Short-and long-term effects of imatinib in patients hospitalised for COVID-19 infection: A randomised controlled trial (preprint)

Objective:To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery.Background:The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain.Methods:We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty.Results:

Annals of Allergy, Asthma & Immunology

BackgroundGuidance addressing atopic dermatitis (AD) management, last issued in 2012 by the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force, requires updating as a result of new treatments and improved guideline and evidence synthesis methodology.ObjectiveTo produce evidence-based guidelines that support patients, clinicians, and other decision-makers in the optimal treatment of AD.MethodsA multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing) convened, prioritized equity, diversity, and inclusiveness, and implemented management strategies to minimize influence of conflicts of interest. The Evidence in Allergy Group …

JAMA

To the Editor Although sometimes considered the pinnacle of scientific evidence, meta-analyses can be problematic. Combining outcomes from heterogeneous trials performed in different settings or populations may give results directly applicable to few. Conclusions are also beholden to methodological design, often discordant from those of subsequent randomized clinical trials. 1 Such may be the case with the recently published dose-response meta-analysis of studies examining efficacy and tolerability of gefapixant for refractory or unexplained chronic cough. 2 Because gefapixant is the first novel efficacious therapy for refractory and unexplained chronic cough, its development involved changes in study design and participant inclusion criteria as well as drug formulation. 3 Four drug formulations were ultimately tested, with maximum bioavailability achieved for the formulation used in the phase 3 trials, such that …

The Lancet

Their stated aim is to summarise the “benefits and harms of weight-lowering drugs”, but the main findings and discussion focus on weight loss, without due consideration to the scarcity of evidence for benefits to health and wellbeing. For instance, quality of life and depression data are reported as low quality or insufficient, and there is no mention of the absence of long-term cardiovascular outcomes. A review on long-term effects of weight-reducing pharmacotherapy included only one trial with cardiovascular outcomes; it found no benefit.

Journal of Critical Care

IntroductionThe objective of this study was to create a definition of patient-important upper gastrointestinal bleeding during critical illness as an outcome for a randomized trial.DesignThis was a sequential mixed-methods qualitative-dominant multi-center study with an instrument-building aim. In semi-structured individual interviews or focus groups we elicited views from survivors of critical illness and family members of patients in the intensive care unit (ICU) regarding which features indicate important gastrointestinal bleeding. Quantitative demographic characteristics were collected. We analyzed qualitative data using inductive content analysis to develop a definition for patient-important upper gastrointestinal bleeding.SettingCanada and the United States.Participants51 ICU survivors and family members of ICU patients.ResultsParticipants considered gastrointestinal bleeding to be important if it resulted in death …

Objective:To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery.Background:The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain.Methods:We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty.Results:

JACC: Heart Failure

BackgroundA recent study showed that the accuracy of heart failure (HF) cardiologists and family doctors to predict mortality in outpatients with HF proved suboptimal, performing less well than models.ObjectivesThe authors sought to evaluate patient and physician factors associated with physician accuracy.MethodsThe authors included outpatients with HF from 11 HF clinics. Family doctors and HF cardiologists estimated patient 1-year mortality. They calculated predicted mortality using the Seattle HF Model and followed patients for 1 year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using multivariable logistic regression, the authors evaluated associations among physician experience and confidence in estimates, duration of patient-physician relationship, patient-physician sex concordance, patient race, and predicted risk, with concordant results …

Journal of Clinical Epidemiology

ObjectiveAssessment of the certainty of evidence (CoE) from network meta-analysis is critical to convey the strength of inferences for clinical decision-making. Both the GRADE Working Group (GWG) and the CINeMA framework have been designed to assess the CoE of treatment effects informed by network meta-analysis; however, the concordance of results is uncertain.Study design and settingWe assessed the CoE for treatment effects of individual opioids on pain relief and physical functioning from a network meta-analysis for chronic noncancer pain using the GWG approach and the CINeMA framework. Both approaches evaluate the CoE as high, moderate, low or very low. We quantified the number of discrepant CoE ratings between approaches, and the magnitude of the difference (i.e., 1-level, 2-levels, or 3-levels).ResultsAcross 105 comparisons among individual opioids for pain relief, the GWG and CINeMA …

Objectives To make inferences regarding the effectiveness of respiratory interventions and case isolation measures in reducing or preventing the transmission of mpox based on synthesis of available literature. Methods The WHO Clinical Management and Infection Prevention and Control 2022 guideline and droplet precautions in healthcare facilities and home isolation infection prevention control measures for patients with mpox. We conducted a systematic review that included a broad search of five electronic databases. In a two-stage process, we initially sought only randomized controlled trials and observational comparative studies; when the search failed to yield eligible studies, the subsequent search included all study designs including clinical and environmental sampling studies. Results No studies were identified that directly addressed airborne and droplet precautions and home isolation infection prevention control measures. To inform the review questions the review team synthesized route of transmission data in mpox. There were 2366/4309 (54.9%) cases in which investigators identified mpox infection occurring following transmission through direct physical sexual contact. There were no reported mpox cases in which investigators identified inhalation as a single route of transmission. There were 2/4309 cases in which investigators identified fomite as a single route of transmission. Clinical and environmental sampling studies isolated mpox virus in a minority of saliva, oropharangeal swabs, mpox skin lesions, and hospital room air. Conclusions Current findings provide compelling evidence that transmission of mpox occurs …

Hypophosphatasia (HPP) is a rare inborn error of metabolism that presents variably in both age of onset and severity. HPP is caused by pathogenic variants in the ALPL gene, resulting in low activity of tissue nonspecific alkaline phosphatase (TNSALP). Patients with HPP tend have a similar pattern of elevation of natural substrates that can be used to aid in diagnosis. No formal diagnostic guidelines currently exist for the diagnosis of this condition in children, adolescents, or adults. The International HPP Working Group is a comprised of a multidisciplinary team of experts from Europe and North America who have expertise in the diagnosis and management of patients with HPP. This group reviewed 93 papers through a Medline, Medline In-Process, and Embase search for the terms “HPP” and “hypophosphatasia” between 2005 and 2020 and that explicitly address either the diagnosis of HPP in children, clinical …

Journal of Evaluation in Clinical Practice

Background To realize the potential of precision medicine, predictive models should be integrated within the framework of decision analysis, such as the decision curve analysis (DCA). To date, its application has required individual patient data (IPD) that are often unavailable. Performing DCA using aggregate data without requiring IPD may advance the goals of precision medicine. Methods We present a statistical framework demonstrating that DCA can be conducted by using only the mean and standard deviation (SD) from the raw probabilities of the predictive model. We tested our theoretical framework by performing extensive simulations and comparing the aggregate‐based DCA with IPD DCA. The latter was conducted using IPD from four predictive models that employed logistic regression, Cox or competing risk time‐to‐event modeling including (a) statins for primary prevention of cardiovascular disease (n …

Background Cough severity represents an important subjective endpoint to assess the impact of therapies for patients with refractory or unexplained chronic cough (RCC/UCC). Objective To develop, using FDA guidance, a new patient-reported outcome measure addressing cough severity in patients with RCC/UCC. Methods Phase 1 (item generation): A systematic survey, patient focus groups, and expert consultation generated 51 items. Phase 2 (item reduction): From a list of 51 items, 100 patients identified those they had experienced in the previous year and rated their importance on a 5-point scale. The draft MCSQ included, in general, items reported to occur most frequently and that had the highest importance scores (impact method). Patient feedback on the draft MCSQ led to elimination of redundant items and selection of a one-week recall period for each item. Phase 3 (cross-sectional testing): Another 100 …

Background Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for preventing upper gastrointestinal bleeding in critically ill patients. However, concerns have arisen about the possible harms of using PPIs, including potentially increased risk of pneumonia, Clostridioides difficile infection, and more seriously, an increased risk of death in the most severely ill patients. Triggered by the REVISE trial, which is a forthcoming large randomized trial comparing pantoprazole to placebo in invasively mechanically ventilated patients, we will conduct this systematic review to evaluate the efficacy and safety of PPIs versus no prophylaxis for critically ill patients. Methods We will systematically search randomized trials that compared gastrointestinal bleeding prophylaxis with PPIs versus placebo or no prophylaxis in adults in the intensive care unit (ICU). Pairs of reviewers will independently screen the …

The commentary of Dr. Clarke and colleagues [1] includes several inaccuracies regarding the 2017 Canadian Guideline for opioid therapy and chronic noncancer pain, including some we have already addressed after three of the authors made the same misrepresentations in a different journal.[2, 3]The authors suggest that the 2017 Canadian opioid Guideline led to regulatory investigations of doctors who prescribe high doses, yet the reference they provide makes clear this investigation began in November 2016, six months before the Guideline was published.[4]

BackgroundCritical bleeding events in adults and children with ITP are medical emergencies; however, evidence-based treatment protocols are lacking. Due to the severe thrombocytopenia, (typically platelet count less than 20 × 109/L), a critical bleed portends a high risk of death or disability. We plan to perform a systematic review and meta-analysis of treatments for critical bleeding in patients with ITP that will inform evidence-based recommendations.MethodsLiterature searches will be conducted in four electronic databases: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed. Eligible studies will be randomized controlled trials or observational studies that enrolled patients with ITP describing one or more interventions for the management of critical bleeding. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation will be …

BackgroundThis manuscript provides a summary of the current evidence to support the criteria for diagnosing a child or adult with hypophosphatasia (HPP). The diagnosis of HPP is made on the basis of integrating clinical features, laboratory profile, radiographic features of the condition, and DNA analysis identifying the presence of a pathogenic variant of the tissue nonspecific alkaline phosphatase gene (ALPL). Often, the diagnosis of HPP is significantly delayed in both adults and children, and updated diagnostic criteria are required to keep pace with our evolving understanding regarding the relationship between ALPL genotype and associated HPP clinical features.MethodsAn International Working Group (IWG) on HPP was formed, comprised of a multidisciplinary team of experts from Europe and North America with expertise in the diagnosis and management of patients with HPP. Methodologists (Romina …

Introduction Clinical practice guidelines provide inconsistent recommendations regarding progestogen supplementation for threatened and recurrent miscarriage. We conducted a systematic review and meta‐analysis to assess the effectiveness and safety of progestogens for these patients. Material and methods We searched Medline, Embase, and Cochrane Central Registry of Controlled Trials up to October 6, 2023 for randomized control trials (RCTs) comparing progestogen supplementation to placebo or no treatment for pregnant women with threatened or recurrent miscarriage. We assessed the risk of bias using a modified version of the Cochrane risk‐of‐bias tool and the certainty of evidence using the GRADE approach. Results Of 15 RCTs (6616 pregnancies) reporting on threatened or recurrent miscarriage, 12 (5610 pregnancies) reported on threatened miscarriage with or without a prior history of …

BackgroundPrognostic models incorporate multiple prognostic factors to estimate the likelihood of future events for individual patients based on their prognostic factor values. Evaluating these models crucially involves conducting studies to assess their predictive performance, like discrimination. Systematic reviews and meta-analyses of these evaluation studies play an essential role in selecting models for clinical practice.MethodsIn this paper, we outline three thresholds to determine the target for certainty rating in the discrimination of prognostic models, as observed across a body of validation studies.Results and ConclusionWe propose three thresholds when rating the certainty of evidence about a prognostic model's discrimination. The first threshold amounts to rating certainty in the model's ability to classify better than random chance. The other two approaches involve setting thresholds informed by other …