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.
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.
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.
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.
CRD42017060473.
Preventable adverse drug reactions (PADRs) in inpatients are associated with harm, including increased length of stay and potential loss of life, and result in elevated costs of care. We conducted an ...overview of reviews (i.e., a systematic review of systematic reviews) to determine the incidence of PADRs experienced by inpatients. Secondary review objectives were related to assessment of the effects of patient age, setting, and clinical specialty on PADR incidence.
The protocol was registered in PROSPERO (CRD42016043220). We performed a search of Medline, Embase, and the Cochrane Library, limiting languages of publication to English and French. We included published systematic reviews that reported quantitative data on the incidence of PADRs in patients receiving acute or ambulatory care in a hospital setting. The full texts of all primary studies for which PADR data were reported in the included reviews were obtained and data relevant to review objectives were extracted. Quality of the included reviews was assessed using the AMSTAR-2 tool. Both narrative summaries of findings and meta-analyses of primary study data were undertaken.
Thirteen systematic reviews encompassing 37 unique primary studies were included. Across primary studies, the PADR incidence was highly varied, ranging from 0.006 to 13.3 PADRs per 100 patients, with a pooled incidence estimate of 0.59 PADRs per 100 patients. Substantial heterogeneity was present across both reviews and primary studies with respect to review/study objectives, patient age, hospital setting, medical discipline, definitions and assessment tools used, event detection methods, endpoints of interest, and units of measure. Thirteen primary studies used prospective event detection methods and had a pooled PADR incidence of 3.13 (2.87-3.38) PADRs per 100 patients; however, extreme statistical heterogeneity (I2 = 97%) indicated this finding should be considered with caution. Subgroup meta-analyses demonstrated that PADR incidence varied significantly with event detection method (prospective > retrospective > voluntary reporting methods), hospital setting (ICU > wards), and medical discipline (medical > surgical). High statistical heterogeneity (I2 > 80%) was present across all analyses, indicating results should be interpreted with caution. Effects of patient age could not be assessed due to poor reporting of age groups used in primary studies.
The method of event detection appeared to significantly influence PADR incidence, with prospective methods having the highest reported PADR rate. This finding is in agreement with the background literature. High methodological and statistical heterogeneity across primary studies evaluating adverse drug events reduces the validity of the overall PADR incidence derived from the meta-analyses of the pooled data. Data pooled from studies using only prospective methods of event detection should provide an overall estimate closest to the true PADR incidence; however, our estimate should be considered with caution due to the statistical heterogeneity found in this group of studies. Future studies should employ prospective methods of detection. This review demonstrates that the true overall incidence of PADRs is likely much greater than the overall pooled incidence estimate of 0.59 PADRs per 100 patients obtained when event detection method was not taken into consideration.
Genetic diagnosis provides important information for prenatal decision-making and management. Promising results from exome sequencing (ES) for genetic diagnosis in fetuses with structural anomalies ...are emerging. The objective of this scoping review was to identify what is known about the use of ES for genetic testing in prenatal cases with known or suspected genetic disease. A rapid scoping review was conducted over a six-week timeframe of English-language peer-reviewed studies. Search strategies for major databases (e.g., Medline) and gray literature were developed, and peer reviewed by information specialists. Identified studies were categorized and charted using tables and diagrams. Twenty-four publications were included from seven countries published between 2014 and 2019. Most commonly reported outcomes were diagnostic yields, which varied widely from 5% to 57%, and prenatal phenotype. Few studies reported clinical outcomes related to impact, decision-making, and clinical utility. Qualitative studies (n = 6) provided useful insights into patient and health-care provider experiences with ES. Findings suggest prenatal ES is beneficial, but more research is needed to better understand the clinical utility, circumstances for ideal use, feasibility, and costs of offering rapid ES as a routine option for prenatal genetic testing.
Hearing loss is one of the leading causes of disability worldwide. Patients with hearing loss experience impaired quality of life, as well as emotional and financial consequences that affect both ...themselves and their families. Idiopathic sudden sensorineural hearing loss (ISSNHL) is a common but difficult to treat condition that has a sudden onset of ≤ 72 hour associated with various etiologies, with the majority of cases being idiopathic. There exists a wide range of therapeutic options, however, the uncertainty surrounding their comparative efficacy and safety makes selection of treatment difficult. This systematic review and network meta-analysis (NMA) assessed the relative effects of competing treatments for management of ISSNHL.
A protocol for this review was registered with PROSPERO (CRD42017073756). A detailed search of MEDLINE, Embase and the Cochrane Library from inception to February 8th, 2018 was carried out by an experienced information specialist. Grey literature was also searched. Screening full-text records, and risk of bias assessment were carried out independently by two reviewers, and disagreements were resolved through consensus or third party adjudication, while data was collected by one reviewer and verified by a second reviewer. Bayesian network meta-analyses (NMA) were performed to inform comparisons between interventions for a priori specified outcomes that included pure tone average (PTA) improvement and hearing recovery.
The search identified a total of 1,138 citations, of which 613 remained for review after removal of duplicates. Of these, 23 publications describing 19 unique studies (total sample size of 1,527) met our a priori eligibility criteria, that were assessed to be at unclear or high risk of bias on several domains. We identified data on several interventions for ISSNHL therapy and were able to construct treatment networks consisting of six intervention groups that included placebo; intratympanic (IT) steroid; IT plus systemic steroid; per oral (PO) steroid; intravenous (IV) steroid; and IV plus PO steroid for our NMAs. IT plus systemic steroids demonstrated the largest difference in PTA improvement compared to placebo (25.85 dB, 95% CrI 7.18-40.58), followed by IV plus PO steroids (22.06 dB, 95% CrI 1.24-39.17), IT steroids (18.24 dB, 95% CrI 3.00-29.81). We observed that the difference of PTA improvement between each intervention and placebo diminished over time, attributed to spontaneous recovery. The binary outcomes of hearing recovery demonstrated similar relative ordering of interventions but were less sensitive than PTA improvement to capture the significant differences between interventions and placebo.
Unclear to high risk of bias trials rated IT plus systemic steroid treatment as the best among the six interventions compared, and all active treatments were better than placebo in improving PTA. However, it should be noted that certain comparisons were based on indirect evidence only or few studies of small sample size, and analyses were unable to control for steroid type and dosage. Given these limitations, further data originating from methodologically sound and rigorous trials with adequate reporting are needed to confirm our findings.
Introduction One of the current challenges in long-term care homes (LTCH) is to identify the optimal model of care, which may include specialty physicians, nursing staff, person support workers, ...among others. There is currently no consensus on the complement or scope of care delivered by these providers, nor is there a repository of studies that evaluate the various models of care. We conducted a rapid scoping review to identify and map what care provider models and interventions in LTCH have been evaluated to improve quality of life, quality of care, and health outcomes of residents. Methods We conducted this review over 10-weeks of English language, peer-reviewed studies published from 2010 onward. Search strategies for databases (e.g., MEDLINE) were run on July 9, 2020. Studies that evaluated models of provider care (e.g., direct patient care), or interventions delivered to facility, staff, and residents of LTCH were included. Study selection was performed independently, in duplicate. Mapping was performed by two reviewers, and data were extracted by one reviewer, with partial verification by a second reviewer. Results A total of 7,574 citations were screened based on the title/abstract, 836 were reviewed at full text, and 366 studies were included. Studies were classified according to two main categories: healthcare service delivery (n = 92) and implementation strategies (n = 274). The condition/ focus of the intervention was used to further classify the interventions into subcategories. The complex nature of the interventions may have led to a study being classified in more than one category/subcategory. Conclusion Many healthcare service interventions have been evaluated in the literature in the last decade. Well represented interventions (e.g., dementia care, exercise/mobility, optimal/appropriate medication) may present opportunities for future systematic reviews. Areas with less research (e.g., hearing care, vision care, foot care) have the potential to have an impact on balance, falls, subsequent acute care hospitalization.
Mitochondrial diseases are a large group of genetically heterogeneous and clinically diverse disorders. Diagnosis often takes many years for which treatment may not exist. Registries are often used ...to conduct research, establish natural disease progression, engage the patient community, and develop best disease management practices. In Canada, there are limited centralized registries for mitochondrial disease patients, presenting a challenge for patients and professionals. To support the creation of such a registry, a systematic scoping review was conducted to map the landscape of mitochondrial disease patient registries worldwide, with a focus on registry design and challenges. Furthermore, it addresses a knowledge gap by providing a narrative synthesis of published literature that describes these registries. Arksey and O'Malley's methodological framework was followed to systematically search English-language literature in PubMed and CINAHL describing the designs of mitochondrial disease patient registries, supplemented by a grey literature search. Data were extracted in Microsoft Excel. Stakeholder consultations were also performed with patient caregivers, advocates, and researchers to provide perspectives beyond those found in the literature. These data were thematically analyzed and were reported in accordance with the PRISMA-ScR reporting guidelines. A total of 17 articles were identified describing 13 unique registries located in North America, Europe, Australia, and West Asia. These papers described the registries' designs, their strengths, and weaknesses, as well as their tangible outcomes such as facilitating recruitment for research and supporting epidemiological studies. Based on our findings in this review, recommendations were formulated. These include establishing registry objectives, respecting patients and their roles in the registry, adopting international data standards, data evaluations, and considerations to privacy legislation, among others. These recommendations could be used to support designing a future Canadian mitochondrial disease patient registry, and to further research directly engaging these registries worldwide.
Existing systematic reviews of Rh immunoprophylaxis include only data from randomized controlled trials, have dated searches, and some do not report on all domains of risk of bias or evaluate the ...certainty of the evidence. Our objective was to perform an updated review, by including new trials, any comparative observational studies, and assessing the certainty of the evidence using the GRADE framework.
We searched MEDLINE, Embase and the Cochrane Library from 2000 to November 26, 2019. Relevant websites and bibliographies of systematic reviews and guidelines were searched for studies published before 2000. Outcomes of interest were sensitization and adverse events. Risk of bias was evaluated with the Cochrane tool and ROBINS-I. The certainty of the evidence was performed using the GRADE framework.
Thirteen randomized trials and eight comparative cohort studies were identified, evaluating 12 comparisons. Although there is some evidence of beneficial treatment effects (e.g., at 6-months postpartum, fewer women who received RhIg at delivery compared to no RhIg became sensitized 70 fewer sensitized women per 1,000 (95%CI: 67 to 71 fewer); I2 = 73%), due to very low certainty of the evidence, the magnitude of the treatment effect may be overestimated. The certainty of the evidence was very low for most outcomes often due to high risk of bias (e.g., randomization method, allocation concealment, selective reporting) and imprecision (i.e., few events and small sample sizes). There is limited evidence on prophylaxis for invasive fetal procedures (e.g. amniocentesis) in the comparative literature, and few studies reported adverse events.
Serious risk of bias and low to very low certainty of the evidence is found in existing RCTs and comparative observational studies addressing optimal effectiveness of Rh immunoprophylaxis. Guideline development committees should exercise caution when assessing the strength of the recommendations that inform and influence clinical practice in this area.
Rationale Methamphetamine use and related harms have risen at alarming rates. While several psychosocial and pharmacologic interventions have been described in the literature, there is uncertainty ...regarding the best approach for the management of methamphetamine use disorder (MUD) and problematic methamphetamine use (PMU). We conducted a scoping review of recent systematic reviews (SR), clinical practice guidelines (CPG), and primary controlled studies of psychosocial and pharmacologic treatments for MUD/PMU. Methods Guided by an a priori protocol, electronic database search updates (e.g., MEDLINE, Embase) were performed in February 2022. Screening was performed following a two-stage process, leveraging artificial intelligence to increase efficiency of title and abstract screening. Studies involving individuals who use methamphetamine, including key subgroups (e.g. those with mental health comorbidities; adolescents/youths; gay, bisexual, and other men who have sex with men) were sought. We examined evidence related to methamphetamine use, relapse, use of other substances, risk behaviors, mental health, harms, and retention. Figures, tables and descriptive synthesis were used to present findings from the identified literature. Results We identified 2 SRs, one CPG, and 54 primary studies reported in 69 publications that met our eligibility criteria. Amongst SRs, one concluded that psychostimulants had no effect on methamphetamine abstinence or treatment retention while the other reported no effect of topiramate on cravings. The CPG strongly recommended psychosocial interventions as well as self-help and family support groups for post-acute management of methamphetamine-related disorders. Amongst primary studies, many interventions were assessed by only single studies; contingency management was the therapy most commonly associated with evidence of potential effectiveness, while bupropion and modafinil were analogously the most common pharmacologic interventions. Nearly all interventions showed signs of potential benefit on at least one methamphetamine-related outcome measure. Discussion This scoping review provides an overview of available interventions for the treatment of MUD/PMU. As most interventions were reported by a single study, the effectiveness of available interventions remains uncertain. Primary studies with longer durations of treatment and follow-up, larger sample sizes, and of special populations are required for conclusive recommendations of best approaches for the treatment of MUD/PMU.
Meniere's disease (MD) is a chronic condition of the inner ear consisting of symptoms that include vertigo attacks, fluctuating sensorineural hearing loss, tinnitus and aural fullness. Despite ...availability of various interventions, there is uncertainty surrounding their relative efficacy, thus making it difficult to select the appropriate treatments for MD. The objective of this systematic review was to assess the relative effects of the available pharmacologic and surgical interventions in patients with MD with regard to vertigo and other key patient outcomes based on data from randomized clinical trials (RCTs).
Our published protocol registered with PROSPERO (CRD42019119129) provides details on eligibility criteria and methods. We searched various databases including MEDLINE, Embase and the Cochrane Library from inception to December 10th, 2018. Screening at citation and full-text levels and risk of bias assessment were performed by two independent reviewers in duplicate, with discrepancies resolved by consensus or third-party adjudication. Bayesian network meta-analyses (NMA) were performed for hearing change and vertigo control outcomes, along with pairwise meta-analyses for these and additional outcomes.
We identified 2,889 unique citations, that yielded 23 relevant publications describing 18 unique RCTs (n = 1,231 patients). Overall, risk-of bias appraisal suggested the evidence base to be at unclear or high risk of bias. Amongst pharmacologics, we constructed treatment networks of five intervention groups that included placebo, intratympanic (IT) gentamicin, oral high-dose betahistine, IT steroid and IT steroid plus high-dose betahistine for NMAs of hearing change (improvement or deterioration) and complete vertigo control. IT steroid plus high-dose betahistine was associated with the largest difference in hearing improvement compared to placebo, followed by high-dose betahistine and IT steroid (though 95% credible intervals failed to rule out the possibility of no difference), while IT gentamicin was worse than IT steroid. The NMA of complete vertigo control suggested IT gentamicin was associated with the highest probability of achieving better complete vertigo control compared to placebo, followed by IT steroid plus high-dose betahistine. Only two studies related to surgical interventions were found, and data suggested no statistically significant difference in hearing changes between endolymphatic duct blockage (EDB) versus endolymphatic sac decompression (ESD), and ESD with or without steroid injection. One trial reported that 96.5% of patients in EDB group compared to 37.5% of the patients in ESD group achieved complete vertigo control 24 months after surgery (p = 0.002).
To achieve both hearing preservation and vertigo control, the best treatment option among the pharmacologic interventions compared may be IT steroid plus high-dose betahistine, considering that IT gentamicin may have good performance to control vertigo but may be detrimental to hearing preservation with high cumulative dosage and short interval between injections. However, IT steroid plus high-dose betahistine has not been compared in head-to-head trials against other interventions except for IT steroid alone in one trial, thus future trials that compare it with other interventions will help establish comparative effectiveness with direct evidence.
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.
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.
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.
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.
PROSPERO registration CRD42018090761.
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