Birth weight in relation to health and disease in later life: an umbrella review of systematic reviews and meta-analyses

BACKGROUND: Birth weight, a marker of the intrauterine environment, has been extensively studied in epidemiological research in relation to subsequent health and disease. Although numerous meta-analyses have been published examining the association between birth weight and subsequent health-related outcomes, the epidemiological credibility of these associations has not been thoroughly assessed. The objective of this study is to map the diverse health outcomes associated with birth weight and evaluate the credibility and presence of biases in the reported associations. METHODS: An umbrella review was performed to identify systematic reviews and meta-analyses of observational studies investigating the association between birth weight and subsequent health outcomes and traits. For each association, we estimated the summary effect size by random-effects and fixed-effects models, the 95 % confidence interval, and the 95 % prediction interval. We also assessed the between-study heterogeneity, evidence for small-study effects and excess significance bias. We further applied standardized methodological criteria to evaluate the epidemiological credibility of the statistically significant associations. RESULTS: Thirty-nine articles including 78 associations between birth weight and diverse outcomes met the eligibility criteria. A wide range of health outcomes has been studied, ranging from anthropometry and metabolic diseases, cardiovascular diseases and cardiovascular risk factors, various cancers, respiratory diseases and allergies, musculoskeletal traits and perinatal outcomes. Forty-seven of 78 associations presented a nominally significant summary effect and 21 associations remained statistically significant at P < 1 × 10(-6). Thirty associations presented large or very large between-study heterogeneity. Evidence for small-study effects and excess significance bias was present in 13 and 16 associations, respectively. One association with low birth weight (increased risk for all-cause mortality), two dose-response associations with birth weight (higher bone mineral concentration in hip and lower risk for mortality from cardiovascular diseases per 1 kg increase in birth weight) and one association with small-for-gestational age infants with normal birth weight (increased risk for childhood stunting) presented convincing evidence. Eleven additional associations had highly suggestive evidence. CONCLUSIONS: The range of outcomes convincingly associated with birth weight might be narrower than originally described under the "fetal origin hypothesis" of disease. There is weak evidence that birth weight constitutes an effective public health intervention marker

Prognostic models for outcome prediction in patients with chronic obstructive pulmonary disease: systematic review and critical appraisal

OBJECTIVE: To map and assess prognostic models for outcome prediction in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Systematic review. DATA SOURCES: PubMed until November 2018 and hand searched references from eligible articles. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Studies developing, validating, or updating a prediction model in COPD patients and focusing on any potential clinical outcome. RESULTS: The systematic search yielded 228 eligible articles, describing the development of 408 prognostic models, the external validation of 38 models, and the validation of 20 prognostic models derived for diseases other than COPD. The 408 prognostic models were developed in three clinical settings: outpatients (n=239; 59%), patients admitted to hospital (n=155; 38%), and patients attending the emergency department (n=14; 3%). Among the 408 prognostic models, the most prevalent endpoints were mortality (n=209; 51%), risk for acute exacerbation of COPD (n=42; 10%), and risk for readmission after the index hospital admission (n=36; 9%). Overall, the most commonly used predictors were age (n=166; 41%), forced expiratory volume in one second (n=85; 21%), sex (n=74; 18%), body mass index (n=66; 16%), and smoking (n=65; 16%). Of the 408 prognostic models, 100 (25%) were internally validated and 91 (23%) examined the calibration of the developed model. For 286 (70%) models a model presentation was not available, and only 56 (14%) models were presented through the full equation. Model discrimination using the C statistic was available for 311 (76%) models. 38 models were externally validated, but in only 12 of these was the validation performed by a fully independent team. Only seven prognostic models with an overall low risk of bias according to PROBAST were identified. These models were ADO, B-AE-D, B-AE-D-C, extended ADO, updated ADO, updated BODE, and a model developed by Bertens et al. A meta-analysis of C statistics was performed for 12 prognostic models, and the summary estimates ranged from 0.611 to 0.769. CONCLUSIONS: This study constitutes a detailed mapping and assessment of the prognostic models for outcome prediction in COPD patients. The findings indicate several methodological pitfalls in their development and a low rate of external validation. Future research should focus on the improvement of existing models through update and external validation, as well as the assessment of the safety, clinical effectiveness, and cost effectiveness of the application of these prognostic models in clinical practice through impact studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017069247

Prognostic factors for adverse outcomes in patients with COVID-19: a field-wide systematic review and meta-analysis

INTRODUCTION: The individual prognostic factors for COVID-19 are unclear. For this reason, we aimed to present a state-of-the-art systematic review and meta-analysis on the prognostic factors for adverse outcomes in COVID-19 patients. METHODS: We systematically reviewed PubMed from January 1, 2020 to July 26, 2020 to identify non-overlapping studies examining the association of any prognostic factor with any adverse outcome in patients with COVID-19. Random-effects meta-analysis was performed, and between-study heterogeneity was quantified using I2 metric. Presence of small-study effects was assessed by applying the Egger's regression test. RESULTS: We identified 428 eligible articles, which were used in a total of 263 meta-analyses examining the association of 91 unique prognostic factors with 11 outcomes. Angiotensin-converting enzyme inhibitors, obstructive sleep apnea, pharyngalgia, history of venous thromboembolism, sex, coronary heart disease, cancer, chronic liver disease, chronic obstructive pulmonary disease, dementia, any immunosuppressive medication, peripheral arterial disease, rheumatological disease and smoking were associated with at least one outcome and had >1000 events, p-value <0.005, I2 <50%, 95% prediction interval excluding the null value, and absence of small-study effects in the respective meta-analysis. The risk of bias assessment using the Quality In Prognosis Studies tool indicated high risk of bias in 302 of 428 articles for study participation, 389 articles for adjustment for other prognostic factors, and 396 articles for statistical analysis and reporting. CONCLUSIONS: Our findings could be used for prognostic model building and guide patients' selection for randomised clinical trials

Pediatric multiple sclerosis: update on diagnostic criteria, imaging, histopathology and treatment choices

Pediatric multiple sclerosis (MS) represents less than 5% of the MS population, but patients with pediatric-onset disease reach permanent disability at a younger age than adult onset patients. Accurate diagnosis at presentation and optimal long-term treatment is vital to mitigate ongoing neuroinflammation and irreversible neurodegeneration. However, it may be difficult to early differentiate pediatric MS from acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica spectrum disorders (NMOSD) as they often have atypical presentation that differs from that of adult-onset MS. The purpose of this review is to summarize the updated views on diagnostic criteria, imaging, histopathology and treatment choices

The association of depression and all-cause and cause-specific mortality: an umbrella review of systematic reviews and meta-analyses

Background: Depression is a prevalent and disabling mental disorder that frequently co-occurs with a wide range of chronic conditions. Evidence has suggested that depression could be associated with excess all-cause mortality across different settings and populations, although the causality of these associations remains unclear. Methods: We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, PsycINFO, and Embase electronic databases were searched through January 20, 2018. Systematic reviews and meta-analyses that investigated associations of depression and all-cause and cause-specific mortality were selected for the review. The evidence was graded as convincing, highly suggestive, suggestive, or weak based on quantitative criteria that included an assessment of heterogeneity, 95% prediction intervals, small-study effects, and excess significance bias. Results: A total of 26 references providing 2 systematic reviews and data for 17 meta-analytic estimates met inclusion criteria (19 of them on all-cause mortality); data from 246 unique studies (N = 3,825,380) were synthesized. All 17 associations had P < 0.05 per random effects summary effects, but none of them met criteria for convincing evidence. Associations of depression and all-cause mortality in patients after acute myocardial infarction, in individuals with heart failure, in cancer patients as well as in samples from mixed settings met criteria for highly suggestive evidence. However, none of the associations remained supported by highly suggestive evidence in sensitivity analyses that considered studies employing structured diagnostic interviews. In addition, associations of depression and all-cause mortality in cancer and post-acute myocardial infarction samples were supported only by suggestive evidence when studies that tried to adjust for potential confounders were considered. Conclusions: Even though associations between depression and mortality have nominally significant results in all assessed settings and populations, the evidence becomes weaker when focusing on studies that used structured interviews and those that tried to adjust for potential confounders. A causal effect of depression on all-cause and cause-specific mortality remains unproven, and thus interventions targeting depression are not expected to result in lower mortality rates at least based on current evidence from observational studies

Elucidating the environmental risk factors for rheumatic diseases: An umbrella review of meta-analyses

AIMS: Although rheumatic diseases constitute a leading cause of disability, the environmental risk factors for these diseases are not clarified. In the present study, we aim to systematically appraise the epidemiological credibility of the environmental risk factors for rheumatic diseases. METHODS: We systematically searched PubMed to capture meta-analyses of observational studies on environmental risk factors for the most prevalent rheumatic diseases. For each association, we estimated the summary effect size estimate, the 95% confidence and prediction intervals, and the I2 metric. We further examined the presence of small-study effects and excess significance bias. RESULTS: Overall, we identified 30 eligible papers describing 42 associations. Thirty-three associations were statistically significant at P < 0.05, whereas 13 of them were statistically significant at P < 1 × 10-6 . Thirty-two associations had large or very large between-study heterogeneity. In 12 associations, evidence of small-study effects and/or excess significance bias was found. Six risk factors (nine associations) presented convincing or highly suggestive evidence of association: smoking and pack-years of smoking for rheumatoid arthritis; BMI (per 5 kg/m2 increase) for gout and hip osteoarthritis; alcohol consumption for gout; BMI (overweight vs lean, obese vs lean), knee injury and participation in heavy work for knee osteoarthritis. CONCLUSION: Our umbrella review indicated that a narrow range of risk factors has been examined for rheumatic diseases. Current evidence strongly supports that smoking, obesity, alcohol consumption, knee injury, and work activities are associated with risk for at least one rheumatic disease