHOSPHAMIDE FOR PATIENTS WITH X-LINKED ADRENOLEUKODYSTROPHY: A SUITABLE CHOICE IN AN URGENT SITUATION. BONE MARROW TRANSPLANT. 2018 APR?53(4):392-399", "literaturereference_normalized": "haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with x linked adrenoleukodystrophy a suitable choice in an urgent situation", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20190527", "receivedate": "20190527", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 16356740, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190711" }, { "companynumb": "BR-PANACEA BIOTEC LIMITED-000006", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "090802", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "8", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "15", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "746730000", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "FLUCONAZOLE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, 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"ACICLOVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TRIMETHOPRIM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMOCYSTIS JIROVECII PNEUMONIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TRIMETHOPRIM." } ], "patientagegroup": null, "patientonsetage": "6", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Adenovirus infection", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute graft versus host disease", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "FERNANDES JF, BONFIM C, KERBAUY FR, RODRIGUES M, ESTEVES I, SILVA NH ET AL. HAPLOIDENTICAL BONE MARROW TRANSPLANTATION WITH POST TRANSPLANT CYCLOPHOSPHAMIDE FOR PATIENTS WITH X-LINKED ADRENOLEUKODYSTROPHY: A SUITABLE CHOICE IN AN URGENT SITUATION. BONE MARROW TRANSPLANT. 2018 APR?53(4):392-399. DOI: 10.1038/S41409-017-0015-2.", "literaturereference_normalized": "haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with x linked adrenoleukodystrophy a suitable choice in an urgent situation", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20190603", "receivedate": "20190603", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16383060, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190711" }, { "companynumb": "BR-PANACEA BIOTEC LIMITED-000004", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "1236100710025", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "FLUCONAZOLE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIFUNGAL PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUCONAZOLE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ACYCLOVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, 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"drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MICAFUNGIN SODIUM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIFUNGAL PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MICAFUNGIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TRIMETHOPRIM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMOCYSTIS JIROVECII PNEUMONIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TRIMETHOPRIM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "SULFAMETHOXAZOLE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMOCYSTIS JIROVECII PNEUMONIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SULFAMETHOXAZOLE" } ], "patientagegroup": "3", "patientonsetage": "7", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute graft versus host disease", "reactionmeddraversionpt": "22.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Cytomegalovirus infection", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "FERNANDES JF, BONFIM C, KERBAUY FR, RODRIGUES M, ESTEVES I, SILVA NH ET AL. HAPLOIDENTICAL BONE MARROW TRANSPLANTATION WITH POST TRANSPLANT CYCLOPHOSPHAMIDE FOR PATIENTS WITH X-LINKED ADRENOLEUKODYSTROPHY: A?SUITABLE CHOICE IN AN URGENT SITUATION. BONE MARROW TRANSPLANT. 2018 APR?53(4):392-399. DOI: 10.1038/S41409-017-0015-2.", "literaturereference_normalized": "haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with x linked adrenoleukodystrophy a suitable choice in an urgent situation", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20190531", "receivedate": "20190531", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16377101, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190711" }, { "companynumb": "BR-PANACEA BIOTEC LIMITED-000007", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "FLUDARABINE PHOSPHATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, 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null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACICLOVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "14.5", 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"actiondrug": null, "activesubstance": { "activesubstancename": "SULFAMETHOXAZOLE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMOCYSTIS JIROVECII PNEUMONIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SULFAMETHOXAZOLE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MICAFUNGIN SODIUM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIFUNGAL PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MICAFUNGIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "090802", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST GRAFT VERSUS HOST DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "15", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TRIMETHOPRIM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMOCYSTIS JIROVECII PNEUMONIA", 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"summary": null }, "primarysource": { "literaturereference": "FERNANDES JF, BONFIM C, KERBAUY FR, RODRIGUES M, ESTEVES I, SILVA NH ET AL. HAPLOIDENTICAL BONE MARROW TRANSPLANTATION WITH POST?TRANSPLANT CYCLOPHOSPHAMIDE FOR PATIENTS WITH X-LINKED ADRENOLEUKODYSTROPHY: A?SUITABLE CHOICE IN AN URGENT SITUATION. BONE MARROW TRANSPLANT. 2018 APR?53(4):392-399. DOI: 10.1038/S41409-017-0015-2.", "literaturereference_normalized": "haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with x linked adrenoleukodystrophy a suitable choice in an urgent situation", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20190603", "receivedate": "20190603", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16383073, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190711" }, { "companynumb": "BR-PANACEA BIOTEC LIMITED-000008", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { 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HAPLOIDENTICAL BONE MARROW TRANSPLANTATION WITH POST TRANSPLANT CYCLOPHOSPHAMIDE FOR PATIENTS WITH X-LINKED ADRENOLEUKODYSTROPHY: A?SUITABLE CHOICE IN AN URGENT SITUATION. BONE MARROW TRANSPLANT. 2018 APR?53(4):392-399. 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{ "abstract": "Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization. It includes benign trophoblastic disease (hydatidiform moles (HM)) and the malignant trophoblastic diseases or gestational trophoblastic neoplasia (GTN). The frequency of the GTD in Tunisia is one per 918 deliveries. The aim of this study is to analyze the clinical characteristics, treatment and outcomes of GTD at Salah Azaiez Institute (ISA). Medical records of women diagnosed with GTD at ISA from January 1st, 1981 to December 31st, 2012 were retrospectively reviewed. FIGO score was determined retrospectively for patients treated before 2002. One hundred and nine patients with GTN were included. Patients presented with metastases at 43% of cases. The most common metastatic sites were lung (30%) and vagina (13%). Fifty six (56 (51%) patients had low-risk and 21 (19%) cases had high-risk, the FIGO score was not assessed in 32 cases. After a median follow-up of 46 months, 21 patients were lost to follow-up, 12 patients died, 19 progressed and 8 relapsed. At 10 years, the OS rate was 85% and the PFS rate 79%. OS was significantly influenced by the presence of metastases at presentation (M0 100 % vs. Metastatic 62 %; p < 0.0001), FIGO stage (I-II 100% VS 61% and 65% for stage III and IV; p < 0.001), FIGO score (low-risk 99 % vs. high-risk 78 %; p < 0.001). GTN is a significant source of maternal morbidity with increased risk of mortality from complications if not detected early and treated promptly.", "affiliations": "Department of Medical Oncology at Salah Azaiz Institute, Tunis, Tunisia.;Department of Medical Oncology at Salah Azaiz Institute, Tunis, Tunisia.;Department of Medical Oncology at Salah Azaiz Institute, Tunis, Tunisia.;Department of Medical Oncology at Salah Azaiz Institute, Tunis, Tunisia.;\"C\" Department of Obstetrics and Gynecology, Tunis Maternity and Neonatology Center, Tunis, Tunisia.;Department of Medical Oncology at Salah Azaiz Institute, Tunis, Tunisia.;Department of Medical Oncology at Salah Azaiz Institute, Tunis, Tunisia.;Department of Medical Oncology at Salah Azaiz Institute, Tunis, Tunisia.;Department of Medical Oncology at Salah Azaiz Institute, Tunis, Tunisia.;Department of Medical Oncology at Salah Azaiz Institute, Tunis, Tunisia.;Department of Medical Oncology at Salah Azaiz Institute, Tunis, Tunisia.", "authors": "Batti|Rim|R|;Mokrani|Amina|A|;Rachdi|Haifa|H|;Raies|Henda|H|;Touhami|Omar|O|;Ayadi|Mouna|M|;Meddeb|Khadija|K|;Letaief|Feryel|F|;Yahiaoui|Yosra|Y|;Chraiet|Nesrine|N|;Mezlini|Amel|A|", "chemical_list": null, "country": "Uganda", "delete": false, "doi": "10.11604/pamj.2019.33.121.13897", "fulltext": "\n==== Front\nPan Afr Med JPan Afr Med JPAMJThe Pan African Medical Journal1937-8688The African Field Epidemiology Network PAMJ-33-12110.11604/pamj.2019.33.121.13897Case SeriesGestational trophoblastic neoplasia: experience at Salah Azaiez Institute Batti Rim 1&Mokrani Amina 1Rachdi Haifa 1Raies Henda 1Touhami Omar 2Ayadi Mouna 1Meddeb Khadija 1Letaief Feryel 1Yahiaoui Yosra 1Chraiet Nesrine 1Mezlini Amel 11 Department of Medical Oncology at Salah Azaiz Institute, Tunis, Tunisia2 “C” Department of Obstetrics and Gynecology, Tunis Maternity and Neonatology Center, Tunis, Tunisia& Corresponding author: Rim Batti, Department of Medical Oncology at Salah Azaiz Institute, Tunis, Tunisia17 6 2019 2019 33 12117 9 2017 14 4 2019 © Rim Batti et al.2019The Pan African Medical Journal - ISSN 1937-8688. This is an Open Access article distributed under the terms of the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization. It includes benign trophoblastic disease (hydatidiform moles (HM)) and the malignant trophoblastic diseases or gestational trophoblastic neoplasia (GTN). The frequency of the GTD in Tunisia is one per 918 deliveries. The aim of this study is to analyze the clinical characteristics, treatment and outcomes of GTD at Salah Azaiez Institute (ISA). Medical records of women diagnosed with GTD at ISA from January 1st, 1981 to December 31st, 2012 were retrospectively reviewed. FIGO score was determined retrospectively for patients treated before 2002. One hundred and nine patients with GTN were included. Patients presented with metastases at 43% of cases. The most common metastatic sites were lung (30%) and vagina (13%). Fifty six (56 (51%) patients had low-risk and 21 (19%) cases had high-risk, the FIGO score was not assessed in 32 cases. After a median follow-up of 46 months, 21 patients were lost to follow-up, 12 patients died, 19 progressed and 8 relapsed. At 10 years, the OS rate was 85% and the PFS rate 79%. OS was significantly influenced by the presence of metastases at presentation (M0 100 % vs. Metastatic 62 %; p < 0.0001), FIGO stage (I-II 100% VS 61% and 65% for stage III and IV; p < 0.001), FIGO score (low-risk 99 % vs. high-risk 78 %; p < 0.001). GTN is a significant source of maternal morbidity with increased risk of mortality from complications if not detected early and treated promptly.\n\nGestational trophoblastic diseasechoriocarcinomaoutcomesprognosis\n==== Body\nIntroduction\nGestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization. It includes benign trophoblastic disease (hydatidiform moles (HM)) and the malignant trophoblastic diseases or gestational trophoblastic neoplasia (GTN). The frequency of the GTD in Tunisia is one per 918 deliveries [1]. The aim of this study was to analyze the clinical characteristics, treatment and outcomes of GTD at Salah Azaiez Institute (ISA).\n\nMethods\nMedical records of women diagnosed with GTD at ISA from January 1st, 1981 to December 31st, 2012 were retrospectively reviewed. Patients with incomplete records were excluded from the study. Disease diagnosis, treatment, follow-up data, overall survival (OS) and progression free survival (PFS) were analyzed. FIGO score was determined retrospectively for patients treated before 2002. The data processing and analysis were carried out using the SPSS software version 20. Survival probabilities were estimated using Kaplan-Meier method. 126 patients were reported and included during 31 years (1981-2012). Of these cases, 17 (13%) were diagnosed hydatidiform mole and were excluded from this study. One hundred and nine (109) patients presented with GTN and were included.\n\nResults\nDuring the study period, 109 patients presented with GTN and were included. Their ages ranged between 18 and 53 years with an average of 34 years. Consanguinity was found in 33 cases (45% first degree). The median delay to diagnosis was 3 months (0-36). Sixty eight patients presented with amenorrhea followed by bleeding per vaginally or abortion followed by irregular bleeding per vaginally. GTN occurred after full-term pregnancy in two cases (after one and 14 months). Initial presenting features and reproductive history are summarized in Table 1. Performance status (PS) was = 0 in 35% (38 pts), PS = 1 in 31% (34 pts), PS = 2 in 11% (12 pts) and PS = 3 in 1 case. Ultra sound imaging was performed in all cases, only 72 reports were available. The typical snow storm appearance was described in 29 cases, heterogeneous mass in 30 cases (mean tumor size = 68 mm), increase in uterine size in 10 cases and there was an intraperitoneal effusion in three cases. Histological evidence was obtained in 66 cases. It was obtained by suction dilation and curettage in 41 cases, hysterectomy specimen in 16 cases and a biopsy of a metastasis in nine cases. Histology confirmed 43 cases of choriocarcinoma and 23 of invasive mole. In the other cases the diagnosis was retained on clinical, biological and radiological data. At diagnosis, 53 patients (48%) had localized disease (M0), whereas 43 had metastases and 13 were classified Mx. The most common metastatic sites at initial diagnosis were the lungs (33 cases), and vagina (15 cases). Three patients had brain metastasis, one patient hepatic metastasis, one patient had a sub diaphragmatic mass of 12 cm, one patient had suspicious pelvic nodes and one patient had a biceps muscle metastasis. The mean βhCG level before treatment was 152 170 UI/l (median 10 068). According to FIGO stage, 56 patients were stage I, 4 patients were stage II, 30 patients were stage III and 8 patients stage IV. The FIGO stage was not evaluable in 11 cases. According to FIGO 2002 scoring system, 56 cases were scored low risk and 21 high risk, the FIGO score was not evaluable for 32 patients.\n\nTable 1 Initial presenting features and reproductive history\n\n\tN\t\nAge at first intercourse\t\t\nMedian\t22\t\nMin\t15\t\nMax\t32\t\nAge at menarche\t\t\nMean\t13\t\nMin\t10\t\nMax\t17\t\nPast medical history\t\t\nPrior Hydatidiform mole\t11\t\nPrior spontaneous miscarriage\t50\t\nVoluntary interruption of pregnancy\t7\t\nGravidity\t\t\n0\t4\t\n1\t6\t\n2\t9\t\n≥3\t60\t\nMedian\t4\t\nParity\t\t\n0\t15\t\n1\t12\t\n2\t9\t\n≥3\t51\t\nMedian\t3\t\nNumber of children\t\t\n0\t11\t\n1\t12\t\n2\t11\t\n≥3\t45\t\nContraception\t\t\nEstrogen/progestin\t14\t\nintrauterine device\t5\t\nNo contraception\t9\t\nUnkown\t81\t\nInitial presenting features\t\t\nAbnormal vagina bleeding\t68\t\nAbdominal pain\t6\t\nMetastases\t8\t\nDuring the monitoring after molar pregnancy\t10\t\nChemotherapy: in the low-risk group, 24 patients received methotrexate (MTX) and 6 patients received ACT-D. Among high-risk patients, 13 received Cisplatin based regimen associated with actinomycin or adriamycin and etoposide, 1 patient did not receive cisplatin because of renal failure, 1 patient received BEP regimen and one patient received EMACO regimen. Patients treated before the WHO scoring system received different chemotherapy regimen, the decision of the type of chemotherapy was based on only clinical features. When retrospectively assessed, we noted that in four cases of high risk FIGO score patients received single agent chemotherapy and 24 patients with low-risk received combination agent chemotherapy. Treatment modalities are detailed in Table 2. Treatment toxicity totally happened in 50 patients. Grade 2 stomatitis was observed in 19 patients treated with MTX. There were two events of transient generalized skin rush after MTX single agent treatment. Five (4%) patients had grade IV toxicity and four patients died due to chemotherapy toxicity, all of them happened after cisplatine based chemotherapy. One patient had renal failure, two patients had grade IV febrile neutropenia, one patient had hepatic toxicity and one patient died after anaphylactic reaction after cisplatine perfusion.\n\nTable 2 Summary of chemotherapeutic protocols. Legend: CRI: complete response to initial chemotherapy\n\nDisease category/ CT\tNumber of patient\tCRIN\t\nLow risk\t\t\t\nSingle agent Methotrexate\t24\t17\t\nSingle agent Actinomycin\t6\t4\t\nCombination chemotherapy\t\t\t\nMTX-vincristine\t6\t6\t\nActinomycin-etoposide\t16\t8\t\nCisplatin-adriamycin-etoposide\t1\t1\t\nCisplatin-actino-etoposide\t1\t1\t\nUnkown\t2\t\t\nHigh Risk\t\t\t\nCombination chemotherapy\t\t\t\nCisplatin-actinomycin-etoposide\t8\t6\t\nCisplatin-adriamycin-etoposide\t3\t2\t\nCisplatin adriamycin\t1\tunkown\t\nEtoposide-actinomycin\t2\t0\t\nCisplatin actinomycin\t1\t0\t\nBEP\t1\t1\t\nEMACO\t1\t\t\nSingle agent CT\t\t\t\nActionomycin\t2\t0\t\nMethotrexate\t1\t0\t\nUnkown\t1\t\t\nPatients with not assessed FIGO score\t\t\t\nSingle agent CT\nMethotrexate\nCombination CT\t8\t\t\nActinomycin-etoposide\t5\t\t\nMethotrexate-oncovin\t8\t\t\nActinomycin-vinblastin\t2\t\t\nMethtrexate-vinblastine\t1\t\t\nEP/EMA\t1\t\t\nBEP\t1\t\t\nCisplatin-actino-etoposide\t1\t\t\nCisplatin-actinomycin-bleo-velbe-Endoxan\t1\t\t\nUnkown\t4\t\t\nSurgery: eighteen patients underwent initial surgery, 4 patients had uterine perforation and 14 had excessive uterine bleeding. One patient had initial surgery for a biceps muscle metastasis. Five patients were operated after chemotherapy for residual disease.\n\nRadiotherapy: two patients had radiotherapy, one for brain metastasis and the other a hemostatic radiotherapy for a bleeding vaginal metastasis.\n\nOutcome and follow up: the response to treatment was evaluated during follow-up by clinical examination, ßhCG levels and imaging as and when required. Twenty one (21) patients were lost to follow-up and were excluded from survival analysis. After a median follow-up from initial diagnosis of 46 months, 72 patients achieved complete response, 12 patients died (eight due to disease progression and four due to chemotherapy toxicity), 19 patients progressed to initial chemotherapy and eight patients relapsed. At 10 years, OS was 82%. The mean OS was 196 months IC95% (175-218) (Figure 1). Mean PFS was 185 months IC95% (164-205), at 10 years PFS rate was 79% (Figure 2). OS was significantly influenced by the presence of metastases at presentation (M0 100% vs. Metastatic 62%; p < 0.0001) (Figure 3). Patients with advanced stage disease had poor survival when compared to the early stage group (I 100%, II 95% vs. III 62%, IV 62%; p = 0.001) (Figure 4). Patients with high-risk prognostic score compared to the low risk group showed poorer outcome (low-risk 99% vs. high-risk 76%; p = 0.003) (Figure 5). After achieving treatment, 13 conceptions were reported resulting in no molar pregnancy: 3 miscarriage and 10 full-term pregnancies. The mean time to pregnancy after achieving treatment was 37 months (range 8-123 months). Nine patients had full-term healthy births and a still birth in one case. One patient had repeated artificial insemination failure.\n\nFigure 1 Kaplan-Meier estimates of overall survival\n\nFigure 2 Kaplan-Meier estimates of progression free survival\n\nFigure 3 Kaplan-Meier estimates of overall survival by distant metastasis\n\nFigure 4 Kaplan-Meier estimates of overall survival by FIGO stage\n\nFigure 5 Kaplan-Meier estimates of overall survival by FIGO prognostic score\n\nDiscussion\nGTD is a heterogeneous rare group of clinical conditions characterized by disordered differentiation and/or the proliferation of trophoblastic epithelium. GTN can arise after any type of pregnancy and can develop months or years after prior pregnancy. It affects women in the age group of 20 to 30 years. In our study, the median age was 34 years which is in comparison to peer reviewed published literature [2]. An increased risk of GTN have been linked to hormonal factors such as light menstrual flow, a menarche after 12 years-old, the use of oral contraceptive [3]. Other potential risk factors have also been reported for example; blood group A, past history of hydatidiform mole and maternal age [4]. GTN is a highly vascular disease and taking a biopsy of lesions are extremely risky. Histological confirmation is not essential before commencing chemotherapy. However, it may be useful to confirm diagnosis and obtain genetic analysis. Genotyping will be helpful to determine the causative pregnancy in patients with multiple pregnancies and to distinguish GTN from non gestational tumor [5]. The ßhCG measurement is essential for diagnosis and management of GTD. Some assays can lead to false negative or false positive results because hCG can exist in different forms in patients with GTN. It's essential that the hCG assay can measure all forms of hCG [3]. Since 2002, the management of GTN is guided by the FIGO prognostic scoring. Patients with high risk disease had 0% chance to be cured with a single-agent chemotherapy. One recent study re-evaluated all prognostic risk factors involved in the FIGO scoring system in 813 patients with GTN and proposed a simplified alternative using only five factors [6]. GTN most frequently spreads to the lung. In our study, vaginal metastases were present in 13%. In reported series vaginal metastases are present in 4-30% in GTN [7, 8]. Patients with low-risk GTN can usually be treated successfully with single-agent chemotherapy. In our series of 56 low-risk patients, we observed a complete remission rate of 70% to single-agent Methotrexate and 66% to single-agent Dactinomycin. A randomized clinical trial compared biweekly Dactinomycin versus weekly Methotrexate demonstrated a superior response rate for Dactinomycin over Methotrexate (69 vs. 53% ; p = 0.015) [9].\n\nRetrospective reviews of patients with low-risk GTN treated with single-agent chemotherapy showed significantly higher primary remission rate with Dactinomycin than with Methotrexate regimen [10, 11]. Due to decreased cost and the good tolerance of Methotrexate, especially for not inducing hair loss, Methotrexate was preferred as first line treatment. However a recent study suggest that women with hCG >400,000 UI/l are unlikely to be cured by single-agent chemotherapy and should be treated by multi-agent chemotherapy as first line treatment [12]. Among the patients with high-risk GTN, our data supports the effectiveness of the combination chemotherapy. The preferred regimen in our study was the actinomycin, cisplatin and etoposide French regimen. The complete response rate with this regimen was 94.7% and the five-year OS 97%. This regimen is highly active as first-line and as treatment for persistent/recurrent GTN [13]. Several regimens were developed. EMACO is used worldwide and is the optimal primary treatment because of short term toxicity and effectiveness [14]. A Korean study demonstrated a higher remission rate (90.6%) with EMACO when compared with others regimens [15]. Patients with advanced disease may benefit from initial low dose chemotherapy to reduce early deaths [16]. Our study confirms the lower outcomes in patients with advanced-stage disease, metastatic disease and high-risk prognostic score [11, 17]. The overall worldwide survival rate of low-risk GTN group is 100%, and 80-90% for high-risk GTN group [11]. The overall survival rate for patients with GTN treated at our institute was 85%. The reproductive success rates and gestational complications have become a concern for women treated for GTD. EMACO regimen may induce menopause three years earlier but fertility is not affected and 83% of women became pregnant after Methotrexate or EMACO [3]. The number of studies in the literature regarding this theme is small. The studies highlight that there is no change in fertility [18]. Under close monitoring, patients may conceive six months after achieving complete response [19]. One study demonstrated a slight increase in stillbirth after GTN treatment [20]. In our study, conception occurred resulting in no molar pregnancy, miscarriage and full-term pregnancy.\n\nConclusion\nGTN is a significant source of maternal morbidity with increased risk of mortality from complications if not detected early and treated promptly. Management of gestational disease should ideally be done in a specialized multi-disciplinary environment.\n\nWhat is known about this topic\nGestational trophoblastic neoplasia are malignant disorders of invasive mole, choriocarcinoma, and the rare placental-site trophoblastic tumour. Overall cure rates can exceed 98%. This success can be explained by the development of effective treatments and centralization of care.\n\nWhat this study adds\nReport a Tunisian experience with gestational trophoblastic neoplasia;\n\nThe results of this study can help to encourage a specialized multi-disciplinary environment for the management of gestational disease.\n\nCompeting interests\nThe authors declare no competing interests.\n\nAuthors’ contributions\nRim Batti, Amina Mokrani and Haifa Rachdi performed acquisition of patient data, analysis and interpretation of patient data. Henda Raies developed the study conception and design. Omar Touhami, Mouna Ayadi, Khadija Meddeb,Feryel Letaief, Yosra Yahiaoui, Nesrine Chraiet, Amel Mezlini performed critical revision of the manuscript. All authors have read and agreed to the final version of this manuscript.\n==== Refs\nReferences\n1 Ben Ayed F Boussen H Kraïem A El May A El May M Jaafoura H Placental tumors in Tunisia: apropos of 35 cases Tunis Med 1986 64 2 137 41 3739023 \n2 Sita-Lumsden A Short D Lindsay I Sebire NJ Adjogatse D Seckl MJ Treatment outcomes for 618 women with gestational trophoblastic tumours following a molar pregnancy at the Charing Cross Hospital, 2000-2009 Br J Cancer 2012 107 11 1810 4 23059744 \n3 Seckl MJ Sebire NJ Berkowitz RS Gestational trophoblastic disease The Lancet 2010 376 9742 717 29 \n4 Strohl AE Lurain JR Clinical epidemiology of gestational trophoblastic disease Curr Obstet Gynecol Rep 2014 3 1 40 3 \n5 Seckl MJ Sebire NJ Fisher RA Golfier F Massuger L Sessa C Gestational trophoblastic disease: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up Ann Oncol 2013 24 Suppl 6 39 50 \n6 Eysbouts YK Ottevanger PB Massuger LFG IntHout J Short D Harvey R Can the FIGO 2000 scoring system for gestational trophoblastic neoplasia be simplified: a new retrospective analysis from a nationwide dataset Ann Oncol 2017 28 8 1856 1861 28459944 \n7 Berry E Hagopian GS Lurain JR Vaginal metastases in gestational trophoblastic neoplasia J Reprod Med 2008 53 7 487 92 18720923 \n8 Cagayan MS Vaginal metastases complicating gestational trophoblastic neoplasia J Reprod Med 2010 55 5-6 229 35 20626179 \n9 Osborne RJ Filiaci V Schink JC Mannel RS Alvarez Secord A Kelley JL Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a gynecologic oncology group study J Clin Oncol 2011 29 7 825 31 21263100 \n10 Matsui H Iitsuka Y Seki K Sekiya S Comparison of chemotherapies with methotrexate, VP-16 and actinomycin-D in low-risk gestational trophoblastic disease: Remission rates and drug toxicities Gynecol Obstet Invest 1998 46 1 5 8 9692333 \n11 Al-Husaini H Soudy H Darwish A Ahmed M Eltigani A Edesa W Gestational trophoblastic neoplasia: treatment outcomes from a single institutional experience Clin Transl Oncol 2015 17 5 409 15 25398721 \n12 McGrath S Short D Harvey R Schmid P Savage PM Seckl MJ The management and outcome of women with post-hydatidiform mole “low-risk” gestational trophoblastic neoplasia, but hCG levels in excess of 100 000IU/l Br J Cancer 2010 102 5 810 4 20160727 \n13 Even C Pautier P Duvillard P Floquet A Kerbrat P Troalen F Actinomycin D, cisplatin, and etoposide regimen is associated with almost universal cure in patients with high-risk gestational trophoblastic neoplasia Eur J Cancer 2014 50 12 2082 9 24910417 \n14 Deng L Zhang J Wu T Lawrie TA Combination chemotherapy for primary treatment of high-risk gestational trophoblastic tumour Cochrane Database Syst Rev 2013 1 CD005196 23440800 \n15 Kim SJ Na YJ Jung SG Kim CJ Bae SN Lee C Management of high-risk hydatidiform mole and persistent gestational trophoblastic neoplasia: the Korean experience J Reprod Med 2007 52 9 819 30 17939600 \n16 Alifrangis C Agarwal R Short D Fisher RA Sebire NJ Harvey R EMA/CO for high-risk gestational trophoblastic neoplasia: good outcomes with induction low-dose etoposide-cisplatin and genetic analysis J Clin Oncol 2013 31 2 280 6 23233709 \n17 Yanaranop M Potikul C Tuipae S A 10-year clinical experience of gestational trophoblastic disease at Rajavithi Hospital, 2001-2010 J Med Assoc Thail 2016 99 Suppl 2 S17 27 \n18 Garcia MT Lin LH Fushida K Francisco RPV Zugaib M Pregnancy outcomes after chemotherapy for trophoblastic neoplasia Rev Assoc Medica Bras 2016 62 9 837 42 \n19 Brown J Naumann RW Seckl MJ Schink J 15 years of progress in gestational trophoblastic disease: Scoring, standardization, and salvage Gynecol Oncol 2017 144 1 200 7 27743739 \n20 Berkowitz RS Tuncer ZS Bernstein MR Goldstein DP Management of gestational trophoblastic diseases: subsequent pregnancy experience Semin Oncol 2000 27 6 678 85 11130475\n\n", "fulltext_license": "CC BY", "issn_linking": null, "issue": "33()", "journal": "The Pan African medical journal", "keywords": "Gestational trophoblastic disease; choriocarcinoma; outcomes; prognosis", "medline_ta": "Pan Afr Med J", "mesh_terms": "D000293:Adolescent; D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D031901:Gestational Trophoblastic Disease; D006801:Humans; D006828:Hydatidiform Mole; D008175:Lung Neoplasms; D008875:Middle Aged; D009367:Neoplasm Staging; D011247:Pregnancy; D000077982:Progression-Free Survival; D012189:Retrospective Studies; D015996:Survival Rate; D014416:Tunisia; D014625:Vaginal Neoplasms; D055815:Young Adult", "nlm_unique_id": "101517926", "other_id": null, "pages": "121", "pmc": null, "pmid": "31489099", "pubdate": "2019", "publication_types": "D016428:Journal Article", "references": "11130475;17939600;18720923;20160727;20626179;20673583;21263100;23059744;23233709;23440800;23999759;24910417;25398721;27266212;27743739;28001257;28459944;3739023;9692333", "title": "Gestational trophoblastic neoplasia: experience at Salah Azaiez Institute.", "title_normalized": "gestational trophoblastic neoplasia experience at salah azaiez institute" }

[ { "companynumb": "TN-MYLANLABS-2019M1095211", "fulfillexpeditecriteria": "1", "occurcountry": "TN", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "091062", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GESTATIONAL TROPHOBLASTIC TUMOUR", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hepatotoxicity", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Maternal exposure during pregnancy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "BATTI R, MOKRANI A, RACHDI H, RAIES H, TOUHAMI O, AYADI M, ET AL. GESTATIONAL TROPHOBLASTIC NEOPLASIA: EXPERIENCE AT SALAH AZAIEZ INSTITUTE. PAN-AFR-MED-J 2019?33:121.", "literaturereference_normalized": "gestational trophoblastic neoplasia experience at salah azaiez institute", "qualification": "3", "reportercountry": "TN" }, "primarysourcecountry": "TN", "receiptdate": "20191011", "receivedate": "20191011", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 16907963, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20200122" } ]

{ "abstract": "Globally, > 5-10 million people are estimated to be infected with Human T-lymphotropic virus type 1 (HTLV-1), of whom ~ 5% develop adult T-cell leukemia/lymphoma (ATL). Despite advances in chemotherapy, overall survival (OS) has not improved in the 35 years since HTLV-1 was first described. In Europe/USA, combination treatment with zidovudine and interferon-α (ZDV/IFN-α) has substantially changed the management of patients with the leukemic subtypes of ATL (acute or unfavorable chronic ATL) and is under clinical trial evaluation in Japan. However, there is only a single published report of long-term clinical remission on discontinuing ZDV/IFN-α therapy and the optimal duration of treatment is unknown. Anecdotal cases where therapy is discontinued due to side effects or compliance have been associated with rapid disease relapse, and it has been widely accepted that the majority of patients will require life-long therapy. The development of molecular methods to quantify minimal residual disease is essential to potentially guide therapy for individual patients. Here, for the first time, we report molecular evidence that supports long-term clinical remission in a patient who was previously treated with ZDV/IFN-α for 5 years, and who has now been off all therapy for over 6 years.", "affiliations": "National Centre for Human Retrovirology, Imperial College Healthcare NHS Trust, Winston Churchill Wing, St Mary's Hospital, Praed Street, London, W2 1NY, UK. [email protected].;Division of Infectious Diseases, Department of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK.;Division of Infectious Diseases, Department of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK.;Division of Infectious Diseases, Department of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK.;Veterinary Department, Faculty of Sciences, Namur Research Institute for Life Sciences, University of Namur, 61 rue de Bruxelles, 5000, Namur, Belgium.;Division of Infectious Diseases, Department of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK.;Division of Infectious Diseases, Department of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK.;Division of Infectious Diseases, Department of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK.;Division of Infectious Diseases, Department of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK.;National Centre for Human Retrovirology, Imperial College Healthcare NHS Trust, Winston Churchill Wing, St Mary's Hospital, Praed Street, London, W2 1NY, UK.", "authors": "Cook|Lucy B|LB|;Rowan|Aileen G|AG|;Demontis|Maria A|MA|;Sagawe|Sophie|S|;Gillet|Nicolas A|NA|;Melamed|Anat|A|;Greiller|Claire|C|;Witkover|Aviva|A|;Bangham|Charles R M|CRM|;Taylor|Graham P|GP|", "chemical_list": "D000998:Antiviral Agents; D016898:Interferon-alpha; D015215:Zidovudine", "country": "Japan", "delete": false, "doi": "10.1007/s12185-017-2361-7", "fulltext": null, "fulltext_license": null, "issn_linking": "0925-5710", "issue": "107(3)", "journal": "International journal of hematology", "keywords": "Chronic ATL; HTLV; Zidovudine/interferon-α", "medline_ta": "Int J Hematol", "mesh_terms": "D000328:Adult; D064591:Allografts; D000998:Antiviral Agents; D016026:Bone Marrow Transplantation; D002908:Chronic Disease; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D015368:Human T-lymphotropic virus 1; D006801:Humans; D016898:Interferon-alpha; D015459:Leukemia-Lymphoma, Adult T-Cell; D008297:Male; D018365:Neoplasm, Residual; D012074:Remission Induction; D013997:Time Factors; D015215:Zidovudine", "nlm_unique_id": "9111627", "other_id": null, "pages": "378-382", "pmc": null, "pmid": "29090417", "pubdate": "2018-03", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": "9028326;7760891;20448111;20348391;25733162;23162541;26361794;21228324;22875625;22955925;7760890;12430931;20479287;27105228;20585095;22894552;1751370;17968021;8874205", "title": "Long-term clinical remission maintained after cessation of zidovudine and interferon-α therapy in chronic adult T-cell leukemia/lymphoma.", "title_normalized": "long term clinical remission maintained after cessation of zidovudine and interferon therapy in chronic adult t cell leukemia lymphoma" }

[ { "companynumb": "GB-ROCHE-2088898", "fulfillexpeditecriteria": "1", "occurcountry": "GB", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "ZIDOVUDINE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZIDOVUDINE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ZIDOVUDINE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ADULT T-CELL LYMPHOMA/LEUKAEMIA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": "200511", "drugstartdateformat": "610", "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZIDOVUDINE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PEGINTERFERON ALFA-2A" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "103964", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "135-180 MCG", "drugenddate": null, "drugenddateformat": null, "drugindication": "ADULT T-CELL LYMPHOMA/LEUKAEMIA", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEGASYS" } ], "patientagegroup": null, "patientonsetage": "4", "patientonsetageunit": "800", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Transaminases increased", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 201102" } }, "primarysource": { "literaturereference": "COOK L, ROWAN AG, DEMONTIS MA, SAGAWE S, GILLET NA, MELAMED A ET AL. LONG-TERM CLINICAL REMISSION MAINTAINED AFTER CESSATION OF ZIDOVUDINE AND INTERFERON- THERAPY IN CHRONIC ADULT T-CELL LEUKEMIA/LYMPHOMA.. INT. J HEMATOL 2018?107 (3):378-382.", "literaturereference_normalized": "long term clinical remission maintained after cessation of zidovudine and interferon therapy in chronic adult t cell leukemia lymphoma", "qualification": "3", "reportercountry": "GB" }, "primarysourcecountry": "GB", "receiptdate": "20180410", "receivedate": "20180326", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14678364, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": 1, "seriousnessother": null, "transmissiondate": "20180711" } ]

{ "abstract": "Cardiac blood cysts are very rare in adults. Their etiology, pathogenesis, and optimal management remain unclear. We report a case of a large left atrial cystic mass with clinical and imaging characteristics of a blood cyst that vanished between chest CT angiogram and trans-esophageal echocardiogram examinations done 2 days apart, without embolic phenomena. This patient likely had a blood cyst that spontaneously ruptured. This case is unusual since we did not find a case published in the English literature of a spontaneously ruptured blood cyst.", "affiliations": "Internal Medicine, University of Kansas School of Medicine - Wichita, 1010 N Kansas Street, Wichita, KS, 67214, United States of America. Electronic address: [email protected].;Internal Medicine, University of Kansas School of Medicine - Wichita, 1010 N Kansas Street, Wichita, KS, 67214, United States of America. Electronic address: [email protected].;Internal Medicine, University of Kansas School of Medicine - Wichita, 1010 N Kansas Street, Wichita, KS, 67214, United States of America.;Internal Medicine, University of Kansas School of Medicine - Wichita, 1010 N Kansas Street, Wichita, KS, 67214, United States of America. Electronic address: [email protected].;Internal Medicine, University of Kansas School of Medicine - Wichita, 1010 N Kansas Street, Wichita, KS, 67214, United States of America; Heartland Cardiology, 3535 N Webb Rd, Wichita, KS, 67226, United States of America.", "authors": "Ndunda|Paul M|PM|;Khayyat|Sinan|S|;Muutu|Tabitha|T|;Munguti|Cyrus|C|;Shaheen|Wassim|W|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1016/j.carrev.2019.05.019", "fulltext": null, "fulltext_license": null, "issn_linking": "1878-0938", "issue": "21(11S)", "journal": "Cardiovascular revascularization medicine : including molecular interventions", "keywords": "Blood cyst; Cystic left atrial mass; Disappearing left atrial mass; Ruptured", "medline_ta": "Cardiovasc Revasc Med", "mesh_terms": "D003560:Cysts; D006801:Humans; D012421:Rupture; D013909:Thorax; D014057:Tomography, X-Ray Computed; D014652:Vascular Diseases", "nlm_unique_id": "101238551", "other_id": null, "pages": "73-76", "pmc": null, "pmid": "31235432", "pubdate": "2020-11", "publication_types": "D002363:Case Reports", "references": null, "title": "A Vanishing Left Atrial Cystic Mass: A Ruptured Blood Cyst?", "title_normalized": "a vanishing left atrial cystic mass a ruptured blood cyst" }

[ { "companynumb": "US-BAYER-2021-034850", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "APIXABAN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "APIXABAN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ASPIRIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "999999", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACETYLSALICYLIC ACID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "HEPARIN SODIUM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HEPARIN" } ], "patientagegroup": "6", "patientonsetage": "74", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Haemorrhagic cyst", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Mitral valve incompetence", "reactionmeddraversionpt": "23.1", "reactionoutcome": null }, { "reactionmeddrapt": "Labelled drug-drug interaction medication error", "reactionmeddraversionpt": "23.1", "reactionoutcome": null } ], "summary": null }, "primarysource": { "literaturereference": "NDUNDA PM, KHAYYAT S, MUUTU T, MUNGUTI C, SHAHEEN W. A VANISHING LEFT ATRIAL CYSTIC MASS: A RUPTURED BLOOD CYST?. 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{ "abstract": "Neonatal hyperglycemia is common in extremely low birth weight (ELBW) infants because of physiologic stress, exogenous glucose infusion, and postnatal corticosteroid therapy for hypotension, adrenal insufficiency, and pulmonary immaturity. The use of long-acting insulin glargine has been described in the treatment of transient neonatal diabetes in the premature infant, but in these reports is a lack of regard to its use in the treatment of iatrogenic neonatal hyperglycemia. We present the case of an ELBW infant with significant hyperglycemia that was refractory to usual treatment but demonstrated a favorable response to long-acting subcutaneous insulin glargine. The pharmacokinetics on regular insulin and long-acting insulin are different. Regular insulin is broken down into biologically active monomers after subcutaneous injection, and long-acting insulin forms microprecipitates and is gradually released to the body at a neutral physiologic pH after subcutaneous injection. Pharmacokinetics of both regular insulin and long-acting insulin are not clear in ELBW infants. However, with further research on long-acting insulin, it can be used safely to achieve consistent euglycemia with once-daily administration in neonatal hyperglycemia.", "affiliations": "Department of Pediatrics, Madigan Army Medical Center, Tacoma, Washington [email protected].;Department of Pediatrics, Madigan Army Medical Center, Tacoma, Washington.;Department of Pediatrics, Madigan Army Medical Center, Tacoma, Washington.;Department of Pediatrics, Madigan Army Medical Center, Tacoma, Washington.", "authors": "Hwang|Min J|MJ|;Newman|Robert|R|;Philla|Katherine|K|;Flanigan|Elizabeth|E|", "chemical_list": "D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D006854:Hydrocortisone", "country": "United States", "delete": false, "doi": "10.1542/peds.2016-1638", "fulltext": null, "fulltext_license": null, "issn_linking": "0031-4005", "issue": "141(Suppl 5)", "journal": "Pediatrics", "keywords": null, "medline_ta": "Pediatrics", "mesh_terms": "D006801:Humans; D006854:Hydrocortisone; D006943:Hyperglycemia; D007004:Hypoglycemic Agents; D007022:Hypotension; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases; D007279:Injections, Subcutaneous; D000069036:Insulin Glargine", "nlm_unique_id": "0376422", "other_id": null, "pages": "S399-S403", "pmc": null, "pmid": "29610159", "pubdate": "2018-04", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Use of Insulin Glargine in the Management of Neonatal Hyperglycemia in an ELBW Infant.", "title_normalized": "use of insulin glargine in the management of neonatal hyperglycemia in an elbw infant" }

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USE OF INSULIN GLARGINE IN THE MANAGEMENT OF NEONATAL HYPERGLYCEMIA IN AN ELBW INFANT. PEDIATRICS 2018?141 (SUPPL. 5):S399-S403.", "literaturereference_normalized": "use of insulin glargine in the management of neonatal hyperglycemia in an elbw infant", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20190606", "receivedate": "20190606", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16400573, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190711" } ]

{ "abstract": "Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox-Gastaut syndrome, a severe developmental epileptic encephalopathy.\n\n\n\nIn this double-blind, placebo-controlled trial conducted at 30 clinical centers, we randomly assigned patients with the Lennox-Gastaut syndrome (age range, 2 to 55 years) who had had two or more drop seizures per week during a 28-day baseline period to receive cannabidiol oral solution at a dose of either 20 mg per kilogram of body weight (20-mg cannabidiol group) or 10 mg per kilogram (10-mg cannabidiol group) or matching placebo, administered in two equally divided doses daily for 14 weeks. The primary outcome was the percentage change from baseline in the frequency of drop seizures (average per 28 days) during the treatment period.\n\n\n\nA total of 225 patients were enrolled; 76 patients were assigned to the 20-mg cannabidiol group, 73 to the 10-mg cannabidiol group, and 76 to the placebo group. During the 28-day baseline period, the median number of drop seizures was 85 in all trial groups combined. The median percent reduction from baseline in drop-seizure frequency during the treatment period was 41.9% in the 20-mg cannabidiol group, 37.2% in the 10-mg cannabidiol group, and 17.2% in the placebo group (P=0.005 for the 20-mg cannabidiol group vs. placebo group, and P=0.002 for the 10-mg cannabidiol group vs. placebo group). The most common adverse events among the patients in the cannabidiol groups were somnolence, decreased appetite, and diarrhea; these events occurred more frequently in the higher-dose group. Six patients in the 20-mg cannabidiol group and 1 patient in the 10-mg cannabidiol group discontinued the trial medication because of adverse events and were withdrawn from the trial. Fourteen patients who received cannabidiol (9%) had elevated liver aminotransferase concentrations.\n\n\n\nAmong children and adults with the Lennox-Gastaut syndrome, the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo. Adverse events with cannabidiol included elevated liver aminotransferase concentrations. (Funded by GW Pharmaceuticals; GWPCARE3 ClinicalTrials.gov number, NCT02224560 .).", "affiliations": "From New York University Langone Comprehensive Epilepsy Center, New York (O.D.); Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus (A.D.P.), and the University of Cincinnati Medical Center, Department of Neurology, Cincinnati (M.P.) - all in Ohio; UCL Great Ormond Street Institute of Child Health, London (J.H.C.), GW Research Ltd., Cambridge (S.M.G., C.R., D.C.), and the Royal Hospital for Children and School of Medicine, University of Glasgow, Glasgow (S.M.Z.) - all in the United Kingdom; Refractory Epilepsy Unit, Neurology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain (V.V.); the Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester, MN (E.C.W.); and Greenwich Biosciences, Carlsbad, CA (K.E.V.).;From New York University Langone Comprehensive Epilepsy Center, New York (O.D.); Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus (A.D.P.), and the University of Cincinnati Medical Center, Department of Neurology, Cincinnati (M.P.) - all in Ohio; UCL Great Ormond Street Institute of Child Health, London (J.H.C.), GW Research Ltd., Cambridge (S.M.G., C.R., D.C.), and the Royal Hospital for Children and School of Medicine, University of Glasgow, Glasgow (S.M.Z.) - all in the United Kingdom; Refractory Epilepsy Unit, Neurology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain (V.V.); the Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester, MN (E.C.W.); and Greenwich Biosciences, Carlsbad, CA (K.E.V.).;From New York University Langone Comprehensive Epilepsy Center, New York (O.D.); Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus (A.D.P.), and the University of Cincinnati Medical Center, Department of Neurology, Cincinnati (M.P.) - all in Ohio; UCL Great Ormond Street Institute of Child Health, London (J.H.C.), GW Research Ltd., Cambridge (S.M.G., C.R., D.C.), and the Royal Hospital for Children and School of Medicine, University of Glasgow, Glasgow (S.M.Z.) - all in the United Kingdom; Refractory Epilepsy Unit, Neurology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain (V.V.); the Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester, MN (E.C.W.); and Greenwich Biosciences, Carlsbad, CA (K.E.V.).;From New York University Langone Comprehensive Epilepsy Center, New York (O.D.); Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus (A.D.P.), and the University of Cincinnati Medical Center, Department of Neurology, Cincinnati (M.P.) - all in Ohio; UCL Great Ormond Street Institute of Child Health, London (J.H.C.), GW Research Ltd., Cambridge (S.M.G., C.R., D.C.), and the Royal Hospital for Children and School of Medicine, University of Glasgow, Glasgow (S.M.Z.) - all in the United Kingdom; Refractory Epilepsy Unit, Neurology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain (V.V.); the Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester, MN (E.C.W.); and Greenwich Biosciences, Carlsbad, CA (K.E.V.).;From New York University Langone Comprehensive Epilepsy Center, New York (O.D.); Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus (A.D.P.), and the University of Cincinnati Medical Center, Department of Neurology, Cincinnati (M.P.) - all in Ohio; UCL Great Ormond Street Institute of Child Health, London (J.H.C.), GW Research Ltd., Cambridge (S.M.G., C.R., D.C.), and the Royal Hospital for Children and School of Medicine, University of Glasgow, Glasgow (S.M.Z.) - all in the United Kingdom; Refractory Epilepsy Unit, Neurology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain (V.V.); the Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester, MN (E.C.W.); and Greenwich Biosciences, Carlsbad, CA (K.E.V.).;From New York University Langone Comprehensive Epilepsy Center, New York (O.D.); Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus (A.D.P.), and the University of Cincinnati Medical Center, Department of Neurology, Cincinnati (M.P.) - all in Ohio; UCL Great Ormond Street Institute of Child Health, London (J.H.C.), GW Research Ltd., Cambridge (S.M.G., C.R., D.C.), and the Royal Hospital for Children and School of Medicine, University of Glasgow, Glasgow (S.M.Z.) - all in the United Kingdom; Refractory Epilepsy Unit, Neurology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain (V.V.); the Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester, MN (E.C.W.); and Greenwich Biosciences, Carlsbad, CA (K.E.V.).;From New York University Langone Comprehensive Epilepsy Center, New York (O.D.); Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus (A.D.P.), and the University of Cincinnati Medical Center, Department of Neurology, Cincinnati (M.P.) - all in Ohio; UCL Great Ormond Street Institute of Child Health, London (J.H.C.), GW Research Ltd., Cambridge (S.M.G., C.R., D.C.), and the Royal Hospital for Children and School of Medicine, University of Glasgow, Glasgow (S.M.Z.) - all in the United Kingdom; Refractory Epilepsy Unit, Neurology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain (V.V.); the Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester, MN (E.C.W.); and Greenwich Biosciences, Carlsbad, CA (K.E.V.).;From New York University Langone Comprehensive Epilepsy Center, New York (O.D.); Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus (A.D.P.), and the University of Cincinnati Medical Center, Department of Neurology, Cincinnati (M.P.) - all in Ohio; UCL Great Ormond Street Institute of Child Health, London (J.H.C.), GW Research Ltd., Cambridge (S.M.G., C.R., D.C.), and the Royal Hospital for Children and School of Medicine, University of Glasgow, Glasgow (S.M.Z.) - all in the United Kingdom; Refractory Epilepsy Unit, Neurology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain (V.V.); the Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester, MN (E.C.W.); and Greenwich Biosciences, Carlsbad, CA (K.E.V.).;From New York University Langone Comprehensive Epilepsy Center, New York (O.D.); Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus (A.D.P.), and the University of Cincinnati Medical Center, Department of Neurology, Cincinnati (M.P.) - all in Ohio; UCL Great Ormond Street Institute of Child Health, London (J.H.C.), GW Research Ltd., Cambridge (S.M.G., C.R., D.C.), and the Royal Hospital for Children and School of Medicine, University of Glasgow, Glasgow (S.M.Z.) - all in the United Kingdom; Refractory Epilepsy Unit, Neurology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain (V.V.); the Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester, MN (E.C.W.); and Greenwich Biosciences, Carlsbad, CA (K.E.V.).;From New York University Langone Comprehensive Epilepsy Center, New York (O.D.); Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus (A.D.P.), and the University of Cincinnati Medical Center, Department of Neurology, Cincinnati (M.P.) - all in Ohio; UCL Great Ormond Street Institute of Child Health, London (J.H.C.), GW Research Ltd., Cambridge (S.M.G., C.R., D.C.), and the Royal Hospital for Children and School of Medicine, University of Glasgow, Glasgow (S.M.Z.) - all in the United Kingdom; Refractory Epilepsy Unit, Neurology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain (V.V.); the Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester, MN (E.C.W.); and Greenwich Biosciences, Carlsbad, CA (K.E.V.).;From New York University Langone Comprehensive Epilepsy Center, New York (O.D.); Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus (A.D.P.), and the University of Cincinnati Medical Center, Department of Neurology, Cincinnati (M.P.) - all in Ohio; UCL Great Ormond Street Institute of Child Health, London (J.H.C.), GW Research Ltd., Cambridge (S.M.G., C.R., D.C.), and the Royal Hospital for Children and School of Medicine, University of Glasgow, Glasgow (S.M.Z.) - all in the United Kingdom; Refractory Epilepsy Unit, Neurology Service, Hospital Universitario y Politécnico La Fe, Valencia, Spain (V.V.); the Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester, MN (E.C.W.); and Greenwich Biosciences, Carlsbad, CA (K.E.V.).", "authors": "Devinsky|Orrin|O|;Patel|Anup D|AD|;Cross|J Helen|JH|;Villanueva|Vicente|V|;Wirrell|Elaine C|EC|;Privitera|Michael|M|;Greenwood|Sam M|SM|;Roberts|Claire|C|;Checketts|Daniel|D|;VanLandingham|Kevan E|KE|;Zuberi|Sameer M|SM|;|||", "chemical_list": "D000927:Anticonvulsants; D002185:Cannabidiol; D000637:Transaminases", "country": "United States", "delete": false, "doi": "10.1056/NEJMoa1714631", "fulltext": null, "fulltext_license": null, "issn_linking": "0028-4793", "issue": "378(20)", "journal": "The New England journal of medicine", "keywords": null, "medline_ta": "N Engl J Med", "mesh_terms": "D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants; D002185:Cannabidiol; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D065768:Lennox Gastaut Syndrome; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012640:Seizures; D000637:Transaminases; D055815:Young Adult", "nlm_unique_id": "0255562", "other_id": null, "pages": "1888-1897", "pmc": null, "pmid": "29768152", "pubdate": "2018-05-17", "publication_types": "D017428:Clinical Trial, Phase III; D003160:Comparative Study; D016428:Journal Article; D016448:Multicenter Study; D016449:Randomized Controlled Trial; D013485:Research Support, Non-U.S. Gov't", "references": null, "title": "Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome.", "title_normalized": "effect of cannabidiol on drop seizures in the lennox gastaut syndrome" }

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{ "abstract": "Pediatric hypertensive crisis is a potentially life threatening medical emergency, usually secondary to an underlying disease. Hypertension commonly occurs during general anesthesia, and is usually promptly and appropriately treated by anesthesiologists. However in children with severe, unexplained, or refractory hypertension, it has the potential to cause morbidity and even mortality in susceptible patients. We report an anesthetic management of an unexpected hypertensive crisis that developed during general anesthesia in a three-year-old girl with undiagnosed severe left renal artery stenosis.", "affiliations": "Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, Ansan, Korea.;Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, Ansan, Korea.;Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, Ansan, Korea.;Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, Ansan, Korea.;Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, Ansan, Korea.;Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, Ansan, Korea.", "authors": "Park|Sang-Hee|SH|;Lee|Yoon-Sook|YS|;Min|Too Jae|TJ|;Kim|Woon Young|WY|;Kim|Jae Hwan|JH|;Park|Young Cheol|YC|", "chemical_list": null, "country": "Korea (South)", "delete": false, "doi": "10.4097/kjae.2014.67.4.275", "fulltext": "\n==== Front\nKorean J AnesthesiolKorean J AnesthesiolKJAEKorean Journal of Anesthesiology2005-64192005-7563The Korean Society of Anesthesiologists 10.4097/kjae.2014.67.4.275Case ReportAnesthetic management of hypertensive crisis in a three-year-old patient with undiagnosed severe renal artery stenosis: a case report Park Sang-hee Lee Yoon-Sook Min Too Jae Kim Woon Young Kim Jae Hwan Park Young Cheol Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, Ansan, Korea.Corresponding author: Yoon-Sook Lee, M.D., Ph.D., Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, 123, Jeokgeum-ro, Danwon-gu, Ansan 425-707, Korea. Tel: 82-31-412-5488, Fax: 82-31-412-5294, [email protected] 2014 27 10 2014 67 4 275 278 05 6 2013 23 8 2013 23 9 2013 Copyright © the Korean Society of Anesthesiologists, 20142014This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Pediatric hypertensive crisis is a potentially life threatening medical emergency, usually secondary to an underlying disease. Hypertension commonly occurs during general anesthesia, and is usually promptly and appropriately treated by anesthesiologists. However in children with severe, unexplained, or refractory hypertension, it has the potential to cause morbidity and even mortality in susceptible patients. We report an anesthetic management of an unexpected hypertensive crisis that developed during general anesthesia in a three-year-old girl with undiagnosed severe left renal artery stenosis.\n\nAnesthesiaChildRenovascular hypertension\n==== Body\nIntroduction\nHypertensive crisis is defined as a sudden and abrupt elevation in blood pressure (BP). It is subclassified into hypertensive emergency and hypertensive urgency based on the presence or absence of end-organ damage [1]. Hypertensive crisis is rare in children, in whom secondary hypertension is predominant. Renal parenchymal disease, renal artery stenosis, coarctation of the aorta, and neuro-endocrine tumors need to be considered in its etiology [2]. Adult patients with hypertensive histories commonly develop severe hypertension while under general anesthesia, which can be successfully treated by anesthesiologists. However, in children with severe anesthesia-associated hypertension, management may be delayed and variable. The anesthetic management of a child with hypertensive crisis during general anesthesia has not been reported. We therefore present a rare case of hypertensive crisis that developed in a three-year-old girl with undiagnosed renovascular hypertension due to left renal artery stenosis, who underwent general anesthesia for preauricular fistulectomy.\n\nCase Report\nA three-year-old girl was admitted to the hospital for right preauricular fistulectomy under general anesthesia. She was well-grown with a weight of 13 kg (25th percentile) and a height of 95.7 cm (50th percentile) and she had no medical history. Preoperative laboratory data including complete blood cell, coagulation test, and renal and liver function test were all within normal limits. Vital signs also were all unremarkable; heart rate (HR) was 114 /min and regular, BP was 90/60 mmHg, and temperature was normal. Her peripheral pulses were normal and symmetrically palpable.\n\nShe was premedicated with midazolam 1 mg and atropine 0.1 mg IM. On arrival in the operating room, electrocardiogram, pulse oxymetry, and non-invasive BP were established. HR was 154 /min with normal sinus rhythm and SpO2 was 100%. Anesthesia was induced with intravenous thiopental 5 mg/kg and rocuronium 0.6 mg/kg. While she was manually ventilated with 2% sevoflurane and 100% oxygen via face mask, initial BP was measured 143/90 mmHg on the right arm. We administered fentanyl 10 µg intravenously and intubated with a 4.5 mm ID cuffed endotracheal tube without difficulty. Anesthesia was maintained with 2% sevoflurane in 50% nitrous oxide and oxygen. ETCO2 was maintained 30 to 35 mmHg and SpO2 was maintained 100%. After intubation, BP increased as high as 180/100 mmHg and HR was 160/min. Because we suggested the cause of high BP was due to inadequate anesthetic depth, sevoflurane concentration was increased to 3% and intravenous fentanyl 10 µg was injected two more times. HR was stabilized to 105 /min, but BP showed only slight decrease to averaging 140 mmHg of systolic blood pressure and was still high throughout the surgery. Immediately before extubation, BP increased up to 190/105 mmHg and HR was 98 /min. Intravenous nicardipine 0.1 mg was given and she was sent to the recovery room. In the recovery room, BP increased to 220/115 mmHg. Intravenous fentanyl 10 µg was given one more time, but BP did not decrease and was sometimes unmeasurable. She had no hypertension-related symptoms like headache or dizziness, but showed irritability and agitation that weren't effectively controlled by opioids. We promptly consulted with the pediatrician and decided to transfer her to the pediatric department. Immediate antihypertensive treatment was started with nicardipine 0.5 µg/kg/min in the recovery room.\n\nIn the pediatric ward, an additional labetalol 0.4-3 mg/kg/h IV infusion was started, and diltiazem 3.5 mg/kg/day, atenolol 1 mg/kg/day, and hydralazine 7.2 mg/kg/day were given orally. Administration of these drugs was effective, but BP still showed fluctuation from 95/45 to 145/75 mmHg. Concurrently, further evaluation to establish the cause of uncontrollable hypertension was performed. She had no past medical history and physical examinations were unremarkable. In laboratory findings, plasma renin activity was elevated up to 24.2 ng/ml/h (normal range: 0.29-3.7 ng/ml/h). Plasma epinephrine and norepinephrine soared to 411.66 pg/ml (normal range: 0-120 pg/ml) and 1,063.31 pg/ml (normal range: 0-410 pg/ml) respectively. Other laboratory findings were all within normal limits. In imaging analyses, renal ultrasound showed a decrease in the size of the left kidney (5.7 cm in length) and no abnormalities were detected in the right kidney. Abdominal CT-angiography scan showed severe stenosis of inner diameter of less than 1 mm at proximal portion of left renal artery, hypoplasia, and decreased perfusion in left kidney (Fig. 1). Tc-99m DMSA renal scan also revealed decreased uptake in left kidney (Fig. 2). Echocardiography and fundoscopy were unremarkable. The options for treatment were balloon angioplasty or renal revascularization or nephrectomy. In this case, left nephrectomy was recommended due to the patient's age and the size of involved renal artery. Therefore, left laparoscopic nephrectomy was planned and she was transferred to the genitourinary department for surgery.\n\nIntravenous infusion of nicardipine 0.5 µg/kg/min and labetalol 1 mg/kg/h were continued until the day of surgery, BP measured in ward was stable at 100/41 mmHg, and HR was 92 /min. Anesthesia was induced with thiopental and rocuronium. During the surgery, anesthesia was maintained with 6% desflurane in 50% nitrous oxide and oxygen. BP showed a mild elevation up to 130/85 mmHg and intravenous infusion of nicardipine 0.5 µg/kg/min and labetalol 1 mg/kg/h were continued during induction and the early period of surgery. HR was maintained between 75 and 84 /min. Since BP was stabilized during the mid-period of surgery and HR fell to 68 /min, intravenous infusion was stopped. The 110 minute course of anesthesia was uneventful. BP was stable in the recovery room without medication and the child was sent to the ward with BP of 108/45 mmHg. There were no perioperative cardiovascular complications.\n\nAlthough the drugs which were given preoperatively were continued, BP showed a certain fluctuation from 100/40 to 150/70 mmHg postoperatively. Enalapril 0.4 mg/kg/day was added orally with careful monitoring of renal function, and then BP was stabilized. After changing all intravenous drugs to oral medications (amlodipine, carvedilol and enalapril), BP remained stable. After 6 months of follow-up, the patient's BP was normalized with the aid of oral antihypertensive medications.\n\nDiscussion\nWe describe a three-year-old girl with hypertensive crisis that developed during induction of anesthesia and was exacerbated during emergence. Hypertensive crisis in early and mid-childhood is rare and is associated with significant morbidity and mortality. Hypertensive crisis in adults is defined as acute, severe elevation of blood pressure above 180/120 mmHg (about 20 mmHg above stage 2 hypertension) [1]; however, hypertensive crisis in children has not been clearly defined. A child is diagnosed with hypertension if the average systolic and diastolic blood pressures are greater than the 95th percentile for age, gender, and height. Stage 1 hypertension is the designation for BP levels that range from 95th percentile to the 99th percentile plus 5 mmHg. Stage 2 hypertension is the designation for BP levels that are above the 99th percentile plus 5 mmHg [3]. Our patient was three-year-old girl with a height of 95.7 cm (50th percentile), and stage 2 hypertension (average BP > 119/79 mmHg) [3]. Yang et al. [4] reported stage 2 hypertension may serve as a critical threshold for a high risk of hypertensive crisis in children.\n\nRenovascular hypertension is caused by an arterial lesion that compromises blood flow in one or both kidneys, and represents 10% of all cases of secondary hypertension in children [5]. Renal artery stenosis is one of the most common abnormalities observed in children with secondary hypertension. The initial treatment of renovascular hypertension is medical therapy with antihypertensive drugs, the side effects of which can be exacerbated by rapid normalization of BP or drugs acting on the renin-angiotensin axis that reduce renal blood flow. Medications commonly used to treat hypertensive crisis in children are nicardipine, labetalol, and sodium nitroprusside. Our patient was given intravenous infusions of nicardipine and labetalol, as well as oral diltiazem, atenolol, and hydralazine. As medical treatment alone is often insufficient to control hypertension, leaving patients at risk for life-threatening events such as cerebrovascular accidents and cardiac failure, more aggressive treatments are required [6]. Management of hypertension can be quite challenging, especially in very young children and children with intra-renal artery involvement. Depending on the size of the vessels involved, endovascular or surgical intervention may not be possible. Nephrectomy may be indicated when the source of hypertension is a small, poorly functioning kidney [7].\n\nThe precipitating factors of hypertension during general anesthesia are most commonly related to drugs, excessive surgical stimulation, light anesthesia, or equipment [8]. If no obvious cause could be identified, it tends to be due to a combination of light anesthesia and/or excessive surgical stimulation and anesthesiologists often increase the depth of anesthesia. This will constitute effective treatment for the great majority of such cases. Once hypertension is identified and confirmed, its rapid control by the careful use of a volatile anesthetic agent, intravenous opioids, or rapid-acting antihypertensives will usually avoid serious morbidity [8]. If hypertension is unresponsive to the treatment indicated, an unusual etiology should be considered.\n\nWe did not measure baseline blood pressure before inducing anesthesia. Our patient presented with normal blood pressure and no signs and symptoms suggestive of hypertension preoperatively. She appeared anxious and irritable during the induction, despite having been premedicated with midazolam. In such cases of anxiety in young children, blood pressure measurement tends to be delayed until the patient loses consciousness. We had difficulty to recognize high BP after endotracheal intubation as hypertensive crisis because maintenance of high concentration of sevoflurane and administration of opioids decreased BP in some extent. However, BP soared to 220/115 mmHg in the recovery room and she was postoperatively diagnosed as renovascular hypertension.\n\nOur patient showed emergence agitation, unmeasurable blood pressure, and a hypertensive crisis with systolic blood pressure of more than 200 mmHg in the postoperative period. Hypertensive crisis not only represents severely elevated blood pressure with end-organ dysfunction, also results from a complex cascade linking neuro-hormonal and hemodynamic pathways, causing blood pressure to spiral out of control. Renin-angiotensin-aldosterone activation, oxidative and mechanical damage to the microvasculature, fluid overload, severe renal dysfunction, sympathetic overstimulation, and endothelial dysfunction may all contribute to the pathology of hypertensive crisis [9,10]. The trigger factors in our patient are assumed to be sympathetic overstimulation due to endotracheal intubation, surgical stimuli, and postoperative pain, with her underlying compromised renal blood flow acting in synergy.\n\nIn conclusion, hypertensive crisis during the induction of anesthesia and postoperative period is rare in children, and anesthetic management can be difficult when there is no evident cause. Blood pressure measurement in perioperative period may be difficult due to uncooperative and restless infants and young children, but it is important nonetheless in diagnosing unexpected severe hypertension. We suggest that blood pressure should be monitored in infants and young children perioperatively, and that anesthesiologists should be aware of the management of the unexpected hypertensive crisis and the possibility of secondary hypertension in children.\n\nFig. 1 Abdomen CT angiography shows stenosis at the proximal portion of left renal artery, hypoplasia, and decreased perfusion in left kidney.\n\nFig. 2 Tc-99m DMSA renal scan shows decreased uptake in left kidney.\n==== Refs\n1 Jones DW Hall JE Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and evidence from new hypertension trials Hypertension 2004 43 1 3 14676222 \n2 Chandar J Zilleruelo G Hypertensive crisis in children Pediatr Nephrol 2012 27 741 751 21773822 \n3 National high blood pressure education program working group on high blood pressure in children and adolescents The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents Pediatrics 2004 114 2 Suppl 4th Report 555 576 15286277 \n4 Yang WC Zhao LL Chen CY Wu YK Chang YJ Wu HP First-attack pediatric hypertensive crisis presenting to the pediatric emergency department BMC Pediatr 2012 12 200 23272766 \n5 Tullus K Brennan E Hamilton G Lord R McLaren CA Marks SD Renovascular hypertension in children Lancet 2008 371 1453 1463 18440428 \n6 Stadermann MB Montini G Hamilton G Roebuck DJ McLaren CA Dillon MJ Results of surgical treatment for renovascular hypertension in children: 30 year single centre experience Nephrol Dial Transplant 2010 25 807 813 19846390 \n7 Meyers K Falkner B Hypertension in children and adolescents: an approach to management of complex hyper-tension in pediatric patients Curr Hypertens Rep 2009 11 315 322 19737447 \n8 Paix AD Runciman WB Horan BF Chapman MJ Currie M Crisis management during anaesthesia: hypertension Qual Saf Health Care 2005 14 e12 15933285 \n9 Flynn JT Tullus K Severe hypertension in children and adolescents: pathophysiology and treatment Pediatr Nephrol 2009 24 1101 1112 18839219 \n10 Patel HP Mitsnefes M Advances in the pathogenesis and management of hypertensive crisis Curr Opin Pediatr 2005 17 210 214 15800414\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "2005-6419", "issue": "67(4)", "journal": "Korean journal of anesthesiology", "keywords": "Anesthesia; Child; Renovascular hypertension", "medline_ta": "Korean J Anesthesiol", "mesh_terms": null, "nlm_unique_id": "101502451", "other_id": null, "pages": "275-8", "pmc": null, "pmid": "25368787", "pubdate": "2014-10", "publication_types": "D016428:Journal Article", "references": "15800414;19737447;18440428;23272766;15286277;19846390;15933285;14676222;18839219;21773822", "title": "Anesthetic management of hypertensive crisis in a three-year-old patient with undiagnosed severe renal artery stenosis: a case report.", "title_normalized": "anesthetic management of hypertensive crisis in a three year old patient with undiagnosed severe renal artery stenosis a case report" }

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ANESTHETIC MANAGEMENT OF HYPERTENSIVE CRISIS IN A THREE-YEAR-OLD PATIENT WITH UNDIAGNOSED SEVERE RENAL ARTERY STENOSIS: A CASE REPORT. KOREAN JOURNAL OF ANESTHESIOLOGY. 2014 OCT 01;67(4):275-278.", "literaturereference_normalized": "anesthetic management of hypertensive crisis in a three year old patient with undiagnosed severe renal artery stenosis a case report", "qualification": "1", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20141203", "receivedate": "20141203", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10623129, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150529" } ]

{ "abstract": "BACKGROUND\nThe utilization of parathyroidectomy (PTX) to manage secondary hyperparathyroidism (SHPT) refractory to medical management (MTX) in end-stage renal disease (ESRD) in the era of calcimimetics is not well known.\n\n\nMETHODS\nAdult ESRD patients receiving dialysis between August 2007 and December 2011 at our institution with an intact parathyroid hormone (iPTH) level ≥88 pmol/L for 6 months associated with hypercalcemia and/or hyperphosphatemia for at least 50% of that period were included. Baseline characteristics and iPTH, calcium, phosphorus, calcium-phosphorus product and alkaline phosphatase (ALP) at baseline, 6 and 12 months were compared between the two groups (PTX versus MTX) using the χ (2) and paired t-tests.\n\n\nRESULTS\nOf the total population of 687 patients, 80 (11.6%) satisfied KDOQI criteria for PTX, most of whom did not receive PTX (81.2%). At baseline, PTX patients had been on dialysis longer (P = 0.001), with higher iPTH (P < 0.001), calcium (P = 0.008) and ALP (P = 0.001) and were less likely to be African-American (P = 0.007). Complete follow-up data at 6 months were available on 75 patients (PTX = 15; MTX = 60). PTX had significantly greater reduction in iPTH (93 versus 23%) and ALP (68 versus 0%) compared with MTX. Changes from baseline in calcium, phosphate or calcium-phosphorus product levels and proportion of patients achieving KDOQI target values were not significant for either intervention. Findings were consistent at 12 months.\n\n\nCONCLUSIONS\nA significant proportion of ESRD patients who met indications for PTX did not receive it. Additional studies are needed to understand the barriers that prevent patients from receiving PTX, thereby resulting in underutilization.", "affiliations": "Department of Surgery , Mount Sinai School of Medicine , New York , NY , USA.;Department of Medicine , Mount Sinai School of Medicine , New York, NY , USA.;Department of Surgery , Mount Sinai School of Medicine , New York , NY , USA.;Department of Medicine , Mount Sinai School of Medicine , New York, NY , USA.", "authors": "Konstantinidis|Ioannis|I|;Nadkarni|Girish|G|;Divino|Celia M|CM|;Lapsia|Vijay|V|", "chemical_list": null, "country": "England", "delete": false, "doi": "10.1093/ckj/sft028", "fulltext": "\n==== Front\nClin Kidney JClin Kidney JckjndtplusClinical Kidney Journal2048-85052048-8513Oxford University Press 10.1093/ckj/sft028sft028Original ContributionsOriginal ArticlesUtilization of parathyroidectomy for secondary hyperparathyroidism in end-stage renal disease Konstantinidis Ioannis 1Nadkarni Girish 2Divino Celia M. 1Lapsia Vijay 21 Department of Surgery, Mount Sinai School of Medicine, New York, NY, USA2 Department of Medicine, Mount Sinai School of Medicine, New York, NY, USACorrespondence and offprint requests to: Vijay Lapsia; E-mail: [email protected] 2013 28 3 2013 28 3 2013 6 3 277 282 23 10 2012 25 2 2013 © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For permissions, please email: [email protected] is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]\nThe utilization of parathyroidectomy (PTX) to manage secondary hyperparathyroidism (SHPT) refractory to medical management (MTX) in end-stage renal disease (ESRD) in the era of calcimimetics is not well known.\n\nMethods\nAdult ESRD patients receiving dialysis between August 2007 and December 2011 at our institution with an intact parathyroid hormone (iPTH) level ≥88 pmol/L for 6 months associated with hypercalcemia and/or hyperphosphatemia for at least 50% of that period were included. Baseline characteristics and iPTH, calcium, phosphorus, calcium–phosphorus product and alkaline phosphatase (ALP) at baseline, 6 and 12 months were compared between the two groups (PTX versus MTX) using the χ2 and paired t-tests.\n\nResults\nOf the total population of 687 patients, 80 (11.6%) satisfied KDOQI criteria for PTX, most of whom did not receive PTX (81.2%). At baseline, PTX patients had been on dialysis longer (P = 0.001), with higher iPTH (P < 0.001), calcium (P = 0.008) and ALP (P = 0.001) and were less likely to be African-American (P = 0.007). Complete follow-up data at 6 months were available on 75 patients (PTX = 15; MTX = 60). PTX had significantly greater reduction in iPTH (93 versus 23%) and ALP (68 versus 0%) compared with MTX. Changes from baseline in calcium, phosphate or calcium–phosphorus product levels and proportion of patients achieving KDOQI target values were not significant for either intervention. Findings were consistent at 12 months.\n\nConclusions\nA significant proportion of ESRD patients who met indications for PTX did not receive it. Additional studies are needed to understand the barriers that prevent patients from receiving PTX, thereby resulting in underutilization.\n\ncinacalcetESRDparathyroidectomysecondary hyperparathyroidism\n==== Body\nIntroduction\nSecondary hyperparathyroidism (SHPT) is a frequent complication of end-stage renal disease (ESRD) [1]. Numerous studies have demonstrated that high serum calcium, phosphorus, calcium–phosphorus product and intact parathyroid hormone (iPTH) levels in ESRD patients on dialysis are associated with an elevated incidence of bone disease and vascular calcification resulting in an increased all-cause and cardiovascular morbidity and mortality [1–4]. Surgical parathyroidectomy (PTX) is the definitive therapy to manage uncontrolled SHPT and is generally considered only when medical management (MTX) has failed. The indications for PTX, however, are not well defined. KDOQI recommends surgery in patients with severe hyperparathyroidism (persistent serum levels of iPTH >88 pmol/L) associated with hypercalcemia and/or hyperphosphatemia refractory to medical therapy. Pathologic bone fractures, bone pain, pruritus and vascular calcification in the setting of elevated iPTH levels are also considered strong indicators for surgery [5, 6]. With the introduction of the oral calcimimetic cinacalcet in 2004, the role of PTX has become less clear. Many ESRD patients who would have undergone PTX are likely to continue on medical therapy with cinacalcet. Also, patients with uncontrolled SPHT who would have initially been referred for surgery are now first being given a trial with cinacalcet. We hypothesized that PTX was underutilized even though it may have better outcomes than MTX, in terms of controlling biochemical abnormalities as well as symptoms and possibly have a mortality benefit. In this study, we present the utilization rate of PTX at our institution and the comparative outcomes of patients treated with PTX and those patients who received only medical treatment despite being indicated for PTX.\n\nMaterials and methods\nParticipants\nAfter obtaining approval from the institutional review board, we retrospectively reviewed the medical records of all adult patients receiving chronic renal replacement therapy at our institution from 1 August 2007 through 31 December 2011. We initially identified all patients that received peritoneal dialysis or hemodialysis. Of these patients, those found to have persistently elevated levels of iPTH (>88 pmol/L for 6 months) associated with hypercalcemia (>2.63 mmol/L) and/or hyperphosphatemia (>1.77 mmol/L) for at least 50% of that time period were considered eligible for PTX. Patients with complete follow-up data at 6 and 12 months were included for analysis. Note: In 2009, Kidney Disease: Improving Global Outcomes (KDIGO) proposed wider range for serum iPTH (two to nine times the upper reference limit for the assay) and calcium (2.12–2.75 mmol/L), while reducing phosphorus levels toward the reference range (0.77–1.52 mmol/L) [7]. However, since most of our patients received care before these guidelines were widely accepted, we chose to use the KDOQI criteria for the purposes of this study.\n\nData collection\nData such as demographics, medical comorbidities, medications and biochemistry [iPTH, calcium, phosphorus, calcium–phosphorus product, albumin and alkaline phosphatase (ALP)] were collected at the time of inclusion. Accurate medication information was not available for six MTX patients. Biochemistry, medications and date of last follow-up or death were recorded at 6 and 12 months thereafter. In addition for patients who underwent PTX, preoperative details such as symptoms of bone pain or pruritus, and post-operative resolution of symptoms were collected.\n\nOutcome measures\nThe clinical effectiveness of PTX compared with continued medical treatment was evaluated based on the control of iPTH (reference range = 1.2–10.8 pmol/L), total corrected calcium (reference range = 2.1–2.62 mmol/L), phosphorus (reference range = 0.80–1.62 mmol/L), calcium–phosphorus product (reference range = 1.1–3.6 mmol2/L2), albumin (reference range = 35–55 g/L) and ALP (reference range = 0.76–2.84 µkat/L) from the time of inclusion to follow-up at both 6 and 12 months. In addition, we compared the proportion of patients in each cohort attaining KDOQI targets for serum iPTH (16.5–33 pmol/L), phosphorus (1.13–1.77 mmol/L), total corrected calcium (2.1–2.37 mg/dL) and calcium–phosphorus product (Ca × P; <4.4 mmol2/L2) at 6 and 12 months.\n\nStatistical analysis\nCategorical variables were presented as counts and percentages, and continuous variables as mean with standard deviations. Categorical variables were compared using the χ2 test and continuous variables were compared with the Student t-test for paired and unpaired samples within and between cohorts. Values of P < 0.05 were considered statistically significant for all tests. All analyses were performed with SPSS for Windows (version 19.0; SPSS, Chicago, IL).\n\nResults\nOf the initial population of 687 adult patients receiving dialysis, 231 patients (33.6%) had elevated iPTH (>88 pmol/L) at least once during their care, 117 (17%) of which had persistently elevated levels for at least 6 months. A total of 80 patients (11.6%) either met indications for PTX or had undergone PTX. Seventy-five patients (MTX—60, PTX—15) and 61 patients (MTX—51, PTX—10) had adequate follow-up data available at 6 and 12 months, respectively. All patients were receiving medical therapy in the form of dietary phosphate restriction, calcium supplementation, phosphate binders and vitamin D sterols, and/or cinacalcet. The demographic characteristics of 75 patients who had follow-up available for at least 6 months are shown in Table 1. Patients who underwent PTX had been on dialysis significantly longer (mean 12 years) than those treated with MTX (mean 5.2 years) (P < 0.001). In addition, 47% of patients undergoing PTX were African-American when compared with 72% of MTX patients (P = 0.05). PTX patients were also more likely to have received a kidney transplant in the past (53 versus 25%), although this difference did not reach statistical significance (P = 0.06). Moreover, PTX patients were also more likely to have a history of cancer (33%) compared with MTX patients (8%) (P = 0.023). Seventy-three percent (n = 11) of surgical patients were receiving cinacalcet at the time of inclusion compared with 28% (n = 15) of patients in the MTX cohort (P = 0.002). In contrast, 74% (n = 39) of MTX patients and 27% (n = 4) of PTX patients were using vitamin D sterols (P = 0.002). The two cohorts were otherwise similar in demographic composition, medical comorbidities and medication usage at inclusion. Follow-up averaged 2.2 (1.0) years for MTX patients and 1.6 (1.0) years for PTX patients. Twenty-five percent (n = 15) of MTX patients and 13% (n = 2) of PTX patients died during the study period for reasons unrelated to management for SHPT. There was no significant difference in mortality between the two cohorts (P = 0.5). These findings were consistent for patients with 12 months of follow-up.\nTable 1. Patient demographics and medication usage at inclusiona\n\n\tMTX cohort (n = 60)\tPTX cohort (n = 15)\tP-value\t\nMale, n (%)\t32 (53)\t6 (40)\t0.40\t\nEthnicity, n (%)\t\nCaucasian\t1 (2)\t2 (3)\t\t\nAfrican American\t43 (72)\t7 (47)\t0.05\t\nHispanic\t7 (12)\t5 (33)\t\t\nOther\t9 (15)\t1 (7)\t\t\nAge in years, mean (SD)\t46.0 (15.8)\t44.6 (11.9)\t0.75\t\nComorbidities, n (%)\t\nHypertension\t54 (90)\t13 (87)\t0.66\t\nDiabetes mellitus\t14 (23)\t4 (27)\t0.75\t\nCoronary artery disease\t17 (28)\t3 (20)\t0.75\t\nMyocardial infarction\t3 (5)\t2 (13)\t0.26\t\nChronic heart failure\t13 (22)\t3 (20)\t1.00\t\nCerebrovascular disease\t6 (10)\t3 (20)\t0.37\t\nPeripheral vascular disease\t6 (10)\t0 (0)\t0.34\t\nDyslipidemia\t7 (12)\t2 (13)\t1.00\t\nAnemia\t30 (50)\t5 (33)\t0.39\t\nCancer\t5 (8)\t5 (33)\t0.023\t\nHistory of fractures\t2 (3)\t1 (7)\t0.49\t\nCurrent smoker, n (%)\t18 (30)\t4 (27)\t1.00\t\nTime on dialysis in years, mean (SD)\t5.2 (5.6)\t12.0 (7.7)\t<0.001\t\nHistory of kidney transplant, n (%)b\t15 (25)\t8 (53)\t0.06\t\nMedications at inclusion, n (%)b\t\nVitamin D sterols\t39 (74)\t4 (27)\t0.002\t\nPhosphate binders\t29 (55)\t11 (73)\t0.24\t\nCalcium acetate\t5 (9)\t1 (7)\t1.0\t\nSevelamer\t27 (51)\t10 (67)\t0.38\t\nLanthanum carbonate\t2 (4)\t0 (0)\t1.0\t\nCinacalcet\t15 (28)\t11 (73)\t0.002\t\nUnknown\t7 (13)\t0 (0)\t\t\nLength of follow-up in years, mean (SD)\t2.2 (1.0)\t1.6 (1.0)\t0.07\t\nCurrent status, n (%)\t\t\t\t\nHD\t27 (45)\t8 (53)\t\t\nPD\t6 (10)\t2 (13)\t\t\nFunctioning transplant\t3 (5)\t1 (7)\t\t\nDeceased\t15 (25)\t2 (13)\t0.50\t\nNot known\t9 (15)\t2 (13)\t\t\naBold values represent statistically significant results.\n\nbAccurate medication information was not available for six patients in the MTX cohort, and these were excluded from the analysis regarding medication usage at inclusion.\n\n\n\nChanges in iPTH\nAt inclusion, PTX patients had iPTH levels of 293.6 (±113.2) pmol/L compared with MTX patients, which had iPTH levels of 155.5 (±81.5) pmol/L. The surgical cohort of patients had significantly higher baseline iPTH levels than the MTX cohort (P < 0.001). Six months after intervention, PTX patients had significantly reduced iPTH levels of 21. 5 (±37.1) pmol/L (P < 0.001). This decrease persisted for 12 months after intervention with PTX patients having significantly reduced iPTH levels of 11.8 (±24.2) pmol/L (P < 0.001). The mean percentage reduction was 93% at 6 months and >96% at 12 months. In comparison, MTX patients had decreased iPTH levels of 119 (±93.6) pmol/L at 6 months and 121.8 (±82.4) pmol/L at 12 months with a mean reduction from baseline of 30% at 6 months (P = 0.001) and 23% at 12 months (P = 0.006). Thus, patients in the PTX cohort had a more significant reduction from baseline compared with those in the MTX cohort (P < 0.001) (Table 2). Seventy-three percent (n = 11) of PTX patients attained KDOQI target values for iPTH (<33 pmol/L) compared with only 22% (n = 13) in the MTX cohort (P < 0.001) (Table 3). This difference was similar both at 6 and 12 months. Two surgical patients developed hypoparathyroidism 12 months following intervention. No MTX patients experienced hypoparathyroidism.\nTable 2. Comparison of changes in bone profile at 6 monthsa\n\n\tMTX cohort (n = 60)\tMTX cohort: significance of change, P-value\tPTX cohort (n = 15)\tPTX cohort: significance of change, P-value\tPTX versus MTX: significance at baseline, P-value\tPTX versus MTX: significance of change, P-value\t\nBaseline serum iPTH (pmol/L)\t155.5 (±81.5)\t0.001\t293.6 (±113.2)\t<0.001\t<0.001\t<0.001\t\n6-month serum iPTH (pmol/L)\t119 (±93.6)\t\t21.5 (±37.1)\t\t\t\t\nBaseline serum calcium (mmol/L)\t2.17 (±0.19)\t0.10\t2.34 (±0.33)\t0.12\t0.008\t0.33\t\n6-month serum calcium (mmol/L)\t2.22 (±0.24)\t\t2.15 (±0.28)\t\t\t\t\nBaseline serum phosphorus (mmol/L)\t2.23 (±0.42)\t0.032\t2.32 (±0.59)\t0.12\t0.48\t0.73\t\n6-month serum phosphorus (mmol/L)\t2.09 (±0.51)\t\t2.03 (±0.67)\t\t\t\t\nBaseline serum albumin (g/L)\t37.1 (±4.7)\t0.98\t37.2 (±3.4)\t0.95\t0.96\t0.95\t\n6-month serum albumin (g/L)\t37.2 (±5.2)\t\t37.3 (±6.0)\t\t\t\t\nBaseline serum alkaline phosphatase (µkat/L)\t2.7 (±2.07)\t0.19\t6.16 (±3.64)\t0.001\t<0.001\t0.42\t\n6-month serum alkaline phosphatase (µkat/L)\t2.43 (±1.9)\t\t1.97 (±0.8)\t\t\t\t\nBaseline Ca × P (mmol2/L2)\t4.82 (±0.93)\t0.18\t5.45 (±1.5)\t0.043\t0.043\t0.61\t\n6-month Ca × P (mmol2/L2)\t4.6 (±1.07)\t\t4.42 (±1.7)\t\t\t\t\naBold values represent statistically significant results.\n\n\nTable 3. Attainment of KDOQI targets at baseline and 6 monthsa\n\n\tMTX cohort (n = 60)\tPTX cohort (n = 15)\tP-value\t\nSerum iPTH: <33 pmol/L\t\nBaseline\t0 (0%)\t0 (0%)\t1.00\t\nAt 6 months\t13 (22%)\t11 (73%)\t<0.001\t\nSerum phosphorus: 1.1–1.8 mmol/L\t\nBaseline\t8 (13%)\t3 (20%)\t0.68\t\nAt 6 months\t14 (23%)\t6 (40%)\t0.21\t\nSerum calcium: 2.1–2.4 mmol/L\t\nBaseline\t36 (60%)\t5 (33%)\t0.08\t\nAt 6 months\t30 (50%)\t8 (53%)\t1.00\t\nCalcium–phosphorus product: <4.4 mmol2/L2\t\nBaseline\t23 (38%)\t4 (27%)\t0.55\t\nAt 6 months\t29 (48%)\t9 (60%)\t0.57\t\naBold values represent statistically significant results.\n\n\n\nChanges in ALP\nPTX patients had significantly higher ALP levels at inclusion compared with MTX patients, 6.16 (±3.64) µkat/L and 2.7 (±2.07) µkat/L, respectively (P < 0.001). ALP among PTX patients had decreased to 1.97 (±0.8) µkat/L at 6 and 1.6 (±0.92) µkat/L at 12 months, representing a reduction of 68% (P = 0.001) and 74%, respectively (P = 0.003). In contrast, MTX patients experienced a decrease in ALP to 2.43 (±1.9) µkat/L at 6 and 2.49 (±1.68) µkat/L at 12 months that was not statistically significant (P = 0.19 and 0.199, respectively). Overall, surgical patients had a more significant decline from baseline compared with MTX patients (P < 0.001) (Table 2).\n\nChanges in calcium, phosphorus and calcium–phosphorus product\nThe two cohorts had similar calcium, phosphorus and calcium–phosphorus product values at inclusion. Among surgical patients, 40% (n = 6), 53% (n = 8) and 60% (n = 9) attained KDOQI target values for phosphorus, calcium and calcium–phosphorus product, respectively. In the MTX cohort, 23% (n = 14), 50% (n = 30) and 48% (n = 29) attained KDOQI target values for phosphorus, calcium and calcium–phosphorus product, respectively (Table 3). This proportion was maintained at 12 months. Changes from baseline in the calcium, phosphate or calcium–phosphorus product levels and proportions of patients achieving KDOQI target values were not statistically significant for either intervention at 6 or 12 months.\n\nChanges in medications\nTotal daily and weekly doses at baseline, 6 and 12 months of calcium acetate, sevelamer, paracalcitol and cinacalcet are presented in Table 4. All patients who underwent PTX were off cinacalcet at 6 and 12 months. The total daily dose of cinacalcet for the MTX group increased from 69.2 mg/day at baseline to 79.3 mg/day at 12 months, but this change was not statistically significant (P = 0.17).\nTable 4. Comparison of changes in medication dosages at baseline, 6 and 12 monthsa\n\n\tMTX cohort (n = 60 and 51)\tPTX cohort (n = 15 and 10)\tP-value\t\nCinacalcet (mg/day)\t\nBaseline\t69.2 (37.5)\t67.5 (26.6)\t0.87\t\nAt 6 months\t67.5 (31.9)\t\t\t\nAt 12 months\t79.3 (41.8)\t\t\t\nParacalcitol (mg/week)\t\nBaseline\t18.6 (12.8)\t25.1 (18.3)\t0.20\t\nAt 6 months\t24.6 (17.8)\t22.6 (11.7)\t0.60\t\nAt 12 months\t21 (20.8)\t19.9 (12.1)\t0.79\t\nCalcium acetate (mg/day)\t\nBaseline\t4562.5 (1399.9)\t3000.0 (1414.2)\t<0.001\t\nAt 6 months\t4450.0 (1571.45)\t7000.0 (1414.2)\t<0.001\t\nAt 12 months\t4277.8 (1563.5)\t5333.3 (3055.1)\t0.06\t\nSevelamer (mg/day)\t\nBaseline\t5515.4 (2928.6)\t5640.0 (2266.3)\t0.88\t\nAt 6 months\t5322.6 (2738.7)\t5000.0 (2674.3)\t0.68\t\nAt 12 months\t5577.8 (2889.9)\t5800.0 (2449.5)\t0.79\t\naBold values represent statistically significant results.\n\n\n\nRecurrence following PTX\nOne patient underwent a repeat PTX 1 year later as iPTH, although substantially lower (>60%) continued to be high. None of the other patients experienced recurrence at 1 year. Longer-term recurrence could not be evaluated due to lack of adequate follow-up data in 8 of the remaining 14 patients.\n\nDiscussion\nTo improve the care of dialysis patients, the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has recommended targets for serum iPTH (16.5–33 pmol/L), phosphorus (1.13–1.77 mmol/L), total corrected calcium (2.10–2.37 mmol/L) and calcium–phosphorus product (Ca × P; <4.4 mmol2/L2) [6]. Consistent control of biochemical markers within KDOQI recommended values strongly predicts survival [8, 9]; however, traditional treatment of SHPT with dietary phosphate restriction, phosphate binders, calcium supplementation and vitamin D sterols has been insufficient for achieving KDOQI targets [10, 11]. An increasing number of therapies are available that assist in achieving these targets, including calcium salts, calcitriol, alfacalcidol and more recently, active vitamin D analogs, cinacalcet hydrochloride and non-calcium/aluminum-based phosphate binders. However, the use of calcium salts and vitamin D sterols to achieve consistent control of biochemical markers within published targets may cause hypercalcemia and/or hyperphosphatemia, which are associated with cardiovascular and soft tissue calcification. This generally necessitates treatment interruption, potentially contributing to inadequate iPTH control and disease progression [12–14]. Calcium-free phosphate binders, such as sevelamer and lanthanum carbonate, decrease serum phosphate levels, but do not significantly control iPTH levels [15]. Calcimimetics have improved the medical treatment options for SHPT. These agents increase the sensitivity of the calcium-sensing receptor on parathyroid cells to extracellular calcium, thereby suppressing serum iPTH, calcium, phosphorus and calcium–phosphorus product levels [16, 17]. Cinacalcet is the only currently available calcimimetic. Therapy with cinacalcet has many physiologic and clinical advantages and multiple randomized, controlled trials and observational studies have shown that cinacalcet improves the likelihood of achieving KDOQI targets for dialysis patients and decreases fracture risk, cardiovascular hospitalization and the number of patients undergoing PTX [18–20].\n\nHowever, the utility of PTX versus medical therapy remains debatable [21]. A retrospective analysis of United States Renal Database System (USRDS) data showed higher short-term but lower long-term mortality rates among dialysis patients undergoing PTX [22]. A recent observational study showed that PTX was superior to cinacalcet in controlling iPTH and ALP at 18 months from baseline [23]. Additionally, the data on long-term utility and outcomes of cinacalcet remain inconclusive [24, 25]. A recent analysis showed that cinacalcet therapy was only cost-effective if the anticipated stay on dialysis was <16 months. This would only include those with a high risk of mortality or those who could expect to receive a transplant quickly. PTX was found to be significantly more cost-effective for all other subgroups [26]. Finally, given its significant gastrointestinal adverse effects, its tolerability as well as patient compliance is questionable. In the recently published EVOLVE study [25], almost two-thirds of patients in the cinacalcet group discontinued active therapy, many of these due to adverse events or patients requests.\n\nIn this study, we found that one out of every six dialysis patients had persistently elevated levels of iPTH and a majority (68.3%) of these patients satisfied KDOQI criteria for PTX. Only a minority (12.8%) underwent surgery, while the others were continued on MTX despite being indicated for PTX. Of the patients on MTX who were eligible for cinacalcet therapy, only a few (28%) were prescribed the medication, highlighting the complexity of real-world practice implementations of published recommendations. Patients in the PTX group in general had relatively more severe disease (as suggested by the differences in serum calcium, ALP and iPTH levels). However, both groups met KDOQI criteria for consideration of PTX. In addition, nearly all patients in the MTX group continued to satisfy criteria for PTX at the end of 1 year of follow-up, a result of either inadequacy or failure of MTX. It is unclear why a significant proportion of patients did not receive PTX despite satisfying criteria. Patients who received PTX were on dialysis for a significantly longer period of time compared with those who received MTX. So the duration of SHPT could have been a deciding factor for referral. The racial distribution of the two groups was significantly different with the MTX group having a higher proportion of African-American patients compared with the PTX group, suggesting the possibility of racial disparity. PTX patients were also more likely to have received a kidney transplant in the past, potentially implicating the ability to access resources and navigate the system. There were no significant differences in the comorbidities between the two groups. In our study, patients in both the PTX and MTX groups were on dialysis for significantly longer than 16 months. Therefore, PTX would have been more cost-effective for this patient cohort. It is possible that with the availability of cinacalcet patients who otherwise meet the criteria for PTX were not referred for surgery. Since the treating nephrologist is the primary source of referral, personal clinical bias may be one of the factors contributing to this underutilization. Data in the literature indicate that PTX can be associated with a high prevalence of low PTH values [27], which could be regarded as undesirable for hard clinical outcomes. Adynamic bone disease is a clear long-term risk, as PTX is irreversible and the PTH suppression resulting from the procedure non-dosable. Finally, a significant proportion of patients who might have been referred for PTX may have refused the intervention due to the potential risks associated with this surgery. Studies on the attitudes of ESRD patients toward PTX are lacking, therefore data on this disparity are limited.\n\nThe limitations of the study largely pertain to the small sample size and single-center experience. The small sample size precluded effective matching of the two groups, thereby resulting in significant and important differences in the baseline characteristics and potentially impacting results. Due to its retrospective design, measures of causation cannot be assessed.\n\nIn conclusion, our study shows that a significant proportion of ESRD patients who met the indications of PTX did not receive it. For reasons still unclear, there continues to be reluctance or lack of enthusiasm for the PTX procedure in actual practice. At our center, PTX was successful at achieving the intended biochemical goals as well as resolution of symptoms (bone pain) in the small number of patients who underwent the procedure. This study, though limited in nature, lays the groundwork for further large-scale, prospective studies to assess the utility of early PTX and better understand the barriers that prevent patients from receiving it in a timely fashion.\n\nConflict of interest statement\nNone declared.\n==== Refs\nReferences\n1 Block GA Hulbert-Shearon TE Levin NW Association of serum phosphorus and calcium × phosphate product with mortality risk in chronic haemodialysis patients: a national study Am J Kidney Dis 1998 31 607 617 9531176 \n2 Ganesh SK Stack AG Levin NW Association of elevated serum PO4 , Ca3 PO4 product, and parathyroid hormone with cardiac mortality risk in chronic haemodialysis patients J Am Soc Nephrol 2001 12 2131 2138 11562412 \n3 Block GA Klassen PS Lazarus JM Mineral metabolism, mortality, and morbidity in maintenance hemodialysis J Am Soc Nephrol 2004 15 2208 2218 15284307 \n4 Tentori F Blayney MJ Albert JM Mortality risk for dialysis patients with different levels of serum calcium, phosphorus and PTH: the Dialysis Outcomes and Practice Patterns Study [DOPPS] Am J Kidney Dis 2008 52 519 530 18514987 \n5 National Kidney Foundation K/DOQI clinical practice guidelines: bone metabolism and disease in chronic kidney disease Am J Kidney Dis 2003 42 Suppl 4 S1 S201 14520607 \n6 Madorin C The surgical management of renal hyperparathyroidism Eur Arch Otorhinolaryngol 2012 269 1565 1576 22101574 \n7 Kidney Disease: Improving Global Outcomes [KDIGO] CKD-MBD Work Group KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder [CKD-MBD] Kidney Int 2009 76 Suppl 113 S1 S130 \n8 Danese MD Belozeroff V Smirnakis K Consistent control of mineral and bone disorder in incident hemodialysis patients Clin J Am Soc Nephrol 2008 3 1423 1429 18596117 \n9 Noordzij M Korevaar JC Boeschoten EW The Kidney Disease Outcomes Quality Initiative [K/DOQI] guideline for bone metabolism and disease in CKD: association with mortality in dialysis patients Am J Kidney Dis 2005 46 925 932 16253734 \n10 Al Aly Z Gonzalez EA Martin KJ Achieving K/DOQI laboratory target values for bone and mineral metabolism: an uphill battle Am J Nephrol 2004 24 422 426 15308874 \n11 Arenas MD Alvarez-Ude F Gil MT Application of NKF-K/DOQI clinical practice guidelines for bone metabolism and disease: changes of clinical practices and their effects on outcomes and quality standards in three haemodialysis units Nephrol Dial Transplant 2006 21 1663 1668 16464885 \n12 Moe S Drueke TB Management of secondary hyperparathyroidism: the importance and the challenge of controlling parathyroid hormone levels without elevating calcium, phosphorus, and calcium phosphorus product Am J Nephrol 2003 23 369 379 14551461 \n13 Brown AJ Dusso AS Slatopolsky E Vitamin D analogues for secondary hyperparathyroidism Nephrol Dial Transplant 2002 17 10 19 12386264 \n14 Goodman WG Recent developments in the management of secondary hyperparathyroidism Kidney Int 2001 59 1187 1201 11231381 \n15 Bleyer AJ Burke SK Dillon M A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients Am J Kidney Dis 1999 33 694 701 10196011 \n16 Nemeth EF Steffey ME Hammerland LG Calcimimetics with potent and selective activity on the parathyroid calcium receptor Proc Natl Acad Sci USA 1998 95 4040 4045 9520489 \n17 Drueke TB Modulation and action of the calcium sensing receptor Nephrol Dial Transplant 2004 19 Suppl 5 V20 V26 15284356 \n18 Ureña P Jacobson SH Zitt E Cinacalcet and achievement of the NKF/K-DOQI recommended target values for bone and mineral metabolism in real-world clinical practice—the ECHO observational study Nephrol Dial Transplant 2009 24 2852 2859 19369690 \n19 Lindberg JS Culleton B Wong G Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study J Am Soc Nephrol 2005 16 800 807 15689407 \n20 St Peter WL Li Q Liu J Cinacalcet use patterns and effect on laboratory values and other medications in a large dialysis organization, 2004 through 2006 Clin J Am Soc Nephrol 2009 4 354 360 19129318 \n21 Tominaga Y Matsuoka S Uno N Parathyroidectomy for secondary hyperparathyroidism in the era of calcimimetics Ther Apher Dial 2008 12 Suppl 1 S21 S26 19032523 \n22 Kestenbaum B Andress DL Schwartz SM Survival following parathyroidectomy among United States dialysis patients Kidney Int 2004 66 2010 2016 15496173 \n23 Ghani A Baxter P Surgical parathyroidectomy versus cinacalcet therapy: in the management of secondary hyperparathyroidism Otolaryngol Head Neck Surg 2012 146 220 225 22075073 \n24 Garside R Pitt M Anderson R The effectiveness and cost-effectiveness of cinacalcet for secondary hyperparathyroidism in end-stage renal disease patients on dialysis: a systematic review and economic evaluation Health Technol Assess 2007 11 1 167 \n25 The EVOLVE Trial Investigators Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis N Engl J Med 2012 367 2482 2494 23121374 \n26 Narayan R Perkins RM Berbano EP Parathyroidectomy versus cinacalcet hydrochloride-based medical therapy in the management of hyperparathyroidism in ESRD: a cost utility analysis Am J Kidney Dis 2007 49 801 813 17533023 \n27 Mazzaferro S Pasquali M Farcomeni A Parathyroidectomy as a therapeutic tool for targeting the recommended NKF-K/DOQI ranges for serum calcium, phosphate and parathyroid hormone in dialysis patients Nephrol Dial Transplant 2008 23 2319 2323 18281320\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "2048-8505", "issue": "6(3)", "journal": "Clinical kidney journal", "keywords": "ESRD; cinacalcet; parathyroidectomy; secondary hyperparathyroidism", "medline_ta": "Clin Kidney J", "mesh_terms": null, "nlm_unique_id": "101579321", "other_id": null, "pages": "277-82", "pmc": null, "pmid": "26064486", "pubdate": "2013-06", "publication_types": "D016428:Journal Article", "references": "22101574;19032523;18596117;19369690;11231381;17533023;23121374;14520607;17462168;15308874;15689407;11562412;12386264;15284356;16464885;22075073;14551461;19129318;18514987;16253734;9531176;19644521;15496173;10196011;18281320;15284307;9520489", "title": "Utilization of parathyroidectomy for secondary hyperparathyroidism in end-stage renal disease.", "title_normalized": "utilization of parathyroidectomy for secondary hyperparathyroidism in end stage renal disease" }

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"drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "STEROL D" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CALCIUM ACETATE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CALCIUM ACETATE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Therapeutic product effect incomplete", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Therapy non-responder", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypoparathyroidism", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Disease recurrence", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Death", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "LAPSIA V.? KONSTANTINIDIS L.? NADKARNI G. ET AL.. UTILIZATION OF PARATHYROIDECTOMY FOR SECONDARY HYPERPARATHYROIDISM IN END-STAGE RENAL DISEASE. CLIN KIDNEY J. 2013?6:277-282", "literaturereference_normalized": "utilization of parathyroidectomy for secondary hyperparathyroidism in end stage renal disease", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20201019", "receivedate": "20201019", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18400496, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210114" } ]

{ "abstract": "Role of non-adherence upon virological success with newer oral regimens is unknown. We sought to determine the impact of treatment adherence upon virological outcomes in hepatitis C virus (HCV) infected persons on sofosbuvir (SOF)-based regimens, using pharmacy prescription data as a measure of adherence.\n\n\n\nWe analysed HCV infected persons in Electronically Retrieved Cohort of HCV Infected Veterans, who were initiated on SOF-based regimens, excluding those with human immunodeficiency virus, positive hepatitis-B surface antigen, hepatocellular carcinoma and missing HCV RNA.\n\n\n\nThe final dataset included following regimens: SOF+simeprevir (SIM) (n = 1050), SOF+ledipasvir (LDV) (n = 974), SOF+ribavirin (RBV) (n = 663, genotype 2 or 3), and SOF+pegylated interferon (PEG)+RBV (n = 519, genotype 1 or 4). Those treated with a SOF-based regimen were older and more likely to have cirrhosis, diabetes, chronic kidney disease, higher HCV RNA levels, higher body mass index, compared with 1652 controls receiving a boceprevir-based (BOC) regimen. Sustained virological response (SVR12) rates for the SOF+SIM and SOF+LDV groups did not decline significantly even when as low as 50% of the full course was prescribed (except SOF+LDV, 90-99% prescriptions had SVR12 of 84.6%; n = 13). SOF+RBV for genotype 2/3 who received 50-80% of the prescriptions, 23/34 (67.6%) achieved SVR12. For persons with genotype 1/4 infection treated with SOF+PEG+RBV, no declines in SVR12 were seen with lower rates of prescriptions (40/43, or 93% SVR12 rate).\n\n\n\nSofosbuvir-based treatment regimens are highly effective in achieving SVR12. This efficacy is not significantly affected when treated persons receive less than a full prescribed course of treatment.", "affiliations": "VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.;VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.;VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.;Massachusetts General Hospital, Boston, MA, USA.;University of Cincinnati College of Medicine/UC Health, Cincinnati, OH, USA.", "authors": "Butt|Adeel A|AA|;Yan|Peng|P|;Shaikh|Obaid S|OS|;Chung|Raymond T|RT|;Sherman|Kenneth E|KE|;|||", "chemical_list": "D000998:Antiviral Agents; D012254:Ribavirin; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D007372:Interferons; D011392:Proline; D000069616:Simeprevir; D000069474:Sofosbuvir", "country": "United States", "delete": false, "doi": "10.1111/liv.13103", "fulltext": null, "fulltext_license": null, "issn_linking": "1478-3223", "issue": "36(9)", "journal": "Liver international : official journal of the International Association for the Study of the Liver", "keywords": "ERCHIVES; HCV; adherence; directly acting antiviral agents; sofosbuvir", "medline_ta": "Liver Int", "mesh_terms": "D000368:Aged; D000998:Antiviral Agents; D016208:Databases, Factual; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus; D019698:Hepatitis C, Chronic; D006801:Humans; D007372:Interferons; D008103:Liver Cirrhosis; D016015:Logistic Models; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D011392:Proline; D012254:Ribavirin; D000069616:Simeprevir; D000069474:Sofosbuvir; D000072230:Sustained Virologic Response; D014481:United States; D014728:Veterans", "nlm_unique_id": "101160857", "other_id": null, "pages": "1275-83", "pmc": null, "pmid": "26928927", "pubdate": "2016-09", "publication_types": "D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't", "references": null, "title": "Treatment adherence and virological response rates in hepatitis C virus infected persons treated with sofosbuvir-based regimens: results from ERCHIVES.", "title_normalized": "treatment adherence and virological response rates in hepatitis c virus infected persons treated with sofosbuvir based regimens results from erchives" }

[ { "companynumb": "US-JNJFOC-20160813265", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "SIMEPREVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "205123", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CAPSULE", "drugdosagetext": "FOR 12 WEEKS IN NON CIRRHOTIC PATIENT AND 24 WEEKS IN CIRRHOTIC. 53.62% COMPLETED THE TREATMENT", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATITIS C", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "2", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SIMEPREVIR" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "SOFOSBUVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNSPECIFIED", "drugdosagetext": "FOR 12 WEEKS IN NON CIRRHOTIC PATIENT AND 24 WEEKS IN CIRRHOTIC. 53.62% COMPLETED THE TREATMENT", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATITIS C", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SOFOSBUVIR" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Treatment noncompliance", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Remission not achieved", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Product use issue", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "BUTT AA, YAN P, SHAIKH OS, CHUNG RT, SHERMAN KE. TREATMENT ADHERENCE AND VIROLOGICAL RESPONSE RATES IN HEPATITIS C VIRUS INFECTED PERSONS TREATED WITH SOFOSBUVIR-BASED REGIMENS: RESULTS FROM ERCHIVES. LIVER INTERNATIONAL 2016;36/9:1275-1283.", "literaturereference_normalized": "treatment adherence and virological response rates in hepatitis c virus infected persons treated with sofosbuvir based regimens results from erchives", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20160912", "receivedate": "20160819", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12669490, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20161109" } ]

{ "abstract": "Type 2 diabetes mellitus is highly prevalent among patients with cirrhosis. The pharmacological management of this disease in patients with chronic liver disease remains controversial, however. Insulin secretagogues such as sulfonylureas are associated with a high risk of hypoglycemia among diabetics. In patients with cirrhosis, this risk is more pronounced due to decreased hepatic clearance, concurrent alcoholism, hypoalbuminemia, and acute liver decompensation. In this case report, we present a case of severe refractory hypoglycemia secondary to glipizide in a patient with alcoholic cirrhosis. We believe that the use of sulfonylureas in this patient population should be contraindicated to avoid debilitating neurologic damage and death following hypoglycemia.", "affiliations": "Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, USA.;Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, USA.;Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, USA.;Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, USA.;Pharmacy, Robert J. Dole Veterans Affairs Medical Center, Wichita, USA.", "authors": "Braet|Corey|C|;Hussein Agha|Yasmine|Y|;Taleb|Ali|A|;Buess|Charles|C|;Millard|John|J|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.7759/cureus.8513", "fulltext": "\n==== Front\nCureus\nCureus\n2168-8184\nCureus\n2168-8184 Cureus Palo Alto (CA) \n\n10.7759/cureus.8513\nEndocrinology/Diabetes/Metabolism\nInternal Medicine\nGastroenterology\nSulfonylurea-Induced Hypoglycemia in a Patient With Cirrhosis\nMuacevic Alexander Adler John R Braet Corey 1 Hussein Agha Yasmine 1 Taleb Ali 1 Buess Charles 1 Millard John 2 \n1 \nInternal Medicine, University of Kansas School of Medicine-Wichita, Wichita, USA \n\n2 \nPharmacy, Robert J. Dole Veterans Affairs Medical Center, Wichita, USA \n\nYasmine Hussein Agha [email protected]\n8 6 2020 \n6 2020 \n12 6 e851325 5 2020 7 6 2020 Copyright © 2020, Braet et al.2020Braet et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article is available from https://www.cureus.com/articles/33768-sulfonylurea-induced-hypoglycemia-in-a-patient-with-cirrhosisType 2 diabetes mellitus is highly prevalent among patients with cirrhosis. The pharmacological management of this disease in patients with chronic liver disease remains controversial, however. Insulin secretagogues such as sulfonylureas are associated with a high risk of hypoglycemia among diabetics. In patients with cirrhosis, this risk is more pronounced due to decreased hepatic clearance, concurrent alcoholism, hypoalbuminemia, and acute liver decompensation. In this case report, we present a case of severe refractory hypoglycemia secondary to glipizide in a patient with alcoholic cirrhosis. We believe that the use of sulfonylureas in this patient population should be contraindicated to avoid debilitating neurologic damage and death following hypoglycemia.\n\nsulfonylurea compoundsliver cirrhosisdrug contraindicationsThe content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.\n==== Body\nIntroduction\nType 2 diabetes mellitus (DM) is highly associated with chronic liver disease, with an overall prevalence estimated at 31% among patients with cirrhosis [1]. Treating DM with sulfonylureas (SUs) in patients with cirrhosis is challenging since these drugs are metabolized by the liver. Most guidelines consider SUs safe in this patient population, whereas others recommend dose reduction [2,3]. The extent of liver damage in patients with cirrhosis is unpredictable and difficult to quantify, whether the patient is in a compensated state or deteriorating. With that in mind, the risk of hypoglycemia is expected to be higher in patients with cirrhosis taking SUs compared with diabetics without liver disease taking SUs. Despite the debilitating and fatal outcomes of hypoglycemia, no guidelines have discussed contraindicating SUs in patients with chronic liver disease. We present a case of severe refractory hypoglycemia secondary to glipizide in a patient with alcoholic cirrhosis.\n\nCase presentation\nA 69-year-old male with a history of alcoholic liver cirrhosis and DM presented to the emergency department with weakness since awakening that morning. He was conscious but lethargic and was not oriented to time or place. Neurological examination was unremarkable for focal neurological deficits other than mild slurring of his speech. He denied having any seizure activity or loss of consciousness prior to arrival. His last alcoholic drink was three days prior to presentation. On physical examination, he had icterus, was mildly jaundiced, and appeared malnourished. He had minimal ascites and mild bilateral non-pitting lower limb edema. His lungs were clear, heart sounds were normal, and abdomen was non-tender.\n\nHe was afebrile, tachycardic with a heart rate of 120 beats per minute, and normotensive. Serum glucose was measured at bedside and was profoundly low (40 mg/dL). He was initially managed with multiple boluses of 50% dextrose, glucose gel every 15 minutes, and a continuous infusion of 10% dextrose in water in a stepwise manner. However, his blood sugar failed to stabilize. Initial laboratory work-up revealed leukocytosis, thrombocytopenia, acute kidney injury, hypoalbuminemia, transaminitis, and hyperbilirubinemia (Table 1). His serum ethanol was undetectable, and urine drug screen was negative. Urine SU screen was ordered as well and was still pending on the first day of admission. His MELD-Na score (Model for End-stage Liver Disease with Sodium) was 25, which translated to a 15% chance of mortality within three months. His liver function test and MELD-Na score obtained six months prior to admission were similar to his current results.\n\nTable 1 Initial laboratory work-up \n\nLaboratory tests\n\t\nResults\n\t\nReference range\n\t\n\nWhite blood cell count\n\t\n18.9\n\t\n4.8–10.8 x 103/µL\n\t\n\nHemoglobin\n\t\n12\n\t\n12–16 gm/dL\n\t\n\nPlatelets\n\t\n100\n\t\n150–400 x 103/µL\n\t\n\nSodium\n\t\n135\n\t\n136–145 meq/L\n\t\n\nPotassium\n\t\n4.5\n\t\n3.5–5.1 meq/L\n\t\n\nChloride\n\t\n102\n\t\n96–106 meq/L\n\t\n\nBicarbonate\n\t\n26\n\t\n23–29 meq/L\n\t\n\nBlood urea nitrogen\n\t\n28\n\t\n6–20 mg/dL\n\t\n\nCreatinine\n\t\n1.85\n\t\n0.6–1.3 mg/dL\n\t\n\nAlbumin\n\t\n1.5\n\t\n3.5–5.5 g/dL\n\t\n\nAspartate aminotransferase\n\t\n152\n\t\n10–40 U/L\n\t\n\nAlanine aminotransferase\n\t\n86\n\t\n10–40 U/L\n\t\n\nAlkaline phosphatase\n\t\n95\n\t\n30–120 U/L\n\t\n\nTotal bilirubin\n\t\n5.5\n\t\n0.3–1.0 mg/dL\n\t\n\nUnconjugated bilirubin\n\t\n4\n\t\n0.2–0.7 mg/dL\n\t\n\nInternational normalized ratio\n\t\n1.5\n\t\n0.8–1.1\n\t\n\nAmmonia\n\t\n30\n\t\n40–70 μg/dL\n\t\n\nEthanol\n\t\n< 5\n\t\n˂5 mg/dL\n\t\nComputed tomography (CT) of the brain without contrast did not show any acute abnormalities. Upon review of his medication list, it was noted that he was on glipizide for the treatment of DM, and his last dose was the night prior to presentation. He had been on this medication for years and had never developed hypoglycemia. Since SU toxicity was the most probable cause of his persistent hypoglycemia, he was given 50 mcg of octreotide subcutaneously every eight hours in addition to a continuous infusion of 5% dextrose in half normal saline until serum glucose increased and was maintained within the normal range. Three days later, his urine SU screen showed a urine glipizide level of 480 ng/mL (reference: <5 ng/mL).\n\nDiscussion\nGlucose intolerance and DM are highly prevalent among patients with cirrhosis [4]. Studies have shown that glucose intolerance is found in 80% of patients with cirrhosis, whereas the prevalence of overt DM was found to range from 10% to 30% [4,5]. This has been reported to be caused by increased insulin resistance in patients with cirrhosis [2]. This association is even more pronounced in patients with alcoholic liver disease given the propensity of alcohol ingestion to decrease insulin-mediated glucose uptake in addition to chronic pancreatic damage [5,6].\n\nPharmacological management of DM in patients with chronic liver disease is still controversial. Due to increased risk of lactic acidosis, metformin is not recommended as a first-line treatment for DM in patients with cirrhosis [2]. Insulin secretagogues such as SUs, which are used as second-line treatment of DM in the general population, are generally considered safe in patients with liver disease, although issues regarding their efficacy have been raised in the setting of alcoholic liver disease and pancreatic damage [2]. In particular, patients with decompensated cirrhosis are more prone to hypoglycemia and have shown a decreased capacity to counteract hypoglycemia secondary to these medications [2,7]. Since SUs are metabolized by the liver, a decrease in breakdown of these medications in the setting of liver cirrhosis may result in increased plasma concentrations, thereby increasing the risk of hypoglycemia [7].\n\nAdditionally, hypoalbuminemia in the setting of chronic liver disease may result in reduced protein-binding of SUs, which may also result in increased SU plasma concentrations, thereby increasing the risk of hypoglycemia [3,8]. In the setting of alcohol consumption, decreased potency of SUs may result from alcohol-induced enzymatic degradation of SUs in addition to damage of beta islet cells of the pancreas [9,10]. Despite this decreased potency, patients taking SUs who have not abstained from alcohol are at an increased risk of hypoglycemia due to the inhibitory effects of alcohol on hepatic gluconeogenesis [7]. Another contributory factor to hypoglycemia is the increased prevalence of malnutrition among patients with chronic liver disease and patients with chronic alcohol use [3,7].\n\nGiven the limited studies evaluating the pharmacokinetics and safety of oral anti-diabetic drugs in patients with cirrhosis, the use of SUs remains a controversial issue. The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) stated that it is “unwise to use sulfonylureas, particularly glyburide” in the setting of severe hepatic disease due to the risk of hypoglycemia [11]. Khan et al. reported the dosage of SUs should be decreased to half of the usual dosage in patients with cirrhosis, particularly if they have not abstained from alcohol [12]. Scheen et al. explained that SUs can be given with close monitoring for hypoglycemia [7]. Gangopadhyay and Singh reported that while SUs should be avoided in patients with cirrhosis, lower doses may be considered in patients with Child-Pugh Class A and B and should be completely avoided in patients with Child-Pugh Class C [3].\n\nThe patient described in this case report had a longstanding history of alcoholic cirrhosis, was still drinking alcohol intermittently, and was on glyburide. He developed hypoglycemia after stopping drinking alcoholic beverages for three days, which may have allowed glipizide to be more potent since its alcohol-induced enzymatic degradation was reduced. Patients with medication non-compliance, alcoholism, malnutrition, and recurrent hospital admissions have unpredictable outcomes regardless of whether their liver disease is decompensated or stable. Given the high risk of death and long-term neurological damage from hypoglycemia, we believe that SUs should be contraindicated in patients with chronic liver disease.\n\nConclusions\nThe risk of hypoglycemia secondary to SUs in patients with cirrhosis is more likely to be higher than the general diabetic population due to associated behavior such as alcoholism, malnutrition, medication interaction, decreased hepatic clearance, and further decompensation. The use of SUs in this patient population should be contraindicated to avoid further decompensation and death following hypoglycemia.\n\nThe authors have declared that no competing interests exist.\n\nHuman Ethics\nConsent was obtained by all participants in this study\n==== Refs\nReferences\n1 Prevalence of diabetes in liver cirrhosis: a systematic review and meta-analysis Diabetes Metab Res Rev Lee WG Wells CI McCall JL Murphy R Plank LD 3157 35 2019 \n2 Spectrum of liver disease in type 2 diabetes and management of patients with diabetes and liver disease Diabetes Care Tolman KG Fonseca V Dalpiaz A Tan MH 734 743 30 2007 17327353 \n3 Consensus statement on dose modifications of antidiabetic agents in patients with hepatic impairment Indian J Endocrinol Metab Gangopadhyay KK Singh P 341 354 21 2017 28459036 \n4 Prevalence of diabetes mellitus in patients with end-stage liver cirrhosis due to hepatitis C, alcohol, or cholestatic disease J Hepatol Zein NN Abdulkarim AS Wiesner RH Egan KS Persing DH 209 217 32 2000 10707860 \n5 Liver cirrhosis and diabetes: risk factors, pathophysiology, clinical implications and management World J Gastroenterol Garcia-Compean D Jaquez-Quintana JO Gonzalez-Gonzalez JA Maldonado-Garza H 280 288 21 2009 \n6 Impact of diabetes on the severity of liver disease Am J Med Hickman IJ Macdonald GA 829 834 120 2007 17904449 \n7 Pharmacokinetic and toxicological considerations for the treatment of diabetes in patients with liver disease Expert Opin Drug Metab Toxicol Scheen AJ 839 857 10 2014 24669954 \n8 Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: a consensus statement Indian J Endocrinol Metab Kalra S Aamir AH Raza A 577 596 19 2015 26425465 \n9 Antidiabetic agents in patients with hepatic impairment World J Meta-Anal Papazafiropoulou A Melidonis A 380 388 7 2019 \n10 Insulin secretagogues, sulfonylurea receptors and K(ATP) channels Curr Pharm Des Bryan J Crane A Vila-Carriles WH Babenko AP Aguilar-Bryan L 2699 2716 11 2005 16101450 \n11 Management of hyperglycemia in type 2 diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetes Davies MJ D'Alessio DA Fradkin J 2669 2701 41 2018 \n12 Managing diabetes in patients with chronic liver disease Postgrad Med Khan R Foster GR Chowdhury TA 130 137 124 2012 22913901\n\n", "fulltext_license": "CC BY", "issn_linking": "2168-8184", "issue": "12(6)", "journal": "Cureus", "keywords": "drug contraindications; liver cirrhosis; sulfonylurea compounds", "medline_ta": "Cureus", "mesh_terms": null, "nlm_unique_id": "101596737", "other_id": null, "pages": "e8513", "pmc": null, "pmid": "32656029", "pubdate": "2020-06-08", "publication_types": "D002363:Case Reports", "references": "24669954;30291106;17327353;30901133;22913901;17904449;26425465;16101450;28459036;19140227;10707860", "title": "Sulfonylurea-Induced Hypoglycemia in a Patient With Cirrhosis.", "title_normalized": "sulfonylurea induced hypoglycemia in a patient with cirrhosis" }

[ { "companynumb": "US-ACCORD-193096", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "GLIPIZIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "074550", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "TYPE 2 DIABETES MELLITUS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLIPIZIDE." } ], "patientagegroup": null, "patientonsetage": "69", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypoglycaemia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "BRAET C, HUSSEIN AGHA Y, TALEB A, BUESS C, MILLARD J. SULFONYLUREA?INDUCED HYPOGLYCEMIA IN A PATIENT WITH CIRRHOSIS. CUREUS. 2020 JUN 8?12(6):E8513.", "literaturereference_normalized": "sulfonylurea induced hypoglycemia in a patient with cirrhosis", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20200729", "receivedate": "20200729", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18083689, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" } ]

{ "abstract": "The potential hazard of blindness from injections in the face, nose, and mouth and the mechanisms by which this complication takes place are discussed. Precautionary measures, which we originally recommended for nasal turbinate injections, appear to be applicable for all injections in this area. We encourage their usage.", "affiliations": null, "authors": "McCleve|D E|DE|;Goldstein|J C|JC|", "chemical_list": null, "country": "United States", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "0145-5613", "issue": "74(3)", "journal": "Ear, nose, & throat journal", "keywords": null, "medline_ta": "Ear Nose Throat J", "mesh_terms": "D001766:Blindness; D003813:Dentistry; D005145:Face; D006801:Humans; D007279:Injections, Subcutaneous; D009055:Mouth; D009666:Nose; D009885:Ophthalmology; D010036:Otolaryngology; D013518:Surgery, Plastic", "nlm_unique_id": "7701817", "other_id": null, "pages": "182-8", "pmc": null, "pmid": "7729344", "pubdate": "1995-03", "publication_types": "D016428:Journal Article; D016454:Review", "references": null, "title": "Blindness secondary to injections in the nose, mouth, and face: cause and prevention.", "title_normalized": "blindness secondary to injections in the nose mouth and face cause and prevention" }

[ { "companynumb": "US-PFIZER INC-202200568701", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE ACETATE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "11757", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Suspension for injection", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE ACETATE" } ], "patientagegroup": null, "patientonsetage": "24", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Wrong technique in product usage process", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Visual impairment", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Skin discolouration", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Mccleve, D.. Blindness secondary to injections in the nose, mouth, and face: Cause and prevention. Ear, Nose and Throat Journal. 1995;74(3):182-188", "literaturereference_normalized": "blindness secondary to injections in the nose mouth and face cause and prevention", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20220427", "receivedate": "20220427", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20759002, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220721" } ]

{ "abstract": "OBJECTIVE\nSymptomatic non-acute intracranial arterial occlusion (NAICO) is not uncommon. We report a single-center experience of the feasibility and safety of endovascular treatment of anterior circulation NAICO and summarize the outcomes of patient groups with successful or failed recanalization.\n\n\nMETHODS\nPatients who underwent endovascular therapy for intracranial arterial stenosis between January 2010 and May 2017 were retrospectively reviewed. Thirty-eight patients with symptomatic NAICO (symptom onset > 24 hours) in the anterior circulation were identified.\n\n\nRESULTS\nSuccessful recanalization was achieved in 76.3% of patients (29/38). Intraprocedural events occurred in 10.5% (4/38), including intima dissection (n = 1), parent artery rupture (n = 1) and acute in-stent thrombosis (n = 2). Mean follow-up duration after successful recanalization was 36.5 months. One patient died 68 days after the procedure because of a newly developed posterior circulation stroke. Acute reocclusion was observed in two patients (6.7%); subacute or delayed reocclusion was observed in three patients (10%). Good final outcome (modified Rankin Scale score ≤ 2) was achieved in 25 of 28 patients (89.3%) at three months. Mean follow-up duration of the nine patients with failed recanalization was 41.4 months. Three patients underwent extra-intracranial bypass for worsening symptoms. The other six patients showed stable or improved neurological status with antiplatelet medications. Good final outcome was achieved in eight of nine patients (88.9%) at three months.\n\n\nCONCLUSIONS\nEndovascular revascularization can be a viable option with an acceptable safety profile in selected patients with symptomatic NAICO in the anterior circulation. Further characterization of aborted cases would facilitate proper patient selection for endovascular treatment.", "affiliations": "1 Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.;1 Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.;1 Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.;1 Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.;1 Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.", "authors": "Yu Jia|Zhen|Z|https://orcid.org/0000-0002-5134-9339;Sun Song|Yun|Y|;Jon Sheen|Jae|J|;Goo Kim|Joong|J|https://orcid.org/0000-0002-4166-6023;Hee Lee|Deok|D|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1177/1591019919826616", "fulltext": null, "fulltext_license": null, "issn_linking": "1591-0199", "issue": "25(4)", "journal": "Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences", "keywords": "Intracranial occlusion; outcomes; stenting", "medline_ta": "Interv Neuroradiol", "mesh_terms": "D000368:Aged; D001157:Arterial Occlusive Diseases; D057510:Endovascular Procedures; D005260:Female; D006801:Humans; D020765:Intracranial Arterial Diseases; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome", "nlm_unique_id": "9602695", "other_id": null, "pages": "380-389", "pmc": null, "pmid": "30813809", "pubdate": "2019-08", "publication_types": "D016428:Journal Article", "references": "10782772;20538827;21506064;21899409;21940974;21990494;23471022;24249733;24635938;25276423;25803345;26067617;26885148;27174525;28434956;28592778;28926782;28955511", "title": "Endovascular recanalization of symptomatic non-acute intracranial artery occlusion: Procedural and mid-term clinical outcomes in the anterior circulation.", "title_normalized": "endovascular recanalization of symptomatic non acute intracranial artery occlusion procedural and mid term clinical outcomes in the anterior circulation" }

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HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "040", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "PATIENT RECEIVED INTRAARTERIAL TIROFIBAN AT RECOMMENDED LOADING DOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": "OFF LABEL USE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AGGRASTAT" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CLOPIDOGREL BISULFATE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "DUAL ANTIPLATELET THERAPY (DAPT)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLOPIDOGREL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ASPIRIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "DUAL 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"drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "300", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLOPIDOGREL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ASPIRIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "DUAL ANTIPLATELET THERAPY (DAPT)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "300", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ASPIRIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TIROFIBAN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "041", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INFUSION", "drugdosagetext": "PATIENT RECEIVED INTRAARTERIAL TIROFIBAN AT RECOMMENDED MAINTENANCE DOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIPLATELET THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AGGRASTAT" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "HEPARIN SODIUM" }, "drugadditional": null, "drugadministrationroute": "041", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INFUSION", "drugdosagetext": "ADDITIONAL 100 IU HEPARIN PER HOUR GIVEN TO MAINTAIN THE ACTIVATED CLOTTING TIME", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "025", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HEPARIN" } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Vascular stent occlusion", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Ischaemic cerebral infarction", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20190107" } }, "primarysource": { "literaturereference": "JIA ZY, SONG YS, SHEEN JJ, KIM JG, AND LEE DH. ENDOVASCULAR RECANALIZATION OF SYMPTOMATIC NON-ACUTE INTRACRANIAL ARTERY OCCLUSION: PROCEDURAL AND MID-TERM CLINICAL OUTCOMES IN THE ANTERIOR CIRCULATION. INTERVENTIONAL NEURORADIOLOGY. FEBRUARY 27, 2019. ?HTTPS://DOI.ORG/10.1177/1591019919826616", "literaturereference_normalized": "endovascular recanalization of symptomatic non acute intracranial artery occlusion procedural and mid term clinical outcomes in the anterior circulation", "qualification": "1", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20190712", "receivedate": "20190712", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "3", "safetyreportid": 16567534, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20191004" } ]

{ "abstract": "We recently found that metformin attenuated weight gain due to mixed dopamine and serotonin receptor antagonists, commonly termed atypical antipsychotics, in children and adolescents with autism spectrum disorder (ASD). Previous studies have found that genetic variation predicts response to metformin in diabetes. In this study, we aimed to assess whether response to metformin for weight gain in this population is associated with variants in five genes previously implicated in metformin response in diabetes. Youth with ASD who experienced significant weight gain while taking mixed receptor antagonist medications were randomly assigned to metformin or placebo for 16 weeks, followed by open-label metformin treatment for 16 weeks. In the 53 participants with available DNA samples, we used a linear, mixed model analysis to assess response in the first 16 weeks of metformin treatment, whether in the randomized or open-label period, based upon genotypes at polymorphisms in five genes previously associated with metformin response in diabetes: ATM, SLC2A2, MATE1, MATE2, and OCT1. In the primary analysis, both ATM and OCT1 showed significant effects of genotype on change in body mass index z-scores, the primary outcome measure, during the first 16 weeks of treatment with metformin. No other polymorphism showed a significant difference. As has been shown for metformin treatment in diabetes, genetic variation may predict response to metformin for weight gain in youth with ASD treated with mixed receptor antagonists. Further work is needed to replicate these findings and evaluate whether they can be used prospectively to improve outcomes.", "affiliations": "1Department of Psychiatry, Columbia University Medical Center, New York, New York.;2Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Canada.;4Nisonger Center, The Ohio State University, Columbus, Ohio.;5Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.;6Department of Psychiatry, Vanderbilt University, Nashville, Tennessee.;7Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts.;7Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts.;1Department of Psychiatry, Columbia University Medical Center, New York, New York.", "authors": "Garfunkel|Danielle|D|;Anagnostou|Evdokia A|EA|;Aman|Michael G|MG|;Handen|Benjamin L|BL|;Sanders|Kevin B|KB|;Macklin|Eric A|EA|;Chan|James|J|;Veenstra-VanderWeele|Jeremy|J|", "chemical_list": "D007004:Hypoglycemic Agents; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D008687:Metformin; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins", "country": "United States", "delete": false, "doi": "10.1089/cap.2018.0171", "fulltext": null, "fulltext_license": null, "issn_linking": "1044-5463", "issue": "29(6)", "journal": "Journal of child and adolescent psychopharmacology", "keywords": "atypical antipsychotic; autism spectrum disorder; diabetes; irritability; weight gain", "medline_ta": "J Child Adolesc Psychopharmacol", "mesh_terms": "D000293:Adolescent; D064007:Ataxia Telangiectasia Mutated Proteins; D000067877:Autism Spectrum Disorder; D002648:Child; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D007004:Hypoglycemic Agents; D008297:Male; D008687:Metformin; D050811:Octamer Transcription Factor-1; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D015430:Weight Gain", "nlm_unique_id": "9105358", "other_id": null, "pages": "448-455", "pmc": null, "pmid": "31188026", "pubdate": "2019-08", "publication_types": "D016428:Journal Article; D016449:Randomized Controlled Trial; D013487:Research Support, U.S. Gov't, P.H.S.", "references": null, "title": "Pharmacogenetics of Metformin for Medication-Induced Weight Gain in Autism Spectrum Disorder.", "title_normalized": "pharmacogenetics of metformin for medication induced weight gain in autism spectrum disorder" }

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{ "abstract": "The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.", "affiliations": "Division of Infection and Immunity, University College London, London, UK.;Division of Infection and Immunity, University College London, London, UK.;Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK.;Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK.;Department of Infectious Diseases, Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK.;Department of Pathology, University of Cambridge, Cambridge, UK.;Department of Pathology, University of Cambridge, Cambridge, UK.;Division of Infection and Immunity, University College London, London, UK.;Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK.;NHS Blood and Transplant, Oxford and BRC Haematology Theme, University of Oxford, Oxford, UK.;NHS Blood and Transplant, Oxford and BRC Haematology Theme, University of Oxford, Oxford, UK.;Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK.;Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent, Canterbury, UK.;Department of Infectious Diseases, Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK.;Department of Medicine, University of Cambridge, Cambridge, UK.;Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK.;Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK.;Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.;Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.;Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK.;Department of Medicine, University of Cambridge, Cambridge, UK.;Department of Virology, Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK.;Department of Clinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge, UK.;Department of Clinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge, UK.;Department of Clinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge, UK.;Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO, USA.;Division of Infection and Immunity, University College London, London, UK.;Department of Pathology, University of Cambridge, Cambridge, UK.;Department of Infectious Diseases, Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK.;Department of Infectious Diseases, Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK.;Department of Pathology, University of Cambridge, Cambridge, UK.;Department of Infectious Diseases, Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK.;Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, UK.;Division of Infection and Immunity, University College London, London, UK.;Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK. [email protected].", "authors": "Kemp|Steven A|SA|;Collier|Dami A|DA|http://orcid.org/0000-0001-5446-4423;Datir|Rawlings P|RP|;Ferreira|Isabella A T M|IATM|;Gayed|Salma|S|;Jahun|Aminu|A|http://orcid.org/0000-0002-4585-1701;Hosmillo|Myra|M|;Rees-Spear|Chloe|C|;Mlcochova|Petra|P|;Lumb|Ines Ushiro|IU|;Roberts|David J|DJ|;Chandra|Anita|A|;Temperton|Nigel|N|http://orcid.org/0000-0002-7978-3815;|||;|||;Sharrocks|Katherine|K|;Blane|Elizabeth|E|;Modis|Yorgo|Y|http://orcid.org/0000-0002-6084-0429;Leigh|Kendra E|KE|;Briggs|John A G|JAG|http://orcid.org/0000-0003-3990-6910;van Gils|Marit J|MJ|;Smith|Kenneth G C|KGC|;Bradley|John R|JR|;Smith|Chris|C|;Doffinger|Rainer|R|;Ceron-Gutierrez|Lourdes|L|;Barcenas-Morales|Gabriela|G|;Pollock|David D|DD|;Goldstein|Richard A|RA|http://orcid.org/0000-0001-5148-4672;Smielewska|Anna|A|;Skittrall|Jordan P|JP|http://orcid.org/0000-0002-8228-3758;Gouliouris|Theodore|T|;Goodfellow|Ian G|IG|;Gkrania-Klotsas|Effrossyni|E|http://orcid.org/0000-0002-0930-8330;Illingworth|Christopher J R|CJR|;McCoy|Laura E|LE|http://orcid.org/0000-0001-9503-7946;Gupta|Ravindra K|RK|http://orcid.org/0000-0001-9751-1808", "chemical_list": "D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D050505:Mutant Proteins; D064370:Spike Glycoprotein, Coronavirus; C000657845:spike protein, SARS-CoV-2; C000606551:remdesivir; D000249:Adenosine Monophosphate; D000409:Alanine", "country": "England", "delete": false, "doi": "10.1038/s41586-021-03291-y", "fulltext": null, "fulltext_license": null, "issn_linking": "0028-0836", "issue": "592(7853)", "journal": "Nature", "keywords": null, "medline_ta": "Nature", "mesh_terms": "D000249:Adenosine Monophosphate; D000368:Aged; D000409:Alanine; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000086382:COVID-19; D002908:Chronic Disease; D019143:Evolution, Molecular; D016679:Genome, Viral; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D057131:Immune Evasion; D007108:Immune Tolerance; D007116:Immunization, Passive; D007165:Immunosuppression Therapy; D008297:Male; D016296:Mutagenesis; D050505:Mutant Proteins; D009154:Mutation; D010802:Phylogeny; D000086402:SARS-CoV-2; D064370:Spike Glycoprotein, Coronavirus; D013997:Time Factors; D019562:Viral Load; D017201:Virus Shedding", "nlm_unique_id": "0410462", "other_id": null, "pages": "277-282", "pmc": null, "pmid": "33545711", "pubdate": "2021-04", "publication_types": "D002363:Case Reports; D016428:Journal Article; D052061:Research Support, N.I.H., Extramural; D013485:Research Support, Non-U.S. Gov't", "references": "32142651;33298935;33176080;33248470;32841599;32692348;32540902;22456633;32694201;33271067;7442695;32645326;32994364;28170438;29212934;32679081;32838340;32737467;32679081;6137996;20451557;15635002;18490657;28382917;3603318;32669681;32011700;28481363;23418397;27153641;32773034;27774277;25675341;32647346;31774913;8876144;20597164;23227216;32905045;33106674;32540902", "title": "SARS-CoV-2 evolution during treatment of chronic infection.", "title_normalized": "sars cov 2 evolution during treatment of chronic infection" }

[ { "companynumb": "GB-GILEAD-2021-0516659", "fulfillexpeditecriteria": "1", "occurcountry": "GB", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "REMDESIVIR" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "214787", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "TWO 10?DAY COURSES WITH A FIVE DAY GAP IN BETWEEN (DAYS 41 AND 54)", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 PNEUMONIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "REMDESIVIR." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "HUMAN PLASMA" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "DAYS 63, 65 AND 95", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PLASMA" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "REMDESIVIR" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "214787", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "THIRD COURSE AT DAY 93", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "REMDESIVIR." } ], "patientagegroup": "6", "patientonsetage": "70", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Death", "reactionmeddraversionpt": "24.0", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "GUPTA, R. SARS?COV?2 EVOLUTION DURING TREATMENT OF CHRONIC INFECTION.. NATURE. 2021?UNK:UNK", "literaturereference_normalized": "sars cov 2 evolution during treatment of chronic infection", "qualification": "3", "reportercountry": "GB" }, "primarysourcecountry": "GB", "receiptdate": "20210526", "receivedate": "20210212", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 18889197, "safetyreportversion": 5, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210717" } ]

{ "abstract": "Standard treatment for class III, IV, and V lupus nephritis (LN) is a combination of oral corticosteroids and mycophenolate mofetil (MMF). There is an estimated failure rate of 16%. Several small studies have looked at the use of tacrolimus in class III, IV, and V LN, both as induction treatment and as maintenance in patients refractory to other treatments. The majority of these studies were conducted in Asian patients. We discuss a cohort of eight female patients of various ethnicities with biopsy proven LN. All patients were evaluated retrospectively. Six were started on tacrolimus after failing to respond to MMF and corticosteroids, and one was started on tacrolimus alone because treatment options were limited by pregnancy. Five were Caucasian, one African American, one Hispanic, and one Vietnamese. Mean tacrolimus dose was 3.3mg daily (range 2-5 mg) titrated to a mean level of 3-6 ng/dl (range 3-6.6 ng/dl) for a mean of duration of 16 months (range 2-54 months). Six patients experienced complete remission (proteinuria <0.33 g/day), and two patients had a partial remission (minimum of 50% reduction in baseline proteinuria). Albumin increased an average of 32%. Average C3/C4 levels were 64/15 mg/dL, respectively, prior to treatment, and 95/25 mg/dL following treatment. No treatment-limiting adverse effects were reported. Our case series supports the growing body of evidence that tacrolimus is an effective therapy in LN patients with refractory proteinuria. Further studies are required to establish the long-term safety and efficacy of tacrolimus.", "affiliations": "Tripler Army Medical Center, Honolulu, HI.", "authors": "Gordon|Sarah|S|;Denunzio|Troy|T|;Uy|Alice|A|", "chemical_list": "D007166:Immunosuppressive Agents; D016559:Tacrolimus", "country": "United States", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "2165-8242", "issue": "72(9 Suppl 4)", "journal": "Hawai'i journal of medicine & public health : a journal of Asia Pacific Medicine & Public Health", "keywords": null, "medline_ta": "Hawaii J Med Public Health", "mesh_terms": "D000328:Adult; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative; D015433:Glomerulonephritis, Membranous; D006801:Humans; D007166:Immunosuppressive Agents; D008181:Lupus Nephritis; D011507:Proteinuria; D012189:Retrospective Studies; D016559:Tacrolimus; D055815:Young Adult", "nlm_unique_id": "101579076", "other_id": null, "pages": "18-23", "pmc": null, "pmid": "24052913", "pubdate": "2013-09", "publication_types": "D016428:Journal Article", "references": "8787947;20581020;18753192;22570338;18596121;7688103;15803929;11112018;19688181;9083285;21917733;16014060;20089610;18003764;20388722;11036121;22295934;21051743;4104337;7138600;22541676;20833738;16412718;3511372;21382917;17971363;22456060", "title": "Success using tacrolimus in patients with proliferative and membranous lupus nephritis and refractory proteinuria.", "title_normalized": "success using tacrolimus in patients with proliferative and membranous lupus nephritis and refractory proteinuria" }

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"activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LOSARTAN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOSARTAN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "090509", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "HYDROXYCHLOROQUINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROXYCHLOROQUINE" } ], "patientagegroup": null, "patientonsetage": "28", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Tremor", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "GORDON S, DENUNZIO T, UY A. SUCCESS USING TACROLIMUS IN PATIENTS WITH PROLIFERATIVE AND MEMBRANOUS LUPUS NEPHRITIS AND REFRACTORY PROTEINURIA. HAWAII J MED PUBLIC HEALTH. 2013;72(4):18-23.", "literaturereference_normalized": "success using tacrolimus in patients with proliferative and membranous lupus nephritis and refractory proteinuria", "qualification": "1", "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20160708", "receivedate": "20160708", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12539324, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20161109" }, { "companynumb": "PHHY2015US076106", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "TACROLIMUS" }, 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SUCCESS USING TACROLIMUS IN PATIENTS WITH PROLIFERATIVE AND MEMBRANOUS LUPUS NEPHRITIS AND REFRACTORY PROTEINURIA.. HAWAII-J-MED-PUBLIC-HEALTH. 2013;72(94):18-23", "literaturereference_normalized": "success using tacrolimus in patients with proliferative and membranous lupus nephritis and refractory proteinuria", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20150630", "receivedate": "20150630", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11229507, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150821" }, { "companynumb": "US-DRREDDYS-USA/USA/15/0049155", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" 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SUCCESS USING TACROLIMUS IN PATIENTS WITH PROLIFERATIVE AND MEMBRANOUS LUPUS NEPHRITIS AND REFRACTORY PROTEINURIA. HAWAII J MED PUBLIC HEALTH. 2013;72(4):18-23.", "literaturereference_normalized": "success using tacrolimus in patients with proliferative and membranous lupus nephritis and refractory proteinuria", "qualification": "1", "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20160708", "receivedate": "20160708", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12539487, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20161109" }, { "companynumb": "US-DRREDDYS-USA/USA/15/0049161", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": 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SUCCESS USING TACROLIMUS IN PATIENTS WITH PROLIFERATIVE AND MEMBRANOUS LUPUS NEPHRITIS AND REFRACTORY PROTEINURIA. HAWAII J MED PUBLIC HEALTH. 2013;72(4):18-23.", "literaturereference_normalized": "success using tacrolimus in patients with proliferative and membranous lupus nephritis and refractory proteinuria", "qualification": "1", "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20160708", "receivedate": "20160708", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12539476, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20161109" }, { "companynumb": "US-DRREDDYS-USA/USA/15/0049162", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": 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"activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TELMISARTAN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MICARDIS" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL." } ], "patientagegroup": null, "patientonsetage": "22", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hyperglycaemia", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Oral candidiasis", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GORDON S, DENUNZIO T, UY A. SUCCESS USING TACROLIMUS IN PATIENTS WITH PROLIFERATIVE AND MEMBRANOUS LUPUS NEPHRITIS AND REFRACTORY PROTEINURIA. HAWAII J MED PUBLIC HEALTH. 2013;72(4):18-23.", "literaturereference_normalized": "success using tacrolimus in patients with proliferative and membranous lupus nephritis and refractory proteinuria", "qualification": "1", "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20160708", "receivedate": "20160708", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12539342, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20161109" }, { "companynumb": "US-DRREDDYS-USA/USA/15/0049143", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "SIMVASTATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SIMVASTATIN." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "090509", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": 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null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." } ], "patientagegroup": null, "patientonsetage": "27", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Treatment noncompliance", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Proteinuria", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GORDON S, DENUNZIO T, UY A. SUCCESS USING TACROLIMUS IN PATIENTS WITH PROLIFERATIVE AND MEMBRANOUS LUPUS NEPHRITIS AND REFRACTORY PROTEINURIA. HAWAII J MED PUBLIC HEALTH. 2013;72(4):18-23.", "literaturereference_normalized": "success using tacrolimus in patients with proliferative and membranous lupus nephritis and refractory proteinuria", "qualification": "1", "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20160708", "receivedate": "20160708", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12539475, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20161109" }, { "companynumb": "PHHY2015US077434", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LUPUS NEPHRITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "080336", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "LUPUS NEPHRITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." } ], "patientagegroup": null, "patientonsetage": "20", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Nephrotic syndrome", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Oedema", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GORDON S, DENUNIZO T, UY A. SUCCESS USING TACROLIMUS IN PATIENTS WITH PROLIFERATIVE AND MEMBRANOUS LUPUS NEPHRITIS AND REFRACTORY PROTEINURIA.. HAWAII-J-MED-PUBLIC-HEALTH. 2013;72(94):18-23", "literaturereference_normalized": "success using tacrolimus in patients with proliferative and membranous lupus nephritis and refractory proteinuria", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20150630", "receivedate": "20150630", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11228691, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150821" }, { "companynumb": "US-DRREDDYS-USA/USA/15/0049158", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "090509", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG ONCE IN THE MORNING AND 1 MG IN THE NIGHT.", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." } ], "patientagegroup": null, "patientonsetage": "20", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hypomagnesaemia", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "GORDON S, DENUNZIO T, UY A. SUCCESS USING TACROLIMUS IN PATIENTS WITH PROLIFERATIVE AND MEMBRANOUS LUPUS NEPHRITIS AND REFRACTORY PROTEINURIA. HAWAII J MED PUBLIC HEALTH. 2013;72(4):18-23.", "literaturereference_normalized": "success using tacrolimus in patients with proliferative and membranous lupus nephritis and refractory proteinuria", "qualification": "1", "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20160708", "receivedate": "20160708", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12539323, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20161109" }, { "companynumb": "US-DRREDDYS-USA/USA/15/0049160", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": 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"patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Tooth abscess", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GORDON S, DENUNZIO T, UY A. SUCCESS USING TACROLIMUS IN PATIENTS WITH PROLIFERATIVE AND MEMBRANOUS LUPUS NEPHRITIS AND REFRACTORY PROTEINURIA. HAWAII J MED PUBLIC HEALTH. 2013;72(4):18-23.", "literaturereference_normalized": "success using tacrolimus in patients with proliferative and membranous lupus nephritis and refractory proteinuria", "qualification": "1", "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20160708", "receivedate": "20160708", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12539473, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20161109" }, { "companynumb": "US-DRREDDYS-USA/USA/15/0049159", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "HYDROXYCHLOROQUINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", 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"drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." } ], "patientagegroup": null, "patientonsetage": "29", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hypomagnesaemia", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "GORDON S, DENUNZIO T, UY A. SUCCESS USING TACROLIMUS IN PATIENTS WITH PROLIFERATIVE AND MEMBRANOUS LUPUS NEPHRITIS AND REFRACTORY PROTEINURIA. HAWAII J MED PUBLIC HEALTH. 2013;72(4):18-23.", "literaturereference_normalized": "success using tacrolimus in patients with proliferative and membranous lupus nephritis and refractory proteinuria", "qualification": "1", "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20160708", "receivedate": "20160708", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12539343, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20161109" } ]

{ "abstract": "BEVZ92 is a proposed biosimilar to bevacizumab. The two molecules have similar physicochemical and functional properties in in-vitro and preclinical studies. In this clinical study, we compared the pharmacokinetic profile, efficacy, safety, and immunogenicity of BEVZ92 with reference bevacizumab as a first-line treatment in patients with metastatic colorectal cancer.\n\n\n\nWe did a randomised, open-label trial at 15 centres in Argentina, Brazil, India, Spain, and Ukraine. Eligible patients were aged 18 years or older, had metastatic colorectal cancer with at least one measurable non-irradiated lesion for which first-line chemotherapy was indicated and Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, had not received previous treatment for advanced disease, and whose bone marrow, hepatic, renal, and coagulation markers were all within normal ranges. Patients were randomly assigned (1:1) to either BEVZ92 or reference bevacizumab (5 mg/kg on day 1 of each cycle every 2 weeks) in combination with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or fluorouracil, leucovorin, and irinotecan (FOLFIRI). Randomisation was done via a web service based on a stochastic minimisation algorithm and was stratified by chemotherapy regimen (FOLFOX vs FOLFIRI), previous adjuvant therapy (yes vs no), ECOG performance status (0-1 vs 2), and study site. The primary endpoint was the area under the concentration-versus-time curve after a single infusion (AUC0-336h) and at steady state (AUCss)-ie, at cycle 7-in the assessable population, which comprised all treated patients for whom serum concentration measurements were available during the first seven cycles. Bioequivalence was established if the 90% CIs for the ratio of BEVZ92 to reference bevacizumab of the geometric means for AUC0-336h and AUCss were within the acceptance interval of 80-125%. Secondary endpoints included objective response, clinical benefit, and progression-free survival in the intention-to-treat population and immunogenicity and safety profiles in all treated patients. This trial is registered with ClinicalTrials.gov, number NCT02069704, and is closed to new participants, with follow-up completed.\n\n\n\n142 patients were randomly assigned, 71 to the BEVZ92 group and 71 to the reference bevacizumab group. Two participants assigned to BEVZ92 did not receive treatment (one withdrew consent, the other had a serious intestinal obstruction before starting treatment); therefore, the treated population comprised 69 patients in the BEVZ92 group and 71 in the reference bevacizumab group. The geometric mean ratio of AUC0-336h in the BEVZ92 versus the control group was 99·4% (90% CI 90·5-109·0) and of AUCss was 100·0% (90·2-112·0). Objective response (35 [49%] of 71 vs 40 [56%] of 71), clinical benefit (62 [87%] vs 65 [92%]), and progression-free survival (median 10·8 months [95% CI 7·4-11·5] vs 11·1 months [95% CI 8·0-12·8]) were similar in the BEVZ92 and reference bevacizumab groups. No relevant differences were noted between the safety profiles of the two study treatments. Neutropenia was the most common grade 3 or 4 adverse event reported in the BEVZ92 (14 [20%] of 69 patients) and reference bevacizumab (19 [27%] of 71 patients) groups. Serious adverse events occurred in 19 (28%) patients in the BEVZ92 group and 21 (30%) in the reference bevacizumab group. Two patients died because of bevacizumab-related serious adverse events: a sudden death in the BEVZ92 group and a serious large intestinal perforation in the reference bevacizumab group. The occurrence of anti-drug antibodies was low and similar in both treatment groups (two patients in the BEVZ92 group and one in the reference bevacizumab group).\n\n\n\nOur results suggest that BEVZ92 and reference bevacizumab are pharmacokinetically bioequivalent and have no appreciable differences in efficacy, immunogenicity, and safety profiles as first-line treatment in combination with FOLFOX or FOLFIRI in patients with metastatic colorectal cancer.\n\n\n\nmAbxience Research SL.", "affiliations": "Centro Oncológico de Rosario, Rosario, Santa Fe, Argentina.;Municipal Healthcare Facility Kharkiv Regional Clinical Oncology Center, Kharkiv, Ukraine.;Danylo Halytsky Lviv National Medical University, Lviv State Oncology Regional Hospital 2a, Lviv, Ukraine.;Dnipropetrovsk State Medical Academy, Dnipropetrovsk, Ukraine.;Instituto do Câncer do Estado de São Paulo Otávio Frias de Oliveira, São Paulo, Brazil.;Fundaçáo Pio XII-Hospital de Câncer de Barretos, Barretos, Brazil.;Hospital de Gastroenterologia Dr Bonorino Udaondo, Buenos Aires, Argentina.;Hospital de Caridade Ijuí, Cacon, Brazil.;Instituto Brasileiro de Controle do Câncer, São Paulo, Brazil.;Saveetha Medical College and Hospital, Chennai, India.;Department of Medical Oncology, Tata Memorial Centre, Parel, Mumbai, India.;M S Patel Cancer Centre, Shree Krishna Hospital, Karamsand, India.;Regional Cancer Center & Medical College, Thiruvananthapuram, India.;mAbxience Research SL, Madrid, Spain.;mAbxience Research SL, Madrid, Spain.;mAbxience Research SL, Madrid, Spain. Electronic address: [email protected].;mAbxience Research SL, Madrid, Spain.", "authors": "Romera|Alvaro|A|;Peredpaya|Sergiy|S|;Shparyk|Yaroslav|Y|;Bondarenko|Igor|I|;Mendonça Bariani|Giovanni|G|;Abdalla|Kathia Cristina|KC|;Roca|Enrique|E|;Franke|Fábio|F|;Melo Cruz|Felipe|F|;Ramesh|Anita|A|;Ostwal|Vikas|V|;Shah|Pradeep|P|;Rahuman|Sajeed Abdul|SA|;Paravisini|Alexandra|A|;Huerga|Camino|C|;Del Campo García|Ana|A|;Millán|Susana|S|", "chemical_list": "D000906:Antibodies; D000074322:Antineoplastic Agents, Immunological; C000631406:BEVZ92; D059451:Biosimilar Pharmaceuticals; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin", "country": "Netherlands", "delete": false, "doi": "10.1016/S2468-1253(18)30269-3", "fulltext": null, "fulltext_license": null, "issn_linking": null, "issue": "3(12)", "journal": "The lancet. Gastroenterology & hepatology", "keywords": null, "medline_ta": "Lancet Gastroenterol Hepatol", "mesh_terms": "D000328:Adult; D000368:Aged; D000906:Antibodies; D000074322:Antineoplastic Agents, Immunological; D000971:Antineoplastic Combined Chemotherapy Protocols; D019540:Area Under Curve; D000068258:Bevacizumab; D059451:Biosimilar Pharmaceuticals; D002166:Camptothecin; D015179:Colorectal Neoplasms; D005260:Female; D005472:Fluorouracil; D006801:Humans; D057194:Intention to Treat Analysis; D002955:Leucovorin; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds; D000077982:Progression-Free Survival; D013810:Therapeutic Equivalency", "nlm_unique_id": "101690683", "other_id": null, "pages": "845-855", "pmc": null, "pmid": "30262136", "pubdate": "2018-12", "publication_types": "D016428:Journal Article; D016448:Multicenter Study; D016449:Randomized Controlled Trial; D013485:Research Support, Non-U.S. Gov't", "references": null, "title": "Bevacizumab biosimilar BEVZ92 versus reference bevacizumab in combination with FOLFOX or FOLFIRI as first-line treatment for metastatic colorectal cancer: a multicentre, open-label, randomised controlled trial.", "title_normalized": "bevacizumab biosimilar bevz92 versus reference bevacizumab in combination with folfox or folfiri as first line treatment for metastatic colorectal cancer a multicentre open label randomised controlled trial" }

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{ "abstract": "BACKGROUND\nThere have been several reports of secondary anemia associated with Graves' disease. There are no reports of secondary anemia resulting from thyrotoxicosis due to painless thyroiditis (silent thyroiditis). We report the case of a patient with pancreatic diabetes who developed anemia caused by thyrotoxicosis due to painless thyroiditis.\n\n\nMETHODS\nThe patient was a 37-year-old man who visited the hospital complaining of fatigue, palpitations, and dyspnea. His hemoglobin was 110 g/l (reference range, 135-176), and mean corpuscular volume was 81.5 fl (81.7-101.6). His free thyroxine (FT4) was high, at 100.4 pmol/l (11.6-21.9); the free triiodothyronine (FT3) was high, at 27.49 pmol/l (3.53-6.14); TSH was low, at < 0.01 mIU/l (0.50-5.00); and TSH receptor antibody was negative. Soluble IL-2 receptor (sIL-2R) was high, at 1340 U/ml (122-496); C-reactive protein (CRP) was high, at 6900 μg/l (< 3000); and reticulocytes was high, at 108 109 /l (30-100). Serum iron (Fe) was 9.5 (9.1-35.5), ferritin was 389 μg/l (13-401), haptoglobin was 0.66 g/l (0.19-1.70. Propranolol was prescribed and followed up. Anemia completely disappeared by 12 weeks after disease onset. Thyroid hormones and sIL-2R had normalized by 16 weeks after onset. He developed mild hypothyroidism and was treated with L-thyroxine at 24 weeks.\n\n\nCONCLUSIONS\nThis is the first case report of transient secondary anemia associated with thyrotoxicosis due to painless thyroiditis. The change in sIL-2R was also observed during the clinical course of thyrotoxicosis and anemia, suggesting the immune processes in thyroid gland and bone marrow.", "affiliations": "Department of Internal Medicine, Okinawa Medical Hospital, 2310 Tsuhako-Nishihara, Sashiki, Nanjo, Okinawa, 9011414, Japan. [email protected].;Department of Hematology, Okinawa Red Cross Hospital, 1-3-1 Yogi, Naha, Okinawa, 9028588, Japan.;Yagi Internal Medicine Clinic, 4-13-9 Kohagura, Naha, Okinawa, 9000029, Japan.;Department of Emergency and Critical Care Medicine, University of Ryukyus Hospital, 207 Uehara, Nishihara, Okinawa, 9030215, Japan.;Department of Internal Medicine, Okinawa Medical Hospital, 2310 Tsuhako-Nishihara, Sashiki, Nanjo, Okinawa, 9011414, Japan.", "authors": "Komiya|Ichiro|I|http://orcid.org/0000-0002-4965-4561;Tomoyose|Takeaki|T|;Yagi|Noriharu|N|;Ouchi|Gen|G|;Wakugami|Tamio|T|", "chemical_list": null, "country": "England", "delete": false, "doi": "10.1186/s13044-021-00100-6", "fulltext": "\n==== Front\nThyroid Res\nThyroid Res\nThyroid Research\n1756-6614\nBioMed Central London\n\n100\n10.1186/s13044-021-00100-6\nCase Report\nA case of thyrotoxicosis-induced anemia in a patient with painless thyroiditis\nhttp://orcid.org/0000-0002-4965-4561\nKomiya Ichiro [email protected]\n\n12\nTomoyose Takeaki 3\nYagi Noriharu 2\nOuchi Gen 4\nWakugami Tamio 1\n1 Department of Internal Medicine, Okinawa Medical Hospital, 2310 Tsuhako-Nishihara, Sashiki, Nanjo, Okinawa 9011414 Japan\n2 Yagi Internal Medicine Clinic, 4-13-9 Kohagura, Naha, Okinawa 9000029 Japan\n3 grid.474867.e 0000 0004 0629 1793 Department of Hematology, Okinawa Red Cross Hospital, 1-3-1 Yogi, Naha, Okinawa 9028588 Japan\n4 grid.267625.2 0000 0001 0685 5104 Department of Emergency and Critical Care Medicine, University of Ryukyus Hospital, 207 Uehara, Nishihara, Okinawa 9030215 Japan\n23 4 2021\n23 4 2021\n2021\n14 916 12 2020\n11 4 2021\n© The Author(s) 2021\nhttps://creativecommons.org/licenses/by/4.0/ Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.\nBackground\n\nThere have been several reports of secondary anemia associated with Graves’ disease. There are no reports of secondary anemia resulting from thyrotoxicosis due to painless thyroiditis (silent thyroiditis). We report the case of a patient with pancreatic diabetes who developed anemia caused by thyrotoxicosis due to painless thyroiditis.\n\nCase presentation\n\nThe patient was a 37-year-old man who visited the hospital complaining of fatigue, palpitations, and dyspnea. His hemoglobin was 110 g/l (reference range, 135–176), and mean corpuscular volume was 81.5 fl (81.7–101.6). His free thyroxine (FT4) was high, at 100.4 pmol/l (11.6–21.9); the free triiodothyronine (FT3) was high, at 27.49 pmol/l (3.53–6.14); TSH was low, at < 0.01 mIU/l (0.50–5.00); and TSH receptor antibody was negative. Soluble IL-2 receptor (sIL-2R) was high, at 1340 U/ml (122–496); C-reactive protein (CRP) was high, at 6900 μg/l (< 3000); and reticulocytes was high, at 108 109 /l (30–100). Serum iron (Fe) was 9.5 (9.1–35.5), ferritin was 389 μg/l (13–401), haptoglobin was 0.66 g/l (0.19–1.70. Propranolol was prescribed and followed up. Anemia completely disappeared by 12 weeks after disease onset. Thyroid hormones and sIL-2R had normalized by 16 weeks after onset. He developed mild hypothyroidism and was treated with L-thyroxine at 24 weeks.\n\nConclusions\n\nThis is the first case report of transient secondary anemia associated with thyrotoxicosis due to painless thyroiditis. The change in sIL-2R was also observed during the clinical course of thyrotoxicosis and anemia, suggesting the immune processes in thyroid gland and bone marrow.\n\nKeywords\n\nPainless thyroiditis\nAnemia\nsiIL-2R\nAnd thyrotoxicosis\nissue-copyright-statement© The Author(s) 2021\n==== Body\nBackground\n\nSecondary anemia associated with hyperthyroidism is a relatively rare complication [1]. Many reports have shown that although anemia progresses with hyperthyroidism in Graves’ disease, it is often transient, improving with treatment of Graves’ disease [2–4]. There are no reports of secondary anemia resulting from thyrotoxicosis due to subacute thyroiditis, painless thyroiditis (silent thyroiditis) [5], or other causes. Here, we report a case of transient anemia that developed after the onset of painless thyroiditis in a patient with pancreatic diabetes treated with insulin.\n\nCase presentation\n\nA 37-year-old man visited our hospital due to gradually progressive fatigue, dyspnea, and palpitations of approximately 14 days duration. His pulse was 104 beats/min, and his body temperature was 36.8 °C. No increase in sweating was observed, goiter was not palpable, and no exophthalmos or ocular movement dysfunction was observed. Laboratory examination showed anemia (Hgb 110 g/l [reference rage, 135–176], mean corpuscular volume [MCV] 81.5 fl [81.7–101.6]), and serum iron (9.5 μmol/l) and ferritin (389 μg/l) were within the normal ranges. Reticulocytes were increased at the time of onset (108 109 /l; reference rage, 30–100), C-reactive protein (CRP) was 6900 μg/l (< 3000), and his haptoglobin was within normal range (0.66 g/l; reference range, 0.19–1.70). The FT4 (free thyroxine) level was high, at 100.4 pmol/l (11.6–21.9), the FT3 (free triiodothyronine) level was high, at 27.49 pmol/l (3.53–6.14), and his TSH was < 0.01 mIU/l (0.50–5.00). TSH receptor antibody, anti-TPO antibody or anti-thyroglobulin antibody were negative. In other clinical tests, soluble interleukin-2 receptor (sIL-2R), measured for differentiation of hematologic malignancies, was high, at 1340 U/ml (122–496); his low-density lipoprotein cholesterol (LDL-C) was low, at 0.78 mmol/l (1.68–3.59); and his high-density lipoprotein cholesterol (HDL-C) was low, at 0.75 mmol/l (1.03–2.48) (Table 1). Table 1 Profile of laboratory data for a diabetes patient with thyrotoxicosis due to painless thyroiditis\n\nVariables\tReference range\tDay − 56\tDay −28\tDay 0\tDay 14\tDay 28\tDay 56\tDay 84\tDay 112\tDay 140\tDay 168\t\nRed blood cells, 1012/l\t4.27–5.70\t4.80\t4.96\t3.78\t3.77\t3.84\t4.50\t4.77\t4.93\t4.88\t4.66\t\nHemoglobin (Hgb), g/l\t135–176\t144\t146\t110\t107\t109\t126\t136\t142\t146\t140\t\nHematocrit (Hct), /l\t0.398–0.518\t0.399\t0.408\t0.308\t0.305\t0.306\t0.352\t0.377\t0.392\t0.386\t0.408\t\nMean corpuscular volume (MCV), fl\t81.7–101.6\t83.1\t82.3\t81.5\t80.9\t79.7\t78.2\t79.0\t79.5\t82.8\t83.4\t\nWhite blood cells (WBC), 109 /l\t3.5–9.8\t6.4\t7.4\t5.3\t7.2\t6.5\t8.8\t8.6\t8.8\t5.8\t7.4\t\nPlatelets, 109 /l\t130–369\t272\t315\t254\t198\t228\t289\t266\t283\t322\t333\t\nReticulocytes, 109 /l\t30–100\t\t\t108\t68\t\t\t\t\t\t\t\nThyroid stimulating hormone (TSH), mIU/l\t0.50–5.00\t\t\t< 0.01\t< 0.01\t< 0.01\t< 0.01\t\t10.1\t15.2\t18.5\t\nFree triiodothyronine (FT3), pmol/l\t3.53–6.14\t\t\t\t27.49\t12.61\t9.37\t\t3.93\t4.35\t4.22\t\nFree thyroxine (FT4), pmol/l\t11.6–21.9\t\t\t100.4\t91.4\t51.5\t33.1\t\t14.0\t13.1\t14.0\t\nTSH receptor antibody (TRAb), mIU/l\t<  2.0\t\t\t\t0.4\t\t\t\t\t\t\t\nAnti-TPO antibody, IU/ml\t<  16\t\t\t\t9\t\t\t\t\t\t\t\nAnt-thyroglobulin antibody, IU/ml\t<  28\t\t\t\t11\t\t\t\t\t\t\t\nC-reactive protein (CRP), μg/l\t<  3000\t\t\t6900\t\t12,100\t5700\t3700\t\t1200\t\t\nIron (Fe), μmol/l\t9.1–35.5\t\t\t9.5\t\t9.5\t\t\t\t\t\t\nTIBC, μmol/l\t43.2–69.0\t\t\t34.2\t\t40.8\t\t\t\t\t\t\nFerritin, μg/l\t13–401\t\t\t389\t\t376\t396\t\t\t\t\t\nHaptoglobin, g/dl\t0.19–1.70\t\t\t0.66\t\t\t\t\t\t\t\t\nSoluble IL-2 receptor (sIL-2R), U/ml\t122–496\t\t\t1340\t\t1010\t808\t\t472\t\t365\t\nHDL-C, mmol/l\t1.03–2.48\t1.27\t1.09\t0.75\t\t0.98\t1.27\t1.42\t1.14\t1.16\t1.14\t\nLDL-C, mmol/l\t1.68–3.59\t1.99\t1.63\t0.78\t\t1.45\t2.12\t2.82\t2.87\t2.90\t2.82\t\nTriglycerides (TG), mmol/l\t0.34–1.68\t0.46\t0.59\t0.54\t\t0.84\t0.68\t0.75\t0.84\t0.59\t0.60\t\nHbA1c (NGSP), %\t4.6–6.2\t6.9\t7.1\t7.6\t\t6.5\t6.6\t6.9\t7.7\t7.6\t7.5\t\nAST, IU/l\t13–33\t19\t18\t21\t\t25\t30\t25\t22\t27\t23\t\nALT, IU/l\t6–30\t13\t14\t19\t\t28\t29\t21\t15\t22\t21\t\nγGTP, IU/l\t10–47\t13\t14\t21\t\t42\t57\t37\t26\t20\t19\t\nAlbumin, g/l\t40–50\t41\t42\t31\t\t32\t36\t36\t35\t41\t41\t\neGFR, ml/min/1.73 m2\t> 60\t103\t97\t111\t\t115\t104\t90\t88\t79.0\t80.0\t\nDrug treatment\t\t\t\t\tPropranolol\n\n30 mg\n\n\tPropranolol\n\n30 mg\n\n\t\t\t\t\tLT4\n\n12.5 μg\n\n\t\nBold data is abnormal value. eGFR estimated glomerular filtration rate\n\nThe patient was previously diagnosed with pancreatic diabetes due to alcoholic pancreatitis at age 25 years, and thus, he was treated with a combination of insulin glargine and insulin aspart. Regular clinical examinations were performed every 28 days, and no abnormalities were found in his biochemical data or complete blood count, other than his plasma glucose and HbA1c. Propranolol (30 mg/day) was prescribed at day 14 and stopped on day 56. Thyroid ultrasonography was performed on day 28, and hypoechoic regions were observed throughout the thyroid gland (Fig. 1). Fig. 1 Thyroid ultrasonography findings. Hypoechoic regions are scattered throughout the thyroid gland. No increase in blood flow in the thyroid gland was observed\n\nThe anemia disappeared by day 84. The patient’s thyroid hormones and sIL-2R normalized by day 112, and CRP normalized by day 140. The clinical courses of Hgb, FT4, and sIL-2R were shown in Fig. 2. There was slight decrease in LDL-C and HDL-C, and increases in liver enzymes at disease onset, but these changes disappeared by day 140 (Table 1). His serum albumin was low at onset but normalized by day 140. The patient’s insulin regimen was not changed over the entire clinical course. He developed mild hypothyroidism on day 112 and was started on 12.5 μg of L-thyroxine replacement therapy on day 168 (Table 1). Fig. 2 Profile of FT4, hemoglobin, and sIL-2R. The patient’s hemoglobin had normalized by day 84. FT4 and sIL-2R returned to be normal by day 112. The shaded area shows the reference range for each variable\n\nDiscussion and conclusions\n\nWe reported a case of painless thyroiditis-induced thyrotoxicosis that suddenly led to anemia within 4 weeks after the patient’s last visit to our hospital. Although it was not possible to prove reduced iodine uptake using thyroid scintigram, negative TSH receptor antibody, the mild increase of CRP, lack of tenderness in thyroid gland, and the diffuse destructive findings on thyroid ultrasonography indicated painless thyroiditis [5]. In addition, FT3/FT4 ratio (0.301) was low, suggesting painless thyroiditis, because the median (IQR) of FT3/FT4 ratio in painless thyroiditis was reported as 0.310 (0.203–0.608) [6]. This is the first report of secondary anemia associated with painless thyroiditis. Although the levels remained within the normal range, slight decrease in WBC and platelets presented at disease onset [1]. Anemia, and the decrease in WBC and platelets completely disappeared by 12 weeks after onset, with spontaneous remission of thyrotoxicosis.\n\nIn addition to the clinical course of thyrotoxicosis and associated anemia, the present case provided interesting laboratory data. First, sIL-2R was high at onset but normalized by 16 weeks after onset of anemia. Elevated levels of sIL-2R have been reported in hyperthyroidism of Graves’ disease and it was suggested that thyroid hormones directly enhance sIL-2R production in lymphocytes [7]. The levels in sIL-2R also increased in patients with the thyrotoxicosis due to painless thyroiditis [8]. Second, LDL-C and HDL-C levels decreased due to thyrotoxicosis. Excessive thyroid hormone levels lower serum LDL-C and HDL-C levels via several mechanisms [9–11]. We previously reported that increased sIL-2R cause significant decreases levels in HDL-C and LDL-C in patients with hematologic malignancies [12]. Increased cytokines were recently reported to be associated with hypolipidemia in COVID-19 patients [13]. Presumably, increases in levels of both thyroid hormones and sIL-2R are associated with the decreases in HDL-C and LDL-C.\n\nPainless thyroiditis (silent thyroiditis) is a self-limiting inflammatory disorder of the thyroid gland characterized by an early thyrotoxicosis phase caused by the release of thyroid hormones and a late hypothyroidism phase, with complete resolution in most cases [5, 14]. The pathophysiologic mechanism of painless thyroiditis is unknown, but the possibility of immune disorder involvement has been suggested [5, 7, 8, 15]. Painless thyroiditis generally manifests as a lymphocyte infiltration of the thyroid follicles, causing thyroid follicular cell damage [5]. In our case, we observed a typical course of painless thyroiditis. The secondary anemia caused by thyrotoxicosis has improved, but we would like to carefully follow up on the continuation of thyroid hormone replacement therapy.\n\nThe mechanism by which anemia develops in thyrotoxicosis is not clear. Shortened erythrocyte survival or ineffective erythropoiesis have been suggested as potential causes of anemia in thyrotoxicosis [2–4]. Moreover, slight decrease in WBC and platelets was observed in present case, which could have been due to a variety of mechanisms. The involvement of autoantibodies in leukocytes and platelets resulting in increased destruction of hematopoietic cells by immunological mechanisms has been reported [16]. The increase in sIL-2R, which had been increasing at the onset of painless thyroiditis, may suggest the result of immune process abnormality rather than the increase in thyroid hormones [8, 17]. The involvement of immune processes in the onset of painless thyroiditis could help explain the pathophysiology of anemia [18]. In present case, however, both anti-TG and anti-TPO antibodies were negative. Anti-thyroglobulin and anti-TPO antibodies prevalence in painless thyroiditis have been reported to be 70 and 30%, respectively [19]. The patient had an history of acute pancreatitis. It is interesting to assume the immune mechanisms as the pathogenesis of acute and chronic pancreatitis [20], and it is natural to assume that the immune mechanism was involved in the development of silent thyroiditis and anemia in present case.\n\nIn conclusion, we reported the case of a diabetes patient with secondary anemia resulting from thyrotoxicosis. Thyrotoxicosis was caused by painless thyroiditis, but there have been no reports of secondary anemia induced by painless thyroiditis. The change in sIL-2R was also observed during the clinical course of thyrotoxicosis and anemia.\n\nAbbreviations\n\nTSH Thyroid stimulating hormone\n\nFT4 Free thyroxine\n\nFT3 Free triiodothyronine\n\nsIL-2R Soluble interleukin-2 receptor\n\nHDL-C High-density lipoprotein cholesterol\n\nLDL-C Low-density lipoprotein cholesterol\n\nAcknowledgements\n\nWe would like to thank FORTE (www.forte-science.co.jp) for English language editing.\n\nAuthors’ contributions\n\nTW has full access to all of the data from the study and takes responsibility for the integrity of the data. IK and TT were involved in study design, interpreting data, statistical analysis, creating tables and figures, and drafting the manuscript. NY and GO were involved in interpreting data and supervised the work. All authors have contributed significantly to this work. All the authors have read the manuscript and have approved this submission.\n\nFunding\n\nThe authors received no specific funding for this work.\n\nAvailability of data and materials\n\nThe collection of data that supports the findings in this study is available from Okinawa Medical Hospital. Data are available from the authors upon reasonable request and with permission of Okinawa Medical Hospital.\n\nDeclarations\n\nEthics approval and consent to participate\n\nNo applicable.\n\nConsent for publication\n\nRegarding publication of the case report, we explained that we could not reveal personal information and obtained verbal consent from the patient.\n\nCompeting interests\n\nThe authors declare no conflict of interest.\n\nPublisher’s Note\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n==== Refs\nReferences\n\n1. Ford HC Carter JM The haematology of hyperthyroidism: abnormalities of erythrocytes, leucocytes, thrombocytes and haemostasis Postgrad Med J 1998 64 735 742 10.1136/pgmj.64.756.735\n2. Szczepanek-Parulska E Hernik A Ruchała M Anemia in thyroid diseases Pol Arch Intern Med 2017 127 5 352 360 10.20452/pamw.3985 28400547\n3. Gianoukakis AG Leigh MJ Richards P Christenson PD Hakimian A Fu P Characterization of the anaemia associated with Graves’ disease Clin Endocrinol (Oxf) 2009 70 781 787 10.1111/j.1365-2265.2008.03382.x 18710465\n4. Das KC Mukherjee M Sarkar TK Dash RJ Rastogi GK Erythropoiesis and erythropoietin in hypo- and hyperthyroidism J Clin Endocrinol Metab 1975 40 2 211 220 10.1210/jcem-40-2-211 1117976\n5. Mizukami Y Michigishi T Hashimoto T Tonami N Hisada K Matsubara F Takazakura E Silent thyroiditis: a histologic and immunohistochemical study Hum Pathol 1988 19 4 423 431 10.1016/S0046-8177(88)80492-1 3284807\n6. Yoshimura JN Momotani N Fukada S Ito K Miyauchi A Amino N Ratio of serum free triiodothyronine to free thyroxine in Graves’ hyperthyroidism and thyrotoxicosis caused by painless thyroiditis Endocr J 2005 52 5 537 542 10.1507/endocrj.52.537 16284430\n7. Koukkou E Panayiotidis P Alevizou-Terzaki V Thalassinos N High levels of serum soluble interleukin-2 receptors in hyperthyroid patients: correlation with serum thyroid hormones and independence from the etiology of the hyperthyroidism J Clin Endocrinol Metab 1991 73 4 771 776 10.1210/jcem-73-4-771 1909702\n8. Hamamoto K Inaba M Yamada S Yoda M Yoda K Goto H Kurajoh M Koyama H Increased soluble IL-2 receptor levels in serum from a patient with painless thyroiditis Thyroid Res 2013 6 1 12 10.1186/1756-6614-6-12 24305463\n9. Lopez D Socarrás JFA Bedi M Ness GC Activation of the hepatic LDL receptor promoter by thyroid hormone Biochim Biophys Acta 1771 2007 1216 1225\n10. Bonde Y Breuer O Lütjohann D Sjöberg S Angelin B Rudling M Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans J Lipid Res 2014 55 11 2408 2415 10.1194/jlr.M051664 25172631\n11. Tan KC Shiu SW Kung AW Plasma cholesteryl ester transfer protein activity in hyper- and hypothyroidism J Clin Endocrinol Metab 1998 83 1 140 143 10.1210/jcem.83.1.4491 9435431\n12. Komiya I Tomoyose T Ouchi G Yara T Higa S Low level of serum HDL-cholesterol with increased sIL-2R predicts a poor clinical outcome for patients with malignant lymphoma and adult T-cell leukemia-lymphoma Cytokine. 2018 105 57 62 10.1016/j.cyto.2018.02.005 29459344\n13. Wei X Zeng W Su J Wan H Yu X Cao X Tan W Wang H Hypolipidemia is associated with the severity of COVID-19 J Clin Lipidol 2020 14 3 297 304 10.1016/j.jacl.2020.04.008 32430154\n14. Strakosch CR Thyroiditis Aust NZ J Med 1986 16 1 91 100 10.1111/j.1445-5994.1986.tb01138.x\n15. Takasu N Komiya I Nagasawa Y Asawa T Yamada T Exacerbation of autoimmune thyroid dysfunction after unilateral adrenalectomy in patients with Cushing's syndrome due to an adrenocortical adenoma N Engl J Med 1990 322 24 1708 1712 10.1056/NEJM199006143222404 2342537\n16. Garla VV Salim SA Yanes-Cardozo LL Pancytopenia: a rare complication of Graves’ disease BMJ Case Rep 2018 2018 bcr2017223887 10.1136/bcr-2017-223887\n17. Dik WA Heron M Clinical significance of soluble interleukin-2 receptor measurement in immune-mediated diseases Neth J Med 2020 78 5 220 231 33093245\n18. Nobili V Liaskos C Luigi G Guidi R Francalanci P Marcellini M Autoimmune thyroiditis associated with autoimmune hepatitis Thyroid. 2005 15 10 1193 1195 10.1089/thy.2005.15.1193 16279855\n19. Nishihara E Amino N Kudo T Ito M Fukata S Nishikawa M Nakamura H Miyauchi A Comparison of thyroglobulin and thyroid peroxidase antibodies measured by five different kits in autoimmune thyroid diseases Endocr J 2017 64 10 955 961 10.1507/endocrj.EJ17-0164 28768936\n20. Lee B Zhao Q Habtezion A Immunology of pancreatitis and environmental factors Curr Opin Gastroenterol 2017 33 5 383 389 10.1097/MOG.0000000000000387 28682796\n\n", "fulltext_license": "CC BY", "issn_linking": "1756-6614", "issue": "14(1)", "journal": "Thyroid research", "keywords": "And thyrotoxicosis; Anemia; Painless thyroiditis; siIL-2R", "medline_ta": "Thyroid Res", "mesh_terms": null, "nlm_unique_id": "101469037", "other_id": null, "pages": "9", "pmc": null, "pmid": "33892761", "pubdate": "2021-04-23", "publication_types": "D016428:Journal Article", "references": "18710465;25172631;33093245;1117976;2342537;28768936;29525760;3284807;1909702;29459344;3076660;28682796;32430154;2939821;16284430;16279855;24305463;28400547;17572141;9435431", "title": "A case of thyrotoxicosis-induced anemia in a patient with painless thyroiditis.", "title_normalized": "a case of thyrotoxicosis induced anemia in a patient with painless thyroiditis" }

[ { "companynumb": "JP-PFM-2022-03520", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PROPRANOLOL HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "205410", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "30 MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "Thyroiditis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "30", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PROPRANOLOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PROPRANOLOL HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "205410", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Off label use", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PROPRANOLOL" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hypothyroidism", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Product use issue", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Komiya I, Tomoyose T, Yagi N, Ouchi G, Wakugami T. A case of thyrotoxicosis-induced anemia in a patient with painless thyroiditis. Thyroid Research. 2021;14(9):1-5", "literaturereference_normalized": "a case of thyrotoxicosis induced anemia in a patient with painless thyroiditis", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20220511", "receivedate": "20220511", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20814234, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220720" } ]

{ "abstract": "During the COVID-19 pandemic in 2020, an 81-year-old afebrile woman was transported to our institute at 44 minutes after she was found to have global aphasia and weakness of the right extremities. The onset time was unclear. CT showed an occlusion of the left middle cerebral artery without early ischemic changes. MRI revealed a negative fluid-attenuated inversion recovery (FLAIR) pattern, in which several small acute infarcts were seen in diffusion-weighted images with no corresponding hyperintensity lesions on FLAIR. Accordingly, intravenous thrombolysis with alteplase (0.6 mg/kg, the dose approved in Japan) was administered at 1,660 minutes after the last known well and 116 minutes after the symptom recognition. An immediate internal carotid angiogram showed severe stenosis at the distal end of the horizontal portion of the left middle cerebral artery. In the follow-up angiogram at 164 minutes after the symptom recognition, the stenotic lesion almost resolved with the restoration of quick and nearly complete antegrade flow. Her symptoms also resolved promptly. Although the use of MRI is recommended to be minimized in the emergency stroke management during the COVID-19 pandemic, MRI is occasionally mandatory for patient selection, such as cases with unclear onset to perform intravenous thrombolysis. The individualized protected code stroke is essential and must be well considered by each institute for diagnosing patients by selecting appropriate modalities.", "affiliations": "Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center.;Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center.;Division of Stroke Care Unit, National Cerebral and Cardiovascular Center.;Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center.;Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center.;Department of Radiology, National Cerebral and Cardiovascular Center.;Department of Radiology, National Cerebral and Cardiovascular Center.;Department of Radiology, National Cerebral and Cardiovascular Center.;Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center.", "authors": "Kamogawa|Naruhiko|N|;Egashira|Shuhei|S|;Tanaka|Kanta|K|;Shiozawa|Masayuki|M|;Inoue|Manabu|M|;Ohta|Yasutoshi|Y|;Nishii|Tatsuya|T|;Fukuda|Tetsuya|T|;Koga|Masatoshi|M|", "chemical_list": "D010959:Tissue Plasminogen Activator", "country": "Japan", "delete": false, "doi": "10.5692/clinicalneurol.cn-001481", "fulltext": null, "fulltext_license": null, "issn_linking": "0009-918X", "issue": "60(10)", "journal": "Rinsho shinkeigaku = Clinical neurology", "keywords": "COVID-19; MRI; intravenous thrombolysis; stroke; unclear onset", "medline_ta": "Rinsho Shinkeigaku", "mesh_terms": "D000369:Aged, 80 and over; D000086382:COVID-19; D018352:Coronavirus Infections; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D058873:Pandemics; D011024:Pneumonia, Viral; D020521:Stroke; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator", "nlm_unique_id": "0417466", "other_id": null, "pages": "706-711", "pmc": null, "pmid": "32893248", "pubdate": "2020-10-24", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "MRI and intravenous thrombolysis for unclear-onset stroke during the COVID-19 pandemic: a case report.", "title_normalized": "mri and intravenous thrombolysis for unclear onset stroke during the covid 19 pandemic a case report" }

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{ "abstract": "BACKGROUND\nRefractory pouchitis is a common cause of pouch failure, which may require surgical excision of the pouch or permanent diversion. We aimed to show the effect of vedolizumab on treatment of the patient with refractory pouchitis.\n\n\nMETHODS\nA 32-year-old male with pancolonic ulcerative colitis since the age of 25 with primary failure of infliximab and mesalamine and intolerance of azathioprine, underwent a total proctocolectomy with ileal pouch-anal anastomosis in 2012. He developed chronic diarrhea in 2014, which was watery, 30 per day and accompanied with blood and mucus affecting his quality of life.\n\n\nCONCLUSIONS\nVedolizumab is safe and effective in the management of anti-tumor necrosis factor alpha refractory pouchitis.", "affiliations": "Department of Gastroenterology and Hepatology, Alanya Alaaddin Keykubat University, School of Medicine, Antalya 07425, Turkey. [email protected].", "authors": "Cakir|Ozlem Ozer|OO|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.12998/wjcc.v7.i16.2316", "fulltext": "\n==== Front\nWorld J Clin CasesWJCCWorld Journal of Clinical Cases2307-8960Baishideng Publishing Group Inc jWJCC.v7.i16.pg231610.12998/wjcc.v7.i16.2316Case ReportEffectiveness of vedolizumab treatment in two different anti-tumor necrosis factor alpha refractory pouchitis: A case report Cakir Ozlem Ozer Department of Gastroenterology and Hepatology, Alanya Alaaddin Keykubat University, School of Medicine, Antalya 07425, Turkey. [email protected] contributions: All of the contributions were made by the author.\n\nCorresponding author: Ozlem Ozer Cakir, MD, Assistant Professor, Doctor, Department of Gastroenterology and Hepatology, Alanya Alaaddin Keykubat University, School of Medicine, Kestel yerleşkesi, Antalya 07425, Turkey. [email protected]\n\nTelephone: +90-532-1754014\n\n26 8 2019 26 8 2019 7 16 2316 2321 24 4 2019 18 6 2019 20 7 2019 ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.2019This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.BACKGROUND\nRefractory pouchitis is a common cause of pouch failure, which may require surgical excision of the pouch or permanent diversion. We aimed to show the effect of vedolizumab on treatment of the patient with refractory pouchitis.\n\nCASE SUMMARY\nA 32-year-old male with pancolonic ulcerative colitis since the age of 25 with primary failure of infliximab and mesalamine and intolerance of azathioprine, underwent a total proctocolectomy with ileal pouch-anal anastomosis in 2012. He developed chronic diarrhea in 2014, which was watery, 30 per day and accompanied with blood and mucus affecting his quality of life.\n\nCONCLUSION\nVedolizumab is safe and effective in the management of anti-tumor necrosis factor alpha refractory pouchitis.\n\nAnti-tumor necrosis factor alphaRefractory pouchitisVedolizumabUlcerative colitis\n==== Body\nCore tip: Vedolizumab, a humanized immunoglobulin G1 monoclonal antibody to α4β7 integrin, has been shown to moderate gut lymphocyte trafficking with an efficacy in treatment of both Crohn’s disease and ulcerative colitis. In our patient who had two different anti-tumor necrosis factor refractory pouchitis, the gut-specific immune modulation mediated by vedolizumab treatment resulted in good responses. This case is important because vedolizumab is the novel therapy for refractory pouchitis. However, further large and prospective studies are needed for efficacy and the underlying mechanisms of efficacy of vedolizumab in treatment of refractory pouchitis.\n\nINTRODUCTION\nRefractory pouchitis is a common cause of pouch failure, which may require surgical excision of the pouch or permanent diversion. Vedolizumab, a humanized immunoglobulin G1 monoclonal antibody to α4β7 integrin, has been shown to moderate gut lymphocyte trafficking with an efficacy in treatment of both Crohn's disease and ulcerative colitis (UC)[1,2]. Although tumor necrosis factor-alpha (TNF-α) inhibitors have been reported to be effective as treatment for pouchitis[3], there is little data regarding the use of vedolizumab in refractory pouchitis[4]. The effect of vedolizumab treatment on chronic antibiotic refractory pouchitis is very limited. Chronic antibiotic refractory pouchitis is a challenging complication in patients with UC who undergo proctocolectomy with ileal pouch-anal anastomosis. Chronic antibiotic refractory pouchitis occurs when patients do not respond to a 2-wk course of ciprofloxacin, metronidazole or rifaximin for pouchitis[5].\n\nCASE PRESENTATION\nChief complaints\nWe report on a 32-year-old male with pancolonic UC.\n\nHistory of present illness\nA 32-year-old male with pancolonic UC since the age of 25 with primary failure of infliximab and mesalamine and intolerance of azathioprine, underwent a total proctocolectomy with ileal pouch-anal anastomosis in 2012.\n\nHistory of past illness\nHe developed chronic diarrhea in 2014, which was watery, 30 per day and accompanied with blood and mucus affecting his quality of life. He could not work. He lost a lot of weight. He had fallen from 55 kg to 43 kg during pouchitis. His body mass index was 15.2 kg/m2. He used meselamine 3 g orally, steroid intermittently, lavman and loperamide orally three times daily.\n\nPersonal and family history\nHis family history was unremarkable.\n\nPhysical examination upon admission\nHis abdominal physical examination was normal.\n\nLaboratory examinations\nLaboratory work-up revealed erythrocyte sedimentation rate of 56 mm/h and C-reactive protein of 3.6 mg/dL with no liver function abnormalities. Autoimmune markers including IgG4, anti-nuclear antibody and anti-mitochondrial antibody were negative. His blood tests for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus antibodies were negative. Stool studies for Clostridium difficile, viruses and bacteria were negative. Blood tests for Epstein-Barr virus and cytomegalovirus antibodies were negative.\n\nImaging examinations\nAn ileoscopy and pouchoscopy were performed that demonstrated normal proximal ileal mucosa, but there were diffuse edema, erythema and nodularity and multiple superficial and deep ulcers in the pouch. His pouchitis disease activity index score was 16. Biopsies obtained were negative for cytomegalovirus. An upper endoscopy was done at the same time to evaluate diarrhea, and it was normal. Duodenal biopsy was negative for the presence of celiac disease. Serum antibodies for celiac disease including anti-gliadin antibodies, endomysial antibodies and anti-transglutaminase antibodies were negative. Therefore, gluten restricted diet was not given to the patient. His chest X-ray was normal. Purified protein derivative skin test was 0 mm.\n\nFINAL DIAGNOSIS\nChronic pouchitis.\n\nTREATMENT\nHe was prescribed metronidazole 500 mg orally three times daily and ciprofloxacin 500 mg orally two times daily. But his symptoms did not improve. Then we added rifaximin 550 mg orally three times daily. We continued meselamine 3000 mg orally two times rectally and loperamide three times daily. He also used probiotics. He continued to have diarrhea with blood and mucus 20 to 30 times per day. Then adalimumab was started at 160 mg, 80 mg and 40 mg subcutaneously at 0, 2, and every 2 wk, respectively. He reported improvement of diarrhea without blood 10 to 15 per day the first week of adalimumab treatment. However, this response decreased within 4 wk, and the diarrhea and weight loss increased. His pouchoscopy was the same as before treatment at 6 mo after the beginning of treatment. Therefore, we stopped adalimumab. We tested the patient again for other etiologies like infections that were negative. Finally, we decided to start vedolizumab. The patient was given 300 mg parenterally at 0, 2, and 6 wk then every 8 wk.\n\nOUTCOME AND FOLLOW-UP\nHe reported improvement in clinical symptoms at 4 wk for frequency of diarrhea (six to eight per day) without blood and mucus. He did not have any abdominal complaints. A pouchoscopy at 6 wk and 15 wk after beginning vedolizumab demonstrated that there were less ulcers after 6 wk, and there was only one small superficial ulcer after 15 wk (Figure 1). A pouchoscopy before beginning vedolizumab treatment is shown in Figure 2. His laboratory tests including C-reactive protein, erythrocyte sedimentation rate and liver test were normal. He gained almost 9 kg during vedolizumab treatment, and his quality of life improved (he started to work again).\n\nFigure 1 Fifteen weeks after vedolizumab treatment.\n\nFigure 2 Before vedolizumab treatment.\n\nDISCUSSION\nThere is only one retrospective study on the efficacy of vedolizumab for refractory pouchitis of the ileo-anal pouch in the literature[6]. This study suggested that vedolizumab is safe and effective for treatment of refractory pouchitis. The other studies found in the literature are case presentations and case series. These presentations showed us vedolizumab was a good choice for refractory pouchitis[7-11]. The effects of vedolizumab for treatment of pouchitis is summarized in Table 1[8-13]. We differentiated our case from other cases in the literature by taking an effective clinical and endoscopic response with vedolizumab treatment in two different anti-TNF alpha refractory pouchitis.\n\nTable 1 Effect of vedolizumab treatment of pouchitis in the literature\n\nCountry and reference\tNumber of patients\tAge and gender\tFeatures of inflammatory bowel disease\tOutcomes\t\nUnited States and reference 8\t1\t41-year-old female\tShe had pouchitis; 2 years later IPAA\tImprovement in clinical symptoms and decreased frequency of bowel movements to four to six per day without blood or mucus were reported with 6 wk of vedolizumab treatment. There were no side effects\t\nItaly and reference 9\t1\t33-year-old male\tAnti-TNF-refractory chronic pouchitis and concomitant PSC\t3 mo after ileostomy closure, chronic pouchitis occurred, refractory to antibiotics and anti-TNF. Thus, vedolizumab was started, leading to a marked improvement in clinical symptoms, which was maintained to the end of follow up (wk 34). There were no side effects\t\nGermany and reference 10\t20\t12 male, 8 female; The median age was 22.5 years old\tAll of the patients were diagnosed with pouchitis\tImprovement of clinical symptoms, the Oresland score and the PDAI score. There were no side effects\t\nGreece and reference 11\t1\t22-year-old female\tShe was first diagnosed with pouchitis 1 year after surgery. Administered infliximab followed by adalimumab, both of which she discontinued after an early severe allergic reaction\tVedolizumab was subsequently initiated, together with a single course of antibiotics, and the patient experienced improvement in clinical symptoms and laboratory results with no documented relapse since then. A new pouchoscopy at wk 33 showed significant improvement\t\nGreece and reference 11\t1\t22-year-old female\tShe was first diagnosed with pouchitis 1 year after surgery. Administered infliximab followed by adalimumab, both of which she discontinued after an early severe allergic reaction\tVedolizumab was subsequently initiated, together with a single course of antibiotics, and the patient experienced improvement in clinical symptoms and laboratory results with no documented relapse since then. A new pouchoscopy at wk 33 showed significant improvement\t\nUnited States and reference 12\t12\t9 female, 3 male; The mean age was 41 years old\tAll of the patients had active pouchitis. Five patients (41.7%) used mesalamine, six (50.0%) took budesonide and four (33.3%) took prednisone prior to using vedolizumab. Eight (66.7%) had used anti-TNF agents prior to vedolizumab use\tEight (66.7%) patients demonstrated significant reduction in mPDAI symptom subscores before and after vedolizumab therapy\t\nPortugal and reference 13\t1\t20-year-old female\tShe was diagnosed with pouchitis and a severe symptomatic autoimmune hemolytic anemia 1 year after IPAA\tPatient reported symptom improvement at wk 12 and a pouchoscopy revealed only mucosal edema after 6 mo of therapy. Her inflammatory markers and hemoglobin normalized on repeat testing, allowing steroid withdrawal\t\nIPAA: Ileal pouch-anal anastomosis; TNF: Tumor necrosis factor; PSC: Primary sclerosing cholangitis; PDAI: Pouchitis disease activity index; mPDAI: Modified pouchitis disease activity index.\n\nVedolizumab, a monoclonal antibody, selectively blocks gut lymphocyte trafficking by interacting with α4β7 heterodimer[1]. There is severe infiltration of the mucosa by both innate and adaptive immune cells in active pouchitis. An increased proportion of mucosal dendritic cells expressing integrin β7 in patients with pouch inflammation has been shown[14]. The integrin signaling in the pathogenesis of this clinical condition of pouchitis may have a pathogenic role. Therefore, blockade of α4β7 integrin with vedolizumab treatment might represent a promising therapeutic strategy for this clinical condition[14].\n\nVedolizumab has been shown to be beneficial for the treatment of chronic antibiotic-refractory pouchitis[15,16]. After 3 mo of therapy with vedolizumab in patients with refractory pouchitis, the small case series of four patients had symptomatic and endoscopic improvements[17].\n\nVedolizumab may be a new choice as a treatment option in patients with refractory pouchitis who showed no improvement with steroids and other biological therapies such as anti-TNFs. Future studies may show when to start vedolizumab and the advantages of vedolizumab therapy in patients with refractory pouchitis.\n\nCONCLUSION\nIn our patient who had anti-TNF refractory pouchitis, the gut-specific immune modulation mediated by vedolizumab treatment resulted in good responses. Further large and prospective studies are needed for the efficacy and the underlying mechanisms of efficacy of vedolizumab in treatment of refractory pouchitis.\n\nInformed consent statement: Patient consent and IRB approval were obtained.\n\nConflict-of-interest statement: The author declares that there are no conflicts of interest.\n\nCARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).\n\nManuscript source: Unsolicited manuscript\n\nPeer-review started: May 8, 2019\n\nFirst decision: May 31, 2019\n\nArticle in press: July 20, 2019\n\nSpecialty type: Medicine, Research and Experimental\n\nCountry of origin: Turkey\n\nPeer-review report classification\n\nGrade A (Excellent): 0\n\nGrade B (Very good): B\n\nGrade C (Good): C\n\nGrade D (Fair): 0\n\nGrade E (Poor): 0\n\nP-Reviewer: Rocha R, Chiba T S-Editor: Dou Y L-Editor: Filipodia E-Editor: Wu YXJ\n==== Refs\n1 Feagan BG Rutgeerts P Sands BE Hanauer S Colombel JF Sandborn WJ Van Assche G Axler J Kim HJ Danese S Fox I Milch C Sankoh S Wyant T Xu J Parikh A GEMINI 1 Study Group Vedolizumab as induction and maintenance therapy for ulcerative colitis N Engl J Med 2013 369 699 710 23964932 \n2 Sandborn WJ Feagan BG Rutgeerts P Hanauer S Colombel JF Sands BE Lukas M Fedorak RN Lee S Bressler B Fox I Rosario M Sankoh S Xu J Stephens K Milch C Parikh A GEMINI 2 Study Group Vedolizumab as induction and maintenance therapy for Crohn's disease N Engl J Med 2013 369 711 721 23964933 \n3 Herfarth HH Long MD Isaacs KL Use of Biologics in Pouchitis: A Systematic Review J Clin Gastroenterol 2015 49 647 654 26084005 \n4 Philpott J Ashburn J Shen B Efficacy of Vedolizumab in Patients with Antibiotic and Anti-tumor Necrosis Alpha Refractory Pouchitis Inflamm Bowel Dis 2017 23 E5 E6 27930413 \n5 Shen B Acute and chronic pouchitis--pathogenesis, diagnosis and treatment Nat Rev Gastroenterol Hepatol 2012 9 323 333 22508158 \n6 Gregory M Weaver KN Hoversten P Hicks SB Patel D Ciorba MA Gutierrez AM Beniwal-Patel P Palam S Syal G Herfarth HH Christophi G Raffals L Barnes EL Deepak P Efficacy of Vedolizumab for Refractory Pouchitis of the Ileo-anal Pouch: Results From a Multicenter US Cohort Inflamm Bowel Dis 2019 \n7 Schmid M Frick JS Malek N Goetz M Successful treatment of pouchitis with Vedolizumab, but not fecal microbiota transfer (FMT), after proctocolectomy in ulcerative colitis Int J Colorectal Dis 2017 32 597 598 28097380 \n8 Mir F Yousef MH Partyka EK Tahan V Successful treatment of chronic refractory pouchitis with vedolizumab Int J Colorectal Dis 2017 32 1517 1518 28698974 \n9 Coletta M Paroni M Caprioli F Successful Treatment With Vedolizumab in a Patient With Chronic Refractory Pouchitis and Primary Sclerosing Cholangitis J Crohns Colitis 2017 11 1507 1508 29106505 \n10 Bär F Kühbacher T Dietrich NA Krause T Stallmach A Teich N Schreiber S Walldorf J Schmelz R Büning C Fellermann K Büning J Helwig U German IBD Study Group Vedolizumab in the treatment of chronic, antibiotic-dependent or refractory pouchitis Aliment Pharmacol Ther 2018 47 581 587 29266360 \n11 Orfanoudaki E Foteinogiannopoulou K Koutroubakis IE Use of vedolizumab in a patient with chronic and refractory pouchitis Ann Gastroenterol 2018 31 379 29720865 \n12 Khan F Gao XH Singh A Philpott JR Shen B Vedolizumab in the treatment of Crohn's disease of the pouch Gastroenterol Rep (Oxf) 2018 6 184 188 30151202 \n13 Martins D Ministro P Silva A Refractory Chronic Pouchitis and Autoimmune Hemolytic Anemia Successfully Treated with Vedolizumab GE Port J Gastroenterol 2018 25 340 341 30480056 \n14 Landy J Al-Hassi HO Ronde E English NR Mann ER Bernardo D Ciclitira PJ Clark SK Knight SC Hart AL Innate immune factors in the development and maintenance of pouchitis Inflamm Bowel Dis 2014 20 1942 1949 25222658 \n15 Fazio VW Kiran RP Remzi FH Coffey JC Heneghan HM Kirat HT Manilich E Shen B Martin ST Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients Ann Surg 2013 257 679 685 23299522 \n16 Shen B Lashner B Can we immunogenotypically and immunophenotypically profile patients who are at risk for pouchitis? Am J Gastroenterol 2004 99 442 444 15056082 \n17 Shen B Achkar JP Lashner BA Ormsby AH Remzi FH Bevins CL Brzezinski A Petras RE Fazio VW Endoscopic and histologic evaluation together with symptom assessment are required to diagnose pouchitis Gastroenterology 2001 121 261 267 11487535\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "2307-8960", "issue": "7(16)", "journal": "World journal of clinical cases", "keywords": "Anti-tumor necrosis factor alpha; Refractory pouchitis; Ulcerative colitis; Vedolizumab", "medline_ta": "World J Clin Cases", "mesh_terms": null, "nlm_unique_id": "101618806", "other_id": null, "pages": "2316-2321", "pmc": null, "pmid": "31531325", "pubdate": "2019-08-26", "publication_types": "D002363:Case Reports", "references": "11487535;15056082;22508158;23299522;23964932;23964933;25222658;26084005;27930413;28097380;28698974;29106505;29266360;29720865;30151202;30480056;30810748", "title": "Effectiveness of vedolizumab treatment in two different anti-tumor necrosis factor alpha refractory pouchitis: A case report.", "title_normalized": "effectiveness of vedolizumab treatment in two different anti tumor necrosis factor alpha refractory pouchitis a case report" }

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null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "160 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "160", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ADALIMUMAB" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Diarrhoea", "reactionmeddraversionpt": "22.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Weight decreased", "reactionmeddraversionpt": "22.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Pouchitis", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Treatment failure", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 2014" } }, "primarysource": { "literaturereference": "CAKIR, OO. EFFECTIVENESS OF VEDOLIZUMAB TREATMENT IN TWO DIFFERENT ANTI-TUMOR NECROSIS FACTOR ALPHA REFRACTORY POUCHITIS: A CASE REPORT. WORLD JOURNAL OF CLINICAL CASES. 2019?7(16):2316-2321", "literaturereference_normalized": "effectiveness of vedolizumab treatment in two different anti tumor necrosis factor alpha refractory pouchitis a case report", "qualification": "1", "reportercountry": "TR" }, "primarysourcecountry": "TR", "receiptdate": "20190930", "receivedate": "20190930", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16869228, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20191005" } ]

{ "abstract": "Clostridium difficile associated diarrhoea or Pseudomembranous colitis occasionally occurs without prior antibiotic usage. While the association of chemotherapy and Clostridium difficile infection has previously been well recorded, the true incidence is unknown. We report a case of Clostridium difficile associated diarrhoea after chemotherapy for lung cancer. The fatal outcome in this case and the increasing use of chemotherapy in this country highlights the need to have a high index of suspicion in any case of unexplained diarrhoea post chemotherapy. A review of the literature is presented.", "affiliations": "Department of Medical Oncology, National University Hospital, Singapore.", "authors": "Wong|A S|AS|;Lam|C S|CS|;Tambyah|P A|PA|", "chemical_list": null, "country": "Singapore", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "0037-5675", "issue": "42(5)", "journal": "Singapore medical journal", "keywords": null, "medline_ta": "Singapore Med J", "mesh_terms": "D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D016360:Clostridioides difficile; D003967:Diarrhea; D004761:Enterocolitis, Pseudomembranous; D017809:Fatal Outcome; D006801:Humans; D008175:Lung Neoplasms; D008297:Male", "nlm_unique_id": "0404516", "other_id": null, "pages": "214-6", "pmc": null, "pmid": "11513059", "pubdate": "2001-05", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Fatal chemotherapy associated Clostridium difficile infection--a case report.", "title_normalized": "fatal chemotherapy associated clostridium difficile infection a case report" }

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FATAL CHEMOTHERAPY ASSOCIATED CLOSTRIDIUM DIFFICILE INFECTION - A CASE REPORT. SINGAPORE MEDICAL JOURNAL. 2001?42(5):214-216", "literaturereference_normalized": "fatal chemotherapy associated clostridium difficile infection a case report", "qualification": "1", "reportercountry": "SG" }, "primarysourcecountry": "SG", "receiptdate": "20181109", "receivedate": "20181109", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15603769, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190205" }, { "companynumb": "SG-PFIZER INC-2018443442", "fulfillexpeditecriteria": "1", "occurcountry": "SG", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBOPLATIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "076517", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBOPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINORELBINE TARTRATE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "076827", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINORELBINE TARTRATE." } ], "patientagegroup": null, "patientonsetage": "73", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pseudomembranous colitis", "reactionmeddraversionpt": "21.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "WONG, A.. FATAL CHEMOTHERAPY ASSOCIATED CLOSTRIDIUM DIFFICILE INFECTION - A CASE REPORT. SINGAPORE MEDICAL JOURNAL. 2001?42(5):214-216", "literaturereference_normalized": "fatal chemotherapy associated clostridium difficile infection a case report", "qualification": "1", "reportercountry": "SG" }, "primarysourcecountry": "SG", "receiptdate": "20181108", "receivedate": "20181031", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15570449, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190205" } ]

{ "abstract": "The purpose of this study was to evaluate the rate at which potentially inappropriate medications were administered for patients diagnosed with Parkinson's disease (PD). This is a single-center, retrospective, case cohort study with data collected at an academic medical center between January 2010 and December 2013. Participants included all adult patients with admission diagnosis codes for PD. Included patients were screened for administrations of 27 potentially inappropriate medications and two potentially appropriate medications to be used for comparison. There were 1736 patients who met inclusion criteria with 175 documented administrations of potentially inappropriate medications to 77 patients. Patients who received potentially inappropriate medications had a longer mean duration of stay than the baseline population of PD patients (3.3 days vs. 1.9 days, p-value < 0.001). Despite recommendations to avoid certain medications in PD patients, a substantial number of administrations still occurred. The use of these medications can have clinical implications and our findings demonstrate increases in duration of stay. The findings from this study can assist in developing technological alerts to reduce inappropriate prescribing to PD patients. Larger prospective studies are warranted to further investigate the administration of inappropriate medications to patients diagnosed with PD.", "affiliations": "Department of Pharmacotherapy, University of Utah College of Pharmacy, 30 S. 2000 E., Salt Lake City, UT 84112, USA. [email protected].;Department of Pharmacy Practice, West Coast University School of Pharmacy, Los Angeles, UT 90004, USA. [email protected].;Department of Pharmacy Services, University of Utah Health, 50 N. Medical Drive, Salt Lake City, UT 84132, USA. [email protected].", "authors": "Cox|Nicholas|N|;Louie|Jessica M|JM|0000-0003-0506-4487;Sederholm|Benson H|BH|", "chemical_list": null, "country": "Switzerland", "delete": false, "doi": "10.3390/pharmacy6030100", "fulltext": "\n==== Front\nPharmacy (Basel)Pharmacy (Basel)pharmacyPharmacy: Journal of Pharmacy Education and Practice2226-4787MDPI 10.3390/pharmacy6030100pharmacy-06-00100ArticleInappropriate Medication Use in Hospitalized Patients Diagnosed with Parkinson’s Disease Cox Nicholas 1*https://orcid.org/0000-0003-0506-4487Louie Jessica M. 2Sederholm Benson H. 31 Department of Pharmacotherapy, University of Utah College of Pharmacy, 30 S. 2000 E., Salt Lake City, UT 84112, USA2 Department of Pharmacy Practice, West Coast University School of Pharmacy, Los Angeles, UT 90004, USA; [email protected] Department of Pharmacy Services, University of Utah Health, 50 N. Medical Drive, Salt Lake City, UT 84132, USA; [email protected]* Correspondence: [email protected]; Tel.: +1-801-587-347215 9 2018 9 2018 6 3 10030 8 2018 12 9 2018 © 2018 by the authors.2018Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).The purpose of this study was to evaluate the rate at which potentially inappropriate medications were administered for patients diagnosed with Parkinson’s disease (PD). This is a single-center, retrospective, case cohort study with data collected at an academic medical center between January 2010 and December 2013. Participants included all adult patients with admission diagnosis codes for PD. Included patients were screened for administrations of 27 potentially inappropriate medications and two potentially appropriate medications to be used for comparison. There were 1736 patients who met inclusion criteria with 175 documented administrations of potentially inappropriate medications to 77 patients. Patients who received potentially inappropriate medications had a longer mean duration of stay than the baseline population of PD patients (3.3 days vs. 1.9 days, p-value < 0.001). Despite recommendations to avoid certain medications in PD patients, a substantial number of administrations still occurred. The use of these medications can have clinical implications and our findings demonstrate increases in duration of stay. The findings from this study can assist in developing technological alerts to reduce inappropriate prescribing to PD patients. Larger prospective studies are warranted to further investigate the administration of inappropriate medications to patients diagnosed with PD.\n\nParkinson’s diseasemedication errorsdrug-related side effects and adverse reactionsantipsychotic agents\n==== Body\n1. Introduction\nParkinson’s disease (PD) is a progressive neurological disorder that currently affects approximately 2% of people over 80 years of age. As of 2011, over 4.1 million individuals over the age of 50 are affected by PD, and that number is expected to double by 2030 [1,2]. Patients with PD are typically managed by neurologists and movement disorder specialists in the outpatient setting. When PD patients are admitted to acute care settings, they transition to non-specialist providers and complications can arise when medications are not managed appropriately [1].\n\nThe initial treatment of PD patients upon admission to hospitals is complicated due to unique factors (e.g., medication management, psychiatric problems, falls), which can have serious implications on the health of patients [3]. A diagnosis of PD is associated with longer hospitalization times and increased hospitalization rates [1]. The quality of care also varies depending on whether the patient is being admitted to a neurology service versus another service. Additionally, the care that the patient receives is dependent on whether the patient is admitted with Parkinsonian features but without a formal diagnosis of PD, the patient has PD but is hospitalized for unrelated problems, or the patient is hospitalized for PD complications [2].\n\nOne critical problem with hospitalized PD patients involves the ordering of potentially inappropriate medications. A number of common inpatient medications can have serious negative impacts on patients with PD. Examples include certain antiemetic medications, antipsychotic medications, pain medications, and others [4]. A survey of National Parkinson Foundation Centers indicated that 71% of centers were not confident that hospital professionals knew that certain antiemetic medications were contraindicated, and 80% were not confident that hospital professionals knew which antipsychotics would least likely exacerbate PD symptoms [1].\n\nThe goal of this study was to evaluate the rate at which potentially inappropriate medications were administered to inpatients diagnosed with PD and to determine if there was an association between these administrations and hospital length of stay.\n\n2. Materials and Methods \nThis was a single-center, retrospective, observational study at a 488-bed academic medical center. The study included patients greater than or equal to 18 years of age with PD who were admitted as inpatients between 1 January 2010 and 31 December 2013. Patients with PD were defined as those having a primary and/or secondary discharge International Statistical Classification of Diseases and Related Health Problems, Ninth Revision, (ICD-9) diagnosis code related to PD (see Table A1 in Appendix A). No exclusion criteria were used. Patients meeting inclusion criteria are referred to in this study as the “Baseline PD Population.” Patients were then filtered for those who received at least one inpatient administration of a potentially inappropriate medication. The following were considered potentially inappropriate medications: aripiprazole, asenapine, chlorpheniramine, chlorpromazine, clozapine, cyclizine, droperidol, fluphenazine, haloperidol, iloperidone, lithium, loxapine, lurasidone, meperidine (if patient concurrently taking a monoamine oxidase B inhibitor), metoclopramide, olanzapine, paliperidone, perphenazine, pimozide, prochlorperazine, promethazine, risperidone, thioridazine, thiothixene, trifluoperazine, valproate, and ziprasidone. \n\nThe primary objective was to assess the rate at which patients with PD received potentially inappropriate medications. This rate was measured using: (1) total number of patients receiving potentially inappropriate medication; and (2) total number of administrations of potentially inappropriate medications. These numbers were then analyzed and summarized in raw totals and also normalized by number of baseline PD patients. The secondary objective was to determine if there was an association between administrations of potentially inappropriate medications and hospital length of stay. This analysis was done by comparing the hospital length of stay amongst three different population pairs: (1) comparison was made between the baseline PD population and those administered a potentially inappropriate medication; (2) amongst patients administered an antipsychotic, comparison was made between those administered quetiapine (an antipsychotic that is not contraindicated in PD patients) and those administered a potentially inappropriate antipsychotic; and (3) amongst patients administered an antiemetic, comparison was made between those administered trimethobenzamide (an antiemetic that is not contraindicated in PD patients) and those administered a potentially inappropriate antiemetic. A potentially inappropriate antipsychotic was defined as one or more inpatient administrations of aripiprazole, chlorpromazine, haloperidol, lithium, olanzapine, or ziprasidone. A potentially inappropriate antiemetic was defined as one or more inpatient administrations of droperidol, metoclopramide, prochlorperazine, or promethazine. An electronic database query was used to identify patients, collect patient demographic information, and collect medication administration outcomes. Baseline demographic and clinical characteristics were summarized using means, frequencies, and percentages. Statistical analyses were performed using SAS V9.3 (Cary, NC) and Stata 13 (College Station, TX) assuming two-sided alpha of 0.05. All study activities were reviewed and approved by the health-system’s institutional review board and deemed exempt.\n\n3. Results\nThere were 1736 patients who met inclusion criteria and who functioned as the baseline PD population. During the four-year study period, there were 175 documented administrations of potentially inappropriate medications to 78 patients. The rates at which patients with Parkinson’s disease received potentially inappropriate medications are summarized in Figure 1. The baseline PD population had a mean age of 52.4 years and patients administered potentially inappropriate medications had a mean age of 56.1 years. The most commonly administered potentially inappropriate medications included droperidol (16% of all potentially inappropriate administrations), aripiprazole (15%), and promethazine (14%). All potentially inappropriate medications that were administered are summarized in Table 1. In regard to the secondary outcome, patients administered potentially inappropriate medications were admitted for 1.4 days longer than the baseline PD population (p-value < 0.001). Patients administered potentially inappropriate antipsychotics and antiemetics also had a longer hospital length of stay than their respective comparators, but this difference was not statistically significant. These secondary outcomes are summarized in Table 2. Of patients who received inpatient administrations of potentially inappropriate antipsychotics, no patients were subsequently transitioned to inpatient administrations of quetiapine.\n\n4. Discussion\nIn this analysis of PD patients, we found two significant findings. First, there was a significant number of PD patients administered inappropriate medications within a four-year timespan. Second, patients who were administered inappropriate medications had a statistically significant longer duration of hospital stay compared to the baseline PD population.\n\nParkinson’s disease has the potential to be overlooked when assessing potential medication errors and contraindications. At our academic medication center, despite long-standing use of electronic medication order entry and verification, there are no alert systems that warn healthcare providers when they are attempting to order inappropriate medications for PD patients. The use of alert systems could potentially decrease complications in PD patients. Examples of potential interventions include: Clinical decision support for antipsychotic or antiemetic medications in patients with PD, electronic alerts or warnings when providers attempt to order these potentially inappropriate medications in patients with PD, and the requirement for a neurological consultation when antipsychotics other than quetiapine or pimavanserin are ordered in patients with PD. Electronic medical records and computerized order entry are technologies purported to promote patient safety, but these systems can fail subsets of the population. In order to assess the effectiveness of a future alert system, and in order to make improvements to the system in the future, it is critical to know the rate at which inappropriate medications have been, and are currently being, ordered for PD patients. This study was designed to support future development and implementation of these types of systems.\n\nIn addition to inappropriate medication ordering, other difficulties arise in the treatment of PD inpatients. One concern is that patients’ outpatient PD medications can be restarted inappropriately at the hospital (e.g., wrong doses, timing, etc.); this can lead to alterations in mental status. Altered mental status can lead providers to order antipsychotic medications, such as quetiapine. These medications may not have been required if outpatient PD medications were restarted more appropriately. As a result, the rate of antipsychotic use was assessed and shown to have significantly high rates of inappropriate antipsychotic administrations compared to a preferred antipsychotic, quetiapine. Finally, the use of inappropriate antiemetic medications represented 46% of all inappropriate administrations.\n\nLimitations should be noted when interpreting study findings. First, with all observational studies, there is a possibility of unmeasured variables affecting causal inferences. One potential confounding variable to note is patient comorbid conditions which was not an outcome included in this study. Differences in comorbid conditions may have impacted duration of hospital stay. Second, this was a single-center study performed in an academic medical center and the practice pattern may not be applicable to hospitals serving small numbers of PD patients. Third, we included medications that are not expressly contraindicated in PD patients, and we also included PD subsets. This conservative approach may have diminished the effect of medications on hospital length of stay and thus understated the impact of more clinically important contraindicated medications (e.g., haloperidol) in PD patients. Fourth, a patient’s baseline outpatient medication regimen can influence inpatient medication decisions, but baseline outpatient medication regimens were not an outcome included in this study.\n\nIn conclusion, at an academic medical center, we observed a high prevalence of administrations of potentially inappropriate medications for patients with Parkinson’s disease (175 administrations over four years). These administrations may cause an extended duration of hospital stay as patients receiving these potentially inappropriate medications were observed to have an increased duration of hospital stay compared to the baseline PD population (3.3 days versus 1.9 days, p-value < 0.001). Larger studies are needed to validate these results and interventions, such as clinical decision support, are warranted to help improve medication use in this population.\n\nAcknowledgments\nThe authors gratefully acknowledge Rishi Deka, PhD, for statistical support.\n\nAuthor Contributions\nConceptualization, N.C., J.M.L. and B.H.S.; Data curation, N.C.; Formal analysis, N.C., J.M.L., and B.H.S.; Investigation, N.C., J.M.L., and B.H.S.; Methodology, N.C., J.M.L. and B.H.S.; Project administration, N.C.; Resources, N.C.; Validation, N.C.; Writing—original draft, N.C.; Writing—review and editing, N.C., J.M.L. and B.H.S.\n\nFunding\nThis research received no external funding.\n\nConflicts of Interest\nThe authors declare no conflict of interest.\n\nAppendix A\npharmacy-06-00100-t0A1_Table A1Table A1 Parkinson’s disease admission diagnosis codes [5].\n\nICD-9 Diagnosis Codes\t\n331.9 Cerebral degeneration, unspecified\t\n332.0 Paralysis agitans\t\n332.1 Secondary parkinsonism\t\n333.0 Other degenerative diseases of the basal ganglia\t\n333.1 Essential and other specified forms of tremor\t\n781.0 Abnormal involuntary movements\t\n781.3 Lack of coordination\t\nAbbreviations: ICD-9 = International Statistical Classification of Diseases and Related Health Problems, Ninth Revision.\n\nFigure 1 Rates of potentially inappropriate medication administration in hospitalized patients with Parkinson’s disease (PD).\n\npharmacy-06-00100-t001_Table 1Table 1 Potentially inappropriate medications administered.\n\nMedications Administered, n (% of Total Potentially Inappropriate Administrations)\tNumber of Administrations (n = 175)\t\nDroperidol\t27 (15)\t\nAripiprazole\t26 (15)\t\nPromethazine\t25 (14)\t\nProchlorperazine\t23 (13)\t\nMeperidine *\t20 (11)\t\nOlanzapine\t19 (11)\t\nLithium\t13 (7)\t\nZiprasidone\t10 (6)\t\nHaloperidol\t5 (3)\t\nMetoclopramide\t5 (3)\t\nChlorpromazine\t2 (1)\t\n* Only included in analysis if patient was concurrently being administered a monoamine oxidase B inhibitor.\n\npharmacy-06-00100-t002_Table 2Table 2 Patient characteristics and outcomes.\n\n\n\tPatients Administered PI Medications\tBaseline PD Population\tPatients Administered PI Antipsychotic ±\tPatients Administered Quetiapine\tPatients Administered PI Antiemetic †\tPatients Administered TMBA\t\nAge, mean\t56.1\t52.4\t51.6\t66.6\t56.4\t64.2\t\nPatients, n\t78\t1736\t12\t5\t70\t105\t\nAdministrations, n\t175\tN/A\t75\t15\t80\t199\t\nDays of hospitalization, n\t3.3\t1.9\t7.0\t6.2\t2.6\t2.1\t\nP-Value\t< 0.001\t0.867\t0.237\t\nAbbreviations: N/A = not applicable; PD = Parkinson’s disease; PI = Potentially inappropriate; TMBA = Trimethobenzamide. ± Defined as one or more inpatient administrations of aripiprazole, chlorpromazine, haloperidol, lithium, olanzapine, or ziprasidone. † Defined as one or more inpatient administrations of droperidol, metoclopramide, prochlorperazine, or promethazine.\n==== Refs\nReferences\n1. Chou K.L. Zamudio J. Schmidt P. Price C.C. Parashos S.A. Bloem B.R. Lyons K.E. Christine C.W. Pajesh R. Bodis-Wollner I. Hospitalization in Parkinson disease: a survey of National Parkinson Foundation Centers Parkinsonism Relat. Disord. 2011 17 440 445 10.1016/j.parkreldis.2011.03.002 21458353 \n2. MacMahon M.J. MacMahon D.G. Management of Parkinson’s disease in the acute hospital environment J. R. Coll. Physicians Edinb. 2012 42 157 162 10.4997/JRCPE.2012.215 22693703 \n3. Aminoff M.J. Christine C.W. Friedman J.H. Chou K.L. Lyons K.E. Pahwa R. Bloem B.R. Parashos S.A. Price C.C. Malaty I.A. Management of the hospitalized patient with Parkinson’s disease: current state of the field and need for guidelines Parkinsonism Relat. Disord. 2011 17 139 145 10.1016/j.parkreldis.2010.11.009 21159538 \n4. Shprecher D. Sederholm B. Avoiding Parkinson’s medication errors in the hospital Am. Parkinson Dis. Assoc. Parkinson’s News 2012 Fall 1 2 \n5. Savica R. Grossardt B.R. Bower J.H. Ahlskog J.E. Rocca W.A. Incidence and pathology of synucleinopathies and tauopathies related to parkinsonism JAMA Neurol. 2013 70 859 866 10.1001/jamaneurol.2013.114 23689920\n\n", "fulltext_license": "CC BY", "issn_linking": "2226-4787", "issue": "6(3)", "journal": "Pharmacy (Basel, Switzerland)", "keywords": "Parkinson’s disease; antipsychotic agents; drug-related side effects and adverse reactions; medication errors", "medline_ta": "Pharmacy (Basel)", "mesh_terms": null, "nlm_unique_id": "101678532", "other_id": null, "pages": null, "pmc": null, "pmid": "30223544", "pubdate": "2018-09-15", "publication_types": "D016428:Journal Article", "references": "21159538;21458353;22693703;23689920", "title": "Inappropriate Medication Use in Hospitalized Patients Diagnosed with Parkinson's Disease.", "title_normalized": "inappropriate medication use in hospitalized patients diagnosed with parkinson s disease" }

[ { "companynumb": "US-JNJFOC-20181018751", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "HALOPERIDOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "015923", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNSPECIFIED", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PARKINSON^S DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HALOPERIDOL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DROPERIDOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "016796", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNSPECIFIED", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PARKINSON^S DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DROPERIDOL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PROMETHAZINE\\PROMETHAZINE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "999999", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNSPECIFIED", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PARKINSON^S DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PROMETHAZINE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hospitalisation", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Product administration error", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "COX N, LOUIE JM, SEDERHOLM BH. INAPPROPRIATE MEDICATION USE IN HOSPITALIZED PATIENTS DIAGNOSED WITH PARKINSON^S DISEASE. PHARMACY 15-SEP-2018?6(3):1-6.", "literaturereference_normalized": "inappropriate medication use in hospitalized patients diagnosed with parkinson s disease", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20181017", "receivedate": "20181017", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15517646, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190205" } ]

{ "abstract": "OBJECTIVE\nWe report a rare case of acute abdomen pain in 27 weeks´ gestation caused by a perforated leiomyoma mimicking pseudomyxoma peritonei on magnetic resonance imaging.\n\n\nMETHODS\nCase report.\n\n\nMETHODS\n1st Department of Gynaecology and Obstetrics. Faculty of Medicine, Comenius University in Bratislava, Slovakia.\n\n\nMETHODS\nIn our reported case report of perforated leiomyoma mimicking pseudomyxoma peritonei on magnetic resonance imaging. Successful myomectomy was done, and the pregnancy continued with good outcome. At week 40, the patient underwent caesarean section.\n\n\nCONCLUSIONS\nUterine fibroids in pregnancy can lead to severe complications. Their spontaneous rupture in pregnancy is very rare. To manage acute abdominal pain in pregnancy a good diagnostic must be performed, and surgical treatment should be carefully considered.", "affiliations": null, "authors": "Korňanová|E|E|;Hammerová|Ľ|Ľ|;Jezberová|M|M|;Borovský|M|M|", "chemical_list": null, "country": "Czech Republic", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "1210-7832", "issue": "85(6)", "journal": "Ceska gynekologie", "keywords": "Magnetic resonance imaging; Pregnancy; myomectomy; perforated leiomyoma; pregnancy; ultrasound; ultrazvuk", "medline_ta": "Ceska Gynekol", "mesh_terms": "D002585:Cesarean Section; D005260:Female; D006801:Humans; D007889:Leiomyoma; D010534:Peritoneal Neoplasms; D011247:Pregnancy; D011553:Pseudomyxoma Peritonei; D018154:Slovakia; D063186:Uterine Myomectomy; D014594:Uterine Neoplasms", "nlm_unique_id": "9423768", "other_id": null, "pages": "403-407", "pmc": null, "pmid": "33711900", "pubdate": "2020", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Laparotomic myomectomy of a spontaneous perforated leiomyoma mimicking pseudomyxoma peritonei at 27 weeks of pregnancy.", "title_normalized": "laparotomic myomectomy of a spontaneous perforated leiomyoma mimicking pseudomyxoma peritonei at 27 weeks of pregnancy" }

[ { "companynumb": "CZ-BAUSCH-BL-2021-008514", "fulfillexpeditecriteria": "1", "occurcountry": "CZ", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "40069", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "GENTAMICIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "64048", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LEIOMYOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GENTAMYCIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMPICILLIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LEIOMYOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMPICILLIN" } ], "patientagegroup": null, "patientonsetage": "42", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Maternal exposure during pregnancy", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Polyhydramnios", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Liver disorder", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "UNKNOWN. LAPAROTOMIC MYOMECTOMY OF A SPONTANEOUS PERFORATED LEIOMYOMA MIMICKING PSEUDOMYXOMA PERITONEI AT 27 WEEKS OF PREGNANCY. CESKA GYNEKOLOGIE. 2020?6:403?407.", "literaturereference_normalized": "laparotomic myomectomy of a spontaneous perforated leiomyoma mimicking pseudomyxoma peritonei at 27 weeks of pregnancy", "qualification": "1", "reportercountry": "CZ" }, "primarysourcecountry": "CZ", "receiptdate": "20210319", "receivedate": "20210319", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19027466, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" } ]

{ "abstract": "Diffuse alveolar haemorrhage (DAH) has been reported as a rare complication of clopidogrel use and is usually a diagnosis of exclusion. We describe the case of an 88-year-old Native American woman who presented with acute hypoxic respiratory failure with CT scan of the chest showing diffuse bilateral ground-glass opacities. She had been on clopidogrel for 6 months for a carotid artery stent. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsies revealed DAH. Infectious and autoimmune work-up were all negative. Clopidogrel was stopped and high-dose steroids were started. Her symptoms gradually improved until she was discharged from the hospital. The differential DAH is broad. Anticoagulant-induced DAH should be part of the differential diagnosis, and is usually a diagnosis of exclusion.", "affiliations": "The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.;Division of Pulmonary, Critical Care, and Sleep Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.;Division of Pulmonary, Critical Care, and Sleep Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA [email protected].", "authors": "Soriano|Rachelle|R|;Al-Rawaf|Saud|S|;Diab|Khalil|K|", "chemical_list": "D000077144:Clopidogrel", "country": "England", "delete": false, "doi": "10.1136/bcr-2021-244314", "fulltext": null, "fulltext_license": null, "issn_linking": "1757-790X", "issue": "14(8)", "journal": "BMJ case reports", "keywords": "adult intensive care; drugs: respiratory system; interstitial lung disease; vasculitis", "medline_ta": "BMJ Case Rep", "mesh_terms": "D000369:Aged, 80 and over; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy; D000077144:Clopidogrel; D005260:Female; D006470:Hemorrhage; D006801:Humans; D008171:Lung Diseases", "nlm_unique_id": "101526291", "other_id": null, "pages": null, "pmc": null, "pmid": "34373244", "pubdate": "2021-08-09", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Diffuse alveolar haemorrhage: a rare complication of clopidogrel use.", "title_normalized": "diffuse alveolar haemorrhage a rare complication of clopidogrel use" }

[ { "companynumb": "US-TEVA-2021-US-1950048", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "CLOPIDOGREL BISULFATE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "076999", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTICOAGULANT THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLOPIDOGREL" } ], "patientagegroup": "6", "patientonsetage": "88", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pulmonary alveolar haemorrhage", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "SORIANO R, AL?RAWAF S, DIAB K. DIFFUSE ALVEOLAR HAEMORRHAGE: A RARE COMPLICATION OF CLOPIDOGREL USE. BMJ?CASE?REP 2021?14:NO. 8.", "literaturereference_normalized": "diffuse alveolar haemorrhage a rare complication of clopidogrel use", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210916", "receivedate": "20210909", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19811794, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": null, "transmissiondate": "20211014" }, { "companynumb": "US-PRINSTON PHARMACEUTICAL INC.-2021PRN00309", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "CLOPIDOGREL BISULFATE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "206376", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "STARTED IN JUNE 2020", "drugenddate": null, "drugenddateformat": null, "drugindication": "CAROTID ARTERY STENT INSERTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLOPIDOGREL" }, { "actiondrug": null, "activesubstance": null, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "COVID?19 MRNA VACCINE" } ], "patientagegroup": null, "patientonsetage": "88", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Pulmonary haemorrhage", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "SORIANO R, AL?RAWAF S, DIAB K. DIFFUSE ALVEOLAR HAEMORRHAGE: A RARE COMPLICATION OF CLOPIDOGREL USE. BMJ CASE REP. 2021?14(8)", "literaturereference_normalized": "diffuse alveolar haemorrhage a rare complication of clopidogrel use", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210831", "receivedate": "20210831", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19772776, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20211014" }, { "companynumb": "US-ACCORD-236516", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CARDIAC FAILURE CONGESTIVE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG PER?DAY FOR 3 DAYS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CLOPIDOGREL BISULFATE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "202925", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": "202012", "drugenddateformat": "610", "drugindication": "ANTICOAGULANT THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202006", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLOPIDOGREL" }, { "actiondrug": "5", "activesubstance": null, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "FIRST DOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "COVID?19 VACCINE" } ], "patientagegroup": null, "patientonsetage": "88", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Diffuse alveolar damage", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Pulmonary alveolar haemorrhage", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 2020" } }, "primarysource": { "literaturereference": "SORIANO R, AL?RAWAF S, DIAB K. DIFFUSE ALVEOLAR HAEMORRHAGE: A RARE COMPLICATION OF CLOPIDOGREL USE. BMJ CASE REP. 2021 AUG 9?14(8):E244314", "literaturereference_normalized": "diffuse alveolar haemorrhage a rare complication of clopidogrel use", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210906", "receivedate": "20210826", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19749590, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20211014" } ]

{ "abstract": "We report the case of a 51-year-old female with stage IV advanced breast cancer accompanied by multiple bone metastases. A hard mass of about 3.0 cm in diameter was palpated just below the nipple. An excisional biopsy was performed and histological examination revealed infiltrated solid tubular adenocarcinoma. There were no estrogen or progesterone receptors in the tumor. Modified radical mastectomy was performed in October, 1998. Postoperative adjuvant therapy with 10 cycles of CEF therapy was undertaken for one year. Combined chemoendocrine therapy with 5'-DFUR and MPA was also conducted for 11 months. Bone scintigraphy showed that all bone metastatic lesions disappeared completely one year after the operation. Mild bone marrow suppression, alopecia and body weight gain were observed as side effects. It is suggested that this combination therapy may be useful for advanced breast cancer patients with multiple bone metastases.", "affiliations": "Dept. of Surgery, Tsukazaki Hospital.", "authors": "Fukuda|Y|Y|;Hirao|S|S|;Koyama|I|I|;Takatori|H|H|;Terakura|M|M|;Mayumi|K|K|;Tsukazaki|Y|Y|;Kinoshita|H|H|", "chemical_list": "D000964:Antimetabolites, Antineoplastic; D045167:Progesterone Congeners; D005467:Floxuridine; D015251:Epirubicin; D003520:Cyclophosphamide; D008525:Medroxyprogesterone; D005472:Fluorouracil; C025034:doxifluridine", "country": "Japan", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "0385-0684", "issue": "28(2)", "journal": "Gan to kagaku ryoho. Cancer & chemotherapy", "keywords": null, "medline_ta": "Gan To Kagaku Ryoho", "mesh_terms": "D000964:Antimetabolites, Antineoplastic; D000971:Antineoplastic Combined Chemotherapy Protocols; D001859:Bone Neoplasms; D001943:Breast Neoplasms; D003520:Cyclophosphamide; D004359:Drug Therapy, Combination; D015251:Epirubicin; D005260:Female; D005467:Floxuridine; D005472:Fluorouracil; D006801:Humans; D008525:Medroxyprogesterone; D008875:Middle Aged; D045167:Progesterone Congeners; D016896:Treatment Outcome", "nlm_unique_id": "7810034", "other_id": null, "pages": "217-20", "pmc": null, "pmid": "11242649", "pubdate": "2001-02", "publication_types": "D002363:Case Reports; D004740:English Abstract; D016428:Journal Article", "references": null, "title": "Advanced breast cancer with multiple bone metastases successfully treated with combined chemoendocrine-therapy of CEF (cyclophosphamide, epirubicin, 5-fluorouracil) and 5'-DFUR (5'-deoxy-5-fluorouridine) + MPA (medroxyprogesterone acetate)--a case report.", "title_normalized": "advanced breast cancer with multiple bone metastases successfully treated with combined chemoendocrine therapy of cef cyclophosphamide epirubicin 5 fluorouracil and 5 dfur 5 deoxy 5 fluorouridine mpa medroxyprogesterone acetate a case report" }

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"activesubstancename": "MEDROXYPROGESTERONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1200 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER STAGE IV", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MEDROXYPROGESTERONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "EPIRUBICIN" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "65445", "drugbatchnumb": "UNCONFIRMED", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNK", "drugdosagetext": "CYCLICAL, 10 CYCLES", "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER STAGE IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "19981110", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EPIRUBICIN (UNKNOWN)" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DOXIFLURIDINE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER STAGE IV", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOXIFLURIDINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG/DAY, CYCLICAL,", "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER STAGE IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "5-FLUOROURACIL /00098801/" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MG/DAY, CYCLICAL, 2 WEEKS THERAPY 2 WEEKS REST", "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER STAGE IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MEDROXYPROGESTERONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MEDROXYPROGESTERONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TAMOXIFEN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "20 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER STAGE IV", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TAMOXIFEN" } ], "patientagegroup": null, "patientonsetage": "51", "patientonsetageunit": "801", "patientsex": "2", "patientweight": "142", "reaction": [ { "reactionmeddrapt": "Alopecia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Weight increased", "reactionmeddraversionpt": "19.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Leukopenia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Bone marrow failure", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "FUKUDA Y, HIRAO S, KOYAMA , TAKATORI H, TERAKURA M, MAYUMI K. [ADVANCED BREAST CANCER WITH MULTIPLE BONE METASTASES SUCCESSFULLY TREATED WITH COMBINED CHEMOENDOCRINE-THERAPY OF CEF (CYCLOPHOSPHAMIDE, EPIRUBICIN, 5-FLUOROURACIL) AND 5^-DFUR (5^-DEOXY-5-FLUOROURIDINE) + MPA (MEDROXYPROGESTERONE ACETATE)--A CASE REPORT]. GAN TO KAGAKU RYOHO. 2001?28(2):217-20. JAPANESE", "literaturereference_normalized": "advanced breast cancer with multiple bone metastases successfully treated with combined chemoendocrine therapy of cef cyclophosphamide epirubicin 5 fluorouracil and 5 dfur 5 deoxy 5 fluorouridine mpa medroxyprogesterone acetate a case report", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20160217", "receivedate": "20160128", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11969532, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20160526" } ]

{ "abstract": "OBJECTIVE\nIdentification of predictors of survival of patients with lower genital tract melanoma (LGTM) and evaluation of the effectiveness of immunotherapy.\n\n\nMETHODS\nData of twenty women with LGTM were retrospectively collected. Survival outcomes were evaluated using the Kaplan-Meier method. Survival distributions were analyzed using the Log rank test.\n\n\nRESULTS\nTwenty patients with LGTM (6 vaginal/14 vulvar) were evaluated. Factors significantly affecting Five-year OS was the stage of the American Joint Committee on Cancer (AJCC 2017) (I+II: 55.6% vs. III+IV: 25.9%; p=0.030) and the T-Stage (I+II: 100% vs. III+IV: 7.5%; p=0.280). Factors negatively affecting Five-year PFS was T-Stage >II (p=0.005), AJCC stage >II (p<0.001), depth of tumor infiltration >3 mm (p=0.008), nodal involvement (p=0.013), distant disease (p=0.002), and resection margins <10 mm (p=0.024). Nine patients received immunotherapy [median duration of response (DOR)=4 months]. Three patients received immuno- and radiation therapy (median DOR of 5 months). Two patients received T-VEC, only one responded.\n\n\nCONCLUSIONS\nSurgery has a therapeutic effect in early stage LGTM. Advanced stages may be treated with immunotherapy, radiation therapy, a combination of both, and oncolytic viral immunotherapy.", "affiliations": "Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany; [email protected].;Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany.;Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany.;Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany.;Department of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany.;Department of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany.;Department of Senology, University Hospital Bonn, Bonn, Germany.;Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Bonn, Germany.", "authors": "Egger|Eva Katharina|EK|;Stope|Matthias B|MB|;Recker|Florian|F|;Konsgen|Dominique|D|;Landsberg|Jennifer|J|;Frohlich|Anne|A|;Abramian|Alina|A|;Mustea|Alexander|A|", "chemical_list": "D000074322:Antineoplastic Agents, Immunological", "country": "Greece", "delete": false, "doi": "10.21873/anticanres.14854", "fulltext": null, "fulltext_license": null, "issn_linking": "0250-7005", "issue": "41(2)", "journal": "Anticancer research", "keywords": "Lower genital tract melanoma; immunotherapy", "medline_ta": "Anticancer Res", "mesh_terms": "D000368:Aged; D000369:Aged, 80 and over; D000074322:Antineoplastic Agents, Immunological; D003131:Combined Modality Therapy; D005260:Female; D013509:Gynecologic Surgical Procedures; D006801:Humans; D007167:Immunotherapy; D053208:Kaplan-Meier Estimate; D000072662:Margins of Excision; D008545:Melanoma; D008875:Middle Aged; D009367:Neoplasm Staging; D050504:Oncolytic Viruses; D011878:Radiotherapy; D012189:Retrospective Studies; D016896:Treatment Outcome; D014625:Vaginal Neoplasms; D014846:Vulvar Neoplasms", "nlm_unique_id": "8102988", "other_id": null, "pages": "999-1004", "pmc": null, "pmid": "33517307", "pubdate": "2021-02", "publication_types": "D016428:Journal Article", "references": null, "title": "Lower Genital Tract Melanomas: Staging, Predictors of Outcome, and New Therapeutic Options.", "title_normalized": "lower genital tract melanomas staging predictors of outcome and new therapeutic options" }

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"Immune-mediated enterocolitis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Immune-mediated hepatitis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Addison^s disease", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Metastatic malignant melanoma", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "RECKER, F. LOWER GENITAL TRACT MELANOMAS: STAGING, PREDICTORS OF OUTCOME, AND NEW THERAPEUTIC OPTIONS. ANTICANCER RESEARCH. 2021?999?1004 (2021)", "literaturereference_normalized": "lower genital tract melanomas staging predictors of outcome and new therapeutic options", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20210222", "receivedate": "20210222", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18924028, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" }, { "companynumb": "DE-AMGEN-DEUSP2021025046", "fulfillexpeditecriteria": "2", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "TALIMOGENE LAHERPAREPVEC" }, "drugadditional": null, 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"drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GENITOURINARY MELANOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEMBROLIZUMAB." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "IPILIMUMAB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GENITOURINARY MELANOMA", 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"PEMBROLIZUMAB." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "NIVOLUMAB" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GENITOURINARY MELANOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NIVOLUMAB" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "TALIMOGENE LAHERPAREPVEC" }, "drugadditional": null, "drugadministrationroute": "036", 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"drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "METASTASES TO LIVER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IPILIMUMAB" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Metastatic malignant melanoma", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Death", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Therapeutic product effect incomplete", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "RECKER, F. LOWER GENITAL TRACT MELANOMAS: STAGING, PREDICTORS OF OUTCOME, AND NEW THERAPEUTIC OPTIONS. ANITICANCER REASEARCH. 2021?41 (2):999?1004", "literaturereference_normalized": "lower genital tract melanomas staging predictors of outcome and new therapeutic options", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20210219", "receivedate": "20210219", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18914472, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" } ]

{ "abstract": "The patient was an 82-year-old man who had undergone resection of a gastrointestinal stromal tumor(GIST)of the small intestine in January 2000, when he was 69 years old. As peritoneal recurrences were diagnosed in June 2002, we performed peritoneal tumorectomy twice, and the perirectal tumor was controlled with imatinib for over 7 years. Resistance to imatinib was diagnosed in March 2011, and treatment was switched to sunitinib. Administration of sunitinib was started at 50mg/day for 28 days followed by treatment withdrawal for 14 days; however, the dose needed to be reduced twice and then discontinued owing to the occurrence of side effects and pemphigoid. During discontinuation of sunitinib, the tumor increased in size and cancer pain appeared; therefore, sunitinib was re-administered at a very low-dose of 12.5mg every alternate day. Low dose sunitinib was effective; the perirectal tumor was reduced and cancer pain disappeared.", "affiliations": "Dept. of Surgery, Kumamoto Rosai Hospital.", "authors": "Yoshida|Yasushi|Y|;Akahoshi|Shinichi|S|;Kiyota|Yoshitaka|Y|;Motooka|Yamato|Y|;Kiyozumi|Yuuki|Y|;Yamaguchi|Risa|R|;Inoue|Katsuhiko|K|", "chemical_list": "D000970:Antineoplastic Agents; D001549:Benzamides; D007211:Indoles; D010879:Piperazines; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; D000077210:Sunitinib", "country": "Japan", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "0385-0684", "issue": "40(13)", "journal": "Gan to kagaku ryoho. Cancer & chemotherapy", "keywords": null, "medline_ta": "Gan To Kagaku Ryoho", "mesh_terms": "D000369:Aged, 80 and over; D000970:Antineoplastic Agents; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D046152:Gastrointestinal Stromal Tumors; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles; D007414:Intestinal Neoplasms; D007421:Intestine, Small; D008297:Male; D010534:Peritoneal Neoplasms; D010879:Piperazines; D011743:Pyrimidines; D011758:Pyrroles; D012008:Recurrence; D016879:Salvage Therapy; D000077210:Sunitinib", "nlm_unique_id": "7810034", "other_id": null, "pages": "2573-5", "pmc": null, "pmid": "24335373", "pubdate": "2013-12", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "A case of imatinib-resistant gastrointestinal stromal tumor treated with low-dose sunitinib.", "title_normalized": "a case of imatinib resistant gastrointestinal stromal tumor treated with low dose sunitinib" }

[ { "companynumb": "JP-MYLANLABS-2015M1013352", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "SUNITINIB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "201275", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "37.5 MG/DAY FOR 2 WEEKS FOLLOWED BY 1 WEEK OF REST", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": [ { "drugrecuraction": "Diarrhoea" } ], "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SUNITINIB" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "SUNITINIB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "201275", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/DAY, 4 WEEKS FOLLOWED BY 2 WEEKS REST", "drugenddate": null, "drugenddateformat": null, "drugindication": "GASTROINTESTINAL STROMAL TUMOUR", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": [ { "drugrecuraction": "Diarrhoea" } ], "drugseparatedosagenumb": null, "drugstartdate": "201104", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SUNITINIB" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "SUNITINIB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "201275", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MG/DAY FOR 2 WEEKS FOLLOWED BY 1 WEEK OF REST", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": [ { "drugrecuraction": "Diarrhoea" } ], "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SUNITINIB" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Decreased appetite", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Diarrhoea", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pemphigoid", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Platelet count decreased", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "YOSHIDA Y, AKAHOSHI S, KIYOTA Y, MOTOOKA Y, KIYOZUMI Y, YAMAGUCHI R, ET AL. A CASE OF IMATINIB-RESISTANT GASTROINTESTINAL STROMAL TUMOR TREATED WITH LOW-DOSE SUNITINIB]. . GAN-TO-KAGAKU-RYOHO 2013; 40(13):2573-5.", "literaturereference_normalized": "a case of imatinib resistant gastrointestinal stromal tumor treated with low dose sunitinib", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20150422", "receivedate": "20150422", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11056308, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150821" } ]

{ "abstract": "Collapsing focal segmental glomerulosclerosis (FSGS) is a variant of FSGS and is associated with severe nephrotic syndrome and acute kidney injury and can occur after kidney transplantation. The exact mechanism of collapsing FSGS after kidney transplantation is unknown, but potential causes include autoimmune diseases, certain malignancies, bisphosphonates, m-TOR inhibitors, interferon-alpha, HIV infection, and other viruses. We describe a case of de novo Cytomegalovirus (CMV)-associated collapsing FSGS in a kidney transplant recipient with a UL97 phosphotransferase mutation that was successfully treated with intravenous ganciclovir, intravenous immunoglobulin, and steroids.", "affiliations": "Renal and Pancreas Transplant Division, Saint Barnabas Medical Center, Livingston, NJ, USA.;Medicine/Nephrology, RWJBarnabas Health, Livingston, NJ, USA.;Renal and Pancreas Transplant Division, Saint Barnabas Medical Center, Livingston, NJ, USA.", "authors": "Patel|Anup M|AM|http://orcid.org/0000-0003-0290-4719;Zenenberg|Robert D|RD|;Goldberg|Ryan J|RJ|", "chemical_list": "D016756:Immunoglobulins, Intravenous; D013256:Steroids; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D015774:Ganciclovir", "country": "Denmark", "delete": false, "doi": "10.1111/tid.12884", "fulltext": null, "fulltext_license": null, "issn_linking": "1398-2273", "issue": "20(3)", "journal": "Transplant infectious disease : an official journal of the Transplantation Society", "keywords": "\nCMV\n; collapsing FSGS; kidney transplant", "medline_ta": "Transpl Infect Dis", "mesh_terms": "D000328:Adult; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections; D018450:Disease Progression; D015774:Ganciclovir; D005923:Glomerulosclerosis, Focal Segmental; D006801:Humans; D016756:Immunoglobulins, Intravenous; D016030:Kidney Transplantation; D008297:Male; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor); D013256:Steroids; D016896:Treatment Outcome", "nlm_unique_id": "100883688", "other_id": null, "pages": "e12884", "pmc": null, "pmid": "29570919", "pubdate": "2018-06", "publication_types": "D002363:Case Reports", "references": null, "title": "De novo CMV-associated collapsing focal segmental glomerulosclerosis in a kidney transplant recipient.", "title_normalized": "de novo cmv associated collapsing focal segmental glomerulosclerosis in a kidney transplant recipient" }

[ { "companynumb": "US-ALKEM LABORATORIES LIMITED-US-ALKEM-2018-05073", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "200197", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." } ], "patientagegroup": null, "patientonsetage": "34", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Focal segmental glomerulosclerosis", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Cytomegalovirus viraemia", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "PATEL AM, ZENENBERG RD AND GOLDBERG RJ.. DE NOVO CMV-ASSOCIATED COLLAPSING FOCAL SEGMENTAL GLOMERULOSCLEROSIS IN A KIDNEY TRANSPLANT RECIPIENT. TRANSPLANT INFECTIOUS DISEASE.. 2018?20:E12884", "literaturereference_normalized": "de novo cmv associated collapsing focal segmental glomerulosclerosis in a kidney transplant recipient", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20190103", "receivedate": "20190103", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15784649, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190417" }, { "companynumb": "US-ASTELLAS-2018US028520", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "050708", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "FORMULATION UNKNOWN", "drugdosagetext": "UNK UNK, UNKNOWN FREQ.", "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MYCOPHENOLIC ACID" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "FORMULATION UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "720", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLIC ACID." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "FORMULATION UNKNOWN", "drugdosagetext": "UNK UNK, UNKNOWN FREQ.", "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANTITHYMOCYTE IMMUNOGLOBULIN (RABBIT)" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MYCOPHENOLIC ACID" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "FORMULATION UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "360", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLIC ACID." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "FORMULATION UNKNOWN", "drugdosagetext": "UNK UNK, UNKNOWN FREQ.", "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." } ], "patientagegroup": null, "patientonsetage": "34", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Device related thrombosis", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Focal segmental glomerulosclerosis", "reactionmeddraversionpt": "21.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Deep vein thrombosis", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cytomegalovirus infection", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "PATEL AM, ZENENBERG RD, GOLDBERG RJ. DE NOVO CMV-ASSOCIATED COLLAPSING FOCAL SEGMENTAL GLOMERULOSCLEROSIS IN A KIDNEY TRANSPLANT RECIPIENT. TRANSPL INFECT DIS. 2018?20(3):E12884", "literaturereference_normalized": "de novo cmv associated collapsing focal segmental glomerulosclerosis in a kidney transplant recipient", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20180629", "receivedate": "20180629", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15090735, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" } ]

{ "abstract": "This study examined the risk of all-cause-mortality in patients with Parkinson's Disease (PD) and comorbid depression using inappropriate atypical antipsychotics (AAPs), based on the 2015 American Geriatrics Society Beers criteria.\n\n\n\nA retrospective analysis of 2007-2010 Minimum Data Set linked Medicare data was conducted using a propensity-matched approach. The cohort included PD patients aged 65 years or older without schizophrenia or bipolar disorder who started AAPs. All patients had a diagnosis of comorbid depression. Risk of 6-month all-cause-mortality was compared across appropriate AAPs (aripiprazole, clozapine, or quetiapine) and inappropriate AAPs (olanzapine, asenapine, brexpiprazole, iloperidone, lurasidone, paliperidone, risperidone, or ziprasidone) using robust Cox regression models involving the matched cohort.\n\n\n\nAll-cause mortality rate was 15.65% in appropriate AAP group (n = 6,038) and 16.91% in inappropriate AAP group (n = 6,038) over 6-month follow-up in the matched cohort. The robust Cox proportional hazards models revealed increased risk of all-cause mortality (hazard ratio [HR] 1.13 [95% confidence interval {CI}: 1.01-1.28)] for patients who used inappropriate compared to appropriate AAPs. Risk of death was also higher for risperidone compared to quetiapine (HR: 1.20 [95% CI: 1.03-1.40]) in sensitivity analysis. However, there was a significant relationship between pneumonia and death in all analyses. The impact of inappropriate AAP use on mortality was not significant when pneumonia was modeled as a mediator.\n\n\n\nInappropriate AAP use is associated with a higher risk of all-cause-mortality in older patients with PD which is mainly mediated by pneumonia. Therefore, inappropriate AAP use should be avoided to improve quality of care in PD.", "affiliations": "Department of Pharmaceutical Health Outcomes and Policy (FC, MLJ, HC, RRA), College of Pharmacy, University of Houston, Houston, TX.;The University of Texas Health Science Center (HMH), Houston, TX; Division of Geriatric and Palliative Medicine (HMH), McGovern Medical School, Houston, TX.;Department of Pharmaceutical Health Outcomes and Policy (FC, MLJ, HC, RRA), College of Pharmacy, University of Houston, Houston, TX.;Department of Pharmaceutical Health Outcomes and Policy (FC, MLJ, HC, RRA), College of Pharmacy, University of Houston, Houston, TX.;Department of Pharmaceutical Health Outcomes and Policy (FC, MLJ, HC, RRA), College of Pharmacy, University of Houston, Houston, TX.;Department of Pharmaceutical Health Outcomes and Policy (FC, MLJ, HC, RRA), College of Pharmacy, University of Houston, Houston, TX. Electronic address: [email protected].", "authors": "Chekani|Farid|F|;Holmes|Holly M|HM|;Johnson|Michael L|ML|;Chen|Hua|H|;Sherer|Jeffrey T|JT|;Aparasu|Rajender R|RR|", "chemical_list": "D014150:Antipsychotic Agents", "country": "England", "delete": false, "doi": "10.1016/j.jagp.2020.01.193", "fulltext": null, "fulltext_license": null, "issn_linking": "1064-7481", "issue": "28(10)", "journal": "The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry", "keywords": "Parkinson's disease; antipsychotics; mortality; pneumonia", "medline_ta": "Am J Geriatr Psychiatry", "mesh_terms": "D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents; D015897:Comorbidity; D003863:Depression; D005260:Female; D006801:Humans; D008297:Male; D010300:Parkinson Disease; D011014:Pneumonia; D012189:Retrospective Studies; D014481:United States", "nlm_unique_id": "9309609", "other_id": null, "pages": "1079-1088", "pmc": null, "pmid": "32147383", "pubdate": "2020-10", "publication_types": "D016428:Journal Article", "references": null, "title": "Risk of Mortality Associated With Atypical Antipsychotic use: A National Cohort Study of Older Adults With Depression and Parkinson's Disease.", "title_normalized": "risk of mortality associated with atypical antipsychotic use a national cohort study of older adults with depression and parkinson s disease" }

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Risk of Mortality Associated With Atypical Antipsychotic use: A National Cohort Study of Older Adults With Depression and Parkinson^s Disease. 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{ "abstract": "Microsporidia are organisms that are known to cause opportunistic infections in immunocompromised individuals. The gastrointestinal tract is the most common affected organ. Enterocytozoon bieneusi is the most common species that infect humans. There are no known established guidelines for the treatment of this particular microsporidium. A 72-year old immunocompetent female presented to our hospital with diarrhea for four weeks. She had failed outpatient oral antimicrobial treatment for suspected traveler's diarrhea and Clostridium difficile. Initial stool cultures were negative but given her persistent symptomatology, stool PCR was sent to rule out microsporidia and was positive for Enterocytozoon bieneusi. Patient failed treatment with albendazole. She was then subsequently treated with nitazoxanide and achieved successful infection resolution. This case demonstrates the importance of considering atypical infections in patient with persistent symptoms and suggest that nitazoxanide is effective in treating infection caused by Enterocytozoon bieneusi microsporidia.", "affiliations": "Ascension Genesys Hospital, 1 Genesys Pkwy, Grand Blanc, MI 48439, United States.;Ascension Genesys Hospital, 1 Genesys Pkwy, Grand Blanc, MI 48439, United States.", "authors": "Saffo|Zaid|Z|;Mirza|Najab|N|", "chemical_list": null, "country": "Netherlands", "delete": false, "doi": "10.1016/j.idcr.2019.e00586", "fulltext": "\n==== Front\nIDCasesIDCasesIDCases2214-2509Elsevier S2214-2509(19)30161-110.1016/j.idcr.2019.e00586e00586ArticleSuccessful treatment of Enterocytozoon bieneusi gastrointestinal infection with nitazoxanide in a immunocompetent patient Saffo Zaid [email protected]⁎Mirza Najab Ascension Genesys Hospital, 1 Genesys Pkwy, Grand Blanc, MI 48439, United States⁎ Corresponding author. [email protected] 7 2019 2019 02 7 2019 18 e0058612 6 2019 28 6 2019 28 6 2019 © 2019 The Authors2019This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Microsporidia are organisms that are known to cause opportunistic infections in immunocompromised individuals. The gastrointestinal tract is the most common affected organ. Enterocytozoon bieneusi is the most common species that infect humans. There are no known established guidelines for the treatment of this particular microsporidium. A 72-year old immunocompetent female presented to our hospital with diarrhea for four weeks. She had failed outpatient oral antimicrobial treatment for suspected traveler’s diarrhea and Clostridium difficile. Initial stool cultures were negative but given her persistent symptomatology, stool PCR was sent to rule out microsporidia and was positive for Enterocytozoon bieneusi. Patient failed treatment with albendazole. She was then subsequently treated with nitazoxanide and achieved successful infection resolution. This case demonstrates the importance of considering atypical infections in patient with persistent symptoms and suggest that nitazoxanide is effective in treating infection caused by Enterocytozoon bieneusi microsporidia.\n\nKeywords\nEnterocytozoon bieneusiMicrosporidiadiarrheanitazoxanide\n==== Body\nIntroduction\nMicrosporidia are unicellular organisms which infect both animal and humans [1]. They were originally known as parasites, but now they are classified as fungi or related to fungi [2]. Infection usually occurs through ingestion or inhalation of spores [1]. Spores have a glycoprotein outer layer that provides environmental protection [1]. Microsporidia can affect multiple organ systems including intestinal, ocular, muscular, pulmonary, and renal. Currently, there are fourteen different organisms reported to infect humans with the two most common being the Enterocytozoon bieneusi and Encephalitozoon intestinalis [3].\n\nIn general, microsporidia are opportunistic infections with most cases reported in HIV positive and immunocompromised individuals [4]. There are a few cases reported in immunocompetent individuals. The most common clinical manifestation is diarrhea which is the result of malabsorption caused by reduced height and surface area of the intestinal villous [5]. Other rare clinical manifestations include pulmonary, ocular, and muscular [1].\n\nThe diagnosis is made by detection of spores in stool. Staining technique by Trichrome has only 63.8 percent sensitivity [6]. Polymerase chain reaction (PCR) stool assays has 100 percent sensitivity and 97.9 percent specificity [6]. Albendazole is generally used for treatment however it is not very effective against Enterocytozoon bieneusi [7]. We report a case of a 72-year old immunocontent female that presented with Enterocytozoon bieneusi gastrointestinal infection who was successfully treated with nitazoxanide.\n\nCase report\nA 72-year old female, with past medical history of hypothyroidism, hypoglycemia and Clostridium difficile colitis, presented with diarrhea ongoing for four weeks. Patient reported the start of her diarrhea after a camping trip to Milwaukee, Wisconsin, USA. She admitted to drinking water from the campsite. Patient reported ten liquid bowel movements per day with associated subjective fevers, chills, nausea, and malaise.\n\nApproximately ten days prior to admission, patient was treated outpatient with oral sulfamethoxazole/trimethoprim and metronidazole by her primary care doctor for presumed Clostridium difficile/traveler’s diarrhea. Clinically, patient’s diarrhea continued to worsen and she presented to the hospital for further evaluation. She was admitted and started on oral vancomycin and metronidazole. Review of outpatient stool studies demonstrated negative C. difficile screen.\n\nLaboratory analysis revealed normal white count (5900 per cubic millimeter); hypokalemia (2.1 mmol); hypophosphatemia (2.1 mg/dL); mildly elevated aspartate aminotransferase (47 U/L); acute kidney injury (creatinine 1.06 mg/dL); normal TSH (0.527 ulU/ml); gram stain demonstrated few fecal leukocytes, few yeast and absence of coliform flora; negative Shiga toxins; negative Clostridium difficile screen (GDH antigen and toxins); negative Giardia lamblia and cryptosporidium; negative rotavirus antigen,; negative serum norovirus 1 and 2 by PCR; negative transglutaminase antibody (IgA and IgG); negative Entamoeba histolytica serology; negative serum HIV 1&2; normal serum immunoglobulins (IgA 346 mg/dL, IgM 80 mg/dL, IgG 1020 mg/dL); normal CRP (<0.15 mg/L), normal calprotectin fecal (<16 ug/g).\n\nThe patient was treated symptomatically with intravenous fluids, antidiarrheal and cholestyramine, however, her diarrhea remained uncontrolled. CT scan of the abdomen and pelvis with intravenous contrast was within normal limit. The gastroenterology service performed colonoscopy to the terminal ileum. Endoscopy revealed non-specific pancolitis with mild terminal ileum erythema and moderate pancolonic diverticulosis. Biopsies of the colon and terminal ileum revealed no morphologic abnormalities.\n\nThe patient had prolonged hospital stay. Repeat stool cultures were negative. Given her persistent diarrhea and camping history, stool PCR was sent to specialty lab to rule out cryptosporidium. Enterocytozoon bieneusi by PCR was detected. Infectious disease team recommended treatment with albendazole 400 mg twice daily. Patient received six doses but the medication was discontinued secondary to concern of its effectiveness. The patient continued to have severe diarrhea and she was eliminating the tablets undigested in her stool. Crushing albendazole tablets failed to make a difference in the clinical response.\n\nAt this time and after literature review, decision was made to start patient on nitazoxanide with reported successful treatment in case reports. She was started on 500 mg by mouth twice daily for fourteen days. Few days after initiating therapy, her stool started to form and became less frequent and she was discharged home. A week later, patient returned to the hospital secondary to decreased oral intake related to nausea which she attributed to nitazoxanide. She was admitted and treated supportively. Repeat PCR testing for microsporidia seven days on therapy was negative. She was started on rifaximin 550 mg by mouth twice daily for possible post-infectious irritable bowel. Patient completed fourteen days of nitazoxanide. PCR testing was repeated 14 days after treatment was completed and remained negative.\n\nDiscussion\nThere are over one thousand species of microsporidia and about fourteen of those can infect humans [8]. Enterocytozoon bieneusi and Encephalitozoon intestinalis are the most common that infect humans [3,8]. Though it more commonly infects immunocompromised individuals (HIV positive, organ and bone marrow recipients), infection has also been described in immunocompetent hosts [9]. In a study involving about two hundred patients in Iran, microsporidia were detected in fourteen percent of immunocompromised patients (n = 20/199) and one and half percent of the immunocompetent patients (n = 1/68) [9]. The most common clinical symptoms were diarrhea and abdominal pain. In another study in Cameron, one-hundred and nighty one patient were studied and the prevalence of microsporidia in immunocompetent patients (n = 126) were surprisingly found to be sixty-seven percent [10]. In this study, patients were asymptomatic suggesting patients developing tolerance to the chronic infection. The mood of transmission is not fully understood and could be waterborne, food-borne, or zoonotic [4]. In a study in China, the rate of microsporidia infection was found to be higher in people that drink unboiled water than those with other sources suggesting water as a potential source of transmission [11].\n\nOur patient was ultimately diagnosed with Enterocytozoon bieneusi when stool was sent for PCR testing for microsporidia as repeat “routine” stool studies were negative. In general, microsporidia are treated with albendazole however this medication is not very effective against the E. Bieneusi [12]. The current recommendation is to use Fumagillin in the treatment of infections due to E. Bieneusi in HIV-infected people [12]. Unfortunately, fumagillin is not available in the United States and its use limited elsewhere secondary to toxicity [13]. Our patient was tried on albendazole without success as she was eliminating the tablets undigested. There has been two cases of E. bieneusi reported in the literature (both in immunocompromised patients) successfully treated using nitazoxanide one-thousand milligram twice daily for sixty days [14,15]. Given the failure to respond to albendazole and after discussion with patient, we decided to trial nitazoxanide 500 mg by mouth twice daily for fourteen days. A few days post therapy, her diarrhea improved, and stool started to form. PCR testing in the stool were negative to detect microsporidia at day seven of treatment. They remained negative at day fourteen post treatment. Two-year follow-up with patient revealed no infection relapse.\n\nIn conclusion, intestinal infection due to the microsporidium E. bieneusi in immunocompetent patients has been reported. A clinical suspicion for atypical infection should be included in the workup specially if symptoms do not self-resolve. Obtaining PCR in the stool is the best method for detection. Management and treatment represent a clinical challenge specially for E. bieneusi species as the drug of choice (fumagillin) is not available in the United States and its use is limited secondary to side effects. The literature review revealed two cases of successful treatment using nitazoxanide. Our case illustrates that importance of considering microsporidial infection even in immunocompetent patients when symptoms fail to self-resolve. Our case suggests that nitazoxanide is effective in eradicating this strain of microsporidium and trials needed to further assess its role.\n\nCRediT authorship contribution statement\nZaid Saffo: Conceptualization, Methodology, Data curation, Formal analysis, Investigation, Writing - original draft. Najab Mirza: Validation, Formal analysis, Writing - review & editing.\n==== Refs\nReferences\n1 Didier E.S. Weiss L.M. Microsporidiosis: current status Curr Opin Infect Dis 19 2006 485 492 16940873 \n2 Corradi N. Keeling P.J. Microsporidia: a journey through radical taxonomical revisions Fungal Biol Rev 23 2009 1 8 \n3 Heyworth M.F. Genetic aspects and environmental sources of microsporidia that infect the human gastrointestinal tract Trans R Soc Trop Med Hyg 111 2017 8 21 \n4 Anane S. Attouchi H. Microsporidiosis: epidemiology, clinical data and therapy Gastroentérol Clin Biol 34 2010 450 464 20702053 \n5 Kotler D.P. Orenstein J.M. Clinical syndromes associated with microsporidiosis Adv Parasitol 40 1998 321 349 9554078 \n6 Saigal K. Khurana S. Sharma A. Sehgal R. Malla N. Comparison of staining techniques and multiplex nested PCR for diagnosis of intestinal microsporidiosis Diagn Microbiol Infect Dis 77 2013 248 249 23993212 \n7 Gross U. Treatment of microsporidiosis including albendazole Parasitol Res 90 2003 14 18 \n8 Didier E.S. Microsporidiosis: an emerging and opportunistic infection in humans and animals Acta Trop 94 2005 61 76 15777637 \n9 Nooshadokht M. Sharifi I. Mohammadi M.A. Intestinal microsporidiosis in Iran: infection in immune-compromised and immunocompetent patients Curr Med Mycol 6 2017 30 36 \n10 Nkinin S.W. Asonganyi T. Didier E.S. Kaneshiro E.S. Microsporidian infection is prevalent in healthy people in Cameroon J Clin Microbiol 45 2007 2841 2846 17609328 \n11 Liu H. Jiang Z. Yuan Z. Infection by and genotype characteristics of Enterocytozoon bieneusi in HIV/AIDS patients from Guangxi Zhuang autonomous region, China BMC Infect Dis 17 2017 684 29029610 \n12 Shane A.L. Mody R.K. Crump J.A. Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea Clin Infect Dis 65 2017 e45 e80 29053792 \n13 Didier E.S. Effects of albendazole, fumagillin, and TNP-470 on microsporidial replication in vitro Antimicrob Agents Chemother 41 1997 1541 1546 9210681 \n14 Bicart-Sée A. Massip P. Linas M.D. Datry A. Successful treatment with nitazoxanide of Enterocytozoon bieneusi microsporidiosis in a patient with AIDS Antimicrob Agents Chemother 44 2000 167 168 10602740 \n15 Pomares C. Santiń M. Miegeville M. A new and highly divergent Enterocytozoon bieneusi genotype isolated from a renal transplant recipient J Clin Microbiol 50 2012 2176 2178 22442321\n\n", "fulltext_license": "CC BY-NC-ND", "issn_linking": "2214-2509", "issue": "18()", "journal": "IDCases", "keywords": "Enterocytozoon bieneusi; Microsporidia; diarrhea; nitazoxanide", "medline_ta": "IDCases", "mesh_terms": null, "nlm_unique_id": "101634540", "other_id": null, "pages": "e00586", "pmc": null, "pmid": "31388488", "pubdate": "2019", "publication_types": "D002363:Case Reports", "references": "29053792;23993212;28339881;17609328;12811545;20702053;9210681;9554078;15777637;29029610;29302628;22442321;16940873;10602740", "title": "Successful treatment of Enterocytozoon bieneusi gastrointestinal infection with nitazoxanide in a immunocompetent patient.", "title_normalized": "successful treatment of enterocytozoon bieneusi gastrointestinal infection with nitazoxanide in a immunocompetent patient" }

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null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CHOLESTYRAMINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "DIARRHOEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CHOLESTYRAMINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "VANCOMYCIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DIARRHOEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VANCOMYCIN" } ], "patientagegroup": null, "patientonsetage": "72", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Treatment failure", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Product residue present", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Wrong technique in product usage process", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SAFFO Z, MIRZA N. SUCCESSFUL TREATMENT OF ENTEROCYTOZOON BIENEUSI GASTROINTESTINAL INFECTION WITH NITAZOXANIDE IN A IMMUNOCOMPETENT PATIENT. IDCASES. 2019?18:E00586", "literaturereference_normalized": "successful treatment of enterocytozoon bieneusi gastrointestinal infection with nitazoxanide in a immunocompetent patient", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20200629", "receivedate": "20200629", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17955274, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" } ]

{ "abstract": "Chronic active Epstein-Barr virus (EBV) infection (CAEBV) is a high-mortality form of EBV infection. However, chronic hypoxemia is rare in these patients. We herein reported a case of severe hypoxemia due to intrapulmonary shunting in CAEBV. A 17-year-old girl presented with fever, dyspnea, cyanosis, and hepatosplenomegaly. Laboratory tests showed mild liver dysfunction and high copy numbers of EBV-DNA in the peripheral blood. A left supratrochlear lymph node biopsy showed infiltration of highly proliferative T lymphocytes with positive EBV encoded small RNA by in situ hybridization. Technetium-99m-labeled macroaggregated albumin and contrast-enhanced echocardiography confirmed the existence of intrapulmonary shunting, which was probably related to hepatopulmonary syndrome. The final diagnosis was CAEBV with intrapulmonary shunting. The patient was treated with cyclosporine A, etoposide, and dexamethasone. Finally, the patient died of respiratory failure. Intrapulmonary shunting is a rare complication of CAEBV. Early recognition and exploring the cause of hypoxemia should be highlighted in patients with CAEBV.", "affiliations": "Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Beijing 100730, China. Electronic address: [email protected].;Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Beijing 100730, China. Electronic address: [email protected].;Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Beijing 100730, China. Electronic address: [email protected].;Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Beijing 100730, China. Electronic address: [email protected].", "authors": "Wang|Zi|Z|;Zhang|Yuying|Y|;Duan|Minghui|M|;Zhang|Yan|Y|", "chemical_list": "D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D004279:DNA, Viral; D003907:Dexamethasone", "country": "Netherlands", "delete": false, "doi": "10.1016/j.jiac.2019.12.012", "fulltext": null, "fulltext_license": null, "issn_linking": "1341-321X", "issue": "26(5)", "journal": "Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy", "keywords": "Chronic active Epstein–Barr virus infection; Hepatopulmonary syndrome; Hypoxemia; Intrapulmonary shunting", "medline_ta": "J Infect Chemother", "mesh_terms": "D000293:Adolescent; D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D001706:Biopsy; D002908:Chronic Disease; D004279:DNA, Viral; D003907:Dexamethasone; D004452:Echocardiography; D020031:Epstein-Barr Virus Infections; D017809:Fatal Outcome; D005260:Female; D020065:Hepatopulmonary Syndrome; D004854:Herpesvirus 4, Human; D006801:Humans; D000860:Hypoxia; D008198:Lymph Nodes; D011652:Pulmonary Circulation; D011659:Pulmonary Gas Exchange", "nlm_unique_id": "9608375", "other_id": null, "pages": "502-505", "pmc": null, "pmid": "31983614", "pubdate": "2020-05", "publication_types": "D002363:Case Reports", "references": null, "title": "Chronic active Epstein-Barr virus infection with intrapulmonary shunting: A case report.", "title_normalized": "chronic active epstein barr virus infection with intrapulmonary shunting a case report" }

[ { "companynumb": "CN-SUN PHARMACEUTICAL INDUSTRIES LTD-2020R1-237017", "fulfillexpeditecriteria": "1", "occurcountry": "CN", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYCLOSPORINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "210913", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC ACTIVE EPSTEIN-BARR VIRUS INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CICLOSPORIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC ACTIVE EPSTEIN-BARR VIRUS INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC ACTIVE EPSTEIN-BARR VIRUS INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." } ], "patientagegroup": null, "patientonsetage": "17", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "WANG Z, ZHANG Y, DUAN M, ZHANG Y.. CHRONIC ACTIVE EPSTEIN-BARR VIRUS INFECTION WITH INTRAPULMONARY SHUNTING: A CASE REPORT.. J INFECT CHEMOTHER. 2020?S1341-321X:30381-2", "literaturereference_normalized": "chronic active epstein barr virus infection with intrapulmonary shunting a case report", "qualification": "3", "reportercountry": "CN" }, "primarysourcecountry": "CN", "receiptdate": "20200218", "receivedate": "20200218", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17425571, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200409" } ]

{ "abstract": "OBJECTIVE\nTo report an unusual case of heparin-induced thrombocytopenia (HIT) with cardiac arrest during hemodialysis (HD).\n\n\nMETHODS\nAn 88-year-old man previously treated with HD under enoxaparin for 3 years presented with dizziness and cyanosis at the beginning of HD on 3 consecutive sessions. Even though the dialyzer membrane was changed, he presented with cardiac arrest, from which he recovered quickly. At the same time, the platelet count fell, and HIT was suspected. No thrombosis was found. Anti-PF4/H, IL8, and NAP2 antibodies were negative, but platelet aggregation tests and serotonin-release assay were positive. After implementing HD with danaparoid, the platelet count returned to normal, and the patient remained asymptomatic.\n\n\nCONCLUSIONS\nGiven the clinical context (low-molecular-weight heparin), complications (cardiac arrest and no thrombosis), and timing (3 years), this was an unusual case of HIT. According to the Naranjo probability scale, the causality of enoxaparin was evaluated as probable. In most reported cases, time to onset was short, clotting occurred in the extracorporeal system, and biological tests, including ELISA (enzyme-linked immunosorbent assay) anti-PF4/heparin, were positive. We found no triggering factor in this case, and given the biological results, a new antigenic target may be involved.\n\n\nCONCLUSIONS\nHIT must be considered when acute systemic reactions occur at the beginning of HD sessions, even after several years of HD and with no change of anticoagulant, including low-molecular-weight heparin. The platelet count should be measured immediately after the reaction. The diagnosis is important because of possible cardiac arrest in this context.", "affiliations": "Pharmacovigilance Regional Centre of Burgundy, Dijon, France [email protected].;University Hospital, Dijon, France.;University Hospital, Nancy, France.;Hyphen Biomed, Neuville sur Oise, France.;Hôpital Tenon, Paris, France.;University Hospital, Dijon, France.", "authors": "Grandvuillemin|Aurélie|A|;Zanetta|Gilbert|G|;Perrin|Julien|J|;Amiral|Jean|J|;Elalamy|Ismail|I|;de Maistre|Emmanuel|E|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1177/1060028014535361", "fulltext": null, "fulltext_license": null, "issn_linking": "1060-0280", "issue": "48(8)", "journal": "The Annals of pharmacotherapy", "keywords": "allergy; hemodialysis; heparin-induced thrombocytopenia", "medline_ta": "Ann Pharmacother", "mesh_terms": null, "nlm_unique_id": "9203131", "other_id": null, "pages": "1086-1089", "pmc": null, "pmid": "24847160", "pubdate": "2014-08", "publication_types": "D016428:Journal Article", "references": null, "title": "Unusual Case of HIT With Cardiac Arrest During Hemodialysis.", "title_normalized": "unusual case of hit with cardiac arrest during hemodialysis" }

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UNUSUAL CASE OF HIT WITH CARDIAC ARREST DURING HEMODIALYSIS.. 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"drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUINDIONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ATORVASTATIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATORVASTATIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ENOXAPARIN SODIUM" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "020164", "drugbatchnumb": "UNK", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INTRAVENOUS INFUSION", "drugdosagetext": "FREQUENCY: 3 TIMES PER WEEK FOR 3 YEARS", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTICOAGULANT THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "4000", "drugstructuredosageunit": "025", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ENOXAPARIN SODIUM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CINACALCET HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CINACALCET HYDROCHLORIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "HEPARIN SODIUM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HEPARIN" } ], "patientagegroup": "6", "patientonsetage": "88", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Heparin-induced thrombocytopenia", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Dizziness", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Dyspnoea", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Cyanosis", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Loss of consciousness", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Cardiac arrest", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "GRANDVUILLEMIN A, ZANETTA G, PERRIN J, AMIRAL J, ELALAMY I, DE MAISTRE E. UNUSUAL CASE OF HIT WITH CARDIAC ARREST DURING HEMODIALYSIS. ANNALS OF PHARMACOTHERAPY 2014;48(8):1086-9. DOI: 10.1177/1060028014535361.", "literaturereference_normalized": "unusual case of hit with cardiac arrest during hemodialysis", "qualification": "3", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20140810", "receivedate": "20140810", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10374061, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150326" } ]

{ "abstract": "BACKGROUND\nThe prognosis for hyper-high-density lipoprotein (HDL) cholesterolemic patients has not been fully elucidated. We conducted a post hoc analysis of MEGA study data to investigate prospectively the incidence of cardiovascular events and cancer in hyper-HDL cholesterolemic patients.\n\n\nMETHODS\nA total of 7832 patients with mild hypercholesterolemia were randomly allocated to either the National Cholesterol Education Program step 1 diet alone (n = 3966) or the diet plus pravastatin (n = 3866) and followed for 5 years. The incidences of coronary heart disease (CHD), CHD plus cerebral infarction (CI), cardiovascular disease (CVD), and cancer were calculated using the Cox proportional hazards model according to the level of HDL cholesterol (HDL-C).\n\n\nRESULTS\nCHD incidence was lower in patients with HDL-C >60-90 mg/dL (-52%, p = 0.0018) and HDL-C > 90 mg/dL (-46%, p = 0.4007) than in patients with HDL-C ≤ 60 mg/dL. The incidences of CHD, CHD plus CI, and CVD were significantly lower in patients with HDL-C >60-90 mg/dL than in those with HDL-C ≤ 60 mg/dL in both diet-alone and diet-plus-pravastatin groups. Cancer incidence was not increased in patients with HDL-C >60-90 mg/dL.\n\n\nCONCLUSIONS\nPatients not receiving statin therapy should aim for a target HDL-C of between 60 and 90 mg/dL to achieve a significant reduction in CHD without the occurrence of adverse events.\n\n\nBACKGROUND\nClinical trials.gov NCT00211705.", "affiliations": "Mitsukoshi Health and Welfare Foundation, 1-24-1, Nishi-shinjuku, Tokyo 160-0023, Japan. [email protected].", "authors": "Nakamura|Haruo|H|;Mizuno|Kyoichi|K|;|||", "chemical_list": "D008076:Cholesterol, HDL", "country": "England", "delete": false, "doi": "10.1186/1476-511X-13-133", "fulltext": "\n==== Front\nLipids Health DisLipids Health DisLipids in Health and Disease1476-511XBioMed Central London 25135178115510.1186/1476-511X-13-133ResearchCardiovascular and cancer events in hyper-high-density lipoprotein cholesterolemic patients: a post hoc analysis of the MEGA study Nakamura Haruo [email protected] Mizuno Kyoichi [email protected] for the MEGA Study Group Mitsukoshi Health and Welfare Foundation, 1-24-1, Nishi-shinjuku, Tokyo, 160-0023 Japan Department of Medicine, Nippon Medical School, 1-5 Sendagi 1-chome, Bunkyo-ku, Tokyo, 113-8603 Japan 18 8 2014 18 8 2014 2014 13 1333 6 2014 11 8 2014 © Nakamura and Mizuno; licensee BioMed Central Ltd. 2014This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background\nThe prognosis for hyper-high-density lipoprotein (HDL) cholesterolemic patients has not been fully elucidated. We conducted a post hoc analysis of MEGA study data to investigate prospectively the incidence of cardiovascular events and cancer in hyper-HDL cholesterolemic patients.\n\nMethods\nA total of 7832 patients with mild hypercholesterolemia were randomly allocated to either the National Cholesterol Education Program step 1 diet alone (n = 3966) or the diet plus pravastatin (n = 3866) and followed for 5 years. The incidences of coronary heart disease (CHD), CHD plus cerebral infarction (CI), cardiovascular disease (CVD), and cancer were calculated using the Cox proportional hazards model according to the level of HDL cholesterol (HDL-C).\n\nResults\nCHD incidence was lower in patients with HDL-C >60–90 mg/dL (-52%, p = 0.0018) and HDL-C > 90 mg/dL (-46%, p = 0.4007) than in patients with HDL-C ≤ 60 mg/dL. The incidences of CHD, CHD plus CI, and CVD were significantly lower in patients with HDL-C >60–90 mg/dL than in those with HDL-C ≤ 60 mg/dL in both diet-alone and diet-plus-pravastatin groups. Cancer incidence was not increased in patients with HDL-C >60–90 mg/dL.\n\nConclusion\nPatients not receiving statin therapy should aim for a target HDL-C of between 60 and 90 mg/dL to achieve a significant reduction in CHD without the occurrence of adverse events.\n\nTrial registration\nClinical trials.gov NCT00211705.\n\nKeywords\nRandomized prospective studyHyper-high-density lipoprotein cholesterolemiaStatinCoronary heart diseaseCancerissue-copyright-statement© The Author(s) 2014\n==== Body\nBackground\nA low level of high-density lipoprotein cholesterol (HDL-C) is one of the risk factors for cardiovascular disease (CVD) [1]. A number of research programs are underway with a view to increasing HDL-C and subsequently reducing atherosclerotic clinical events. However, the extent to which we should increase HDL-C and the prognosis for patients with hyper-HDL cholesterolemia has not been fully elucidated.\n\nIn Japan, 57% of individuals with HDL-C > 100 mg/dL have mutations of the cholesterol ester transfer protein (CETP) gene [2]. Furthermore, 37% of Japanese with HDL-C between 75 and 100 mg/dL have mutations of the CETP gene [3].\n\nSome genetic mechanisms that increase HDL-C do not seem to lower the risk of myocardial infarction, for example a single nucleotide polymorphism (SNP) in the endothelial lipase gene [4]. In fact, lower plasma CETP activity was not associated with a reduced incidence of CVD in Framingham Heart Study participants [5]. Therefore it remains unclear whether a lower incidence of atherosclerotic disease is associated with increasing the HDL-C level or the genes that affect it.\n\nIn the primary prevention MEGA study [6] of the effects of low-dose pravastatin in Japanese patients with mild-to-moderate hypercholesterolemia and without CVD, total cholesterol and low-density lipoprotein cholesterol (LDL-C) were reduced by 12% and 18%, respectively. HDL-C was increased by 5.8% and, importantly, coronary heart disease (CHD) was significantly reduced by 33%.\n\nThe aim of the present study was to investigate prospectively the incidence of cardiovascular events and cancer in patients with hyper-HDL cholesterolemia in a post hoc analysis of the MEGA study and the results are reported in this article.\n\nResults\nPatient characteristics\nThe baseline characteristics of the patients according to HDL-C level are shown in Table 1. Of the 7832 patients, 2936 (37.5%) had HDL-C > 60 mg/dL and 239 (3.1%) had HDL > 90 mg/dL. The burden of atherosclerotic risk factors was less in patients with HDL-C > 60 mg/dL than in those with HDL-C ≤ 60 mg/dL.Table 1 \nBaseline characteristics\n\n\n\tHDL-C (mg/dL)\t\n\t≤ 60\t> 60 to ≤ 90\t> 90\t\n\nN\n\t4896\t2697\t239\t\nAge (years)\t58.1\t58.7\t58.2\t\nMale (%)\t37.8\t21.4a\n\t19.7a\n\t\nBody mass index (kg/m2)\t24.4\t23.0a\n\t21.4a\n\t\nHypertension (%)\t44.8\t37.3a\n\t33.5a\n\t\nDiabetes mellitus (%)\t23.2\t17.0a\n\t15.5a\n\t\nTotal cholesterol (mg/dL)\t242.3\t243.1\t242.5\t\nLDL-C (mg/dL)\t161.3\t150.9a\n\t126.4a\n\t\nHDL-C (mg/dL)\t48.4\t70.3a\n\t97.0a\n\t\nTriglycerides (mg/dL)\t172.2\t110.2a\n\t80.5a\n\t\nNon–HDL-C (mg/dL)\t193.9\t172.8a\n\t143.5a\n\t\nLipoprotein(a) (mg/dL)\t23.9\t26.1a\n\t25.7a\n\t\nBlood pressure (mmHg)\t\t\t\t\n Systolic\t132.9\t131.1a\n\t130.0a\n\t\n Diastolic\t79.1\t77.7a\n\t77.8a\n\t\nFasting blood glucose (mg/dL)\t110\t105a\n\t96a\n\t\nFormer or current smokers (%)\t24.5\t14.2a\n\t13.4a\n\t\n\nHDL-C high-density lipoprotein cholesterol, LDL-C low-density lipoprotein cholesterol.\n\n\na\nP < 0.01 versus ≤ 60 mg/dL group.\n\n\n\nTable 2 shows the incidence of major CVD and death in all patients according to HDL-C level.Table 2 \nIncidence of cardiovascular events according to high-density lipoprotein cholesterol level (5-year follow-up, all patients)\n\n\n\tBaseline high-density lipoprotein cholesterol (mg/dL)\tNo. of cardiovascular events (cardiovascular events/1000 person-years)\tHazard ratio\t95% CI\t\np\n\t\np\nfor trend\t\nCHD\t≤ 60\t117/4896 (5.36)\t1.0000\t\t0.0066a\n\t0.4007\t\n> 60 to ≤ 90\t23/2697 (1.88)\t0.4784\t0.3011–0.7600\t0.0018\t\n> 90\t2/239 (1.87)\t0.5396\t0.1280–2.2752\t0.4007\t\nStroke\t≤ 60\t72/4896 (3.29)\t1.0000\t\t0.8803a\n\t0.9729\t\n> 60 to ≤ 90\t27/2697 (2.21)\t0.8870\t0.5565–1.4140\t0.6144\t\n> 90\t0/239 (0.00)\t0.0000\t0.0000–0.0000\t0.9729\t\nCerebral infarction\t≤ 60\t53/4896 (2.41)\t1.0000\t\t0.6707a\n\t0.9768\t\n> 60 to ≤ 90\t17/2697 (1.39)\t0.7696\t0.4333–1.3670\t0.3717\t\n> 90\t0/239 (0.00)\t0.0000\t0.0000–0.0000\t0.9768\t\nCHD plus cerebral infarction\t≤ 60\t166/4896 (7.65)\t1.0000\t\t0.0048a\n\t0.1425\t\n> 60 to ≤ 90\t40/2697 (3.28)\t0.5733\t0.4002–0.8212\t0.0024\t\n> 90\t2/239 (1.87)\t0.3453\t0.0834–1.4299\t0.1425\t\nCardiovascular disease\t≤ 60\t199/4896 (9.21)\t1.0000\t\t0.0099a\n\t0.1043\t\n> 60 to ≤ 90\t54/2697 (4.44)\t0.6496\t0.4746–0.8891\t0.0071\t\n> 90\t2/239 (1.87)\t0.3094\t0.0751–1.2742\t0.1043\t\nTotal deaths\t≤ 60\t82/4896 (3.66)\t1.0000\t\t0.0927a\n\t0.2513\t\n> 60 to ≤ 90\t26/2697 (2.09)\t0.6335\t0.4003–1.0023\t0.0512\t\n> 90\t1/239 (0.91)\t0.3091\t0.0416–2.2980\t0.2513\t\n\nCHD coronary heart disease, CI confidence interval.\n\n\na\nP versus > 60 mg/dL group adjusted for age, sex, body mass index, hypertension, diabetes mellitus, low-density lipoprotein cholesterol, and smoking habit.\n\n\n\nThe risk of CHD, CHD plus cerebral infarction (CI), and all CVDs was significantly reduced in patients with HDL-C between 60 and 90 mg/dL, adjusted for age, sex, body mass index, hypertension, diabetes mellitus, LDL-C, and smoking habit. In contrast, the risk of stroke or CI was unchanged.\n\nThe incidence of cardiovascular events was also compared in the diet-alone and diet-plus-pravastatin groups separately (Figure 1). The hazard ratios for CHD, CHD plus CI, and CVD in the diet-alone and diet-plus-pravastatin groups were significantly lower in patients with HDL-C 60–90 mg/dL.Figure 1 \nIncidence of cardiovascular events according to high-density lipoprotein cholesterol level; in all patients (\nn \n= 7832), patients in the diet-alone group (\nn \n= 3966), and patients in the diet-plus-pravastatin group (\nn \n= 3866) (5-year follow-up): (a) coronary heart disease; (b) stroke; (c) cerebral infarction; (d), coronary heart disease plus cerebral infarction; (e) cardiovascular disease; and (f) total deaths. *p < 0.05, **p < 0.01.\n\n\n\nConclusive evidence for a reduction in cardiovascular risk was not obtained for patients with HDL-C > 90 mg/dL. Two patients developed CHD during the follow-up period. One of them was a 68-year-old woman with normal blood pressure (106/72 mmHg), normal LDL-C (67.5 mg/dL) and triglycerides (81.7 mg/dL), no smoking habit, and HDL-C of 142.8 mg/dL. She had angina with coronary spasm, confirmed by coronary angiography. The other was a 59-year-old woman with high blood pressure (140–160/70–80 mmHg), normal LDL-C (130.6 mg/dL), and no smoking habit. Her HDL-C was 97.5 mg/dL. She was admitted to hospital and treated for angina confirmed by angiography.\n\nTable 3 shows the incidence of cancer during the average 5.3-year follow-up period according to HDL-C level. There were no significant differences in total incidence of cancer or in incidence of cancer at any site according to HDL-C level. Cancer incidence was further analyzed in the diet-alone group and diet-plus-pravastatin group separately. There were no significant differences in either group according to HDL-C level (Figure 2).Table 3 \nIncidence of cancer according to high-density cholesterol level (during follow-up, all patients)\n\n\nCancer type\tHigh-density lipoprotein cholesterol (mg/dL)\tNo. of patients (%)\t\np\n\t\nAll\t≤ 60\t164/4896 (3.3)\t0.5654\t\n> 60 to ≤ 90\t77/2697 (2.9)\t\t\n> 90 to ≤ 120\t6/225 (2.7)\t\t\n> 120\t0/14 (0.0)\t\t\nDigestive organs\t≤ 60\t80/4896 (1.6)\t0.6998\t\n> 60 to ≤ 90\t38/2697 (1.4)\t\t\n> 90 to ≤ 120\t5/225 (2.2)\t\t\n> 120\t0/14 (0.0)\t\t\nRespiratory organs\t≤ 60\t13/4896 (0.3)\t0.7093\t\n> 60 to ≤ 90\t10/2697 (0.4)\t\t\n> 90 to ≤ 120\t0/225 (0.0)\t\t\n> 120\t0/14 (0.0)\t\t\nBreast\t≤ 60\t14/3045 (0.5)\t0.7375\t\n> 60 to ≤ 90\t12/2119 (0.6)\t\t\n> 90 to ≤ 120\t0/185 (0.0)\t\t\n> 120\t0/7 (0.0)\t\t\nFemale reproductive organs\t≤ 60\t18/3045 (0.6)\t0.3139\t\n> 60 to ≤ 90\t6/2119 (0.3)\t\t\n> 90 to ≤ 120\t0/185 (0.0)\t\t\n> 120\t0/7 (0.0)\t\t\nOther\t≤ 60\t46/4896 (0.9)\t0.2190\t\n> 60 to ≤ 90\t14/2697 (0.5)\t\t\n> 90 to ≤ 120\t1/225 (0.4)\t\t\n> 120\t0/14 (0.0)\t\t\nFigure 2 \nIncidence of cancer according to high-density lipoprotein cholesterol level; in all patients (\nn \n= 7832), patients in the diet-alone group (\nn \n= 3966), and patients in the diet-plus-pravastatin group (\nn \n= 3866) (during follow-up).\n\n\n\n\nDiscussion\nThe results of this prospective study show that the incidences of CHD, CHD plus CI, and CVD are reduced in patients with HDL-C 60–90 mg/dL (i.e. mild hyper-HDL cholesterolemia). This finding is consistent with the results of a previous prospective study on Japanese-American men in Hawaii [7] and an observational prevalence study on the population of Western Japan [8]. Elderly Japanese-American men in Hawaii with heterozygous CETP deficiency and intermediate HDL-C (41–60 mg/dL) have an increased prevalence of CHD [9]. However, the present study shows that patients with increased HDL-C (>60 mg/dL) have a low risk of CHD regardless of the presence of CETP abnormality.\n\nThe incidence of stroke and total death in this study did not differ significantly between patients with HDL-C ≤ 60 mg/dL and those with HDL-C > 60 mg/dL.\n\nA recent study showed that some genetic mechanisms that increase HDL-C do not seem uniformly to lower the risk of myocardial infarction [4]. The authors tested for an SNP in endothelial lipase. In most patients, the presence of this SNP did not increase HDL-C to > 60 mg/dL. Neither the mass nor activity of CETP was available in this study. Plasma CETP activity was measured in 1,978 participants of the Framingham Heart Study, and lower CETP activity was found to be associated with greater risk of CVD [5]. However, there seems to be no association between CETP activity and HDL-C level, which remained to be at < 60 mg/dL.\n\nFurther investigations of the association between three CETP genotypes and the incidence of CHD have shown higher HDL-C to have a weakly inverse association with coronary risk [10]. Also, CETP-deficient families, including heterozygous persons, have increased levels of HDL-C (>60 mg/dL) and no evidence of premature atherosclerosis [11].\n\nA higher HDL-C level (>60 mg/dL) seems to be the threshold for preventing CHD. However, two patients in the diet-alone group developed CHD despite having HDL-C > 90 mg/dL. One of these patients had hypertension and the other had HDL-C > 120 mg/dL, and both developed spastic angina confirmed by coronary angiography, which was relieved by the coadministration of nitrate and statin.\n\nHigh-density lipoprotein plays several roles, including reverse cholesterol transport and endothelial, antioxidative, and immunological functions. CETP inhibitors increase HDL by promoting reverse cholesterol transport [12], with small HDL remaining [13]. Therefore patients with spastic angina may have had endothelial dysfunction. No cases of angina were found in the diet-plus-pravastatin group in the present analysis. Therefore the precise mechanism should be clarified under further experimental conditions.\n\nThese findings suggest that the target threshold HDL-C for patients not receiving statin therapy should be between 60 and 90 mg/dL for them to achieve a significant reduction in CHD without the occurrence of adverse events.\n\nRegarding the incidence of cancer, there were no significant differences in the incidence of cancer at any site according to HDL-C level. Cancer-related mortality was reduced with statin use in previous studies [14, 15].\n\nTo exclude selection bias, we separated the diet-alone group from the diet-plus-pravastatin group. There were no significant differences in the total incidence of cancer or the incidence of cancer at different sites according to HDL-C level.\n\nThe limitations of this study include the relatively short follow-up period and the small number of participants. However, the study included participants from all over Japan (from Hokkaido in the north to Okinawa in the south) approximately in proportion to the population in different areas.\n\nThree percent of patients with mild hypercholesterolemia (total cholesterol ≥ 220 mg/dL) had hyper-HDL-C cholesterolemia (HDL-C > 90 mg/dL) and 38% had mildly increased HDL-C (>60 mg/dL). These figures are considered to be representative for Japanese. Furthermore, figures for the incidence of cardiovascular events and cancer were reliable because of the high follow-up rate (99.4%) [6].\n\nAnother limitation to this study is the lack of information on the markers or mechanisms for the increase in HDL-C. However, this was not a purpose of the original investigation. Also, a previous study has confirmed the reduction in cardiovascular events in patients with high HDL-C irrespective of the presence or absence of CETP deficiency [8].\n\nConclusions\nPatients with high HDL-C (>60 mg/dL) have a low incidence of cardiovascular events, and the incidence of cancer was not increased at any site.\n\nMethods\nPatients\nAll 7832 MEGA study patients were included in this post hoc analysis. The details of the MEGA study have been reported [6]. Briefly, this prospective randomized, open-label, blinded endpoint study was conducted in Japan between 1994 and 2004 in men and postmenopausal women aged 40–70 years with a moderate level of hypercholesterolemia (total cholesterol, 220–270 mg/dL) and without a history of CHD or cerebrovascular disease. A total of 3966 patients were randomly assigned to the diet-alone group and 3866 patients to the diet-plus-pravastatin group. Patients in both groups followed the National Cholesterol Education Program step 1 diet. Physicians and dieticians estimated that > 70% of patients adhered to the diet, with no significant differences between the two groups. The dose of pravastatin was 10–20 mg/day, the approved dose range in Japan.\n\nThe primary endpoint was incidence of CHD defined as a composite of fatal and non-fatal myocardial infarction, angina, cardiac sudden death, and revascularization procedure. Secondary endpoints were stroke, CHD plus CI, all cardiovascular events, and total mortality.\n\nPatients were examined at 1, 3, and 6 months after the start of follow-up, and every 6 months thereafter. All patients provided written informed consent. The trial was conducted according to the ethical principles of the Declaration of Helsinki and the Japanese Ministry of Health, Labour and Welfare ordinance regarding post-marketing surveillance. The MEGA study is registered at clinical trials.gov as trial no. http://NCT00211705.\n\nBiochemical measurements\nBlood samples were taken in the fasting state before randomization and at the start of the study; 1, 3, and 6 months after the start of follow-up; and every 6 months thereafter. Total cholesterol and triglycerides were measured by enzymatic methods. LDL-C was calculated by using Friedewald’s formula [16]. All lipid values were measured centrally in a blinded manner at Special Reference Laboratory (SRL, Hachioji, Tokyo, Japan), which is certified for major lipid measurement by the Centers for Disease Control (Atlanta, GA, USA). Biological markers related to the change in HDL-C were not analyzed.\n\nThe subgroups of this study were classified as follows. In the previous analysis, no significant differences were found in the incidence of CHD between patients with HDL-C < 55 mg/dL and patients with HDL-C ≥ 55 mg/dL, using the Cox proportional hazards model [6]. Therefore the cut-off level for hyper-HDL cholesterolemia was increased to 60 mg/dL, with mild hyper-HDL cholesterolemia and hyper-HDL cholesterolemia arbitrarily considered as HDL-C > 60 and > 90 mg/dL, respectively.\n\nStatistical analyses\nBaseline characteristics were compared across three groups (patients with HDL-C ≤ 60 mg/dL, 60 < HDL-C ≤ 90 mg/dL, and HDL-C > 90 mg/dL) using the chi-squared test for categorical variables or the Wilcoxon rank sum test for continuous variables. The incidence of cardiovascular events and cancer was compared in all patients, patients in the diet-alone group, and patients in the diet-plus-pravastatin group. Hazard ratios and their 95% confidence intervals were calculated by using the Cox proportional hazards model adjusted for baseline risk factors, which were age, sex, body mass index, hypertension, diabetes, LDL-C, and lipoprotein(a). All p values were two-sided and a significance cut-off of 0.05 was used.\n\nAbbreviations\nCETPCholesterol ester transfer protein\n\nCHDCoronary heart disease\n\nCICerebral infarction\n\nCVDCardiovascular disease\n\nHDL-CHigh-density lipoprotein cholesterol\n\nLDL-CLow-density lipoprotein cholesterol\n\nSNPSingle nucleotide polymorphism.\n\nCompeting interests\n\nBoth authors have received consultancy fees from Daiichi Sankyo Co., Ltd. Dr. Nakamura has stock ownership in Daiichi Sankyo and MSD.\n\nThe MEGA Study Publication Committee controlled the writing of this manuscript, and all analyses were conducted independently in the MEGA Study Data Center.\n\nResearch funds were provided by the Japanese Ministry of Health, Labour and Welfare for the first 2 years of the study, thereafter the study was funded by Sankyo Pharmaceutical Co. Ltd. (now Daiichi-Sankyo Co., Ltd.), Tokyo.\n\nAuthors’ contributions\n\nBoth authors contributed to data analysis, data interpretation, and the writing of this report. Both authors read and approved the final manuscript.\n\nWe thank all the patients, physicians, other medical staff, and coworkers who participated in this study.\n==== Refs\nReferences\n1. Di Angelantonio E Sarwar N Perry P Kaptoge S Ray KK Thompson A Wood AM Lewington S Sattar N Packard CJ Collins R Thompson SG Danesh J Emerging Risk Factors Collaboration Major lipids, apolipoproteins, and risk of vascular disease JAMA 2009 302 1993 2000 10.1001/jama.2009.1619 19903920 \n2. Maruyama T Sakai N Ishigami M Hirano K Arai T Okada S Okuda E Ohya A Nakajima N Kadowaki K Fushimi E Yamashita S Matsuzawa Y Prevalence and phenotypic spectrum of cholesteryl ester transfer protein gene mutations in Japanese hyperalphalipoproteinemia Atherosclerosis 2003 166 177 185 10.1016/S0021-9150(02)00327-1 12482565 \n3. Nagano M Yamashita S Hirano K Ito M Maruyama T Ishihara M Sagehashi Y Oka T Kujiraoka T Hattori H Nakajima N Egashira T Kondo M Sakai N Matsuzawa Y Two novel missense mutations in the CEPT gene in Japanese hyperalphalipoproteinemic subjects: high-throughput assay by Invader assay J Lipid Res 2002 43 1011 1018 10.1194/jlr.M200024-JLR200 12091484 \n4. Voight BF Peloso GM Orho-Melander M Frikke-Schmidt R Barbalic M Jensen MK Hindy G Hólm H Ding EL Johnson T Schunkert H Samani NJ Clarke R Hopewell JC Thompson JF Li M Thorleifsson G Newton-Cheh C Musunuru K Pirruccello JP Saleheen D Chen L Stewart A Schillert A Thorsteinsdottir U Thorgeirsson G Anand S Engert JC Morgan T Spertus J Plasma HDL cholesterol and risk of myocardial infarction: a Mendelian randomisation study Lancet 2012 380 572 580 10.1016/S0140-6736(12)60312-2 22607825 \n5. Vasan RS Pencina MJ Robins SJ Zachariah JP Kaur G D’Agostino RB Ordovas JM Association of circulating cholesteryl ester transfer protein activity with incidence of cardiovascular disease in the community Circulation 2009 120 2414 2420 10.1161/CIRCULATIONAHA.109.872705 19948972 \n6. Nakamura H Arakawa K Itakura H Kitabatake A Goto Y Toyota T Nakaya N Nishimoto S Muranaka M Yamamoto A Mizuno K Ohashi Y MEGA Study Group Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial Lancet 2006 368 1155 1163 10.1016/S0140-6736(06)69472-5 17011942 \n7. Curb JD Abbott RD Rodriguez BL Masaki K Chen R Sharp DS Tall AR A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly J Lipid Res 2004 45 948 953 10.1194/jlr.M300520-JLR200 14967821 \n8. Moriyama Y Okamura T Inazu A Doi M Iso H Mouri Y Ishikawa Y Suzuki H Iida M Koizumi J Mabuchi H Komachi Y A low prevalence of coronary heart disease among subjects with increased high density lipoprotein cholesterol levels, including those with plasma cholesteryl ester transfer protein deficiency Prev Med 1998 27 659 667 10.1006/pmed.1998.0340 9808796 \n9. Zhong S Sharp DS Grove JS Bruce C Yano K Curb JD Tall AR Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels J Clin Invest 1996 97 2917 2923 10.1172/JCI118751 8675707 \n10. Thompson A Di Angelatonio E Sarwar N Erqou S Saleheen D Dullaart RP Keavney B Ye Z Danesh J Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk JAMA 2008 299 2777 2788 10.1001/jama.299.23.2777 18560005 \n11. Inazu A Brown ML Hesler CB Agellon LB Koizumi J Takata K Maruhama Y Mabuchi H Tall AR Increased high-density lipoprotein levels caused by a common cholesterol-ester transfer protein gene mutation N Engl J Med 1990 323 1234 1238 10.1056/NEJM199011013231803 2215607 \n12. Castro-Perez J Briand F Gagen K Wang SP Chen Y McLaren DG Shah V Vreeken RJ Hankemeier T Sulpice T Roddy TP Hubbard BK Johns DG Anacetrapib promotes reverse cholesterol transport and bulk cholesterol excretion in Syrian golden hamsters J Lipid Res 2011 52 1965 1973 10.1194/jlr.M016410 21841206 \n13. Krauss RM Wojnooski K Orr J Geaney JC Pinto CA Liu Y Wagner JA Luk JM Johnson-Levonas AO Anderson MS Dansky HM Changes in lipoprotein subfraction concentration and composition in healthy individuals treated with the CETP inhibitor anacetrapib J Lipid Res 2012 53 540 547 10.1194/jlr.M018010 22180633 \n14. Nielsen SF Nordestgaard BG Bojesen SE Statin use and reduced cancer-related mortality N Engl J Med 2012 367 1792 1802 10.1056/NEJMoa1201735 23134381 \n15. Baigent C Blackwell L Emberson J Holland LE Reith C Bhala N Peto R Barnes EH Keech A Simes J Collins R Cholesterol Treatment Trialists’ (CTT) Collaboration Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials Lancet 2010 376 1670 1681 10.1016/S0140-6736(10)61350-5 21067804 \n16. Friedewald WT Levy RI Fredrickson DS Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge Clin Chem 1972 18 499 502 4337382\n\n", "fulltext_license": "CC BY", "issn_linking": "1476-511X", "issue": "13()", "journal": "Lipids in health and disease", "keywords": null, "medline_ta": "Lipids Health Dis", "mesh_terms": "D002544:Cerebral Infarction; D008076:Cholesterol, HDL; D003327:Coronary Disease; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic", "nlm_unique_id": "101147696", "other_id": null, "pages": "133", "pmc": null, "pmid": "25135178", "pubdate": "2014-08-18", "publication_types": "D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't", "references": "12091484;19903920;21841206;19948972;22180633;9808796;2215607;18560005;22607825;17011942;12482565;21067804;4337382;14967821;8675707;23134381", "title": "Cardiovascular and cancer events in hyper-high-density lipoprotein cholesterolemic patients: a post hoc analysis of the MEGA study.", "title_normalized": "cardiovascular and cancer events in hyper high density lipoprotein cholesterolemic patients a post hoc analysis of the mega study" }

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CARDIOVASCULAR AND CANCER EVENTS IN HYPER-HIGH-DENSITY LIPOPROTEIN CHOLESTEROLEMIC PATIENTS: A POST HOC ANALYSIS OF THE MEGA STUDY", "literaturereference_normalized": "cardiovascular and cancer events in hyper high density lipoprotein cholesterolemic patients a post hoc analysis of the mega study", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20140904", "receivedate": "20140904", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10428816, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150326" }, { "companynumb": "JP-CIPLA LTD.-2014JP01223", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PRAVASTATIN\\PRAVASTATIN SODIUM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HYPERCHOLESTEROLAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PRAVASTATIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PRAVASTATIN\\PRAVASTATIN SODIUM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HYPER HDL CHOLESTEROLAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PRAVASTATIN" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neoplasm malignant", "reactionmeddraversionpt": "17.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAKAMURA H, MIZUNO K. 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{ "abstract": "Exposure to synthetic drugs such as amphetamines may lead to significant consequences on the cardiovascular system. The prognosis of young adults with amphetamine-induced cardiomyopathy remains poor. We present 2 young patients (aged <40 years) who developed severe dilated cardiomyopathy after chronic amphetamine use. Thorough psychological evaluations demonstrated favorable features with patients being reliable and committed to their health problems. A left ventricular assist device (HeartMate II; Abbott, Chicago, IL) was implanted in the patients shortly after admission to optimize hemodynamic support and evaluate the potential for recovery. Within less than 1 year, significant improvement was achieved and successful explantation of left ventricular assist device was performed in both patients.", "affiliations": "Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Quebec, Canada.;Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Quebec, Canada.;Department of Cardiac Surgery, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Quebec, Canada.;Department of Cardiac Surgery, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Quebec, Canada.;Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Quebec, Canada.;Research Center, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Quebec, Canada.;Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Quebec, Canada. Electronic address: [email protected].", "authors": "Soucy-Giguère|Marie-Camille|MC|;Cinq-Mars|Alexandre|A|;Charbonneau|Éric|É|;Voisine|Pierre|P|;Beaudoin|Jonathan|J|;Dubois|Michelle|M|;Sénéchal|Mario|M|", "chemical_list": "D000697:Central Nervous System Stimulants; D000661:Amphetamine", "country": "England", "delete": false, "doi": "10.1016/j.cjca.2019.09.024", "fulltext": null, "fulltext_license": null, "issn_linking": "0828-282X", "issue": "36(2)", "journal": "The Canadian journal of cardiology", "keywords": null, "medline_ta": "Can J Cardiol", "mesh_terms": "D000328:Adult; D000661:Amphetamine; D002311:Cardiomyopathy, Dilated; D000697:Central Nervous System Stimulants; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D012720:Severity of Illness Index; D019966:Substance-Related Disorders; D055815:Young Adult", "nlm_unique_id": "8510280", "other_id": null, "pages": "317.e5-317.e7", "pmc": null, "pmid": "31932114", "pubdate": "2020-02", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Usefulness of Left Ventricular Assist Device in the Recovery of Severe Amphetamine-Associated Dilated Cardiomyopathy.", "title_normalized": "usefulness of left ventricular assist device in the recovery of severe amphetamine associated dilated cardiomyopathy" }

[ { "companynumb": "CA-NEOS THERAPEUTICS, LP-2020NEO00006", "fulfillexpeditecriteria": "1", "occurcountry": "CA", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "AMPHETAMINE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "204326", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5-6 PILLS, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMPHETAMINE" } ], "patientagegroup": null, "patientonsetage": "35", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cardiomyopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Cardiac failure", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hepatic failure", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SOUCY-GIGUERE MC, CINQ-MARS A, CHARBONNEAU E, ET AL.. USEFULNESS OF LEFT VENTRICULAR ASSIST DEVICE IN THE RECOVERY OF SEVERE AMPHETAMINE-ASSOCIATED DILATED CARDIOMYOPATHY. CANADIAN JOURNAL OF CARDIOLOGY. 2020", "literaturereference_normalized": "usefulness of left ventricular assist device in the recovery of severe amphetamine associated dilated cardiomyopathy", "qualification": "1", "reportercountry": "CA" }, "primarysourcecountry": "CA", "receiptdate": "20200129", "receivedate": "20200129", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17343377, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200409" }, { "companynumb": "CA-EPIC PHARMA LLC-2020EPC00033", "fulfillexpeditecriteria": "1", "occurcountry": "CA", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "AMPHETAMINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "040444", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2-4 PILLS, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMPHETAMINE" } ], "patientagegroup": null, "patientonsetage": "22", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cardiac failure", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Cardiomyopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "SOUCY-GIGUERE MC, CINQ-MARS A, CHARBONNEAU E, ET AL.. USEFULNESS OF LEFT VENTRICULAR ASSIST DEVICE IN THE RECOVERY OF SEVERE AMPHETAMINE-ASSOCIATED DILATED CARDIOMYOPATHY. CANADIAN JOURNAL OF CARDIOLOGY. 2020", "literaturereference_normalized": "usefulness of left ventricular assist device in the recovery of severe amphetamine associated dilated cardiomyopathy", "qualification": "1", "reportercountry": "CA" }, "primarysourcecountry": "CA", "receiptdate": "20200203", "receivedate": "20200203", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17362528, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200409" }, { "companynumb": "CA-EPIC PHARMA LLC-2020EPC00032", "fulfillexpeditecriteria": "1", "occurcountry": "CA", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "AMPHETAMINE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "040444", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5-6 PILLS, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMPHETAMINE" } ], "patientagegroup": null, "patientonsetage": "35", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cardiac failure", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hepatic failure", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cardiomyopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "SOUCY-GIGUERE MC, CINQ-MARS A, CHARBONNEAU E, ET AL.. USEFULNESS OF LEFT VENTRICULAR ASSIST DEVICE IN THE RECOVERY OF SEVERE AMPHETAMINE-ASSOCIATED DILATED CARDIOMYOPATHY. CANADIAN JOURNAL OF CARDIOLOGY. 2020", "literaturereference_normalized": "usefulness of left ventricular assist device in the recovery of severe amphetamine associated dilated cardiomyopathy", "qualification": "1", "reportercountry": "CA" }, "primarysourcecountry": "CA", "receiptdate": "20200203", "receivedate": "20200203", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17362526, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200409" }, { "companynumb": "CA-NEOS THERAPEUTICS, LP-2020NEO00007", "fulfillexpeditecriteria": "1", "occurcountry": "CA", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "AMPHETAMINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "204326", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2-4 PILLS, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMPHETAMINE" } ], "patientagegroup": null, "patientonsetage": "22", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cardiac failure", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Cardiomyopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "SOUCY-GIGUERE MC, CINQ-MARS A, CHARBONNEAU E, ET AL.. USEFULNESS OF LEFT VENTRICULAR ASSIST DEVICE IN THE RECOVERY OF SEVERE AMPHETAMINE-ASSOCIATED DILATED CARDIOMYOPATHY. CANADIAN JOURNAL OF CARDIOLOGY. 2020", "literaturereference_normalized": "usefulness of left ventricular assist device in the recovery of severe amphetamine associated dilated cardiomyopathy", "qualification": "1", "reportercountry": "CA" }, "primarysourcecountry": "CA", "receiptdate": "20200129", "receivedate": "20200129", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17343379, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200409" } ]

{ "abstract": "We describe a 35-year-old woman who ingested 16 g (approximately 20 mg/kg) of diphenhydramine with resultant hypotension requiring pressor support and marked QRS prolongation. After treatment with sodium bicarbonate failed to improve cardiac status, the patient underwent emergency charcoal hemoperfusion and hemodialysis with rapid improvement in the ECG findings within the first 40 minutes of treatment and with no further need for pressors. Major texts in toxicology state that diphenhydramine is unsuitable for hemodialysis or charcoal hemoperfusion. However, our case suggests that charcoal hemoperfusion may be appropriate therapy in cases of massive diphenhydramine overdoses when standard supportive measures fail. This case represents the largest documented diphenhydramine overdose that resulted in survival.", "affiliations": "Oregon Poison Center, Oregon Health Sciences University, Portland 97201-3098, USA.", "authors": "Mullins|M E|ME|;Pinnick|R V|RV|;Terhes|J M|JM|", "chemical_list": "D000931:Antidotes; D006993:Hypnotics and Sedatives; D002606:Charcoal; D004155:Diphenhydramine", "country": "United States", "delete": false, "doi": "10.1016/s0196-0644(99)70425-7", "fulltext": null, "fulltext_license": null, "issn_linking": "0196-0644", "issue": "33(1)", "journal": "Annals of emergency medicine", "keywords": null, "medline_ta": "Ann Emerg Med", "mesh_terms": "D000328:Adult; D000931:Antidotes; D002606:Charcoal; D004155:Diphenhydramine; D004562:Electrocardiography; D004638:Emergency Treatment; D005260:Female; D006464:Hemoperfusion; D006801:Humans; D006993:Hypnotics and Sedatives; D006435:Renal Dialysis; D013406:Suicide, Attempted", "nlm_unique_id": "8002646", "other_id": null, "pages": "104-7", "pmc": null, "pmid": "9867896", "pubdate": "1999-01", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Life-threatening diphenhydramine overdose treated with charcoal hemoperfusion and hemodialysis.", "title_normalized": "life threatening diphenhydramine overdose treated with charcoal hemoperfusion and hemodialysis" }

[ { "companynumb": "US-SA-2020SA361657", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "DIPHENHYDRAMINE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "16 G (APPROXIMATELY 20 MG/KG) (10 BOXES 32 TABLETS EACH)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "16", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIPHENHYDRAMINE." } ], "patientagegroup": "5", "patientonsetage": "35", "patientonsetageunit": "801", "patientsex": "2", "patientweight": "90", "reaction": [ { "reactionmeddrapt": "Lethargy", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Electrocardiogram QT prolonged", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Electrocardiogram QRS complex prolonged", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Seizure", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Intentional overdose", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Toxicity to various agents", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "MULLINS ME, PINNICK RV, TERHES JM.. LIFE?THREATENING DIPHENHYDRAMINE OVERDOSE TREATED WITH CHARCOAL HEMOPERFUSION AND HEMODIALYSIS.. ANNALS OF EMERGENCY MEDICINE. 1999?33(1):104?7", "literaturereference_normalized": "life threatening diphenhydramine overdose treated with charcoal hemoperfusion and hemodialysis", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210901", "receivedate": "20201222", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18647899, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20211014" }, { "companynumb": "US-PFIZER INC-202200813043", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DIPHENHYDRAMINE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "16000 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "16000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "UNISOM SLEEPMELTS" } ], "patientagegroup": null, "patientonsetage": "35", "patientonsetageunit": "801", "patientsex": "2", "patientweight": "90", "reaction": [ { "reactionmeddrapt": "Overdose", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cardiovascular disorder", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Seizure", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Mullins, M.. Life-threatening diphenhydramine overdose treated with charcoal hemoperfusion and hemodialysis. Ann Emerg Med. 1999;33(1):104-107", "literaturereference_normalized": "life threatening diphenhydramine overdose treated with charcoal hemoperfusion and hemodialysis", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20220617", "receivedate": "20220615", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20963652, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 2, "transmissiondate": "20220720" } ]

{ "abstract": "OBJECTIVE\nMultiple myeloma is a malignancy of plasma cells and is characterized by increased marrow angiogenesis. Thalidomide, an agent with antiangiogenic properties, is effective in relapsed myeloma. We report the results of a study combining thalidomide and dexamethasone as initial therapy for myeloma.\n\n\nMETHODS\nFifty patients with newly diagnosed myeloma were studied. Thalidomide was given at a dose of 200 mg/d orally. Dexamethasone was given at a dose of 40 mg/d orally on days 1 to 4, 9 to 12, and 17 to 20 (odd cycles) and 40 mg/d on days 1 to 4 (even cycles), repeated monthly.\n\n\nRESULTS\nOf all 50 patients, a confirmed response was seen in 32 patients yielding a response rate of 64% (95% confidence interval, 49% to 77%). Thirty-one patients (62%) proceeded to stem-cell collection after four cycles of therapy including 26 who underwent stem-cell transplantation and five who chose stem-cell cryopreservation. Major grade 3 or 4 toxicities were observed in 16 patients (32%), and the most frequent were deep vein thrombosis (six patients), constipation (four patients), rash (three patients), and dyspnea (two patients). Three deaths occurred during active therapy because of a pancreatitis, pulmonary embolism, and infection.\n\n\nCONCLUSIONS\nWe conclude that the combination of thalidomide plus dexamethasone is a feasible and active regimen in the treatment of multiple myeloma. It merits further study as an oral alternative to infusional chemotherapy with vincristine, doxorubicin, and dexamethasone and other intravenous regimens currently used as pretransplantation induction therapy for myeloma.", "affiliations": "Division of Hematology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. [email protected]", "authors": "Rajkumar|S Vincent|SV|;Hayman|Suzanne|S|;Gertz|Morie A|MA|;Dispenzieri|Angela|A|;Lacy|Martha Q|MQ|;Greipp|Philip R|PR|;Geyer|Susan|S|;Iturria|Nancy|N|;Fonseca|Rafael|R|;Lust|John A|JA|;Kyle|Robert A|RA|;Witzig|Thomas E|TE|", "chemical_list": "D013792:Thalidomide; D003907:Dexamethasone", "country": "United States", "delete": false, "doi": "10.1200/JCO.2002.02.116", "fulltext": null, "fulltext_license": null, "issn_linking": "0732-183X", "issue": "20(21)", "journal": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology", "keywords": null, "medline_ta": "J Clin Oncol", "mesh_terms": "D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D003248:Constipation; D003907:Dexamethasone; D004417:Dyspnea; D005076:Exanthema; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma; D013792:Thalidomide; D020246:Venous Thrombosis", "nlm_unique_id": "8309333", "other_id": null, "pages": "4319-23", "pmc": null, "pmid": "12409330", "pubdate": "2002-11-01", "publication_types": "D016430:Clinical Trial; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't; D013487:Research Support, U.S. Gov't, P.H.S.", "references": null, "title": "Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma.", "title_normalized": "combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma" }

[ { "companynumb": "US-CELGENEUS-USA-2016075162", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "THALIDOMIDE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "020785", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CAPSULES", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THALOMID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "THALIDOMIDE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "020785", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CAPSULES", "drugdosagetext": "200MG UP TO 800MG", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THALOMID" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pancreatitis acute", "reactionmeddraversionpt": "19.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "SV R. COMBINATION THERAPY WITH THALIDOMIDE PLUS DEXAMETHASONE FOR NEWLY DIAGNOSED MYELOMA.. J. CLIN. ONCOL.. 2002 JUL 19;V 20 NO. 2:4319-4323.", "literaturereference_normalized": "combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20160801", "receivedate": "20160801", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12611216, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20161109" }, { "companynumb": "US-CELGENEUS-USA-2016075165", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "THALIDOMIDE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "020785", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CAPSULES", "drugdosagetext": "200 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THALOMID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Syncope", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Blood alkaline phosphatase increased", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Sedation", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Deep vein thrombosis", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Constipation", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fatigue", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Neuropathy peripheral", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Tremor", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Arrhythmia", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Skin exfoliation", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Inner ear inflammation", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Depression", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Rash", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Oedema", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Epidermal necrosis", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "RAJKUMAR S. COMBINATION THERAPY WITH THALIDOMIDE PLUS DEXAMETHASONE FOR NEWLY DIAGNOSED MYELOMA. 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COMBINATION THERAPY WITH THALIDOMIDE PLUS DEXAMETHASONE FOR NEWLY DIAGNOSED MYELOMA.. JOURNAL OF CLINICAL ONCOLOGY. 2002 NOV 01;21:4319-4323.", "literaturereference_normalized": "combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20160729", "receivedate": "20160729", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12608550, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20161109" }, { "companynumb": "US-CELGENEUS-USA-2016075159", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "THALIDOMIDE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "020785", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CAPSULES", "drugdosagetext": "200 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THALOMID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Infection", "reactionmeddraversionpt": "19.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "RAJKUMAR S. 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{ "abstract": "Hepatitis B virus (HBV) reactivation is a common complication in chronic or resolved HBV infection patients undergoing immunosuppressive chemotherapy. Furthermore, few articles have been published regarding the risk of HBV reactivation in lymphoma patients receiving chimeric antigen receptor (CAR) T-cell therapy and anti-HBV prophylaxis. Few guidelines or clear optimal strategies are available for managing these patients. Here, we present two cases of patients who underwent CAR-T-cell cocktail therapy with anti-CD19 and anti-CD22 CAR (CAR19/22) T cell for lymphoma. Patients had previous history of HBV infection, and blood tests on initial admission indicated positive results for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and antibody to hepatitis B e antigen (anti-HBe), while serum HBV DNA level was undetectable. Therefore, two patients received entecavir as antiviral prophylactic therapy during their entire treatment. They were diagnosed with HBV reactivation based on positive serum HBV DNA test results, 2 weeks after CAR-T-cell infusion. Liver function assay indicated elevated levels of alanine transaminase (ALT) and aspartate transaminase (AST), combined with increased levels of total bilirubin (TBIL) and direct bilirubin (DBIL). Subsequently, they received anti-HBV treatment with entecavir and tenofovir. As a result, their serum HBV DNA copies and AST/ALT levels returned to normal after 1 week. These cases show that there is a risk of HBV reactivation in lymphoma patients with CAR-T-cell therapy despite entecavir preventive therapy, and combination treatment of entecavir and tenofovir may be an effective treatment option for such patients with HBV reactivation.", "affiliations": "Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.;Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.;Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.;Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.;Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.;Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.", "authors": "Ma|Yaxian|Y|;Yang|Li|L|;Bao|Yuhan|Y|;Yang|Yang|Y|;Chen|Liting|L|;Zheng|Miao|M|", "chemical_list": null, "country": "Switzerland", "delete": false, "doi": "10.3389/fimmu.2021.751754", "fulltext": "\n==== Front\nFront Immunol\nFront Immunol\nFront. Immunol.\nFrontiers in Immunology\n1664-3224\nFrontiers Media S.A.\n\n10.3389/fimmu.2021.751754\nImmunology\nCase Report\nCase Report: Post-CAR-T Infusion HBV Reactivation in Two Lymphoma Patients Despite Entecavir Preventive Therapy\nMa Yaxian †\n\nYang Li †\n\nBao Yuhan\nYang Yang\nChen Liting\n\nZheng Miao *\nDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China\nEdited by: Ye Li, University of Texas MD Anderson Cancer Center, United States\n\nReviewed by: Yutaka Kawano, Health Sciences University of Hokkaido, Japan; Atsushi Satake, Kansai Medical University, Japan\n\n*Correspondence: Miao Zheng, [email protected]\n†These authors have contributed equally to this work and share first authorship\n\nThis article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology\n\n08 10 2021\n2021\n12 75175402 8 2021\n21 9 2021\nCopyright © 2021 Ma, Yang, Bao, Yang, Chen and Zheng\n2021\nMa, Yang, Bao, Yang, Chen and Zheng\nhttps://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.\nHepatitis B virus (HBV) reactivation is a common complication in chronic or resolved HBV infection patients undergoing immunosuppressive chemotherapy. Furthermore, few articles have been published regarding the risk of HBV reactivation in lymphoma patients receiving chimeric antigen receptor (CAR) T-cell therapy and anti-HBV prophylaxis. Few guidelines or clear optimal strategies are available for managing these patients. Here, we present two cases of patients who underwent CAR-T-cell cocktail therapy with anti-CD19 and anti-CD22 CAR (CAR19/22) T cell for lymphoma. Patients had previous history of HBV infection, and blood tests on initial admission indicated positive results for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and antibody to hepatitis B e antigen (anti-HBe), while serum HBV DNA level was undetectable. Therefore, two patients received entecavir as antiviral prophylactic therapy during their entire treatment. They were diagnosed with HBV reactivation based on positive serum HBV DNA test results, 2 weeks after CAR-T-cell infusion. Liver function assay indicated elevated levels of alanine transaminase (ALT) and aspartate transaminase (AST), combined with increased levels of total bilirubin (TBIL) and direct bilirubin (DBIL). Subsequently, they received anti-HBV treatment with entecavir and tenofovir. As a result, their serum HBV DNA copies and AST/ALT levels returned to normal after 1 week. These cases show that there is a risk of HBV reactivation in lymphoma patients with CAR-T-cell therapy despite entecavir preventive therapy, and combination treatment of entecavir and tenofovir may be an effective treatment option for such patients with HBV reactivation.\n\nhepatitis B virus\nreactivation\nCAR T\nlymphoma\nantiviral therapy\n==== Body\npmcIntroduction\n\nReactivation of hepatitis B virus (HBV), a phenomenon characterized by increased HBV DNA serum values of about 1 log, by the HBV DNA turning positive if previously undetectable in serum or by reverse seroconversion from hepatitis B surface antigen (HBsAg) negative to HBsAg positive, is a well-recognized complication in patients with some cytotoxic chemotherapies (e.g., anthracyclines) or immunochemotherapy for hematologic malignancies (1–4). Guidelines suggest that anti-HBV prophylaxis should be initiated as soon as possible before or, at the latest, simultaneously with starting chemotherapy (4, 5). Once started, antiviral prophylaxis should continue during chemotherapy and for at least 12 months after completion of chemotherapy (4, 5). In patients with lymphoma and resolved HBV infection, entecavir and tenofovir should be considered the drugs for HBV prophylaxis (5).\n\nAmong immunotherapies, chimeric antigen receptor-engineered (CAR) T-cell therapy is emerging as a novel and rapidly evolving treatment modality for lymphoma patients (6–8). However, current clinical trials of CAR T-cell therapy have generally excluded lymphoma patients with HBV infection. Thus, the safety and the efficacy of CAR T-cell therapy in patients with lymphoma and HBV infection remain largely unexplored, and reports of HBV reactivation and corresponding clinical solutions are lacking for CAR-T patients, with only a few cases described (2, 9–11). To date, few guidelines or clear optimal strategies are available for the management of HBV reactivation in lymphoma patients undergoing CAR T-cell therapy.\n\nHere, we describe two cases of two patients with lymphoma who experienced HBV reactivation after entecavir preventive therapy and CAR T-cell cocktail therapy with anti-CD19 and anti-CD22 CAR T-cell infusion; HBV hepatitis successfully improved with the combination treatment of entecavir and tenofovir.\n\nCases Report\n\nThe key clinical courses of the two patients are summarized in Figure 1 .\n\nFigure 1 Summaries of the two cases. The first day of chimeric antigen receptor (CAR) T-cell infusion is established as day 0. (A) Key clinical course of case 1. (B) Key clinical course of case 2.\n\nCase 1\n\nA 55-year-old man was diagnosed with stomach lymphoblastic lymphoma at the IB stage (Ann Arbor staging system) 2 years ago. He received six cycles of standard-dose R-CHOP (rituximab, cyclophosphamide, vincristine, adriamycin, and prednisone). Positron emission tomography–computed tomography (PET-CT) scan showed multiple mass with elevated metabolic activity in the cervical and peritoneal cavities, right clavicula fossa, mediastinal region. Bilateral renal tumor invasion was also detected (Deauville score 5). Progressive disease was considered and rebiopsy of the renal mass was performed. Pathology indicated relapse of the primary disease. The patient then received three cycles of R-IMED/DHAP (rituximab, ifosfamide, methotrexate, etoposide,dexamethasone, cytarabine, and cisplatin) therapy. Posttreatment PET-CT reanalysis suggested partial remission as the metabolic activity of the stomach was significantly repressed (Deauville score 1).\n\nThe patient had previous history of HBV infection, and blood test on initial admission indicated positive results for HBsAg, antibody to hepatitis B core antigen (anti-HBc), and antibody to hepatitis B e antigen (anti-HBe), while the serum HBV DNA level was undetectable. His results for human immunodeficiency virus (HIV) and anti-hepatitis C virus (HCV) antibody detection were negative. As for his liver function, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were within the normal range, and no abnormal ultrasound findings were identified suggesting chronic hepatitis. On admission to our clinical center, the patient was required to receive anti-HBV prophylactic treatment with entecavir (0.5 mg/day) during his entire treatment.\n\nLymphoma of the patient progressed after multiline chemotherapy. In order to control his present conditions, we selected CAR-T cocktail therapy with anti-CD19 and anti-CD22 CAR T-cell infusion. The patient was enrolled in our trial and agreed to receive CAR-T treatment. Informed consent was provided by the patient. Peripheral blood mononuclear cells (PBMCs) were harvested and CAR T cells were constructed and cultured for 14 days by Bio-Rad Corporation (Hercules, CA, USA). Then, standardized FC (fludarabine and cyclophosphamide) regimen was conducted for lymphodepletion (25 mg/m2 fludarabine and 20 mg/kg cyclophosphamide on days −4 to −2). Sequential infusion strategy was planned as follows: anti-CD19 CAR-T infusion 2 × 106/kg on days 1 and 3 and anti-CD22 CAR-T infusion 2 × 106/kg on days 0 and 2. The patient gradually developed cytokine release syndrome (grade 1), with peak ferritin level of 952.1 μg/L and interleukin-6 (IL-6) level of 118.50 pg/ml ( Figures 2A–C ). Lentiviral copy surveillance conducted with quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) suggested that CAR T-cell expansion reached a maximum point +9 days post-infusion (copy numbers for CD19 27297 and CD22 6212) ( Figure 2D ).\n\nFigure 2 Clinical evolutions after infusion of anti-CD19 and anti-CD22 CAR T-cell cocktail in patients. (A) Levels of serum ferritin after CAR T-cell infusion. (B) Levels of IL-6 after CAR T-cell infusion. (C) Levels of serum CRP after CAR T-cell infusion. (D) Lentiviral copy numbers after CAR T-cell infusion. (E) Dynamic changes in ALT, AST, TBIL, and HBV DNA levels after CAR T-cell infusion. CAR, chimeric antigen receptor; IL-6, interleukin-6; CRP, C-reactive protein; ALT, alanine transaminase; AST, aspartate transaminase; TBIL, total bilirubin.\n\nAlthough this patient continuously received entecavir (0.5 mg, q.d.) antiviral treatment, he suffered from vomiting and stomach discomfort +11 days post-CAR-T infusion. The liver function assay indicated elevated ALT and AST levels, combined with increased levels of total bilirubin (TBIL) and direct bilirubin (DBIL) ( Figure 2E ). After exclusion of other potential causes of acute liver injury, we examined his HBV DNA copy level, and the results indicated that HBV reactivation was highly possible (+16 days HBV DNA, 2.58 × 102) ( Figure 2E ). Therefore, we quickly implemented combinatory rescuing anti-HBV treatment with entecavir and tenofovir. Reexamination suggested that the patient’s HBV DNA and abnormal liver function recovered on +24 days.\n\nCase 2\n\nA 46-year old woman was diagnosed with diffuse large B-cell lymphoma 6 months ago (stage IIB). The MRI scan indicated that the lymphoma invaded her liver, pancreas, stomach, and right kidney. She received one cycle of R-CHOP, three cycles of R-EPOCH (rituximab, etoposide phosphate, prednisone, oncovin, cyclophosphamide, and hydroxydaunorubicin), one cycle of large-dose methotrexate (MTX), and one cycle of R-DHAP plus Bruton’s tyrosine kinase (BTK) inhibitor chemotherapy. Posttreatment evaluation indicated that the remaining tumor (13 mm × 10 mm) resided in her lower common bile duct.\n\nThis patient had previous history of HBV infection and took entecavir treatment before chemotherapy initiation. On her first admission into our center, serum test indicated that she had positive results of HBsAg, anti-HBe, and anti-HBc. The results for hepatitis C virus (HCV) and HIV antibodies were negative. Her HBV DNA level was undetectable. Her initial liver function test result was quite abnormal as serum AST was 121 U/L and ALT was 190 U/L. Her TBIL level reached 223.9 μmol/L, and the DBIL level was 212.1 μmol/L. We then performed magnetic resonance cholangiopancreatography (MRCP), and the results demonstrated tumor nodule localizing in the lower common bile duct, with notable dilation of the bile duct and pancreatic duct. As her tumor caused serious obstruction, percutaneous transhepatic cholangial drainage (PTCD) was conducted and her liver function quickly recovered.\n\nBecause the patient had suffered rapid progression of lymphoma and obstructive jaundice during chemotherapy, chemotherapy resistance was considered. In order to control her pancreatic tumor progression, we performed CAR-T cocktail therapy with anti-CD19 and anti-CD22 CAR-T therapy. Her CAR-T culturing and lymphodepletion chemotherapy were the same as those of case 1. Sequential infusion strategy was planned as follows: anti-CD19 CAR-T infusion 2 × 106/kg on days 1 and 5 and anti-CD22 CAR-T infusion 2 × 106/kg on days 0 and 2. The patient developed mild nausea, vomiting, and fever post-infusion, with peak ferritin level of 2,583 μg/L and IL-6 level of 197.7 pg/ml ( Figures 2A–C ). Lentiviral copy surveillance conducted using qRT-PCR suggested that CAR T-cell expansion reached a maximum point +10 days post-infusion (copy numbers for CD19 6541 and CD22 3602) ( Figure 2D ).\n\nHer liver function remained steady under entecavir treatment until +14 days post-CAR-T infusion. Blood test on +14 days indicated elevated ALT (53 U/L)/AST (66 U/L), with mild elevations of TBIL (22.5 μmol/L) and DBIL (20.7 μmol/L) ( Figure 2E ). After ruling out possibilities of obstruction of the PTCD tube and a retest of HBV copy (+14 days, 2.25 × 102 IU/ml) ( Figure 2E ), reactivation of HBV was suspected. We quickly implemented combinatory rescuing anti-HBV treatment with entecavir and tenofovir. As a result, her HBV DNA copy and her AST/ALT levels returned to normal at +21 days.\n\nDiscussion\n\nIn the past two decades, CAR T-cell therapy has been rapidly emerging as a promising novel treatment for hematological malignancies (6–8). CAR T-cell cocktail infusion strategy can reduce tumor antigen escape and improve therapeutic effects (12, 13). Therefore, CAR T-cell cocktail therapy with anti-CD19 and anti-CD22 CAR T-cell infusion was selected for these two patients.\n\nHowever, as the medical community continues to explore unknown territories that target the immune system to treat various diseases, HBV reactivation remains a vexatious and persistent problem (14). As curative and eradicative therapies for HBV are not currently available, HBV reactivation is a common and potentially fatal complication in patients with previous HBV infection who receive chemotherapies or immunosuppressive therapies (3, 14, 15). HBV is a double-stranded DNA virus that has various genotypes, subtypes, mutants, recombinants, and even quasispecies. Ten genotypes of HBV have been identified, labeled A through J (4). The distribution of these HBV genotypes has obvious geographic-associated features. Infections in East Asia are most commonly HBV genotypes B and C (16). Accumulating lines of evidence have clarified the clinical significance of HBV genotypes and mutants over the past decade (17). HBV genotype is increasingly associated with treatment response, disease severity, and progression (17).\n\nPatients being considered for chemotherapy should be screened for hepatitis B infection with HBsAg, anti-HBe, and anti-HBc and, if needed, subsequent determination of the HBV DNA levels (14, 15, 18, 19). Guidelines suggest that patients with chronic HBV receiving anticancer therapy should receive antiviral prophylactic therapy not only for the entire duration of anticancer therapy but also for at least 12 months post-therapy (4, 5, 15, 18). In those patients with negative HBV DNA levels in serum, periodic determination of the HBV DNA levels and liver enzymes during treatment should be performed (14, 15, 18, 19). With close and regular monitoring of HBV DNA, reactivation events can be captured and the appropriate therapy can be started on time (19).\n\nPatients receiving chemotherapy with hematologic malignancies are at high risk of HBV reactivation. Similarly, CAR T-cell therapy represents a uniquely high-risk group based on the progressive B-cell depletion induced by CAR T cells (15). Our clinical center have reported quickly exacerbated post-CAR-T HBV reactivation cases (9), suggesting that rapid clinical interventions should be made. Case reports of HBV reactivation have been reported after CAR-T therapy in patients with lymphoma and known HBV infection, but the degree of risk has not yet been established (2, 9–11). Taken together, these reports indicate that patients positive for HBsAg may need careful monitoring and require anti-HBV prophylaxis during CAR T-cell therapy (2, 9–11).\n\nThe nucleos(t)ide analogues (NAs) of entecavir and tenofovir are considered first-line regimens because of their high potency and low rates of resistance (4, 20). Nucleotide analogue tenofovir has no cross-resistance with nucleoside analogues and can be used to rescue drug resistance during entecavir therapy (21). The American Association for the Study of Liver Diseases (AASLD) guidelines recommend that patients with virologic failure should switch to another first-line agent or add a second drug (4). The consensus of Chinese experts advocates for either a switch to tenofovir monotherapy or a combination entecavir–tenofovir when faced with HBV reactivation in patients treated with entecavir as anti-HBV prophylaxis (22).\n\nIn these cases, despite entecavir being chosen as antiviral prophylactic therapy, two lymphoma patients still suffered HBV reactivation after CAR19/22 T-cell cocktail therapy. Reactivation of HBV was successfully treated with the combinatory treatment of entecavir and tenofovir. This prompts us to design a more detailed clinical research to further define the optimal preventive strategy for HBV-infected lymphoma patients receiving CAR T-cell therapy.\n\nIn summary, in this study, we demonstrated the risk of HBV reactivation in lymphoma patients receiving CAR T-cell therapy despite entecavir preventive intervention. Our report also indicated the usefulness of entecavir and tenofovir combined therapy for the treatment of HBV reactivation. More data from further clinical studies should be collected to provide clear indications on the following: the risk of HBV reactivation in lymphoma patients receiving CAR T-cell therapy, the duration of anti-HBV prophylaxis and the proper prevention strategy in lymphoma patients receiving CAR T-cell therapy with chronic or resolved HBV infection, and the best drug or combination of drugs for recurrent HBV hepatitis therapy.\n\nData Availability Statement\n\nThe original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.\n\nEthics Statement\n\nThe studies involving human participants were reviewed and approved by the Medical Ethics Committee of the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. The patients/participants provided written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.\n\nAuthor Contributions\n\nYM analyzed the data and wrote the first draft of the manuscript. LY managed the patients, collected the clinical data, and wrote a section of the manuscript. YB, YY, LC, and MZ managed the patients. MZ revised the manuscript and was in charge of the final approval of the manuscript. All authors contributed to the article and approved the submitted version.\n\nFunding\n\nThe work was supported by the National Natural Science Foundation of China (no. 81974005) and the Chen Xiao-Ping Foundation for the development of Science and Technology of Hubei Province.\n\nConflict of Interest\n\nThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\n\nPublisher’s Note\n\nAll claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.\n\nAcknowledgments\n\nWe are grateful to all members of the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.\n==== Refs\nReferences\n\n1 Sagnelli C Pisaturo M Calò F Martini S Sagnelli E Coppola N . Reactivation of Hepatitis B Virus Infection in Patients With Hemo-Lymphoproliferative Diseases, and Its Prevention. World J Gastroenterol (2019) 25 (26 ):3299–312. doi: 10.3748/wjg.v25.i26.3299\n2 Cao W Wei J Wang N Xu H Xiao M Huang L . Entecavir Prophylaxis for Hepatitis B Virus Reactivation in Patients With CAR T-Cell Therapy. Blood (2020) 136 (4 ):516–9. doi: 10.1182/blood.2020004907\n3 Kusumoto S Arcaini L Hong X Jin J Kim WS Kwong YL . Risk of HBV Reactivation in Patients With B-Cell Lymphomas Receiving Obinutuzumab or Rituximab Immunochemotherapy. Blood (2019) 133 (2 ):137–46. doi: 10.1182/blood-2018-04-848044\n4 Terrault NA Lok ASF McMahon BJ Chang KM Hwang JP Jonas MM . Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance. Hepatology (2018) 67 (4 ):1560–99. doi: 10.1002/hep.29800\n5 Sarmati L Andreoni M Antonelli G Arcese W Bruno R Coppola N . Recommendations for Screening, Monitoring, Prevention, Prophylaxis and Therapy of Hepatitis B Virus Reactivation in Patients With Haematologic Malignancies and Patients Who Underwent Haematologic Stem Cell Transplantation-a Position Paper. Clin Microbiol Infect (2017) 23 (12 ):935–40. doi: 10.1016/j.cmi.2017.06.023\n6 June CH O'Connor RS Kawalekar OU Ghassemi S Milone MC . CAR T Cell Immunotherapy for Human Cancer. Science (2018) 359 (6382 ):1361–5. doi: 10.1126/science.aar6711\n7 Brudno JN Kochenderfer JN . Chimeric Antigen Receptor T-Cell Therapies for Lymphoma. Nat Rev Clin Oncol (2018) 15 (1 ):31–46. doi: 10.1038/nrclinonc.2017.128 28857075\n8 Neelapu SS Tummala S Kebriaei P Wierda W Gutierrez C Locke FL . Chimeric Antigen Receptor T-Cell Therapy - Assessment and Management of Toxicities. Nat Rev Clin Oncol (2018) 15 (1 ):47–62. doi: 10.1038/nrclinonc.2017.148 28925994\n9 Wei J Zhu X Mao X Huang L Meng F Zhou J . Severe Early Hepatitis B Reactivation in a Patient Receiving Anti-CD19 and Anti-CD22 CAR T Cells for the Treatment of Diffuse Large B-Cell Lymphoma. J Immunother Cancer (2019) 7 (1 ):315. doi: 10.1186/s40425-019-0790-y 31753002\n10 Yang C Xie M Zhang K Liu H Liang A Young KH . Risk of HBV Reactivation Post CD19-CAR-T Cell Therapy in DLBCL Patients With Concomitant Chronic HBV Infection. Leukemia (2020) 34 (11 ):3055–9. doi: 10.1038/s41375-020-0913-y\n11 Strati P Nastoupil LJ Fayad LE Samaniego F Adkins S Neelapu SS . Safety of CAR T-Cell Therapy in Patients With B-Cell Lymphoma and Chronic Hepatitis B or C Virus Infection. Blood (2019) 133 (26 ):2800–2. doi: 10.1182/blood.2019000888\n12 Schneider D Xiong Y Wu D Hu P Alabanza L Steimle B . Trispecific CD19-CD20-CD22-Targeting duoCAR-T Cells Eliminate Antigen-Heterogeneous B Cell Tumors in Preclinical Models. Sci Transl Med (2021) 13 (586 ):eabc6401. doi: 10.1126/scitranslmed.abc6401 33762438\n13 Hamieh M Dobrin A Cabriolu A van der Stegen SJC Giavridis T Mansilla-Soto J . CAR T Cell Trogocytosis and Cooperative Killing Regulate Tumour Antigen Escape. Nature (2019) 568 (7750 ):112–6. doi: 10.1038/s41586-019-1054-1\n14 Kusumoto S Tanaka Y Suzuki R Watanabe T Nakata M Takasaki H . Monitoring of Hepatitis B Virus (HBV) DNA and Risk of HBV Reactivation in B-Cell Lymphoma: A Prospective Observational Study. Clin Infect Dis (2015) 61 (5 ):719–29. doi: 10.1093/cid/civ344\n15 Hwang JP Feld JJ Hammond SP Wang SH Alston-Johnson DE Cryer DR . Hepatitis B Virus Screening and Management for Patients With Cancer Prior to Therapy: ASCO Provisional Clinical Opinion Update. J Clin Oncol (2020) 38 (31 ):3698–715. doi: 10.1200/jco.20.01757\n16 Li HM Wang JQ Wang R Zhao Q Li L Zhang JP . Hepatitis B Virus Genotypes and Genome Characteristics in China. World J Gastroenterol (2015) 21 (21 ):6684–97. doi: 10.3748/wjg.v21.i21.6684\n17 Lin CL Kao JH . Natural History of Acute and Chronic Hepatitis B: The Role of HBV Genotypes and Mutants. Best Pract Res Clin Gastroenterol (2017) 31 (3 ):249–55. doi: 10.1016/j.bpg.2017.04.010\n18 Loomba R Liang TJ . Hepatitis B Reactivation Associated With Immune Suppressive and Biological Modifier Therapies: Current Concepts, Management Strategies, and Future Directions. Gastroenterology (2017) 152 (6 ):1297–309. doi: 10.1053/j.gastro.2017.02.009\n19 Tan CJ Kumar R Koomanan N Loo WS Farid M Tao M . Clinical and Economic Evaluation of a Surveillance Protocol to Manage Hepatitis B Virus (HBV) Reactivation Among Lymphoma Patients With Resolved HBV Infection Receiving Rituximab. Pharmacotherapy (2021) 41 (4 ):332–41. doi: 10.1002/phar.2508\n20 Tang LSY Covert E Wilson E Kottilil S . Chronic Hepatitis B Infection: A Review. JAMA (2018) 319 (17 ):1802–13. doi: 10.1001/jama.2018.3795\n21 Chien RN Liaw YF . Nucleos(t)ide Analogues for Hepatitis B Virus: Strategies for Long-Term Success. Best Pract Res Clin Gastroenterol (2008) 22 (6 ):1081–92. doi: 10.1016/j.bpg.2008.11.003\n22 Chinese Society of Lymphoma CA-cA. Chinese Society of Hematology CMA. The Consensus on the Prophylaxis and Treatment of HBV Reactivation in B or Plasma Cell-Directed CAR-T Cell Therapy(2021). Zhonghua Xue Ye Xue Za Zhi (2021) 42 (6 ):441–6. doi: 10.3760/cma.j.issn.0253-2727.2021.06.001\n\n", "fulltext_license": "CC BY", "issn_linking": "1664-3224", "issue": "12()", "journal": "Frontiers in immunology", "keywords": "CAR T; antiviral therapy; hepatitis B virus; lymphoma; reactivation", "medline_ta": "Front Immunol", "mesh_terms": null, "nlm_unique_id": "101560960", "other_id": null, "pages": "751754", "pmc": null, "pmid": "34691067", "pubdate": "2021", "publication_types": "D002363:Case Reports; D013485:Research Support, Non-U.S. Gov't", "references": "33547823;28857075;29715359;32716741;33762438;29567707;30341058;28774406;34384148;29405329;31341357;26074707;32533094;31753002;28668466;19187868;31101626;25935551;28925994;28219691;32291456;30918399", "title": "Case Report: Post-CAR-T Infusion HBV Reactivation in Two Lymphoma Patients Despite Entecavir Preventive Therapy.", "title_normalized": "case report post car t infusion hbv reactivation in two lymphoma patients despite entecavir preventive therapy" }

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"drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE" } ], "patientagegroup": null, "patientonsetage": "55", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hepatitis B reactivation", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Ma, Y.. Case Report: Post-CAR-T Infusion HBV Reactivation in Two Lymphoma Patients Despite Entecavir Preventive Therapy. Front-Immunol. 2021", "literaturereference_normalized": "case report post car t infusion hbv reactivation in two lymphoma patients despite entecavir preventive therapy", "qualification": "3", "reportercountry": "CN" }, "primarysourcecountry": "CN", "receiptdate": "20220107", "receivedate": "20220107", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20309436, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220423" }, { "companynumb": "CN-ROCHE-2969248", "fulfillexpeditecriteria": "1", "occurcountry": null, "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "RITUXIMAB" }, "drugadditional": "3", "drugadministrationroute": "065", 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progression", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Jaundice cholestatic", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Ma Y, Yang L, Bao Y, Yang Y, Chen L and Zheng M. Case Report: Post-CAR-T Infusion HBV Reactivation in Two Lymphoma Patients Despite Entecavir Preventive Therapy. Frontiers in Immunology 2021 Oct 08;12:1-6.", "literaturereference_normalized": "case report post car t infusion hbv reactivation in two lymphoma patients despite entecavir preventive therapy", "qualification": "3", "reportercountry": "CN" }, "primarysourcecountry": "CN", "receiptdate": "20211129", "receivedate": "20211129", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "3", "safetyreportid": 20126226, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220304" }, { "companynumb": "CN-PDX-000004", "fulfillexpeditecriteria": "1", "occurcountry": "CN", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ENTECAVIR" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "212106", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Antiviral prophylaxis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ENTECAVIR" } ], "patientagegroup": "5", "patientonsetage": "46", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hepatitis B reactivation", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Ma Y, Yang L, Bao Y, Yang Y, Chen L, Zheng M. Case Report: Post-CAR-T Infusion HBV Reactivation in Two Lymphoma Patients Despite Entecavir Preventive Therapy. Front Immunol. 2021 Oct 8;12:751754. doi: 10.3389/fimmu.2021.751754. 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"drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUDARABINE" } ], "patientagegroup": null, "patientonsetage": "46", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hepatitis B reactivation", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Ma, Y.. Case Report: Post-CAR-T Infusion HBV Reactivation in Two Lymphoma Patients Despite Entecavir Preventive Therapy. Front-Immunol. 2021", "literaturereference_normalized": "case report post car t infusion hbv reactivation in two lymphoma patients despite entecavir preventive therapy", "qualification": "3", "reportercountry": "CN" }, "primarysourcecountry": "CN", "receiptdate": "20220107", "receivedate": "20220107", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20309440, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220423" }, { "companynumb": "CN-PDX-000003", "fulfillexpeditecriteria": "1", "occurcountry": "CN", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ENTECAVIR" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "212106", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Antiviral prophylaxis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "0.5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ENTECAVIR" } ], "patientagegroup": "5", "patientonsetage": "55", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hepatitis B reactivation", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Ma Y, Yang L, Bao Y, Yang Y, Chen L, Zheng M. Case Report: Post-CAR-T Infusion HBV Reactivation in Two Lymphoma Patients Despite Entecavir Preventive Therapy. Front Immunol. 2021 Oct 8;12:751754. doi: 10.3389/fimmu.2021.751754. PMID: 34691067", "literaturereference_normalized": "case report post car t infusion hbv reactivation in two lymphoma patients despite entecavir preventive therapy", "qualification": "3", "reportercountry": "CN" }, "primarysourcecountry": "CN", "receiptdate": "20211103", "receivedate": "20211103", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20028181, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" } ]

{ "abstract": "PI has been rarely reported following pediatric live-related liver transplantation. Such a disorder is characterized by accumulation of gas in the bowel wall. The cause of PI has not been yet established; however, it has been strongly linked with steroid therapy. In this report, we present a case of PI following pediatric live-related liver transplantation that has been successfully managed conservatively.", "affiliations": "Kasr El Aini Teaching Hospitals, Cairo University, Cairo, Egypt.", "authors": "Abdel-Aziz|Omer|O|;Elaffandi|Ahmed H|AH|;El Shazly|Mostafa|M|;Hosny|Adel|A|;El-Karaksy|Hanaa|H|", "chemical_list": "D013256:Steroids", "country": "Denmark", "delete": false, "doi": "10.1111/petr.12195", "fulltext": null, "fulltext_license": null, "issn_linking": "1397-3142", "issue": "18(1)", "journal": "Pediatric transplantation", "keywords": "living related liver transplantation; pediatric transplantation; pneumatosis intestinalis", "medline_ta": "Pediatr Transplant", "mesh_terms": "D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation; D016031:Liver Transplantation; D019520:Living Donors; D011006:Pneumatosis Cystoides Intestinalis; D013256:Steroids; D016896:Treatment Outcome", "nlm_unique_id": "9802574", "other_id": null, "pages": "E18-21", "pmc": null, "pmid": "24283569", "pubdate": "2014-02", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Pneumatosis intestinalis following pediatric live-related liver transplant: a case report and successful conservative approach.", "title_normalized": "pneumatosis intestinalis following pediatric live related liver transplant a case report and successful conservative approach" }

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PNEUMATOSIS INTESTINALIS FOLLOWING PEDIATRIC LIVE-RELATED LIVER TRANSPLANT: A CASE REPORT AND SUCCESSFUL CONSERVATIVE APPROACH.. PEDIATR-TRANSPLANT. 2014;18(1):E18-21", "literaturereference_normalized": "pneumatosis intestinalis following pediatric live related liver transplant a case report and successful conservative approach", "qualification": "3", "reportercountry": "EG" }, "primarysourcecountry": "EG", "receiptdate": "20150922", "receivedate": "20150922", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11536946, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20151125" }, { "companynumb": "EG-FRESENIUS KABI-FK201504625", "fulfillexpeditecriteria": "1", "occurcountry": "EG", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".3", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "040583", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "2", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".5", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE (MANUFACTURER UNKNOWN)" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "040583", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "2", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE (MANUFACTURER UNKNOWN)" } ], "patientagegroup": null, "patientonsetage": "14", "patientonsetageunit": "802", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pneumatosis intestinalis", "reactionmeddraversionpt": "18.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "ABDEL-AZIZ O,ELAFFANDI A,EL SHAZLY M,HOSNY A,EL-KARAKSY H. PNEUMATOSIS INTESTINALIS FOLLOWING PEDIATRIC LIVE RELATED LIVER TRANSPLANT A CASE REPORT AND SUCCESSFUL CONSERVATIVE APPROACH. PEDIATRIC TRANSPLANTATION 2014 FEB?NO. 1:E18-21.", "literaturereference_normalized": "pneumatosis intestinalis following pediatric live related liver transplant a case report and successful conservative approach", "qualification": "3", "reportercountry": "EG" }, "primarysourcecountry": "EG", "receiptdate": "20151002", "receivedate": "20151001", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11585929, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20160304" }, { "companynumb": "EG-MYLANLABS-2015M1031918", "fulfillexpeditecriteria": "1", "occurcountry": "EG", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "0.5MG/KG/DAY FOR ANOTHER 3 DAYS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "202179", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.3MG/KG/DAY FOR ONE MONTH", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "INCREASED GRADUALLY TO ATTAIN TROUGH LEVEL OF 10-15 NG/ML.", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "1MG/KG/DAY FOR FIRST 3 DAYS AND THEN REDUCED TO 0.5MG/KG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pneumatosis intestinalis", "reactionmeddraversionpt": "18.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "ABDEL-AZIZ O, ELAFFANDI AH, EL SHAZLY M, HOSNY A, EL-KARAKSY H. PNEUMATOSIS INTESTINALIS FOLLOWING PEDIATRIC LIVE-RELATED LIVER TRANSPLANT: A CASE REPORT AND SUCCESSFUL CONSERVATIVE APPROACH. PEDIATR-TRANSPLANT 2014; 18(1):E18-21.", "literaturereference_normalized": "pneumatosis intestinalis following pediatric live related liver transplant a case report and successful conservative approach", "qualification": "3", "reportercountry": "EG" }, "primarysourcecountry": "EG", "receiptdate": "20150924", "receivedate": "20150924", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11547299, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20151125" }, { "companynumb": "EG-SUN PHARMACEUTICAL INDUSTRIES LTD-2015R1-103529", "fulfillexpeditecriteria": "1", "occurcountry": "EG", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "089245", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." } ], "patientagegroup": "3", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pneumatosis intestinalis", "reactionmeddraversionpt": "18.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "ABDEL-AZIZ O, ELAFFANDI AH, EL SHAZLY M, HOSNY A, EL-KARAKSY H. PNEUMATOSIS INTESTINALIS FOLLOWING PEDIATRIC LIVE-RELATED LIVER TRANSPLANT: A CASE REPORT AND SUCCESSFUL CONSERVATIVE APPROACH. PEDIATR-TRANSPLANT. 2014;18(1):E18-21", "literaturereference_normalized": "pneumatosis intestinalis following pediatric live related liver transplant a case report and successful conservative approach", "qualification": "3", "reportercountry": "EG" }, "primarysourcecountry": "EG", "receiptdate": "20150925", "receivedate": "20150925", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11553021, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20151125" } ]

{ "abstract": "We describe the case of a woman, who had previously undergone tubal sterilization, and later experienced two episodes of orthostatic hypotension during menstruation, as a result of an ectopic pregnancy.", "affiliations": "Emergency Division of la Tour Hospital, Geneva University Hospitals, Geneva, Switzerland. [email protected]", "authors": "Dussoix|Philippe|P|;Hagelberg|Tessa|T|;Vermeulen|Bernard|B|", "chemical_list": null, "country": "England", "delete": false, "doi": "10.1097/00063110-200402000-00013", "fulltext": null, "fulltext_license": null, "issn_linking": "0969-9546", "issue": "11(1)", "journal": "European journal of emergency medicine : official journal of the European Society for Emergency Medicine", "keywords": null, "medline_ta": "Eur J Emerg Med", "mesh_terms": "D000005:Abdomen; D015746:Abdominal Pain; D000328:Adult; D004635:Emergency Medicine; D005260:Female; D006801:Humans; D011247:Pregnancy; D011258:Pregnancy Tests; D011271:Pregnancy, Ectopic; D013245:Sterilization, Reproductive; D013575:Syncope; D016896:Treatment Outcome; D014463:Ultrasonography", "nlm_unique_id": "9442482", "other_id": null, "pages": "59", "pmc": null, "pmid": "15167197", "pubdate": "2004-02", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "An unusual case of syncope.", "title_normalized": "an unusual case of syncope" }

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{ "abstract": "OBJECTIVE\nTo analyze the reproductive outcomes of women with high-risk gestational trophoblastic neoplasia (GTN) treated with multiagent EMA-CO chemotherapy.\n\n\nMETHODS\nOf 212 patients treated with chemotherapy for GTN between 1986 and 2012, 65 (31%) could be contacted by telephone or mail and consented to participate in a questionnaire designed to assess their menstrual and reproduction outcomes.\n\n\nRESULTS\nTwenty-four high-risk (HR) and 41 low-risk (LR) patients consented to the study. Fifteen (63%) HR and 34 (83%) LR women had not undergone hysterectomy (p = 0.08). Of the 12 HR and 33 LR women who could recall their menstrual history, all 12 (100%) HR and 32 (97%) LR women resumed menses after chemotherapy. Both groups also had a similar age of menopause (HR, 43.8 years; LR, 48.5 years) (p = 0.19). Although fewer women in the HR group desired to become pregnant after chemotherapy (HR 5/15 [33%] vs. LR 25/34 [74%]) (p = 0.01), 8 HR women (53%) and 29 LR women (85%) eventually became pregnant (p = 0.03), with equivalent live birth rates of 74% and 76%, respectively.\n\n\nCONCLUSIONS\nMultiagent EMA-CO chemotherapy did not significantly alter menstrual or reproductive outcomes compared to single-agent methotrexate chemotherapy for GTN.", "affiliations": null, "authors": "Wong|Jacqueline M K|JM|;Liu|Dachao|D|;Lurain|John R|JR|", "chemical_list": "D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D008727:Methotrexate", "country": "United States", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "0024-7758", "issue": "59(5-6)", "journal": "The Journal of reproductive medicine", "keywords": null, "medline_ta": "J Reprod Med", "mesh_terms": "D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols; D003520:Cyclophosphamide; D003609:Dactinomycin; D005047:Etoposide; D005260:Female; D031901:Gestational Trophoblastic Disease; D006801:Humans; D007044:Hysterectomy; D050498:Live Birth; D008598:Menstruation; D008727:Methotrexate; D008875:Middle Aged; D011247:Pregnancy; D011256:Pregnancy Outcome; D012098:Reproduction; D012307:Risk Factors; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014750:Vincristine", "nlm_unique_id": "0173343", "other_id": null, "pages": "204-8", "pmc": null, "pmid": "24937958", "pubdate": "2014", "publication_types": "D016428:Journal Article", "references": null, "title": "Reproductive outcomes after multiagent chemotherapy for high-risk gestational trophoblastic neoplasia.", "title_normalized": "reproductive outcomes after multiagent chemotherapy for high risk gestational trophoblastic neoplasia" }

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REPRODUCTIVE OUTCOMES AFTER MULTIAGENT CHEMOTHERAPY FOR HIGH-RISK GESTATIONAL TROPHOBLASTIC NEOPLASIA. 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null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE" } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Maternal exposure before pregnancy", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "No adverse event", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LURAIN J, WONG J, LIU D. REPRODUCTIVE OUTCOMES AFTER MULTIAGENT CHEMOTHERAPY FOR HIGH-RISK GESTATIONAL TROPHOBLASTIC NEOPLASIA. JOURNAL OF REPRODUCTIVE MEDICINE. 2014 MAY 01;59:204-208.", "literaturereference_normalized": "reproductive outcomes after multiagent chemotherapy for high risk gestational trophoblastic neoplasia", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20140829", "receivedate": "20140829", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10418487, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150326" }, { "companynumb": "US-BAXTER-2014BAX052607", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, 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null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GESTATIONAL TROPHOBLASTIC TUMOUR", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GESTATIONAL 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"drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACTINOMYCIN D" } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Maternal exposure before pregnancy", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "No adverse event", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LURAIN J, WONG J, LIU D. REPRODUCTIVE OUTCOMES AFTER MULTIAGENT CHEMOTHERAPY FOR HIGH-RISK GESTATIONAL TROPHOBLASTIC NEOPLASIA. JOURNAL OF REPRODUCTIVE MEDICINE. 2014 MAY 01;59:204-208.", "literaturereference_normalized": "reproductive outcomes after multiagent chemotherapy for high risk gestational trophoblastic neoplasia", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20140829", "receivedate": "20140829", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10419686, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150326" }, { "companynumb": "US-BAXTER-2014BAX052425", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, 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null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "FOETAL EXPOSURE TIMING UNSPECIFIED", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACTINOMYCIN D" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "064", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "FOETAL EXPOSURE TIMING UNSPECIFIED", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "064", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "FOETAL EXPOSURE TIMING UNSPECIFIED", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, 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null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE" } ], "patientagegroup": "1", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Reproductive tract disorder", "reactionmeddraversionpt": "17.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Syndactyly", "reactionmeddraversionpt": "17.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Maternal exposure before pregnancy", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LURAIN J, WONG J, LIU D. REPRODUCTIVE OUTCOMES AFTER MULTIAGENT CHEMOTHERAPY FOR HIGH-RISK GESTATIONAL TROPHOBLASTIC NEOPLASIA. JOURNAL OF REPRODUCTIVE MEDICINE. 2014 MAY 01;59:204-208.", "literaturereference_normalized": "reproductive outcomes after multiagent chemotherapy for high risk gestational trophoblastic neoplasia", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20140828", "receivedate": "20140828", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10416849, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150326" }, { "companynumb": "US-BAXTER-2014BAX052606", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHOTREXATE" }, 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null, "drugindication": "GESTATIONAL TROPHOBLASTIC TUMOUR", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE FOR INJECTION, USP" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GESTATIONAL TROPHOBLASTIC TUMOUR", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, 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"drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Maternal exposure before pregnancy", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "No adverse event", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LURAIN J, WONG J, LIU D. REPRODUCTIVE OUTCOMES AFTER MULTIAGENT CHEMOTHERAPY FOR HIGH-RISK GESTATIONAL TROPHOBLASTIC NEOPLASIA. JOURNAL OF REPRODUCTIVE MEDICINE. 2014 MAY 01;59:204-208.", "literaturereference_normalized": "reproductive outcomes after multiagent chemotherapy for high risk gestational trophoblastic neoplasia", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20140829", "receivedate": "20140829", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10418489, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150326" }, { "companynumb": "US-BAXTER-2014BAX050691", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE" }, 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null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GESTATIONAL TROPHOBLASTIC TUMOUR", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACTINOMYCIN D" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "040745", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "POWDER FOR SOLUTION FOR INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GESTATIONAL TROPHOBLASTIC TUMOUR", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE FOR INJECTION, USP" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GESTATIONAL TROPHOBLASTIC TUMOUR", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, 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null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE" } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "No adverse event", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Maternal exposure before pregnancy", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LURAIN J, WONG J, LIU D. REPRODUCTIVE OUTCOMES AFTER MULTIAGENT CHEMOTHERAPY FOR HIGH-RISK GESTATIONAL TROPHOBLASTIC NEOPLASIA. JOURNAL OF REPRODUCTIVE MEDICINE. 2014 MAY 01;59:204-208.", "literaturereference_normalized": "reproductive outcomes after multiagent chemotherapy for high risk gestational trophoblastic neoplasia", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20140828", "receivedate": "20140828", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10416872, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150326" }, { "companynumb": "US-BAXTER-2014BAX051689", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, 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null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GESTATIONAL TROPHOBLASTIC TUMOUR", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GESTATIONAL 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REPRODUCTIVE OUTCOMES AFTER MULTIAGENT CHEMOTHERAPY FOR HIGH-RISK GESTATIONAL TROPHOBLASTIC NEOPLASIA. JOURNAL OF REPRODUCTIVE MEDICINE. 2014 MAY 01;59:204-208.", "literaturereference_normalized": "reproductive outcomes after multiagent chemotherapy for high risk gestational trophoblastic neoplasia", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20140828", "receivedate": "20140828", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10416850, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150326" }, { "companynumb": "US-BAXTER-2014BAX052608", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DACTINOMYCIN" }, 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null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE" } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "No adverse event", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Maternal exposure before pregnancy", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LURAIN J, WONG J, LIU D. REPRODUCTIVE OUTCOMES AFTER MULTIAGENT CHEMOTHERAPY FOR HIGH-RISK GESTATIONAL TROPHOBLASTIC NEOPLASIA. JOURNAL OF REPRODUCTIVE MEDICINE. 2014 MAY 01;59:204-208.", "literaturereference_normalized": "reproductive outcomes after multiagent chemotherapy for high risk gestational trophoblastic neoplasia", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20140829", "receivedate": "20140829", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10418520, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150326" }, { "companynumb": "US-BAXTER-2014BAX051690", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, 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REPRODUCTIVE OUTCOMES AFTER MULTIAGENT CHEMOTHERAPY FOR HIGH-RISK GESTATIONAL TROPHOBLASTIC NEOPLASIA. 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{ "abstract": "BACKGROUND\nMultiple myeloma is a cancer of plasma cells that often leads to complications including osteolytic bone lesions, nephropathy and neuropathy. Multiple myeloma is only one etiology of many cancer pain conditions that may necessitate interventional pain treatment when refractory to multimodal medications. Notably, local anesthetic systemic toxicity is a rare but life-threatening complication of local anesthetic administered for these interventions.\n\n\nMETHODS\nA 50-60-year-old woman presented with multiple myeloma complicated by chronic bone pain and in an acute pain crisis. A fluoroscopic-guided L4-5 epidural catheter was placed with clinical doses of bupivacaine for comfort to undergo MRI of the spine. Soon after, she became tachycardic, tachypneic and hypoxic requiring non-invasive positive pressure airway support. As this respiratory distress was attributed to a large pleural effusion, a pigtail catheter was inserted in the intensive care unit with submaximally dosed lidocaine infiltration. She then developed a left bundle branch block followed by cardiovascular collapse minimally responsive to high-dose inotrope and vasopressor support. Lipid emulsion was started with dramatic therapeutic response and recovery to baseline. A CT of the thoracolumbar spine showed worsening extensive lytic lesions throughout all vertebral bodies and ribs from diffuse myeloma.\n\n\nCONCLUSIONS\nPatients with oncologic lesions focal to the thoracolumbar spine may be at higher risk for local anesthetic systemic toxicity from palliative epidurals due to increased cancer-related angiogenesis. Likewise, local anesthetic infiltration for procedures near any malignant sites could have a similar risk and may require lower initial fractionated dosages with increased vigilance.", "affiliations": "Department of Anesthesiology and Perioperative Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA [email protected].;College of Osteopathic Medicine, Touro University Nevada, Henderson, Nevada, USA.;Department of Anesthesiology and Perioperative Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA.", "authors": "Lim|Victoria M|VM|http://orcid.org/0000-0002-1993-5178;Barney|Taylor|T|;Jayaraman|Arun L|AL|", "chemical_list": null, "country": "England", "delete": false, "doi": "10.1136/rapm-2021-102845", "fulltext": null, "fulltext_license": null, "issn_linking": "1098-7339", "issue": "46(12)", "journal": "Regional anesthesia and pain medicine", "keywords": "anesthesia; cancer pain; drug-related side effects and adverse reactions; local; neurotoxicity syndromes; pain management", "medline_ta": "Reg Anesth Pain Med", "mesh_terms": null, "nlm_unique_id": "9804508", "other_id": null, "pages": "1103-1106", "pmc": null, "pmid": "34535547", "pubdate": "2021-12", "publication_types": "D016428:Journal Article", "references": null, "title": "Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity.", "title_normalized": "multiple myeloma and malignant lesions a potential risk factor for local anesthetic systemic toxicity" }

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Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity.. Regional anesthesia and pain medicine.. 2021", "literaturereference_normalized": "multiple myeloma and malignant lesions a potential risk factor for local anesthetic systemic toxicity", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20211202", "receivedate": "20211029", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20011618, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20220304" }, { "companynumb": "US-PURDUE-USA-2021-0288148", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "3", 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"drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "OTHER", "drugdosagetext": "200 MG, UNK [20ML 1%]", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "EPINEPHRINE\\LIDOCAINE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "3 ML, UNK [1%]", "drugenddate": null, "drugenddateformat": null, "drugindication": "Local anaesthesia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE HYDROCHLORIDE AND EPINEPHRINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BUPIVACAINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "8 ML, UNK [0.5%]", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "8", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPIVACAINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "IOHEXOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "unknown", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 ML, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IOHEXOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "IODINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "unknown", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "180 MG/ML, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IODINE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Local anaesthetic systemic toxicity", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute respiratory failure", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bundle branch block left", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Lim, Victoria M., Barney, Taylor, Jayaraman, Arun L.. Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity. 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INJECTION", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "BUPIVACAINE" }, "drugadditional": "4", "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "8 ML, ONCE", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pain", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "8", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPIVACAINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "IOHEXOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 ML, ONCE AT 180 MG IODINE/ML", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IOHEXOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "EPINEPHRINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EPINEPHRINE" } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Local anaesthetic systemic toxicity", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Bundle branch block left", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tachycardia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypertension", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tachypnoea", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Acute respiratory failure", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hyporesponsive to stimuli", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Circulatory collapse", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Lim VM, Barney T, Jayaraman AL. Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity. 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"drugadministrationroute": "008", "drugauthorizationnumb": "207266", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Solution for injection", "drugdosagetext": "CLINICAL DOSES", "drugenddate": null, "drugenddateformat": null, "drugindication": "Local anaesthesia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPIVACAINE HYDROCHLORIDE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BUPIVACAINE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "008", "drugauthorizationnumb": "207266", "drugbatchnumb": null, "drugcharacterization": "1", 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null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EPINEPHRINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "IOHEXOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "180 MG IODINE/ ML", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IOHEXOL" } ], "patientagegroup": null, "patientonsetage": "6", "patientonsetageunit": "800", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Bundle branch block left", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypoxia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Local anaesthetic systemic toxicity", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Respiratory distress", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Circulatory collapse", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Atrial fibrillation", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Ventricular hypokinesia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Ejection fraction decreased", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Electrocardiogram QT prolonged", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tachycardia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tachypnoea", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Depression", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypertension", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Lim V, Barney T, Jayaraman A. MULTIPLE MYELOMA AND MALIGNANT LESIONS: A POTENTIAL RISK FACTOR FOR LOCAL ANESTHETIC SYSTEMIC TOXICITY. REGIONAL ANESTHESIA AND PAIN MEDICINE. 2021 SEP 17;46:1103-1106.", "literaturereference_normalized": "multiple myeloma and malignant lesions a potential risk factor for local anesthetic systemic toxicity", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20220105", "receivedate": "20211029", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20013268, "safetyreportversion": 4, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20220424" }, { "companynumb": "US-PFIZER INC-202101394428", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "BUPIVACAINE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "008", "drugauthorizationnumb": "016964", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Solution for injection", "drugdosagetext": "8 ML", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "8", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPIVACAINE HYDROCHLORIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": null, "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "2 ML", "drugenddate": null, "drugenddateformat": null, "drugindication": "Local anaesthesia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": null, "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "3 ML", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "200 MILLIGRAM, LOCAL INFILTRATION A LOCAL INFILTRATION OF 1% LIDOCAINE 20ML (200MG)......", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "LIDOCAINE WAS GIVEN WITH FREQUENT ASPIRATION AND INCREMENTAL INJECTION", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "IOHEXOL" }, "drugadditional": null, "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "1 MILLILITER, 1 ML OF 180 MG IODINE/ ML", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IOHEXOL" } ], "patientagegroup": null, "patientonsetage": "6", "patientonsetageunit": "800", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "PO2 decreased", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Tachycardia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypertension", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Tachypnoea", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Respiratory rate increased", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Lim, V.. Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity. Regional anesthesia and pain medicine. 2021;10.1136/rapm-2021-102845", "literaturereference_normalized": "multiple myeloma and malignant lesions a potential risk factor for local anesthetic systemic toxicity", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20211206", "receivedate": "20211027", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20002126, "safetyreportversion": 4, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "US-DENTSPLY-2021SCDP000320", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "3", "drugadministrationroute": "008", "drugauthorizationnumb": "21380", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "3 MILLILITER INJECTION (SUBMAXIMALLY DOSED)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "21380", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "20 MILLILITER", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "3", "drugadministrationroute": "008", "drugauthorizationnumb": "21380", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "UNK INCREMENTAL (INJECTION)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "3", "drugadministrationroute": "061", "drugauthorizationnumb": "21380", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "2 MILLILITER", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BUPIVACAINE" }, "drugadditional": "3", "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "8 MILLILITER OF 0.25 % BUPIVACAINE (CLINICAL DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "8", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPIVACAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "EPINEPHRINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EPINEPHRINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IOHEXOL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 MILLILITER (180 MG IODINE/ML)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IOHEXOL" } ], "patientagegroup": null, "patientonsetage": "6", "patientonsetageunit": "800", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Tachypnoea", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Bundle branch block left", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tachycardia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Ventricular hypokinesia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Ejection fraction decreased", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Electrocardiogram QT prolonged", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypertension", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Atrial fibrillation", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypoxia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Respiratory distress", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Local anaesthetic systemic toxicity", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Circulatory collapse", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Depression", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Lim V M, Barney T, Jayaraman A L. Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity. Regional anesthesia and pain medicine. 2021", "literaturereference_normalized": "multiple myeloma and malignant lesions a potential risk factor for local anesthetic systemic toxicity", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20211208", "receivedate": "20211103", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20027376, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "US-SA-2021SA340832", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "SUBMAXIMALLY DOSED", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BUPIVACAINE" }, "drugadditional": "3", "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "CLINICAL DOSES", "drugenddate": null, "drugenddateformat": null, "drugindication": "Magnetic resonance imaging spinal", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPIVACAINE" } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Bundle branch block left", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Circulatory collapse", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Local anaesthetic systemic toxicity", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Lim VM, Barney T, Jayaraman AL.. Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity.. Reg Anesth Pain Med.. 2021;unknown:unknown", "literaturereference_normalized": "multiple myeloma and malignant lesions a potential risk factor for local anesthetic systemic toxicity", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20211025", "receivedate": "20211020", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19977306, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "US-drreddys-LIT/USA/21/0144039", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "DOBUTAMINE HYDROCHLORIDE" }, "drugadditional": "4", 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null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.2 MICROGRAM/KG/MIN", "drugenddate": null, "drugenddateformat": null, "drugindication": "Circulatory collapse", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EPINEPHRINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "VASOPRESSIN" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.04 U/MIN", "drugenddate": null, "drugenddateformat": null, "drugindication": 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"LIDOCAINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN,UNKNOWN,UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "1 PERCENT 20 ML", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "IOHEXOL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IOHEXOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "EPINEPHRINE" }, "drugadditional": null, "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EPINEPHRINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "BUPIVACAINE" }, "drugadditional": null, "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.25 PERCENT 8 ML", "drugenddate": null, "drugenddateformat": null, "drugindication": "Local anaesthesia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPIVACAINE" }, { "actiondrug": null, "activesubstance": null, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "epidural" } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Lim V, Barney T, Jayaraman A. Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity. Reg Anesth Pain Med. 2021;UNK:UNK-UNK. doi:10.1136/rapm-2021-102845", "literaturereference_normalized": "multiple myeloma and malignant lesions a potential risk factor for local anesthetic systemic toxicity", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20211125", "receivedate": "20211125", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20111306, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "US-Vitruvias Therapeutics-2121358", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": null, "drugadministrationroute": "008", "drugauthorizationnumb": "208822", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "BUPIVACAINE" }, "drugadditional": null, "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "8", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPIVACAINE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Local anaesthetic systemic toxicity", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Lim VM, Barney T, Jayaraman AL. Multiple myeloma and malignant lesions: a potential?risk factor for local anesthetic systemic toxicity. Reg Anesth Pain Med Epub ahead of print: [September 17, 2021]. doi:10.1136/rapm-2021-102845.", "literaturereference_normalized": "multiple myeloma and malignant lesions a potential risk factor for local anesthetic systemic toxicity", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": null, "receiptdate": "20211102", "receivedate": "20211102", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "3", "safetyreportid": 20026106, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": 1, "seriousnessother": null, "transmissiondate": "20220303" }, { "companynumb": "US-INNOCOLL PHARMACEUTICALS LIMITED-2021INN00004", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "BUPIVACAINE" }, "drugadditional": "4", "drugadministrationroute": "008", "drugauthorizationnumb": "209511", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "8 ML, ONCE", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pain", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "8", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPIVACAINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "4", "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 ML, ONCE", "drugenddate": null, "drugenddateformat": null, "drugindication": "Pain", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "20 ML - INJECTION", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "IOHEXOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 ML, ONCE AT 180 MG IODINE/ML", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IOHEXOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "EPINEPHRINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EPINEPHRINE" } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Local anaesthetic systemic toxicity", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Bundle branch block left", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tachycardia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypertension", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tachypnoea", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Acute respiratory failure", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hyporesponsive to stimuli", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Circulatory collapse", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Lim VM, Barney T, Jayaraman AL. Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity. Reg Anesth Pain Med. 2021", "literaturereference_normalized": "multiple myeloma and malignant lesions a potential risk factor for local anesthetic systemic toxicity", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20211102", "receivedate": "20211102", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20025799, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 2, "transmissiondate": "20220303" }, { "companynumb": "US-STRIDES ARCOLAB LIMITED-2021SP030143", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "3", 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"drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "200 MILLIGRAM, A LOCAL INFILTRATION OF 1% LIDOCAINE 20ML (200MG) INJECTION", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "210958", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, LIDOCAINE WAS GIVEN WITH FREQUENT ASPIRATION AND 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"drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BUPIVACAINE" }, "drugadditional": "3", "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "8 MILLILITER", "drugenddate": null, "drugenddateformat": null, "drugindication": "Local anaesthesia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, 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"medicinalproduct": "IOHEXOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "EPINEPHRINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.2 MICROGRAM/KILOGRAM PER MIN", "drugenddate": null, "drugenddateformat": null, "drugindication": "Circulatory collapse", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "0.2", "drugstructuredosageunit": "008", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EPINEPHRINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "EPINEPHRINE" }, "drugadditional": null, "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK (ALONG WITH LIDOCAINE)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EPINEPHRINE" } ], "patientagegroup": null, "patientonsetage": "6", "patientonsetageunit": "800", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bundle branch block 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Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity. 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"drugdosageform": null, "drugdosagetext": "2ML", "drugenddate": null, "drugenddateformat": null, "drugindication": "Local anaesthesia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BUPIVACAINE" }, "drugadditional": "3", "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "8ML", "drugenddate": null, "drugenddateformat": null, "drugindication": "Local anaesthesia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "8", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPIVACAINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DOBUTAMINE HYDROCHLORIDE" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "14400 UG/KG DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "Circulatory collapse", "drugintervaldosagedefinition": "806", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "008", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOBUTAMINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "VASOPRESSIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "57.6 IU (INTERNATIONAL UNIT) DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "Circulatory collapse", "drugintervaldosagedefinition": "806", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "0.04", "drugstructuredosageunit": "025", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VASOPRESSIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "200MG A LOCAL INFILTRATION OF 1% LIDOCAINE 20ML (200MG) INJECTION", "drugenddate": null, "drugenddateformat": null, "drugindication": "Local anaesthesia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "LIDOCAINE WAS GIVEN WITH FREQUENT ASPIRATION AND INCREMENTAL INJECTION", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "3", "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "EPINEPHRINE" }, "drugadditional": "3", "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "ALONG WITH LIDOCAINE", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EPINEPHRINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "EPINEPHRINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "288 UG/KG DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "Circulatory collapse", "drugintervaldosagedefinition": "806", "drugintervaldosageunitnumb": "1", 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"drugstructuredosagenumb": "1", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IOHEXOL" } ], "patientagegroup": "5", "patientonsetage": "6", "patientonsetageunit": "800", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Local anaesthetic systemic toxicity", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Bundle branch block left", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Circulatory collapse", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Lim VM, Barney T, Jayaraman AL. Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity. Region-Anesth-Pain-Med 2021;:.", "literaturereference_normalized": "multiple myeloma and malignant lesions a potential risk factor for local anesthetic systemic toxicity", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20211213", "receivedate": "20211201", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20137202, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": null, "transmissiondate": "20220303" }, { "companynumb": "US-MACLEODS PHARMACEUTICALS US LTD-MAC2021032828", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": 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"Bundle branch block left", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Local anaesthetic systemic toxicity", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tachypnoea", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tachycardia", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypoxia", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Respiratory distress", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypertension", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Atrial fibrillation", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Ventricular hypokinesia", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Ejection fraction decreased", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Electrocardiogram QT prolonged", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Depression", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Circulatory collapse", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Lim VM, Barney T, Jayaraman AL.. Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity. 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"drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 GRAM PER KILOGRAM PER MINUTE", "drugenddate": null, "drugenddateformat": null, "drugindication": "Circulatory collapse", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOBUTAMINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "EPINEPHRINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.2 GRAM PER KILOGRAM PER MINUTE", "drugenddate": null, "drugenddateformat": null, "drugindication": "Circulatory collapse", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EPINEPHRINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IODINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IODINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IOHEXOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 MILLILITER (180 MG IODINE/ ML)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IOHEXOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NOREPINEPHRINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.3 GRAM PER KILOGRAM PER MINUTE", "drugenddate": null, "drugenddateformat": null, "drugindication": "Circulatory collapse", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NOREPINEPHRINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VASOPRESSIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.4 INTERNATIONAL UNIT PER MILLILITRE", "drugenddate": null, "drugenddateformat": null, "drugindication": "Circulatory collapse", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VASOPRESSIN" } ], "patientagegroup": null, "patientonsetage": "6", "patientonsetageunit": "800", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hypoxia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tachycardia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tachypnoea", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Bundle branch block left", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Respiratory distress", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Circulatory collapse", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypertension", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Atrial fibrillation", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Local anaesthetic systemic toxicity", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Depression", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Ventricular hypokinesia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Ejection fraction decreased", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Electrocardiogram QT prolonged", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Lim VM, Barney T, Jayaraman AL. Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity. Regional anesthesia and pain medicine. 2021;0:1-4", "literaturereference_normalized": "multiple myeloma and malignant lesions a potential risk factor for local anesthetic systemic toxicity", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20211203", "receivedate": "20210930", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19897205, "safetyreportversion": 4, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "US-MYLANLABS-2021M1086655", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "3", 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"drugdosagetext": "3 MILLILITER", "drugenddate": null, "drugenddateformat": null, "drugindication": "Local anaesthesia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BUPIVACAINE" }, "drugadditional": "3", "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "8 MILLILITER", "drugenddate": null, "drugenddateformat": null, "drugindication": "Local anaesthesia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "8", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPIVACAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": "3", "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MILLILITER", "drugenddate": null, "drugenddateformat": null, "drugindication": "Local anaesthesia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, 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"summary": null }, "primarysource": { "literaturereference": "Lim VM, Barney T, Jayaraman AL. Multiple myeloma and malignant lesions: a potential risk factor for local anesthetic systemic toxicity. Region-Anesth-Pain-Med 2021;null:null.", "literaturereference_normalized": "multiple myeloma and malignant lesions a potential risk factor for local anesthetic systemic toxicity", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20211129", "receivedate": "20211129", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20127713, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 2, "transmissiondate": "20220303" } ]

{ "abstract": "BACKGROUND\nKaposi's sarcoma (KS) is a rare vascular tumor associated with human herpesvirus (HHV)-8 infection. One of the variants of KS is defined iatrogenic and is overall reported in transplanted patient but also, although less frequently, in patients treated with long-standing immunosuppressive therapy, such as in inflammatory bowel disease including ulcerative colitis and Crohn's disease.\n\n\nMETHODS\nHerein, we report the first case of KS in a human immunodeficiency virus (HIV)-negative 47-year old male with UC after treatment with the α4-β7 integrin inhibitor vedolizumab (VDZ). The patient underwent to colectomy for a medical refractory disease and the histological examination of the surgical specimen showed the typical findings of KS together with the HHV-8 positivity. The patient achieved a good health status, without any sign of disease recurrence.\n\n\nCONCLUSIONS\nIn the present case, we can assume that VDZ may have promoted the reactivation of a latent HHV-8 infection endowed with oncogenic potentialities and, in turn, the onset of KS. We also briefly reviewed all the cases of KS in HIV-negative patients with inflammatory bowel disease.", "affiliations": "Department of Surgery, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.;Department of Pathology, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.;UOC Medicina Interna e Gastroenterologia, Area Gastroenterologia ed Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168, Rome, Italy.;UOC Medicina Interna e Gastroenterologia, Area Gastroenterologia ed Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168, Rome, Italy. [email protected].", "authors": "Papa|Valerio|V|;Giustiniani|Maria Cristina|MC|;Lopetuso|Loris Riccardo|LR|;Papa|Alfredo|A|", "chemical_list": "D061067:Antibodies, Monoclonal, Humanized; D005765:Gastrointestinal Agents; C543529:vedolizumab", "country": "England", "delete": false, "doi": "10.1186/s12876-020-01221-2", "fulltext": "\n==== Front\nBMC Gastroenterol\nBMC Gastroenterol\nBMC Gastroenterology\n1471-230X BioMed Central London \n\n1221\n10.1186/s12876-020-01221-2\nCase Report\nHuman herpesvirus 8-associated colonic Kaposi’s sarcoma during vedolizumab treatment in ulcerative colitis: a case report and review of the literature\nPapa Valerio 123 Giustiniani Maria Cristina 4 Lopetuso Loris Riccardo 56 Papa Alfredo [email protected] 56 1 grid.414603.4Department of Surgery, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy \n2 Istituto di Clinica Chirurgica, Università Cattolica del S.Cuore, Rome, Italy \n3 Department of Surgery, Ospedale S. Carlo di Nancy, Rome, Italy \n4 grid.414603.4Department of Pathology, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy \n5 grid.414603.4UOC Medicina Interna e Gastroenterologia, Area Gastroenterologia ed Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy \n6 grid.8142.f0000 0001 0941 3192Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Rome, Italy \n24 3 2020 \n24 3 2020 \n2020 \n20 7621 7 2019 12 3 2020 © The Author(s) 2020Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background\nKaposi’s sarcoma (KS) is a rare vascular tumor associated with human herpesvirus (HHV)-8 infection. One of the variants of KS is defined iatrogenic and is overall reported in transplanted patient but also, although less frequently, in patients treated with long-standing immunosuppressive therapy, such as in inflammatory bowel disease including ulcerative colitis and Crohn’s disease.\n\nCase presentation\nHerein, we report the first case of KS in a human immunodeficiency virus (HIV)-negative 47-year old male with UC after treatment with the α4-β7 integrin inhibitor vedolizumab (VDZ). The patient underwent to colectomy for a medical refractory disease and the histological examination of the surgical specimen showed the typical findings of KS together with the HHV-8 positivity. The patient achieved a good health status, without any sign of disease recurrence.\n\nConclusions\nIn the present case, we can assume that VDZ may have promoted the reactivation of a latent HHV-8 infection endowed with oncogenic potentialities and, in turn, the onset of KS. We also briefly reviewed all the cases of KS in HIV-negative patients with inflammatory bowel disease.\n\nKeywords\nUlcerative colitisKaposi’s sarcomaVedolizumabHuman Herpesvirus-8issue-copyright-statement© The Author(s) 2020\n==== Body\nBackground\nKaposi’s sarcoma (KS) is a rare vascular tumor associated with human herpesvirus (HHV)-8 infection [1]. KS lesions typically involve the skin or mucosal surfaces and are characterized by multiple red-purple or brown-black macules, papules, and nodules [2]. Definitive diagnosis requires histologic examination revealing peculiar angio-proliferative features with the typical spindle cell proliferation [1–3]. There are four recognized epidemiologic-clinical types of KS, which are histologically indistinguishable: classic, endemic (African), epidemic (acquired immunedeficiency syndrome-associated) and iatrogenic (immunosuppressive therapy-related) [1]. Iatrogenic KS has been described overall in transplanted patient but has also less frequently been reported in other categories of patients who underwent to long-standing immunosuppressive treatment, such as patients with inflammatory bowel disease including ulcerative colitis (UC) and Crohn’s disease (CD) [2, 3].\n\nCase presentation\nHerein, we report a case of a 47-year-old heterosexual Caucasian man, who was diagnosed with UC in 2010. At the onset, the disease was localized to the entire colon and the patient was initially treated with oral prednisone and then with mesalazine for about 3 years. In 2013, following a severe relapse with partial response to steroids he started infliximab (IFX) at standard dosage (5 mg/Kg) and achieved a clinical and endoscopic remission. IFX was maintained every 8 weeks until July 2017 when it was withdrawn for a progressive loss of response. At September 2017, the patient experienced a disease flare characterized by 5–6 bowel movements/day of liquid and bloody stools and abdominal pain. Partial Mayo index score was 7 (7–9 indicates severe disease). Laboratory exams revealed anemia (hemoglobin 10.3 g/L) and elevated C-reactive protein (18 mg/L, normal value < 5). So, after the exclusion of intestinal infections, the α4-β7 integrin inhibitor vedolizumab (VDZ) was started at the standard dosage of 300 mg (intravenous infusion). VDZ was administered at time 0, 2 and 6 weeks following the standard induction protocol. The patient reported an early clinical benefit and thus received other three administrations every 8 weeks. Nevertheless, he showed a progressive loss of clinical response and consequently VDZ was discontinued. The patient underwent to a colonoscopy in April 2018, which showed a severe pancolitis with deep ulceration, spontaneous bleeding and nodular mucosa particularly in the transverse and in the right colon (Mayo endoscopic score 3) (Fig. 1). Rectal biopsies were taken. Histopathological evaluation of intranuclear cytomegalovirus inclusions resulted negative. Finally, a laparoscopic colectomy with temporary ileostomy was performed. Surprisingly, histological examination of the surgical specimen at level of rectal mucosa and submucosa showed a spindle cells submucosal nodular proliferation suggestive of KS (Fig. 2a-b) and subsequent immunohistochemical staining detected spindle cells stained with HHV-8 (Fig. 3) confirming the diagnosis of colonic KS. HIV serology resulted negative and skin examination and upper digestive tract endoscopy were normal. Four months after the colectomy, the patient underwent to ileal pouch-anal anastomosis surgery. At present, the patient shows an overall good health state without any sign of KS recurrence.\nFig. 1 Endoscopic aspects of the transverse colon before colectomy. There are diffuse mucosal ulcerations and nodules/pseudopolyps\n\nFig. 2 a Histologic examination of the colonic surgical specimen (hematoxylin-eosin 1x): spindle cells submucosal nodular proliferation. b Histologic examination of the colonic surgical specimen (Hematoxylin –eosin 4x): spindle cells-shaped cells forming vascular spaces with red blood cells percolating between them\n\nFig. 3 Spindle cells stained with HHV-8\n\n\n\nDiscussion and conclusions\nImmunosuppression plays a crucial role in KS pathogenesis by stimulating HHV-8 proliferation and, in turn, proto-oncogene expression [1–3]. In most cases, iatrogenic KS appears in kidney-transplanted patients. However, it has also been reported in chronic inflammatory conditions that require immunosuppressive therapies for a long period such as UC [4–20] and CD [21–24]. In this scenario, the anti-TNF-α agents, the anti-integrin agent VDZ and, recently, the anti-interleukin (IL)-12/23 ustekinumab have been added to the IBD therapeutic armamentarium, which already included steroids and the traditional immunosuppressants (i.e., azathioprine, methotrexate, and cyclosporine). All these biologics, as easily predictable, carry out a variable increased risk of opportunistic infection. Overall, 21 cases of KS in HIV-negative patients with IBD are reported. Most of them are adult males with UC refractory to medical therapy, who assumed steroids and/or traditional immunosuppressants at the time of diagnosis and did not show any cutaneous lesions (Table 1). However, in the last years, some cases of KS have been reported in patients treated with IFX and, as far as we know, the present case is the first associated to the administration of the humanized monoclonal antibody VDZ. Indeed, herein we report an HHV-8-associated colonic KS in a patient with UC treated for 8 months with VDZ. Although we cannot rule out the role of previous treatments with steroids and especially with IFX to which the patient had previously undergone in promote the reactivation of HHV-8.\nTable 1 Characteristics of HIV-negative patients with inflammatory bowel disease (IBD) and intestinal Kaposi’s sarcoma (KS)\n\nAuthor (References)\tSex\tAge yrs\tType of IBD\tDisease duration yrs\tImmuno-suppressive therapy\tHHV-8 in colon\tSkin involvement\tColectomy or small bowel resection\t\nPioche M [11]\tM\t49\tUC\t2\tCS/AZA/CYCL/IFX\t+\t–\t+\t\nRodriquez-Pelaez M [13]\tM\t65\tUC\t15\tCS/MTX\t+\t+\t+\t\nHerculano R [15]\tM\t63\tUC\t< 1\tCS\t+\t–\t–\t\nKumar V [16]\tM\t70\tUC\t4\tCS/IFX\n\n(1 infusion)\n\n\t+\t–\t+\t\nHamzaoui L [14]\tM\t30\tUC\t2\tCS/AZA/IFX\t+\t–\t+\t\nBursics A [8]\tM\t49\tUC\t5\tCS\t–\t+\t+\t\nDuh E [17]\tM\t48\tUC\t25\tCS/AZA\t+\t–\t+\t\nCarmo J [18]\tM\t58\tUC\tNA\tCS\tNA\t–\t–\t\nGirelli GM [10]\tM\t43\tUC\t< 1\tCS/CYCL\t+\t–\t+\t\nCetin B [12]\tM\t42\tUC\t13\tCS/AZA\t–\t+\t–\t\nThompson (1989)\tM\t23\tUC\t1\tCS\tNA\t–\t+\t\nSvrcek M [9]\tM\t62\tUC\t30\tCS/AZA\t+\t–\t+\t\nTedesco M [7]\tM\t68\tUC\t8\tCS\tNA\t–\t+\t\nMeltzer SJ [4]\tM\t83\tUC\t< 1\tCS\tNA\t+\t+\t\nPedulla F [5]\tM\t35\tUC\t2\tCS/AZA\tNA\t–\tNA\t\nChtourou L [19]\tM\t53\tUC\t< 1\tCS/AZA\t+\t–\t+\t\nShah N [20]\tM\t49\tUC\tNA\tCS/AZA\t+\t–\t+\t\nKoop HO [21]\t\t\tCD\t\tCS\tNA\t+\t+\t\nPuy-Montbrun T [22]\tF\t36\tCD\tNA\tCS/AZA\tNA\t–\t–\t\nCohen RL [23]\tF\t67\tCD\t25\tCS\tNA\t–\t+\t\nWindon AL [24]\tM\t21\tCD\t1\tCS/IFX\t–\t–\t+\t\nUC ulcerative colitis, CD Crohn’s disease, CS corticosteroids, AZA azathioprine, CYCL cyclosporine, MTX methotrexate, IFX infliximab, VDZ vedolizumab, HHV-8 human herpes virus-8, NA not available\n\n\n\nVDZ selectively targets the α4-β7 integrin that binds to mucosal addressin-cell adhesion molecule-1 (MadCAM-1) to mediate T cell homing to the lamina propria of the small intestine [25, 26]. VDZ has been approved for the treatment of moderately to severely active UC and CD in adults who failed to respond to at least one conventional drug. Differently from the other available anti-integrin agent Natalizumab (approved in the United States and Europe as monotherapy for multiple sclerosis and only available through a specific risk-minimization program), VDZ selectively acts at intestinal level in order to avoid the risk of progressive multifocal leukoencephalopathy (PME) that due to the reactivation of JC polyomavirus (JCV) [27]. A recent systematic review on VDZ safety profile included data not only from registration studies but also from real life experiences and concluded that overall data are insufficient to draw definitive conclusions about the risk of malignancy linked to VDZ. Indeed, a reduction in immuno-surveillance, as a consequence of leucocyte trafficking inhibition, represents a theoretical concern for gastrointestinal malignancies [26]. In the future, we will definitely assess an increasing number of IBD patients treated in sequence with different biological and immunosuppressive drugs (as in this case-report). Thus, the number of neoplasms, such as KS, linked to a state of immunosuppression that allows a reactivation of latent oncogenic viruses together with a reduced local immuno-surveillance will probably become a more frequent problem. Luckily, all cases of KS occurred in HIV-negative IBD patients, resolved with the discontinuation of immunosuppressive therapy and with colectomy or resection of the affected intestinal tract. In conclusion, this and the other cases described should alert clinicians regarding the possibility of the occurrence of colonic KS in patients with IBD (particularly UC) refractory to medical therapy and who have been treated for a long-time with several immunosuppressive and biological drugs. For the first time we described a case of VDZ-associated colonic KS. VDZ thanks to its specificity of action at the intestinal level may cause the reactivation of latent HHV-8 infection with a consequent initiation of the oncogenic processes that can lead to the onset of KS. Unfortunately, at the moment we do not have reliable tests to identify patients at increased risk of developing KS (there are few data on the usefulness of a specific PCR for the detection of HHV-8 in the blood) that should be recommended for early surgery rather than other rescue therapy. Therefore, further studies are necessary to identify early risk markers of intestinal KS. In the meantime, careful monitoring is required.\n\nAbbreviations\nKSKaposi’s sarcoma\n\nHHVHuman herpesvirus\n\nUCUlcerative colitis\n\nHIVHuman immunodeficiency virus\n\nCDCrohn’s disease\n\nIFXInfliximab\n\nMadCAM-1Mucosal addressin-cell adhesion molecule-1\n\nPMEProgressive multifocal leukoencephalopathy\n\nJCVJC polyomavirus\n\nPublisher’s Note\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n\nAcknowledgements\nNot applicable.\n\nAuthors’ contributions\nVP and AP recruited the patient and wrote up the first draft of the manuscript, MCG evaluated the histological samples, LRL revised the overall data and prepared the final draft of the manuscript. All authors read and approved the final manuscript.\n\nFunding\nNo specific funding has been received for this publication.\n\nAvailability of data and materials\nAll data generated or analyzed in this manuscript are included in this published article.\n\nEthics approval and consent to participate\nNo formal ethics approval was needed. Ethics committee of Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy, ruled that no formal ethics approval was required in this particular case.\n\nConsent for publication\nWritten informed consent was obtained from the patient for publication of this case report and any accompanying images.\n\nCompeting interests\nThe authors declare that they have no competing interests.\n==== Refs\nReferences\n1. Antman K Chang Y Kaposi's sarcoma N Engl J Med 2000 342 1027 1038 10.1056/NEJM200004063421407 10749966 \n2. De Paoli P Carbone A Kaposi’s sarcoma herpesvirus: twenty years after its discovery Eur Rev Med Pharmacol Sci 2016 20 1288 1294 27097948 \n3. Ruocco E Ruocco V Tornesello ML Gambardella A Wolf R Buonaguro FM Kaposi’s sarcoma: etiology and pathogenesis, inducing factors, causal associations, and treatments: facts and controversies Clin Dermatol 2013 31 413 422 10.1016/j.clindermatol.2013.01.008 23806158 \n4. Meltzer SJ Rotterdam HZ Korelitz BI Kaposi’s sarcoma occurring in association with ulcerative colitis Am J Gastroenterol 1987 82 378 381 3565348 \n5. Pedulla F Sisteron O Chevallier P Piche T Saint-Paul MC Bruneton JN Kaposi’s sarcoma confined to the colorectum: a case report Clin Imaging 2004 28 33 35 10.1016/S0899-7071(03)00075-5 14996445 \n6. Thompson GB Pemberton JH Morris S Bustamante MA Delong B Carpenter HA Wright AJ Kaposi’s sarcoma of the colon in a young hiv-negative man with chronic ulcerative colitis. Report of a case Dis Colon Rectum 1989 32 73 76 10.1007/BF02554731 2910664 \n7. Tedesco M Benevolo M Frezza F Mancini R Carone MD Mottolese M Cosimelli M Colorectal Kaposi’s sarcoma in an hiv-negative male in association with ulcerative rectocolitis: a case report Anticancer Res 1999 19 3045 3048 10652590 \n8. Bursics A Morvay K Abraham K Marschalkó M Kardos M Járay B Nagy K HHV-8 positive, HIV negative disseminated Kaposi’s sarcoma complicating steroid dependent ulcerative colitis: a successfully treated case Gut 2005 54 1049 1050 10.1136/gut.2005.069500 15951561 \n9. Svrcek M Tiret E Bennis M Guyot P Flejou JF KSHV/HHV8-associated intestinal Kaposi’s sarcoma in patient with ulcerative colitis receiving immunosuppressive drugs: report of a case Dis Colon Rectum 2009 52 154 158 10.1007/DCR.0b013e318197217f 19273971 \n10. Girelli CM Serio G Rocca E Rocca F Refractory ulcerative colitis and iatrogenic colorectal Kaposi’s sarcoma Dig Liver Dis 2009 41 170 174 10.1016/j.dld.2007.10.007 18054849 \n11. Rodriguez-Pelaez M Fernandez-Garcia MS Gutierrez-Corral N de Francisco R Riestra S García-Pravia C Rodríguez JI Rodrigo L Kaposi’s sarcoma: an opportunistic infection by human herpesvirus-8 in ulcerative colitis J Crohns Colitis 2010 4 586 590 10.1016/j.crohns.2010.03.006 21122564 \n12. Cetin B Buyukberber S Yilmaz IB Yildiz R Coşkun U Beneklı M Kaposi’s sarcoma in patients with ulcerative colitis receiving immunosuppressive drugs: report of a case Turk J Gastroenterol 2011 22 621 625 10.4318/tjg.2011.0280 22287409 \n13. Pioche M Boschetti G Cotte E Graber I Moussata D François Y Berger F Nancey S Flourie B Human herpesvirus 8-associated colorectal Kaposi’s sarcoma occurring in a drug-induced immunocompromised patient with refractory ulcerative colitis: report of a new case and review of the literature Inflamm Bowel Dis 2013 19 E12 E15 10.1002/ibd.21921 22344863 \n14. Hamzaoui L Kilani H Bouassida M Mahmoudi M Chalbi E Siai K Ezzine H Touinsi H Azzouz MM Sassi S Iatrogenic colorectal Kaposi sarcoma complicating a refractory ulcerative colitis in a human immunodeficiency negative-virus patient Pan Afr Med J 2013 15 154 10.11604/pamj.2013.15.154.2988 24396560 \n15. Herculano R Barreiro P Hann A Chapim I Bispo M Santos S Monteiro L Chagas C Matos L Drug-induced colonic Kaposi’s sarcoma in a HIV-negative patient with ulcerative colitis: a case report and review of the literature Int J Color Dis 2014 29 1441 1442 10.1007/s00384-014-1912-0 \n16. Kumar V Soni P Garg M Abduraimova M Harris J Kaposi sarcoma mimicking acute flare of ulcerative colitis J Investig Med High Impact Case Rep 2017 5 2324709617713510 28638838 \n17. Duh E Fine S Human herpesvirus-8 positive iatrogenic Kaposi’s sarcoma in the setting of refractory ulcerative colitis World J Clin Cases 2017 5 423 427 10.12998/wjcc.v5.i12.423 29291200 \n18. Carmo J Marques SC Bispo M Pinto D Chagas C Clinical and endoscopic features of gastrointestinal Kaposi sarcoma: a single-center portuguese experience over the last decade GE Port J Gastroenterol 2017 24 219 226 10.1159/000461592 29255756 \n19. Chtourou L Ayedi L Rejab H Boudabous M Mnif L Grati A Boudaouara T Mzali R Amouri A Tahri N Iatrogenic colorectal Kaposi’s sarcoma complicating a refractory ulcerative colitis in a human immunodeficiency negative-virus patient Pathologica 2017 109 371 374 29449725 \n20. Shah N Lidofsky S Laskiewicz L Colorectal Kaposi sarcoma in an immunosuppressed ulcerative colitis patient J Gastrointest Surg 2018 22 1301 1302 10.1007/s11605-017-3649-x 29247422 \n21. Koop HO Holodniy M List AF Fulminant Kaposi’s sarcoma complicating long-term corticosteroid therapy Am J Med 1987 83 87 89 10.1016/0002-9343(87)90916-8 \n22. Puy-Montbrun T Pigot F Vuong PN Ganansia R Denis J Kaposi’s sarcoma of the colon in a young HIV-negative woman with Crohn's disease Dig Dis Sci 1991 36 528 531 10.1007/BF01298888 2007372 \n23. Cohen RL Tepper RE Urmacher C Katz S Kaposi’s sarcoma and cytomegaloviral ileocolitis complicating long-standing Crohn’s disease in an HIV-negative patient Am J Gastroenterol 2001 96 3028 3031 10.1111/j.1572-0241.2001.04676.x 11693345 \n24. Windon AL Shroff SG Iatrogenic Kaposi’s sarcoma in an HIV-negative young male with Crohn’s disease and IgA nephropathy: a case report and brief review of the literature Int J Surg Pathol 2018 26 276 282 10.1177/1066896917736610 29169276 \n25. Colombel JF Sands BE Rutgeerts P Sandborn W Danese S D'Haens G Panaccione R Loftus EV Jr Sankoh S Fox I Parikh A Milch C Abhyankar B Feagan BG The safety of vedolizumab for ulcerative colitis and Crohn’s disease Gut 2017 66 839 851 10.1136/gutjnl-2015-311079 26893500 \n26. Bye WA Jairath V Travis SPL Systematic review: the safety of vedolizumab for the treatment of inflammatory bowel disease Aliment Pharmacol Ther 2017 46 3 15 10.1111/apt.14075 28449273 \n27. Redelman-Sidi G Michielin O Cervera C Ribi C Aguado JM Fernández-Ruiz M Manuel O ESCMID study group for infections in compromised hosts (ESGICH) consensus document on the safety of targeted and biological therapies: an infectious diseases perspective (immune checkpoint inhibitors, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors) Clin Microbiol Infect 2018 24 Suppl 2 S95 S107 10.1016/j.cmi.2018.01.030 29427804\n\n", "fulltext_license": "CC BY", "issn_linking": "1471-230X", "issue": "20(1)", "journal": "BMC gastroenterology", "keywords": "Human Herpesvirus-8; Kaposi’s sarcoma; Ulcerative colitis; Vedolizumab", "medline_ta": "BMC Gastroenterol", "mesh_terms": "D061067:Antibodies, Monoclonal, Humanized; D003082:Colectomy; D003093:Colitis, Ulcerative; D003110:Colonic Neoplasms; D005765:Gastrointestinal Agents; D019288:Herpesvirus 8, Human; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged; D012514:Sarcoma, Kaposi", "nlm_unique_id": "100968547", "other_id": null, "pages": "76", "pmc": null, "pmid": "32204698", "pubdate": "2020-03-24", "publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review", "references": "10749966;28449273;3565348;24396560;29247422;11693345;2910664;15951561;29427804;29255756;29449725;29291200;26893500;29169276;21122564;22287409;2823601;18054849;28638838;22344863;10652590;24898591;27097948;19273971;23806158;14996445;2007372", "title": "Human herpesvirus 8-associated colonic Kaposi's sarcoma during vedolizumab treatment in ulcerative colitis: a case report and review of the literature.", "title_normalized": "human herpesvirus 8 associated colonic kaposi s sarcoma during vedolizumab treatment in ulcerative colitis a case report and review of the literature" }

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HUMAN HERPESVIRUS 8?ASSOCIATED COLONIC KAPOSI^S SARCOMA DURING VEDOLIZUMAB TREATMENT IN ULCERATIVE COLITIS: A CASE REPORT AND REVIEW OF THE LITERATURE. BMC GASTROENTEROLOGY. 2020?20(1):76", "literaturereference_normalized": "human herpesvirus 8 associated colonic kaposi s sarcoma during vedolizumab treatment in ulcerative colitis a case report and review of the literature", "qualification": "1", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20200827", "receivedate": "20200404", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17625302, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201102" } ]

{ "abstract": "Patients with congenital central hypoventilation syndrome (CCHS) develop alveolar hypoventilation resulting from a failure of central ventilatory control. Late-onset CCHS (LO-CCHS), which may be precipitated by severe respiratory infection or exposure to sedatives or general anesthesia, presents after the neonatal period. Since CCHS patients require lifelong mechanical-assisted ventilation, in western countries, diaphragm pacing is used to provide adequate alveolar ventilation and oxygenation during rest and daily activities. The main anesthesia-related concern regarding CCHS is postoperative respiratory failure or apnea, and anesthetic agents should be minimized to avoid further respiratory depression after surgery. A 5-year-old girl with LO-CCHS was referred to our hospital for implantation of a phrenic nerve stimulator for diaphragm pacing. Respiratory infection triggered the need for permanent nocturnal ventilator support at age 3 years and tracheotomy was performed at age 4 years. Repeated self-dislodgement of the ventilator tube led to hypoxic ischemic encephalopathy. The patient was thought to require mechanical ventilation under minimum sedation and pain management during the early postoperative period. The co-administration of dexmedetomidine and morphine provided effective conscious sedation with protection of the surgical site and without adverse events. She was discharged from the intensive care unit with a home ventilator at 3 days post-operation.", "affiliations": "1Department of Anesthesiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 Japan.;1Department of Anesthesiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 Japan.;2Department of Neurosurgery, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 Japan.;1Department of Anesthesiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 Japan.;2Department of Neurosurgery, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 Japan.;1Department of Anesthesiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 Japan.", "authors": "Hirooka|Keiko|K|;Kamata|Kotoe|K|0000-0002-7224-5993;Horisawa|Shiro|S|;Nomura|Minoru|M|;Taira|Takaomi|T|;Ozaki|Makoto|M|", "chemical_list": null, "country": "Germany", "delete": false, "doi": "10.1186/s40981-017-0117-2", "fulltext": "\n==== Front\nJA Clin RepJA Clin RepJA Clinical Reports2363-9024Springer Berlin Heidelberg Berlin/Heidelberg 2945709011710.1186/s40981-017-0117-2Case ReportConscious sedation with dexmedetomidine for implantation of a phrenic nerve stimulator in a pediatric case of late-onset congenital central hypoventilation syndrome Hirooka Keiko [email protected] 1http://orcid.org/0000-0002-7224-5993Kamata Kotoe [email protected] 1Horisawa Shiro [email protected] 2Nomura Minoru [email protected] 1Taira Takaomi [email protected] 2Ozaki Makoto [email protected] 11 0000 0001 0720 6587grid.410818.4Department of Anesthesiology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 Japan 2 0000 0001 0720 6587grid.410818.4Department of Neurosurgery, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 Japan 31 8 2017 31 8 2017 12 2017 3 4611 8 2017 24 8 2017 © The Author(s) 2017\nOpen AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Patients with congenital central hypoventilation syndrome (CCHS) develop alveolar hypoventilation resulting from a failure of central ventilatory control. Late-onset CCHS (LO-CCHS), which may be precipitated by severe respiratory infection or exposure to sedatives or general anesthesia, presents after the neonatal period. Since CCHS patients require lifelong mechanical-assisted ventilation, in western countries, diaphragm pacing is used to provide adequate alveolar ventilation and oxygenation during rest and daily activities. The main anesthesia-related concern regarding CCHS is postoperative respiratory failure or apnea, and anesthetic agents should be minimized to avoid further respiratory depression after surgery. A 5-year-old girl with LO-CCHS was referred to our hospital for implantation of a phrenic nerve stimulator for diaphragm pacing. Respiratory infection triggered the need for permanent nocturnal ventilator support at age 3 years and tracheotomy was performed at age 4 years. Repeated self-dislodgement of the ventilator tube led to hypoxic ischemic encephalopathy. The patient was thought to require mechanical ventilation under minimum sedation and pain management during the early postoperative period. The co-administration of dexmedetomidine and morphine provided effective conscious sedation with protection of the surgical site and without adverse events. She was discharged from the intensive care unit with a home ventilator at 3 days post-operation.\n\nKeywords\nCongenital central hypoventilation syndromeDiaphragm pacingPostoperative sedationDexmedetomidineissue-copyright-statement© The Author(s) 2017\n==== Body\nBackground\nCongenital central hypoventilation syndrome (CCHS) is characterized by the lack of adequate autonomic control of respiration with decreased sensitivity to hypercapnia and hypoxia in the absence of neuromuscular or lung disease or an identifiable brainstem lesion [1]. In the latest Japanese survey, 22 of 37 CCHS patients survived without further disability, 8 survived with disability, and 7 died [2]. However, there are no data on the prevalence of late-onset CCHS (LO-CCHS), which refers to patients who are diagnosed with CCHS after 28 days of age [3]. Since respiratory dysfunction is pathognomonic of CCHS, when such patients must undergo surgery, relatively short-acting sedatives are preferred to reduce the incidence of postoperative apnea. Recently, CCHS has been recognized as a variant of generalized autonomic nervous system dysregulation because complications extend to various organ systems [4]. These presentations involve cardiac rhythm disturbance, transient asystole, decreased heart rate variability, diminished cardiovascular compensatory mechanisms, altered pain perception, and abnormal thermoregulation [5]. In our case, the presence of sympathetic nervous system tumor represented further clinical evidence of generalized autonomic nervous system dysregulation; 5–10% of CCHS cases have a neurocristopathy [6]. Central nervous system disorders in this population, including neurodevelopmental defects, may affect the decision-making process regarding anesthesia.\n\nPatients with CCHS require lifetime ventilation support to avoid pulmonary hypertension and cor pulmonale, which results from a prolonged period of hypoxia. Diaphragm pacing, as an alternative to a mechanical ventilator that can eliminate the need for positive pressure ventilation (PPV), has been shown to improve quality of life and extend survival in patients with advanced respiratory muscle weakness [7]. Nevertheless, this surgical treatment has seen only limited use in eastern Asian countries, including Japan; in fact, a device that is specially made for phrenic nerve stimulation can only be obtained by private import. There has been only one report of a CCHS patient who underwent diaphragmatic pacing in Japan, but the patient details were not provided [2]. As Taira et al. proposed, diaphragm pacing by stimulation of the phrenic nerve with a spinal cord stimulator could be a substitute for such a device [8].\n\nIn this report, we present a pediatric case of LO-CCHS who underwent implantation of a phrenic nerve stimulator for diaphragm pacing. Due to her history of repeated self-dislodgement of a ventilator tube, which was associated with her mental retardation, postoperative sedation that protected the surgical site without severe respiratory depression was considered to be required during the early postoperative period.\n\nCase presentation\nPre-operative course\nA 5-year-old, 17-kg girl, who had been diagnosed elsewhere as LO-CCHS and who had required nocturnal PPV through a tracheostomy since the age of 4 years, was referred to our hospital for implantation of a phrenic nerve stimulator for diaphragm pacing. She was born at 40-week gestation and weighed 3170 g without fetal distress. She did not show any developmental disability until the age of 2 years, when irregular breathing during sleep was recognized. Behavioral disorders, such as self-mutilation, also became evident. She was diagnosed with complex sleep apnea syndrome and noninvasive bi-level positive airway pressure was introduced. Repeated respiratory infection, which frequently caused hypoventilation while she was asleep, triggered the need for permanent nocturnal PPV. Self-dislodgement of the ventilator tube associated with her mental retardation led to hypoxic encephalopathy. Tracheotomy was performed at age 4 years for chronic home mechanical ventilation. Though progressive hypoventilation extended into the daytime, the patient refused ventilator support and managed disconnection of the respiratory circuit when she was awake. Finally, the other institution gave a diagnosis of LO-CCHS. There was no response to respiratory stimulants, including theophylline and progesterone.\n\nAt the initial evaluation at our hospital, pure oxygen (0.12–0.25 L/min) was supplied through a speech cannula during the daytime if it was acceptable to her. PPV was managed during the nighttime with a Trilogy 200 Plus™ (Philips Respironics GK, Tokyo, Japan) in synchronized intermittent mandatory ventilation (SIMV) mode as follows: respiration rate of 20 breaths/min, positive end-expiratory pressure (PEEP) of 5 cm H2O, tidal volume of 160 mL, and inspiratory phase time of 0.8 s. Her peripheral venous blood gases on room air without ventilator support were pH 7.1, PO2 24 mmHg, PCO2 116 mmHg, and HCO3 41.9 mmol/L. She showed neither carbon dioxide narcosis nor overt respiratory distress even though her EtCO2 level was 60–85 mmHg. Preoperative computed tomography revealed a posterior mediastinal tumor, which was suspected to have originated from the sympathetic nervous system, such as neuroblastoma or ganglioneuroma. Because this tumor did not compress the pulmonary artery or trachea, and thus was not considered to have affected her hemodynamics or respiratory status, further investigation has not been performed before operation. Echocardiography confirmed that her cardiac function was preserved. Additionally, lactic acidosis and 3-hydroxy-3-methylglutaric acidemia, which suggest potential mitochondrial dysfunction, were observed at a preoperative examination, but definitive diagnoses were not obtained. After approval by the ethics committee at our institution, a multidisciplinary conference was held to discuss the perioperative strategy for our patient. Based on a consideration of her mental status, mechanical ventilation under minimum sedation during the early postoperative period was deemed to be required to stabilize the surgical site. She was classified as American Society of Anesthesiologists Physical Status Class 3.\n\nAnesthesia\nNo premedication was given. On the day of the operation, the patient received her usual morning doses of valproic acid (200 mg) and levocarnitine (100 mg). She arrived at the operating room in a wheelchair without a ventilator. The standard American Society of Anesthesiologists monitoring devices were attached, and inhalation was induced via the tracheostomy using an increasing concentration of sevoflurane. Atropine (0.3 mg), midazolam (1 mg), fentanyl (30 μg), and rocuronium (20 mg) were given. The tracheotomy tube was then replaced by an endotracheal tube to facilitate surgical intervention. General anesthesia was maintained with sevoflurane and remifentanil. Acetate Ringer solution containing 5% dextrose was prepared to prevent hypoglycemia and lactic acidosis; the blood glucose level was 181–192 mg/dL, and the lactate level was 1.3–3.5 mmol/L. Volume control ventilation (VCV) with a tidal volume of 120 mL and a respiratory rate of 14 breaths/min was adopted to achieve an EtCO2 level over 45 mmHg.\n\nThe operative procedure was based on a previous report of diaphragm pacing by stimulation of the phrenic nerve with a spinal cord stimulator in patients with central hypoventilation syndrome [8]. Linear horizontal skin incisions about 3 cm long were made bilaterally 2 cm rostral to the clavicle, crossing the posterior border of the sternocleidomastoid muscle (SCM). After the dissection of subcutaneous tissue and medial retraction of the SCM, sugammadex (80 mg) was given for phrenic nerve identification. The anterior scalene muscle and the phrenic nerve were identified over the scalene muscle by monopolar electrical stimulation (5 Hz, 0.1-ms pulse width, 1–10 V) with muscle contraction of the diaphragm. The nerve sheath of the phrenic nerve was carefully dissected about 1 cm in length. A quadri-polar stimulating electrode was placed across the phrenic nerve and fixed with sutures to the surrounding connective tissue. Two seconds of phrenic nerve stimulation could induce a tidal volume of about 120 mL. An implanted pulse generator (IPG) (Brio Dual 8; Abbott Laboratories, Chicago, IL, USA) was placed under the fascia of the right abdominal rectus muscle. The generator and electrodes were connected by extension leads via subcutaneous tunnels. Approximately 2 h before the end of surgery, dexmedetomidine infusion was commenced at 6 μg/kg/h, which was changed to 0.7 μg/kg/h after 10 min. Intravenous acetaminophen (600 mg) and infiltration analgesia with a total of 6.8 mL of 0.75% ropivacaine were also given. At the end of anesthesia, the patient did not show any clinical signs of emergence. Dexmedetomidine infusion was decreased to 0.4 μg/kg/h. Blood pressure and heart rate remained within 20% of the baseline level without pharmacological manipulation.\n\nPost-operative course\nThe patient showed body movement in response to verbal stimulation when she arrived in the intensive care unit (ICU). Continuous intravenous infusion of morphine was commenced at 0.1 μg/kg/min. Then, postoperative sedation and pain control were managed by combining dexmedetomidine (0.4–1.0 μg/kg/h) and morphine (0.1–0.5 μg/kg/min) to achieve a score on the Richmond Agitation-Sedation Scale of from −1 to −2. She was initially placed on mechanical ventilation with a Puritan Bennett™ 760 (Medtronic, Minneapolis, MN, USA) in VCV, but this was subsequently changed to SIMV with pressure support mode as follows: inspiratory pressure of 14 cm H2O, PEEP of 4 cm H2O, respiration rate of 10 breaths/min, and pressure support of 6 cm H2O. An arterial blood gas analysis performed with FiO2 at 0.4 on the ventilator showed pH 7.38, PaO2 102 mmHg, PaCO2 66 mmHg, and HCO3 39 mmol/L. Intravenous medications were gradually replaced by phenobarbital and acetaminophen suppositories from postoperative day (POD) 1. Since postoperative pain and hemostasis were confirmed to be well controlled, phrenic nerve stimulation was tried on POD 3. To avoid fatigue of the phrenic nerve and diaphragm, we applied unilateral stimulation (2 s on/4 s off) for 30 min on each side: 3.5 mA to the left phrenic nerve and 3.0 mA to the right phrenic nerve. The level of EtCO2 subsequently decreased from over 80 to 60 mmHg. Because the patient was able to tolerate phrenic nerve stimulation without overt respiratory distress, intravenous morphine was discontinued and a Trilogy 200 Plus™ was reintroduced with her preoperative settings. Following monitoring of the blood concentration of phenobarbital, dexmedetomidine infusion was tapered. On POD 3, dexmedetomidine was terminated and the patient was discharged from ICU with a home ventilator for pacemaker adjustment and management [Fig. 1]. Since it gradually became impossible to achieve sufficient ventilation by left phrenic nerve stimulation, probably due to stimulator detachment, the output strength of the IPG for right phrenic nerve stimulation and the duration of stimulation were managed to achieve a target EtCO2 level of 50–60 mmHg. On POD 17, the daily dose of suppository phenobarbital was increased from 60 to 75 mg to attenuate nociception for pacemaker adaptation. Since phrenic nerve stimulation provided substantially physiological sleep, the patient showed an increase in appetite. Her mother also showed reduced levels of physical and psychological stress. On POD 19, the patient was discharged from the hospital with a final setting for stimulation of the right phrenic nerve of 2.5 mA. Because the cost of the device is not reimbursed by the health care insurance system in Japan, all medical expenses were covered by the patient’s family.Fig. 1 Post-operative course. Post-operative course of her medication and respiratory support\n\n\n\n\nDiscussion\nThis case highlights that the perioperative management of CCHS must be modified based on coexisting diseases, since CCHS includes several specific issues in various organ systems. Due to the autonomic dysregulation caused by CCHS itself and potential mitochondrial dysfunction, we used sevoflurane instead of propofol and gave a lactate-free infusion containing 5% dextrose under blood glucose monitoring to avoid perioperative hypoglycemia and lactic acidosis [9, 10].\n\nThere are no guidelines or randomized trials to identify the optimal anesthetic approach in CCHS. According to the latest systematic review by Basu et al., there have been few reports on the use of anesthesia in patients with established CCHS [1]. In fact, little is known even about the use of muscle relaxants and their impact on postoperative apnea. It is recommended that, if neuromuscular blockade is considered to facilitate surgical intervention, neuromuscular blockade should be monitored and sugammadex is needed to avoid residual blockade [1]. In the present case, the tracheostomy tube was replaced by orotracheal intubation because surgical intervention that reaches the cervical region may cause accidental extubation of the former. Moreover, early extubation was not required as postoperative respiratory support was planned in advance. In addition, relatively short-acting anesthetic agents were preferred to minimize postoperative respiratory depression. Drugs that directly decrease blood pressure and heart rate are not recommended since CCHS is a multisystem disorder that causes autonomic instability, resulting in possible bradycardia and transient asystole [9].\n\nDexmedetomidine, an alpha-2 agonist which has a sedative effect by reducing the activity in the locus coeruleus in the central nervous system, has been used as a perioperative adjunct drug to reduce complications such as agitation, delirium, shivering, and pain in pediatric patients [11]. Although minimal depression of the respiratory system while maintaining a patent airway is a considerable advantage of dexmedetomidine, there have been few reports of its use in CCHS. Kameyama et al. described a 2-year-old girl with CCHS who required postoperative mechanical ventilation due to poor intraoperative oxygenation. The co-administration of dexmedetomidine and midazolam was selected to avoid continuous sedation. However, they did not suspend sedative infusions because the patient became agitated [12]. This suggests that a combination of dexmedetomidine and midazolam is insufficient to attenuate nociception caused by artificial ventilation. Thus, in our case, low-dose intravenous morphine was supplemented with dexmedetomidine to attenuate the levels of pain and nociception. Morphine is not a short-acting agent and potentially causes respiratory depression if an overdose is given, but we estimated that several days would be required for pacemaker adjustment and adaptation. Therefore, we chose low-dose intravenous morphine as a reliable analgesia. It has been reported that opioid-free continuous paravertebral block provided appropriate analgesia with less respiratory depression [13]. However, the surgical site of our patient extended to the abdomen, and her history of repeated self-dislodgement of the ventilator tube suggested the possibility of accidental catheter removal. The mechanism of the analgesic effect of dexmedetomidine is still unclear and may be partly due to its function as an anxiolytic. The ability to reduce opioid consumption through the use of dexmedetomidine is an advantage for patients with CCHS. Our patient seemed to be well-sedated with a combination of dexmedetomidine (1.0 μg/kg/h) and morphine (0.1 μg/kg/min), but she was easily aroused and responded to nursing intervention. When dexmedetomidine was decreased to 0.7 μg/kg/h, spontaneous ventilation was regained. Dexmedetomidine has not been extensively studied in terms of its pharmacologic and physiologic effects in a pediatric population [11]. Therefore, we initiated dexmedetomidine infusion beginning in the intraoperative period under strict observation and monitoring by anesthesiologists. We observed neither cardiac instability caused by loading infusion nor inadequate sedation during patient transfer.\n\nConclusions\nPatients with CCHS can have systemic comorbidities, and the obvious concern to anesthesiologists is the defective autonomic control of ventilation, which may cause postoperative complications. In the present case, a combination of intravenous dexmedetomidine and morphine provided effective conscious sedation with protection of the surgical site even when CCHS was the known diagnosis.\n\nAbbreviations\nCCHSCongenital central hypoventilation syndrome\n\nICUIntensive care unit\n\nIPGImplanted pulse generator\n\nLO-CCHSLate-onset congenital central hypoventilation syndrome\n\nPEEPPositive end-expiratory pressure\n\nPODPostoperative day\n\nPPVPositive pressure ventilation\n\nSCMSternocleidomastoid muscle\n\nSIMVSynchronized intermittent mandatory ventilation\n\nVCVVolume control ventilation\n\nAcknowledgements\nThis report was previously presented as a poster presentation at the IARS 2017 Annual Meeting and International Science Symposium in Washington, D.C.\n\nAuthors’ informations\nKH is a senior resident in the Department of Anesthesiology at Tokyo Women’s Medical University. KK is an assistant professor in the Department of Anesthesiology at Tokyo Women’s Medical University. SH is an assistant professor in the Department of Neurosurgery at Tokyo Women’s Medical University. MN is a professor in the Department of Anesthesiology at Tokyo Women’s Medical University. TT is a professor in the Department of Neurosurgery at Tokyo Women’s Medical University. MO is a professor in the Department of Anesthesiology at Tokyo Women’s Medical University.\n\nAuthors’ contributions\nKH managed the anesthetic care of the patient and prepared the manuscript. KK managed the anesthetic care of the patient, prepared the manuscript, and obtained written parental consent. SH coordinated the patient care and helped to draft the manuscript. MN helped to draft the manuscript. TT managed the surgical care of the patient and provided valuable expertise in writing the manuscript. MO coordinated the patient care and helped to draft the manuscript. All authors have read and approved the final version of the manuscript.\n\nConsent for publication\nWritten parental informed consent was obtained for publication of this case report. A copy of the written consent is available for review from the Editor-in-Chief of this journal.\n\nCompeting interests\nThe authors declare that they have no competing interests. The present report was supported solely by hospital and/or departmental sources.\n\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n==== Refs\nReferences\n1. Basu SM Chung FF AbdelHakim SF Wong J Anesthetic considerations for patients with congenital central hypoventilation syndrome: a systematic review of the literature Anesth Analg 2017 124 169 178 10.1213/ANE.0000000000001470 27918326 \n2. Hasegawa H Kawasaki K Inoue H Umehara M Takase M Japanese Society of Pediatric Pulmonology Working Group Epidemiologic survey of patients with congenital central hypoventilation syndrome in Japan Pediatr Int 2012 54 123 126 10.1111/j.1442-200X.2011.03484.x 21958325 \n3. Bittencourt LR Pedrazzoli M Yagihara F Late-onset, insidious course and invasive treatment of congenital central hypoventilation syndrome in a case with the Phox2B mutation: case report Sleep Breath 2012 16 951 955 10.1007/s11325-011-0614-x 22102181 \n4. Anonymous. Idiopathic congenital central hypoventilation syndrome: diagnosis and management. American Thoracic Society. Am J Respir Crit Care Med. 1999; 160: 368-373.\n5. Strauser LM Helikson MA Tobias JD Anesthetic care for the child with congenital central alveolar hypoventilation syndrome (Ondine’s curse) J Clin Anesth 1999 11 431 437 10.1016/S0952-8180(99)00073-2 10526817 \n6. Weese-Mayer DE Rand CM Berry-Kravis EM Congenital central hypoventilation syndrome from past to future: model for translational and transitional autonomic medicine Pediatr Pulmonol 2009 44 521 535 10.1002/ppul.21045 19422034 \n7. DiMarco AF Onders RP Kowalski KE Miller ME Ferek S Mortimer JT Phrenic nerve pacing in a tetraplegic patient via intramuscular diaphragm electrode Am J Respir Crit Care Med 2002 166 12 Pt 1 1604 1606 10.1164/rccm.200203-175CR 12471076 \n8. Taira T Takeda N Itoh K Oikawa A Hori T Phrenic nerve stimulation for diaphragm pacing with a spinal cord stimulator: technical note Surg Neurol 2003 59 128 132 10.1016/S0090-3019(02)00997-7 12648917 \n9. Sochala C Deenen D Ville A Govaerts MJ Heart block following propofol in a child Paediatr Anaesth 1999 9 349 351 10.1046/j.1460-9592.1999.00373.x 10411774 \n10. Saettele AK Sharma A Murray DJ Case scenario: hypotonia in infancy: anesthetic dilemma Anesthesiology 2013 119 443 446 10.1097/ALN.0b013e31829c2dc8 23845921 \n11. Mason KP Lerman J Dexmedetomidine in children: current knowledge and future applications Anesth Analg 2011 113 1129 1142 10.1213/ANE.0b013e31822b8629 21821507 \n12. Kameyama Y Wagatsuma T Nakamura M Kurosawa S Saito K Hoshi K A case of congenital central hypoventilation syndrome J Anesth 2012 26 922 924 10.1007/s00540-012-1451-1 22790414 \n13. Visser WA Fanyar Z Luiten EJ Thoracic paravertebral block hypoventilation syndrome (Ondine’s Curse) J Clin Anesth 2013 25 604 605 10.1016/j.jclinane.2013.05.012 23994702\n\n", "fulltext_license": "CC BY", "issn_linking": "2363-9024", "issue": "3(1)", "journal": "JA clinical reports", "keywords": "Congenital central hypoventilation syndrome; Dexmedetomidine; Diaphragm pacing; Postoperative sedation", "medline_ta": "JA Clin Rep", "mesh_terms": null, "nlm_unique_id": "101682121", "other_id": null, "pages": "46", "pmc": null, "pmid": "29457090", "pubdate": "2017", "publication_types": "D016428:Journal Article", "references": "12471076;27918326;10411774;22790414;19422034;23994702;12648917;21821507;10526817;10390427;21958325;23845921;22102181", "title": "Conscious sedation with dexmedetomidine for implantation of a phrenic nerve stimulator in a pediatric case of late-onset congenital central hypoventilation syndrome.", "title_normalized": "conscious sedation with dexmedetomidine for implantation of a phrenic nerve stimulator in a pediatric case of late onset congenital central hypoventilation syndrome" }

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CONSCIOUS SEDATION WITH DEXMEDETOMIDINE FOR IMPLANTATION OF A PHRENIC NERVE STIMULATOR IN A PEDIATRIC CASE OF LATE-ONSET CONGENITAL CENTRAL HYPOVENTILATION SYNDROME. 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