Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) updates the KDIGO 2012 guideline and has been developed with patient partners, clinicians, and researchers around the world, using robust methodology. This update, based on a substantially broader base of evidence than has previously been available, reflects an exciting time in nephrology. New therapies and strategies have been tested in large and diverse populations that help to inform care; however, this guideline is not intended for people receiving dialysis nor those who have a kidney transplant. The document is sensitive to international considerations, CKD across the lifespan, and discusses special considerations in implementation. The scope includes chapters dedicated to the evaluation and risk assessment of people with CKD, management to delay CKD progression and its complications, medication management and drug stewardship in CKD, and optimal models of CKD care. Treatment approaches and actionable guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence and the strength of recommendations which followed the "Grading of Recommendations Assessment, Development, and Evaluation" (GRADE) approach. The limitations of the evidence are discussed. The guideline also provides practice points, which serve to direct clinical care or activities for which a systematic review was not conducted, and it includes useful infographics and describes an important research agenda for the future. It targets a broad audience of people with CKD and their healthcare, while being mindful of implications for policy and payment.

Methods proposed for monitoring the implementation of evidence-based research: a cross-sectional study.

OBJECTIVES: Evidence-based research (EBR) is the systematic and transparent use of prior research to inform a new study so that it answers questions that matter in a valid, efficient, and accessible manner. This study surveyed experts about existing (e.g., citation analysis) and new methods for monitoring EBR and collected ideas about implementing these methods. STUDY DESIGN AND SETTING: We conducted a cross-sectional study via an online survey between November 2022 and March 2023. Participants were experts from the fields of evidence synthesis and research methodology in health research. Open-ended questions were coded by recurring themes; descriptive statistics were used for quantitative questions. RESULTS: Twenty-eight expert participants suggested that citation analysis should be supplemented with content evaluation (not just what is cited but also in which context), content expert involvement, and assessment of the quality of cited systematic reviews. They also suggested that citation analysis could be facilitated with automation tools. They emphasized that EBR monitoring should be conducted by ethics committees and funding bodies before the research starts. Challenges identified for EBR implementation monitoring were resource constraints and clarity on responsibility for EBR monitoring. CONCLUSION: Ideas proposed in this study for monitoring the implementation of EBR can be used to refine methods and define responsibility but should be further explored in terms of feasibility and acceptability. Different methods may be needed to determine if the use of EBR is improving over time.

Perspectives on systematic review protocol registration: a survey amongst stakeholders in the clinical research publication process.

BACKGROUND: As systematic reviews (SRs) inform healthcare decisions, it is key that they address relevant questions and use rigorous methodology. Registration of SR protocols helps researchers identify relevant topics for future reviews and aims to prevent bias and duplication of effort. However, most SRs protocols are currently not registered, despite its significance. To guide future recommendations to enhance preregistration of SRs, it is important to gain a comprehensive understanding of the perspectives within the research community. Therefore, this study aims to examine the experiences with and factors of influence (barriers and facilitators) on prospective SR registration amongst researchers, peer reviewers and journal editors. METHODS: Two different surveys were distributed to two groups: researchers and journal editors both identified from an existing sample of SRs. Researchers who indicated to have peer reviewed a SR were surveyed on their perspectives as peer reviewers as well. Survey design and analysis were informed by the Consolidated Framework for Implementation Research (CFIR). Shared and unique subthemes from the perspectives of researchers, peer reviewers and journal editors were identified and linked to the SR registration process (Innovation), to team, organisation (Inner setting) and (inter)national research community (Outer setting), and to characteristics of researchers, peer reviewers or journal editors (Individuals). RESULTS: The survey's response rates were 65/727 (9%) for researchers, of which 37 were peer reviewers, and 22/308 (7%) for journal editors. Most respondents (n = 76, 94%) were familiar with SR protocol registration and 81% of researchers had registered minimally one SR protocol. Shared SR registration process subthemes were the importance and advantages of SR protocol registration, as well as barriers such as a high administrative burden. Shared subthemes regarding the inner and outer setting centred on journal processes, external standards and time. Shared individual factors were knowledge, skills and awareness. CONCLUSIONS: The majority of the respondents were familiar with SR protocol registration and had a positive attitude towards it. This study identified suboptimal registration process, administrative burden and lack of mandatory SR protocol registration as barriers. By overcoming these barriers, SR protocol registration could contribute more effectively to the goals of open science. SYSTEMATIC REVIEW REGISTRATION: osf.io/gmv6z.

High incidence of antibiotic resistance amongst isolates of Helicobacter pylori collected in Nottingham, UK, between 2001 and 2018.

Introduction. Helicobacter pylori is the leading cause of peptic ulcers and gastric cancer. The most common treatment regimens use combinations of two or three antibiotics and a proton pump inhibitor (PPI) to suppress stomach acid. The World Health Organization designated clarithromycin-resistant H. pylori as a high priority pathogen for drug development, due to increasing antibiotic resistance globally.Hypothesis/Gap Statement. There is no routine surveillance of H. pylori primary antimicrobial sensitivities in the UK, and published data are lacking.Aim. This study aimed to characterize antimicrobial sensitivities of isolates collected in Nottingham, UK, between 2001 and 2018.Methodology. Gastric biopsy samples were collected, with informed written consent and ethics approval, from 162 patients attending the Queen's Medical Centre in Nottingham for an upper GI tract endoscopy. Antibiotic sensitivity was assessed using E-Tests and a more cost-effective disc diffusion test.Results. The clarithromycin, amoxicillin and levofloxacin disc diffusion tests provided identical results to E-Tests on a subset of 30 isolates. Disparities were observed in the metronidazole test results, however. In total, 241 isolates from 162 patients were tested using at least one method. Of all isolates, 28 % were resistant to clarithromycin, 62 % to metronidazole and 3 % to amoxicillin, which are used in first-line therapies. For those antibiotics used in second- and third-line therapies, 4 % were resistant to levofloxacin and none of the isolates were resistant to tetracycline. Resistance to more than one antibiotic was found in 27 % of isolates. The frequency of patients with a clarithromycin-resistant strain increased dramatically over time: from 16 % between 2001 and 2005 to 40 % between 2011 and 2018 (P=0.011). For the same time periods, there was also an increase in those with a metronidazole-resistant strain (from 58 to 78 %; P=0.05). The frequencies of clarithromycin and metronidazole resistance were higher in isolates from patients who had previously received eradication therapy, compared to those who had not (40 % versus 77 %, and 80 % versus 92 %, respectively). Of 79 pairs of isolates from the antrum and corpus regions of the same patient's stomach, only six had differences in their antimicrobial susceptibility profiles.Conclusion. Although there was high and increasing resistance to clarithromycin and metronidazole, there was no resistance to tetracycline and the frequencies of amoxicillin and levofloxacin resistance were very low.

Multiple chemical sensitivity scoping review protocol: overview of research and MCS construct.

INTRODUCTION: Multiple chemical sensitivity (MCS) has been characterised by reported adverse responses to environmental exposures of common chemical agents (eg, perfumes, paint, cleaning products and other inhaled or ingested agents) in low doses considered non-toxic for the general population. There is currently no consensus on whether MCS can be established as a distinct disorder. METHODS AND ANALYSIS: The scoping review of the literature will be guided by five questions: How is MCS defined and which diagnostic criteria have been proposed? What methods are used to report prevalence and incidence estimates of MCS? What are the characteristics of the body of scientific evidence that addresses whether MCS is a distinct disorder or syndrome? What underlying mechanisms for MCS have been proposed in the scientific literature? Which treatment and management approaches for MCS have been evaluated in empirical research studies? We will conduct a comprehensive search in 14 research databases. Citation screening will be supported by machine learning algorithms. Two independent reviewers will assess eligibility of full-text publications against prespecified criteria. Data abstraction will support concise evidence tables. A formal consultation exercise will elicit input regarding the review results and presentation. The existing research evidence will be documented in a user-friendly visualisation in the format of an evidence map. ETHICS AND DISSEMINATION: Determined to be exempt from review (UP-22-00516). Results will be disseminated through a journal manuscript and data will be publicly accessible through an online data repository. REGISTRATION DETAILS: The protocol is registered in Open Science Framework (osf.io/4a3wu).

Re-evaluating the role of pilot trials in informing effect and sample size estimates for full-scale trials: a meta-epidemiological study.

BACKGROUND: Some have argued that pilot trials have little value for informing the expected effect size of a subsequent large trial. This study aims to empirically evaluate the roles of pilot trials in informing the effect and sample size estimates of a full-scale trial. METHODS: We conducted a search in PubMed on 19 February 2022, for all pilot trials published between 2005 and 2018 and their subsequent full-scale trials. We analysed the agreement in results by comparing the direction and magnitude of the effect size in the pilot trial and full-scale trial. Logistic regression was used to explore whether a significant pilot trial and other characteristics were associated with a significant full-scale trial. RESULTS: A total of 248 pairs of pilot and full-scale trials were analysed. Full-scale trials with a significant pilot trial were 2.72 times more likely to find a significant result for the primary efficacy outcome than those with a non-significant pilot trial (95% CI 1.52 to 4.86, p=0.001). The association remained significant irrespective of changes made to the trial design. In 73% of the pairs, the pilot trial produced a larger point estimate than the subsequent full-scale trial, but 87% of pairs had a 95% CI estimated by the pilot trial that covered the full-scale trial point estimate. Full-scale trials with a sample size estimated using the SD from the pilot trial were less likely to yield a significant result (OR=0.26, 95% CI 0.10 to 0.65, p=0.004). CONCLUSION: Pilot trials can provide strong signals on intervention efficacy. When determining the sample size for full-scale trials, using the CI bounds from the pilot trials instead of the point estimate may improve power estimation.

Characterization of a Helicobacter pylori strain with high biofilm-forming ability.

Introduction. Helicobacter pylori is highly polymorphic, and some strains are much more likely to cause disease than others. Biofilm formation can help bacteria to survive antibiotic treatment, immune attack and other stresses, promoting persistent infection.Hypothesis/Gap Statement. We hypothesized that H. pylori isolates from patients with more severe H. pylori-associated disease would be better at forming biofilms than isolates from patients with less severe disease.Aim. We initially aimed to determine whether or not the biofilm-forming ability of H. pylori isolates was associated with disease in the UK-based patients from whom the bacteria were isolated.Methodology. Biofilm-forming ability of H. pylori isolates was determined using a crystal violet assay on glass coverslips. The complete genome sequence of strain 444A was generated by hybrid assembly of Nanopore MinION and Illumina MiSeq data.Results. Although we found no associations between biofilm-forming ability of H. pylori and disease severity in patients, we discovered that strain 444A had particularly high biofilm-forming ability. This strain had been isolated from a patient with gastric ulcer disease and moderate to severe scores for H. pylori-induced histopathology. Analysis of the genome of the high biofilm-forming H. pylori strain 444A revealed that it possesses numerous biofilm- and virulence-associated genes and a small cryptic plasmid encoding a type II toxin-antitoxin system.Conclusion. There is substantial variation in biofilm-forming ability in H. pylori, but this was not significantly associated with disease severity in our study. We identified and characterized an interesting strain with high biofilm-forming ability, including generation and analysis of the complete genome.

The FORCIS database: A global census of planktonic Foraminifera from ocean waters.

Planktonic Foraminifera are unique paleo-environmental indicators through their excellent fossil record in ocean sediments. Their distribution and diversity are affected by different environmental factors including anthropogenically forced ocean and climate change. Until now, historical changes in their distribution have not been fully assessed at the global scale. Here we present the FORCIS (Foraminifera Response to Climatic Stress) database on foraminiferal species diversity and distribution in the global ocean from 1910 until 2018 including published and unpublished data. The FORCIS database includes data collected using plankton tows, continuous plankton recorder, sediment traps and plankton pump, and contains ~22,000, ~157,000, ~9,000, ~400 subsamples, respectively (one single plankton aliquot collected within a depth range, time interval, size fraction range, at a single location) from each category. Our database provides a perspective of the distribution patterns of planktonic Foraminifera in the global ocean on large spatial (regional to basin scale, and at the vertical scale), and temporal (seasonal to interdecadal) scales over the past century.

The synergistic effect of Levilactobacillus brevis IBRC-M10790 and vitamin D3 on Helicobacter pylori-induced inflammation.

Background: Owing to the emergence and spread of multidrug resistance mechanisms in Helicobacter pylori, achieving a successful eradication has become exceedingly difficult. Thus, this study for the first time determines the effect of a combination of vitamin D3 and probiotic on the pathogenesis and treatment of H. pylori. Methods: We established an in vitro experimental system using AGS human gastric carcinoma cells and explored the synergistic effect of Levilactobacillus brevis IBRC-M10790 and vitamin D3 on H. pylori. Live and pasteurized L. brevis, L. brevis-derived membrane vesicles (MVs), and L. brevis cell-free supernatant (CFS), as well as their combination with vitamin D3 were used during this study. We assessed the anti-inflammatory and anti-oxidative effects of these combinations using RT-qPCR and ELISA, respectively. We further performed an adhesion assay to evaluate the influence of L. brevis and vitamin D3 on the adherence rate of H. pylori to AGS cells. Results: Our results demonstrated that L. brevis and vitamin D3 possess anti-inflammatory and anti-oxidative effects against H. pylori infection in AGS cells. The combination of vitamin D3 with the probiotic strain (particularly live L. brevis and its CFS) can more efficiently reduce the expression of pro-inflammatory cytokines IL-6, IL-8, IFN-γ, and TNF-α in the AGS cells. Moreover, vitamin D3 and L. brevis exhibited an additive impact preserving the integrity of the epithelial barrier by increasing the expression of the tight junction protein ZO-1. Furthermore, this combination can potentially reduce H. pylori adherence to AGS cells. Conclusions: This study indicates the advantage of combining vitamin D3 and probiotic to attenuate H. pylori-induced inflammation and oxidative stress. Consequently, probiotic and vitamin D3 co-supplementation can be considered as a novel therapeutic approach to manage and prevent H. pylori infection.

Impact of Clinician Training Background and Stroke Location on Bedside Diagnostic Test Accuracy in the Acute Vestibular Syndrome - A Meta-Analysis.

OBJECTIVE: Acute dizziness/vertigo is usually due to benign inner-ear causes but is occasionally due to dangerous neurologic ones, particularly stroke. Because symptoms and signs overlap, misdiagnosis is frequent and overuse of neuroimaging is common. We assessed the accuracy of bedside findings to differentiate peripheral vestibular from central neurologic causes. METHODS: We performed a systematic search (MEDLINE and Embase) to identify studies reporting on diagnostic accuracy of physical examination in adults with acute, prolonged dizziness/vertigo ("acute vestibular syndrome" [AVS]). Diagnostic test properties were calculated for findings. Results were stratified by examiner type and stroke location. RESULTS: We identified 6,089 citations and included 14 articles representing 10 study cohorts (n = 800). The Head Impulse, Nystagmus, Test of Skew (HINTS) eye movement battery had high sensitivity 95.3% (95% confidence interval [CI] = 92.5-98.1) and specificity 92.6% (95% CI = 88.6-96.5). Sensitivity was similar by examiner type (subspecialists 94.3% [95% CI = 88.2-100.0] vs non-subspecialists 95.0% [95% CI = 91.2-98.9], p = 0.55), but specificity was higher among subspecialists (97.6% [95% CI = 94.9-100.0] vs 89.1% [95% CI = 83.0-95.2], p = 0.007). HINTS sensitivity was lower in anterior cerebellar artery (AICA) than posterior inferior cerebellar artery (PICA) strokes (84.0% [95% CI = 65.3-93.6] vs 97.7% [95% CI = 93.3-99.2], p = 0.014) but was "rescued" by the addition of bedside hearing tests (HINTS+). Severe (grade 3) gait/truncal instability had high specificity 99.2% (95% CI = 97.8-100.0) but low sensitivity 35.8% (95% CI = 5.2-66.5). Early magnetic resonance imaging (MRI)-diffusion-weighted imaging (DWI; within 24-48 hours) was falsely negative in 15% of strokes (sensitivity 85.1% [95% CI = 79.2-91.0]). INTERPRETATION: In AVS, HINTS examination by appropriately trained clinicians can differentiate peripheral from central causes and has higher diagnostic accuracy for stroke than MRI-DWI in the first 24-48 hours. These techniques should be disseminated to all clinicians evaluating dizziness/vertigo. ANN NEUROL 2023;94:295-308.

Are ChatGPT and large language models "the answer" to bringing us closer to systematic review automation?

In this commentary, we discuss ChatGPT and our perspectives on its utility to systematic reviews (SRs) through the appropriateness and applicability of its responses to SR related prompts. The advancement of artificial intelligence (AI)-assisted technologies leave many wondering about the current capabilities, limitations, and opportunities for integration AI into scientific endeavors. Large language models (LLM)-such as ChatGPT, designed by OpenAI-have recently gained widespread attention with their ability to respond to various prompts in a natural-sounding way. Systematic reviews (SRs) utilize secondary data and often require many months and substantial financial resources to complete, making them attractive grounds for developing AI-assistive technologies. On February 6, 2023, PICO Portal developers hosted a webinar to explore ChatGPT's responses to tasks related to SR methodology. Our experience from exploring the responses of ChatGPT suggest that while ChatGPT and LLMs show some promise for aiding in SR-related tasks, the technology is in its infancy and needs much development for such applications. Furthermore, we advise that great caution should be taken by non-content experts in using these tools due to much of the output appearing, at a high level, to be valid, while much is erroneous and in need of active vetting.

Standards of care for CFTR variant-specific therapy (including modulators) for people with cystic fibrosis.

Cystic fibrosis (CF) has entered the era of variant-specific therapy, tailored to the genetic variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. CFTR modulators, the first variant-specific therapy available, have transformed the management of CF. The latest standards of care from the European CF Society (2018) did not include guidance on variant-specific therapy, as CFTR modulators were becoming established as a novel therapy. We have produced interim standards to guide healthcare professionals in the provision of variant-specific therapy for people with CF. Here we provide evidence-based guidance covering the spectrum of care, established using evidence from systematic reviews and expert opinion. Statements were reviewed by key stakeholders using Delphi methodology, with agreement (≥80%) achieved for all statements after one round of consultation. Issues around accessibility are discussed and there is clear consensus that all eligible people with CF should have access to variant-specific therapy.

Trends of Randomized Clinical Trials Citing Prior Systematic Reviews, 2007-2021.

Importance: Systematic reviews can help to justify a new randomized clinical trial (RCT), inform its design, and interpret its results in the context of prior evidence. Objective: To assess trends and factors associated with citing (a marker of the use of) prior systematic reviews in RCT reports. Design, Setting, and Participants: This cross-sectional study investigated 737 Cochrane reviews assessing health interventions to identify 4003 eligible RCTs, defined as those included in an updated version but not in the first version of a Cochrane review and published 2 years after the first version of the Cochrane review was published. Main Outcomes and Measures: The primary outcome was the citation of prior systematic reviews, Cochrane or others, as determined by screening references of eligible RCTs. Factors that may be associated with the citation of prior systematic reviews were also examined. Results: Among 4003 eligible RCTs, 1241 studies (31.0%) cited Cochrane reviews, 1698 studies (42.4%) cited prior non-Cochrane reviews, and 2265 studies (56.6%) cited either type of systematic review or both; 1738 RCTs (43.4%) cited no systematic reviews. The percentage of RCTs citing prior Cochrane reviews, non-Cochrane reviews, and either or both types of review increased from 28 studies (15.3%), 46 studies (25.1%), and 65 studies (35.5%) of 183 RCTs before 2008 to 42 studies (40.8%), 65 studies (64.1%), and 73 studies (71.8%) of 102 RCTs since 2020, respectively; the annual increases were 1.9% (95% CI, 1.4%-2.3%), 3.3% (95% CI, 2.9%-3.7%), and 3.0% (95% CI, 2.5%-3.5%), respectively. The proportion of RCTs citating prior systematic reviews varied considerably across clinical specialties, ranging from 28 of 106 RCTs (26.4%) in ophthalmology to 386 of 553 RCTs (69.8%) in psychiatry (P < .001). RCTs with 100 participants or more (risk ratio [RR], 1.16; 95% CI, 1.03-1.30), nonindustry funding (RR, 1.43; 95% CI, 1.27-1.61), and authors from high-income countries (RR, 1.10; 95% CI, 1.03-1.17) were more likely to cite systematic reviews than those with fewer than 100 participants, industry funding, and authors from low- and middle-income countries, respectively. A journal requirement to cite systematic reviews was not associated with the likelihood of citing a systematic review. Conclusions and Relevance: This study found that the citation of prior systematic reviews in RCT reports improved over time, but approximately 40% of RCTs failed to do so. These findings suggest that reference to prior evidence for initiating, designing, and reporting RCTs should be further emphasized to assure clinical relevance, improve methodological quality, and facilitate interpretation of new results.

Comparing Experiences of Women Who Were Direct Breastfeeding and Women Who Used Expressed Breast Milk to Feed Their Infants.

PURPOSE: To provide understanding about feeding experiences of women who provide breast milk through direct breastfeeding and exclusive expression and to compare these experiences. STUDY DESIGN AND METHODS: A qualitative study was conducted to gather experiences from the perspectives of women who had given birth to a healthy, term infant within the past 12 months and exclusively fed breast milk for at least 2 weeks. The sample was recruited from motherhood and breastfeeding support groups on Facebook. Groups had state- or national-based memberships. Interviews were examined for themes that were compared between feeding groups using thematic analysis. RESULTS: Fifteen new mothers participated. Under the primary themes of Similarities and Differences, seven subthemes were identified: Fatigue, Importance of Support, Finding Joy in a Common Goal, Mixed Feelings, Trusting versus Tracking, Latching versus Body Failure, and Pumping in Isolation. CLINICAL IMPLICATIONS: Mothers who provide breast milk share common experiences and feelings of satisfaction. Expressed breast milk feeding offers some mothers a way to provide the benefits of breast milk while preserving a balance between maternal and infant physical and mental health needs. Understanding the different ways in which women manage breast milk feeding while balancing maternal and infant needs can prepare nurses to discuss various methods of breast milk feeding and provide individualized support.

Active cycle of breathing technique for cystic fibrosis.

BACKGROUND: People with cystic fibrosis (CF) experience chronic airway infections as a result of mucus buildup within the lungs. Repeated infections often cause lung damage and disease. Airway clearance therapies aim to improve mucus clearance, increase sputum production, and improve airway function. The active cycle of breathing technique (ACBT) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control, thoracic expansion exercises, and the forced expiration technique. This is an update of a previously published review. OBJECTIVES: To compare the clinical effectiveness of ACBT with other airway clearance therapies in CF. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched clinical trials registries and the reference lists of relevant articles and reviews. Date of last search: 29 March 2021. SELECTION CRITERIA: We included randomised or quasi-randomised controlled clinical studies, including cross-over studies, comparing ACBT with other airway clearance therapies in CF. DATA COLLECTION AND ANALYSIS: Two review authors independently screened each article, abstracted data and assessed the risk of bias of each study. We used GRADE to assess our confidence in the evidence assessing quality of life, participant preference, adverse events, forced expiratory volume in one second (FEV1) % predicted, forced vital capacity (FVC) % predicted, sputum weight, and number of pulmonary exacerbations. MAIN RESULTS: Our search identified 99 studies, of which 22 (559 participants) met the inclusion criteria. Eight randomised controlled studies (259 participants) were included in the analysis; five were of cross-over design. The 14 remaining studies were cross-over studies with inadequate reports for complete assessment. The study size ranged from seven to 65 participants. The age of the participants ranged from six to 63 years (mean age 18.7 years). In 13 studies follow up lasted a single day. However, there were two long-term randomised controlled studies with follow up of one to three years. Most of the studies did not report on key quality items, and therefore, have an unclear risk of bias in terms of random sequence generation, allocation concealment, and outcome assessor blinding. Due to the nature of the intervention, none of the studies blinded participants or the personnel applying the interventions. However, most of the studies reported on all planned outcomes, had adequate follow up, assessed compliance, and used an intention-to-treat analysis. Included studies compared ACBT with autogenic drainage, airway oscillating devices (AOD), high-frequency chest compression devices, conventional chest physiotherapy (CCPT), positive expiratory pressure (PEP), and exercise. We found no difference in quality of life between ACBT and PEP mask therapy, AOD, other breathing techniques, or exercise (very low-certainty evidence). There was no difference in individual preference between ACBT and other breathing techniques (very low-certainty evidence). One study comparing ACBT with ACBT plus postural exercise reported no deaths and no adverse events (very low-certainty evidence). We found no differences in lung function (forced expiratory volume in one second (FEV1) % predicted and forced vital capacity (FVC) % predicted), oxygen saturation or expectorated sputum between ACBT and any other technique (very low-certainty evidence). There were no differences in the number of pulmonary exacerbations between people using ACBT and people using CCPT (low-certainty evidence) or ACBT with exercise (very low-certainty evidence), the only comparisons to report this outcome. AUTHORS' CONCLUSIONS: There is little evidence to support or reject the use of the ACBT over any other airway clearance therapy and ACBT is comparable with other therapies in outcomes such as participant preference, quality of life, exercise tolerance, lung function, sputum weight, oxygen saturation, and number of pulmonary exacerbations. Longer-term studies are needed to more adequately assess the effects of ACBT on outcomes important for people with cystic fibrosis such as quality of life and preference.

Assessment of redundant randomized clinical trials among patients with ST segment elevation myocardial infarction.

BACKGROUND: Redundant clinical trials waste resources and unnecessarily put patients at risk for harm. The objectives of the study were to assess redundant randomized clinical trials (RCTs) conducted in mainland China or the USA among patients with ST segment elevation myocardial infarction (STEMI) and estimate the harm to patients enrolled in redundant RCTs. METHODS: We searched bibliographic databases for eligible RCTs comparing a routine therapy with a placebo or no treatment among patients with STEMI in mainland China or the United States. The routine therapy for STEMI included reperfusion (percutaneous coronary intervention or fibrinolytic therapy), P2Y12 receptor inhibitors, statins, and anticoagulants. Redundant RCTs were defined as those initiated or continued recruiting new patients 1 year after the experimental intervention was established as routine therapy in clinical practice guidelines. Cumulative meta-analyses were conducted to confirm the efficacy of these routine therapies. The primary outcome was the number of extra major adverse cardiac events (MACEs) attributable to the deprivation of routine therapies among patients in the control groups of redundant RCTs-that is, the number of extra MACEs that could have been prevented had these patients received routine therapy. RESULTS: Nine hundred eighty-three eligible RCTs conducted in mainland China were identified, of which 775 (78.8%) were redundant. None of the five eligible RCTs conducted in the United States were redundant. All redundant RCTs have reiterated the benefits of routine therapies for patients with STEMI, while none were cited by the 2019 clinical practice guideline for the management of STEMI. The 18,819 patients in the control groups of redundant RCTs experienced 3305 (95% CI: 3169-3441) extra MACEs, including 1091 (1014-1165) deaths, 576 (519-633) recurrent myocardial infarctions, 31 (19-42) revascularizations, 39 (23-54) strokes, 744 (679-810) heart failures, and 823 (754-893) patients with recurrent or exacerbated angina pectoris. Cumulative meta-analyses confirmed the efficacy of the routine therapies among patients in mainland China and supported using practice guidelines to define redundant RCTs. CONCLUSIONS: Redundant RCTs conducted in mainland China have resulted in unnecessary MACEs among patients with STEMI. While the reasons behind redundant RCTs need to be further investigated, these results suggest potential research waste and violation of research ethics.

Parent perceptions and decision making about treatments for epilepsy: a qualitative evidence synthesis.

OBJECTIVES: Epilepsy treatment decision making is complex and understanding what informs caregiver decision making about treatment for childhood epilepsy is crucial to better support caregivers and their children. We synthesised evidence on caregivers' perspectives and experiences of treatments for childhood epilepsy. DESIGN: Systematic review of qualitative studies using a best-fit framework and Grading of Recommendations Assessment, Development and Evaluation Confidence in the Evidence from Reviews of Qualitative Research (GRADE-CERQual) approach. DATA SOURCES: Searched Embase, PubMed, CINAHL, PsycINFO, SocINDEX and Web of Science from 1 January 1999 to 19 August 2021. ELIGIBILITY CRITERIA: We included qualitative studies examining caregiver's perspectives on antiseizure medication, diet or surgical treatments for childhood epilepsy. We excluded studies not reported in English. DATA EXTRACTION AND SYNTHESIS: We extracted qualitative evidence into 1 of 14 domains defined by the Theoretical Domains Framework (TDF). One reviewer extracted study data and methodological characteristics, and two reviewers extracted qualitative findings. The team verified all extractions. We identified themes within TDF domains and synthesised summary statements of these themes. We assessed our confidence in our summary statements using GRADE-CERQual. RESULTS: We identified five studies (in six reports) of good methodological quality focused on parent perceptions of neurosurgery; we found limited indirect evidence on parents' perceptions of medications or diet. We identified themes within 6 of the 14 TDF domains relevant to treatment decisions: knowledge, emotion; social/professional role and identity; social influence; beliefs about consequences; and environmental context and resources. CONCLUSIONS: Parents of children with epilepsy navigate a complex process to decide whether to have their child undergo surgery. Educational resources, peer support and patient navigators may help support parents through this process. More qualitative studies are needed on non-surgical treatments for epilepsy and among caregivers from different cultural and socioeconomic backgrounds to fully understand the diversity of perspectives that informs treatment decision making.

Parenchymal lung abnormalities following hospitalisation for COVID-19 and viral pneumonitis: a systematic review and meta-analysis.

INTRODUCTION: Persisting respiratory symptoms in COVID-19 survivors may be related to development of pulmonary fibrosis. We assessed the proportion of chest CT scans and pulmonary function tests consistent with parenchymal lung disease in the follow-up of people hospitalised with COVID-19 and viral pneumonitis. METHODS: Systematic review and random effects meta-analysis of proportions using studies of adults hospitalised with SARS-CoV-2, SARS-CoV, MERS-CoV or influenza pneumonia and followed up within 12 months. Searches performed in MEDLINE and Embase. Primary outcomes were proportion of radiological sequelae on CT scans; restrictive impairment; impaired gas transfer. Heterogeneity was explored in meta-regression. RESULTS: Ninety-five studies (98.9% observational) were included in qualitative synthesis, 70 were suitable for meta-analysis including 60 SARS-CoV-2 studies with a median follow-up of 3 months. In SARS-CoV-2, the overall estimated proportion of inflammatory sequelae was 50% during follow-up (0.50; 95% CI 0.41 to 0.58; I2=95%), fibrotic sequelae were estimated in 29% (0.29; 95% CI 0.22 to 0.37; I2=94.1%). Follow-up time was significantly associated with estimates of inflammatory sequelae (-0.036; 95% CI -0.068 to -0.004; p=0.029), associations with fibrotic sequelae did not reach significance (-0.021; 95% CI -0.051 to 0.009; p=0.176). Impaired gas transfer was estimated at 38% of lung function tests (0.38 95% CI 0.32 to 0.44; I2=92.1%), which was greater than restrictive impairment (0.17; 95% CI 0.13 to 0.23; I2=92.5%), neither were associated with follow-up time (p=0.207; p=0.864). DISCUSSION: Sequelae consistent with parenchymal lung disease were observed following COVID-19 and other viral pneumonitis. Estimates should be interpreted with caution due to high heterogeneity, differences in study casemix and initial severity. PROSPERO REGISTRATION NUMBER: CRD42020183139.

Diet-Related and Gut-Derived Metabolites and Health Outcomes: A Scoping Review.

We conducted a scoping review to map available evidence about the health impact of gut microbiota-derived metabolites. We searched PubMed and Embase for studies that assessed the health impact of ten metabolites on any health condition: deoxycholate or deoxycholic acid (DCA), lithocholate or lithocholic acid (LCA), glycolithocholate or glycolithocholic acid, glycodeoxycholate or glycodeoxycholic acid, tryptamine, putrescine, d-alanine, urolithins, N-acetylmannosamine, and phenylacetylglutamine. We identified 352 eligible studies with 168,072 participants. Most (326, 92.6%) were case-control studies, followed by cohort studies (14, 4.0%), clinical trials (8, 2.3%), and cross-sectional studies (6, 1.7%). Most studies assessed the following associations: DCA on hepatobiliary disorders (64 studies, 7976 participants), colorectal cancer (19 studies, 7461 participants), and other digestive disorders (27 studies, 2463 participants); LCA on hepatobiliary disorders (34 studies, 4297 participants), colorectal cancers (14 studies, 4955 participants), and other digestive disorders (26 studies, 2117 participants); putrescine on colorectal cancers (16 studies, 94,399 participants) and cancers excluding colorectal and hepatobiliary cancers (42 studies, 4250 participants). There is a need to conduct more prospective studies, including clinical trials. Moreover, we identified metabolites and conditions for which systemic reviews are warranted to characterize the direction and magnitude of metabolite-disease associations.