Efficacy and safety of COVID-19 vaccination in solid organ transplant recipients: A systematic review and network meta-analysis.

The impact of COVID-19 vaccination on clinical outcomes in solid organ transplant (SOT) recipients remains unclear. This systematic review and network meta-analysis sought to assess the efficacy and safety of COVID-19 vaccination in SOT recipients. We searched 6 databases from inception to March 1, 2024 for randomized controlled trials (RCTs) and observational studies evaluating different COVID-19 vaccination strategies in SOT recipients. Based on patient-important outcomes, we performed frequentist random-effects pairwise meta-analyses and network meta-analyses, separating RCTs and nonrandomized evidence, and used the Grading of Recommendation, Assessment, Development, and Evaluation approach to assess our certainty in the evidence. We included 6 RCTs (N = 814) and 43 observational studies (N = 125 199). Overall, there is a paucity of randomized evidence evaluating COVID-19 vaccines in SOT recipients. The nonrandomized evidence evaluating COVID-19 vaccination strategies patient-important outcomes, including COVID-19 infection, mortality, hospitalization, ICU admission, and rejection, demonstrated low to very low certainty due to the included studies' risk of bias. Throughout the COVID-19 pandemic, clinicians and SOT recipients worked with minimal, very low-quality evidence in relation to COVID-19 vaccines in this population. In the instance of future public health emergencies, clinicians and researchers should collaborate closely with patient partners to ensure there is sufficient evidence in the transplant population on patient-important outcomes.

Patient-Reported Outcome Measures in Cancer Care: An Updated Systematic Review and Meta-Analysis.

Importance: Patient-reported outcome measures (PROMs) come directly from the patient, without clinician interpretation, to provide a patient-centered perspective. Objective: To understand the association of PROM integration into cancer care with patient-related, therapy-related, and health care utilization outcomes. Data Sources: Searches included MEDLINE and MEDLINE Epub ahead of print, in-process, and other nonindexed citations; Embase databases (OvidSP); PsychINFO; CENTRAL; and CINAHL from January 1, 2012 to September 26, 2022. Study Selection: Randomized clinical trials (RCTs) that enrolled adult patients (ages 18 years and older) with active cancer receiving anticancer therapy using a PROM as an intervention. Data Extraction and Synthesis: Pairs of review authors, using prepiloted forms, independently extracted trial characteristics, disease characteristics, and intervention details. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline was followed. Random-effects analyses were conducted. Main Outcomes and Measures: Overall mortality, health-related quality of life (HRQoL) measures, and hospital utilization outcomes. Results: From 1996 to 2022, 45 RCTs including 13 661 participants addressed the association of PROMs with outcomes considered important to patients. The addition of a PROM likely reduced the risk of overall mortality (HR, 0.84; 95% CI, 0.72-0.98; moderate certainty), improved HRQoL (range 0-100) at 12 weeks (mean difference [MD], 2.45; 95% CI, 0.42-4.48; moderate certainty). Improvements of HRQoL at 24 weeks were not significant (MD, 1.87; 95% CI, -1.21 to 4.96; low certainty). There was no association between the addition of a PROM and HRQoL at 48 weeks. The addition of a PROM was not associated with reduced ED visits (OR, 0.74; 95% CI, 0.54-1.02; low certainty) or hospital admissions (OR, 0.86; 95% CI, 0.73-1.02; low certainty). Conclusion and Relevance: The findings of this study suggest that the integration of PROMs into cancer care may improve overall survival and quality of life.

Topical corticosteroids for hives and itch (urticaria): Systematic review and Bayesian meta-analysis of randomized trials.

BACKGROUND: Topical corticosteroids are widely used as a treatment for itch and wheals (urticaria), but their benefits and harms are unclear. OBJECTIVE: To systematically synthesize the benefits and harms of topical corticosteroids for the treatment of urticaria. METHODS: We searched MEDLINE, EMBASE, and CENTRAL from database inception to March 23, 2024, for randomized trials comparing topical corticosteroids with placebo for patients with urticaria (either chronic spontaneous or inducible urticaria or acute urticaria elicited from skin/intradermal allergy testing). Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects meta-analyses addressed urticaria severity, itch severity (numeric rating scale; range 0-10; higher is worse), and adverse events. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed certainty of evidence ratings. PROSPERO registration: CRD42023455182. RESULTS: A total of 19 randomized controlled trials enrolled 379 participants with a median of mean age of 30.1 (range 21.1-44.0) years. Compared with placebo, topical corticosteroids may reduce wheal size (ratio of means 0.47, 95% CI 0.38-0.59; low certainty) and itch severity (mean difference -1.30, 95% CI -5.07 to 2.46; very low certainty). Topical corticosteroids result in little to no difference in overall adverse events (94 fewer patients per 1000, 95% credible intervals 172 fewer to 12 more; high certainty). CONCLUSION: Compared with placebo, topical corticosteroids may result in a reduction of wheal size and little to no difference in overall adverse events. Topical corticosteroids may reduce itch severity, but the evidence is very uncertain. Future large, randomized trials addressing the use of topical corticosteroids would further support optimal urticaria management.

Leukotriene receptor antagonists as add-on therapy to antihistamines for urticaria: Systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The benefits and harms of adding antileukotrienes to H1 antihistamines (AHs) for the management of urticaria (hives, itch, and/or angioedema) remain unclear. OBJECTIVE: We sought to systematically synthesize the treatment outcomes of antileukotrienes in combination with AHs versus AHs alone for acute and chronic urticaria. METHODS: As part of updating American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters urticaria guidelines, we searched Medline, Embase, Central, LILACS, WPRIM, IBECS, ICTRP, CBM, CNKI, VIP, Wanfang, US Food and Drug Administration, and European Medicines Agency databases from inception to December 18, 2023, for randomized controlled trials (RCTs) evaluating antileukotrienes and AHs versus AHs alone in patients with urticaria. Paired reviewers independently screened citations, extracted data, and assessed risk of bias. Random effects models pooled effect estimates for urticaria activity, itch, wheal, sleep, quality of life, and harms. The GRADE approach informed certainty of evidence ratings. The study was registered at the Open Science Framework (osf.io/h2bfx/). RESULTS: Thirty-four RCTs enrolled 3324 children and adults. Compared to AHs alone, the combination of a leukotriene receptor antagonist with AHs probably modestly reduces urticaria activity (mean difference, -5.04; 95% confidence interval, -6.36 to -3.71; 7-day urticaria activity score) with moderate certainty. We made similar findings for itch and wheal severity as well as quality of life. Adverse events were probably not different between groups (moderate certainty); however, no RCT reported on neuropsychiatric adverse events. CONCLUSION: Among patients with urticaria, adding leukotriene receptor antagonists to AHs probably modestly improves urticaria activity with little to no increase in overall adverse events. The added risk of neuropsychiatric adverse events in this population with leukotriene receptor antagonists is small and uncertain.

Barriers and facilitators to perioperative smoking cessation: A scoping review.

OBJECTIVE: Smoking cessation interventions are underutilized in the surgical setting. We aimed to systematically identify the barriers and facilitators to smoking cessation in the surgical setting. METHODS: Following the Joanna Briggs Institute (JBI) framework for scoping reviews, we searched 5 databases (MEDLINE, Embase, Cochrane CENTRAL, CINAHL, and PsycINFO) for quantitative or qualitative studies published in English (since 2000) evaluating barriers and facilitators to perioperative smoking cessation interventions. Data were analyzed using thematic analysis and mapped to the theoretical domains framework (TDF). RESULTS: From 31 studies, we identified 23 unique barriers and 13 facilitators mapped to 11 of the 14 TDF domains. The barriers were within the domains of knowledge (e.g., inadequate knowledge of smoking cessation interventions) in 23 (74.2%) studies; environmental context and resources (e.g., lack of time to deliver smoking cessation interventions) in 19 (61.3%) studies; beliefs about capabilities (e.g., belief that patients are nervous about surgery/diagnosis) in 14 (45.2%) studies; and social/professional role and identity (e.g., surgeons do not believe it is their role to provide smoking cessation interventions) in 8 (25.8%) studies. Facilitators were mainly within the domains of environmental context and resources (e.g., provision of quit smoking advice as routine surgical care) in 15 (48.4%) studies, reinforcement (e.g., surgery itself as a motivator to kickstart quit attempts) in 8 (25.8%) studies, and skills (e.g., smoking cessation training and awareness of guidelines) in 5 (16.2%) studies. CONCLUSION: The identified barriers and facilitators are actionable targets for future studies aimed at translating evidence informed smoking cessation interventions into practice in perioperative settings. More research is needed to evaluate how targeting these barriers and facilitators will impact smoking outcomes.

The role of mitochondrial genes in ischemia-reperfusion injury: A systematic review of experimental studies.

Mitochondrial dysfunction contributes to pathological conditions like ischemia-reperfusion (IR) injury. To address the lack of effective therapeutic interventions for IR injury and potential knowledge gaps in the current literature, we systematically reviewed 3800 experimental studies across 5 databases and identified 20 mitochondrial genes impacting IR injury in various organs. Notably, CyPD, Nrf2, and GPX4 are well-studied genes consistently influencing IR injury outcomes. Emerging genes like ALDH2, BNIP3, and OPA1 are supported by human genetic evidence, thereby warranting further investigation. Findings of this review can inform future research directions and inspire therapeutic advancements.

Induction therapy in heart transplantation: A systematic review and network meta-analysis for developing evidence-based recommendations.

INTRODUCTION: Induction therapy (IT) utility in heart transplantation (HT) remains contested. Commissioned by a clinical-practice guidelines panel to evaluate the effectiveness and safety of IT in adult HT patients, we conducted this systematic review and network meta-analysis (NMA). METHODS: We searched for studies from January 2000 to October 2022, reporting on the use of any IT agent in adult HT patients. Based on patient-important outcomes, we performed frequentist NMAs separately for RCTs and observational studies with adjusted analyses, and assessed the certainty of evidence using the GRADE framework. RESULTS: From 5156 publications identified, we included 7 RCTs and 12 observational studies, and report on two contemporarily-used IT agents-basiliximab and rATG. The RCTs provide only very low certainty evidence and was uninformative of the effect of the two agents versus no IT or one another. With low certainty in the evidence from observational studies, basiliximab may increase 30-day (OR 1.13; 95% CI 1.06-1.20) and 1-year (OR 1.11; 95% CI 1.02-1.22) mortality compared to no IT. With low certainty from observational studies, rATG may decrease 5-year cardiac allograft vasculopathy (OR .82; 95% CI .74-.90) compared to no IT, as well as 30-day (OR .85; 95% CI .80-.92), 1-year (OR .87; 95% CI .79-.96), and overall (HR .84; 95% CI .76-.93) mortality compared to basiliximab. CONCLUSION: With low and very low certainty in the synthetized evidence, these NMAs suggest possible superiority of rATG compared to basiliximab, but do not provide compelling evidence for the routine use of these agents in HT recipients.

A brief step-by-step guide on conducting a systematic review and meta-analysis of prognostic model studies.

Prognostic models provide an avenue to predict the risk of individual patients and support shared-decision making. Many prognostic models are published annually, and systematic reviews provide an avenue to collate the existing evidence behind prognostic models to determine whether a model demonstrates adequate predictive performance and is ready for real-world use. This article provides a brief step-by-step guide on how to conduct a systematic review and meta-analysis of prognostic model studies and how these reviews differ from systematic reviews of therapy and diagnosis.

GRADE concept paper 8: judging the certainty of discrimination performance estimates of prognostic models in a body of validation studies.

BACKGROUND: Prognostic 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 validation studies play an essential role in selecting models for clinical practice. METHODS: In this paper, we outline 3 thresholds to determine the target for certainty rating in the discrimination of prognostic models, as observed across a body of validation studies. RESULTS AND CONCLUSION: We propose 3 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 2 approaches involve setting thresholds informed by other mechanisms for classification: clinician intuition or an alternative prognostic model developed for the same disease area and outcome. The choice of threshold will vary based on the context. Instead of relying on arbitrary discrimination cut-offs, our approach positions the observed discrimination within an informed spectrum, potentially aiding decisions about a prognostic model's practical utility.

Comparison of Self-Reported and Capacity-Based Measures of Mobility in Community-Dwelling Older Adults in Nigeria: The Mediating Role of Age, Cognitive Status, and Chronic Conditions.

Background and Objectives: Although the association between self-reported and capacity-based mobility outcomes is prominently researched, the pathways through which self-reported measures affect capacity-based measures remains poorly understood. Therefore, our study examines the association between self-reported and capacity-based mobility measures and explores which mobility determinants mediate the association in Nigerian community-dwelling older adults. Research Design and Methods: This cross-sectional study included 169 older adults [mean age (SD) = 67.7 (7.0)]. Capacity-based mobility outcomes included the Short Physical Performance Battery (SPPB), the 6-Minute Walk Test (6MWT), and the 10-Meter Walk Test (10mWT), whereas the self-reported mobility outcomes included the Lower Extremity Functional scale (LEFS), the Life Space Questionnaire (LSQ), and the Mänty Preclinical Mobility scale (inability to walk 2 km, 0.5 km, or climb a flight of stairs). Spearman's correlations were conducted to examine the relationship between self-reported and capacity-based mobility measures, whereas structural equation modeling was used to determine the mediators. Results: The correlation between SPPB and LEFS (rho = 0.284) and 0.5 km (rho = -0.251) were fair, whereas the correlation between SPPB and inability to walk 2 km (rho = -0.244) and inability to climb a flight of stairs (rho = -0.190) were poor. Similarly, correlations between 6MWT and the LEFS (rho = 0.286), inability to walk 2 km (rho = -0.269), and 0.5 km (rho = -0.303) were fair. The 6WMT was poorly correlated with inability to climb one flight of stairs (rho = -0.233). The LSQ was not correlated with SPPB or 10mWT. Age was the only significant mediator, whereas the number of chronic conditions and cognitive status were not. Discussion and Implications: The correlation between self-reported and capacity-based mobility outcomes in older adults in Nigeria is lower than those in developed countries. Our analysis provides a foundation to explore mobility determinants that could be predictive mediators for mobility outcomes, making meaningful contributions to explaining mobility complexities.

Longitudinal Studies of Aging in Sub-Saharan Africa: Review, Limitations, and Recommendations in Preparation of Projected Aging Population.

Background and Objectives: The United Nations has projected a 218% increase in older people in Sub-Saharan Africa (SSA) between 2019 and 2050, underscoring the need to explore changes that would occur over this time. Longitudinal studies are ideal for studying and proffering solutions to these changes. This review aims to understand the breadth and use of longitudinal studies on aging in the SSA regions, proffering recommendations in preparation for the projected aging population. Research Design and Methods: This paper is the third of a four-part series paper of a previous systematic mapping review of aging studies in SSA. We updated the search (between 2021 and 2023) and screened the titles/abstracts and full-text articles by a pair of independent reviewers. Data were extracted using a standardized data-charting form, identifying longitudinal studies in SSA. Results: We identified 193 studies leveraging 24 longitudinal study data sets conducted at 28 unique sites. The World Health Organization's Study on Global AGEing and Adult Health (WHO-SAGE) (n = 59, 30.5%) and Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) (n = 51, 26.4%) were the most used longitudinal data sets. Four studies used more than one longitudinal study data set. Eighteen of the longitudinal study data sets were used only in 1-4 studies. Most (n = 150, 77.7%) of the studies used a cross-sectional analytical approach. Discussion and Implications: Longitudinal studies on aging are sparingly being utilized in SSA. Most analyses conducted across the longitudinal data set were cross-sectional, which hindered the understanding of aging changes that occurred over time that could better inform aging policy and interventions. We call for funding bodies, such as WHO-SAGE, to develop funding competitions that focus on conducting longitudinal analyses, such as structural equation modeling, highlighting changes occurring among the aging population in SSA.

Use of induction therapy post-heart transplantation: Clinical practice recommendations based on systematic review and network meta-analysis of evidence.

BACKGROUND: The use of induction therapy (IT) agents in the early post-heart transplant period remains controversial. The following recommendations aim to provide guidance on the use of IT agents, including Basiliximab and Thymoglobulin, as part of routine care in heart transplantation (HTx). METHODS: We recruited an international, multidisciplinary panel of 15 stakeholders, including patient partners, transplant cardiologists and surgeons, nurse practitioners, pharmacists, and methodologists. We commissioned a systematic review on benefits and harms of IT on patient-important outcomes, and another on patients' values and preferences to inform our recommendations. We used the GRADE framework to summarize our findings, rate certainty in the evidence, and develop recommendations. The panel considered the balance between benefits and harms, certainty in the evidence, and patient's values and preferences, to make recommendations for or against the routine post-operative use of Thymoglobulin or Basiliximab. RESULTS: The panel made recommendations on three major clinical problems in HTx: (1) We suggest against the routine post-operative use of Basiliximab compared to no IT, (2) we suggest against the routine use of Thymoglobulin compared to no IT, and (3) for those patients for whom IT is deemed desirable, we suggest for the use of Thymoglobulin as compared to Basiliximab. CONCLUSION: This report highlights gaps in current knowledge and provides directions for clinical research in the future to better understand the clinical utility of IT agents in the early post heart transplant period, leading to improved management and care.

Risk factors for long COVID in children and adolescents: a systematic review and meta-analysis.

BACKGROUND: The long-term sequelae of COVID-19 in children and adolescents remain poorly understood and characterized. This systematic review and meta-analysis sought to summarize the risk factors for long COVID in the pediatric population. METHODS: We searched six databases from January 2020 to May 2023 for observational studies reporting on risk factors for long COVID or persistent symptoms those were present 12 or more weeks post-infection using multivariable regression analyses. Trial registries, reference lists of included studies, and preprint servers were hand-searched for relevant studies. Random-effects meta-analyses were conducted to pool odds ratios for each risk factor. Individual study risk of bias was rated using QUIPS, and the GRADE framework was used to assess the certainty of evidence for each unique factor. RESULTS: Sixteen observational studies (N = 46,262) were included, and 19 risk factors were amenable to meta-analysis. With moderate certainty in the evidence, age (per 2-year increase), allergic rhinitis, obesity, previous respiratory diseases, hospitalization, severe acute COVID-19, and symptomatic acute COVID-19 are probably associated with an increased risk of long COVID. Female sex, asthma, comorbidity, and heart diseases may be associated with an increased risk of long COVID, and Asian and Black races may be associated with a decreased risk of long COVID. We did not observe any credible subgroup effects for any risk factor. CONCLUSIONS: The current body of literature presents several compelling risk factors for the development of long COVID in the pediatric population. Further research is necessary to elucidate the pathophysiology of long COVID.

Prognostic factors for multisystem inflammatory syndrome in children: A systematic review and meta-analysis.

AIM: Multisystem inflammatory syndrome in children (MIS-C) is a novel condition that can occur post-SARS-CoV-2 infection in children and adolescents. There is a paucity of evidence on the prognostic factors associated with MIS-C. The aim of this systematic review and meta-analysis was to summarise the prognostic factors for MIS-C development. METHODS: Five databases were systematically searched from January 2020 to May 2023 for studies reporting on prognostic factors for MIS-C using multivariable regression models. Random-effects meta-analyses were conducted to pool odds ratios for each prognostic factor. Risk of bias was rated using QUIPS and the GRADE framework was used to assess the certainty of evidence for each unique factor. RESULTS: Twelve observational studies (N = 18 024) were included, and 13 unique prognostic factors were amenable to meta-analysis. With moderate certainty, age <12 years, male sex and Black race probably increase the risk of MIS-C. Malignancy and underlying respiratory disease probably decrease the risk of MIS-C. Low-certainty evidence suggests that Asian race may increase the risk of MIS-C, and comorbidity may decrease the risk of MIS-C. CONCLUSION: Current literature presents several prognostic factors related to MIS-C following SARS-CoV-2 infection. Further research is necessary to elucidate the pathophysiologic mechanisms related to MIS-C.

Evaluating fluvoxamine for the outpatient treatment of COVID-19: A systematic review and meta-analysis.

This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to evaluate the efficacy, safety, and tolerability of fluvoxamine for the outpatient management of COVID-19. We conducted this review in accordance with the PRISMA 2020 guidelines. Literature searches were conducted in MEDLINE, EMBASE, International Pharmaceutical Abstracts, CINAHL, Web of Science, and CENTRAL up to 14 September 2023. Outcomes included incidence of hospitalisation, healthcare utilization (emergency room visits and/or hospitalisation), mortality, supplemental oxygen and mechanical ventilation requirements, serious adverse events (SAEs) and non-adherence. Fluvoxamine 100 mg twice a day was associated with reductions in the risk of hospitalisation (risk ratio [RR] 0.75, 95% confidence interval [CI] 0.58-0.97; I 2  = 0%) and reductions in the risk of healthcare utilization (RR 0.68, 95% CI 0.53-0.86; I 2  = 0%). While no increased SAEs were observed, fluvoxamine 100 mg twice a day was associated with higher treatment non-adherence compared to placebo (RR 1.61, 95% CI 1.22-2.14; I 2  = 53%). In subgroup analyses, fluvoxamine reduced healthcare utilization in outpatients with BMI ≥30 kg/m2 , but not in those with lower BMIs. While fluvoxamine offers potential benefits in reducing healthcare utilization, its efficacy may be most pronounced in high-risk patient populations. The observed non-adherence rates highlight the need for better patient education and counselling. Future investigations should reassess trial endpoints to include outcomes relating to post-COVID sequelaes. Registration: This review was prospectively registered on PROSPERO (CRD42023463829).

Topical treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD prescription topical treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT databases to September 5, 2022, for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using 7 groups-group 1 being most potent. This review is registered in the Open Science Framework (https://osf.io/q5m6s). RESULTS: The 219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty evidence, pimecrolimus improved 6 of 7 outcomes-among the best for 2; high-dose tacrolimus (0.1%) improved 5-among the best for 2; low-dose tacrolimus (0.03%) improved 5-among the best for 1. With moderate- to high-certainty evidence, group 5 TCS improved 6-among the best for 3; group 4 TCS and delgocitinib improved 4-among the best for 2; ruxolitinib improved 4-among the best for 1; group 1 TCS improved 3-among the best for 2. These interventions did not increase harm. Crisaborole and difamilast were intermediately effective, but with uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus. CONCLUSIONS: For individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective.

Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD systemic treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna). RESULTS: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.

Global Comparison of Readmission Rates for Patients With Heart Failure.

BACKGROUND: Heart failure (HF) readmission rates are low in some jurisdictions. However, international comparisons are lacking and could serve as a foundation for identifying regional patient management strategies that could be shared to improve outcomes. OBJECTIVES: This study sought to summarize 30-day and 1-year all-cause readmission and mortality rates of hospitalized HF patients across countries and to explore potential differences in rates globally. METHODS: We performed a systematic review and meta-analysis using MEDLINE, Embase, and CENTRAL for observational reports on hospitalized adult HF patients at risk for readmission or mortality published between January 2010 and March 2021. We conducted a meta-analysis of proportions using a random-effects model, and sources of heterogeneity were evaluated with meta-regression. RESULTS: In total, 24 papers reporting on 30-day and 23 papers on 1-year readmission were included. Of the 1.5 million individuals at risk, 13.2% (95% CI: 10.5%-16.1%) were readmitted within 30 days and 35.7% (95% CI: 27.1%-44.9%) within 1 year. A total of 33 papers reported on 30-day and 45 papers on 1-year mortality. Of the 1.5 million individuals hospitalized for HF, 7.6% (95% CI: 6.1%-9.3%) died within 30 days and 23.3% (95% CI: 20.8%-25.9%) died within 1 year. Substantial variation in risk across countries was unexplained by countries' gross domestic product, proportion of gross domestic product spent on health care, and Gini coefficient. CONCLUSIONS: Globally, hospitalized HF patients exhibit high rates of readmission and mortality, and the variability in readmission rates was not explained by health care expenditure, risk of mortality, or comorbidities.

Testing the Webber's Comprehensive Mobility Framework Using Self-Reported and Performance-Based Mobility Outcomes Among Community-Dwelling Older Adults in Nigeria.

Background and Objectives: In 2010, Webber and colleagues conceptualized the interrelationships between mobility determinants, and researchers tested Webber's framework using data from developed countries. No studies have tested this model using data from developing nations (e.g., Nigeria). This study aimed to simultaneously explore the cognitive, environmental, financial, personal, physical, psychological, and social influences and their interaction effects on the mobility outcomes among community-dwelling older adults in Nigeria. Research Design and Methods: This cross-sectional study recruited 227 older adults (mean age [standard deviation] = 66.6 [6.8] years). Performance-based mobility outcomes included gait speed, balance, and lower extremity strength, and were assessed using the Short Physical Performance Battery, whereas the self-reported mobility outcomes included inability to walk 0.5 km, 2 km, or climb a flight of stairs, assessed using the Manty Preclinical Mobility Limitation Scale. Regression analysis was used to determine the predictors of mobility outcomes. Results: The number of comorbidities (physical factor) negatively predicted all mobility outcomes, except the lower extremity strength. Age (personal factor) negatively predicted gait speed (ß = -0.192), balance (ß = -0.515), and lower extremity strength (ß = -0.225), and a history of no exercise (physical factor) positively predicted inability to walk 0.5 km (B = 1.401), 2 km (B = 1.295). Interactions between determinants improved the model, explaining the most variations in all the mobility outcomes. Living arrangement is the only factor that consistently interacted with other variables to improve the regression model for all mobility outcomes, except balance and self-reported inability to walk 2 km. Discussion and Implications: Interactions between determinants explain the most variations in all mobility outcomes, highlighting the complexity of mobility. This finding highlighted that factors predicting self-reported and performance-based mobility outcomes might differ, but this should be confirmed with a large data set.

Obesity as an independent risk factor for COVID-19 severity and mortality.

BACKGROUND: Since December 2019, the world has struggled with the COVID-19 pandemic. Even after the introduction of various vaccines, this disease still takes a considerable toll. In order to improve the optimal allocation of resources and communication of prognosis, healthcare providers and patients need an accurate understanding of factors (such as obesity) that are associated with a higher risk of adverse outcomes from the COVID-19 infection. OBJECTIVES: To evaluate obesity as an independent prognostic factor for COVID-19 severity and mortality among adult patients in whom infection with the COVID-19 virus is confirmed. SEARCH METHODS: MEDLINE, Embase, two COVID-19 reference collections, and four Chinese biomedical databases were searched up to April 2021. SELECTION CRITERIA: We included case-control, case-series, prospective and retrospective cohort studies, and secondary analyses of randomised controlled trials if they evaluated associations between obesity and COVID-19 adverse outcomes including mortality, mechanical ventilation, intensive care unit (ICU) admission, hospitalisation, severe COVID, and COVID pneumonia. Given our interest in ascertaining the independent association between obesity and these outcomes, we selected studies that adjusted for at least one factor other than obesity. Studies were evaluated for inclusion by two independent reviewers working in duplicate.  DATA COLLECTION AND ANALYSIS: Using standardised data extraction forms, we extracted relevant information from the included studies. When appropriate, we pooled the estimates of association across studies with the use of random-effects meta-analyses. The Quality in Prognostic Studies (QUIPS) tool provided the platform for assessing the risk of bias across each included study. In our main comparison, we conducted meta-analyses for each obesity class separately. We also meta-analysed unclassified obesity and obesity as a continuous variable (5 kg/m2 increase in BMI (body mass index)). We used the GRADE framework to rate our certainty in the importance of the association observed between obesity and each outcome. As obesity is closely associated with other comorbidities, we decided to prespecify the minimum adjustment set of variables including age, sex, diabetes, hypertension, and cardiovascular disease for subgroup analysis.  MAIN RESULTS: We identified 171 studies, 149 of which were included in meta-analyses.  As compared to 'normal' BMI (18.5 to 24.9 kg/m2) or patients without obesity, those with obesity classes I (BMI 30 to 35 kg/m2), and II (BMI 35 to 40 kg/m2) were not at increased odds for mortality (Class I: odds ratio [OR] 1.04, 95% confidence interval [CI] 0.94 to 1.16, high certainty (15 studies, 335,209 participants); Class II: OR 1.16, 95% CI 0.99 to 1.36, high certainty (11 studies, 317,925 participants)). However, those with class III obesity (BMI 40 kg/m2 and above) may be at increased odds for mortality (Class III: OR 1.67, 95% CI 1.39 to 2.00, low certainty, (19 studies, 354,967 participants)) compared to normal BMI or patients without obesity. For mechanical ventilation, we observed increasing odds with higher classes of obesity in comparison to normal BMI or patients without obesity (class I: OR 1.38, 95% CI 1.20 to 1.59, 10 studies, 187,895 participants, moderate certainty; class II: OR 1.67, 95% CI 1.42 to 1.96, 6 studies, 171,149 participants, high certainty; class III: OR 2.17, 95% CI 1.59 to 2.97, 12 studies, 174,520 participants, high certainty). However, we did not observe a dose-response relationship across increasing obesity classifications for ICU admission and hospitalisation. AUTHORS' CONCLUSIONS: Our findings suggest that obesity is an important independent prognostic factor in the setting of COVID-19. Consideration of obesity may inform the optimal management and allocation of limited resources in the care of COVID-19 patients.