Citations

Abstract Objectives Breast milk is the recommended nutritional source for newborns and has been associated with decreased morbidity in low‐birth‐weight and preterm infants. In situations where breast milk is not available, donor breast milk is an alternative. Milk banking is becoming increasingly common worldwide to meet this need. Although the benefits of donor breast milk for the recipient infant are well established, the health impact on the breast milk donor and the infant of the breast milk donor is an area of current research. We aim to synthesize and evaluate the available evidence regarding the impact of donating breast milk on the health, lactation, and well‐being of the breast milk donor, and the health and growth of the infant of the breast milk donor. Methods We will search electronic databases, grey literature, and the websites of relevant international organizations. We will include studies that involve lactating women and their infants, healthy or with health conditions, who donate breast milk, without restrictions on study date, language, or study design. If sufficient homogeneity exists between studies, we will complete meta‐analyses. We will evaluate the risk of bias using the Risk of Bias tool or the Cochrane Risk of Bias in Non‐Randomized Studies tool. We will evaluate the overall certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Conclusion In this systematic review and meta‐analysis, we will summarize the current literature regarding the effects of human milk donation on human milk donors and their infants.

Abstract Objectives Human milk has been shown to reduce severe morbidity in preterm/low‐birth‐weight infants and is therefore the recommended nutritional source. When infants cannot receive maternal milk, donor human milk (DHM) is recommended. The use of human milk banking facilities is increasing to meet the need for DHM. DHM is unique compared to maternal milk as it must be processed and stored. The processing and storage of animal milk has been more rigorously studied than human milk and can serve as proxy to create DHM banking guidelines. Methods and Analysis We will search electronic databases, grey literature, and the websites of relevant international organizations. We will include studies that evaluated the impact of storage, handling, and treatment on the nutritional quality and safety of animal milk. We will not restrict study date, language, or design. If sufficient homogeneity exists between studies, we will conduct a meta‐analysis. We will evaluate the methodological quality of each study using the SYRCLE's (Systematic Review Centre for Laboratory Animal Experimentation) risk of bias tool. (1) We will evaluate the overall certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Conclusion In this systematic review and meta‐analysis, commissioned by the World Health Organization, we will synthesize the available literature regarding the impact of various storage, handling, and treatment practices on the nutritional quality and safety of animal milk.

Abstract Context Low vitamin D status is common and is associated with various common medical conditions. Objective To support the development of the Endocrine Society's Clinical Practice Guideline on Vitamin D for the Prevention of Disease. Methods We searched multiple databases for studies that addressed 14 clinical questions prioritized by the guideline panel. Of the 14 questions, 10 clinical questions assessed the effect of vitamin D vs no vitamin D in the general population throughout the lifespan, during pregnancy, and in adults with prediabetes; 1 question assessed dosing; and 3 questions addressed screening with serum 25-hydroxyvitamin D (25[OH]D). The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess certainty of evidence. Results Electronic searches yielded 37 007 citations, from which we included 151 studies. In children and adolescents, low-certainty evidence suggested reduction in respiratory tract infections with empiric vitamin D. There was no significant effect on select outcomes in healthy adults aged 19 to 74 years with variable certainty of evidence. There was a very small reduction in mortality among adults older than 75 years with high certainty of evidence. In pregnant women, low-certainty evidence suggested possible benefit on various maternal, fetal, and neonatal outcomes. In adults with prediabetes, moderate certainty of evidence suggested reduction in the rate of progression to diabetes. Administration of high-dose intermittent vitamin D may increase falls, compared to lower-dose daily dosing. We did not identify trials on the benefits and harms of screening with serum 25(OH)D. Conclusion The evidence summarized in this systematic review addresses the benefits and harms of vitamin D for the prevention of disease. The guideline panel considered additional information about individuals’ and providers’ values and preferences and other important decisional and contextual factors to develop clinical recommendations.

Abstract Background We compared long-term mortality and readmission rates after COVID-19 hospitalization based on rural-urban status and assessed the impact of COVID-19 vaccination introduction on clinical outcomes by rurality. Methods The study comprised adults hospitalized for COVID-19 at 17 hospitals in 4 US states between March 2020 and July 2022, followed until May 2023. The main analysis included all patients, whereas a sensitivity analysis focused on residents from 4 states containing 17 hospitals. Additional analyses compared the pre- and postvaccination periods. Results The main analysis involved 9325 COVID-19 hospitalized patients: 31% were from 187 rural counties in 31 states; 69% from 234 urban counties in 44 states; the mean age was 65 years (rural, 66 years; urban, 64 years); 3894 women (rural, 41%; urban, 42%); 8007 Whites (rural, 87%; urban, 83%); 1738 deaths (rural, 21%; urban, 17%); and 2729 readmissions (rural, 30%; urban, 29%). During a median follow-up of 602 days, rural residence was associated with a 22% higher all-cause mortality (log-rank, P < .001; hazard ratio, 1.22; 95% confidence interval, 1.10-1.34, P < .001), and a trend toward a higher readmission rate (log-rank, P = .038; hazard ratio, 1.06; 95% confidence interval, .98-1.15; P = .130). The results remained consistent in the sensitivity analysis and in both pre- and postvaccination time periods. Conclusions and Relevance Patients from rural counties experienced higher mortality and tended to be readmitted more frequently following COVID-19 hospitalization over the long term compared with those from urban counties, a difference that remained even after the introduction of COVID-19 vaccines.

Background and Aims: Blood-based biomarkers have been proposed as an alternative to liver biopsy for noninvasive liver disease assessment in chronic liver disease. Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4), as compared to biopsy in chronic liver disease. Approach and Results: We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in HBV and HCV, HIV-HCV/HBV coinfection, and NAFLD. Positive (LR+) and negative (LR−) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66–6.25 and 0.23–0.80, 1.89–5.24 and 0.12–0.64, and 1.32–7.15 and 0.15–0.86, respectively; LR+ and LR− for NAFLD F2-4, F3-4, and F4 were 2.65–3.37 and 0.37–0.39, 2.25–6.76 and 0.07–0.87, and 3.90 and 0.15, respectively. Overall, the proportional odds ratio indicated FIB-4 <1.45 was better than aspartate aminotransferase-to-platelet ratio index <0.5 for F2-4. FIB-4 >3.25 was also better than aspartate aminotransferase-to-platelet ratio index >1.5 for F3-4 and F4. There was limited data for combined tests. Conclusions: Blood-based biomarkers are associated with small-to-moderate change in pretest probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV coinfection, and NAFLD, with limited comparative or combination studies for other chronic liver diseases.

SummaryBackgroundStudies exploring the association between inflammatory bowel disease (IBD) and pancreatic cancer have reported inconsistent results.AimsTo provide a comprehensive overview of the risk of pancreatic cancer development in patients with IBD.MethodsWe searched Embase, PubMed, Scopus and ProQuest from inception to 31 October 2023. We included population‐based cohort studies examining the risk of incident pancreatic cancer in adult patients with IBD compared to the non‐IBD population. We also retrieved Mendelian randomisation (MR) studies investigating the relationship of IBD with pancreatic cancer risk. We conducted random‐effects meta‐analyses and provided pooled relative risks (RRs) with 95% confidence intervals (CIs).ResultsWe included 13 studies. Among 11 cohort studies, the risk of developing pancreatic cancer increased by 79% in patients with IBD (RR = 1.79 [95% CI: 1.16–2.75]; I2 = 95.7%). Patients either with Crohn's disease (RR = 1.42 [95% CI: 1.24–1.63]) or ulcerative colitis (RR = 1.50 [95% CI: 1.17–1.92]) had increased risk (p for interaction = 0.72). The annual incidence of pancreatic cancer potentially attributable to IBD increased by 55 cases (95% CI: 17–103) per million. Two MR studies demonstrated that genetic liability to IBD was associated with an increased risk of pancreatic cancer.ConclusionsOur results suggest a moderate increase in the risk of pancreatic cancer in patients with IBD, which may be further heightened by genetic predisposition to IBD. The increased risk of pancreatic cancer is probably similar in Crohn's disease and ulcerative colitis.

Abstract Aims We developed new machine learning (ML) models and externally validated existing statistical models [ischaemic stroke predictive risk score (iScore) and totalled health risks in vascular events (THRIVE) scores] for predicting the composite of recurrent stroke or all-cause mortality at 90 days and at 3 years after hospitalization for first acute ischaemic stroke (AIS). Methods and results In adults hospitalized with AIS from January 2005 to November 2016, with follow-up until November 2019, we developed three ML models [random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGBOOST)] and externally validated the iScore and THRIVE scores for predicting the composite outcomes after AIS hospitalization, using data from 721 patients and 90 potential predictor variables. At 90 days and 3 years, 11 and 34% of patients, respectively, reached the composite outcome. For the 90-day prediction, the area under the receiver operating characteristic curve (AUC) was 0.779 for RF, 0.771 for SVM, 0.772 for XGBOOST, 0.720 for iScore, and 0.664 for THRIVE. For 3-year prediction, the AUC was 0.743 for RF, 0.777 for SVM, 0.773 for XGBOOST, 0.710 for iScore, and 0.675 for THRIVE. Conclusion The study provided three ML-based predictive models that achieved good discrimination and clinical usefulness in outcome prediction after AIS and broadened the application of the iScore and THRIVE scoring system for long-term outcome prediction. Our findings warrant comparative analyses of ML and existing statistical method–based risk prediction tools for outcome prediction after AIS in new data sets.

AbstractMeta‐analysis is commonly used to combine results from multiple clinical trials, but traditional meta‐analysis methods do not refer explicitly to a population of individuals to whom the results apply and it is not clear how to use their results to assess a treatment's effect for a population of interest. We describe recently‐introduced causally interpretable meta‐analysis methods and apply their treatment effect estimators to two individual‐participant data sets. These estimators transport estimated treatment effects from studies in the meta‐analysis to a specified target population using the individuals' potentially effect‐modifying covariates. We consider different regression and weighting methods within this approach and compare the results to traditional aggregated‐data meta‐analysis methods. In our applications, certain versions of the causally interpretable methods performed somewhat better than the traditional methods, but the latter generally did well. The causally interpretable methods offer the most promise when covariates modify treatment effects and our results suggest that traditional methods work well when there is little effect heterogeneity. The causally interpretable approach gives meta‐analysis an appealing theoretical framework by relating an estimator directly to a specific population and lays a solid foundation for future developments.

Abstract Background Optimizing therapy and monitoring response are integral aspects of inflammatory bowel disease treatment. We conducted a systematic review and meta-analysis to determine whether serum ustekinumab trough concentrations during maintenance therapy were associated with ustekinumab treatment response in patients with inflammatory bowel disease. Methods A systematic review was performed to March 21, 2022, to identify studies using MEDLINE, EMBASE, and the Cochrane library. We included studies that reported the association between serum ustekinumab trough concentrations with clinical or endoscopic remission. Outcome measures were combined across studies using the random-effects model with an odds ratio (OR) for binary outcomes of endoscopic and clinical remission. Results We identified 14 observational studies that were included in the analysis for clinical remission (919 patients, 63% with Crohn’s disease) or endoscopic remission (290 patients, all with Crohn’s disease). Median ustekinumab trough concentrations were higher amongst individuals achieving clinical remission compared with those not achieving remission (mean difference, 1.6 ug/mL; 95% confidence interval [CI], 0.21-3.01 ug/mL). Furthermore, individuals with median serum trough concentration in the fourth quartile were significantly more likely to achieve clinical (OR, 3.61; 95% CI, 2.11-6.20) but not endoscopic remission (OR, 4.67; 95% CI, 0.86-25.19) compared with those with first quartile median trough concentrations. Conclusion Based on the results of this meta-analysis primarily relating to patients with Crohn’s disease on maintenance ustekinumab treatment, it appears that there is an association between higher ustekinumab trough concentration and clinical outcomes. Prospective studies are required to determine whether proactive dose adjustments of ustekinumab therapy provides additional clinical benefit.

INTRODUCTION: Rapidity of symptom resolution informs treatment choice in patients with moderate-severe ulcerative colitis (UC). We conducted a systematic review and network meta-analysis comparing early symptomatic remission with approved therapies. METHODS: Through a systematic literature review to December 31, 2022, we identified randomized trials in adult outpatients with moderate-severe UC treated with approved therapies (tumor necrosis factor α antagonists, vedolizumab, ustekinumab, janus kinase inhibitors, or ozanimod), compared with each other or placebo, reporting rates of symptomatic remission (based on partial Mayo score, with resolution of rectal bleeding and near-normalization of stool frequency) at weeks 2, 4, and/or 6. We performed random-effects network meta-analysis using a frequentist approach and estimated relative risk (RR) and 95% confidence interval values. RESULTS: On network meta-analysis, upadacitinib was more effective than all agents in achieving symptomatic remission at weeks 2 (range of RR, 2.85–6.27), 4 (range of RR, 1.78–2.37), and 6 (range of RR, 1.84–2.79). Tumor necrosis factor α antagonists and filgotinib, but not ustekinumab and vedolizumab, were more effective than ozanimod in achieving symptomatic remission at week 2, but not at weeks 4 and 6. With approximately 10% placebo-treated patients achieving symptomatic remission at 2 weeks, we estimated 68%, 22%, 23.7%, 23.9%, 22.2%, 18.4%, 15.7%, and 10.9% of upadacitinib-, filgotinib-, infliximab-, adalimumab-, golimumab-, ustekinumab-, vedolizumab-, and ozanimod-treated patients would achieve early symptomatic remission, ustekinumab and vedolizumab achieving rapid remission only in biologic-naïve patients. DISCUSSION: In a systematic review and network meta-analysis, upadacitinib was most effective in achieving early symptomatic remission, whereas ozanimod was relatively slower acting.