Predicting hospital admissions from individual patient data (IPD): an applied example to explore key elements driving external validity.

OBJECTIVE: To explore factors that potentially impact external validation performance while developing and validating a prognostic model for hospital admissions (HAs) in complex older general practice patients. STUDY DESIGN AND SETTING: Using individual participant data from four cluster-randomised trials conducted in the Netherlands and Germany, we used logistic regression to develop a prognostic model to predict all-cause HAs within a 6-month follow-up period. A stratified intercept was used to account for heterogeneity in baseline risk between the studies. The model was validated both internally and by using internal-external cross-validation (IECV). RESULTS: Prior HAs, physical components of the health-related quality of life comorbidity index, and medication-related variables were used in the final model. While achieving moderate discriminatory performance, internal bootstrap validation revealed a pronounced risk of overfitting. The results of the IECV, in which calibration was highly variable even after accounting for between-study heterogeneity, agreed with this finding. Heterogeneity was equally reflected in differing baseline risk, predictor effects and absolute risk predictions. CONCLUSIONS: Predictor effect heterogeneity and differing baseline risk can explain the limited external performance of HA prediction models. With such drivers known, model adjustments in external validation settings (eg, intercept recalibration, complete updating) can be applied more purposefully. TRIAL REGISTRATION NUMBER: PROSPERO id: CRD42018088129.

Use of the GRADE approach in health policymaking and evaluation: a scoping review of nutrition and physical activity policies.

BACKGROUND: Nutrition and physical activity policies have the potential to influence lifestyle patterns and reduce the burden of non-communicable diseases. In the world of health-related guidelines, GRADE (Grading of Recommendations, Assessment, Development and Evaluation) is the most widely used approach for assessing the certainty of evidence and determining the strength of recommendations. Thus, it is relevant to explore its usefulness also in the process of nutrition and physical activity policymaking and evaluation. The purpose of this scoping review was (i) to generate an exemplary overview of documents using the GRADE approach in the process of nutrition and physical activity policymaking and evaluation, (ii) to find out how the GRADE approach has been applied, and (iii) to explore which facilitators of and barriers to the use of GRADE have been described on the basis of the identified documents. The overarching aim of this work is to work towards improving the process of evidence-informed policymaking in the areas of dietary behavior, physical activity, and sedentary behavior. METHODS: A scoping review was conducted according to current reporting standards. MEDLINE via Ovid, the Cochrane Library, and Web of Science were systematically searched up until 4 July 2019. Documents describing a body of evidence which was assessed for the development or evaluation of a policy, including documents labeled as "guidelines," or systematic reviews used to inform policymaking were included. RESULTS: Thirty-six documents were included. Overall, 313 GRADE certainty of evidence ratings were identified in systematic reviews and guidelines; the strength of recommendations/policies was assessed in four documents, and six documents mentioned facilitators or barriers for the use of GRADE. The major reported barrier was the initial low starting level of a body of evidence from non-randomized studies when assessing the certainty of evidence. CONCLUSION: This scoping review found that the GRADE approach has been used for policy evaluations, in the evaluation of the effectiveness of policy-relevant interventions (policymaking), as well as in the development of guidelines intended to guide policymaking. Several areas for future research were identified to explore the use of GRADE in health policymaking and evaluation.

Milk A1 ß-casein and health-related outcomes in humans: a systematic review.

CONTEXT: Various epidemiological studies suggest a positive association between exposure to cow's milk A1 ß-casein protein and risk for noncommunicable chronic diseases. The consumption of A2 cow's milk is increasing, likely because A2 milk is postulated to have positive effects on digestive health. OBJECTIVE: A systematic review was conducted to investigate associations between A1 ß-casein and health-related outcomes in humans. DATA SOURCES: Five electronic databases, 3 clinical trial registries, and the internet were searched systematically. STUDY SELECTION: Using predefined inclusion criteria, 2 authors independently selected studies investigating the effect of A1 ß-casein or ß-casomorphin-7 intake/exposure on any health-related outcome in humans. Discrepancies were resolved by consensus. DATA EXTRACTION: Two authors independently extracted data and assessed risk of bias. The certainty of evidence per outcome was evaluated using the GRADE approach. Discrepancies were resolved by consensus. RESULTS: Fifteen randomized controlled trials, 2 case-control studies, and 8 ecological studies were included. Most randomized controlled studies and case-control studies investigating a potential effect on various outcomes were based on intermediate markers and found no significant difference between the 2 milk types. In contrast, most ecological studies reported that population-level A1 ß-casein exposure is associated with adverse health outcomes. The certainty of the evidence for the included outcomes, as assessed by the GRADE approach, was rated as moderate for digestive symptoms and as low to very low for all other outcomes. CONCLUSIONS: Human-based evidence from clinical trials and epidemiological studies published prior to October 2017 provides moderate certainty for adverse digestive health effects of A1 ß-casein compared with A2 ß-casein but low or very low certainty for other health effects. These conclusions may change in the future, given the emergent nature of this topic and the ongoing research in this area. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42016043795.

Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies.

OBJECTIVE: To assess the association between intake of non-sugar sweeteners (NSS) and important health outcomes in generally healthy or overweight/obese adults and children. DESIGN: Systematic review following standard Cochrane review methodology. DATA SOURCES: Medline (Ovid), Embase, Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov, and reference lists of relevant publications. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies including generally healthy adults or children with or without overweight or obesity were eligible. Included study designs allowed for a direct comparison of no intake or lower intake of NSS with higher NSS intake. NSSs had to be clearly named, the dose had to be within the acceptable daily intake, and the intervention duration had to be at least seven days. MAIN OUTCOME MEASURES: Body weight or body mass index, glycaemic control, oral health, eating behaviour, preference for sweet taste, cancer, cardiovascular disease, kidney disease, mood, behaviour, neurocognition, and adverse effects. RESULTS: The search resulted in 13 941 unique records. Of 56 individual studies that provided data for this review, 35 were observational studies. In adults, evidence of very low and low certainty from a limited number of small studies indicated a small beneficial effect of NSSs on body mass index (mean difference -0.6, 95% confidence interval -1.19 to -0.01; two studies, n=174) and fasting blood glucose (-0.16 mmol/L, -0.26 to -0.06; two, n=52). Lower doses of NSSs were associated with lower weight gain (-0.09 kg, -0.13 to -0.05; one, n=17 934) compared with higher doses of NSSs (very low certainty of evidence). For all other outcomes, no differences were detected between the use and non-use of NSSs, or between different doses of NSSs. No evidence of any effect of NSSs was seen on overweight or obese adults or children actively trying to lose weight (very low to moderate certainty). In children, a smaller increase in body mass index z score was observed with NSS intake compared with sugar intake (-0.15, -0.17 to -0.12; two, n=528, moderate certainty of evidence), but no significant differences were observed in body weight (-0.60 kg, -1.33 to 0.14; two, n=467, low certainty of evidence), or between different doses of NSSs (very low to moderate certainty). CONCLUSIONS: Most health outcomes did not seem to have differences between the NSS exposed and unexposed groups. Of the few studies identified for each outcome, most had few participants, were of short duration, and their methodological and reporting quality was limited; therefore, confidence in the reported results is limited. Future studies should assess the effects of NSSs with an appropriate intervention duration. Detailed descriptions of interventions, comparators, and outcomes should be included in all reports. SYSTEMATIC REVIEW REGISTRATION: Prospero CRD42017047668.

Dietary supplementation with n-3-fatty acids in patients with pancreatic cancer and cachexia: marine phospholipids versus fish oil - a randomized controlled double-blind trial.

BACKGROUND: Like many other cancer patients, most pancreatic carcinoma patients suffer from severe weight loss. As shown in numerous studies with fish oil (FO) supplementation, a minimum daily intake of 1.5 g n-3-fatty acids (n-3-FA) contributes to weight stabilization and improvement of quality of life (QoL) of cancer patients. Given n-3-FA not as triglycerides (FO), but mainly bound to marine phospholipids (MPL), weight stabilization and improvement of QoL has already been seen at much lower doses of n-3-FA (0,3 g), and MPL were much better tolerated. The objective of this double-blind randomized controlled trial was to compare low dose MPL and FO formulations, which had the same n-3-FA amount and composition, on weight and appetite stabilization, global health enhancement (QoL), and plasma FA-profiles in patients suffering from pancreatic cancer. METHODS: Sixty pancreatic cancer patients were included into the study and randomized to take either FO- or MPL supplementation. Patients were treated with 0.3 g of n-3-fatty acids per day over six weeks. Since the n-3-FA content of FO is usually higher than that of MPL, FO was diluted with 40% of medium chain triglycerides (MCT) to achieve the same capsule size in both intervention groups and therefore assure blinding. Routine blood parameters, lipid profiles, body weight, and appetite were measured before and after intervention. Patient compliance was assessed through a patient diary. Quality of life and nutritional habits were assessed with validated questionnaires (EORTC-QLQ-C30, PAN26). Thirty one patients finalized the study protocol and were analyzed (per-protocol-analysis). RESULTS: Intervention with low dose n-3-FAs, either as FO or MPL supplementation, resulted in similar and promising weight and appetite stabilization in pancreatic cancer patients. MPL capsules were slightly better tolerated and showed fewer side effects, when compared to FO supplementation. CONCLUSION: The similar effects between both interventions were unexpected but reliable, since the MPL and FO formulations caused identical increases of n-3-FAs in plasma lipids of included patients after supplementation. The effects of FO with very low n-3-FA content might be explained by the addition of MCT. The results of this study suggest the need for further investigations of marine phospholipids for the improvement of QoL of cancer patients, optionally in combination with MCT.

Analysis of German nutrition brochures for pregnant women with evidence-based patient information criteria.

OBJECTIVE: To evaluate nutrition brochures for pregnant women in Germany based on evidence-based patient information (EBPI) criteria. METHODS: Nutrition brochures for pregnant women in Germany were collected. Brochures addressing the risk of salmonellosis, toxoplasmosis or listeriosis were analyzed by two researchers independently. RESULTS: Fifty brochures reporting any information on the risk of infection were analyzed. Most brochures did not include literature citations and only few brochures gave a risk description, predominantly verbally, which usually leads to an overestimation of the actual risk. Advertisement was present in 22% of the brochures. CONCLUSION: German nutrition brochures for pregnant women should be adapted to comply with evidence-based patient information (EBPI) criteria for achieving a better quality of the disseminated information. PRACTICE IMPLICATIONS: The findings highlight the need of high quality nutrition brochures for pregnant women, which are relevant not only for pregnant women, but also to those responsible for creating brochures, and to physicians in charge of patient information.

Effects of Marine Phospholipids Extract on the Lipid Levels of Metastatic and Nonmetastatic Prostate Cancer Patients.

High intake of omega-3 fatty acids (n-3 FAs) from fish has shown to reduce metastatic progression of prostate cancer. This clinical trial investigated the influence of high n-3 FA intake (marine phospholipids, MPL) on the FA composition of blood lipids, lysophosphatidylcholine (LPC), and on lipoproteins in prostate cancer patients and elderly men without prostate cancer. MPL supplementation resulted in a significant increase of n-3 FAs (eicosapentaenoic and docosahexaenoic acid) in blood lipids, while arachidonic acid (n-6 FA) decreased significantly. Low density lipoprotein (LDL) and high density lipoprotein (HDL) increased significantly, but the LDL increase was observed only in subjects with an inactive tumour. Similarly, LPC plasma concentration increased significantly only in patients without tumour. The missing increase of LDL and LPC after MPL supplementation in patients with actively growing (metastasizing) prostate cancer suggests that tumour cells have an elevated demand for LDL and LPC. Due to the MPL-induced increase of n-3 FAs in these blood lipids, it can be assumed that especially actively growing and metastasizing prostate cancer cells are provided with elevated amounts of these antimetastatic n-3 FAs. A hypothetic model explaining the lower incidence of metastatic progression in prostate cancer patients with high fish consumption is presented.