Targeted next-generation sequencing to diagnose drug-resistant tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Targeted next-generation sequencing (NGS) can rapidly and simultaneously detect mutations associated with resistance to tuberculosis drugs across multiple gene targets. The use of targeted NGS to diagnose drug-resistant tuberculosis, as described in publicly available data, has not been comprehensively reviewed. We aimed to identify targeted NGS assays that diagnose drug-resistant tuberculosis, determine how widely this technology has been used, and assess the diagnostic accuracy of these assays. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Cochrane Library, Web of Science Core Collection, Global Index Medicus, Google Scholar, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform for published and unpublished reports on targeted NGS for drug-resistant tuberculosis from Jan 1, 2005, to Oct 14, 2022, with updates to our search in Embase and Google Scholar until Feb 13, 2024. Studies eligible for the systematic review described targeted NGS approaches to predict drug resistance in Mycobacterium tuberculosis infections using primary samples, reference strain collections, or cultured isolates from individuals with presumed or confirmed tuberculosis. Our search had no limitations on study type or language, although only reports in English, German, and French were screened for eligibility. For the meta-analysis, we included test accuracy studies that used any reference standard, and we assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The primary outcomes for the meta-analysis were sensitivity and specificity of targeted NGS to diagnose drug-resistant tuberculosis compared to phenotypic and genotypic drug susceptibility testing. We used a Bayesian bivariate model to generate summary receiver operating characteristic plots and diagnostic accuracy measures, overall and stratified by drug and sample type. This study is registered with PROSPERO, CRD42022368707. FINDINGS: We identified and screened 2920 reports, of which 124 were eligible for our systematic review, including 37 review articles and 87 reports of studies collecting samples for targeted NGS. Sequencing was mainly done in the USA (14 [16%] of 87), western Europe (ten [11%]), India (ten [11%]), and China (nine [10%]). We included 24 test accuracy studies in the meta-analysis, in which 23 different tuberculosis drugs or drug groups were assessed, covering first-line drugs, injectable drugs, and fluoroquinolones and predominantly comparing targeted NGS with phenotypic drug susceptibility testing. The combined sensitivity of targeted NGS across all drugs was 94·1% (95% credible interval [CrI] 90·9-96·3) and specificity was 98·1% (97·0-98·9). Sensitivity for individual drugs ranged from 76·5% (52·5-92·3) for capreomycin to 99·1% (98·3-99·7) for rifampicin; specificity ranged from 93·1% (88·0-96·3) for ethambutol to 99·4% (98·3-99·8) for amikacin. Diagnostic accuracy was similar for primary clinical samples and culture isolates overall and for rifampicin, isoniazid, ethambutol, streptomycin, and fluoroquinolones, and similar after excluding studies at high risk of bias (overall sensitivity 95·2% [95% CrI 91·7-97·1] and specificity 98·6% [97·4-99·3]). INTERPRETATION: Targeted NGS is highly sensitive and specific for detecting drug resistance across panels of tuberculosis drugs and can be performed directly on clinical samples. There is a paucity of data on performance for some currently recommended drugs. The barriers preventing the use of targeted NGS to diagnose drug-resistant tuberculosis in high-burden countries need to be addressed. FUNDING: National Institutes of Allergy and Infectious Diseases and Swiss National Science Foundation.

Systematic review and meta-analysis use in the field of spinal cord injury research: A bibliometric analysis.

OBJECTIVE: To subvert issues of low sample sizes and high attrition rates and generate epidemiologically-sound evidence, collaborative research-through international consortia and multi-centric studies-and meta-analysis approaches are encouraged in spinal cord injury (SCI) research. We investigated the use of systematic reviews and meta-analyses (SRMA) methodology in SCI research and evaluated the quality of evidence across publications we identified. METHODS: We searched the Web of Science Core Collection database by topic without time or language restrictions through 16 December 2022. We identified additional relevant articles through Embase.com. SRMA including human and animal SCI populations were eligible for inclusion. We analyzed data using Bibliometrix and VOSviewer. We used the JBI tool (former Joanna Briggs Institute) to assess methodological quality of a subset of 50 randomly selected articles. RESULTS: We based our analysis on data from 1'224 documents authored by 5'237 scholars and published in 424 sources between 1985 and 2022. The use of SRMA methodology in the field gained momentum in 2009 and a steady increase followed with an annual growth rate of ≈15%. Our findings indicate major research themes in the field include recovery, SCI management, rehabilitation, and quality of life. Over the past 30 years there has been a shift from SRMA concerning functional recovery, secondary health complications, and quality of life toward biomarkers and neuro-regeneration. The major methodological issues across articles we evaluated included opaquely described search strategies, poorly reported critical appraisals, and insufficiently addressing publication bias. In addition, only one-fifth of articles reported review protocol registration. CONCLUSIONS: : Our bibliometric analysis clearly shows a rapid increase of SRMA applications in SCI research. We discuss the most important methodological concerns we identified among a randomly selected set of articles and provide guidance for improving adherence to methodological and reporting SRMA guidelines.

Urban Governance, Multisectoral Action, and Civic Engagement for Population Health, Wellbeing, and Equity in Urban Settings: A Systematic Review.

Objectives: To identify the validated and reliable indicators and tools to assess good governance for population health, wellbeing, and equity in urban settings, and assess processes of multisectoral action and civic engagement as reported by peer-reviewed articles. Methods: We conducted a systematic review searching six databases for observational studies reporting strategies of either urban health, multisectoral action or civic engagement for wellbeing, health, or equity. Results: Out of 8,154 studies initially identified we included 17. From the included studies, 14 presented information about high-income countries. The general population was the main target in most studies. Multisectoral action was the most frequently reported strategy (14 studies). Three studies used Urban Health Equity Assessment and Response Tool (Urban HEART). Health indicators were the most frequently represented (6 studies). Barriers and facilitators for the implementation of participatory health governance strategies were reported in 12 studies. Conclusion: Data on the implementation of participatory health governance strategies has been mainly reported in high-income countries. Updated and reliable data, measured repeatedly, is needed to closely monitor these processes and further develop indicators to assess their impact on population health, wellbeing, and equity.

Prognostic models in COVID-19 infection that predict severity: a systematic review.

Current evidence on COVID-19 prognostic models is inconsistent and clinical applicability remains controversial. We performed a systematic review to summarize and critically appraise the available studies that have developed, assessed and/or validated prognostic models of COVID-19 predicting health outcomes. We searched six bibliographic databases to identify published articles that investigated univariable and multivariable prognostic models predicting adverse outcomes in adult COVID-19 patients, including intensive care unit (ICU) admission, intubation, high-flow nasal therapy (HFNT), extracorporeal membrane oxygenation (ECMO) and mortality. We identified and assessed 314 eligible articles from more than 40 countries, with 152 of these studies presenting mortality, 66 progression to severe or critical illness, 35 mortality and ICU admission combined, 17 ICU admission only, while the remaining 44 studies reported prediction models for mechanical ventilation (MV) or a combination of multiple outcomes. The sample size of included studies varied from 11 to 7,704,171 participants, with a mean age ranging from 18 to 93 years. There were 353 prognostic models investigated, with area under the curve (AUC) ranging from 0.44 to 0.99. A great proportion of studies (61.5%, 193 out of 314) performed internal or external validation or replication. In 312 (99.4%) studies, prognostic models were reported to be at high risk of bias due to uncertainties and challenges surrounding methodological rigor, sampling, handling of missing data, failure to deal with overfitting and heterogeneous definitions of COVID-19 and severity outcomes. While several clinical prognostic models for COVID-19 have been described in the literature, they are limited in generalizability and/or applicability due to deficiencies in addressing fundamental statistical and methodological concerns. Future large, multi-centric and well-designed prognostic prospective studies are needed to clarify remaining uncertainties.

Concepts and definitions of healthy ageing: a systematic review and synthesis of theoretical models.

Background: Healthy ageing (HA) has been defined using multiple approaches. We aim to produce a comprehensive overview and analysis of the theoretical models underpinning this concept and its associated normative terms and definitions. Methods: We conducted a systematic review of peer-reviewed HA models in Embase.com, Medline (Ovid), Cochrane CENTRAL, CINAHL, PsycINFO, and Web of Science until August 2022. Original theoretical papers, concept analyses, and reviews that proposed new models were included. Operational models/definitions, development psychology theories and mechanisms of ageing were excluded. We followed an iterative approach to extract the models' characteristics and thematically analyze them based on the approach of Walker and Avant. The protocol was registered in PROSPERO (CRD42021238796). Findings: Out of 10,741 records, we included 59 papers comprising 65 models/definitions, published in English (1960-2022) from 16 countries in Europe, Asia, and America. Human ageing was described using 12 normative terms, mainly (models (%)): successful (34 (52%)), healthy (eight (12%)), well (five (8%)), and active (four (6%)). We identified intrinsic/extrinsic factors interacting throughout the life course, adaptive processes as attributes, and outcomes describing ageing patterns across objective and subjective dimensions (number of models/definitions): cognitive (62), psychological (53), physical (49), social (49), environmental (19), spiritual (16), economic (13), cultural (eight), political (six), and demographic (four) dimensions. Three types of models emerged: health-state outcomes (three), adaptations across the life course (31), or a combination of both (31). Two additional sub-classifications emphasized person-environment congruence and health promotion. Interpretation: HA conceptualizations highlight its multidimensionality and complexity that renders a monistic model/definition challenging. It has become evident that life long person-environment interactions, adaptations, environments, and health promotion/empowerment are essential for HA. Our model classification provides a basis for harmonizing terms and dimensions that can guide research and comparisons of empirical findings, and inform social and health policies enabling HA for various populations and contexts. Funding: MM, ZMRD, and OI are supported by the European Union's Horizon 2020 Marie Sklodowska-Curie grant No 801076, and MM is also supported by the Swiss National Foundation grant No 189235.

Endocrinological and inflammatory markers in individuals with spinal cord injury: A systematic review and meta-analysis.

Spinal cord injury (SCI) can lead to dramatic physiological changes which can be a factor in developing secondary health conditions and might be reflected in biomarker changes in this elevated risk group. We focused specifically on the endocrine and inflammation profile differences between SCI and able-bodied individuals (ABI). Our aim was to determine the differences in inflammatory markers and endocrine profiles between SCI and ABI. We systematically searched 4 electronic databases for relevant studies. Human observational (cross-sectional, cohort, case-control) studies that compared biomarkers of interest between SCI and ABI population were included. Weighted mean difference between SCI and ABI was calculated using random-effects models. Heterogeneity was computed using I2 statistic and chi-squared test. Study quality was evaluated through the Newcastle-Ottawa Scale. The search strategy yielded a total of 2,603 studies from which 256 articles were selected for full-text assessment. Sixty-two studies were included in the meta-analysis. SCI individuals had higher levels of pro-inflammatory C-reactive protein and IL-6 than ABI. Creatinine and 25-hydroxyvitamin D3 levels were lower in SCI than ABI. Total testosterone levels and IGF-1 were also found to be lower, while cortisol and leptin levels were higher in SCI when compared to ABI. Accordingly, meta-regression, subgroup analysis, and leave-one-out analysis were performed, however, they were only able to partially explain the high levels of heterogeneity. Individuals with SCI show higher levels of inflammatory markers and present significant endocrinological changes when compared to ABI. Moreover, higher incidence of obesity, diabetes, osteoporosis, and hypogonadism in SCI individuals, together with decreased creatinine levels reflect some of the readily measurable aspects of the phenotype changes in the SCI group. These findings need to be considered in anticipating medically related complications and personalizing SCI medical care.

Reducing systematic review burden using Deduklick: a novel, automated, reliable, and explainable deduplication algorithm to foster medical research.

BACKGROUND: Identifying and removing reference duplicates when conducting systematic reviews (SRs) remain a major, time-consuming issue for authors who manually check for duplicates using built-in features in citation managers. To address issues related to manual deduplication, we developed an automated, efficient, and rapid artificial intelligence-based algorithm named Deduklick. Deduklick combines natural language processing algorithms with a set of rules created by expert information specialists. METHODS: Deduklick's deduplication uses a multistep algorithm of data normalization, calculates a similarity score, and identifies unique and duplicate references based on metadata fields, such as title, authors, journal, DOI, year, issue, volume, and page number range. We measured and compared Deduklick's capacity to accurately detect duplicates with the information specialists' standard, manual duplicate removal process using EndNote on eight existing heterogeneous datasets. Using a sensitivity analysis, we manually cross-compared the efficiency and noise of both methods. DISCUSSION: Deduklick achieved average recall of 99.51%, average precision of 100.00%, and average F1 score of 99.75%. In contrast, the manual deduplication process achieved average recall of 88.65%, average precision of 99.95%, and average F1 score of 91.98%. Deduklick achieved equal to higher expert-level performance on duplicate removal. It also preserved high metadata quality and drastically reduced time spent on analysis. Deduklick represents an efficient, transparent, ergonomic, and time-saving solution for identifying and removing duplicates in SRs searches. Deduklick could therefore simplify SRs production and represent important advantages for scientists, including saving time, increasing accuracy, reducing costs, and contributing to quality SRs.

Eating behaviors and health-related quality of life: A scoping review.

Discrepancies between total life expectancy and healthy life expectancy are in part due to unhealthy lifestyles, in which diet plays an important role. Despite this knowledge, observational studies and randomized trials have yet to show consistent improvements in health and well-being, also known as health-related quality of life (HRQoL), given the variety of elements that conform a healthy diet aside from its content. As such, we aimed to describe the evidence and common topics concerning the effects of modifiable eating behaviors and HRQoL in patients with non-communicable diseases (NCD). This scoping review of six electronic databases included 174 reports (69 % were experimental studies, 10 % longitudinal studies, and 21 % cross-sectional studies). Using VOSviewer, a bibliometric tool with text mining functionalities, we identified relevant aspects of dietary assessments and interventions. Commonly observed topics in experimental studies were those related to diet quality (micro- and macronutrients, food items, and dietary patterns). In contrast, less was found regarding eating schedules, eating locations, culturally accepted food items, and the role of food insecurity in HRQoL. Disregarding these aspects of diets may be limiting the full potential of nutrition as a key element of health and well-being in order to ensure lengthy and fulfilling lives.

Gene-diet interactions and cardiovascular diseases: a systematic review of observational and clinical trials.

BACKGROUND: Both genetic background and diet are important determinants of cardiovascular diseases (CVD). Understanding gene-diet interactions could help improve CVD prevention and prognosis. We aimed to summarise the evidence on gene-diet interactions and CVD outcomes systematically. METHODS: We searched MEDLINE® via Ovid, Embase, PubMed®, and The Cochrane Library for relevant studies published until June 6th 2022. We considered for inclusion cross-sectional, case-control, prospective cohort, nested case-control, and case-cohort studies as well as randomised controlled trials that evaluated the interaction between genetic variants and/or genetic risk scores and food or diet intake on the risk of related outcomes, including myocardial infarction, coronary heart disease (CHD), stroke and CVD as a composite outcome. The PROSPERO protocol registration code is CRD42019147031. RESULTS AND DISCUSSION: We included 59 articles based on data from 29 studies; six articles involved multiple studies, and seven did not report details of their source population. The median sample size of the articles was 2562 participants. Of the 59 articles, 21 (35.6%) were qualified as high quality, while the rest were intermediate or poor. Eleven (18.6%) articles adjusted for multiple comparisons, four (7.0%) attempted to replicate the findings, 18 (30.5%) were based on Han-Chinese ethnicity, and 29 (49.2%) did not present Minor Allele Frequency. Fifty different dietary exposures and 52 different genetic factors were investigated, with alcohol intake and ADH1C variants being the most examined. Of 266 investigated diet-gene interaction tests, 50 (18.8%) were statistically significant, including CETP-TaqIB and ADH1C variants, which interacted with alcohol intake on CHD risk. However, interactions effects were significant only in some articles and did not agree on the direction of effects. Moreover, most of the studies that reported significant interactions lacked replication. Overall, the evidence on gene-diet interactions on CVD is limited, and lack correction for multiple testing, replication and sample size consideration.

Effects of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on ß-Cell Function at 1 Year After Surgery: A Systematic Review.

Bariatric surgery is a highly effective obesity treatment resulting in substantial weight loss and improved glucose metabolism. We hereby aimed to summarize available evidence of the effect of the 2 most common bariatric surgery procedures, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), on dynamic measures of ß-cell function (BCF). A systematic search of the literature was conducted in 3 bibliographic databases for studies reporting effects of RYGB and/or SG on BCF assessed using dynamic metabolic perturbation (oral or intravenous bolus stimulation), performed before and 1 year (±3 months) after surgery. Twenty-seven unique studies (6 randomized controlled trials and 21 observational studies), involving a total of 1856 obese adults, were included for final analysis. Twenty-five and 9 studies report effects of RYGB and SG on BCF, respectively (7 studies compared the 2 procedures). Seven studies report results according to presurgical diabetes status. Owing to variable testing procedures and BCF indices reported, no meta-analysis was feasible, and data were summarized qualitatively. For both surgical procedures, most studies suggest an increase in BCF and disposition index, particularly when using oral stimulation, with a more pronounced increase in diabetic than nondiabetic individuals. Additionally, limited indications for greater effects after RYGB versus SG were found. The quality of the included studies was, in general, satisfactory. The considerable heterogeneity of test protocols and outcome measures underscore the need for a harmonization of BCF testing in future research.

Risk Prediction Models of Natural Menopause Onset: A Systematic Review.

CONTEXT: Predicting the onset of menopause is important for family planning and to ensure prompt intervention in women at risk of developing menopause-related diseases. OBJECTIVE: We aimed to summarize risk prediction models of natural menopause onset and their performance. METHODS: Five bibliographic databases were searched up to March 2022. We included prospective studies on perimenopausal women or women in menopausal transition that reported either a univariable or multivariable model for risk prediction of natural menopause onset. Two authors independently extracted data according to the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist. Risk of bias was assessed using a prediction model risk of bias assessment tool (PROBAST). RESULTS: Of 8132 references identified, we included 14 articles based on 8 unique studies comprising 9588 women (mainly Caucasian) and 3289 natural menopause events. All included studies used onset of natural menopause (ONM) as outcome, while 4 studies also predicted early ONM. Overall, there were 180 risk prediction models investigated, with age, anti-Müllerian hormone, and follicle-stimulating hormone being the most investigated predictors. Estimated C-statistic for the prediction models ranged from 0.62 to 0.95. Although all studies were rated at high risk of bias mainly due to the methodological concerns related to the statistical analysis, their applicability was satisfactory. CONCLUSION: Predictive performance and generalizability of current prediction models on ONM is limited given that these models were generated from studies at high risk of bias and from specific populations/ethnicities. Although in certain settings such models may be useful, efforts to improve their performance are needed as use becomes more widespread.

Diabetes and Myocardial Fibrosis: A Systematic Review and Meta-Analysis.

OBJECTIVES: This systematic review and meta-analysis investigated the association of diabetes and glycemic control with myocardial fibrosis (MF). BACKGROUND: MF is associated with an increased risk of heart failure, coronary artery disease, arrhythmias, and death. Diabetes may influence the development of MF, but evidence is inconsistent. METHODS: The authors searched EMBASE, Medline Ovid, Cochrane CENTRAL, Web of Science, and Google Scholar for observational and interventional studies investigating the association of diabetes, glycemic control, and antidiabetic medication with MF assessed by histology and cardiac magnetic resonance (ie, extracellular volume fraction [ECV%] and T1 time). RESULTS: A total of 32 studies (88% exclusively on type 2 diabetes) involving 5,053 participants were included in the systematic review. Meta-analyses showed that diabetes was associated with a higher degree of MF assessed by histological collagen volume fraction (n = 6 studies; mean difference: 5.80; 95% CI: 2.00-9.59) and ECV% (13 studies; mean difference: 2.09; 95% CI: 0.92-3.27), but not by native or postcontrast T1 time. Higher glycosylated hemoglobin levels were associated with higher degrees of MF. CONCLUSIONS: Diabetes is associated with higher degree of MF assessed by histology and ECV% but not by T1 time. In patients with diabetes, worse glycemic control was associated with higher MF degrees. These findings mostly apply to type 2 diabetes and warrant further investigation into whether these associations are causal and which medications could attenuate MF in patients with diabetes.

Systematic Review of Physical Activity Trajectories and Mortality in Patients With Coronary Artery Disease.

BACKGROUND: The role of lifestyle physical activity (PA) trajectories in the mortality risk of patients with coronary heart disease (CHD) remains unclear. OBJECTIVES: The purpose of this study was to determine the association of longitudinal PA trajectories with all-cause and cardiovascular disease (CVD) mortality in patients with CHD. METHODS: Longitudinal cohorts reporting the association of PA trajectories with mortality in patients with CHD were identified in April 2021 by searching 5 databases without language restrictions. Published HRs and 95% CIs were pooled using random effects models and bias assessed by Egger regression. RESULTS: A total of 9 prospective cohorts included 33,576 patients. The mean age was 62.5 years. The maximum follow-up was 15.7 years. All of the studies assessed PA through validated questionnaires, and mortality was well documented. Changes in PA defined 4 nominal PA trajectories. Compared with always-inactive patients, the risk of all-cause mortality was 50% lower in those who remained active (HR: 0.50; 95% CI: 0.39-0.63); 45% lower in those who were inactive but became active (HR: 0.55; 95% CI: 0.44-0.7); and 20% lower in those who were active but became inactive (HR: 0.80; 95% CI: 0.64-0.99). Similar results were observed for CVD mortality, except for the category of decreased activity (HR: 0.91; 95% CI: 0.67-1.24). The overall risk of bias was low. No evidence of publication bias was found. Multiple sensitivity analyses provided consistent results. CONCLUSIONS: This study illustrates how patients with CHD may benefit by preserving or adopting an active lifestyle. The observation that the benefits of past activity can be weakened or lost if PA is not maintained may be confounded by disease progression.

Mental health of migrants with pre-migration exposure to armed conflict: a systematic review and meta-analysis.

BACKGROUND: Exposure to armed conflict has been associated with negative mental health consequences. We aimed to estimate the prevalence of generalised anxiety disorder, major depressive disorder, and post-traumatic stress disorder among migrants exposed to armed conflict. METHODS: In this systematic review and meta-analysis, we searched online databases (Cochrane Library, Embase, LILACS, PsycInfo [via Ovid], PubMed, and Web of Science Core Collection) for relevant observational studies published between Jan 1, 1994, and June 28, 2021. We included studies that used standardised psychiatric interviews to assess generalised anxiety disorder, major depressive disorder, or post-traumatic stress disorder among migrants (refugees or internally displaced persons; aged ≥18 years) with pre-migration exposure to armed conflict. We excluded studies in which exposure to armed conflict could not be ascertained, studies that included a clinical population or people with chronic diseases that can trigger the onset of mental disease, and studies published before 1994. We used a random effects model to estimate each mental health disorder's pooled prevalence and random effects meta-regression to assess sources of heterogeneity. Two independent reviewers assessed the risk of bias for each study using the Joanna Briggs Institute Checklist for Prevalence Studies. The protocol was registered with PROSPERO, CRD42020209251. FINDINGS: Of the 13 935 studies identified, 34 met our inclusion criteria; these studies accounted for 15 549 migrants. We estimated a prevalence of current post-traumatic stress disorder of 31% (95% CI 23-40); prevalence of current major depressive disorder of 25% (17-34); and prevalence of generalised anxiety disorder of 14% (5-35). Younger age was associated with a higher prevalence of current post-traumatic stress disorder (odds ratio 0·95 [95% CI 0·90-0·99]), lifetime post-traumatic stress disorder (0·88 [0·83-0·92]), and current generalised anxiety disorder (0·87 [0·78-0·97]). A longer time since displacement was associated with a lower lifetime prevalence of post-traumatic stress disorder (0·88 [0·81-0·95]) and major depressive disorder (0·81 [0·77-0·86]). Migrating to a middle-income (8·09 [3·06-21·40]) or low-income (39·29 [11·96-129·70]) country was associated with increased prevalence of generalised anxiety disorder. INTERPRETATION: Migrants who are exposed to armed conflict are at high risk of mental health disorders. The mental health-care needs of migrants should be assessed soon after resettlement, and adequate care should be provided, with particular attention paid to young adults. FUNDING: Marie Sklodowska-Curie Actions (Horizon 2020-COFUND), MinCiencias (Colombia), and Swiss National Science Foundation.

Physical activity and cardiometabolic risk factors in individuals with spinal cord injury: a systematic review and meta-analysis.

Physical inactivity in individuals with spinal cord injury (SCI) has been suggested to be an important determinant of increased cardiometabolic disease (CMD) risk. However, it remains unclear whether physically active SCI individuals as compared to inactive or less active individuals have truly better cardiometabolic risk profile. We aimed to systematically review and quantify the association between engagement in regular physical activity and/or exercise interventions and CMD risk factors in individuals with SCI. Four medical databases were searched and studies were included if they were clinical trials or observational studies conducted in adult individuals with SCI and provided information of interest. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the certainty of evidence. Of 5816 unique citations, 11 randomized clinical trials, 3 non-randomized trial and 32 cross-sectional studies comprising more than 5500 SCI individuals were included in the systematic review. In meta-analysis of RCTs and based on evidence of moderate certainty, physical activity in comparison to control intervention was associated with: (i) better glucose homeostasis profile [WMD of glucose, insulin and Assessment of Insulin Resistance (HOMA-IR) were - 3.26 mg/dl (95% CI - 5.12 to - 1.39), - 3.19 µU/ml (95% CI - 3.96 to - 2.43)] and - 0.47 (95% CI - 0.60 to - 0.35), respectively], and (ii) improved cardiorespiratory fitness [WMD of relative and absolute oxygen uptake relative (VO2) were 4.53 ml/kg/min (95% CI 3.11, 5.96) and 0.26 L/min (95% CI 0.21, 0.32) respectively]. No differences were observed in blood pressure, heart rate and lipids (based on evidence of low/moderate certainty). In meta-analysis of cross-sectional studies and based on the evidence of very low to low certainty, glucose [WMD - 3.25 mg/dl (95% CI - 5.36, - 1.14)], insulin [- 2.12 µU/ml (95% CI - 4.21 to - 0.03)] and total cholesterol [WMD - 6.72 mg/dl (95% CI - 13.09, - 0.34)] were lower and HDL [WMD 3.86 mg/dl (95% CI 0.66, 7.05)] and catalase [0.07 UgHb-1 (95% CI 0.03, 0.11)] were higher in physically active SCI individuals in comparison to reference groups. Based on limited number of cross-sectional studies, better parameters of systolic and diastolic cardiac function and lower carotid intima media thickness were found in physically active groups. Methodologically sound clinical trials and prospective observational studies are required to further elaborate the impact of different physical activity prescriptions alone or in combination with other life-style interventions on CMD risk factors in SCI individuals.

Association Between Ultra-Processed Food Intake and All-Cause Mortality: A Systematic Review and Meta-Analysis.

Consumption of ultra-processed foods (UPF) has increased worldwide during the last decades because they are hyperpalatable, cheap, and ready-to-consume products. However, uncertainty exists about their impact on health. We conducted a systematic review and meta-analysis evaluating the association of UPF consumption with all-cause mortality risk. Five bibliographic databases were searched for relevant studies. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). Of 6,951 unique citations, 40 unique prospective cohort studies comprising 5,750,133 individuals were included; publication dates ranged from 1984 to 2021. Compared with low consumption, highest consumption of UPF (RR = 1.29, 95% CI: 1.17, 1.42), sugar-sweetened beverages (RR = 1.11, 95% CI, 1.04, 1.18), artificially sweetened beverages (RR = 1.14, 95% CI, 1.05, 1.22), and processed meat/red meat (RR = 1.15, 95% CI, 1.10, 1.21) were significantly associated with increased risk of mortality. However, breakfast cereals were associated with a lower mortality risk (RR = 0.85, 95% CI, 0.79, 0.92). This meta-analysis suggests that high consumption of UPF, sugar-sweetened beverages, artificially sweetened beverages, processed meat, and processed red meat might increase all-cause mortality, while breakfast cereals might decrease it. Future studies are needed to address lack of standardized methods in UPF categorization.

Dietary factors and onset of natural menopause: A systematic review and meta-analysis.

BACKGROUND: Diet has been suggested to play a role in determining the age at natural menopause; however, the evidence is inconsistent. OBJECTIVE: We systematically reviewed and evaluated published research about associations between diet and onset of natural menopause (ONM). METHODS: We searched 6 databases (Medline, Embase, Cochrane, PubMed, Web of Science and Google Scholar) through January 21,2021 to identify prospective studies assessing the association between diet and ONM. Two independent reviewers extracted data using a predesigned data-collection form. Pooled hazard risks (HRs) were calculated using random effect models. RESULTS: Of the 6,137 eligible references we reviewed, we included 15 articles in our final analysis. Those 15 articles included 91,554 women out of 298,413 who experienced natural menopause during follow-up. Overall, there were 89 food groups investigated, 38 macronutrients and micronutrients, and 6 dietary patterns. Among the food groups, higher intake of green and yellow vegetables was associated with earlier age of ONM, while high intakes of some dairy products, such as low-fat, skimmed milk, and low intake of alcohol were associated with a later onset. We observed no consistent association between macronutrient and micronutrient intake and ONM. Our results suggests that a vegetarian diet could be associated with early ONM; we did not observe any other consistent effect from other dietary patterns. Limitations included the number of studies, lack of replication studies and the research being of an observational nature; most studies (11/15) were at medium risk of bias. CONCLUSION: Although some food items were associated with ONM, the overall evidence about associations between diet and ONM remains controversial. Prospero id: CRD42021232087.

Effect of oat supplementation interventions on cardiovascular disease risk markers: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Oat supplementation interventions (OSIs) may have a beneficial effect on cardiovascular disease (CVD) risk. However, dietary background can modulate such effect. This systematic review assesses the effects of OSIs on CVD risk markers among adults, accounting for different dietary backgrounds or control arms. METHODS: We included randomized clinical trials (RCTs) that assessed the effect of oat, oat beta-glucan-rich extracts or avenanthramides on CVD risk markers. RESULTS: Seventy-four RCTs, including 4937 predominantly hypercholesterolemic, obese subjects, with mild metabolic disturbances, were included in the systematic review. Of these, 59 RCTs contributed to the meta-analyses. Subjects receiving an OSI, compared to control arms without oats, had improved levels of total cholesterol (TC) [weighted mean difference and (95% CI) - 0.42 mmol/L, (- 0.61; - 0.22)], LDL cholesterol [- 0.29 mmol/L, (- 0.37; - 0.20)], glucose [- 0.25 nmol/L, (- 0.36; - 0.14)], body mass index [- 0.13 kg/m2, (- 0.26; - 0.01)], weight [- 0.94 kg, (- 1.84: - 0.05)], and waist circumference [- 1.06 cm, (- 1.85; - 0.27)]. RCTs on inflammation and/or oxidative stress markers were scarce and with inconsistent findings. RCTs comparing an OSI to heterogeneous interventions (e.g., wheat, eggs, rice, etc.), showed lowered levels of glycated haemoglobin, diastolic blood pressure, HDL cholesterol and apolipoprotein B. The majority of included RCTs (81.1%) had some concerns for risk of bias. CONCLUSION: Dietary OSIs resulted in lowered levels of blood lipids and improvements in anthropometric parameters among participants with predominantly mild metabolic disturbances, regardless of dietary background or control. Further high-quality trials are warranted to establish the role of OSIs on blood pressure, glucose homeostasis and inflammation markers.

A systematic review of the safety and efficacy of currently used treatment modalities in the treatment of patients with PIK3CA-related overgrowth spectrum.

BACKGROUND: PIK3CA (activating mutations of the p110α subunit of phosphatidylinositol 3-kinases)-related overgrowth spectrums (PROS) include a variety of clinical presentations that are associated with hypertrophy of different parts of the body. We performed a systematic literature review to assess the current treatment options and their efficacy and safety for PROS. METHODS: A literature search was performed in Embase, MEDLINE (Ovid), Web of Science Core Collection, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar to retrieve studies on the treatment of hypertrophy in PROS. Randomized controlled trials, cohort studies, and case series with ≥10 patients were included in the present review. The titles, abstracts, and full text were assessed by two reviewers independently. The risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: We included 16 studies of the treatment of hypertrophy in PROS patients, 13 (81.3%) from clinical retrospective studies and 3 (13.7%) from prospective cohort studies. The risk of bias grade was low for 2, medium for 12, and high for 2 studies. Of the 16 studies, 13 reported on surgical treatment and 3 reported pharmacologic treatment using phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway inhibitors in PROS patients. In 3 studies, PROS was defined by a mutation in the PIK3CA gene, and 13 studies relied on a clinical definition of PROS. Surgical therapy was beneficial for a specific subgroup of PROS (macrodactyly). However, little has been reported concerning surgery and the potential benefits for other PROS entities. The reported side effects after surgical therapy were mostly prolonged wound healing or scarring. PI3K/mTOR pathway inhibition was beneficial in patients with PROS by reducing hypertrophy and systemic symptoms. The adverse effects reported included infection, changes in blood count, liver enzymes, and metabolic measures. CONCLUSIONS: Surgery is a locally limited treatment option for specific types of PROS. A promising treatment option for PROS is pharmacologic PIK3CA inhibition. However, the level of evidence on the treatment of overgrowth in PROS patients is limited.

Association of diabetes with atrial fibrillation types: a systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia classified as paroxysmal and non-paroxysmal. Non-paroxysmal AF is associated with an increased risk of complications. Diabetes contributes to AF initiation, yet its role in AF maintenance is unclear. We conducted a systematic review and meta-analysis to summarize the evidence regarding the association of diabetes with AF types. METHODS: We searched 5 databases for observational studies investigating the association of diabetes with the likelihood of an AF type (vs another type) in humans. Study quality was evaluated using the Newcastle-Ottawa Scale. Studies classifying AF types as paroxysmal (reference) and non-paroxysmal were pooled in a meta-analysis using random effects models. RESULTS: Of 1997 articles we identified, 20 were included in our systematic review. The population sample size ranged from 64 to 9816 participants with mean age ranging from 40 to 75 years and percentage of women from 24.8 to 100%. The quality of studies varied from poor (60%) to fair (5%) to good (35%). In the systematic review, 8 studies among patients with AF investigated the cross-sectional association of diabetes with non-paroxysmal AF (vs paroxysmal) of which 6 showed a positive association and 2 showed no association. Fourteen studies investigated the longitudinal association of diabetes with "more sustained" AF types (vs "less sustained") of which 2 showed a positive association and 12 showed no association. In the meta-analysis of cross-sectional studies, patients with AF and diabetes were 1.31-times more likely to have non-paroxysmal AF than those without diabetes [8 studies; pooled OR (95% CI), 1.31 (1.13-1.51), I2 = 82.6%]. The meta-analysis of longitudinal studies showed that for patients with paroxysmal AF, diabetes is associated with 1.32-times increased likelihood of progression to non-paroxysmal AF [five studies; pooled OR (95% CI), 1.32 (1.07-1.62); I2 = 0%]. CONCLUSIONS: Our findings suggest that diabetes is associated with an increased likelihood of non-paroxysmal AF rather than paroxysmal AF. However, further high quality studies are needed to replicate these findings, adjust for potential confounders, elucidate mechanisms linking diabetes to non-paroxysmal AF, and assess the impact of antidiabetic medications on AF types. These strategies could eventually help decrease the risk of non-paroxysmal AF among patients with diabetes.