Determinants of non-adherence to treatment for tuberculosis in high-income and middle-income settings: a systematic review protocol

INTRODUCTION: Treatment for tuberculosis (TB) is highly effective if taken according to prescribed schedules. However, many people have difficulty adhering to treatment which can lead to poorer clinical outcomes, the development of drug resistance, increased duration of infectivity and consequent onward transmission of infection. A range of approaches are available to support adherence but in order to target these effectively a better understanding of the predictors of poor adherence is needed. This review aims to highlight the personal, sociocultural and structural factors that may lead to poor adherence in high-income and middle-income settings. METHODS AND ANALYSIS: Seven electronic databases, Medline, EMBASE, CINAHL, PsycInfo, The Cochrane Library, Scopus and Web of Science, will be searched for relevant articles using a prespecified search strategy. Observational studies will be targeted to explore factors that influence adherence to treatment in individuals diagnosed with TB. Screening title and abstract followed by full-text screening and critical appraisal will be conducted by two researchers. Data will be extracted using the Population, Exposure, Comparator, Outcomes, Study characteristics framework. For cross-study assessment of strength of evidence for particular risk factors affecting adherence we will use the Grading of Recommendations, Assessment, Development and Evaluation tool modified for prognostic studies. A narrative synthesis of the studies will be compiled. A meta-analysis will be considered if there are sufficient numbers of studies that are homogenous in study design, population and outcomes. DISSEMINATION: A draft conceptual framework will be identified that (A) identifies key barriers to adherence at each contextual level (eg, personal, sociocultural, health systems) and (B) maps the relationships, pathways and mechanisms of effect between these factors and adherence outcomes for people with TB. The draft conceptual framework will guide targeting of adherence interventions and further research. PROSPERO REGISTRATION NUMBER: CRD42017061049

Personalized modeling for prediction with decision-path models

Deriving predictive models in medicine typically relies on a population approach where a single model is developed from a dataset of individuals. In this paper we describe and evaluate a personalized approach in which we construct a new type of decision tree model called decision-path model that takes advantage of the particular features of a given person of interest. We introduce three personalized methods that derive personalized decision-path models. We compared the performance of these methods to that of Classification And Regression Tree (CART) that is a population decision tree to predict seven different outcomes in five medical datasets. Two of the three personalized methods performed statistically significantly better on area under the ROC curve (AUC) and Brier skill score compared to CART. The personalized approach of learning decision path models is a new approach for predictive modeling that can perform better than a population approach

Interaction effects at crossings of spin-polarized one-dimensional subbands

We report conductance measurements of ballistic one-dimensional (1D) wires defined in GaAs/AlGaAs heterostructures in an in-plane magnetic field, B. When the Zeeman energy is equal to the 1D subband energy spacing, the spin-split subband Nup arrow intersects (N+1)down arrow, where N is the index of the spin-degenerate 1D subband. At the crossing of N=1up arrow and N=2down arrow subbands, there is a spontaneous splitting giving rise to an additional conductance structure evolving from the 1.5(2e(2)/h) plateau. With further increase in B, the structure develops into a plateau and lowers to 2e(2)/h. With increasing temperature and magnetic field the structure shows characteristics of the 0.7 structure. Our results suggest that at low densities a spontaneous spin splitting occurs whenever two 1D subbands of opposite spins cross

Whole slide image registration for the study of tumor heterogeneity

Consecutive thin sections of tissue samples make it possible to study local variation in e.g. protein expression and tumor heterogeneity by staining for a new protein in each section. In order to compare and correlate patterns of different proteins, the images have to be registered with high accuracy. The problem we want to solve is registration of gigapixel whole slide images (WSI). This presents 3 challenges: (i) Images are very large; (ii) Thin sections result in artifacts that make global affine registration prone to very large local errors; (iii) Local affine registration is required to preserve correct tissue morphology (local size, shape and texture). In our approach we compare WSI registration based on automatic and manual feature selection on either the full image or natural sub-regions (as opposed to square tiles). Working with natural sub-regions, in an interactive tool makes it possible to exclude regions containing scientifically irrelevant information. We also present a new way to visualize local registration quality by a Registration Confidence Map (RCM). With this method, intra-tumor heterogeneity and charateristics of the tumor microenvironment can be observed and quantified.Comment: MICCAI2018 - Computational Pathology and Ophthalmic Medical Image Analysis - COMPA

Weight Trajectories from Birth and Bone Mineralization at 7 Years of Age

Objective: To assess whether different trajectories of weight gain since birth influence bone mineral content (BMC) and areal bone mineral density (aBMD) at 7 years of age. Study design: We studied a subsample of 1889 children from the Generation XXI birth cohort who underwent whole-body dual-energy radiograph absorptiometry. Weight trajectories identified through normal mixture modeling for model-based clustering and labeled “normal weight gain,” “weight gain during infancy,” “weight gain during childhood,” and “persistent weight gain” were used. Differences in subtotal BMC, aBMD, and size-corrected BMC (scBMC) at age 7 years according to weight trajectories were estimated through analysis of covariance. Results: Compared with the “normal weight gain” trajectory, children in the remaining trajectories had significantly greater BMC, aBMD, and scBMC at age 7 years, with the strongest associations for “persistent weight gain” (girls [BMC: 674.0 vs 559.8 g, aBMD: 0.677 vs 0.588 g/cm2, scBMC: 640.7 vs 577.4 g], boys [BMC: 689.4 vs 580.8 g, aBMD: 0.682 vs 0.611 g/cm2, scBMC: 633.0 vs 595.6 g]). After adjustment for current weight, and alternatively for fat and lean mass, children with a “weight gain during childhood” trajectory had greater BMC and aBMD than those with a “normal weight gain” trajectory, although significant differences were restricted to girls (BMC: 601.4 vs 589.2 g, aBMD: 0.618 vs 0.609 g/cm2). Conclusion: Overall, children following a trajectory of persistent weight gain since birth had clearly increased bone mass at 7 years, but weight gain seemed slightly more beneficial when it occurred later rather than on a normal trajectory during the first 7 years of life

Finite element models of the tibiofemoral joint: A review of validation approaches and modelling challenges

The knee joint is a complex mechanical system, and computational modelling can provide vital information for the prediction of disease progression and of the potential for therapeutic interventions. This review provides an overview of the challenges involved in developing finite element models of the tibiofemoral joint, including the representation of appropriate geometry and material properties, loads and motions, and establishing pertinent outputs. The importance of validation for computational models in biomechanics has been highlighted by a number of papers, and finite element models of the tibiofemoral joint are a particular area in which validation can be challenging, due to the complex nature of the knee joint, its geometry and its constituent tissue properties. A variety of study designs have emerged to tackle these challenges, and these can be categorised into several different types. The role of validation, and the strategies adopted by these different study types, are discussed. Models representing trends and sensitivities often utilise generic representations of the knee and provide conclusions with relevance to general populations, usually without explicit validation. Models representing in vitro specimens or in vivo subjects can, to varying extents, be more explicitly validated, and their conclusions are more subject-specific. The potential for these approaches to examine the effects of patient variation is explored, which could lead to future applications in defining how treatments may be stratified for subgroups of patients

Epidemiological evidence of higher susceptibility to vCJD in the young

BACKGROUND: The strikingly young age of new variant Creutzfeldt-Jacob disease (vCJD) cases remains unexplained. Age dependent susceptibility to infection has been put forward, but differential dietary exposure to contaminated food products in the UK population according to age and sex during the bovine spongiform encephalopathy (BSE) epidemic may provide a simpler explanation. METHODS: Using recently published estimates of dietary exposure in mathematical models of the epidemiology of the new variant Creutzfeldt Jacob disease (vCJD), we examine whether the age characteristics of vCJD cases may be reproduced. RESULTS: The susceptibility/exposure risk function has likely peaked in adolescents and was followed by a sharp decrease with age, evocative of the profile of exposure to bovine material consumption according to age. However, assuming that the risk of contamination was proportional to exposure, with no age dependent susceptibility, the model failed to reproduce the observed age characteristics of the vCJD cases: The predicted cumulated proportion of cases over 40 years was 48%, in strong disagreement with the observed 10%. Incorporating age dependent susceptibility led to a cumulated proportion of cases over 40 years old of 12%. CONCLUSIONS: This analysis provides evidence that differential dietary exposure alone fails to explain the pattern of age in vCJD cases. Decreasing age related susceptibility is required to reproduce the characteristics of the age distribution of vCJD cases

Patient-specific parameterised cam geometry in finite element models of femoroacetabular impingement of the hip

Background Impingement resulting in soft tissue damage has been observed in hips with abnormal morphologies. Geometric parameterisation can be used to automatically generate a range of bone geometries for use in computational models, including femurs with cam deformity on the femoral neck. Methods This study verified patient-specific parametric finite element models of 20 patients with cam deformity (10 female, 10 male) through comparison to their patient-specific segmentation-based equivalents. The parameterisation system was then used to generate further models with parametrically defined geometry to investigate morphological changes in both the femur and acetabulum and their effects on impingement. Findings Similar findings were observed between segmentation-based and parametric models when assessing soft tissue strains under impingement conditions, resulting from high flexion and internal rotations. Parametric models with cam morphology demonstrated that clinically used alpha angles should not be relied on for estimating impingement severity since planar views do not capture the full three-dimensional geometry of the joint. Furthermore, the parametric approach allowed study of labral shape changes, indicating higher strains can result from bony overcoverage. Interpretation The position of cams, as well as their size, can affect the level of soft tissue strain occurring in the hip. This highlights the importance of reporting the full details of three-dimensional geometry used when developing computational models of the hip joint and suggests that it could be beneficial to stratify the patient population when considering treatment options, since certain morphologies may be at greater risk of elevated soft tissue strain

Updated projections of future vCJD deaths in the UK

BACKGROUND: Past projections of the future course of the vCJD epidemic in the UK have shown considerable uncertainty, with wide confidence bounds. However, recent vCJD case data have indicated a decrease in the annual incidence of deaths over the past two years. METHODS: A detailed survival model is fitted to the 121 vCJD deaths reported by the end of 2002 stratified by age and calendar time to obtain projections of future incidence. The model is additionally fitted to recent results from a survey of appendix tissues. RESULTS: Our results show a substantial decrease in the uncertainty of the future course of the primary epidemic in the susceptible genotype (MM-homozygous at codon 129 of the prion protein gene), with a best estimate of 40 future deaths (95% prediction interval 9–540) based on fitting to the vCJD case data alone. Additional fitting of the appendix data increases these estimates (best estimate 100, 95% prediction interval 10–2,600) but remains lower than previous projections. CONCLUSIONS: The primary vCJD epidemic in the known susceptible genotype in the UK appears to be in decline