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British Journal of Sports Medicine Aug 2023To estimate the efficacy of exercise on depressive symptoms compared with non-active control groups and to determine the moderating effects of exercise on depression and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To estimate the efficacy of exercise on depressive symptoms compared with non-active control groups and to determine the moderating effects of exercise on depression and the presence of publication bias.
DESIGN
Systematic review and meta-analysis with meta-regression.
DATA SOURCES
The Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, Embase, SPORTDiscus, PsycINFO, Scopus and Web of Science were searched without language restrictions from inception to 13 September2022 (PROSPERO registration no CRD42020210651).
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials including participants aged 18 years or older with a diagnosis of major depressive disorder or those with depressive symptoms determined by validated screening measures scoring above the threshold value, investigating the effects of an exercise intervention (aerobic and/or resistance exercise) compared with a non-exercising control group.
RESULTS
Forty-one studies, comprising 2264 participants post intervention were included in the meta-analysis demonstrating large effects (standardised mean difference (SMD)=-0.946, 95% CI -1.18 to -0.71) favouring exercise interventions which corresponds to the number needed to treat (NNT)=2 (95% CI 1.68 to 2.59). Large effects were found in studies with individuals with major depressive disorder (SMD=-0.998, 95% CI -1.39 to -0.61, k=20), supervised exercise interventions (SMD=-1.026, 95% CI -1.28 to -0.77, k=40) and moderate effects when analyses were restricted to low risk of bias studies (SMD=-0.666, 95% CI -0.99 to -0.34, k=12, NNT=2.8 (95% CI 1.94 to 5.22)).
CONCLUSION
Exercise is efficacious in treating depression and depressive symptoms and should be offered as an evidence-based treatment option focusing on supervised and group exercise with moderate intensity and aerobic exercise regimes. The small sample sizes of many trials and high heterogeneity in methods should be considered when interpreting the results.
Topics: Humans; Depression; Depressive Disorder, Major; Exercise; Exercise Therapy
PubMed: 36731907
DOI: 10.1136/bjsports-2022-106282 -
JAMA Oncology Nov 2023Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging of patients with early breast cancer (BC), but its necessity can be questioned since...
Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes: The SOUND Randomized Clinical Trial.
IMPORTANCE
Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging of patients with early breast cancer (BC), but its necessity can be questioned since surgery for examination of axillary nodes is not performed with curative intent.
OBJECTIVE
To determine whether the omission of axillary surgery is noninferior to SLNB in patients with small BC and a negative result on preoperative axillary lymph node ultrasonography.
DESIGN, SETTING, AND PARTICIPANTS
The SOUND (Sentinel Node vs Observation After Axillary Ultra-Sound) trial was a prospective noninferiority phase 3 randomized clinical trial conducted in Italy, Switzerland, Spain, and Chile. A total of 1463 women of any age with BC up to 2 cm and a negative preoperative axillary ultrasonography result were enrolled and randomized between February 6, 2012, and June 30, 2017. Of those, 1405 were included in the intention-to-treat analysis. Data were analyzed from October 10, 2022, to January 13, 2023.
INTERVENTION
Eligible patients were randomized on a 1:1 ratio to receive SLNB (SLNB group) or no axillary surgery (no axillary surgery group).
MAIN OUTCOMES AND MEASURES
The primary end point of the study was distant disease-free survival (DDFS) at 5 years, analyzed as intention to treat. Secondary end points were the cumulative incidence of distant recurrences, the cumulative incidence of axillary recurrences, DFS, overall survival (OS), and the adjuvant treatment recommendations.
RESULTS
Among 1405 women (median [IQR] age, 60 [52-68] years) included in the intention-to-treat analysis, 708 were randomized to the SLNB group, and 697 were randomized to the no axillary surgery group. Overall, the median (IQR) tumor size was 1.1 (0.8-1.5) cm, and 1234 patients (87.8%) had estrogen receptor-positive ERBB2 (formerly HER2 or HER2/neu), nonoverexpressing BC. In the SLNB group, 97 patients (13.7%) had positive axillary nodes. The median (IQR) follow-up for disease assessment was 5.7 (5.0-6.8) years in the SLNB group and 5.7 (5.0-6.6) years in the no axillary surgery group. Five-year distant DDFS was 97.7% in the SLNB group and 98.0% in the no axillary surgery group (log-rank P = .67; hazard ratio, 0.84; 90% CI, 0.45-1.54; noninferiority P = .02). A total of 12 (1.7%) locoregional relapses, 13 (1.8%) distant metastases, and 21 (3.0%) deaths were observed in the SLNB group, and 11 (1.6%) locoregional relapses, 14 (2.0%) distant metastases, and 18 (2.6%) deaths were observed in the no axillary surgery group.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, omission of axillary surgery was noninferior to SLNB in patients with small BC and a negative result on ultrasonography of the axillary lymph nodes. These results suggest that patients with these features can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02167490.
Topics: Humans; Female; Middle Aged; Sentinel Lymph Node Biopsy; Breast Neoplasms; Prospective Studies; Negative Results; Neoplasm Recurrence, Local; Lymph Nodes; Ultrasonography; Recurrence
PubMed: 37733364
DOI: 10.1001/jamaoncol.2023.3759 -
Science (New York, N.Y.) Jul 2023Antimicrobial peptides are host-encoded immune effectors that combat pathogens and shape the microbiome in plants and animals. However, little is known about how the...
Antimicrobial peptides are host-encoded immune effectors that combat pathogens and shape the microbiome in plants and animals. However, little is known about how the host antimicrobial peptide repertoire is adapted to its microbiome. Here, we characterized the function and evolution of the antimicrobial peptide family of Diptera. Using mutations affecting the two () of , we reveal the specific role of for the pathogen and for the gut mutualist . The presence of or like genes across Diptera correlates with the presence of and in their environment. Moreover, and like sequences predict host resistance against infection by these bacteria across the genus . Our study explains the evolutionary logic behind the bursts of rapid evolution of an antimicrobial peptide family and reveals how the host immune repertoire adapts to changing microbial environments.
Topics: Animals; Antimicrobial Peptides; Drosophila melanogaster; Drosophila Proteins; Evolution, Molecular; Microbiota; Host-Pathogen Interactions; Providencia; Acetobacter
PubMed: 37471548
DOI: 10.1126/science.adg5725 -
Journal of Clinical Oncology : Official... Dec 2023JCO The phase III, double-blind KEYNOTE-826 trial of pembrolizumab 200 mg or placebo once every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with or...
First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826.
JCO The phase III, double-blind KEYNOTE-826 trial of pembrolizumab 200 mg or placebo once every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with or without bevacizumab, showed statistically significant survival benefits with the addition of pembrolizumab for patients with persistent, recurrent, or metastatic cervical cancer (primary data cutoff: May 3, 2021). This article reports the protocol-specified final overall survival (OS) results tested in the PD-L1 combined positive score (CPS) ≥1, all-comer, and CPS ≥10 populations. At the final data cutoff (October 3, 2022), the median study follow-up duration was 39.1 months (range, 32.1-46.5 months). In the PD-L1 CPS ≥1 (N = 548), all-comer (N = 617), and CPS ≥10 (N = 317) populations, median OS with pembrolizumab-chemotherapy versus placebo-chemotherapy was 28.6 months versus 16.5 months (hazard ratio [HR] for death, 0.60 [95% CI, 0.49 to 0.74]), 26.4 months versus 16.8 months (HR, 0.63 [95% CI, 0.52 to 0.77]), and 29.6 months versus 17.4 months (HR, 0.58 [95% CI, 0.44 to 0.78]), respectively. The incidence of grade ≥3 adverse events was 82.4% with pembrolizumab-chemotherapy and 75.4% with placebo-chemotherapy. These results show that pembrolizumab plus chemotherapy, with or without bevacizumab, continued to provide clinically meaningful improvements in OS for patients with persistent, recurrent, or metastatic cervical cancer.
Topics: Female; Humans; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Uterine Cervical Neoplasms; Clinical Trials, Phase III as Topic; Double-Blind Method
PubMed: 37910822
DOI: 10.1200/JCO.23.00914 -
Lancet (London, England) Mar 2024Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or... (Meta-Analysis)
Meta-Analysis
Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults.
BACKGROUND
Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories.
METHODS
We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5-19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m) and obesity (BMI ≥30 kg/m). For school-aged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median).
FINDINGS
From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness.
INTERPRETATION
The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity.
FUNDING
UK Medical Research Council, UK Research and Innovation (Research England), UK Research and Innovation (Innovate UK), and European Union.
Topics: Male; Adult; Child; Humans; Female; Adolescent; Young Adult; Child, Preschool; Thinness; Body Mass Index; Bayes Theorem; Pediatric Obesity; Research Design; Prevalence; Overweight
PubMed: 38432237
DOI: 10.1016/S0140-6736(23)02750-2 -
Ophthalmology. Glaucoma 2023
PubMed: 37302548
DOI: 10.1016/j.ogla.2023.06.003 -
Nutrients Jul 2023Atherosclerosis, chronic non-communicable diseases, and metabolic syndrome are highly interconnected and collectively contribute to global health concerns that reduce... (Review)
Review
Atherosclerosis, chronic non-communicable diseases, and metabolic syndrome are highly interconnected and collectively contribute to global health concerns that reduce life expectancy and quality of life. These conditions arise from multiple risk factors, including inflammation, insulin resistance, impaired blood lipid profile, endothelial dysfunction, and increased cardiovascular risk. Adopting a plant-based diet has gained popularity as a viable alternative to promote health and mitigate the incidence of, and risk factors associated with, these three health conditions. Understanding the potential benefits of a plant-based diet for human health is crucial, particularly in the face of the rising prevalence of chronic diseases like diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Thus, this review focused on the plausible advantages of consuming a type of food pattern for the prevention and/or treatment of chronic diseases, emphasizing the dietary aspects that contribute to these conditions and the evidence supporting the benefits of a plant-based diet for human health. To facilitate a more in-depth analysis, we present separate evidence for each of these three concepts, acknowledging their intrinsic connection while providing a specific focus on each one. This review underscores the potential of a plant-based diet to target the underlying causes of these chronic diseases and enhance health outcomes for individuals and populations.
Topics: Humans; Metabolic Syndrome; Quality of Life; Health Promotion; Atherosclerosis; Diet, Vegetarian; Chronic Disease
PubMed: 37513660
DOI: 10.3390/nu15143244 -
JAMA Oncology Feb 2024The KEYNOTE-826 randomized clinical trial showed statistically significant and clinically meaningful survival benefits with the addition of pembrolizumab to chemotherapy... (Randomized Controlled Trial)
Randomized Controlled Trial
Pembrolizumab or Placebo Plus Chemotherapy With or Without Bevacizumab for Persistent, Recurrent, or Metastatic Cervical Cancer: Subgroup Analyses From the KEYNOTE-826 Randomized Clinical Trial.
IMPORTANCE
The KEYNOTE-826 randomized clinical trial showed statistically significant and clinically meaningful survival benefits with the addition of pembrolizumab to chemotherapy with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer. Treatment effects in patient subgroups of the study population are unknown.
OBJECTIVE
To assess efficacy outcomes in patient subgroups of KEYNOTE-826.
DESIGN, SETTING, AND PARTICIPANTS
Exploratory subgroup analyses were conducted in a global, phase 3, randomized, double-blind, placebo-controlled clinical trial. Participants included women with persistent, recurrent, or metastatic adenocarcinoma, adenosquamous carcinoma, or squamous cell carcinoma of the cervix that had not been treated with systemic chemotherapy and was not amenable to curative treatment. This subanalysis was conducted from November 20, 2018, to May 3, 2021.
INTERVENTIONS
Pembrolizumab, 200 mg, every 3 weeks or placebo for up to 35 cycles plus chemotherapy (paclitaxel, 175 mg/m2, plus cisplatin, 50 mg/m2, or carboplatin AUC 5 [area under the free carboplatin plasma concentration vs time curve]) with or without bevacizumab, 15 mg/kg.
MAIN OUTCOMES AND MEASURES
Overall survival (OS) and progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 in subgroups defined by use of bevacizumab (yes or no), choice of platinum (carboplatin or cisplatin), prior chemoradiotherapy (CRT) exposure only (yes or no), and histologic type (squamous or nonsquamous) in patients with programmed cell death ligand 1-positive tumors (defined as a combined positive score [CPS] ≥1) and in the intention-to-treat population.
RESULTS
A total of 617 patients (median age, 51 years; range, 22-82 years) were enrolled in the trial. In the CPS greater than or equal to 1 population, hazard ratios (HRs) for OS favored the pembrolizumab group in all subgroups: with bevacizumab (HR, 0.62; 95% CI, 0.45-0.87) and without bevacizumab (HR, 0.67; 95% CI, 0.47-0.96), use of carboplatin (HR, 0.65; 95% CI, 0.50-0.85) and cisplatin (HR, 0.53; 95% CI, 0.27-1.04), with prior CRT only (HR, 0.56; 95% CI, 0.39-0.81) and without prior CRT only (HR, 0.72; 95% CI, 0.52-1.00), and squamous (HR, 0.60; 95% CI, 0.46-0.79) and nonsquamous (HR, 0.70; 95% CI, 0.41-1.20) histologic type. In the intention-to-treat population, HRs for OS also favored the pembrolizumab group in all subgroups: with bevacizumab (HR, 0.63; 95% CI, 0.47-0.87) and without bevacizumab (HR, 0.74; 95% CI, 0.53-1.04), use of carboplatin (HR, 0.69; 95% CI, 0.54-0.89) or cisplatin (HR, 0.59; 95% CI, 0.32-1.09), with prior CRT only (HR, 0.64; 95% CI, 0.45-0.91) and without prior CRT only (HR, 0.71; 95% CI, 0.53-0.97), and squamous (HR, 0.61; 95% CI, 0.47-0.80) and nonsquamous (HR, 0.76; 95% CI, 0.47-1.23) histologic type. Similar to OS, the addition of pembrolizumab prolonged PFS across all subgroups in the CPS greater than or equal to 1 and intention-to-treat populations.
CONCLUSIONS AND RELEVANCE
The findings of this trial suggest that adding pembrolizumab to chemotherapy with or without bevacizumab improved OS across subgroups of patients with persistent, recurrent, or metastatic cervical cancer.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03635567.
Topics: Humans; Female; Middle Aged; Bevacizumab; Carboplatin; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Cisplatin; Uterine Cervical Neoplasms; Carcinoma, Squamous Cell; Antineoplastic Combined Chemotherapy Protocols; Antibodies, Monoclonal, Humanized
PubMed: 38095881
DOI: 10.1001/jamaoncol.2023.5410 -
The Lancet. Diabetes & Endocrinology Jan 2024Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of... (Observational Study)
Observational Study
BACKGROUND
Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks.
METHODS
Observational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality.
FINDINGS
Observational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically predicted 25(OH)D with coronary heart disease (odds ratio [OR] per 10 nmol/L higher genetically-predicted 25(OH)D concentration 0·98, 95% CI 0·95-1·01), stroke (1·01, [0·97-1·05]), or all-cause mortality (0·99, 0·95-1·02). Null findings were also observed in genetic analyses for cause-specific mortality outcomes, and in stratified genetic analyses for all outcomes at all observed levels of 25(OH)D concentrations.
INTERPRETATION
Stratified Mendelian randomisation analyses suggest a lack of causal relationship for 25(OH)D concentrations with both cardiovascular and mortality outcomes for individuals at all levels of 25(OH)D. Our findings suggest that substantial reductions in mortality and cardiovascular morbidity due to long-term low-dose vitamin D supplementation are unlikely even if targeted at individuals with low vitamin D status.
FUNDING
British Heart Foundation, Medical Research Council, National Institute for Health Research, Health Data Research UK, Cancer Research UK, and International Agency for Research on Cancer.
Topics: Middle Aged; Humans; Prospective Studies; Vitamin D; Coronary Disease; Vitamins; Stroke; Myocardial Infarction
PubMed: 38048800
DOI: 10.1016/S2213-8587(23)00287-5 -
Emerging Microbes & Infections Dec 2023as an opportunistic pathogen can cause serious infection, and moreover the emergence of multi-drug-resistant strains poses a potentially life-threatening risk to...
as an opportunistic pathogen can cause serious infection, and moreover the emergence of multi-drug-resistant strains poses a potentially life-threatening risk to public health. However, a comprehensive genomic study to reveal the population structure and dissemination of is still lacking. In this study, we conducted a genomic epidemiology analysis on the 580 global sequenced isolates, including 257 ones sequenced in this study (42 ones were fully sequenced). We established a genome sequence-based species classification scheme for , redefining the conventional 11 species into seven genocomplexes that were further divided into 18 genospecies, providing an extensively updated reference for species discrimination based on the largest genome dataset to date. We then dissected the profile of antimicrobial resistance genes and the prevalence of multi-drug-resistant strains among these genocomplexes/genospecies, disclosing the presence of diverse and abundant antimicrobial resistance genes and high resistance ratios against multiple classes of drugs in . We further dissected the genetic basis for the spread of in . genes were mainly carried by five incompatible (Inc) groups of plasmids: IncC, IncW, Inc, Inc, and Inc, and the last three were newly designated in this study. By tracking the spread of -carrying plasmids, IncC, Inc, Inc, and Inc plasmids were found to be highly involved in parallel horizontal transfer or vertical clonal expansion of among . Overall, our study provided a comprehensive genomic view of species differentiation, antimicrobial resistance prevalence, and plasmid-mediated dissemination in .
Topics: Providencia; Anti-Bacterial Agents; Plasmids; beta-Lactamases; Genomics; Microbial Sensitivity Tests
PubMed: 37874004
DOI: 10.1080/22221751.2023.2275596