Analyzing weight loss intervention studies with missing data: which method should be used?

Objective: Missing data due to study dropout is common in weight loss trials and several statistical methods exist to account for it. The aim of this study was to identify methods in the literature and to compare the effects of methods of analysis using simulated data sets. Methods: Literature was obtained for a 1-y period to identify analytical methods used in reporting weight loss trials. A comparison of methods with large or small between-group weight loss, and missing data that was, or was not, missing randomly was conducted in simulated data sets based on previous research. Results: Twenty-seven studies, some with multiple analyses, were retrieved. Complete case analysis (n ¼ 17), last observation carried forward (n ¼ 6), baseline carried forward (n ¼ 4), maximum likelihood (n ¼ 6), and multiple imputation (n ¼ 2) were the common methods of accounting for missing data. When comparing methods on simulated data, all demonstrated a significant effect when the between-group weight loss was large (P \u3c 0.001, interaction term) regardless of whether the data was missing completely at random. When the weight loss interaction was small, the method used for analysis gave considerably different results with mixed models (P ¼ 0.180) and multiple imputations (P ¼ 0.125) closest to the full data model (P ¼ 0.033). Conclusion: The simulation analysis showed that when data were not missing at random, treatment effects were small, and the amount of missing data was substantial, the analysis method had an effect on the significance of the outcome. Careful attention must be paid when analyzing or appraising studies with missing data and small effects to ensure appropriate conclusions are drawn

Using data mining to predict success in a weight loss trial

Background: Traditional methods for predicting weight loss success use regression approaches, which make the assumption that the relationships between the independent and dependent (or logit of the dependent) variable are linear. The aim of the present study was to investigate the relationship between common demographic and early weight loss variables to predict weight loss success at 12 months without making this assumption. Methods: Data mining methods (decision trees, generalised additive models and multivariate adaptive regression splines), in addition to logistic regression, were employed to predict: (i) weight loss success (defined as ≥5%) at the end of a 12-month dietary intervention using demographic variables [body mass index (BMI), sex and age]; percentage weight loss at 1 month; and (iii) the difference between actual and predicted weight loss using an energy balance model. The methods were compared by assessing model parsimony and the area under the curve (AUC). Results: The decision tree provided the most clinically useful model and had a good accuracy (AUC 0.720 95% confidence interval = 0.600-0.840). Percentage weight loss at 1 month (≥0.75%) was the strongest predictor for successful weight loss. Within those individuals losing ≥0.75%, individuals with a BMI (≥27 kg m-2) were more likely to be successful than those with a BMI between 25 and 27 kg m-2. Conclusions: Data mining methods can provide a more accurate way of assessing relationships when conventional assumptions are not met. In the present study, a decision tree provided the most parsimonious model. Given that early weight loss cannot be predicted before randomisation, incorporating this information into a post randomisation trial design may give better weight loss results

Improving Information on Maternal Medication Use by Linking Prescription Data to Congenital Anomaly Registers: A EUROmediCAT Study

Research on associations between medication use during pregnancy and congenital anomalies is significative for assessing the safe use of a medicine in pregnancy. Congenital anomaly (CA) registries do not have optimal information on medicine exposure, in contrast to prescription databases. Linkage of prescription databases to the CA registries is a potentially effective method of obtaining accurate information on medicine use in pregnancies and the risk of congenital anomalies. We linked data from primary care and prescription databases to five European Surveillance of Congenital Anomalies (EUROCAT) CA registries. The linkage was evaluated by looking at linkage rate, characteristics of linked and non-linked cases, first trimester exposure rates for six groups of medicines according to the prescription data and information on medication use registered in the CA databases, and agreement of exposure. Of the 52,619 cases registered in the CA databases, 26,552 could be linked. The linkage rate varied between registries over time and by type of birth. The first trimester exposure rates and the agreements between the databases varied for the different medicine groups. Information on anti-epileptic drugs and insulins and analogue medicine use recorded by CA registries was of good quality. For selective serotonin reuptake inhibitors, anti-asthmatics, antibacterials for systemic use, and gonadotropins and other ovulation stimulants, the recorded information was less complete. Linkage of primary care or prescription databases to CA registries improved the quality of information on maternal use of medicines in pregnancy, especially for medicine groups that are less fully registered in CA registries

Limited risks of major congenital anomalies in children of mothers with IBD and effects of medications

Background & aims: Concerns persist about the risk of major congenital anomalies in children of women with inflammatory bowel disease (IBD), and whether medication use affects risk. We assessed these risks, and variations in use of medications by women with IBD before, during, and after pregnancy. Methods: We accessed data on children born to women 15-45 y old from 1990 through 2010, using a mother-child linked dataset from an electronic database of primary care records containing medical diagnoses, events, and drug prescriptions from across the United Kingdom. We identified pregnant women with IBD, and all prescriptions for 5-aminosalicylates azathioprine/6-mercaptopurine, and corticosteroids were extracted from their primary care records. We calculated risks of major congenital anomaly in children of mothers with and without IBD, and in children exposed or not exposed to 5-aminosalicylates, azathioprine/6-mercaptopurine, or corticosteroids during their first trimester of fetal development. Logistic regression with a generalized estimating equation was used to provide risk estimates adjusted for confounders. We calculated proportions of women taking medications before, during, and after pregnancy and assessed whether cessation was associated with subsequent disease flares. Results: Risks of a major congenital anomaly in 1703 children of mothers with IBD and 384,811 children of mothers without IBD were 2.7% and 2.8%, respectively. This corresponded to an adjusted odds ratio of 0.98 (95% confidence interval [CI], 0.73-1.31). In children of women with IBD, the adjusted odds ratios of a major congenital anomaly associated with drug use were 0.82 (95% CI, 0.42-1.61) for 5-aminosalicylates 0.48 (95% CI, 0.15-1.50) for corticosteroids, and 1.27 (95% CI, 0.48-3.39) for azathioprine/6-mercaptopurine. No increases in heart, limb, or genital anomalies were found in children of women with IBD; 31.2% of women discontinued 5-aminosalicylates and 24.6% discontinued azathioprine/6-mercaptopurine in early pregnancy. The risk of flares later in pregnancy was not related to cessation of medication. Conclusions: We found no evidence that IBD during pregnancy or medical therapy for IBD during pregnancy increases the risk of a major congenital anomaly in children. Patients should receive appropriate guidance on use of medication before and during pregnancy

Avelines's Hole: An Unexpected Twist in the Tale

Aveline’s Hole is the largest known Early Mesolithic cemetery in Britain, previously thought to have no evidence for subsequent burial activity. Thus, it came as some surprise when the results of a recent ancient human DNA study found that, of four individuals from the site yielding genomic data, two showed high levels of ancestry from Early Neolithic Aegean farmers. Radiocarbon dating confirmed that these two individuals were indeed British Early Neolithic in date, while the other two had the expected ‘Western Hunter-Gatherer’ ancestry genomic signatures, with the two groups separated in time by nearly five millennia. Moreover, the two Neolithic samples were both crania, while the two Mesolithic samples were long bones. Given the absence of Neolithic dates in the previous sizeable dating programme combined with the difficult history of the collection, i.e., the WWII bombing of its Bristol repository, this raised the question of whether the crania might in fact be from another site. As we show in this paper, a very strong case can be made that the crania do in fact originate from Aveline’s Hole. Additional radiocarbon dating (14 in total, including the above mentioned four) suggests that about half the cranial elements from the site fall within the Early Neolithic, though there is still no evidence for the deposition of post-cranial remains at this time, nor is there any burial evidence in the long intervening period between the Early Mesolithic and the Early Neolithic. Intriguingly, craniometric analyses of legacy data including three crania lost in the bombing suggest that one, Aveline’s Hole ‘A’, may be Upper Palaeolithicin date. As part of this re-investigation of the human remains from the site, we present new stable carbon and nitrogen isotope analyses that differ significantly from those originally reported for the Early Mesolithic, with the new results more in keeping with other isotopic data for this period. We also present new stable carbon and nitrogen isotope results on human remains from the nearby Early Mesolithic sites of Badger Hole and Greylake, and report new Early Mesolithic radiocarbon dates and isotopic data from Cannington Park Quarry. Clear isotopic differences between the Early Mesolithic and the Neolithic remains can be seen, but these are argued to relate primarily to shifts in the underlying ecological baselines, rather than to differences in types of foods consumed (with the caveat that terrestrial wild and domesticated foods will be isotopically similar). The genetic data are summarised, giving evidence not only of the ancestry of Mesolithic and Neolithic individuals from Aveline’s Hole, but also suggesting something of their physical appearance. The degree of population replacement now indicated by ancient DNA suggests that there was a substantial migration of farmers into Britain at the start of the Neolithic. This new information demonstrates the archaeological importance of Aveline's Hole for both the Mesolithic and Neolithic periods."Funding for nine of the new radiocarbon dates from Aveline’s Hole reported here was provided by NERC’s NRCF programme (NF/2016/2/16). The ancient DNA study was funded by the Wellcome Trust (100713/Z/12/Z), as were three new radiocarbon dates from Aveline’s Hole. The isotopic analysis of the Badger Hole human remains was funded as part of a NERC studentship (NE/K500987/1)."https://www.ubss.org.uk/resources/proceedings/vol28/UBSS_Proc_28_1_9-63.pd

Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD.English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies.The presence and severity of NAFLD are associated with an increased risk and severity of CKD. Please see later in the article for the Editors' Summary.Italian Ministry of University/FIRB/MERIT RBNE08NKH7_00

Consumers' salient beliefs regarding dairy products in the functional food era: a qualitative study using concepts from the theory of planned behaviour

<p>Abstract</p> <p>Background</p> <p>Inadequate consumption of dairy products without appropriate dietary substitution may have deleterious health consequences. Social research reveals the factors that may impede compliance with dietary recommendations. This is particularly important given the recent introduction of functional dairy products. One of the challenges for public health professionals is to demonstrate the efficacy of nutrition education in improving attitudes toward nutrient rich foods. The aim of this study was to explore the salient beliefs of adult weight loss trial participants regarding both traditional and functional dairy products and to compare these with a control group not exposed to nutrition education.</p> <p>Methods</p> <p>Six focus groups were conducted, three with weight loss trial completers (<it>n </it>= 15) that had received nutrition education and three with individuals from the same region (<it>n </it>= 14) to act as controls. Transcribed focus groups were coded using the Theory of Planned Behaviour theoretical framework.</p> <p>Results</p> <p>Non-trial participants perceived dairy foods as weight inducing and were sceptical of functional dairy products. A lack of time/ability to decipher dairy food labels was also discussed by these individuals. In contrast trial participants discussed several health benefits related to dairy foods, practised label reading and were confident in their ability to incorporate dairy foods into their diet. Normative beliefs expressed were similar for both groups indicating that these were more static and less amenable to change through nutrition education than control and behavioural beliefs.</p> <p>Conclusions</p> <p>Nutrition education provided as a result of weight loss trial participation influenced behavioural and control beliefs relating to dairy products. This study provides a proof of concept indication that nutrition education may improve attitudes towards dairy products and may thus be an important target for public health campaigns seeking to increase intake of this food group.</p