Clinical Practice Guidelines for Pancreatic Cancer was first published in 2006 by the Japan Pancreas Society, and revised in 2009, 2013, 2016, and 2019. In July 2022, Clinical Practice Guidelines for Pancreatic Cancer was newly revised in Japanese.For this revision, we developed an entirely new guideline according to the Minds Manual for Guideline Development 2020, which includes the concepts of GRADE—Grading Recommendations Assessment, Development, and Evaluation, to enable a better understanding of the current guidelines. Patients and the public were actively involved in both the development and implementation of the guideline.The guideline includes algorithms for diagnosis, treatment, chemotherapy, and precision medicine of pancreatic cancer, and addresses 7 subjects: diagnosis, surgical therapy, adjuvant therapy, radiation therapy, chemotherapy, stent therapy, and supportive & palliative medical care. It includes 73 clinical questions and 112 statements. The statements correspond to the clinical questions, evidence levels, recommendation strengths, and agreement rates.This guideline represents the most standard clinical and practical management guideline available until date in Japan. This is the English synopsis of the Clinical Practice Guidelines for Pancreatic Cancer 2022 in Japanese, and is an attempt to disseminate the Japanese guideline worldwide to introduce the Japanese approach to the clinical management of pancreatic cancer. The Clinical Practice Guidelines for Pancreatic Cancer based on Evidence-Based Medicine 2006  was firsThe composition of the committee for Revision of the Clinical Guidelines for Pancreatic Cancer in the JPS was as follows: Takuji Okusaka, Chairman; Masafumi Nakamura, Vice-Chairman; Masahiro Yoshida, Masayuki Kitano, Yoshinori Ito, Nobumasa Mizuno, Keiji Hanada, Masato Ozaka, and Chigusa Morizane, chiefs of the various groups; and 42 other specialists , 4 representatives of patients and/or members of the public were members of the committee for revision of the guidelines Fig. . In addiThe committee members proposed the guideline, which includes algorithms for the diagnosis Fig. , treatmeWe used the Minds manual, following the GRADE system approach. The overall quality of the body of evidence across gross studies for each important outcome was assessed. The evidence level was graded on a scale of A (strongest) to D (least strong). Each committee member specialized in the topic of each CQ prepared a draft of the statement, the evidence level, and the recommended strength. Committee members added some references from their own searches and performed meta-analyses independently, as necessary. These were then reviewed, modified, and finalized by all the committee members. The recommended strength was decided considering 4 factors: evidence level, balance of benefits and harms/burdens, patient preferences, and cost–benefits. Finally, the recommendation strengths were divided into 5 categories . When the total agreement rate with recommendation of adopting or not adopting the approach was 50% or more and the total rate of agreement with the opposite view was less than 20%, the recommendation supported by 50% or more members was accepted by the committee. When the agreement rate for adopting or not adopting the approach was 70% or more, the strong recommendation was accepted by the committee members. When the agreement rate for “no recommendation” was 50% or more and that for each of the other recommendations was less than 20%, the “no recommendation” was accepted by the committee. If the voting results did not fulfill any of the above-mentioned criteria, the committee members held discussions again and a final voting was held. Non-fulfillment of the above criteria in the final voting led to the decision of “no recommendation”. Acceptability was determined by voting using an online voting system by the committee members who attended.Patients and the public have been actively involved in both the guideline development and implementation Fig. . For thiClinical Guidelines for Pancreatic Cancer 2022 [General Rules for the Study of Pancreatic Cancer published by the JPS in September 2020[To improve and confirm the validity of the guidelines, they were released in a draft form on the JPS website, inviting comments from the public. Simultaneously, they were reviewed by two external appraisal committees independently using the AGREE Reporting Checklists: a group assigned by the JPS that consisted of surgeons , gastroenterologists , a medical oncologist (Junji Furuse), an epidemiologist (Yosuke Hatakeyama), and two patient representatives with pancreatic cancer, and another group assigned by Minds, including specialists in guidelines methodology , independent of the revision committee members. Finally, taking into account the comments from the public and the external reviewers, the guidelines were reviewed and modified again by the revision committee members and finalized. These new cer 2022  are in cmber 2020.These guidelines represent the most standard guidelines for clinical and practical care of patients with pancreatic cancer available at this time. However, they should not be used inflexibly for the practical management of individual patients. The JPS is responsible for the statements in these guidelines. The JPS and the committee members are, however, not liable for any consequences arising from any treatment, for which individual physicians involved in the treatment are responsible.The algorithms present the flows for the diagnosis, treatment, chemotherapy, and precision medicine of pancreatic cancer. For a detailed explanation of each CQ, please refer to the indicated box Figs. –5.D1 Are further investigations recommended, considering the possibility of pancreatic cancer in patients with new-onset diabetes and exacerbation of diabetes?Statement:Further investigations are recommended in patients with new-onset diabetes and diabetes exacerbation, considering the possibility of pancreatic cancer.N = 51): 1 = 0%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 2%*.Recommendation strength: weak; evidence level: C; agreement rates .*D2 Are monitoring and follow-up recommended, in view of the possible development of pancreatic cancer, in patients with chronic pancreatitis?Statement:Follow-up observation is recommended in consideration of the possible development of pancreatic cancer in patients with chronic pancreatitis.N = 51): 1 = 0%, 2 = 100%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 4%, 2 = 96%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 0%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 2%.Recommendation strength: weak; evidence level: C; agreement rates (D5 Is cancer gene panel testing using tumor tissue recommended in patients with unresectable pancreatic cancer?Statement:Cancer gene panel testing using tumor tissue is recommended in patients with unresectable pancreatic cancer.N = 48): 1 = 0%, 2 = 100%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates (D5L (L: liquid biopsy) Is cancer gene panel testing using liquid biopsy recommended in patients with unresectable pancreatic cancer?Statement:Cancer gene panel testing using liquid biopsy is recommended in patients with unresectable pancreatic cancer.N = 48): 1 = 0%, 2 = 96%, 3 = 0%, 4 = 0%, and 5 = 4%.Recommendation strength: weak; evidence level: C; agreement rates  is recommended for the purpose of further assessing the risk of carcinogenesis in patients with pancreatic cancer and their relatives.N = 47): 1 = 0%, 2 = 98%, 3 = 2%, 4 = 0%, and 5 = 0%.2.Genetic testing for germline BRCA1/2 is recommended as a companion diagnostic test for olaparib in patients with locally advanced pancreatic cancer.Recommendation strength: weak; evidence level: C; agreement rates (N = 47): 1 = 2%, 2 = 96%, 3 = 0%, 4 = 0%, and 5 = 2%.3.Genetic testing for germline BRCA1/2 is recommended as a companion diagnostic test for olaparib in pancreatic cancer patients with distant metastases.Recommendation strength: weak; evidence level: C; agreement rates (N = 47): 1 = 2%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 2%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 2%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 4%, 2 = 96%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: B; agreement rates  recommended as a diagnostic tool in patients with suspected pancreatic cancer?Statement:Abdominal MRI is recommended as a diagnostic tool in patients with suspected pancreatic cancer.N = 51): 1 = 2%, 2 = 96%, 3 = 0%, 4 = 0%, and 5 = 2%.Recommendation strength: weak; evidence level: C; agreement rates (D11 Is endoscopic ultrasonography (EUS) recommended as a diagnostic tool in patients with suspected pancreatic cancer?Statement:Endoscopic ultrasonography is recommended as a diagnostic tool in patients with suspected pancreatic cancer, especially as it is more sensitive than other imaging modalities for the diagnosis of pancreatic cancer.N = 50): 1 = 4%, 2 = 96%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: B; agreement rates : 1 = 0%, 2 = 94%, 3 = 4%, 4 = 0%, and 5 = 2%.Recommendation strength: weak; evidence level: C; agreement rates (D13 Is positron emission tomography (PET) recommended as a diagnostic method in patients with suspected pancreatic cancer?Statement:Positron emission tomography is not recommended as a diagnostic or qualitative diagnostic tool in patients with suspected pancreatic cancer.N = 50): 1 = 0%, 2 = 10%, 3 = 84%, 4 = 2%, and 5 = 4%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 11%, 2 = 87%, 3 = 2%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: B; agreement rates : 1 = 2%, 2 = 94%, 3 = 2%, 4 = 0%, and 5 = 2%.Recommendation strength: weak; evidence level: B; agreement rates : 1 = 0%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 2%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 0%, 2 = 100%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: D; agreement rates : 1 = 0%, 2 = 98%, 3 = 2%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 2%, 2 = 96%, 3 = 2%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: B; agreement rates : 1 = 2%, 2 = 92%, 3 = 6%, 4 = 0%, and 5 = 0%Recommendation strength: weak; evidence level: C; agreement rates : 1 = 2%, 2 = 94%, 3 = 4%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates (D22 Is preoperative assessment of nutrition and body composition (muscle and fat mass) along with blood biochemistry recommended in patients with pancreatic cancer?Statement:Assessment of the preoperative nutritional status and body composition is recommended in patients with pancreatic cancer, because these variables have been shown to contribute to prediction of the long-term prognosis and postoperative complications in patients undergoing surgery for pancreatic cancer.N = 49): 1 = 8%, 2 = 90%, 3 = 2%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: D; agreement rates : 1 = 10%, 2 = 88%, 3 = 2%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: B; agreement rates : 1 = 2%, 2 = 8%, 3 = 80%, 4 = 6%, and 5 = 4%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 6%, 2 = 88%, 3 = 2%, 4 = 2%, and 5 = 2%.Recommendation strength: weak; evidence level: D; agreement rates : 1 = 0%, 2 = 4%, 3 = 22%, 4 = 74%, and 5 = 0%.Recommendation strength: strong; evidence level: A; agreement rates : 1 = 2%, 2 = 86%, 3 = 2%, 4 = 0%, and 5 = 10%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 2%, 2 = 94%, 3 = 0%, 4 = 0%, and 5 = 4%.2.Robot-assisted distal pancreatectomy is recommended in patients with invasive ductal carcinoma who are candidates for distal pancreatectomy, but only at facilities specializing in the treatment of pancreatic cancer. Recommendation strength: weak; evidence level: C; agreement rates (N = 49): 1 = 2%, 2 = 92%, 3 = 2%, 4 = 0%, and 5 = 4%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 4%, 2 = 94%, 3 = 2%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: D; agreement rates (RO8 Is perioperative pancreatic enzyme replacement therapy recommended in pancreatic cancer patients?Statement:Perioperative pancreatic enzyme replacement therapy is recommended in pancreatic cancer patients with suspected/confirmed pancreatic exocrine insufficiency.N = 51): 1 = 2%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 0%, 2 = 98%, 3 = 2%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 0%, 2 = 98%, 3 = 0%, 4 = 2%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates (RA1 Is neoadjuvant therapy recommended for patients with resectable pancreatic cancer?Statement:Combined gemcitabine + S-1 therapy is recommended as preoperative neoadjuvant therapy in patients with resectable pancreatic cancer.N = 49): 1 = 14%, 2 = 86%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 82%, 2 = 18%, 3 = 0%, 4 = 0%, and 5 = 0%.2.S-1 monotherapy is recommended as an adjuvant chemotherapeutic agent in patients with pancreatic cancer.Recommendation strength: strong; evidence level: A; agreement rates (N = 47): 1 = 87%, 2 = 13%, 3 = 0%, 4 = 0%, and 5 = 0%.3.Gemcitabine hydrochloride monotherapy is recommended for patients showing poor tolerance to S-1.Recommendation strength: strong; evidence level: A; agreement rates (N = 47): 1 = 74%, 2 = 23%, 3 = 2%, 4 = 0%, and 5 = 0%.4.Combined gemcitabine hydrochloride + capecitabine therapy  and modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (modified FOLFIRINOX) therapy  are recommended for patients with pancreatic cancer, based on the results of phase III studies conducted outside Japan.Recommendation strength: strong; evidence level: A; agreement rates (N = 47): 1 = 4%, 2 = 87%, 3 = 4%, 4 = 0%, and 5 = 4%.Recommendation strength: weak; evidence level: A; agreement rates : 1 = 2%, 2 = 94%, 3 = 4%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 0%, 2 = 96%, 3 = 2%, 4 = 2%, and 5 = 0%.3.Combined resection of the superior mesenteric artery is not recommended.Recommendation strength: weak; evidence level: C; agreement rates (N = 49): 1 = 0%, 2 = 100%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates (N = 49): 1 = 0%, 2 = 0%, 3 = 90%, 4 = 8%, and 5 = 2%.BA1 What is the recommended preoperative neoadjuvant therapy for borderline resectable pancreatic cancer?Statement:Chemoradiotherapy is recommended.As neoadjuvant therapy for borderline resectable pancreatic cancer,N = 44): 1 = 2%, 2 = 93%, 3 = 2%, 4 = 0%, and 5 = 2%.2.Chemotherapy alone is recommended.Recommendation strength: weak; evidence level: C; agreement rates (N = 44): 1 = 2%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates (BA2 Is postoperative adjuvant chemotherapy recommended for patients with borderline resectable pancreatic cancer?Statement:Postoperative adjuvant chemotherapy is recommended for patients with borderline resectable pancreatic cancer.N = 49): 1 = 8%, 2 = 92%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 6%, 2 = 94%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: B; agreement rates : 1 = 4%, 2 = 96%, 3 = 0%, 4 = 0%, and 5 = 0%.2.For patients with locally advanced, unresectable pancreatic cancer scheduled to receive chemoradiotherapy, concurrent use of gemcitabine hydrochloride with radiotherapy is recommended.Recommendation strength: weak; evidence level: C; agreement rates (N = 47): 1 = 4%, 2 = 94%, 3 = 0%, 4 = 0%, and 5 = 2%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 0%, 2 = 14%, 3 = 84%, 4 = 0%, and 5 = 2%.Recommendation strength: weak; evidence level: D; agreement rates : 1 = 0%, 2 = 6%, 3 = 89%, 4 = 0%, and 5 = 4%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 0%, 2 = 100%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates  recommended as radiation therapy in patients with locally advanced, unresectable pancreatic cancer?Statement:Increased radiation dose using high-precision radiotherapy is recommended in patients with locally advanced, unresectable pancreatic cancer.N = 50): 1 = 0%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 2%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 0%, 2 = 2%, 3 = 6%, 4 = 0%, and 5 = 92%.Recommendation strength: no recommendation; evidence level: D; agreement rates  therapy is recommended.N = 43): 1 = 19%, 2 = 81%, 3 = 0%, 4 = 0%, and 5 = 0%.4.Combined gemcitabine hydrochloride + nab-paclitaxel therapy is recommended.Recommendation strength: weak; evidence level: C; agreement rates (N = 43): 1 = 23%, 2 = 77%, 3 = 0%, 4 = 0%, and 5 = 0%.5.Gemcitabine hydrochloride monotherapy is recommended.Recommendation strength: weak; evidence level: C; agreement rates (N = 43): 1 = 2%, 2 = 93%, 3 = 2%, 4 = 0%, and 5 = 2%.6.S-1 monotherapy is recommended.Recommendation strength: weak; evidence level: C; agreement rates (N = 43): 1 = 5%, 2 = 91%, 3 = 5%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates (LC2 (MC2) Is second-line chemotherapy recommended for patients with unresectable pancreatic cancer?Statement:7.Second-line chemotherapy is recommended for unresectable pancreatic cancer patients who are refractory to first-line therapy. N = 44): 1 = 68%, 2 = 32%, 3 = 0%, 4 = 0%, and 5 = 0%.8.Combined fluorouracil + calcium folinate + nanoliposomal irinotecan is recommended after first-line treatment with a gemcitabine hydrochloride-containing regimen. Recommendation strength: weak; evidence level: B; agreement rates (N = 44): 1 = 55%, 2 = 45%, 3 = 0%, 4 = 0%, and 5 = 0%.9.Use of a fluorouracil-containing regimen (including FOLFIRINOX therapy and S-1 monotherapy) is recommended after first-line therapy with a gemcitabine hydrochloride-containing regimen. Recommendation strength: weak; evidence level: B; agreement rates (N = 44): 1 = 5%, 2 = 95%, 3 = 0%, 4 = 0%, and 5 = 0%.10.Use of a gemcitabine hydrochloride-containing regimen is recommended after first-line treatment with a fluorouracil-containing regimen. Recommendation strength: weak; evidence level: C; agreement rates (N = 44): 1 = 2%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 0%.11.Pembrolizumab monotherapy is recommended for microsatellite instability-high cases.Recommendation strength: weak; evidence level: C; agreement rates (N = 44): 1 = 0%, 2 = 100%, 3 = 0%, 4 = 0%, and 5 = 0%.12.Pembrolizumab monotherapy is recommended for tumor mutational burden-high cases. Recommendation strength: weak; evidence level: C; agreement rates (N = 44): 1 = 0%, 2 = 95%, 3 = 0%, 4 = 0%, and 5 = 5%.13.Entrectinib monotherapy or larotrectinib monotherapy is recommended for cases with tumors harboring NTRK gene fusions.Recommendation strength: weak; evidence level: C; agreement rates (N = 44): 1 = 0%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 2%.Recommendation strength: weak; evidence level: C; agreement rates (LC3 (MC3) What is the first-line chemotherapy recommended for elderly patients with advanced pancreatic cancer?Statement:Combined gemcitabine hydrochloride + nab-paclitaxel therapy is recommended.As first-line chemotherapy for elderly patients with advanced pancreatic cancer in consideration of the performance status and comorbidities,N = 42): 1 = 0%, 2 = 100%, 3 = 0%, 4 = 0%, and 5 = 0%.2.Gemcitabine hydrochloride monotherapy is recommendedRecommendation strength: weak; evidence level: C; agreement rates (N = 42): 1 = 0%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 2%.3.S-1 monotherapy is recommended.Recommendation strength: weak; evidence level: C; agreement rates (N = 42): 1 = 0%, 2 = 100%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates (LC4 (MC4) What is the chemotherapy regimen recommended for pancreatic cancer patients with a germline pathogenic variant of BRCA1/2?Use of a platinum-containing regimen is recommended for pancreatic cancer patients with pathological germline variants of BRCA1/2.StatementN = 47): 1 = 4%, 2 = 96%, 3 = 0%, 4 = 0%, and 5 = 0%.2.Maintenance therapy with olaparib is recommended as one of the treatment options for pancreatic cancer patients with distant metastases in whom disease progression has been suppressed for a certain period of time with a platinum-containing regimen.Recommendation strength: weak; evidence level: C; agreement rates (N = 47): 1 = 4%, 2 = 94%, 3 = 0%, 4 = 0%, and 5 = 2%.3.Maintenance therapy with olaparib is recommended as one of the treatment options for patients with locally advanced pancreatic cancer in whom disease progression has been suppressed for a certain period of time with a platinum-containing regimen.Recommendation strength: weak; evidence level: C; agreement rates (N = 47): 1 = 4%, 2 = 96%, 3 = 0%, 4 = 0%, and 5 = 0%Recommendation strength: weak; evidence level: C; agreement rates : 1 = 0%, 2 = 96%, 3 = 2%, 4 = 0%, and 5 = 2%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 4%, 2 = 94%, 3 = 0%, 4 = 0%, and 5 = 2%.Recommendation strength: weak; evidence level: D; agreement rates : 1 = 91%, 2 = 9%, 3 = 0%, 4 = 0%, and 5 = 0%.15.Combined gemcitabine hydrochloride + nab-paclitaxel therapy is recommended. Recommendation strength: strong; evidence level: A; agreement rates (N = 43): 1 = 91%, 2 = 9%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: strong; evidence level: A; agreement rates : 1 = 5%, 2 = 93%, 3 = 2%, 4 = 0%, and 5 = 0%.17.S-1 monotherapy is recommended. Recommendation strength: weak; evidence level: A; agreement rates (N = 43): 1 = 2%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: A; agreement rates (MC2 (LC2) Is second-line chemotherapy recommended for patients with unresectable pancreatic cancer?Statement:18.Second-line chemotherapy is recommended for patients with unresectable pancreatic cancer who are refractory to first-line therapy. N = 44): 1 = 68%, 2 = 32%, 3 = 0%, 4 = 0%, and 5 = 0%.19.Combined fluorouracil + calcium folinate + nanoliposomal irinotecan is recommended after first-line treatment with a gemcitabine hydrochloride-containing regimen. Recommendation strength: strong; evidence level: B; agreement rates (N = 44): 1 = 55%, 2 = 45%, 3 = 0%, 4 = 0%, and 5 = 0%.20.Use of a fluorouracil-containing regimen (including FOLFIRINOX therapy and S-1 monotherapy) is recommended after first-line treatment with a gemcitabine hydrochloride-containing regimen. Recommendation strength: weak; evidence level: B; agreement rates (N = 44): 1 = 5%, 2 = 95%, 3 = 0%, 4 = 0%, and 5 = 0%.21.Use of a gemcitabine hydrochloride-containing regimen is recommended after first-line treatment with a fluorouracil-containing regimen. Recommendation strength: weak; evidence level: C; agreement rates (N = 44): 1 = 2%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 0%.22.Pembrolizumab monotherapy is recommended for microsatellite instability-high cases. Recommendation strength: weak; evidence level: C; agreement rates (N = 44): 1 = 0%, 2 = 100%, 3 = 0%, 4 = 0%, and 5 = 0%.23.Pembrolizumab monotherapy is recommended for tumor mutational burden-high cases.Recommendation strength: weak; evidence level: C; agreement rates (N = 44): 1 = 0%, 2 = 95%, 3 = 0%, 4 = 0%, and 5 = 5%.24.Entrectinib monotherapy or larotrectinib monotherapy is recommended for cases with tumors harboring NTRK gene fusions. Recommendation strength: weak; evidence level: C; agreement rates (N = 44): 1 = 0%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 2%.Recommendation strength: weak; evidence level: C; agreement rates (MC3 (LC3) What is the first-line chemotherapy recommended in elderly patients with advanced pancreatic cancer?Statement:Combined gemcitabine hydrochloride + nab-paclitaxel therapy is recommended.As first-line chemotherapy in elderly patients with advanced pancreatic cancer, in consideration of the performance status and comorbidities,N = 42): 1 = 0%, 2 = 100%, 3 = 0%, 4 = 0%, and 5 = 0%.2.Gemcitabine hydrochloride monotherapy is recommended.Recommendation strength: weak; evidence level: C; agreement rates (N = 42): 1 = 0%, 2 = 98%, 3 = 0%, 4 = 0%, and 5 = 2%.3.S-1 monotherapy is recommended.Recommendation strength: weak; evidence level: C; agreement rates (N = 42): 1 = 0%, 2 = 100%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates (MC4 (LC4) What is the recommended chemotherapy for pancreatic cancer patients with germline pathogenic variants of BRCA1/2?Statement:Use of a platinum-containing regimen is recommended for pancreatic cancer patients with pathological germline variants of BRCA1/2.N = 47): 1 = 4%, 2 = 96%, 3 = 0%, 4 = 0%, and 5 = 0%.2.Maintenance therapy with olaparib is recommended as one of the treatment options for pancreatic cancer patients with distant metastases in whom disease progression has remained suppressed for a certain period of time with a platinum-containing regimen.Recommendation strength: weak; evidence level: C; agreement rates (N = 47): 1 = 4%, 2 = 94%, 3 = 0%, 4 = 0%, and 5 = 2%.3.Maintain therapy with olaparib is recommended as one of the treatment options for patients with locally advanced pancreatic cancer in whom disease progression has remained suppressed for a certain period of time with a platinum-containing regimen.Recommendation strength: weak; evidence level: C; agreement rates (N = 47): 1 = 4%, 2 = 96%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 0%, 2 = 92%, 3 = 4%, 4 = 0%, and 5 = 4%.26.Surgical resection is recommended for lung metastases after carefully confirming the surgical indication.Recommendation strength: weak, evidence level: D, agreement rates (N = 50): 1 = 0%, 2 = 90%, 3 = 8%, 4 = 0%, and 5 = 2%.27.Surgical resection is not recommended for metastases other than lung metastases .Recommendation strength: weak, evidence level: D, agreement rates (N = 47): 1 = 0%, 2 = 4%, 3 = 94%, 4 = 2%, and 5 = 0%.Recommendation strength: weak, evidence level: D, agreement rates : 1 = 0%, 2 = 6%, 3 = 8%, 4 = 0%, and 5 = 86%.Recommendation strength: no recommendation, evidence level: D, agreement rates (MR1 Is radiotherapy recommended for the management of painful bone metastases in patients with advanced pancreatic cancer?Statement:Radiotherapy is recommended for the management of painful bone metastases in patients with advanced pancreatic cancer.N = 50): 1 = 84%, 2 = 16%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: strong; evidence level: B; agreement rates : 1 = 2%, 2 = 92%, 3 = 2%, 4 = 0%, and 5 = 4%.29.Radiotherapy is recommended for the management of lung metastases.Recommendation strength: weak; evidence level: D; agreement rates (N = 50): 1 = 2%, 2 = 94%, 3 = 2%, 4 = 0%, and 5 = 2%.30.Radiotherapy is not recommended for the management of liver metastases.Recommendation strength: weak; evidence level: D; agreement rates (N = 50): 1 = 0%, 2 = 12%, 3 = 84%, 4 = 2%, and 5 = 2%.Recommendation strength: weak; evidence level: D; agreement rates (Stenting or StSSt1 Is the endoscopic transpapillary route recommended for biliary drainage in patients with unresectable pancreatic cancer?Statement:The endoscopic transpapillary route is recommended for biliary drainage in patients with unresectable pancreatic cancer.N = 45): 1 = 9%, 2 = 91%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: B; agreement rates : 1 = 13%, 2 = 82%, 3 = 4%, 4 = 0%, and 5 = 0%.32.When the waiting period for surgery is short, use of a plastic stent is recommended.Recommendation strength: weak; evidence level: C; agreement rates (N = 34): 1 = 0%, 2 = 82%, 3 = 15%, 4 = 0%, and 5 = 3%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 12%, 2 = 88%, 3 = 0%, 4 = 0%, and 5 = 0%Recommendation strength: weak; evidence level: B; agreement rates : 1 = 4%, 2 = 96%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 10%, 2 = 88%, 3 = 0%, 4 = 0%, and 5 = 3%.Recommendation strength: weak; evidence level: D; agreement rates : 1 = 8%, 2 = 80%, 3 = 3%, 4 = 0%, and 5 = 10%.2.No clear recommendation can be made at this time for the use of metallic stents in pancreatic cancer patients with obstructive jaundice receiving radiation therapy.Recommendation strength: weak; evidence level: D; agreement rates (N = 36): 1 = 0%, 2 = 14%, 3 = 11, 4 = 0%, and 5 = 75%.Recommendation strength: no recommendation; evidence level: D; agreement rates : 1 = 4%, 2 = 96%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: D; agreement rates  is recommended for pancreatic cancer patients with cancer pain.N = 48): 1 = 63%, 2 = 38%, 3 = 0%, 4 = 0%, and 5 = 0%.Nerve blocks are recommended for pancreatic cancer patients with cancer pain.Recommendation strength: weak; evidence level: C; agreement rates (N = 48): 1 = 0%, 2 = 92%, 3 = 6%, 4 = 0%, and 5 = 2%.Adjuvant analgesics are not recommended for pancreatic cancer patients with cancer pain.Recommendation strength: weak; evidence level: B; agreement rates (N = 48): 1 = 6%, 2 = 10%, 3 = 67%, 4 = 2%, and 5 = 15%.Recommendation strength: weak; evidence level: D; agreement rates (SSp3 Is exercise therapy recommended for patients with pancreatic cancer?Statement:Exercise therapy is recommended for patients with pancreatic cancer.N = 49): 1 = 0%, 2 = 94%, 3 = 0%, 4 = 0%, and 5 = 6%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 0%, 2 = 88%, 3 = 0%, 4 = 0%, and 5 = 12%.Recommendation strength: weak; evidence level: C; agreement rates (SSp5 Is advance care planning recommended for patients with advanced pancreatic cancer?Statement:Advance care planning is recommended for patients with advanced pancreatic cancer.N = 49): 1 = 0%, 2 = 100%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 0%, 2 = 100%, 3 = 0%, 4 = 0%, and 5 = 0%.2.Use of pregabalin is recommended for managing peripheral neuropathy associated with FOLFIRINOX therapy or combined gemcitabine hydrochloride + nab-paclitaxel therapy in patients with pancreatic cancer.Recommendation strength: weak; evidence level: C; agreement rates (N = 48): 1 = 0%, 2 = 96%, 3 = 0%, 4 = 0%, and 5 = 4%.3.Use of mirogabalin may be considered for managing peripheral neuropathy associated with FOLFIRINOX therapy or combined gemcitabine hydrochloride + nab-paclitaxel therapy in patients with pancreatic cancer.Recommendation strength: weak; evidence level: C; agreement rates (N = 48): 1 = 0%, 2 = 94%, 3 = 0%, 4 = 0%, and 5 = 6%.Recommendation strength: weak; evidence level: D; agreement rates .N = 48): 1 = 0%, 2 = 92%, 3 = 4%, 4 = 0%, and 5 = 4%.Anticoagulant therapy with direct-acting oral anticoagulants to prevent new onset of venous thromboembolism is recommended in pancreatic cancer patients undergoing chemotherapy .Recommendation strength: weak; evidence level: B; agreement rates (N = 48): 1 = 0%, 2 = 94%, 3 = 2%, 4 = 0%, and 5 = 4%.Recommendation strength: weak; evidence level: C; agreement rates : 1 = 0%, 2 = 100%, 3 = 0%, 4 = 0%, and 5 = 0%.In patients with advanced pancreatic cancer, a clear recommendation cannot be made at this time for using a combination of nutritional and exercise interventions centered on essential amino acids to manage cachexia.Recommendation strength: weak; evidence level: D; agreement rates (N = 44): 1 = 0%, 2 = 7%, 3 = 0%, 4 = 0%, and 5 = 93%.Recommendation strength: no recommendation; evidence level: D; agreement rates : 1 = 0%, 2 = 16%, 3 = 0%, 4 = 0%, and 5 = 84%.Recommendation strength: no recommendation; evidence level: D; agreement rates (SSp10 Is Communication Technology Training (CST) recommended for physicians expected to participate in important cancer-related discussions?Statement:Communication skills’ training is recommended for physicians expected to participate in important cancer-related discussions.N = 47): 1 = 62%, 2 = 38%, 3 = 0%, 4 = 0%, and 5 = 0%.Recommendation strength: weak; evidence level: B; agreement rates (


Health evidence needs to be communicated and disseminated in a manner that is clearly understood by decision-makers. As an inherent component of health knowledge translation, communicating results of scientific studies, effects of interventions and health risk estimates, in addition to understanding key concepts of clinical epidemiology and interpreting evidence, represent a set of essential instruments to reduce the gap between science and practice. The advancement of digital and social media has reshaped the concept of health communication, introducing new, direct and powerful communication platforms and gateways between researchers and the public. The objective of this scoping review was to identify strategies for communicating scientific evidence in healthcare to managers and/or population.We searched Cochrane Library, Embase®, MEDLINE® and other six electronic databases, in addition to grey literature, relevant websites from related organizations for studies, documents or reports published from 2000, addressing any strategy for communicating scientific evidence on healthcare to managers and/or population.Our search identified 24 598 unique records, of which 80 met the inclusion criteria and addressed 78 strategies. Most strategies focused on risk and benefit communication in health, were presented by textual format and had been implemented and somehow evaluated. Among the strategies evaluated and appearing to yield some benefit are (i) risk/benefit communication: natural frequencies instead of percentages, absolute risk instead relative risk and number needed to treat, numerical instead nominal communication, mortality instead survival; negative or loss content appear to be more effective than positive or gain content; (ii) evidence synthesis: plain languages summaries to communicate the results of Cochrane reviews to the community were perceived as more reliable, easier to find and understand, and better to support decisions than the original summaries; (iii) teaching/learning: the Informed Health Choices resources seem to be effective for improving critical thinking skills.Our findings contribute to both the knowledge translation process by identifying communication strategies with potential for immediate implementation and to future research by recognizing the need to evaluate the clinical and social impact of other strategies to support evidence-informed policies.Trial registration protocol is prospectively available in MedArxiv (doi.org/10.1101/2021.11.04.21265922).The online version contains supplementary material available at 10.1186/s12961-023-01017-2. Communicating results of scientific studies, effects of interventions and health risk estimates, in addition to understanding key concepts of clinical epidemiology and interpreting evidence, account for a set of essential instruments to bridging the gap between science and practice.There is still a lack of understanding about the exact types of strategies for communicating scientific evidence.The findings of this manuscript, specifically the extensive and detailed list of strategies mapped out to communicate scientific evidence in health to managers and the population, may support the decision-making of stakeholders involved in the process of knowledge translation within the realms of evidence-informed policies.Within the context of evidence-informed policy (EIP), evidence syntheses should provide scientifically based information on health conditions, interventions, procedures, policies and programmes to meet the needs of health professionals, patients and public or private health managers. However, evidence obtained from scientific studies, especially from systematic reviews, other syntheses of multiple studies and clinical trials, is complex and often difficult for the general public to comprehend . Health As an inherent component of health knowledge translation, communicating results of scientific studies, effects of interventions and health risk estimates, in addition to understanding key concepts of clinical epidemiology and interpreting evidence, represent a set of essential instruments to reduce the gap between science and practice. These needs have represented a challenge within the EIP worldwide.Strategies for communication of evidence in health have the initial goal of increasing the understanding of the results of scientific research and should cover products, actions and approaches aligned to the needs of the manager  and the population (reliable information based on the best scientific evidence available) . NeverthIn this sense, expanding investment and improving skills in communication enables the identification of the best strategies to be used to overcome the barrier between evidence in health and managers and the population. Clear communication and active dissemination of health evidence to all relevant audiences in an understandable and accessible manner are essential to raise awareness of the importance of using scientific evidence, to support individual and population health-related decisions , and conIn the last decade, the advancement of digital and social media has reshaped the concept of health communication, introducing new, direct and powerful communication platforms and gateways between researchers and the public –4. VarioSome synthesis of strategies for communication of scientific evidence are available in the literature, including overviews of systematic reviews that address knowledge translation and general health communication strategies  , 5, systThus, a mapping is necessary, through a scoping review, to identify the available strategies for communication of scientific evidence; the characteristics, barriers and facilitators for its implementation; the target audience and the context, as well as the gaps in the literature about its impact on healthcare. The results identified may constitute a valuable instrument for decision-making for sectors involved in promoting the use of scientific knowledge in decision-making processes related to the communication of evidence in the context of EIP.This scoping review is a component of the project Apoio à Formulação e Implementação de Políticas Públicas de Saúde Informadas por Evidências (ESPIE), triennium 2021/2023, conducted at the Hospital Sírio-Libanês , within the scope of the Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde (PROADI-SUS), in partnership with the Department of Science and Technology of the Secretariat of Science, Technology, Innovation and Strategic Inputs of the Ministry of Health. This review was planned and conducted according to the recommendations of the Joanna Briggs Institute Manual for scoping reviews .The report of the review followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses – extension for scoping reviews (PRISMA-ScR) . The revStakeholder consultation was carried out throughout the development of the protocol, with the aim of increasing the applicability of its results and supporting the communication and translation of its results to the community. To this end, the following stakeholders were informally consulted: consumers , experts in ‘knowledge translation’ and ‘health communication’ and information specialists.P : health managers and the general population.C (concept): strategies for communicating scientific evidence to health managers and/or the community. In this review, scientific evidence was considered as information obtained from the results of scientific studies and used to support or refute a health recommendation or the planning of health systems and policies. Thus, strategies were considered as those aiming to translate scientific and/or methodological information in a format/content geared to ensure the understanding of health managers and society of terms, criteria, tools and approaches related to scientific evidence in health. Any strategy focused on the communication of scientific evidence for this target audience was considered, including, for example, communication strategies to support health managers in decision-making, communications used during the organization of services and/or health systems, communication strategies to encourage the use of scientific evidence in the decision-making process, to increase access to health information from the perspective of the population, strategies for adapting the knowledge obtained by evidence to the local context, and so on. Studies on individual professional–patient communication  or specific to a particular health condition were not considered. Studies addressing the process of knowledge translation were included only when they reported, implemented and/or evaluated strategies for communication of scientific evidence as part of this process. Studies specifically addressing evidence dissemination and implementation strategies were not included.C (context): individual or public health; within public, private or supplementary health systems; at any level of care .The question of interest for this review was structured using the acronym PCC, which then guided the eligibility criteria as follows:Any primary  or secondary study design was considered.https://opengrey.eu), Thesis Commons (https://thesiscommons.org/) and Open Access Theses and Dissertations (https://oatd.org/).A broad and sensitive literature search was conducted using structured search strategies, with relevant descriptors and synonyms, for the following databases on 8 September 2021: Campbell Collaboration, Cochrane Library (via Wiley), Excerpta Medica dataBASE , Biblioteca Virtual em Saúde (BVS), Epistemonikos, Health Evidence, Health Systems Evidence, Medical Literature Analysis and Retrieval System Online  and PDQ-Evidence. A structured electronic search was conducted in the following grey literature bases on 24 February 2022: Opengrey (https://europepmc.org/) and Open Science Preprints (https://osf.io/preprints/).Structured electronic searches were conducted on the following repositories of preprints on 24 February 2022: Europe PMC (www.guidelines.gov), Centre for Reviews and Dissemination (CRD), Service Delivery and Organisation (https://www.york.ac.uk/crd/research/service-delivery/), Cochrane Effective Practice and Organization of Care (EPOC) (https://epoc.cochrane.org/), EPPI-Centre (https://eppi.ioe.ac.uk/cms/Default.aspx?tabid=56), Evidence Informed Policy and Practice in Education in Europe (EIPPEE) (http://www.eippee.eu/cms/Default.aspx?tabid=3179), European Observatory on Health Systems and Policies , ECRAN Project. European Communication on Research Awareness Needs (http://www.ecranproject.eu/en), Evidence Informed Policy Networks (EVIPNet) (https://www.who.int/initiatives/evidence-informed-policy-network), Global Evaluation Initiative , Informed Health Choices , International Bibliography of the Social Sciences (IBSS) (https://about.proquest.com/en/products-services/ibss-set-c/), International Initiative for Impact Evaluation (3ie) (https://www.3ieimpact.org/), McMaster University's Health Forum (https://www.mcmasterforum.org/), Rx for Change (https://www.cadth.ca/rx-change), Supporting the use of Research Evidence (SURE)  and What Works Centres (https://www.gov.uk/guidance/what-works-network).Additional unstructured searches were conducted on the following sources related to evidence-informed policy or health education on 27 February 2022: Agency for Healthcare Research and Quality AHRQ/EUA, Guidelines and Measures (https://www.amwa.org/), European Medical Writers Association  and International Society for Medical Publication Professionals . A manual search was performed in reference lists of relevant studies and through contact with experts in the field.Additional unstructured searches were conducted on the following sources related to health science communication on 24 February 2022: American Medical Writers Association  or negative (losses) words/terms, verbal versus visual communication of the effects of interventions, communicating health risks and benefits with bar charts or bar charts and histograms, strategies for communication of health evidence and strategies for communicating risks and benefits in health with different animated graphical presentations.communication of uncertainty in health: including the subcategory communication of uncertainties about the effects of interventions on health.teaching/learning: including the subcategories communication/learning of key concepts related to the effects of health interventions, communication/learning resources from the IHC initiative on key concepts of evidence for health, communication/learning of key concepts of health evidence, educational podcasts from the IHC initiative on key health evidence concepts, training for parliamentarians on scientific health evidence and inclusion of stakeholders in the working group for preparing comparative effectiveness summaries.evidence synthesis frameworks using plain language: including the subcategories blogshots to communicate the results of systematic reviews, evidence synthesis summary template, plain language abstract, Cochrane plain language summaries, templates for plain language abstracts of systematic reviews, printed newsletters for communicating health evidence and systematic review summaries of evidence templates for policy-makers and health system managers.guidelines for elaborating/evaluating communication products: including the subcategories guidelines for designing and evaluating health evidence communication products (CDC Clear Communication Index) and tool for evaluating the quality of health texts in plain language.For this categorization, a new taxonomy was elaborated with an unstructured method, which is detailed in Additional file Target audience: health managers, population, both.Type of strategy: language, content or format of the communication.Health system and level of care for which the strategy was proposed or used .Approach to the strategy: textual communication , visual communication , verbal communication  and others.Strategy length: permanent or temporary.Strategy status: proposed, implemented and not evaluated, or implemented and evaluated.Costs for implementing the strategy (as predicted by the authors of the studies included).Barriers and facilitators for implementing the strategy (as identified by the authors of the studies included).Data on the of strategies identified and included in this review were extracted by two researchers independently and inconsistencies were solved by consulting a third researcher. The following data were collected for each included study: author, year of publication, type of publication , study design, name and description of the communication strategy, institution proposing the strategy and source of funding for the study. The following data were collected, when available, for each strategy identified:For the scientific evidence communication strategies that were implemented and evaluated by the included studies, information on the results was collected. These strategies were subsequently classified, at the discretion of the reviewing authors, according to the feasibility of implementation, immediate or after the adoption of actions. This classification was performed considering facilities, costs, need for regulation or local policies, and regardless of the certainty of the available evidence.The authors of the included studies could be contacted if additional information was needed.As the aim of this scoping review is to map strategies presented in descriptive studies or to use pieces of analytical studies reporting strategies, no checklists or tools for assessing the methodological quality of the studies were applied, as recommended by the Joanna Briggs Institute for scoping reviews .Strategies were classified using the categories determined based on the data described above. A narrative synthesis was presented using graphs and/or tables. Depending on the availability of information, descriptive statistics would be performed using Microsoft Excel® and/or STATA® software, but this was not undertaken due to the format and/or scarcity of the data presented.Structured searches in electronic databases resulted in 25 284 references and unstructured searches in additional sources retrieved 58 references, totaling 25 342 references. After removing 744 duplicates, 24 598 references were analyzed through titles and abstracts and 24 467 were eliminated for not meeting the eligibility criteria. Thus, in the second stage of the selection process, the full texts of 131 references were analyzed. Of these, 50 were excluded –66 and tAt the end of the selection process, this review included 80 studies or documents Fig.  1, 2, 6, 68–138.The main characteristics of the included studies/documents are detailed in Additional file Seventy-eight strategies were identified in the included studies and are presented in Additional file Table Regarding the target audience, 71.8% of the strategies were intended for the general population, 20.5% specifically for managers and 7.7% were applicable to both groups  or numerical , to communicate attributes or effects of health interventions or exposures. The 17 strategies in the ‘teaching/learning’ category, comprised structural actions in schools (many of them conducted by the IHC initiative), virtual environments (websites), and even in parliament  of the identified strategies had already been implemented and evaluated in some degree, 44.9% had already been implemented but not yet evaluated and 2.6% were merely proposed without any sort of implementation or evaluation  and sensitive  search. As shown in Fig. https://www.informedhealthchoices.org/) and the ECRAN project (http://ecranproject.eu/) were particularly noteworthy.One strength was the identification of communication strategies that used structuring learning approaches to continuously and progressively build a more favourable scenario for the population and managers to receive communication products. In this respect, the IHC initiative , there was no nominal definition of possible strategies. Along the construction of the search strategies, the term ‘risk communication’ and its synonyms were not used, but instead, less specific terms were used to sensitize the search. However, throughout the study selection process, a considerable number of studies specific to risk communication were identified. Thus, although 29.9% of the communication strategy included were specific to risk communication and health benefits, it is not possible to rule out that studies targeting this approach were not retrieved.Another concern was that despite a number of different attempts  it was not possible to obtain the full text of one of the identified studies . The reaSome studies addressed combined strategies and it was not possible to quantify the exact number of different strategies addressed in the 78 strategies identified given a high rate of overlap of their components. To mitigate this shortcoming, we have chosen to present a detailed (and therefore longer than we would have preferred) table describing each strategy  rather than relative risk or NNT.Escola Nacional de Administração , is producing prototype products for communicating scientific evidence in accessible language using design thinking methodology [The elaboration and dissemination of communication products in parallel with scientific publications, and aimed at different audiences, is a reality (as exemplified by Cochrane’s plain language summary). This approach could be replicated and adopted by other organizations or scientific publishers, using results from reviews such as this one. In the same direction, the Brazilian Ministry of Health, in a recent initiative in partnership with the hodology , 142.As implications for forthcoming research, this scoping review identified a number of knowledge gaps that still need to be addressed by studies with appropriate designs and methods. These gaps include evidence on (i) the efficacy of communication strategies on outcome measures, such as behaviour change and clinical benefits related to the control or prevention of health conditions, (ii) the costs associated with implementing the strategies, (iii) effects of the strategies for low-income, lower sociocultural and/or resource-poor populations, and (iv) effects of the strategies for subgroups such as the elderly, adolescents and children.This scoping review identified 80 studies, reports or other documents that addressed 78 strategies for communicating scientific health evidence to the population and/or managers. Some of these strategies have been implemented and evaluated, and may have some benefit in improving these audiences’ comprehension of evidence concepts and promoting behaviour change. The findings of this review have important potential for applicability in the area of evidence-informed policy, with direct application or adaptation of identified strategies to improve the communication of scientific evidence on healthcare to managers and the population. Future efforts are needed to evaluate the effects of evidence communication strategies on relevant clinical outcomes, identify the most appropriate strategies for different settings and contexts, and promote the use of those strategies that show benefits for individual or public health and health systems.Additional file 1. Strategies of electronic and structured searches.Additional file 2. Proposed taxonomy to categorize strategies for communicating scientific evidence in health to the population/managers.Additional file 3. Studies/documents excluded and reasons for exclusions after reading the full text (second phase of the selection process).Additional file 4. Main characteristics of included studies.Additional file 5. Main characteristics of the identified strategies or sets of strategies for communicating scientific evidence.


Porphyromonas gingivalis has been identified as a keystone pathogen. The immune-modulatory function of P. gingivalis is well characterized, but the mechanism by which this bacterium secretes peptidyl arginine deiminase (PPAD), a protein/peptide citrullinating enzyme, thus contributing to the infinite feed-forward loop of inflammation, is not fully understood. To determine the functional role of citrullination in periodontitis, neutrophils were stimulated by P. gingivalis bearing wild-type PPAD and by a PPAD mutant strain lacking an active enzyme. Flow cytometry showed that PPAD contributed to prolonged neutrophil survival upon bacterial stimulation, accompanied by the secretion of aberrant IL-6 and TNF-α. To further assess the complex mechanism by which citrullination sustains a chronic inflammatory state, the ROS production and phagocytic activity of neutrophils were evaluated. Flow cytometry and colony formation assays showed that PPAD obstructs the resolution of inflammation by promoting neutrophil survival and the release of pro-inflammatory cytokines, while enhancing the resilience of the bacteria to phagocytosis. Periodontitis is a widespread chronic inflammatory disease caused by a changed dysbiotic oral microbiome. Although multiple species and risk factors are associated with periodontitis,  Porphyromonas gingivalis is considered a key pathogen [The World Health Organization (WHO) has estimated that nearly 10% of the global population is affected by periodontitis, an inflammatory disease progressing in the presence of a complex, dysbiotic oral microbiome ,3. Becaupathogen . P. gingivalis, has emerged as a key link between these two diseases. This enzyme, which is unique among prokaryotes, catalyzes the post-translational conversion of arginine to peptidyl citrulline [P. gingivalis is associated with a wide range of diseases and pathological conditions [Rheumatoid arthritis was recently reported to be a comorbidity of periodontitis , with matrulline ,8,9, witnditions . NeverthP. gingivalis survival rate under aerobic conditions [PPAD can promote biofilm formation both in single- and dual-species systems enhancing the nditions ,12. Thisnditions . ProlongNeutrophils, also known as polymorphonuclear leukocytes (PMNs) are the most abundant immune cell type in blood, circulating in a dormant state. Upon stimulation by a chemoattractant, neutrophils cross the endothelium to enter the infected site . PathogeApoptosis is a type of programmed cell death that guarantees control and balance of the numbers of neutrophils, triggering the resolution of inflammation and preventing extensive damage to the surrounding tissue . In the P. gingivalis may delay PMN apoptosis, the involvement of specific Bcl-2 family members has not been determined. The pro-survival effect of P. gingivalis is thought to be due mainly to the presence of lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria [P. gingivalis-associated virulence factors, inducing the expression of pro-inflammatory cytokines and prolonging neutrophil survival [During infection, the expression of anti-apoptotic proteins is upregulated, prolonging cell survival and blocking the resolution of inflammation. Although bacteria . LPS is survival ,23,24. P. gingivalis has been shown to induce the expression of PPAD, which has a direct effect on apoptosis inhibition. These effects, however, were not observed when epithelial cells were invaded by P. gingivalis, indicating that PPAD-mediated survival is restricted to particular types of cells [Infection of human dental follicle stem cells with of cells ,26. Thesof cells ,28. Althof cells ,30, the P. gingivalis and the anti-apoptotic properties of its virulence factor towards neutrophils were evaluated by analyzing the time-dependence of programmed cell death induced by this bacterium. Unstimulated neutrophils (UN) were incubated with wild-type P. gingivalis (ATCC33277 WT) or a mutant lacking the enzymatic activity of PPAD, resulting from the substitution of the catalytic amino acid Cys351 by Ala (PPAD mut), at various multiplicities of infection (MOIs) for 3 h, 24 h, and 48 h, and the neutrophil survival rates were determined.P. gingivalis than with the PPAD mutant , is induced by different transcription factors, including NF-κB and STAT . NF-κB, P. gingivalis. Similarly, IL-6 secretion differed in neutrophils infected with WT and PPAD-deficient P. gingivalis. These findings indicated that PPAD strongly contributes to the immunomodulatory activity of P. gingivalis through these pro-inflammatory cytokines. Stimulation of neutrophils with WT bacteria induced the production of TNF-α in a time-dependent manner. By contrast, stimulation with the PPAD mutant strain induced a substantial increase in TNF-α production between 3 and 24 h. The diminished neutrophil response might be due to the lower pathogenic activity of the PPAD mutant strain. Unlike TNF-α, IL-6 concentration markedly increased over time in the presence of both bacteria strains. This finding suggests that, at the beginning of the infection when the pathogen is present in low numbers, the observed response might be attenuated to provide sufficient time for colonization.The release of pro-inflammatory cytokines during infection indicates activation of the host’s innate immune system . TNF-α rP. gingivalis, as it ensures access to an elevated amount of nutrients . P. gingivalis also requires evading the antibacterial activities of the host immune system. The citrullination of host proteins, such as antimicrobial peptides, signaling molecules, and histones, diminishes host defenses by the innate immune system. This may manifest as a reduced efficiency in capturing pathogens by NETs, providing further evidence for the essential role of PPAD during pathogenesis [P. gingivalis were more protected from phagocytosis than the PPAD-deficient strain, indicating that PPAD was associated with this protective activity, findings consistent with previous results [Pg, challenge with the PPAD mutant strain increased the phagocytosis-induced apoptosis of neutrophils, which could explain the diminished expression of the anti-apoptotic proteins A1 and Bcl-xL. The shielding effect of PPAD was further indicated by the significant release of ROS following stimulation with the PPAD-deficient strain, as phagocytosis is the main signal for the release of enzymes catalyzing the production of ROS. Because PPAD activity is required for maximum gingipains activity, the present results are in agreement with results showing decreased phagocytic activity in the presence of RgpA [Prolongation of inflammation and bleeding is crucial for ogenesis ,63. Addi results . Moreove of RgpA .The long-term goal of this research is to identify and develop novel diagnostic markers for periodontal disease and other chronic inflammatory diseases. This might result in the establishment of new diagnostic tests. At present, the diagnosis of periodontitis is based on clinical examinations, which indicate the degree of tissue damage. These examinations, however, are time-consuming, painful, and subjective ,66. SurgThroughout the study, the HoxB8 model system was used   was grown for 7 days on Brain–Heart Infusion  agar plates supplemented with yeast extract, 0.5 mg/mL L-cysteine (reducing agent), 10 µg/mL hemin, 0.5 µg/mL vitamin K and with 1 µg/mL tetracycline  for the mutant strain. On day -1, the optical density (OD600) was set to 1.0 in liquid BHI media using a DeNovix (DS-11+) spectrophotometer. The C351A mutant strain (“PPAD mut”) expresses an inactive PPAD enzyme constructed by a mutation in the catalytic site  [alanine) . P. gingivalis. Following the selected time point, supernatants were collected for ELISA assay. Cells were collected for viability, ROS production analysis, and Bradford protein quantification using accutase treatment. On the day of the experiment (day 0), differentiated HoxB8 neutrophils were challenged with + was measured using FACS: Calibur  or LSR Fortessa (BD). Data were analyzed using FlowJo v10  software. The percentage of viable cells was measured by staining with Annexin-V-APC at 1:400  or Annexin-V eFluor450 diluted at 1:200  in 1× Annexin Binding Buffer . Alternatively, to determine the amount of generated reactive oxygen species, cells were stained for 20 min at 37 °C with 20 μM 2′,7′-dichlorofluorescein diacetate (DCFH-DA #D6883) (Sigma-Aldrich). The fluorescent signal from DCF®-PSQ membrane (Merck-Millipore) using electro-transfer. The membrane was blocked for one hour in 5% BSA-PBS-Tween 20 or 5% Milk-PBS-Tween 20 (BioShop). The protein of interest was detected using primary antibody against Mcl-1 , Bcl-xL , A1 , GAPDH  and horseradish peroxidase (HRP) conjugated anti-rat/anti-rabbit secondary antibody . Finally, the membrane was treated with Pierce™ ECL Western Blotting Substrate  and imaged on Hyperfilm . Pictureswere captured by the ChemiDoc™ MP imaging system . WEHI-231 cell line was kindly provided by Prof. Andreas Villunger .After indicated stimulations, cells were harvested and lysed in CHAPS buffer . ProteiSecreted TNF-α and IL-6 levels were evaluated using standard ELISA carried out with commercially available kits  according to the manufacturer’s instructions. Absorbance was measured using Flex Station 3  at 450 nm and corrected at 570 nm. ® SK diagnostic microscope with a 4.5× magnification. The phagocytic activity of neutrophils was assessed by invasion assay. Neutrophils were seeded along with bacteria in MOI:50 for 1 h at 37 °C. Cells were washed twice in PBS and then lysed with distilled water for 20 min. The lysate containing invading bacteria was transferred to a BHI agar plate (without antibiotics) and incubated for 3 days in anaerobic conditions at 37 °C. After 3 days, colonies were counted using an OPTA-TECHp < 0.05) was assessed using an unpaired t-test. Analysis was carried out using GraphPad Prism 8.0.1.Statistical significance (P. gingivalis. Inhibition of neutrophil apoptosis hinders the resolution of inflammation, prolonging the chronic state of periodontitis and eroding tooth-supporting tissues. In addition to elevating the expression of anti-apoptotic proteins, PPAD significantly increased the release of pro-inflammatory cytokines, such as TNF-α and IL-6. Moreover, PPAD was found to play a role in shielding P. gingivalis from phagocytosis while quenching the release of ROS by neutrophils.The present study was designed to better understand the contribution of PPAD to the infinite loop of inflammation. Study results showed that the expression of A1/Bfl-1, a neglected Bcl-2 family member, is strongly dependent on PPAD expression by


Insanity as a defence against criminal conduct has been known since antiquity. Going through significant reformulations across centuries, different jurisdictions across the globe, including Nigeria, have come to adopt various strains of the insanity defence, with the presence of mental disorder being the causative mechanism of the crime as their central theme. A critical ingredient in the Nigerian insanity plea is the presence of ‘mental disease’ or ‘natural mental infirmity’ as the basis for the lack of capacity in certain cognitive and behavioural domains resulting in the offence. Mental disorders, which are the biomedical formulations of this critical legal constituent are primarily subjective experiences with variable objective features. Using illustrative cases based on psycho-legal formulation as well as reform-oriented and fundamental legal research, it is shown that Nigerian courts have held that claims of insanity based on the accused person’s evidence alone should be regarded as “suspect” and not to be “taken seriously.” Thus, Nigerian judicial opinions rely on non-expert accounts of defendants’ apparent behavioural abnormalities and reported familial vulnerability to mental illness, amongst other facts while conventionally discountenancing the defendants’ plausible phenomenological experiences validated by expert psychiatric opinion in reaching a conclusion of legal insanity. While legal positivism would be supportive of the prevailing judicial attitude in entrenching the validity of the disposition in its tenuous precedential utility, legal realism invites the proponents of justice and fairness to interrogate the merit of such preferential views which are not supported by scientific evidence or philosophical reasoning. This paper argues that disregarding the subjective experience of the defendant, particularly in the presence of sustainable expert opinion when it stands unrebutted is not in the interest of justice. This judicial posturing towards mentally abnormal offenders should be reformed on the basis of current multidisciplinary knowledge. Learning from the South African legislation, formalising the involvement of mental health professionals in insanity plea cases, ensures that courts are guided by professional opinion and offers a model for reform. Since ancient times, the defence of insanity against criminal behaviour has been recognised . The M’NThus, the M’Naghten’s rules’ elements were essentially replicated in the Nigerian insanity defence until 1948, when a volitional prong was added by judicial pronouncement . The M’Naghten’s rule has been criticised in the legal literature for having an excessively cognitivistic slant that ignores the importance of volition in human conduct . The extEvidence as to the past history of the accused.Evidence as to the conduct of the accused immediately preceding the killing of the deceased.Evidence of prison officials who had custody of the accused before and during his trial.Evidence of medical officers who examined the accused.Evidence of relatives about the general behaviour of the accused and the reputation he enjoyed for sanity or insanity in the neighbourhood.Evidence showing the insanity runs in the family of the accused.Other facts which will help to discharge the burden of proof.Furthermore, the Supreme Court of Nigeria has maintained a view that insanity is to be determined in the legal sense and is an issue of fact that should be decided by the courts rather than physicians in the practical formulation of insanity in Nigerian courts . It is aA crucial evidentiary formulation was added by the Supreme court in Guobadia v State (2004) when it held that: “evidence of insanity tendered by an accused person himself is suspect and is not usually taken seriously.”A number of reasons may be adduced for this judicial position. First, the court may be wary of deception on the part of the accused, given the seriousness of the crime of murder which is the usual impetus for the insanity plea . A recencum grano salis. The right to a fair hearing is guaranteed under Section 36(4) of the Nigerian constitution .On the other hand, this judicial position has inherent problems. First, it appears arbitrary. Arbitrary, in general, has been defined as “not supported by fair, solid, and substantial cause, and without reason given” while arbitrary discretion has been described as: “a decision that is made wrongfully, possibly due to whim or for the wrong or unsound reasons” . The couMore importantly, mental disorders constitute phenomenological issues primarily since they are essentially ‘lived experience’. Phenomenology is the study of structures of consciousness as experienced from the first-person point of view . The patOn the basis of the foregoing formulation, this paper argues that Nigerian courts rely with greater confidence on non-expert fact-based accounts of defendants’ apparent behavioural abnormalities and familial vulnerability to mental illness  rather than their plausible phenomenological experiences (largely subjective contemporaneous facts) in reaching a conclusion of insanity. This is against a background of judicial neglect of medical opinion in insanity cases based on the notion that the determination of insanity in the legal sense is the sole preserve of the courts. Research has shown that expert opinion is sought in a little over a third of reported criminal cases with the insanity plea being mainly utilized in murder trials . Yet theThe inquiry addressed by this paper is relevant to the practice of forensic psychiatry and psychology for a number of reasons. In its focus on interrogating the application of legal tests for insanity, it has implication for the education and training of expert psychiatric witnesses as well as the development of forensic psychiatric practice in Nigeria. This review similarly highlights the importance of utilizing expert witnesses by the courts especially in cases where there is only a subjective claim of psychiatric illness. This paper also has psycho-legal implications as well. From a fundamental research and reform-focused perspective , 34, it The conceptual analysis in this paper is underpinned by two legal theories: the theory of legal positivism and the legal realism theory. Legal positivists seem to agree that the validity of a norm in any legal system is solely based on its endorsement, invocation, practice or enforcement by some relevant agents at a relevant time . Thus, tOn the other hand, legal realism  holds thThis paper presents its arguments using illustrative cases as well as a conceptual critique of judicial reasoning in decided insanity cases. The rest of the paper is arranged as follows: section two conducts a brief review of the Nigerian insanity plea with applicable rules of evidence while section three offers a critical analysis of illustrative cases involving the insanity plea.Section four focuses on a summary of the South African legal position on the insanity defence for the purpose of jurisdictional comparisons. Section five presents the discussion of the findings while section six provides a recommended model for judicial decision-making in relevant instances and conclusions are presented in section seven.The Nigerian insanity defence is composed of two parts . The first limb serves as an exoneration by recognising that mental illness or a natural mental infirmity can impair one’s ability to understand, control, or recognise the wrongness of behaviour. A second limb is non-exculpatory in that it holds the defendant accountable for the extent to which particular delusions cause him or her to act legally or illegally. Despite this, the M’Naghten’s laws  are largely preserved by the Penal Code Act, Section 51 (Northern Nigeria), and it lacks a volitional component.“a defect in mental power neither produced by his own default nor the result of the disease of the mind” . A similar dimensional perspective has been adopted in Ghana since the second half of the 20th century , the court was inclined to recognize a disordered state of the mind as a spectrum stretching from ‘disease of the mind’ to ‘natural mental infirmity’. Fortunately, natural mental infirmity has been fairly defined as:  century , 44. Con century , 10. IntFrom a biomedical perspective, the two variants of mental abnormality imply the presence of recognizable mental disorders and is a point of science upon which expert opinion ought to be sought . Section 136 provides that the burden of proof regarding any fact  is on the party which seeks to convince the court as to the existence of that fact. This provision may also ensure that the party adducing such evidence is allowed to prevent the opposing party from adducing evidence on any other relevant matter (section 138). While section 135 places a burden of proof beyond reasonable doubt on the prosecution in criminal matters, this shifts once the defence raises any exception to criminal liability as afforded by section 139(1). Where the insanity defence is thus raised as an exemption to the criminal conduct, section 137 places the burden of proof on the balance of probability on the defendant. However, section 138 of the Evidence Act (2011) grants the court wide powers with regard to the existence of facts related to the admissibility of any evidence by indicating that the existence or non-existence of those facts is to be determined by the courts.It is here submitted that this determination becomes an opinion of the court. With regard to insanity, this opinion is formed on a matter that is largely one of science and not merely one of every-day facts. The Evidence Act (2011) provides guidance in respect of such opinions. Section 68 stipulates that persons who have special skills in certain foreign laws, customs, science or art are regarded as “experts” and their opinions in such specialized matters aid the courts in framing legal decisions. An expert is defined by a combination of knowledge, experience and skill .Unfortunately, the courts are not compelled by this act to call expert evidence. Research evidence suggests that expert opinion is sought in slightly over a third of reported criminal cases which are murder trials . Its rat“evidence of insanity tendered by an accused person himself is suspect and is not usually taken seriously.”This was an appeal case in which a man was charged with the murder of his 2-year-old step-brother. His plea of insanity was made on the basis of a strange experience of being in ‘dream land’ and being ‘pursued by someone’. He thereafter ran into ‘something’ and found that he had stabbed the two-year-old. The appellant’s father testified for the prosecution and indicated that the defendant had a history of mental illness treated by traditional healers (previous act). The psychiatrist who saw the accused in custody (1 year and 2 months after the crime) found no evidence of mental disorder. However, the investigating police officer who took the defendant’s statement observed that the behaviour of the appellant was ‘abnormal’ (contemporaneous act). The trial court disbelieved the appellant’s testimony that he did not know what he was doing. Subsequently, the Supreme court held as follows: previous act as required in Madjemu. The explanatory power of this previous act with its need for intervention  is that it antedated the crime suggesting its role in affording the accused the legal excuse of insanity. An objective observation of his contemporaneous abnormal acts not long after the crime by the investigating police officer provides another acceptable criterion. However, the medical opinion negated the subjective experience of the appellant perhaps suggesting that he had no symptoms at the period of the psychiatric consultation and at the time of the offence. The failure of his defence under limb one of the insanity plea  is not the bone of contention since the court has the final say in the determination of legal insanity.In this instance, a history of mental illness existed although not treated by orthodox means. The fact that it was not treated in an orthodox setting does not negate its existence since the Supreme court had not indicated that treatment in orthodox settings alone constituted validation of a history of mental illness. This gives rise to a obiterHowever, the This was an appeal case in which the defendant killed a woman by striking her with a cutlass. He had strange beliefs in which he claimed that his supposed lover was being hidden from him by the woman. He claimed he felt he was ‘possessed’ by a spirit on the day of the offence and believed he was under a spell cast upon him by a witch (Contemporaneous acts) and this led to his attacking the woman. The overall opinion of the expertGoubodia); (ii) the opinion of the expert witness could not be relied upon since there was no ‘conclusive diagnosis’ of insanity; (iii) the history of mental illness in the mother not backed up by ‘scientific’ or ‘medical’ analysis and that neither the mother of the patient nor the social worker who got the history of mental illness in the mother testified in the case; (iv) there was no cogent evidence of the past mental state of the accused person before the alleged incident.In spite of the above, the trial court held that the defendant was not insane in the legal sense for the following reasons: (i) accounts of the abnormal state of mind came from the defendant himself (‘suspect’ and ‘not taken seriously’ per via tenuous inference but on the basis of the evidence before the court. The court further held that the proof of insanity could be constituted by “any or a combination” of the criteria outlined by the Supreme court as evidence supportive of insanity (see section 1.0 above). The list not qua conclusive, the court might equally rely on any other relevant fact which may assist it in coming to a conclusion of legal insanity. Additionally, the burden of proof of insanity was interpreted carefully as not one “beyond reasonable doubt.” Once the accused had led relevant probable/preponderant evidence in support of his claim, the burden was shifted to the prosecution to rebut the claims of the accused. If the resultant burden on the prosecution was not discharged, the claim of insanity should succeed.However, the appeal court held that the burden of proof with regard to insanity was a light one and one to be discharged on the balance of probability or preponderance of evidence. It was not to be viewed speculatively or The court declared that to require more from the accused would be to demand proof of innocence or sanity which are constitutionally and statutorily presumed . The court cautioned that while the trial court had the discretion to believe or disbelieve the testimony of the medical expert, the decision to reject expert opinion ought to be supported by a “reasonable hypothesis derived from the evidence on record.” Based on the failure of the prosecution to controvert the evidence of insanity (subjective claims supported by expert opinion), the initial finding of guilt was reversed on appeal and a verdict of “Not Guilty By Reason of Insanity” was substituted with the accused remanded in an asylum during the pleasure of the Governor.The South-African legal framework that regulates the insanity defence, also has its roots in the M’Naghten rule  as the cThe burden of proof regarding the accused’s criminal liability rests on the party who raised the issue . The preIt was pointed out earlier that Nigerian courts do not attach a lot of weight to the personal account of an accused who alleges that he had a mental illness when the crime was committed. The South African position is that a court must refer such an accused for a forensic assessment by a court appointed mental health professional or panel of such professionals (CPA s78(2)). Where it appeared from the accused’s general demeanour in court and his interactions with his legal representative that mental abnormalities may be inferred, the court ought to proceed in terms of s 78(2) . SnymanThus, it is not left up to the court to decide if the “alleged” presence of a mental illness is real or credible. This is determined by experts in the field with the necessary knowledge and experience. In S v Mabena (2007), Nugent JA observed as follows:“Mental illness” and “mental defect” are morbid disorders that are not capable of being diagnosed by a lay court without the guidance of expert psychiatric evidence. An inquiry into the mental state of an accused person that is embarked upon without such guidance is bound to be directionless and futile.”inter alia focuses on the individual’s account of the crime (a) of the CPA). For more serious offences, the court appoints a panel of experts consisting of the head of the psychiatric hospital or a psychiatrist appointed by him or her, two further psychiatrists (one appointed by the court and one by the accused) and a clinical psychologist where the court so directs . The psyhe crime . The acche crime  adds thaThe mental health professionals must provide a report to the court setting out the diagnosis (s 79(4)(b) of the CPA) and a recommendation on whether the accused was criminally responsible at the time of the commission of the offence or not (s 79(4)(d) of the CPA). Where the finding is not unanimous, this must be stated in the report and the differing findings must be stated. (s 79(5) of the CPA).If the report is unanimous, the court may determine the matter based on that report without hearing evidence on it – provided the prosecutor and the accused do not dispute it (s 79(3) of the CPA; S v Sithole, 2005; S v Vika, 2014). If the report is not unanimous, the court may hear evidence including from those who conducted the psychiatric assessment under section 79. The same applies if the accused or prosecutor disputes the findings in the report .If the recommendation is that the accused was indeed criminally responsible but that his ability to appreciate the wrongfulness of his act or to act in accordance with such appreciation was diminished, such diminished capacity will be taken into account during sentencing per section 78(7) of the CPA . Factors like mental illness, provocation, jealousy, severe emotional stress or even intoxication may affect the offender’s emotions to such an extent that his/her criminal responsibility may be diminished. Diminished criminal responsibility presupposes criminal capacity but reduces culpability. Diminished criminal responsibility is not a defence against a charge  but rather a factor to be considered during sentencing. (S v Mnisi 2009 (2) SACR 227 (SCA) at para 4).Furthermore, diminished criminal responsibility allows for the impact of perhaps a less serious mental illness to be taken into account when delivering a sentence in cases where the mental illness did not have a “serious enough” impact on the accused’s criminal capacity to render him/her not criminally responsible. Cases where diminished criminal capacity is alleged present an exception to the rule in the South African criminal justice system that mental health professionals should be approached for a forensic assessment in cases involving mental illness. This exception may be because diminished criminal capacity presupposes criminal capacity. The court may, however, consider expert evidence (if available) in mitigation of the sentence.The above process allows an accused to convey his personal experience of how the mental illness impacts him/her to a mental health professional with the necessary skills and experience to interpret such information. The court’s initial “suspicion” that an accused might have a mental illness may very well be confirmed through this process. Such an enquiry may also clear up the position for the court in cases where the court was doubtful of the authenticity of the display of what seemed like symptoms of a mental illness. The burden is not placed on the court to decide whether the accused has a mental illness or intellectual disability, this decision is made by mental health professionals, as it should be.The final decision concerning the criminal capacity of the accused is a legal one and is ultimately taken by the court . This leFrom the above, it is clear that South African courts are not left to their own devices when deciding whether a mentally disordered accused is criminally responsible. Whenever the court suspects that an accused may have a mental illness that impacts his/her criminal capacity, its presence or otherwise must be determined by mental health professionals. This position ensures that expert opinion is duly considered in cases involving mental illness, which aids in the delivery of justice.The aim of this paper was to demonstrate the misalignment between the subjective experience of the mentally ill defendant and the objective judicial unawareness of their internal states in certain cases. This discrepancy could potentially lead to a miscarriage of justice as shown by one case reversed on appeal. The implications of our findings for the practice of forensic psychiatry and psychology are numerous. First, this paper has broadened our understanding of the application of legal rules relevant to the insanity plea in Nigeria  and seeks to refine such applications , 59, 60.Second, this paper contributes to expert witness education in reminding the expert witness that their clinical assessments seek to answer critical legal questions which have direct bearing on justice and the culpability or otherwise of patient-defendants , 68. In Third, this review could potentially educate judicial actors in Nigeria on the need to rely appropriately on the assistance of credible expert witnesses in making non-dispositive determination of the existence of mental disorder in defendants within the overall context of the adjudication of insanity cases , 43, 69.A most significant issue raised by our analysis is the fact that symptoms of mental disorder are largely phenomenological – first-person in nature , 75–77. Beyond the subjectivity of psychiatric symptoms however, it is important to address the existence of objective psychiatric and psychological assessments of alleged mentally ill defendants. These are admittedly often based on client self-report but go beyond the subjective by treating speech acts, empirically based psychometric measures, and motor behaviors which are objectively observable and measurable. Such assessments include scores on cognitive tests and personality inventories as well as findings on mental state examination , 86 evenIn particular, there are tools that could assist in assessing the likelihood of malingering , 89, 90.It is reasonable to concede that where this subjective experience of mental symptoms is the sole ground for an insanity defence, the court ought to entertain the danger of deception. Even then, it is better to err on the side of justice by resolving the doubt in favour of the accused except in instances where other relevant circumstances would lead to a different conclusion. However, where corroborative expert opinion is sought and obtained, the mere fact that the claim of symptoms is from the accused alone should not weaken its credibility or overall merit in the determination of the presence of clinical mental disorder and/or legal insanity.While legal insanity is a legal determination, the central theme in its formulation is whether a mental disorder exists in the first place. Medico-legal debates continue as to the definition of insanity especially with regard to insane delusions . For insThis clearly raises the question of the position of the psychiatric expert with regard to the ultimate issue which in this case refers to whether the mental disorder deprived the defendant of the capacity to understand conduct, control action or appreciate the wrongfulness of act/omission. Jurisdictional variations exist as to whether or not the expert should address the ultimate issue . In NigeThis paper also contributes to the legal literature and policy in a number of significant ways. First, to the knowledge of the authors, it is the first to interrogate the settled but non-evidence-based judicial inclination towards discountenancing subjective insanity claims even when consistent with psychiatric expert opinion. It adopts both reform-oriented and fundamental research approaches , 34 in oSecond, it contributes to judicial policy by proposing a conceptual model that is supported by case law and contemporary exemplification for dealing with instances in which only the accused gives factual evidence as to their experience of psychiatric symptoms and when this evidence is validated by medical opinion. The premise of the current argument is that the courts ought to defer to the accused as an “expert by experience” as well as to objective expert opinion regarding the presence of mental disorder unless rebutted or discredited . Such an approach shows respect for the epistemic reality of the patient and avoids testimonial and hermeneutical epistemic injustice . This faThird, it contributes to the utility of legal theory in relation to the insanity defence by interrogating the stance of legal positivism as well as legal realism in the judicial construction of insanity in Nigerian courts. On the one hand, legal positivists would argue that judicial suspicion of uncorroborated subjective claims of insanity represents the precedential position , 36 and On the other hand, legal realism suggests that this judicial position is not one arrived at on the basis of objective and mechanistic logical processes but one that could have been informed by judges’ personal prejudices  towards Saidi Oseni gives expert witnesses and judicial actors a sense of what might constitute the “balance of probability or preponderance of evidence” regarding the presence of insanity in the accused. Given the lightness of the burden of proof in insanity cases, the court has provided guidance in the frame that “any or a combination” of the outlined evidentiary criteria supportive of insanity may be regarded by the court as satisfying the burden of proof. Yet within this space of probative value, there is a tendency to discountenance the subjective experience of the defendant-patient based on the sometimes erroneous belief that mental illness would have been observable to third parties prior to the offence. This may not always be the case especially with first episode psychosis in which other people might not have particularly noticed aberrant behaviour in the defendant for a substantial period of time. Since the burden of proof for insanity cases is on a balance of probability, criminal courts need not impose a heavier burden on the mentally ill by requiring the ‘scientific’ or ‘medical’ analysis of the history of insanity . Such a requirement seems to be an unduly high confirmatory threshold and tellingly introduces the bias instituted in Goubodia and related cases against a simplified (not simplistic) view of what constitutes a legal test for the presence of mental disease or natural mental infirmity.Perhaps another important psycho-legal issue to consider is that the pronouncement by the court of appeal in The current formulation of legal insanity in Nigerian courts indicates that insanity is conceived by the judiciary as a legal opinion in its entirety and medical opinion is typically treated as one of the facts presented as evidence before the court in support of the claim. This resembles an omnibus approach. The recommended decision-making model is onewhich describes a three-stage algorithmic model which starts with entertaining expert opinion on the ground of fact and science (the doctor is the expert by knowledge and skill while the defendant-patient is the “expert by experience”). The second stage involves determining the effect of the disorder on cognitive or volitional capacity. The last stage is the adjudicatory phase in which the judge makes a ruling on culpability.The courts ought to take the subjective uncorroborated claims of insanity  seriously and make certain that all necessary steps are taken to ensure that the claim is properly heard and examined. To refuse to attach any seriousness to it is to start the defence off on a platform of negative bias or prejudice. The attendant incredulity of the court may equally be extended to the opinion of the expert since a major portion of the substance of the expert’s opinion  was not to be taken seriously in the first place. In instances where expert evidence is called and is regarded as credible, the courts should hold such opinions as valid for the determination of the presence of “mental disease or natural mental infirmity” strictly. This, not being the ultimate issue, does not detract from the powers of the court to adjudicate independently.Saidi Oseni, the trial court disagreed with the only expert as to the conclusiveness of mental illness. In this way, judicial reasoning was substituted for expert knowledge and skill. To avoid this, it may be suggested that Nigerian courts should consider the possibility of allowing one expert on each side such that the court can exercise its discretion as to which expert to believe when experts disagree  submit(s) a report to the court with their recommendations. The court remains the final decision maker but is guided by experts in the field. South African courts rarely deviate from the recommendations in the mental health professional’s report as to the presence or otherwise of mental illness, illustrating that the court acknowledges that it lacks expert knowledge on the topic and has confidence in medical opinion.Based on the foregoing, the following recommendations are made:Overall, Nigerian courts currently place significant weight on non-expert accounts of defendants’ apparent behavioural disorder and familial vulnerability to mental illness as findings of fact and history. Plausible phenomenological experiences volunteered by defendants are regarded as generally suspect. This is not consistent with a valid phenomenological view of mental disorder and could eventually perpetuate epistemic as well as actual injustice. Thus, discounting the subjective experience of the defendant particularly in the presence of sustainable expert opinion could lead to miscarriage of justice and this judicial posturing should be reformed on the basis of current knowledge and exemplary developments in comparable commonwealth jurisdictions such as South Africa. To further assist itself in the transparent dispensation of justice, the Nigerian judiciary ought to more readily require the services of psychiatric expert witnesses especially in cases where non-expert corroborative evidence for insanity is lacking. Within this context, there should be greater emphasis on expert witness training for psychiatrists who are medically qualified to provide psychiatric expert opinions in Nigeria in order to enhance the credibility and reliability of such opinions presented to the courts in the process of adjudicating cases involving the insanity plea.Anubalu v. State (2019) LPELR 48088 (CA).Dasuki v Federal Republic of Nigeria (2016) (ECW/CCJ/JUD/23/16) ECOWASCJ 54.Emeryl v State (1973).Guobadia v State (2004) 6 NWLR 360.Madjemu v State (200a) (Pt. 52) FWLR 2210.Rex v Ashigifuwo (1948) 389. W.A.C.A.Rex v Omoni (1949) 12 W.A.C.A 511–513.Saidi Oseni v. The State (2017) LCN/10139(CA).De Vos N.O and Another v Minister of Justice And Constitutional Development and Others; InRe: Snyders and Another v Minister of Justice And Constitutional Development and Others 2015 (1) SACR 18 (WCC).Ngobeni v The State (A684/16) [2018] ZAGPPHC 715 (23 February 2018).S v Mabena 2007 (1) SACR 482 (SCA).S v Magongo 1987 (3) SA 519 (A).S v McBride 1979 (4) SA 313 (W).S v Mnisi 2009 (2) SACR 227 (SCA).S v Mphela 1994 (1) SACR 488 (A).S v Romer 2011 (2) SACR 153 (SCA).S v Sithole 2005 (1) SACR 311 (W).S v Vika (14519) [2014] ZAWCHC 155 (14 October 2014).M’Naghten’s case. (1843). UKHL J16.R v M’Naghten (1843) E. R. (Vol. 8).Constitution of the Federal Republic of Nigeria (1999).Evidence Act (2011).Criminal Code Act Chapter C39., (2004).Laws of the Federation of Nigeria. Criminal Procedure Act, Cap C41.Laws of the Federation of Nigeria (2004b). Interpretation Act. Cap 123. Federal Ministry of Justice.Laws of the Federation of Nigeria (2004c). Penal Code Law (1959).Criminal Procedure Act 51 of 1977.AO conceptualised the study and wrote the first draft of the manuscript. LP contributed the section on the South African insanity jurisprudence. OO contributed to the write up of the final version of the manuscript and provided critical comments on scope. All authors contributed to the article and approved the submitted version.The authors thank Unisa for funding the processing fees of this article.The 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.All 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.