Protein Metrics (United States)

To assess the effects of and related evidence certainty of interventions for attention deficit/hyperactivity disorder (ADHD) across an individual's lifespan, and to develop a continuously updated web platform for people with lived experience of ADHD as a method to disseminate living evidence synthesis for shared decision making. Umbrella review and platform for shared decision making. Six databases from inception to 19 January 2025. Study authors were contacted for additional information when necessary. Systematic reviews that used meta-analyses of randomised controlled trials were eligible if they compared a drug or non-drug intervention with a passive control in individuals with a diagnosis of ADHD. Primary outcomes were severity of ADHD symptoms, analysed by rater type (clinician-rated, parent-rated, teacher-rated, or self-rated) and time point (short term (12 weeks, or study endpoint), medium term (26 weeks), and long term (52 weeks)),acceptability (participants dropping out for any reason), and tolerability (participants dropping out owing to any side effects). Secondary outcomes included daily functioning, quality of life, comorbid symptoms, and key side effects (decreased sleep and appetite). Eligible meta-analyses were re-estimated with a standardised statistical approach. Methodological quality was assessed using AMSTAR-2. Evidence certainty was evaluated using an algorithmic version of the GRADE framework, adapted for drug and non-drug interventions. 115 of 414 full text articles were deemed eligible and 299 were excluded; the eligible articles comprised 221 unique combinations of participants, interventions, comparators, and outcomes. For each combination, the most recent and methodologically robust meta-analysis was selected for re-estimation, which gave 221 re-estimated meta-analyses in total, derived from 47 meta-analytic reports. In the short term, alpha-2 agonists, amphetamines, atomoxetine, methylphenidate, and viloxazine showed medium to large effect sizes in reducing the severity of ADHD symptoms in children and adolescents, with moderate to high certainty evidence. Methylphenidate showed consistent benefits across raters (standardised mean difference >0.75, 95% confidence interval (CI) 0.56 to 1.03; moderate or high certainty evidence). These interventions showed lower tolerability than the placebo, but this effect was not significant for methylphenidate and atomoxetine. In adults, atomoxetine, cognitive behavioural therapy, methylphenidate (and, when restricting analyses to high quality trials, amphetamines) showed at least moderate certainty evidence of efficacy on ADHD symptoms, with medium effect sizes. Methylphenidate, amphetamines, and atomoxetine had worse tolerability than placebo (methylphenidate, risk ratio 0.50, 95% CI 0.36 to 0.69; amphetamines, 0.40, 0.22 to 0.72; atomoxetine, 0.45, 0.35 to 0.58). Some non-drug interventions (acupuncture and cognitive behavioural therapy in children and adolescents, and mindfulness in adults) showed large effect sizes for ADHD symptoms, but with low certainty evidence. No high certainty, long term evidence was found for any intervention. An online platform showing effects and evidence certainty of each intervention across age groups, time points, and outcomes (https://ebiadhd-database.org/) was developed. This review provides updated evidence to inform patients, practitioners, and guideline developers how best to manage ADHD symptoms. The online platform should facilitate the implementation of shared decision making in daily practice. Open Science Framework https://osf.io/ugqy6/.

ABSTRACT Our profession has an established reputation for advancing clinical knowledge, professional growth, and patient care, and we continue to share and refine best practices. One important aspect of value has received little attention – whether educational resources are used as efficiently as possible to achieve meaningful outcomes. This paper builds on a recent systematic review of the literature which found that only a small fraction of the CME professional literature measures or even mentions costs or concepts related to cost-effectiveness. This paper offers insights into how the field has been hesitant to explore cost-effectiveness, including realistic challenges related to data access and analysis, complexity, and perceived misalignment with the educational mission. This paper also highlights real opportunities and practical steps to consider cost-effectiveness in CE/CME in a way that mitigates risk while maximising learning. By looking at cost alongside traditional educational outcomes, providers may better demonstrate the full value of our work. Evaluating cost-effectiveness is not about turning education into a financial exercise. It is about showing that the precious resources available to CE/CME are allocated as wisely as possible to improve patient care. This perspective can help CME providers take a proactive leadership role in demonstrating an entirely new dimension of educational value in an environment increasingly focused on value.

In-house editorials and journalistic pieces are massively published in peer-reviewed scientific journals. This corpus has remained outside the efforts of evidence-based medicine and research reform, and it can be imbued with unchecked biases. High-impact journals publish such pieces massively and may generate strong support for specific narratives and perspectives. Pieces with a political slant are also a major issue. Besides high-impact journals, across the entire scientific corpus, such pieces may be (mis)used to boost impact factors, create implausibly prolific CVs (occasionally even fraudulent) and can be powerful instruments of opinion making favouring some sponsors. Here we propose how this influential literature corpus may be strengthened to maximize its benefits and diminish its potential harms. Helpful measures to consider may include bolstering transparency (on authorship, financial compensation, disclosures of publication-specific and generic conflicts of interest, handling of political issues, peer-review, commissioning and timing); self-regulation with limits per author, improvement of subject matter expertise (with experts, meta-researchers and methodologists); balance of perspectives (with debates and for choice of topics); and post-publication review, audit, correction and potential retraction, as needed. A systematic research agenda is needed to study better this phenomenon and also the effectiveness of proposed interventions.

Critical appraisal of the quality of randomised trials is possible only if their design, conduct, analysis, and results are completely and accurately reported. Without transparent reporting of the methods and results, readers will not be able to fully evaluate the reliability and validity of trial findings. The CONSORT (Consolidated Standards of Reporting Trials) statement aims to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996 and was updated in 2001 and 2010. CONSORT comprises a checklist of essential items that should be included in reports of randomised trials and a diagram for documenting the flow of participants through a trial. The CONSORT statement has been updated (CONSORT 2025) to reflect recent methodological advancements and feedback from end users, ensuring that it remains fit for purpose. Here, we present the updated CONSORT explanation and elaboration document, which has been extensively revised and describes the rationale and scientific background for each CONSORT 2025 checklist item and provides published examples of good reporting. The objective is to enhance the use, understanding, and dissemination of CONSORT 2025 and provide guidance to authors about how to improve the reporting of their trials and ensure trial reports are complete, and transparent.

Peptidoglycan is an essential component of the bacterial cell envelope—a mesh-like macromolecule that protects the bacterium from osmotic stress and its internal turgor pressure. The composition and architecture of peptidoglycan is heterogeneous and changes as bacteria grow, divide, and respond to their environment. Though peptidoglycan has long been studied via LC-MS/MS, the analysis of this data remains challenging as peptidoglycan’s unusual composition and branching can’t be handled by proteomics software. Here we describe user-friendly open-source tools and a web interface for building peptidoglycan databases, performing MS searches, and predicting the MS/MS fragmentation of muropeptides. We then use Rhizobium leguminosarum to describe a step-by-step strategy for the high-resolution analysis of peptidoglycan. The unprecedented detail of R. leguminosarum’s peptidoglycan composition (>250 muropeptides) reveals even the subtlest remodelling between growth conditions. These new and easier to use tools enable more systematic analyses of peptidoglycan dynamics.

The aims of the study were to describe inpatient harm events detected via an automatic electronic trigger system (ETS) and to consider their financial consequences. Over a 27-month period, inpatient harm events were identified and documented in 1 healthcare system with 37 acute care facilities. Patients who experienced harm (all harm or preventable harm only) were compared with similar patients who did not. Clinical, financial, and demographic data were used to identify labor-adjusted direct variable costs (DVC) and potential differences in length of stay (LOS) associated with all-harm, preventable-harm, and nonharmed cohorts. Age-adjusted Charlson Comorbidity Index, case mix index, diagnosis-related groups, major diagnostic category, sex, age, location, diagnosis, adverse event category and subcategory, preventability, and harm severity were used to compare cohorts. Total harm events reported via the ETS and the health system's voluntary event reporting system were compared. Nearly 93,000 encounters for all-harm (n = 25,665) and nonharmed cohorts (n = 67,217) were compared by random sampling of diagnosis-related group-matched all-harm and nonharmed groups to ensure similar clinical conditions, as measured by Charlson Comorbidity Index and case mix index. Sampling (2 groups, n = 100 and n = 200) showed that increased LOS was associated with harm; yet other clinical comparators were similar across groups. the preventable-harm subcohort had longer LOS (10.7 versus 5.9 days) and higher DVC ($13,442 versus $8024) than the nonharmed cohort. Identification of harm events was nearly 6-fold higher with the ETS than with the voluntary event reporting system. Patients with preventable harm had increased LOS that was associated with higher DVC per preventable-harm encounter in a large US healthcare system.