Drug induced pancreatitis: A systematic review of case reports to determine potential drug associations.

OBJECTIVE:A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with potential associations with acute pancreatitis and the burden of evidence supporting these associations. METHODS:A protocol was developed a priori (PROSPERO CRD42017060473). We searched MEDLINE, Embase, the Cochrane Library, and additional sources to identify cases of drug-induced pancreatitis that met accepted diagnostic criteria of acute pancreatitis. Cases caused by multiple drugs or combination therapy were excluded. Established systematic review methods were used for screening and data extraction. A classification system for associated drugs was developed a priori based upon the number of cases, re-challenge, exclusion of non-drug causes of acute pancreatitis, and consistency of latency. RESULTS:Seven-hundred and thirteen cases of potential drug-induced pancreatitis were identified, implicating 213 unique drugs. The evidence base was poor: exclusion of non-drug causes of acute pancreatitis was incomplete or poorly reported in all cases, 47% had at least one underlying condition predisposing to acute pancreatitis, and causality assessment was not conducted in 81%. Forty-five drugs (21%) were classified as having the highest level of evidence regarding their association with acute pancreatitis; causality was deemed to be probable or definite for 19 of these drugs (42%). Fifty-seven drugs (27%) had the lowest level of evidence regarding an association with acute pancreatitis, being implicated in single case reports, without exclusion of other causes of acute pancreatitis. DISCUSSION:Much of the case report evidence upon which drug-induced pancreatitis associations are based is tenuous. A greater emphasis on exclusion of all non-drug causes of acute pancreatitis and on quality reporting would improve the evidence base. It should be recognized that reviews of case reports, are valuable scoping tools but have limited strength to establish drug-induced pancreatitis associations. REGISTRATION:CRD42017060473

Optimising weight-loss interventions in cancer patients-A systematic review and network meta-analysis.

BackgroundExcess weight has been associated with increased morbidity and a worse prognosis in adult patients with early-stage cancer. The optimal lifestyle interventions to optimize anthropometric measures amongst cancer patients and survivors remain inconsistent.ObjectiveTo conduct a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing the effects of exercise and dietary interventions alone or in combination on anthropometric measures of adult cancer patients and survivors.MethodsA systematic search of Medline, Embase and the Cochrane Trials Registry was performed. Outcomes of interest included changes in weight, body mass index (BMI), and waist circumference. Screening and data collection were performed by two reviewers. Bayesian NMAs were performed.ResultsOverall, 98 RCTs were included; 75 were incorporated in NMAs (n = 12,199). Groups of intervention strategies included: 3 exercise interventions, 8 dietary interventions, 7 combination interventions of diet and exercise and standard care. Median intervention duration was 26 weeks. NMA suggested that diet alone (mean difference [MD] -2.25kg, 95% CrI -3.43 to -0.91kg) and combination strategies (MD -2.52kg, 95% CrI -3.54 to -1.62kg) were associated with more weight loss compared to standard care. All dietary interventions achieved a similar magnitude of weight loss (MD range from -2.03kg to -2.52kg). Both diet alone and combination strategies demonstrated greater BMI reductions versus standard care, and each of diet alone, exercise alone and combination strategies demonstrated greater reductions in waist circumference than standard care.ConclusionDiet and exercise alone or in combination are effective lifestyle interventions to improve anthropometric measures in cancer patients and survivors. All reputable diets appear to be similarly effective to achieve weight loss

High-Throughput Screening of TRPV1 Ligands in the Light of the Bioluminescence Resonance Energy Transfer Technique

International audienceIon channels are attractive drug targets for many therapeutic applications. However, high-throughput screening (HTS) of drug candidates is difficult and remains very expensive. We thus assessed the suitability of the bioluminescence resonance energy transfer (BRET) technique as a new HTS method for ion-channel studies by taking advantage of our recently characterized intra- and intermolecular BRET probes targeting the transient receptor potential vanilloid type 1 (TRPV1) ion channel. These BRET probes monitor conformational changes during TRPV1 gating and subsequent coupling with calmodulin, two molecular events that are intractable using reference techniques such as automated calcium assay (ACA) and automated patch-clamp (APC). We screened the small-sized Prestwick chemical library, encompassing 1200 compounds with high structural diversity, using either intra- and intermolecular BRET probes or ACA. Secondary screening of the detected hits was done using APC. Multiparametric analysis of our results shed light on the capability of calmodulin inhibitors included in the Prestwick library to inhibit TRPV1 activation by capsaicin. BRET was the lead technique for this identification process. Finally, we present data exemplifying the use of intramolecular BRET probes to study other transient receptor potential (TRP) channels and non-TRPs ion channels. Knowing the ease of use of BRET biosensors and the low cost of the BRET technique, these assays may advantageously be included for extending ion-channel drug screening. SIGNIFICANCE STATEMENT: This study screened a chemical library against TRPV1 ion channel using bioluminescence resonance energy transfer (BRET) molecular probes and compared the results with the ones obtained using reference techniques such as automated calcium assay and automated patch-clamp. Multiparametric analysis of our results shed light on the capability of calmodulin antagonists to inhibit chemical activation of TRPV1 and indicates that BRET probes may advantageously be included in ion channel drug screening campaigns

Stop this waste of people, animals and money

Predatory journals have shoddy reporting and include papers from wealthy nations, find David Moher, Larissa Shamseer, Kelly Cobey and colleagues

Evaluating comparative effectiveness of psychosocial interventions adjunctive to opioid agonist therapy for opioid use disorder: a systematic review with network meta-analyses.

BACKGROUND: Guidelines recommend that individuals with opioid use disorder (OUD) receive pharmacological and psychosocial interventions; however, the most appropriate psychosocial intervention is not known. In collaboration with people with lived experience, clinicians, and policy makers, we sought to assess the relative benefits of psychosocial interventions as an adjunct to opioid agonist therapy (OAT) among persons with OUD. METHODS: A review protocol was registered a priori (CRD42018090761), and a comprehensive search for randomized controlled trials (RCT) was conducted from database inception to June 2020 in MEDLINE, Embase, PsycINFO and the Cochrane Central Register of Controlled Trials. Established methods for study selection and data extraction were used. Primary outcomes were treatment retention and opioid use (measured by urinalysis for opioid use and opioid abstinence outcomes). Odds ratios were estimated using network meta-analyses (NMA) as appropriate based on available evidence, and in remaining cases alternative approaches to synthesis were used. RESULTS: Seventy-two RCTs met the inclusion criteria. Risk of bias evaluations commonly identified study limitations and poor reporting with regard to methods used for allocation concealment and selective outcome reporting. Due to inconsistency in reporting of outcome measures, only 48 RCTs (20 unique interventions, 5,404 participants) were included for NMA of treatment retention, where statistically significant differences were found when psychosocial interventions were used as an adjunct to OAT as compared to OAT-only. The addition of rewards-based interventions such as contingency management (alone or with community reinforcement approach) to OAT was superior to OAT-only. Few statistically significant differences between psychosocial interventions were identified among any other pairwise comparisons. Heterogeneity in reporting formats precluded an NMA for opioid use. A structured synthesis was undertaken for the remaining outcomes which included opioid use (n = 18 studies) and opioid abstinence (n = 35 studies), where the majority of studies found no significant difference between OAT plus psychosocial interventions as compared to OAT-only. CONCLUSIONS: This systematic review offers a comprehensive synthesis of the available evidence and the limitations of current trials of psychosocial interventions applied as an adjunct to OAT for OUD. Clinicians and health services may wish to consider integrating contingency management in addition to OAT for OUD in their settings to improve treatment retention. Aside from treatment retention, few differences were consistently found between psychosocial interventions adjunctive to OAT and OAT-only. There is a need for high-quality RCTs to establish more definitive conclusions

Evaluating comparative effectiveness of psychosocial interventions adjunctive to opioid agonist therapy for opioid use disorder: A systematic review with network meta-analyses.

BackgroundGuidelines recommend that individuals with opioid use disorder (OUD) receive pharmacological and psychosocial interventions; however, the most appropriate psychosocial intervention is not known. In collaboration with people with lived experience, clinicians, and policy makers, we sought to assess the relative benefits of psychosocial interventions as an adjunct to opioid agonist therapy (OAT) among persons with OUD.MethodsA review protocol was registered a priori (CRD42018090761), and a comprehensive search for randomized controlled trials (RCT) was conducted from database inception to June 2020 in MEDLINE, Embase, PsycINFO and the Cochrane Central Register of Controlled Trials. Established methods for study selection and data extraction were used. Primary outcomes were treatment retention and opioid use (measured by urinalysis for opioid use and opioid abstinence outcomes). Odds ratios were estimated using network meta-analyses (NMA) as appropriate based on available evidence, and in remaining cases alternative approaches to synthesis were used.ResultsSeventy-two RCTs met the inclusion criteria. Risk of bias evaluations commonly identified study limitations and poor reporting with regard to methods used for allocation concealment and selective outcome reporting. Due to inconsistency in reporting of outcome measures, only 48 RCTs (20 unique interventions, 5,404 participants) were included for NMA of treatment retention, where statistically significant differences were found when psychosocial interventions were used as an adjunct to OAT as compared to OAT-only. The addition of rewards-based interventions such as contingency management (alone or with community reinforcement approach) to OAT was superior to OAT-only. Few statistically significant differences between psychosocial interventions were identified among any other pairwise comparisons. Heterogeneity in reporting formats precluded an NMA for opioid use. A structured synthesis was undertaken for the remaining outcomes which included opioid use (n = 18 studies) and opioid abstinence (n = 35 studies), where the majority of studies found no significant difference between OAT plus psychosocial interventions as compared to OAT-only.ConclusionsThis systematic review offers a comprehensive synthesis of the available evidence and the limitations of current trials of psychosocial interventions applied as an adjunct to OAT for OUD. Clinicians and health services may wish to consider integrating contingency management in addition to OAT for OUD in their settings to improve treatment retention. Aside from treatment retention, few differences were consistently found between psychosocial interventions adjunctive to OAT and OAT-only. There is a need for high-quality RCTs to establish more definitive conclusions.Trial registrationPROSPERO registration CRD42018090761

Additional file 1: of Establishing core outcome sets for phenylketonuria (PKU) and medium-chain Acyl-CoA dehydrogenase (MCAD) deficiency in children: study protocol for systematic reviews and Delphi surveys

Additional details on the methods for the rapid review and evidence map. (PDF 174 kb