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

Reproducibility of prediction models in health services research

The field of health services research studies the health care system by examining outcomes relevant to patients and clinicians but also health economists and policy makers. Such outcomes often include health care spending, and utilization of care services. Building accurate prediction models using reproducible research practices for health services research is important for evidence-based decision making. Several systematic reviews have summarized prediction models for outcomes relevant to health services research, but these systematic reviews do not present a thorough assessment of reproducibility and research quality of the prediction modelling studies. In the present commentary, we discuss how recent advances in prediction modelling in other medical fields can be applied to health services research. We also describe the current status of prediction modelling in health services research, and we summarize available methodological guidance for the development, update, external validation and systematic appraisal of prediction models

Conducting umbrella reviews

In this article, Lazaros Belbasis and colleagues explain the rationale for umbrella reviews and the key steps involved in conducting an umbrella review, using a working example

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

Multiple sclerosis between genetics and infections: human endogenous retroviruses in monocytes and macrophages

The etiology of multiple sclerosis (MS) is still unknown, but there is strong evidence that genetic predisposition associated with environmental factors can trigger the disease. An estimated 30 million years ago, exogenous retroviruses are thought to have integrated themselves into human germ line cells, becoming part of human DNA and being transmitted over generations. Usually such human endogenous retroviruses (HERVs) are silenced or expressed at low levels, but in some pathological conditions, such as MS, their expression is higher than that in the healthy population. Three HERV families have been associated with MS: HERV-H, HERV-K, and HERV-W. The envelope protein of MS-associated retrovirus (MSRV) from the HERV-W family currently has the strongest evidence as a potential trigger for MS. In addition to expression in peripheral immune cells, MSRV is expressed in monocytes and microglia in central nervous system lesions of people with MS and, through the activation of toll-like receptor 4, it has been shown to drive the production of proinflammatory cytokines, reduction of myelin protein expression, and death of oligodendrocyte precursors. In conclusion, the association between HERVs and MS is well documented and a pathological role for MSRV in MS is plausible. Further studies are required to determine whether the presence of these HERVs is a cause or an effect of immune dysregulation in MS

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

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 randomized clinical trials

Fifty-Year Fate and Impact of General Medical Journals

Background: Influential medical journals shape medical science and practice and their prestige is usually appraised by citation impact metrics, such as the journal impact factor. However, how permanent are medical journals and how stable is their impact over time? Methods and Results: We evaluated what happened to general medical journals that were publishing papers half a century ago, in 1959. Data were retrieved from ISI Web of Science for citations and PubMed (Journals function) for journal history. Of 27 eligible journals publishing in 1959, 4 have stopped circulation (including two of the most prestigious journals in 1959) and another 7 changed name between 1959 and 2009. Only 6 of these 27 journals have been published continuously with their initial name since they started circulation. The citation impact of papers published in 1959 gives a very different picture from the current journal impact factor; the correlation between the two is non-significant and very close to zero. Only 13 of the 5,223 papers published in 1959 received at least 5 citations in 2009. Conclusions: Journals are more permanent entities than single papers, but they are also subject to major change and their relative prominence can change markedly over time