Erector spinae block (ESPB) is an effective therapy for chronic shoulder pain. However, ESPB has not been used as a postoperative analgesia method in shoulder surgeries. In this case report, we report three patients undergoing shoulder surgeries that received ESPB preoperatively for postoperative analgesia. All patients had relief of preoperative pain and no associated motor block. Two of the patients manifested with low maximum pain scores  on a numeric rating scale (NRS). The other patient reported a maximum pain score of 8/10 on NRS. While this patient’s shoulder mobility immediately improved after ESPB application, the ESPB did not provide adequate analgesia for the postoperative period. The use of the ESPB for acute postoperative analgesia after shoulder surgery is novel and clinically interesting. However, postoperative analgesia was not completely opioid-sparing. Consequently, the efficiency of ESPB at the level of T2 for postoperative analgesia should be considered for surgeries that involve the shoulder cap given the possible inadequate migration of local anesthetic into the cervical plexus. Clinicians should carefully consider an ESPB as a postoperative analgesic option when considering shoulder operations and the possibility for the incomplete spread of local anesthetic in targeted neural structures. Erector spinae plane block (ESPB) has been reported for a variety of indications -2. ESPB Written informed consent was obtained from all patients in this report. Ethics board approval for case reports is not required by our institute.All of the patients received identical protocols for the induction and maintenance of general anesthesia, application of ESPB, preoperative and postoperative analgesia, and patient-controlled analgesia (PCA). Intravenous (IV) midazolam (2 mg) was given for sedation. After providing standard basic anaesthetic monitoring, each patient was placed in a sitting position. A 10-MHz ultrasound device  was used, and the T2 transverse process was selected as the needle insertion point. The ultrasound probe was placed 3 cm lateral to the T2 spinous process in a longitudinal parasagittal orientation to visualise the transverse process. Under sterile conditions, a 5-cm, 21-gauge needle  was inserted using the out-of-plane technique parallel to the sagittal plane directly over the transverse process. We confirmed the location by visualization of hydrodissection with 0.9% NaCl. We injected 25 mL 0.375% bupivacaine with 5 mL of 2% lidocaine and observed the linear spread of the local anaesthetic over the transverse process. Following injection, all patients expressed sudden pain relief in their shoulders and increased mobility. Induction of anesthesia was completed with the patients in a supine position with propofol (2 mg/kg), fentanyl (100 µg), and rocuronium bromide (0.6 mg/kg). General anesthesia was maintained with remifentanil infusion at the rate of 0.08 µg/kg/minute and 0.6 minimum alveolar concentration sevoflurane as the inhaled agent. For postoperative analgesia, all patients received 1 g paracetamol and 20 mg tenoxicam via IV administration. In the postanesthesia care unit (PACU), 25 µg fentanyl was applied if the patient reported a pain score of 4/10 or higher on a numeric rating scale (NRS). In case of pain persisting longer than 20 minutes, an additional 25 µg fentanyl was added to the treatment. For postoperative analgesia, all patients were scheduled to receive 1 g paracetamol via IV administration every eight hours. As rescue analgesia , diclofenac sodium (75 mg) was administered intramuscularly (IM). If the pain remained at the same level after a further hour had passed, IV meperidine (50 mg) was added. PCA with tramadol at 3 mg/mL concentration was programmed with no basal infusion; the demand dose was 10 mg with a 20-minute lock-out interval and was started in the PACU. Patients were closely monitored by a trained nurse, and a PCA follow-up form was completed in 24 hours.Patient One was a 30-year-old woman, American Society of Anesthesiologists (ASA) Classification I  with no coexisting diseases. She was scheduled for arthroscopic shoulder surgery. Her preoperative shoulder mobility over the shoulder joint was limited to 120° with severe pain. The patient described acute relief of the pain in her shoulder and increased mobility after ESPB performed before the surgery started. She was treated surgically for arthroscopic acromioplasty and bursectomy. Her pain was recorded as 1/10 on NRS and needed no additional analgesia in the PACU. Her maximum dynamic pain score was 4/10 on NRS. Her 24-hour PCA tramadol consumption was 40 mg total.Patient Two was a 65-year-old woman, ASA Class I  registered for a Neer Type 3 humeral fracture and surgical repair. She reported sudden pain relief after the application of ESPB. An open reduction and internal fixation via the anterolateral method was performed under general anaesthesia. In the PACU, she reported her pain as 2/10 on NRS with mobilization. At the 24-hour follow-up evaluation, she reported no pain score higher than 3/10 on NRS, and no rescue analgesic treatment was administered. Her total PCA consumption was 240 mg in 24 hours. Although her PCA consumption was high, she needed no fentanyl in the PACU nor additional diclofenac sodium and meperidine as rescue analgesia.Patient Three was a 39-year-old woman, ASA Class I  who presented for arthroscopic shoulder surgery. She had severe pain (8/10) on NRS with abduction-adduction at the shoulder and was not able to move over 30°. After ESPB, the patient was able to move her arm at the shoulder to approximately to 70° abduction without pain. She had acromioplasty and fibrous tissue resection in the shoulder joint including shoulder cap. In the PACU, her pain score was 8/10 on NRS, so she was given 50 µg fentanyl. Her PCA tramadol consumption was 240 mg in 24 hours. Despite the rescue analgesia treatment , her level of pain remained constant between 4/10 to 6/10 on NRS.Shoulder surgeries, especially arthroscopic procedures, cause significant postoperative pain in the first 24 hours following surgery . The intPrevious examinations of cadavers with radiographic evidence have demonstrated that local anesthetic penetration develops through connective tissues and ligaments towards the final paravertebral area when it is injected deep (anterior) into the erector spinae muscle -4. When The intensity of the postoperative pain is related to the extent of the surgical intervention and tissue damage created by the extent of adhesiolysis . RotatorThere are no examples or guidelines for the use of ESPB for the treatment of postoperative pain in shoulder surgeries in the literature. The surgery type, varying concentrations of local anesthesia, volumes, and individual anatomical variations may result in different outcomes. Further randomised controlled clinical trials in shoulder surgeries may reveal the analgesic range, opioid-sparing effect, and ideal dose concentration of ESPB, along with the possible drawbacks.


Low back pain is a costly healthcare problem and the leading cause of disability among adults in the United States. Primary care providers urgently need effective ways to deliver evidence-based, nonpharmacological therapies for chronic low back pain. Guidelines published by several government and national organizations have recommended nonpharmacological and nonopioid pharmacological therapies for low back pain.The Pain eHealth Platform (PEP) pilot trial aims to test the feasibility of a highly innovative intervention that (1) uses an electronic health record (EHR) query to systematically identify a phenotype of obese, older adults with chronic low back pain who may benefit from Web-based behavioral treatments; (2) delivers highly tailored messages to eligible older adults with chronic low back pain via the patient portal; (3) links affected patients to a Web app that provides education on the efficacy of evidence-based, nonpharmacological, behavioral pain treatments; and (4) directs patients to existing Web-based health treatment tools.Using a three-step modified Delphi method, an expert panel of primary care providers will define a low back pain phenotype for an EHR query. Using the defined low back pain phenotype, an EHR query will be created to identify patients who may benefit from the PEP. Up to 15 patients with low back pain will be interviewed to refine the tailored messaging, esthetics, and content of the patient-facing Web app within the PEP. Up to 10 primary care providers will be interviewed to better understand the facilitators and barriers to implementing the PEP, given their clinic workflow. We will assess the feasibility of the PEP in a single-arm pragmatic pilot study in which secure patient portal invitations containing a hyperlink to the PEP Web app are sent to 1000 patients. The primary outcome of the study is usability as measured by the System Usability Scale.Qualitative interviews with primary care providers were completed in April 2019. Qualitative interviews with patients will begin in December 2019.The PEP will leverage informatics and the patient portal to deliver evidence-based nonpharmacological treatment information to adults with chronic low back pain. Results from this study may help inform the development of Web-based health platforms for other pain and chronic health conditions.DERR1-10.2196/14525 Low back pain is the leading cause of disability worldwide and its prevalence increases with age . The mosPrimary care providers (PCPs) are typically the first clinicians to see patients with pain and treat approximately 52% of patients with chronic pain . ChronicThere is a growing body of evidence showing that nonpharmacological behavioral treatment programs, which promote self-management techniques  in April 2018.Application Use is of central importance, as it is the strongest predictor of successful behavior change in internet-based treatments [Mechanisms of Change such as improved knowledge and the development of self-efficacy, supported by the appropriate resources for behavior change, is anticipated to impact actual short-term behavior. Behavior maintenance is more likely when the behavior change promotes noticeable symptom improvement [The study is guided by social cognitive theory  and the eatments . Mechanirovement .The PEP will consist of an EHR query to identify patients who may benefit from the intervention, an invitation sent to patients via the patient portal to visit the PEP Web app, and the PEP Web app that includes three animated videos with evidence-based information about nonpharmacological treatments for low back pain including mindfulness meditation and physical activity .To define the low back pain phenotype to be used for the EHR query, we will employ a three-step modified Delphi method. This method is an iterative process that uses a systematic progression of three rounds of voting and is effective for determining expert group consensus that does not necessitate multiple face-to-face meetings . PCPs fr2, and opioid use.Prior to initiating the modified Delphi process, the expert panel will be briefed about the benefits of mindfulness meditation and physical activities for chronic low back pain. In step 1 of the modified Delphi process, PCPs will be contacted via email to vote on a list of preliminary ICD-10 codes for low back pain. The list will also include patient characteristics such as age≥50-79 years, body mass index (BMI)≥30 kg/mIn step 2, the list of criteria that did not meet consensus from step 1 will be distributed to the group of PCP experts for consideration and another vote will be taken. Finally, in step 3, the expert consensus panel will convene via videoconferencing or face-to-face to deliberate and agree upon the final pain phenotyping for the EHR query. Provider participants will receive a US $50 incentive for their time and participation.The portal invitation will be created using a user-centered design approach -36 to reFrom: The WFBH chronic pain study teamSubject: New treatments for low back painDear ____,click here.An automated analysis of your Wake Forest Baptist Health primary care record indicates you may benefit from new treatment options for low back pain. To learn more, The PEP Web app will be fully Web-based, requiring no downloading, and will be functionally available on both desktop and mobile browsers. Prior to beginning the PEP Web app program, patients will be asked to provide their highest level of education and to rate their low back pain on a sliding scale (0=no pain to 10=worst pain imaginable), on average, over the past week. The Web app will contain three animated videos narrated by a PCP named “Doc” who discusses non-pharmacological treatments for low back pain including mindfulness meditation ,37 and p2, report of low back pain for ≥3 months, and English speaking. Excluded patients will have cognitive impairment, with a Montreal Cognitive Assessment [To develop the PEP Web app, we will conduct semistructured, qualitative interviews with obese, older adults with chronic low back pain. Because older adults are likely to have unique requirements, needs, and desires with regard to the Web app design and functionality within the PEP, a user-centered design process is essential . At leassessment  score<22We will combine the EHR query, patient portal invitation, and PEP Web app into a seamless system to create the PEP .Epic serves as the EHR for WFBH. The Web app will run external to Epic. The EHR query will be limited to data elements that are common to all EHRs. Variable names may differ between EHRs, but the query logic will be universal. The EHR query will be validated using iterative testing cycles of 20 randomly selected individuals . Two reviewers who are blinded to the query output will independently review the EHR for these individuals. Disagreements between manual EHR review and query output will be reviewed, and the query will be modified, as needed. Testing cycles will continue until we reach 100% agreement between the query and manual chart review. The final EHR query will run weekly to identify potential candidates who already have an active patient portal account to receive a PEP portal invitation. Upon completion of the validation process, we will send a secure patient portal message to 1000 patients identified by the EHR query, inviting them to view three-animated videos and a list of recommended Web-based treatments about low back pain. The portal invitation will be sent two times, 1 week apart.To measure usability of the Web app, participants will be prompted to complete items from the System Usability Scale (SUS)  after viSecondary outcomes of using the PEP include feasibility and process measures including the reach of our portal outreach strategy . Effectiveness of the portal message invitation will be measured by the proportion of those who read the message that clicked on the Web app hyperlink. Lastly, a follow-up survey will be sent to patients 1 week after completion of the Web app, asking if they have tried any of the recommended techniques. Reponses to this survey will provide initial evidence regarding uptake of the recommended nonpharmacological treatments. All outcome data will be obtained by querying the EHR and Web app databases.Descriptive statistics for continuous variables (mean and SD) or categorical variables (frequencies) will be presented for patient characteristics and the outcome measures. Multiple linear regression will be used to examine potential associations between SUS scores and participant characteristics such as age, race, gender, and BMI. Logistic regression will be used to determine which participant characteristics are associated with the proportion who read the portal invitation, those who click on the embedded Web app PEP link, and those who click on all the Web-based included treatments links. These analyses will determine which patients are more receptive to the intervention and which patients may require alternative strategies or messages. A large population of 1000 patients will allow the estimate of primary and secondary outcomes and will provide sufficient variability to plan a future larger study. If 300 patients (30%) complete the SUS, it will be possible to estimate the average usability within 2.8%, with 95% confidence.Internet use among older adults is increasing, with 67% of those aged ≥65 years reporting internet use . HoweverQualitative interviews with primary care providers were completed in April 2019. Qualitative interviews with patients will begin in December 2019.This is the first study to examine the usability and reach of a patient portal outreach strategy for delivering evidence-based, nonpharmacological treatment information to adults with chronic low back pain. Given the limited efficacy and frequent adverse effects of opioid medications used to treat chronic low back pain, PCPs require methods for implementing evidence-based, nonpharmacological therapies in their clinical practices without substantial additional burden.This study is not designed to determine the effectiveness of the Web app. However, the findings from the follow-up survey will provide initial evidence regarding uptake of recommended nonpharmacological interventions. The long-term goals of this project are to test the efficacy of the PEP in a large-scale, hybrid, efficacy-implementation trial that will measure clinical outcomes including pain, physical function, and opioid prescription use over time and to adapt this research platform to a variety of other chronic health conditions including other pain conditions, for which there are established evidenced-based treatment guidelines.


It is estimated that the total annual financial cost for pain management in the U.S. exceeds 100 billion dollars. However, when indirect costs are included, such as functional disability and reduction in working hours, the cost can reach more than 300 billion dollars. In chronic pain patients, the role of pharmacogenetics is determined by genetic effects on various pain types, as well as the genetic effect on drug safety and efficacy. In this review article, we discuss genetic polymorphisms present in different types of chronic pain, such as fibromyalgia, low back pain, migraine, painful peripheral diabetic neuropathy and trigeminal neuralgia. Furthermore, we discuss the role of CYP450 enzymes involved in metabolism of drugs, which have been used for treatment of chronic pain . We also discuss how pharmacogenetics can be applied towards improving drug efficacy, shortening the time required to achieve therapeutic outcomes, reducing risks of side effects, and reducing medical costs and reliance upon polypharmacy. Approximately 44 million Americans are suffering from moderate to severe chronic pain . The cosTreatment of the chronic pain patients has a high risk of having poor outcomes, especially when patients are treated with opioid medications. Individualized approaches to treating chronic non-cancer pain are paramount in improving patient’s quality of life and functionality, and in preventing severe adverse effects from opioid therapy .In 2000, the completion of the Human Genome Project Research revolutionized the world of medicine; it opened up a new scope for disease process diagnosis, drug development and practicing medicine using an individualized approach. Advances in research, technology and policies that empower patients, also enable the development of personalized medicine in the field of pain management.When health care providers are diagnosing and treating chronic pain patients, a multitude of factors influence both processes, such as age, sex, ethnicity, comorbidities, multi-drug therapy and lifestyle. All of these factors, to a certain degree, including the genetic contribution to different types of pain and the genetic influence on drug efficacy and safety, will influence the outcome of pharmacotherapy.Fibromyalgia (FM) is a disease herald by chronic widespread pain, without any obvious organic lesions. It has an incidence of 2% in the general population and affects women predominantly . A varieSLC6A4) and transient receptor potential vanilloid 2 genes (TRPV2) are coinciding with a signal in the chromosome 17p11.2–q11.2 regions, suggesting the linkage of these two genes with FM [Arnold et al. performed linkage analysis with a genome-wide linkage scan for FM in a cohort of 116 families . Coordin with FM . Studies with FM .O-methyltransferase (COMT), the enzyme involved in the degradation of dopamine, norepinephrine and epinephrine, has been found to contribute to FM susceptibility through genetic polymorphism [Val15Met (rs4680). Studies have found associations between rs4680 and FM susceptibilities in Brazilian, Spanish, Turkish, and Israeli populations, whereas a Korean population displayed COMT SNP rs4818 and rs4633 association with FM [Catechol-morphism . One of 5Met rs460. Studie with FM .DRD4), monoamine oxidase (MAO-A), β-2 adrenergic receptor, guanosine triphosphate cyclohydrolase (GTPCH) , γ-aminobutyric acid (GABA), a receptor β3 subunit (GABRB3); sodium channel NaV1.7 (SCN9A); apolipoprotein (APOE); myelin transcription factor 1-like (MYT1L)  and neurexin (NRXN3), a synaptic scaffolding stabilizer in glutamate and GABA neurotransmission [ACE) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in 200 FM Turkish patients [MTHFR C677T polymorphisms were associated with symptoms of stiffness and xerophthalmia [Other associated genes involved in the susceptibilities of FM are: Dopamine receptor D4  and serotoninergic system (HTR2A) variations , there aA118G, rs1799971, in the opioid receptor µ 1 (OPRM1) gene [OPRM1 A118G genotype during recovery of low back pain and sciatica [The genetic factors increase the susceptibility for chronic low back pain (CLBP) by 50%. The risk for persistent CLBP and sciatica is increased by the SNPs M1) gene . A studysciatica . Women wsciatica .A substitution of glutamine to tryptophan (Gln326 to Trp) in the α2 chain of collagen IX  showed association with inherited lumbar disk disease (LDD) . The Trprs4680 with long-term disability and delayed recovery in European patients with LDD, whereas another study showed that COMT SNPs rs4680 has been associated with improvement of CLBP after treatment [CG for rs165656 and CT for rs4633), but none was observed in patients with two minor alleles (CC for rs165656 and TT for rs4633) [COMT polymorphisms was demonstrated to influence pain phenotypes in women with chronic pain, which reveals that gender is a significant factor in tailoring pain management . COMT SNreatment . The hig rs4633) . COMT poGDF5), with the variable nucleotide tandem repeat (VNTR) in the chondroitin sulfate-1 encoding domain of the aggrecan gene (ACAN), with matrix metalloproteinase SNPs [An increased risk for LDD has been associated with caspase-9 polymorphisms (CASP9)—an enzyme that activates the intrinsic pathway of apoptosis, with elevated levels of growth differentiation factor 5 (ase SNPs . It is sEDNRA), encoding MTHFR, encoding endothelial nitric oxide synthase (NOS3), encoding ACE, encoding β-2 transforming growth factor (TGFB2), encoding β-2 transforming growth factor receptor (TGFBR2) and neurogenic locus notch homolog protein 3 (NOTCH3) (a receptor that is involved in vascular development and integrity) [ESR1) genetic variability [ESR1 is a receptor and a nuclear transcription factor that regulates the endogenous steroid hormones, and promotes cell proliferation and differentiation, including neuronal cells. Therefore, SNPs in the ESR1 gene can interfere with these functions. Individuals that displayed CC or CG genotypes, and CC combined phenotypes, have an approximately 50% increased risk for migraine in a Caucasian population [ESR1 rs1801132 (325C>G) is positively associated with migraine in a Spanish population. ESR1 rs2228480 (594G>A) carries a higher risk for migraine in an Australian population, whereas ESR1 rs2234693 is associated with migraine susceptibility in a Chinese population [5,10-MTHFR C677T (rs1801133), A1298C (rs1801131), and nicotinamide-N-methyltransferase (NNMT), an enzyme that catalyzes the transfer of methyl group from S-adenosylhomocysteine to nicotinamide, are shown to significantly increase the plasma level of homocysteine [Similar to the pain conditions mentioned above, migraine headache has a 50% genetic component to its etiology . The inctegrity) . These gtegrity) . The horiability . ESR1 ispulation . In addipulation . The glupulation . High le1801132 3C>G is pocysteine .rs4633, rs6267, rs4680, rs6270, rs740602) was found, although the authors have concluded that an association between COMT genetic polymorphisms and migraine pathogenesis cannot be entirely excluded [The association between five COMT polymorphisms and migraine with or without aura and tension-type headache was studied in a Japanese sample population . No assoexcluded .Nav1.7 and its association with painful DPN. Ten patients with painful DPN were identified for 12 rare variants of Nav1.7; these patients were diagnosed for a significantly shorter period, reported more severe burning pain, and were more sensitive to deep pressure [Nav1.7 can increase the risk of developing painful DPN, and that further research is needed to understand how channel dysfunction contributes to the mechanism of specific pain phenotypes [Painful diabetic peripheral neuropathy (DPN) is a disabling complication in diabetic patients, which negatively affects their quality of life . Two of pressure . Furtherenotypes .Chr1p35.1 (ZSCAN20-TLR12P) at rs71647933 in females and Chr8p23.1 at rs6986153 in males. In addition, males displayed a higher heritability for DPN (30%), compared to females (14.7%) [Meng et al. conducted a GWAS on 961 patients with peripheral DPN with 3260 diabetic patients as controls . The aut (14.7%) .APOE is an important component in mitigating the cellular oxidative stress and inflammation response. Animal models with sciatic nerve injury demonstrate an increased level of APOE. Conversely, animal models with sciatic nerve injury and a decreased level of APOE, displayed impaired nerve regeneration . On the Despite addressing the modifiable risk factors for developing peripheral DPN , and supporting a tight glycemic control, studies have not demonstrated a decreased incidence of associated neuropathic pain in diabetic patients . Genetic5-HTT-linked polymorphic region (5-HTTLPR) and the susceptibility and severity of trigeminal neuralgia (TN) in 244 Chinese patients, and a close association with treatment response to carbamazepine monotherapy [5-HTTLPR were determined as study limitations , which are membrane-associated proteins in the endoplasmic reticulum [Metabolism of many medications involves Cytochrome P450  [CYP2D6, CYP2C9, and predominantly CYP1A2, contribute to duloxetine metabolism into its active forms: glucoronate conjugate 4-hydroxy and sulfate conjugate 5-hydroxy-6 methoxy duloxetine. Inhibition of some of these enzymes can lead to interactions and changes in the outcome of therapy for the FM patient population [CYP2D6 enzyme subset. The administration of duloxetine to CYP2D6 poor metabolizers (PMs), along with inhibition of CYP1A2, demonstrated clinically significant higher duloxetine exposure, emphasizing that co-administration with a potent CYP1A2 inhibitor should be avoided. However, a CYP2D6 PM in the absence of CYP1A2 inhibition does not require dose adjustments, despite the 1–3 fold increase in plasma duloxetine [CYP2D6 substrate  is not recommended, due to potential increases in toxic levels of the substrates [Pharmacotherapy of FM involves diverse classes of medications, such as antidepressants, anticonvulsants, non-steroidal anti-inflammatory and narcotic medications . The majnd CYP3) . Duloxetnd CYP3) . CYP2D6,pulation . It is kloxetine . Furtherbstrates .CYP2C19, and into hydroxyl metabolites through CYP2D6 [CYP2D6 to pharmacologically active metabolite desmethyltramadol [CYP2D6 result in reductions of desired therapeutic effects or increased incidence of side effects [Amitriptyline, a tricyclic antidepressant (TCA) prescribed for FM, is metabolized into its active compound nortriptyline through isoenzyme h CYP2D6 . Additiotramadol . Genetic effects .CYP450 metabolism. CYP2C9 enzyme contributes to the oxidation and metabolism of NSAIDs, and N-demethylation of some antidepressants  [CYP2C9*3 genetic polymorphisms have an increased risk for gastrointestinal bleeding [CYP2C9 genetic variations [Pharmacotherapy of CLBP includes classes of medications that extensively depend on oxetine) . There ariations .CYP2C9, the genetic polymorphisms of CYP2D6 have been of substantial interest in chronic pain management, particularly due to a bimodal distribution of individuals classified as PMs and ultra-rapid metabolizers (UMs) [In contrast to rs (UMs) . This dirs (UMs) .CYP2D6 enzyme demethylatilation into hydromorphone (stronger µ receptor binding), and on the CYP3A4 enzyme for metabolism into norhydrocodone [CYP3A4 inhibitor in these patients, due to an increased risk of a drug–drug interaction [Hydrocodone is a semi-synthetic opioid medication that depends on rocodone . Althougeraction .CYP3A4 enzyme metabolizes oxycodone by N-demethylation to noroxycodone, and the CYP2D6 enzyme catalyzes O-demethylation of oxycodone to oxymorphone, which is 14-fold more potent than the parent oxycodone [CYP2D6 genetic polymorphisms have a major effect on analgesic efficacy and the side effect profile of oxycodone; CYP2D6 UM displays an increased analgesic effect and toxicity, whereas CYP2D6 PM demonstrates reduced oxycodone efficacy [CYP3A4 inhibitors can significantly increase the analgesic effect and toxicity of oxycodone in patients with CYP2D6 UM phenotype [xycodone . CYP2D6 efficacy . Furtherhenotype .rs1799971) on chromosome 6 in the OPRM1 gene coding for µ-opioid receptor leads to a substitution of aspartate for asparagine, altering the N-glycosylation of the receptor protein [OPRM1 rs589046, and OPRM1 rs563649 with poor oxycodone analgesic response has been demonstrated [OPRD1 rs419335 that showed decreased analgesia, following oxycodone for visceral heat stimulation. The T allele of OPRM1 rs563649 carriers and C allele of OPRM1 rs589046 demonstrate decreased oxycodone efficacy to experimental skin heat stimulation.SNP 118A>G  patients, whereas rs2651899 is nominally associated with increased effects in conditions of migraine with typical aura (MTA) [rs2651899 allele, whereas rs10504861 is nominally associated with a higher effect in “all migraine” patients [Prophylactic treatment of migraine is non-specific for the condition, and a “trial and error” approach is more typically adopted. ra (MTA) . Finallypatients . Migrainpatients .Although genetic testing of COMT haplotypes has been proven to predict the level of pain perception, it is not a frequently used clinical practice tool. However, genetic testing for pain perception would potentially guide physicians’ clinical decision making for a better outcome in patients suffering from various chronic pain conditions, either for initiating a treatment or for re-evaluating an ongoing treatment.rs6269, rs4633, rs4818 and rs4680 were genotyped, followed by pain perception haplotypes and score calculation: low pain perception (G_C_G_G)-1–2, moderate pain perception (A_T_C_A)-3, and high pain perception (A_C_C_G)-4–5 [Sharma et al. conducted an observational study on the impact of genetic testing on pain perception in the setting of chronic non-cancer pain management . COMT SNC_G)-4–5 . The datC_G)-4–5 . AlthougCYP2D6 phenotype can help guide physicians in selecting the most appropriate medication and dosage for increased efficacy and decreased side effects [Knowing the patient’s  effects . The Dut effects . Recomme effects .CYP2D6 phenotypes [CYP2D6 PM phenotype, the recommendations were to reduce the dose for clomipramine, haloperidol, (both 50% reduction), doxepin, nortriptyline (both 60% reduction) and imipramine (70% reduction) due to the high risk of toxicity; whereas for amitriptyline, risperidone, and venlafaxine, insufficient evidence was reported for making dose adjustment [CYP2D6 intermediate-metabolizer (IM) patients, dose reductions for doxepin, amitriptyline, imipramine and nortriptyline range between 20–50% [CYP2D6 UM, the range of dose adjustments for doxepin, imipramine, nortriptyline, venlafaxine and tramadol widely varies from 30–150%, attributed to significantly greater gene copies [CYP2D6 metabolic pathway drugs, was reported to have insufficient evidence for dosing reduction in patients with CYP2D6 PM and IM phenotypes, whereas tramadol use in CYP2D6 UM has a wide range of dose adjustments [CYP2D6 PM treated with codeine receives a score of 4B for clinical impact, whereas patients with CYP2D6 UM phenotype are attributed a score of 3F for clinical impact [CYP2D6 predominant metabolic pathway. Clinical Pharmacogenetics Implementation Consortium (CPIC), along with DPWG, established recommendations for pharmacogenetic-based dosing for patients with common enotypes . The clienotypes . For then 20–50% . In CYP2e copies . With reustments . The DPWl impact . The recCYP genetic polymorphisms in a mixed-race study population [CYP isoenzymes , and then categorize subjects into the four phenotypes: UM, extensive metabolizer (EM), IM and PM. The phenotypes, along with the submitted individuals’ medications list, was analyzed by web-based software and categorized into three types of interactions: DDIs, drug–gene interactions (DGIs), and drug–drug–gene interactions (DDGIs) [Hocum et al. conducted another notable study that demonstrated a potentially considerable clinical implication of pulation . They ha (DDGIs) . Among t (DDGIs) . Even mo (DDGIs) .CYP enzyme system metabolism, primarily by CYP2B6 enzyme subset, which has demonstrated high polymorphisms [CYP2B6 SNPs before initiating methadone therapy may identify patients at risk for poor treatment responsiveness, as well as patients at high risk of drug toxicity from poor metabolism [Approximately one-third of opioid-related prescription drug deaths are attributed to methadone . Methadoorphisms . Testingtabolism .rs1045642 in ABCB1 between the deceased opioid addiction (DOA) population of patients, living patients with active opioid addiction (LOA) getting opioid replacement therapy and healthy volunteers [ABCB1) rs9282564 in DOA compared to LOA was found when adjusted for age and sex, and lower COMT rs4680 AA genotype frequency in DOA (25%), compared to LOA (35%), and healthy volunteers (31%), suggesting lower risk of death in patients with opioid addiction [A pharmacogenetic study conducted by Christoffersen et.al examined whether certain genotypes are associated with sudden death due to opioid addiction. They found no statistically significant differences in the frequency of the TT genotype of lunteers . Howeverddiction . FurtherThe impacts of different SNPs in clinical outcomes are listed in Genetic polymorphisms have a significant clinical impact in diagnosing and treating different types of chronic pain; it can manifest as increased pain sensitivity in certain individuals, increased opioid consumption, poor therapy response, high incidence of side effects and disease process complications.Health care professionals have a significant number of tools available to use to manage patients’ chronic non-cancer pain using an individualized approach. Physicians have a low threshold for suspecting decreased efficacy or increased toxicity attributed to age, concomitant advanced or poorly managed disease processes, drug–drug interactions, inappropriate dosing of medication and even metabolic phenotypes. After eliminating and correcting these factors without significant improvement, physicians often do not proceed to use advanced available diagnostic tools, mainly due to their cost and lack of clear guidelines.


As one of the novel therapeutic drugs that targets Calcitonin gene-related peptide (CGRP), 75 mg rimegepant has been used for the acute management of migraine, which is one of the most common neurological diseases worldwide. Several clinical trials have been conducted to investigate the efficacy and safety of rimegepant for the acute management of migraine, but no systematic review of existing literature has been performed. We therefore performed a meta-analysis to investigate the efficacy and safety of rimegepant in treatment of patients with migraine.Pubmed, Embased, and Cochrane Library were searched from January 2001 to August 2019 for randomized controlled trials (RCTs). Four RCTs with 3,827 patients were finally included in our study.We pooled 3,827 patients from four RCTs, and the primary endpoints were freedom from pain, most bothersome symptom, and pain relief at 2 hr post dose. We found that 75 mg rimegepant led to significant freedom from pain (P < 0.001), pain relief (P < 0.001), and freedom from the most bothersome symptom (P < 0.001) at 2 hr post dose compared with the placebo. In addition, there was no statistically significant increase in adverse events compared with the placebo.75 mg rimegepant had good efficacy and safety for acute treatment of migraine. Further studies are needed to compare the efficacy of rimegepant with traditional drugs for acute management of migraine. However, only 34% patients who use triptans s a good response while 30–40% patients have recurrences of pain. , (“BMS-927711 and migraine”), (“BHV-3000 and migraine”)]—until August 2019 to find potentially eligible studies. In addition, we manually screened reference lists from RCTs and systematic reviews to ensure all relevant studies had been included in this study.Inclusion criteria were as follows: (a) study type: RCTs; (b) language restriction: no language restriction was applied in our study; (c) participants: patients aged >18 years with migraine for at least 1 year; (d) intervention: rimegepant and placebo; (e) outcomes: efficacy outcomes including freedom from pain, freedom from most bothersome symptom and pain relief at 2 hr, and safety outcomes. Exclusion criteria were as follows: (a) study types: case reports, case reviews, post-hoc analyses studies, retrospective studies, and cohort studies; (b) patients with a history of any clinically significant or unstable medical condition; and patients who received nonbiologic investigational agents within 30 days of the baseline visit or received biologic investigational agents within 90 days before the baseline visit.All articles and reference lists of the RCTs and reviews from the systematic search in the electronic database were assessed in accordance with the mentioned inclusion and exclusion criteria. After several selections and assessments, the basic information of the included trails , patient characteristics , and outcome measures were used to extract the data Table 1.The primary outcomes included freedom from pain at 2 hr post dose, freedom from most bothersome symptom at 2 hr post dose, and pain relief at 2 hr post dose. Secondary endpoints included freedom from photophobia at 2 hr post dose, freedom from phonophobia at 2 hr post dose, freedom from nausea at 2 hr post dose, sustained pain relief from 2 to 24 hr post dose, sustained freedom from pain from 2 to 24 hr post dose, sustained pain relief from 2 to 48 hr post dose, and sustained freedom from pain from 2 to 48 hr postdose. The adverse events included nausea, urinary tract infection, dizziness, and serum AST or ALT above ULN.I2 statistic: I2 < 30% represents “low heterogeneity”, 30% < I2 < 50% means “moderate heterogeneity” and I2 > 50% means “substantial heterogeneity”. The stability of the consolidated results was explored by sensitivity analysis. A value less than 0.05 P was considered to be significant for all analyses and the results were made up of two-tailed tests.STATA (Version 12.0) was used to evaluate the data. Estimated proportions with the risk ratio  were calculated using a random-effects model. Statistical heterogeneity was estimated by the The Review manager 5.2 software was used to create the risk of bias plot in individual studies. The Cochrane collaboration uniform criteria were used for assessing the risk of bias of RCTs. Selection bias, performance bias, detection bias, attrition bias, reporting bias, and other possible biases were included in the criteria.A total of 155 researches and abstracts from Pubmed, Embase, and Cochrane library were identified. Sixty-four studies were removed due to duplicates. Seventy-eight studies were removed because they were irrelevant, such as research on other drugs or into the etiological analysis of migraine, etc. After removing duplicates and uncorrelated titles, 13 of these articles were directly related to the topic of interest. Among them, nine full-text articles were excluded, which included two protocols, one post-hoc analysis study, one network meta-analysis, three comments, and two reviews. Finally, four RCTs containing 3,827 patients were included in our meta-analysis. The specific process and included study characteristics are shown in I2 regarding the result of freedom from most bothersome symptoms was over 50%. Therefore, a sensitivity analysis was performed to detect the statistical heterogeneity. The sensitivity analysis confirmed that the results were stable , urinary tract infection , dizziness , and serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above the upper limit of normal (ULN) . A total of 75 mg rimegepant showed a neutral effect on any adverse events compared with placebo  Figure 5The independent risk of bias of the four included studies are shown in In our meta-analysis, we pooled 3,827 patients from four multicentered RCTs, which provided higher levels of clinical reliability for evaluating the efficacy and safety of the rimegepant. Based on the results of this meta-analysis, rimegepant was significantly more effective compared to placebo measured by the improvement of symptoms in the acute phase of migraine. By comparing three primary outcomes, whether in the freedom or relief from pain within 2 hours, or the freedom from the most bothersome symptoms within 2 hours, rimegepant had the obvious effect of relieving symptoms. After using rimegepant, the duration of pain freedom or relief after using the rimegepant was significantly longer than that after using placebo; in addition, the symptoms of photophobia or phonophobia were more obviously improved than nausea. This may prove that rimegepant is more effective for patients with the symptom of photophobia or phonophobia. After the meta-analysis, it was found that there was no difference in adverse events between the rimegepant and the placebo.Previously, triptans were the most frequently used drugs for acute management of migraine, but 10% of the patients who received triptans developed cardiovascular symptoms, and, due to their potent vasoconstrict effect, triptans were contraindicated for patients with cardiovascular diseases. As a CGRP blocker, rimegepant has good efficacy and safety.  PreviousDue to the belief that drug treatment of acute migraine is aimed mainly at the short term, previous studies have focused on freedom from pain 2 hours post dose and freedom from the most bothersome symptoms  2 hours post dose. This meta-analysis also included pain relief 2 hours post dose as a primary outcome to draw a comparison with the improvement of symptoms in patients with different degrees of pain. For patients with migraine, symptoms can be divided into mild, moderate, and severe pain. Severe pain may be more difficult to relieve than mild or moderate pain. If freedom from pain only is considered as the main measure of outcome of treatment, it will inevitably lead to deviations. Therefore, we also use pain relief as a primary outcome. For these three prognoses (freedom or relief from pain within 2 hours and freedom from the most bothersome symptoms within 2 hours), rimegepant was 8.1%, 14.0%, and 11.9% more effective than the placebo, respectively. This indicated that the effect of rimegepant on pain relief was more obvious than its effect on freedom from pain or the most bothersome symptoms.These patients, due to the diversity of bothersome symptoms, can be roughly divided into three most common symptoms: photophobia, phonophobia, and nausea. However, in terms of improvement of nausea symptoms, the conclusions of the four RCTs were not consistent. After meta-analysis, it was proven that rimegepant had a significant effect on the improvement of nausea, and for these three prognoses, the rimegepant was 11.5%, 11.0%, and 5.6% more effective than the placebo, respectively. After using rimegepant, the symptoms of photophobia or phonophobia were more obviously improved than nausea. Meanwhile, in both Lipton studies, the most bothersome symptom for patients was photophobia.  This thuAfter 24 hours of rimegepant, patients had 9.8% more sustained pain freedom and 17.8% more sustained pain relief than with the placebo. After 48 hours, 7.0% people had no pain and 15.5% people still experienced sustained pain relief as compared to the placebo. By comparison, it can be seen that the use of rimegepant did not only relieve the migraine in the acute phase, but it also stabilized the symptoms of migraine to a certain extent, ensuring that the migraine did not recur in the short term. Also, the percentage of people who experienced sustained pain relief was greater than those that experienced sustained freedom from pain. It was indicated that rimegepant is more effective for pain relief. In addition, it can be seen that there was not much difference in the symptoms in the 24-hour to 48-hour interval, which may be related to the rate of metabolism of the rimegepant in the body.To investigate the safety of rimegepant, we selected several of the most common adverse events of different doses in Marcus’s study for evaluation. Although the results of the rimegepant safety assessment were different in the four RCTs, after meta-analysis, we found that there was no difference between the rimegepant and placebo (4.4% vs 3.7%). Previous studies of other types of CGRP blockers, such as olcegepant, have found that the most obvious adverse event of CGRP blockers is damage to liver function. Two of the four RCTs used liver function damage as a criterion for assessing the safety of rimegepant. In one of the Lipton studies, the use of rimegepant could cause liver injury, but in the other study there was no difference between the rimegepant and placebo. Meta-analysis showed there was no significant liver damage found in the rimegepant compared with the placebo (2.2% vs 2.9%).The purpose of developing this new drug is to avoid the adverse events of using other drugs to treat migraine. For example, triptans can cause adverse cardiovascular events, and non-steroidal anti-inflammatory drugs can cause digestive ulcers. Compared with the current mainstay of specific acute migraine treatment, CGRP receptor antagonists did not cause vasoconstriction and could, instead, decrease the likelihood of adverse cardiovascular events.  AlthoughA limitation of this meta-analysis is that it can prove that rimegepant is effective for migraine, but it cannot prove that rimegepant is superior in effectiveness to other kinds of drugs. In 2014, Marcus’s study  found thThe assessment of pain was subjective to the patients, and relevant outcome scales were not used in previous RCTs. All the patients were followed up by using an electronic diary to log their current pain and most bothersome migraine-associated symptoms. There may be a bias in patients’ assessment of their current symptoms.Another limitation, regarding to selection of patients, is that subjects of these four RCTs were roughly 40-year-old non-Hispanic and non-Latino white women with a BMI of about 31. Since the original data of each institute could not be obtained, the study was limited to the abovementioned characteristics of the population, and there was no subgroup analysis of populations of other ages, statures, races, and genders. In this regard, the people with the above characteristics had the highest incidence of migraine, so the effectiveness of the rimegepant is still meaningful. In addition, in order to prove that the scope of application of rimegepant can be more extensive, there should be more research done on migraine patients of different characteristics.Rimegepant exhibits good efficacy and safety for the acute treatment of migraine. A dose of 75 mg rimegepant was proven to be effective against acute migraine headache as measured by freedom from pain and bothersome symptoms or pain relief 2 hours post dose after drug ingestion as compared to the placebo. The use of 75 mg rimegepant was not related to a significant increase in these specific adverse events.ZhW was the principal investigator. BG and YY designed the study and developed the analysis plan. ZiW and YS analyzed the data and performed the meta-analysis. BG, YY, and ZC contributed to the writing of the article. YZ and ZhW revised the manuscript and polished the language.This work was supported by the Suzhou Health Talents Training Project (GSWS2019002).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.https://www.frontiersin.org/articles/10.3389/fphar.2019.01577/full#supplementary-materialThe Supplementary Material for this article can be found online at: Click here for additional data file.Click here for additional data file.


While total joint replacements (TJR) are frequently performed, there is little qualitative research to define the outcomes most important to patients.Patients who had received total hip (THR) or total knee replacements (TKR) participated in 8 nominal groups to answer the question “What result/results matter the most to a patient undergoing/having a knee or hip replacement?” Total 270 votes were allocated.Eight nominal groups were performed with 45 patients, 6 groups with mean age (71.1 ± 9.3), and 2 with 9 younger patients (mean age 36.8 ± 7.4). All had TJR between 2016 and 2018; overall, 40% were male, 15.6% were Black, and 75% were performed for osteoarthritis. While all groups ranked the same top 3 outcomes, responses varied with age: 1) relief of pain (46% vs. 35% in the young groups); 2) improved function including mobility (29% vs. 18% in the young groups); 3) restored quality of life (13% vs 33% of votes in the younger group).Relief of pain and restoration of function, and improved quality of life are the 3 outcomes ranked highest by patients, confirming their inclusion in TJR clinical trials. Total joint replacement(TJR), including total hip(THR) and total knee replacement(TKR) are effective surgical procedures for patients with advanced symptomatic arthritis . These tThe Outcomes Measures in Rheumatology(OMERACT) Total joint Replacement(TJR) Special Interest Group(SIG) is an international group of stakeholders including rheumatologists, orthopedists, methodologists, physical therapists, and patients. This group has previously developed a core domain set for use in TJR clinical trials performed for end-stage hip and knee arthritis . The sixNominal Group Technique(NGT) is a highly structured and efficient method for achieving consensus in small face-to-face discussion groups, where a single question can be studied in depth . The iniThe purpose of this study is to hold group discussions with patients who have received THR and TKR, and use an open ended question to elicit the most important outcomes after TJR from the patients’ perspective, and then rank the outcomes. We hypothesize that TJR patients evaluated with the NGT will rank the relief of pain, improved function, satisfaction with their surgical outcome, and quality of life the outcomes most important to them and validate their inclusion in the core domain set.Patients over the age of 18 who had undergone TKR or THR between 2016-2018 were identified by their surgeons. All participants were selected from the surgical practices of high volume orthopedic surgeons who operate at a high volume orthopedic hospital, where approximately 10,000 TKR and THR are performed each year. The collaborating surgeons sent a letter to each potential participant informing them of the study and inviting them to participate in the nominal groups. Patients who did not respond to the letter directly were contacted by telephone or e-mail, invited to participate and scheduled for a nominal group session. Two of 8 groups were purposefully sampled from patients under age 45, to examine whether the perspective of younger patients differs from those across the age range. We preferentially recruited from a practice with a high proportion of African-American patients to increase inclusion of African-Americans in the groups. All patients provided written and informed consent, and the study was approved by the institution’s ethical review board .Patient demographics including age, sex, education, race, marital status, and employment status were collected immediately prior to the nominal group after informed consent was obtained. As TJR outcomes in a high volume hospital typically include better outcomes and higher satisfaction, we wanted to be transparent about the characteristics of the study cohort , 14. PatNGT is a highly structured group discussion format derived from traditional focus discussion groups. NGT leads to a group consensus and permits the group to define their priorities in response to a specific question that is analyzed in depth. Using NGT, in the first step the participants independently consider and record their responses to a specific question. Next, in a round-robin fashion, each participant presents one idea at a time, and the ideas are recorded verbatim. This phase continues until no new ideas are generated by the group. The groups then discuss and clarify the responses; responses are grouped together where thematically appropriate. In the final step, ideas are ranked and prioritized. The major benefit of using NGT is the patient group can reach consensus; in this study the question of interest was to have post TJR patients discuss and determine the most important outcomes of TJR. NGT provides qualitative data acquired in an open ended manner that can subsequently be quantified by ranking. Themes are not selected a priori, but are determined by the group discussion as responses are grouped into themes. After completion, the responses were distributed into final themes that emerged in the groups as agreed on by the investigators.The patient discussions lasted approximately 1 hour and were held in non-clinical conference rooms in the hospital. All groups were led by an experienced leader in NGT assisted by a research assistant (SM). A question selected by the senior authors was presented to the group after informal testing with patients in their clinics . All participants were asked to consider the question “What result/results matter the most to a patient undergoing/having a knee or hip replacement?”. Each participant was given a blank sheet of paper with the question written on it and asked to list as many items that they think of to answer the question. The answers were clarified if necessary, and the responses were recorded on an easel by the moderator. The group then discussed the responses, collapsing some responses together as themes emerged after discussion. The responses were ranked on index cards by allocating a score to the three most important responses, with 3 being the highest score; each participant had a total of 6 votes to distribute. The rank order was then determined by the total scores. The most important items received the most votes by the greatest number of participants.The group discussions were held in January and February 2019 and were recorded for accuracy. The recorded discussions were subsequently reviewed for accuracy and completeness of the nominated responses. The comprehensive list of the patients’ statements were further divided into the themes identified during the group sessions, with agreement of the investigators. The sessions were continued until theme saturation was confirmed, and no new themes emerged .(Table 1). Groups included 15.6% African Americans, by purposely sampling a practice with a high proportion of African Americans, who comprise ≤4% of most arthroplasty cohorts [(Table ).Eight nominal groups were held in January and February 2019. Of 592 patients who had undergone THR or TKR between 2016 and 2018 and were sent letters of introduction by their surgeon or called, 45 were enrolled and participated in 1 of 8 nominal groups . A total of 216 votes was cast in NG 1-6, and 54 in NG 7-8, each participant had 6 votes to distribute among their top three choices Additional file es Table . A totalTaking less medication was included as a subdomain in the relief of pain theme. This theme received 29/216(13%) votes in NGT 1-6 and 9/54(9%) votes in NGT 7-8. Patients expressed the concern that they would be able to take less pain medication after surgery, a concern that was linked to relief of pain, and aggregated with the domain relief of pain during the discussion. A patient in NG#1 told the group “I had a good friend, years before I was thinking about it(THR) and he spoke to me on the phone and he was taking pain meds like M&Ms. He died because he mixed the wrong meds. I remember taking pain meds and the pain was so severe that I convinced myself I had not taken pain meds a few hours ago and took more pain meds and that’s when I realized I needed the surgery”. Patients wanted to take “less medication if at all”. Patients were concerned about pain management after surgery that was “So important in this day and age of opioid abuse and terrible outcomes of that”. A patient commented “I was eating Advil like they’re candy”. Patients in NG 7-8 wanted to “stop using Advil” and “stop using alcohol to eliminate the pain”.Relief of pain was the most highly ranked priority for NG 1-6, and achieved 98 of 216(45%) total votes. Similar to the older patients, NG 7-8 also ranked pain the highest, with 19 of 54(35%) total votes. In NG#1, a patient reported that he “woke up one morning unable to get out of bed, I was in total pain, I asked God what did you do to me”. Patients in NG#2 described the desired outcome “to be pain free”, and “not to have to think about it”, to “stand without pain” and “to eliminate pain overall”. In NG#3, one patient described “it goes beyond physical pain, it isolates you, you’re not living the way you’re used to living”. This theme was described by the groups, receiving 64/216(29%) total votes in NG 1-6, and included mobility, motion, and strength, as well as the functional ability to perform activities of daily living and sports. For NG 7&8, function ranked third, with 9 of 54(16%) total votes. In NG#1, a patient described “I was able to walk, to dance, now I can go back to do it. Going back to normal routine”. In NG#2, patients discussed knee flexibility and strength, such as the ability to “lift objects without fear of my knee buckling”, to be able to “climb stairs without difficulty”, and to regain an “excellent ability to walk and exercise”. They noted that “Living in Manhattan all you do is walk, when you slow down, people bump into you, once someone had a dog on the leash; if you are too slow, someone with a push cart bumps into you; having two knees with the problem, it was difficult”, and “Being able to do what we need to do when we need to do it- its life”. One young patient mentioned “no more overcompensation for abnormal walking and pain”, and being able to walk long distances.This specific theme garnered 28 /216(13%) votes in the older patients and 19/54(35%) of the votes among the younger patients. For younger patients in NG#7 and 8, quality of life including social participation was the second most significant outcome. In NG#2, patients described “Before I was captive to the pain and immobility, now I have an ability to be participating in life” and to “be involved with my kid’s activities” and achieve “normalcy in life”, and in NG#3 the patients described the expectation that they would be able to "return to normal life in all its aspects post-surgery”. A young patient in NG8 described being “an outcast in a group of friends, and now feels like a normal person her age”. Another patient described wanting to go out and “wear a bikini, I still want to feel normal”, and another that he “can finally walk to meet friends”. Another felt she could “Stop worrying about her future job or life logistics due to pain, and could think about marriage and kids”.This priority received 16/216(7%) votes in groups 1-6, and was less highly ranked among the younger patients 2/54(4%). Patients described wanting “everything to go alright during surgery, after surgery, my greatest fear–what if it got worse, infection”. Another patient mentioned “Coming out alive- not worse off than when you went in”. Revision surgery as a specific theme received 2 votes from the older population, the patient desired “longevity” of the TJR with “no repeated replacement of the joint in my lifetime”.This theme received 5/54(9%) votes from the younger patients and 13/216(6%) of the votes in the older group. A younger patient described having a “hard time my entire life, so it was huge to get answers….about what life will look like moving forward”. Another young man noted that he “had friends who didn’t understand and I needed a community who understood, where I could connect”.“it kept waking me up, the pain before the surgery. My niece said to me I was crying in my sleep”. Patients desired the “ability to sleep again without prescription drugs or assistance”.This subdomain received no unique votes, but was mentioned in 7% of the comments within the pain, function, and quality of life domains in NGT 1-6 and 16% in NGT 7-8, .A patient told the group The emotional impact described by patients was profound, aggregating with other domains that provided the context for the emotional response, but received no unique votes. Older patients in NG 1-6 included the emotional impact of relief of pain, improved function and improved quality of life in 60% of their comments, while the younger groups described emotional responses in 7% of their comments. Another patient said “I have 4 little grand kids and we’re on the floor all together wrestling – that’s very emotional; The thing is that I used to do it with my son and he likes to see me do it with his kids” and “one of the things that always keeps me going “. A younger patient described the emotional change from “losing the sense of depression caused by constant pain”.This qualitative study using nominal group technique explored the question “What result/results matter the most to a patient undergoing/having a knee or hip replacement?”. To our knowledge, this is the first study asking patients to provide the TJR outcomes of importance to them in an open-ended manner. Previously, patients have been queried whether they concur with expert-selected outcomes determined by literature review or survey. Although the themes that emerged were concordant with the themes previously identified by the OMERACT TJR working group, this was not known a priori and therefore this study fills an important gap in domain selection for a patient reported outcome measure.Most participants had undergone TJR for osteoarthritis, and most were very satisfied with the results of their surgery. Women and African Americans were well represented in the groups. African Americans comprise ≤ 4% of most arthroplasty cohorts , 19, so The results of this study confirm that TJR patients of all ages think that alleviation of pain is the most important outcome after TJR. For the older groups, improved function was the next most important, while the younger participants ranked improved quality of life and social participation higher than improved function. Concerns about adverse events and complications were also important to these patients, but ranked significantly lower for all ages. These findings, using an open ended qualitative research technique, are concordant with the domains selected by the expert-led OMERACT TJR SIG, that determined that pain, functional improvement, satisfaction and improved quality of life, and adverse events were core domains that should be included in all TJR clinical trials .The OMERACT core domain set was determined by extensive surveys and systematic literature review, and has been endorsed by both patients and surgeons, but there was no open-ended qualitative research with patients contributing to the initial domain selection process , 11, 20.The mean age of the first six nominal group participants was over 70 years, so we added 2 groups of patients under the age of 45 to explore the perspectives of younger patients, which is important as the mean age for people undergoing TJR is decreasing over time . While tThis study has certain limitations. While the participants were typical of TJR patients in age and sex, the educational attainment was very high, and may make these results less generalizable. In addition, all patients received their surgery in a tertiary referral hospital for musculoskeletal diseases that performs a high volume of joint replacement surgeries, whereas most patients receive their joint replacements in lower volume hospitals . PatientSeveral areas may contribute to overall patient satisfaction and have not, to our knowledge been described. Patients described the emotional toll of both their pre-operative disability and sense of isolation, and the emotional impact of their post-operative improvement, mentioning effects on both self-confidence and self-esteem. As one patient put it “I got my mojo back”, referring to sexual intimacy. Another described the importance of “wearing pretty shoes again” contributing to her self-image.In summary, this study assessed the outcomes most important to patients after hip or knee replacement surgery. We confirm that patients prioritized relief of pain, improved function, restored quality of life and the avoidance of adverse events when considering hip or knee replacement surgery.Relief of pain and restoration of function, and improved quality of life are the 3 outcomes ranked highest by patients, confirming their inclusion in TJR clinical trials. These are the domains that are most important to both patients and clinicians, and should be measured routinely in all TJR clinical trials.Additional file 1 Table S1. Appendix – Question: “What result/results matter the most to a patient undergoing a hip or knee replacement?”.


Preoperative anxiety and depression are predominant risk factors for increased postoperative pain. Thoracic wall deformities in adolescents often cause low self-esteem, which contributes to psychological concerns. Several studies have suggested a relationship between preoperative mental health support and enhanced recovery after surgery.This study investigated the validity of screening questionnaires concerning psychological trait and state characteristics via a patient-specific online platform.Patients scheduled for elective pectus surgery between June 2017 and August 2017 were invited to participate in clinical interviews and online self-report questionnaires. All patients were recruited in the Anesthesiology Department, Antwerp University Hospital, Belgium. This single-center observational cohort study was performed in accordance with the ethical standards of the International Council for Harmonisation–Good Clinical Practice guidelines and the Declaration of Helsinki after obtaining study approval by the Institutional Review Board and Ethics Committee of the Antwerp University Hospital, Belgium (study identifier: 17/08/082). An online preoperative psychological inventory was performed using the Rosenberg Self-Esteem Scale, Hospital Anxiety and Depression Scale, and State-Trait Anxiety Inventory. Postoperatively, pain intensity and interference were assessed using the Multidisciplinary Pain Inventory, Coping With Pain Questionnaire, and numeric pain rating scale assessment. Patient satisfaction of the Web-based platform was evaluated.R=–0.72, P<.001) and overall anxiety characteristics . There was a positive correlation between depressive and anxiety characteristics and the anxiety trait  measured by the online self-report questionnaires. Moreover, preoperative anxiety was positively correlated with postoperative pain interference . Finally, there was a negative correlation between self-esteem and pain interference .A total of 21 adolescent patients used our Web-based psychological perioperative screening platform. Patients rated the mobile phone app, usability, and accessibility of the digital platform as good or excellent in 85% (17/20), 89% (17/19), and 95% (20/21) of the cases, respectively. A total of 89% (17/19) of the patients rated the effort of generating answers to the online questionnaires as low. The results from the completed questionnaires indicated a strong negative correlation between self-esteem and the anxiety trait  Pectus excavatum and carinatum occur in 1 of 400 to 1000 children, with a 4:1 male-to-female predominance -4.Recently, several authors assessed quality of life and self-esteem following surgical pectus repair -7. Not sLittle research has been conducted on the influence of preoperative psychological questionnaires on postoperative pain via eHealth services. With such services, patients and their relatives can complete questionnaires when and where they want, making participation less demanding. Even more, caregivers can introduce mental health screening before surgery as part of the surgical care.The primary aim of the study was to develop and implement a Web-based patient platform for preoperative psychological yellow flag screening and early identification of risk factors for subacute or persistent postoperative pain. In addition, the applied screening battery was evaluated for usefulness in adolescents undergoing elective pectus surgery and feasibility for online questionnaire completion.Psychological variables and their relationship with postoperative outcome parameters such as persistent, subacute pain were assessed. Finally, self-esteem was evaluated, being an important indirect factor contributing to persistent pain via the development of anxiety, depression, or maladaptive coping strategies.A total of 22 patients were scheduled for elective pectus surgery during summer holidays (June to August 2017) and were invited for clinical interviews and to complete online self-report questionnaires. All patients were recruited in the Anesthesiology Department, Antwerp University Hospital, Belgium . This siAnalyses of variance revealed no significant differences between pectus excavatum and pectus carinatum patients with respect to age or body mass index. The Haller index for defining the severity of the deformity in pectus excavatum patients based on computed tomography (CT) varied from 3.00 to 7.00  in the 50% of pectus excavatum patients who had CT performed. The mean age of the subjects was 14.82 (SD 1.30) years, and the majority of the participants  were men; 90% (19/21) were not the only child in the family, and 52% (11/21) had a high education level . To provide patients with an individualized approach, we developed an electronic medical record coupled with a set of questionnaires. The Antwerp Personalized Pain Initiative app  in adolescents, healthy adults, and military samples [The State-Trait Anxiety Inventory (STAI) Form Y is an instrument used to assess state and trait anxiety. State anxiety is defined as fear, nervousness, and discomfort temporarily induced by situations perceived as dangerous or threatening in which the autonomic nervous system is activated. State anxiety can vary in intensity and change over time. Trait anxiety involves rather stable individual differences in the predisposition to experiencing fear, stress, and discomfort. People with high trait anxiety characteristics will experience certain situations as more threatening or dangerous than people with low trait anxiety. In this study, the Dutch version (STAI-version-DY-2) was used. This 20-item scale is designed to assess pervasive feelings of trait anxiety. Items are rated by respondents on a 4-point Likert-type scale. Higher scores indicate higher levels of anxiety, and norm tables are available for different groups. The STAI-version-DY-2 has demonstrated acceptable internal consistency  and 1-month test/retest reliability  has been developed to detect states of depression and anxiety in a hospital setting. It assesses core components of anxiety and depression without involving physical complaints. The questionnaire has 2 subscales, anxiety and fear, and each subscale consists of 7 items. Higher scores indicate more emotional complaints. Cutoff scores are available for quantification. For each subscale, a score of 8 or greater is associated with possible anxiety or depression. A score of 11 or greater is associated with probable anxiety or depression. The questionnaire was developed as a screening tool and can exclude but not assess emotional disorders ,13. The The Rosenberg Self-Esteem Scale (RSES) is a self-report measure for self-esteem containing 10 items that was constructed for the investigation of a person’s feelings about themselves in terms of self-confidence and intrinsic value. Self-esteem is an important measure for screening problems of social adaptation and predicting mental health problems. Items are rated by respondents on a 4-point Likert-type scale . We usedKerns et al  applied The Coping Strategy Questionnaire (CSQ) is an instrument developed to assess the coping strategies people use when experiencing pain. Research has shown that people develop their own coping style resulting from past experiences with pain and a general coping style for difficult situations. This instrument contains 44 items designed to evaluate 8 strategies for coping with pain . The perceived effectiveness of the coping efforts was assessed with 2 items: control over pain and the ability to decrease pain . SpinhovThe numerical rating scale (NRS) is an 11-point scale used for pain assessment. Self-report by a patient is considered the gold standard for pain intensity measurement. Caregivers familiar with communicating with patients in pain asked the patient how much pain they had suffered from in the previous 24-hour period. All patients were educated in pain rating, where 0 represents “no pain” and 10 represents “the worst pain possible,” using whole numbers. The mean score after the first 5 postoperative days was calculated [Patients were assessed according to their mobility and daily activity by the attending physiotherapist. Every patient was given a daily score based on the exercise executed as part of the rehabilitation process after surgery during hospitalization. Scores ranged from 1 (exercise in the supine position), 2 (sitting), 3 (standing), to 4 .t test was used to assess differences in RSES bifactor questionnaire scoring after data normality assessment with the Shapiro-Wilk test. Associations between questionnaire scores were determined with a Spearman correlation coefficient. Statistical analyses were performed with SPSS Statistics software (IBM Corp). Statistical significance was considered when P<.05.A paired sample The demographic patient characteristics are presented in The HADS fear subscale indicated the presence of an anxiety disorder. The overall mean score was 6.11 (SD 3.27). The mean score ranged from 0 to 7, which indicated the absence of anxiety states prior to surgery. Thirteen patients scored between the range of 0 to 7 (no anxiety), 3 patients scored between the range of 8 to 10 (possible anxiety), and 2 patients scored in the range of 11 or higher (probable anxiety).The HADS depression subscale indicated the presence of a depressive disorder. The overall mean score was 3.50 (SD 2.81). This mean score ranged from 0 to 7, which indicated the absence of depressive states prior to surgery. Sixteen patients scored between the range of 0 to 7 (no depression), and 2 patients scored between the range of 8 to 10 (possible depression).The DY-2 version of the STAI measured trait anxiety. The overall mean score of the study sample was 37.94 (SD 6.88). Compared with available data on controls , the overall mean score was in decile 6 indicating a mean level of anxiety.The RSES is a measure of global self-esteem. The mean score of the overall patient sample was 21.56 (SD 3.55) and was above the theoretical midpoint of 15. No single patient scored beneath this cutoff. The results can be compared with the data from the study by Schmitt and Allik , in whicThe MPI measured different pain-relevant aspects. The mean score of the study sample was compared with available normative data (mean and standard deviation) of the International Association for the Study of Pain Primary Site: Thoracic Region . The oveThe CPQ assessed different pain coping strategies. The mean raw subscale scores were compared with those of a normal group of patients with chronic low back pain or neck pain. The decile scores are written in parentheses below. The overall mean diverting attention score was 23.29 . The overall mean reinterpreting pain sensation score was 8.47 . The overall mean catastrophizing score was 9.59 . The overall mean ignoring pain sensation score was 25.18 . The overall mean praying/hoping score was 23.47 . The overall mean coping self-statements score was 38.94 . The overall mean increasing behavioral activities score was 21.71 . The overall mean perceiving pain control score was 11.59 . Note that these scores represent the pain coping ability of the study sample. The mean postoperative pain (day 1 to day 5) was low , reflecting the need to develop strategies to cope with pain.As shown in The primary variable was a patient’s global assessment of the feasibility for the mobile phone app, internet platform, and accessibility of the questionnaires . Twenty patients rated the eHealth implementation at the final interview after questionnaire completion.Secondary end points included the time burden for questionnaire completion  and response burden after a single reminder of the importance of questionnaire completion.Patients rated the mobile phone app, individual online platform usability, and accessibility as good or excellent in 85% (17/20), 89% (17/19), and 95% (20/21) of responses, respectively. No individual scored the usability or accessibility as poor. Regarding the time burden assessment, 67% (12/18) indicated a (rather) low effort for questionnaire completion, and 22% (4/18) mentioned an average effort was required. Overall, 76% (16/21) of the patients were able to complete the online questionnaires within the imposed deadline.Assessing the usefulness of the online implemented questionnaires, correlations have been calculated. The results see  showed aR=0.35, P=.18), although the differences were not significant. No correlation was found between daily activity scores and pain severity and pain interference.The study findings showed a low positive correlation between the mean pain scores for the first 5 days after surgery and the pain severity scores measured with the postoperative questionnaire after hospital discharge . A clearly positive correlation was noted between postoperative pain score after hospital discharge and pain severity assessed by the MPI .Finally, the results demonstrated a negative but nonsignificant correlation between self-esteem and pain interference .No significant correlation was found between preoperative psychological screening questionnaires and mean postoperative pain scores or between coping and pain  involved in the transition from acute to persistent (subacute) pain in adolescent pectus patients. Finally, self-esteem was measured as an indirect parameter for pain persistence, as it is shown to be related with the incidence of yellow flags.eHealth is a relatively new practice in health care that includes electronic processes and communication. Although concerns are rising about user privacy and confidentiality, its importance is growing significantly ,28. We cThis study confirmed the easy accessibility of internet-based psychological screening questionnaires. Most patients quoted a low effort for questionnaire completion, reflecting patient compliance. Since we introduced an internet platform, patients can complete their tasks when and where they want, highlighting the importance of patient independency and responsibility.In general, the implementation of Web-based questionnaires containing a preoperative psychological assessment can improve surgical outcomes for patients and their families if the optimal screening questionnaire depending on the surgical population is chosen.It is well known that psychological characteristics play an important role in the development of persistent postsurgical pain; previous studies  have shoOur results showed that anxious patients tended to engage more often in passive coping, which leads to maladaptive behaviors and cognitions about pain. This finding is in accordance with the literature on the chronification of pain. A study by Kaczynski et al  evaluateThere was no correlation between anxiety, depressive states, catastrophizing, and the experience of self-control. The overall mean catastrophizing score was low. This result is inconsistent with the literature on coping behaviors ,34. HoweWe found several significant correlations: anxious predisposition and interference of pain, self-esteem and interference of pain, anxiety states and passive coping, self-esteem and anxiety measures, and depressive states and anxious predisposition. It is most likely that the relationships between anxiety, pain coping, and disability are bidirectional and contribute to a vicious circle of increasing pain-related disability as outlined in the fear avoidance model of pain by Vlaeyen and Linton  Figure .It is important to note that all study patients followed a specific postsurgical pathway that focused on pain (recovery). All patients had a preoperative consultation in the multidisciplinary pain center in which education about the eHealth system was provided. In addition to this practical information, the medical staff also provided information on acute, subacute, and chronic pain and self-management methods. During hospitalization, a multidisciplinary team of anesthesiologists, surgeons, physiotherapists, and nurses followed the postoperative rehabilitation protocol. Each provider could anticipate the concerns of the patients very quickly. This process of reassurance, encouraging questions, and cognitive reappraisal is important to reduce distress and anxiety, consistent with the findings of Sjoling et al . This peOur results showed that preoperative anxiety is related to lower self-esteem, which is in accordance with the literature ,41,42. TSelf-esteem is an interesting measure in this population. There is a high comorbidity between depression and anxiety disorders. Low self-esteem is a transdiagnostic factor, for example, in both disorders. Improving self-esteem is an important treatment goal for therapy in depressive or anxious patients. Sowislo and Orth  evaluateWe can question the use of the RSES in the measurement of self-esteem in children with pectus pathology. The RSES is a frequently used, short, and well-studied measure. In our study sample, all scores were relatively high. The study by Knudsen et al  reportedP=.06), indicating that patients answered consistently, independent of the positive or negative formulation of the items.Some authors ,50 questThe limitations of our exploratory study need to be acknowledged. First, all questionnaires used were self-report instruments. Therefore, response bias may play a role, as results can vary due to small introspective abilities or socially desirable answering ,52. SecoIf caregivers involved in a surgical care process use innovative eHealth techniques as a simple, accessible psychological screening tool, along with adequate treatment if necessary, postoperative outcome parameters may further improve. As a fast, straightforward, and accessible instrument, an online platform can not only increase patient participation in rehabilitation but also alert the provider when yellow flags are present. To determine if this technique may be helpful in reducing postoperative pain, the length of hospital stay, and the development of chronic pain after surgery, more research is imperative.


The objective of this retrospective study was to evaluate the impact of myofascial trigger points (MTrPs) in patients with articular disc displacement with reduction (DDWR) and to identify which clinical variables are associated with the concomitant presence of DDWR and MTrPs. 130 patients were selected that sought treatment due to joint pain, with ages ≥18 years, of both genders, with DDWR confirmed by magnetic resonance imaging. The sample was divided into two groups: Group 1, patients with DDWR and MTrPs (N=101); and Group 2, patients with DDWR and no MTrPs (N=29). Information on gender, age, pain duration, pain scores, and maximal interincisal distance (MID) were collected. The logistic regression model was used and the odds ratios (OR) was calculated (p<0.05). Group 1 presented statistically significant higher mean pain scores (p=0.007), and smaller MID (p=0.0268) than Group 2. OR were significant for the pain scores (1.429), MID (0.937) and gender (women) (2.810). Patients with DDWR and MTrPs had increased pain scores and a MID decrease compared to patients with DDWR and no MTrPs. The variables pain scores, MID, and gender (women) showed a significant association with the concomitant presence of DDWR and MTrPs. Temporomandibular disorders (TMDs) are a group of musculoskeletal disorders that affect the stomatognathic system,,,,DDWR is one of the most common internal derangements of the TMJ-,MFP alone represents 45.3% of TMD diagnoses,The literature shows an important relation between MTrPs and several conditions such as fibromyalgia, migraine, chronic tension-type headache and osteoarthritisThis retrospective observational cross-sectional analytical study was approved by the Ethics Committee for the Research Involving Human Beings of the State University of Maringá, Maringá, Brazil (Number: 1.664.590/2016). This study was conducted in accordance with the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology (Strobe) guidelinesFor this study, initial selection encompassed records of 520 individuals that sought treatment due to joint pain, with ages ≥18 years, of both genders, with clinical signs and symptoms of intra-articular TMJ disorders compatible with DDWR, according to the parameters and criteria established by the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) - Axis IInformation about the presence, quantity, location and classification of the MTrPs were also obtained from the records. MTrPs data were obtained during bilateral muscle palpation of the anterior, middle and posterior temporalis; masseter, upper trapezius and sternocleidomastoid by an examiner with more than 30 years of experience in MTrPs examination. MTrPs examination in these muscles was performed following the criteria described by Gerwin, et al.,The following clinical data were studied: gender; age (years); pain duration (months); pain scores (0-10) obtained with the visual analogue scale (VAS)To evaluate the impact of MTrPs in patients with DDRW, the sample was divided into two groups: Group 1 (n=101): patients with DDWR and MTrPs; and Group 2 (n=29): patients with DDWR and no MTrPs. All demographic data of the groups, frequency distribution, means and standard deviations (SD±) of the variables studied are presented in All data were tabulated and submitted to a descriptive analysis. The Hosmer and Lemeshow logistic regression testAll the tests were conducted with SAS version 9.3  with a 5% significance level.In the gross OR calculation performed with univariate analysis comparing Groups 1 and 2, only the variables VAS pain scores, MID, and gender (women) demonstrated to be statistically significant . Then, these three variables were analyzed through multivariate analysis. The variables age (p=0.8048) and pain duration (p=0.4254) showed no statistical significance, and were therefore excluded from additional analyses .Multivariate analysis was performed with the multiple logistic regression model. The variables VAS pain scores, MID, and gender (women) were analysed together. The results showed that the three variables were, in fact, significantly associated with the concomitant presence of DDWR and MTrPs. Comparing the groups, patients in Group 1 presented statistically significant higher mean VAS pain scores and smaller MID than patients in Group 2 (p<0.05) . The gooPatients in Group 1 presented 526 MTrPs, of which 491 classified as latent and 35 as active. The distribution of MTrPs on the muscles analyzed, in decreasing order of prevalence, is shown in , and were shown to be associated with the presence of MTrPs in individuals with DDWR, supporting the rejection of the null hypothesis.To the best of our knowledge, this is the first study to assess the impact of MTrPs in patients with DDWR. By comparing patients with and without MTrPs, the variables VAS pain score, MID and gender (women), presented statistically significant differencesTMJ-related pain is considered the most common reason for referral to a TMD specialist,In TMJ arthralgia, peripheral neurogenic inflammation increases excitability of afferent nerve endings, resulting in peripheral sensitization of trigeminal neurons-In healthy individuals, MID ranges between 45 and 53 mm,The women:men ratio in the present sample (2.4:1) is similar to the gender distribution found in previous studies (2.2:1 to 4.6:1),,,The mean age of participants in the present sample (36.45±14.06 years) was within the range previously reported for TMD patients (20 to 40 years)Although the duration of the complaint is not the only determinant factor for pain chronicity, musculoskeletal pain may be considered to be chronic when lasting for ≥6 months,-While subjective, when muscle palpation is performed by an examiner with large experience with MTrPs, their clinical identification has been shown to be reliable--,In this study, 526 MTrPs were identified, of which 491 were classified as latent, and 35 active. This higher frequency of latent MTrPs was expected, since they are not only prevalent in patients with musculoskeletal pain, but also in individuals without clinical complaints, consisting of one of the potential sources of motor dysfunctionEven though the goodness-of-fit test indicated that the statistical model and the variables used were significantly well fitted (p=0.5962), there is the limitation of this study being a monocentric study, with restricted population. Although all participants presented painful complaints, no minimum number of pain level was stipulated and no mapping of referred pain pattern elicited by MTrPs palpation was conducted, and, as a result, the identification of whether joint pain symptoms were secondary to some point was not possible. Besides that, the patients’ mental health was not assessed. More investigations with the inclusion of a TMD-free control group, and/or with other specific conditions such as disc displacement without reduction, using more objective instruments of analysis, such as a pressure pain threshold algometer, as well as assessing the patients’ mental health, are suggested. In addition to that, ideally, prospective studies should be conducted in order to elucidate the impact of a particular disorder on another.In view of the results and limitations of this study, it can be concluded that patients with DDWR and MTrPs had increased VAS pain scores and a decrease of MID compared to patients with DDWR and no MTrPs. The variables VAS pain scores, MID, and gender (women) showed a significant association with the concomitant presence of DDWR and MTrPs.