Search

Background: In large-scale epidemiology, bloodspot sampling by fingerstick onto filter paper has many advantages, including ease and low costs of collection, processing and transport. We describe the development of an enzyme-linked immunoassay (ELISA) for quantifying insulin from dried blood spots and demonstrate its application in a large trial. Methods: We adapted an existing commercial kit (Mercodia Human Insulin ELISA, 10-1113-01) to quantify insulin from two 3-mm diameter discs (≈6 µL of blood) punched from whole blood standards and from trial samples. Paediatricians collected dried blood spots in a follow-up of 13,879 fasted children aged 11.5 years (interquartile range 11.3–11.8 years) from 31 trial sites across Belarus. We quantified bloodspot insulin levels and examined their distribution by demography and anthropometry. Results: Mean intra-assay (n = 157) coefficients of variation were 15% and 6% for ‘low’ (6.7 mU/L) and ‘high’ (23.1 mU/L) values, respectively; the respective inter-assay values (n = 33) were 23% and 11%. The intraclass correlation coefficient between 50 paired whole bloodspot versus serum samples, collected simultaneously, was 0.90 (95% confidence interval 0.85 to 0.95). Bloodspot insulin was stable for at least 31 months at −80°C, for one week at +30°C and following four freeze-thaw cycles. Paediatricians collected a median of 8 blood spots from 13,487 (97%) children. The geometric mean insulin (log standard deviation) concentrations amongst 12,812 children were 3.0 mU/L (1.1) in boys and 4.0 mU/L (1.0) in girls and were positively associated with pubertal stage, measures of central and peripheral adiposity, height and fasting glucose. Conclusions: Our simple and convenient bloodspot assay is suitable for the measurement of insulin in very small volumes of blood collected on filter paper cards and can be applied to large-scale epidemiology studies of the early-life determinants of circulating insulin.

Introduction: Respondent-driven sampling (RDS) offers a recruitment strategy for hard-to-reach populations. However, RDS faces logistical and theoretical challenges that threaten efficiency and validity in settings worldwide. We present innovative adaptations to conventional RDS to overcome barriers encountered in recruiting a large, representative sample of men who have sex with men (MSM) who travel internationally. Methods: Novel methodological adaptations for the “International Travel Research to Inform Prevention” or “I-TRIP” study were offering participants a choice between electronic and paper coupons referrals for recruitment and modifying the secondary incentives structure from small cash amounts to raffle entries for periodic large cash prize raffle drawings. Staged referral limit increases from 3 to 10 referrals and progressive addition of 70 seeds were also implemented. Results: There were 501 participants enrolled in up to 13 waves of growth. Among participants with a choice of referral methods, 81% selected electronic referrals. Of participants who were recruited electronically, 90% chose to remain with electronic referrals when it was their turn to recruit. The mean number of enrolled referrals was 0.91 for electronic referrals compared to 0.56 for paper coupons. Median referral lag time, i.e., the time interval between when recruiters were given their referrals and when a referred individual enrolled in the study, was 20 days (IQR 10–40) for electronic referrals, 20 days (IQR 8–58) for paper coupons, 20 days (IQR 10–41) for raffle entries and 33 days (IQR 16–148) for small cash incentives. Conclusions: The recruitment of MSM who travel internationally required maximizing known flexible tools of RDS while at the same time necessitating innovations to increase recruitment efficiency. Electronic referrals emerged as a major advantage in recruiting this hard-to-reach population who are of high socio-economic status, geographically diffuse and highly mobile. These enhancements may improve the performance of RDS in target populations with similar characteristics. [ABSTRACT FROM AUTHOR]

In a stratified analysis, the results from different strata if homogeneity assumption is met are pooled together to obtain a single summary estimate for the common effect parameter. However, the effect can appear homogeneous across strata using one measure but heterogeneous using another. Consequently, two researchers analyzing the same data can arrive at conflicting conclusions if they use different effect measures. In this paper, the author draws on the sufficient component cause model to develop a stratified-analysis method regarding a particular effect measure, the ‘peril ratio’. When there is no mechanistic interaction between the exposure under study and the stratifying variable (i.e., when they do not work together to complete any sufficient cause), the peril ratio is constant across strata. The author presents formulas for the estimation of such a common peril ratio. Three real data are re-analyzed for illustration. When the data is consistent with peril-ratio homogeneity in a stratified analysis, researchers can use the formulas in this paper to pool the strata. [ABSTRACT FROM AUTHOR]

Background: More than two-thirds of the world's HIV-positive individuals live in sub-Saharan Africa, where genetic susceptibility to kidney disease is high and resources for kidney disease screening and antiretroviral therapy (ART) toxicity monitoring are limited. Equations to estimate glomerular filtration rate (GFR) from serum creatinine were derived in Western populations and may be less accurate in this population. Methods: We compared results from published GFR estimating equations with a direct measure of GFR by iohexol clearance in 99 HIV-infected, ART-naïve Kenyan adults. Iohexol concentration was measured from dried blood spots on filter paper. The bias ratio (mean of the ratio of estimated to measured GFR) and accuracy (percentage of estimates within 30% of the measured GFR) were calculated. Results: The median age was 35 years, and 60% were women. The majority had asymptomatic HIV, with median CD4+ cell count of 355 cells/mm3. Median measured GFR was 115 mL/min/1.73 m2. Overall accuracy was highest for the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation. Consistent with a prior report, bias and accuracy were improved by eliminating the coefficient for black race (85% of estimates within 30% of measured GFR). Accuracy of all equations was poor in participants with GFR 60–90 mL/min/1.73 m2 (<65% of estimates within 30% of measured GFR), although this subgroup was too small to reach definitive conclusions. Conclusions: Overall accuracy was highest for the CKD-EPI equation. Eliminating the coefficient for race further improved performance. Future studies are needed to determine the most accurate GFR estimate for use in individuals with GFR <90 mL/min/1.73 m2, in whom accurate estimation of kidney function is important to guide drug dosing. Direct measurement of GFR by iohexol clearance using a filter paper based assay is feasible for research purposes in resource-limited settings, and could be used to develop more accurate GFR estimates in African populations. [ABSTRACT FROM AUTHOR]

Sample size calculations are an important part of research to balance the use of resources and to avoid undue harm to participants. Effect sizes are an integral part of these calculations and meaningful values are often unknown to the researcher. General recommendations for effect sizes have been proposed for several commonly used statistical procedures. For the analysis of tables, recommendations have been given for the correlation coefficient for binary data; however, it is well known that suffers from poor statistical properties. The odds ratio is not problematic, although recommendations based on objective reasoning do not exist. This paper proposes odds ratio recommendations that are anchored to for fixed marginal probabilities. It will further be demonstrated that the marginal assumptions can be relaxed resulting in more general results. [ABSTRACT FROM AUTHOR]

As a performance measure for a prediction model, the area under the receiver operating characteristic curve (AUC) is insensitive to the addition of strong markers. A number of measures sensitive to performance change have recently been proposed; however, these relative-performance measures may lead to self-contradictory conclusions. This paper examines alternative performance measures for prediction models: the Lorenz curve-based Gini and Pietra indices, and a standardized version of the Brier score, the scaled Brier. Computer simulations are performed in order to study the sensitivity of these measures to performance change when a new marker is added to a baseline model. When the discrimination power of the added marker is concentrated in the gray zone of the baseline model, the AUC and the Gini show minimal performance improvements. The Pietra and the scaled Brier show more significant improvements in the same situation, comparatively. The Pietra and the scaled Brier indices are therefore recommended for prediction model performance measurement, in light of their ease of interpretation, clinical relevance and sensitivity to gray-zone resolving markers. [ABSTRACT FROM AUTHOR]

Background: It is known that experience of a previous crash is related to incidence of future crashes in a cohort of New Zealand cyclists. This paper investigated if the strength of such association differed by crash involvement propensity and by the need for medical care in the previous crash. Methods: The Taupo Bicycle Study involved 2590 adult cyclists recruited in 2006 and followed over a median period of 4.6 years through linkage to four national databases. The crash involvement propensity was estimated using propensity scores based on the participants' demographic, cycling and residential characteristics. Cox regression modelling for repeated events was performed with multivariate and propensity score adjustments. Analyses were then stratified by quintiles of the propensity score. Results: A total of 801 (31.0%) participants reported having experienced at least one bicycle crash in the twelve months prior to the baseline survey. They had a higher risk of experiencing crash events during follow-up (hazard ratio (HR): 1.43; 95% CI: 1.28, 1.60) but in the stratified analysis, this association was significant only in the highest two quintiles of the propensity score where the likelihood of having experienced a crash was more than 33%. The association was stronger for previous crashes that had received medical care (HR 1.63; 95% CI: 1.41, 1.88) compared to those that had not (HR 1.30; 95% CI: 1.14, 1.49). Conclusions: Previous crash experience increased the risk of future crash involvement in high-risk cyclists and the association was stronger for previous crashes attended medically. What distinguishes the high risk group warrants closer investigation, and the findings indicate also that health service providers could play an important role in prevention of bicycle crash injuries. [ABSTRACT FROM AUTHOR]

With the proliferation of social networks and blogs, the Internet is increasingly being used to disseminate personal health information rather than just as a source of information. In this paper we exploit the wealth of user-generated data, available through the micro-blogging service Twitter, to estimate and track the incidence of health conditions in society. The method is based on two stages: we start by extracting possibly relevant tweets using a set of specially crafted regular expressions, and then classify these initial messages using machine learning methods. Furthermore, we selected relevant features to improve the results and the execution times. To test the method, we considered four health states or conditions, namely flu, depression, pregnancy and eating disorders, and two locations, Portugal and Spain. We present the results obtained and demonstrate that the detection results and the performance of the method are improved after feature selection. The results are promising, with areas under the receiver operating characteristic curve between 0.7 and 0.9, and f-measure values around 0.8 and 0.9. This fact indicates that such approach provides a feasible solution for measuring and tracking the evolution of health states within the society. [ABSTRACT FROM AUTHOR]

Individual behavioral response to the spreading of an epidemic plays a crucial role in the progression of the epidemic itself. The risk perception induces individuals to adopt a protective behavior, as for instance reducing their social contacts, adopting more restrictive hygienic measures or undergoing prophylaxis procedures. In this paper, starting with a previously developed lattice-gas SIR model, we construct a coupled behavior-disease model for influenza spreading with spontaneous behavioral changes. The focus is on self-initiated behavioral changes that alter the susceptibility to the disease, without altering the contact patterns among individuals. Three different mechanisms of awareness spreading are analyzed: the local spreading due to the presence in the neighborhood of infective individuals; the global spreading due to the news published by the mass media and to educational campaigns implemented at institutional level; the local spreading occurring through the “thought contagion” among aware and unaware individuals. The peculiarity of the present approach is that the awareness spreading model is calibrated on available data on awareness and concern of the population about the risk of contagion. In particular, the model is validated against the A(H1N1) epidemic outbreak in Italy during the season, by making use of the awareness data gathered by the behavioral risk factor surveillance system (PASSI). We find that, increasing the accordance between the simulated awareness spreading and the PASSI data on risk perception, the agreement between simulated and experimental epidemiological data improves as well. Furthermore, we show that, within our model, the primary mechanism to reproduce a realistic evolution of the awareness during an epidemic, is the one due to globally available information. This result highlights how crucial is the role of mass media and educational campaigns in influencing the epidemic spreading of infectious diseases. [ABSTRACT FROM AUTHOR]

The number of travel-acquired dengue infections has seen a consistent global rise over the past decade. An increased volume of international passenger air traffic originating from regions with endemic dengue has contributed to a rise in the number of dengue cases in both areas of endemicity and elsewhere. This paper reports results from a network-based risk assessment model which uses international passenger travel volumes, travel routes, travel distances, regional populations, and predictive species distribution models (for the two vector species, Aedes aegypti and Aedes albopictus) to quantify the relative risk posed by each airport in importing passengers with travel-acquired dengue infections. Two risk attributes are evaluated: (i) the risk posed by through traffic at each stopover airport and (ii) the risk posed by incoming travelers to each destination airport. The model results prioritize optimal locations (i.e., airports) for targeted dengue surveillance. The model is easily extendible to other vector-borne diseases. [ABSTRACT FROM AUTHOR]

Background: Up to 2% of suicides in young people may occur in clusters i.e., close together in time and space. In early 2008 unprecedented attention was given by national and international news media to a suspected suicide cluster among young people living in Bridgend, Wales. This paper investigates the strength of statistical evidence for this apparent cluster, its size, and temporal and geographical limits. Methods and findings: The analysis is based on official mortality statistics for Wales for 2000–2009 provided by the UK's Office for National Statistics (ONS). Temporo-spatial analysis was performed using Space Time Permutation Scan Statistics with SaTScan v9.1 for suicide deaths aged 15 and over, with a sub-group analysis focussing on cases aged 15–34 years. These analyses were conducted for deaths coded by ONS as: (i) suicide or of undetermined intent (probable suicides) and (ii) for a combination of suicide, undetermined, and accidental poisoning and hanging (possible suicides). The temporo-spatial analysis did not identify any clusters of suicide or undetermined intent deaths (probable suicides). However, analysis of all deaths by suicide, undetermined intent, accidental poisoning and accidental hanging (possible suicides) identified a temporo-spatial cluster (p = 0.029) involving 10 deaths amongst 15–34 year olds centred on the County Borough of Bridgend for the period 27th December 2007 to 19th February 2008. Less than 1% of possible suicides in younger people in Wales in the ten year period were identified as being cluster-related. Conclusions: There was a possible suicide cluster in young people in Bridgend between December 2007 and February 2008. This cluster was smaller, shorter in duration, and predominantly later than the phenomenon that was reported in national and international print media. Further investigation of factors leading to the onset and termination of this series of deaths, in particular the role of the media, is required. [ABSTRACT FROM AUTHOR]

Advances in next-generation sequencing technologies have enabled the identification of multiple rare single nucleotide polymorphisms involved in diseases or traits. Several strategies for identifying rare variants that contribute to disease susceptibility have recently been proposed. An important feature of many of these statistical methods is the pooling or collapsing of multiple rare single nucleotide variants to achieve a reasonably high frequency and effect. However, if the pooled rare variants are associated with the trait in different directions, then the pooling may weaken the signal, thereby reducing its statistical power. In the present paper, we propose a backward support vector machine (BSVM)-based variant selection procedure to identify informative disease-associated rare variants. In the selection procedure, the rare variants are weighted and collapsed according to their positive or negative associations with the disease, which may be associated with common variants and rare variants with protective, deleterious, or neutral effects. This nonparametric variant selection procedure is able to account for confounding factors and can also be adopted in other regression frameworks. The results of a simulation study and a data example show that the proposed BSVM approach is more powerful than four other approaches under the considered scenarios, while maintaining valid type I errors. [ABSTRACT FROM AUTHOR]

We consider the recently introduced edge-based compartmental models (EBCM) for the spread of susceptible-infected-recovered (SIR) diseases in networks. These models differ from standard infectious disease models by focusing on the status of a random partner in the population, rather than a random individual. This change in focus leads to simple analytic models for the spread of SIR diseases in random networks with heterogeneous degree. In this paper we extend this approach to handle deviations of the disease or population from the simplistic assumptions of earlier work. We allow the population to have structure due to effects such as demographic features or multiple types of risk behavior. We allow the disease to have more complicated natural history. Although we introduce these modifications in the static network context, it is straightforward to incorporate them into dynamic network models. We also consider serosorting, which requires using dynamic network models. The basic methods we use to derive these generalizations are widely applicable, and so it is straightforward to introduce many other generalizations not considered here. Our goal is twofold: to provide a number of examples generalizing the EBCM method for various different population or disease structures and to provide insight into how to derive such a model under new sets of assumptions. [ABSTRACT FROM AUTHOR]

Background: Physical activity is inversely correlated to morbidity and mortality risk. Large cohort studies use wearable accelerometer devices to measure physical activity objectively, providing data potentially relevant to identify different activity patterns and to correlate these to health-related outcome measures. A method to compute relevant characteristics of such data not only with regard to duration and intensity, but also to regularity of activity events, is necessary. The aims of this paper are to propose a new method – the ATLAS index (Activity Types from Long-term Accelerometric Sensor data) – to derive generic measures for distinguishing different characteristic activity phenotypes from accelerometer data, to propose a comprehensive graphical representation, and to conduct a proof-of-concept with long-term measurements from different devices and cohorts. Methods: The ATLAS index consists of the three dimensions regularity (reg), duration (dur) and intensity (int) of relevant activity events identified in long-term accelerometer data. It can be regarded as a 3D vector and represented in a 3D cube graph. 12 exemplary data sets of three different cohort studies with 99,467 minutes of data were chosen for concept validation. Results: Five archetypical activity types are proposed along with their dimensional characteristics (insufficiently active: low reg, int and dur; busy bee: low dur and int, high reg; cardio-active: medium reg, int and dur, endurance athlete: high reg, int and dur; and weekend warrior: high int and dur, low reg). The data sets are displayed in one common graph, indicating characteristic differences in activity patterns. Conclusion: The ATLAS index incorporates the relevant regularity dimension apart from the widely-used measures of duration and intensity. Along with the 3D representation, it allows to compare different activity types in cohort study populations, both visually and computationally using vector distance measures. Further research is necessary to validate the ATLAS index in order to find normative values and group centroids. [ABSTRACT FROM AUTHOR]

Background: Recent focus on earlier detection of pathogen introduction in human and animal populations has led to the development of surveillance systems based on automated monitoring of health data. Real- or near real-time monitoring of pre-diagnostic data requires automated classification of records into syndromes–syndromic surveillance–using algorithms that incorporate medical knowledge in a reliable and efficient way, while remaining comprehensible to end users. Methods: This paper describes the application of two of machine learning (Naïve Bayes and Decision Trees) and rule-based methods to extract syndromic information from laboratory test requests submitted to a veterinary diagnostic laboratory. Results: High performance (F1-macro = 0.9995) was achieved through the use of a rule-based syndrome classifier, based on rule induction followed by manual modification during the construction phase, which also resulted in clear interpretability of the resulting classification process. An unmodified rule induction algorithm achieved an F1-micro score of 0.979 though this fell to 0.677 when performance for individual classes was averaged in an unweighted manner (F1-macro), due to the fact that the algorithm failed to learn 3 of the 16 classes from the training set. Decision Trees showed equal interpretability to the rule-based approaches, but achieved an F1-micro score of 0.923 (falling to 0.311 when classes are given equal weight). A Naïve Bayes classifier learned all classes and achieved high performance (F1-micro = 0.994 and F1-macro = .955), however the classification process is not transparent to the domain experts. Conclusion: The use of a manually customised rule set allowed for the development of a system for classification of laboratory tests into syndromic groups with very high performance, and high interpretability by the domain experts. Further research is required to develop internal validation rules in order to establish automated methods to update model rules without user input. [ABSTRACT FROM AUTHOR]

Measurement of malaria burden is fraught with complexity, due to the natural history of the disease, delays in seeking treatment or failure of case management. Attempts to establish an appropriate case definition for a malaria episode has often resulted in ambiguities and challenges because of poor information about treatment seeking, patterns of infection, recurrence of fever and asymptomatic infection. While the primary reason for treating malaria is to reduce disease burden, the effects of treatment are generally ignored in estimates of the burden of malaria morbidity, which are usually presented in terms of numbers of clinical cases or episodes, with the main data sources being reports from health facilities and parasite prevalence surveys. The use of burden estimates that do not consider effects of treatment, leads to under-estimation of the impact of improvements in case management. Official estimates of burden very likely massively underestimate the impact of the roll-out of ACT as first-line therapy across Africa. This paper proposes a novel approach for estimating burden of disease based on the point prevalence of malaria attributable disease, or equivalently, the days with malaria fever in unit time. The technique makes use of data available from standard community surveys, analyses of fever patterns in malaria therapy patients, and data on recall bias. Application of this approach to data from Zambia for 2009–2010 gave an estimate of 2.6 (95% credible interval: 1.5–3.7) malaria attributable fever days per child-year. The estimates of recall bias, and of the numbers of days with illness contributing to single illness recalls, could be applied more generally. To obtain valid estimates of the overall malaria burden using these methods, there remains a need for surveys to include the whole range of ages of hosts in the population and for data on seasonality patterns in confirmed case series. [ABSTRACT FROM AUTHOR]

Background: Research using electronic health records (EHRs) relies heavily on coded clinical data. Due to variation in coding practices, it can be difficult to aggregate the codes for a condition in order to define cases. This paper describes a methodology to develop ‘indicator markers’ found in patients with early rheumatoid arthritis (RA); these are a broader range of codes which may allow a probabilistic case definition to use in cases where no diagnostic code is yet recorded. Methods: We examined EHRs of 5,843 patients in the General Practice Research Database, aged ≥30y, with a first coded diagnosis of RA between 2005 and 2008. Lists of indicator markers for RA were developed initially by panels of clinicians drawing up code-lists and then modified based on scrutiny of available data. The prevalence of indicator markers, and their temporal relationship to RA codes, was examined in patients from 3y before to 14d after recorded RA diagnosis. Findings: Indicator markers were common throughout EHRs of RA patients, with 83.5% having 2 or more markers. 34% of patients received a disease-specific prescription before RA was coded; 42% had a referral to rheumatology, and 63% had a test for rheumatoid factor. 65% had at least one joint symptom or sign recorded and in 44% this was at least 6-months before recorded RA diagnosis. Conclusion: Indicator markers of RA may be valuable for case definition in cases which do not yet have a diagnostic code. The clinical diagnosis of RA is likely to occur some months before it is coded, shown by markers frequently occurring ≥6 months before recorded diagnosis. It is difficult to differentiate delay in diagnosis from delay in recording. Information concealed in free text may be required for the accurate identification of patients and to assess the quality of care in general practice. [ABSTRACT FROM AUTHOR]

Background: Graphical representation of data is one of the most easily comprehended forms of explanation. The current study describes a simple visualization tool which may allow greater understanding of medical and epidemiological data. Method: We propose a simple tool for visualization of data, known as a “quilt plot”, that provides an alternative to presenting large volumes of data as frequency tables. Data from the Australian Needle and Syringe Program survey are used to illustrate “quilt plots”. Conclusion: Visualization of large volumes of data using “quilt plots” enhances interpretation of medical and epidemiological data. Such intuitive presentations are particularly useful for the rapid assessment of problems in the data which cannot be readily identified by manual review. We recommend that, where possible, “quilt plots” be used along with traditional quantitative assessments of the data as an explanatory data analysis tool. [ABSTRACT FROM AUTHOR]

Disease control is of paramount importance in public health, with infectious disease extinction as the ultimate goal. Although diseases may go extinct due to random loss of effective contacts where the infection is transmitted to new susceptible individuals, the time to extinction in the absence of control may be prohibitively long. Intervention controls are typically defined on a deterministic schedule. In reality, however, such policies are administered as a random process, while still possessing a mean period. Here, we consider the effect of randomly distributed intervention as disease control on large finite populations. We show explicitly how intervention control, based on mean period and treatment fraction, modulates the average extinction times as a function of population size and rate of infection spread. In particular, our results show an exponential improvement in extinction times even though the controls are implemented using a random Poisson distribution. Finally, we discover those parameter regimes where random treatment yields an exponential improvement in extinction times over the application of strictly periodic intervention. The implication of our results is discussed in light of the availability of limited resources for control. [ABSTRACT FROM AUTHOR]

Background: The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. Methods and Results: This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i)As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13–0.67 and 0.20,0.09–0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50–0.93 and 0.55,0.28–1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57–0.92 and 0.43,0.22–0.83). ii)Mothers interested in probiotics or research or reporting infants’ adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9–13.1%) to 4.6%(−1.4–+10.5%), and OR from 0.40(0.18–0.91) to 0.56(0.26–1.21). Other findings were unchanged. Conclusions: Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. Trial Registration: This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children. [ABSTRACT FROM AUTHOR]

The objectives of this paper are to predict life years lost associated with obesity-related diseases (ORDs) for U.S. non-smoking adults, and to examine the relationship between those ORDs and mortality. Data from the National Health Interview Survey, 1997–2000, were used. We employed mixed proportional hazard models to estimate the association between those ORDs and mortality and used simulations to project life years lost associated with the ORDs. We found that obesity-attributable comorbidities are associated with large decreases in life years and increases in mortality rates. The life years lost associated with ORDs is more marked for younger adults than older adults, for blacks than whites, for males than females, and for the more obese than the less obese. Using U.S. non-smoking adults aged 40 to 49 years as an example to illustrate percentage of the life years lost associated with ORDs, we found that the mean life years lost associated with ORDs for U.S. non-smoking black males aged 40 to 49 years with a body mass index above 40 kg/m2 was 5.43 years, which translates to a 7.5% reduction in total life years. White males of the same age range and same degree of obesity lost 5.23 life years on average – a 6.8% reduction in total life years, followed by black females (5.04 years, a 6.5% reduction in life years), and white females (4.7 years, a 5.8% reduction in life years). Overall, ORDs increased chances of dying and lessened life years by 0.2 to 11.7 years depending on gender, race, BMI classification, and age. [ABSTRACT FROM AUTHOR]

Background: Population-based studies provide the understanding of health-need required for effective public health policy and service-planning. Mental disorders are an important but, until recently, neglected agenda in global health. This paper reviews the coverage and limitations in global epidemiological data for mental disorders and suggests strategies to strengthen the data. Methods: Systematic reviews were conducted for population-based epidemiological studies in mental disorders to inform new estimates for the global burden of disease study. Estimates of population coverage were calculated, adjusted for study parameters (age, gender and sampling frames) to quantify regional coverage. Results: Of the 77,000 data sources identified, fewer than 1% could be used for deriving national estimates of prevalence, incidence, remission, and mortality in mental disorders. The two major limitations were (1) highly variable regional coverage, and (2) important methodological issues that prevented synthesis across studies, including the use of varying case definitions, the selection of samples not allowing generalization, lack of standardized indicators, and incomplete reporting. North America and Australasia had the most complete prevalence data for mental disorders while coverage was highly variable across Europe, Latin America, and Asia Pacific, and poor in other regions of Asia and Africa. Nationally-representative data for incidence, remission, and mortality were sparse across most of the world. Discussion: Recent calls to action for global mental health were predicated on the high prevalence and disability of mental disorders. However, the global picture of disorders is inadequate for planning. Global data coverage is not commensurate with other important health problems, and for most of the world's population, mental disorders are invisible and remain a low priority. [ABSTRACT FROM AUTHOR]

Objectives: The paper describes the creation of a new scale to measure intimate partner violence (IPV) among gay and bisexual men. Methods: Seven focus group discussions were held with gay and bisexual men, focusing on defining intimate partner violence: 30 forms of IPV were identified. A venue-recruited sample of 912 gay and bisexual men was surveyed, examining definitional understanding and recent experiences of each of the 30 forms of IPV. Participants were also asked questions from the CDC definition of intimate partner violence and the short-form of the Conflicts Tactics Scale (CTS2S). Factor analysis of responses to the definitional questions was used to create the IPV-GBM scale, and the prevalence of intimate partner violence was compared with that identified by the CDC and CTS2S measures of intimate partner violence. Results: A 23-item scale, with 5 unique domains, was created, with strong internal reliability (Cronbach Alpha >.90). The IPV-GBM scale mirrored both the CDC and CTS2S definitions of intimate partner violence, but contained additional domains such as controlling violence, monitoring behaviors, emotional violence, and HIV-related violence. The new scale identified a significantly higher prevalence of IPV than either of the more commonly used measures. Conclusions: The results presented here provide encouraging evidence for a new, more accurate measure of intimate partner violence among gay and bisexual men in the U.S. [ABSTRACT FROM AUTHOR]

Background: Intravaginal practices (IVP) are highly prevalent in sub-Saharan African and have been implicated as risk factors for HIV acquisition. However, types of IVP vary between populations, and detailed information on IVP among women at risk for HIV in different populations is needed. We investigated IVP among women who practice transactional sex in two populations: semi-urban, facility workers in Tanzania who engage in opportunistic sex work; and urban, self-identified sex workers and bar workers in Uganda. The aim of the study was to describe and compare IVP using a daily pictorial diary. Methodology/Principal Findings: Two hundred women were recruited from a HIV prevention intervention feasibility study in Kampala, Uganda and in North-West Tanzania. Women were given diaries to record IVP daily for six weeks. Baseline data showed that Ugandan participants had more lifetime partners and transactional sex than Tanzanian participants. Results from the diary showed that 96% of Tanzanian participants and 100% of Ugandan participants reported intravaginal cleansing during the six week study period. The most common types of cleansing were with water only or water and soap. In both countries, intravaginal insertion (e.g. with herbs) was less common than cleansing, but insertion was practiced by more participants in Uganda (46%) than in Tanzania (10%). In Uganda, participants also reported more frequent sex, and more insertion related to sex. In both populations, cleansing was more often reported on days with reported sex and during menstruation, and in Uganda, when participants experienced vaginal discomfort. Participants were more likely to cleanse after sex if they reported no condom use. Conclusions: While intravaginal cleansing was commonly practiced in both cohorts, there was higher frequency of cleansing and insertion in Uganda. Differences in IVP were likely to reflect differences in sexual behaviour between populations, and may warrant different approaches to interventions targeting IVP. Vaginal practices among women at high risk in Uganda and Tanzania: recorded behaviour from a daily pictorial diary. [ABSTRACT FROM AUTHOR]

This article provides a fully Bayesian approach for modeling of single-dose and complete pharmacokinetic data in a population pharmacokinetic (PK) model. To overcome the impact of outliers and the difficulty of computation, a generalized linear model is chosen with the hypothesis that the errors follow a multivariate Student t distribution which is a heavy-tailed distribution. The aim of this study is to investigate and implement the performance of the multivariate t distribution to analyze population pharmacokinetic data. Bayesian predictive inferences and the Metropolis-Hastings algorithm schemes are used to process the intractable posterior integration. The precision and accuracy of the proposed model are illustrated by the simulating data and a real example of theophylline data. [ABSTRACT FROM AUTHOR]

Background: MDM2 is a major negative regulator of p53, and a single nucleotide polymorphism (SNP) in the MDM2 promoter region SNP309 has been demonstrated to be associated with an increased MDM2 expression and a significantly earlier age of onset of several tumors, including gastric cancer. Several studies were published to evaluate the association between SNP309 and gastric cancer risk. However, the results remain conflicting rather than conclusive. Objective: The aim of this study was to assess the association between the MDM2 SNP309 polymorphism and gastric risk. Methods: We performed a meta-analysis to investigate this relationship. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Results: Five published case-control studies, including 1,621 gastric cancer cases and 2,639 controls were identified. We found that the MDM2 SNP309 polymorphism was associated with a significantly increased risk of gastric cancer risk when all studies were pooled into the meta-analysis (GG versus TT, OR = 1.54; 95%CI = 1.04–2.29, and GG versus GT/TT, OR = 1.49, 95%CI = 1.30–1.72). Furthermore, Egger's test did not show any evidence of publication bias (P = 0.799 for GG versus TT). Conclusion: Our results suggest that the MDM2 SNP309 polymorphism may be a low-penetrant risk factor for the development of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: In epidemiological studies, measures of body fat generally are obtained through anthropometric indices such as the body mass index (BMI), waist (WC), and hip circumferences (HC). Such indices, however, can only provide estimates of a person’s true body fat content, overall or by adipose compartment, and may have limited accuracy, especially for the visceral adipose compartment (VAT). Objective: To determine the extent to which different body adipose tissue compartments are adequately predicted by anthropometry, and to identify anthropometric measures alone, or in combination to predict overall adiposity and specific adipose tissue compartments, independently of age and body size (height). Methods: In a sub-study of 1,192 participants of the German EPIC (European Prospective Investigation into Cancer and Nutrition) cohorts, whole-body MRI was performed to determine adipose and muscle tissue compartments. Additional anthropometric measurements of BMI, WC and HC were taken. Results: After adjusting for age and height, BMI, WC and HC were better predictors of total body volume (TBV), total adipose tissue (TAT) and subcutaneous adipose tissue (SAT) than for VAT, coronary adipose tissue (CAT) and skeletal muscle tissue (SMT). In both sexes, BMI was the best predictor for TBV (men: r = 0.72 [0.68–0.76], women: r = 0.80 [0.77–0.83]) and SMT (men: r = 0.52 [0.45–0.57], women: r = 0.48 [0.41–0.54]). WC was the best predictor variable for TAT (r = 0.48 [0.41–0.54]), VAT (r = 0.44 [0.37–0.50]) and CAT (r = 0.34 [0.26–0.41]) (men), and for VAT (r = 0.42 [0.35–0.49]) and CAT (r = 0.29 [0.22–0.37]) (women). BMI was the best predictor for TAT (r = 0.49 [0.43–0.55]) (women). HC was the best predictor for SAT (men (r = 0.39 [0.32–0.45]) and women (r = 0.52 [0.46–0.58])). Conclusions: Especially the volumes of internal body fat compartments are poorly predicted by anthropometry. A possible implication may be that associations of chronic disease risks with the sizes of internal body fat as measured by BMI, WC and HC may be strongly underestimated. [ABSTRACT FROM AUTHOR]

Genotyping of Klebsiella pneumoniae is indispensable for management of nosocomial infections, monitoring of emerging strains –including extended-spectrum beta-lactamase (ESBL) producers-, and general epidemiology. Such objectives require a high-resolution genotyping method with a fixed scheme that allows (1) long-term retrospective and prospective assessment, (2) objective result readout and (3) library storage for database development and exchangeable results. We have developed a multiple-locus variable number tandem repeat analysis (MLVA) using a single-tube fluorescently primed multiplex PCR for 8 Variable Number Tandem Repeats (VNTRs) and automated fragment size analysis. The type allocation scheme was optimized using 224 K. pneumoniae clinical isolates, which yielded 101 MLVA types. The method was compared to the gold standard multilocus sequence typing (MLST) using a subset of these clinical isolates (n = 95) and found to be highly concordant, with at least as high a resolution but with considerably less hands-on time. Our results position this MLVA scheme as an appropriate, high-throughput and relatively low-cost tool for K. pneumoniae epidemiology. [ABSTRACT FROM AUTHOR]

Background: We investigated the relationship between average monthly temperature and the most common clinical pathogens causing infections in intensive care patients. Methods: A prospective unit-based study in 73 German intensive care units located in 41 different hospitals and 31 different cities with total 188,949 pathogen isolates (102,377 Gram-positives and 86,572 Gram-negatives) from 2001 to 2012. We estimated the relationship between the number of clinical pathogens per month and the average temperature in the month of isolation and in the month prior to isolation while adjusting for confounders and long-term trends using time series analysis. Adjusted incidence rate ratios for temperature parameters were estimated based on generalized estimating equation models which account for clustering effects. Results: The incidence density of Gram-negative pathogens was 15% (IRR 1.15, 95%CI 1.10–1.21) higher at temperatures ≥20°C than at temperatures below 5°C. E. cloacae occurred 43% (IRR = 1.43; 95%CI 1.31–1.56) more frequently at high temperatures, A. baumannii 37% (IRR = 1.37; 95%CI 1.11–1.69), S. maltophilia 32% (IRR = 1.32; 95%CI 1.12–1.57), K. pneumoniae 26% (IRR = 1.26; 95%CI 1.13–1.39), Citrobacter spp. 19% (IRR = 1.19; 95%CI 0.99–1.44) and coagulase-negative staphylococci 13% (IRR = 1.13; 95%CI 1.04–1.22). By contrast, S. pneumoniae 35% (IRR = 0.65; 95%CI 0.50–0.84) less frequently isolated at high temperatures. For each 5°C increase, we observed a 3% (IRR = 1.03; 95%CI 1.02–1.04) increase of Gram-negative pathogens. This increase was highest for A. baumannii with 8% (IRR = 1.08; 95%CI 1.05–1.12) followed by K. pneumoniae, Citrobacter spp. and E. cloacae with 7%. Conclusion: Clinical pathogens vary by incidence density with temperature. Significant higher incidence densities of Gram-negative pathogens were observed during summer whereas S. pneumoniae peaked in winter. There is increasing evidence that different seasonality due to physiologic changes underlies host susceptibility to different bacterial pathogens. Even if the underlying mechanisms are not yet clear, the temperature-dependent seasonality of pathogens has implications for infection control and study design. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis is a bacterial disease caused by Mycobacterium bovis in livestock and wildlife with hosts that include Eurasian badgers (Meles meles), brushtail possum (Trichosurus vulpecula), and white-tailed deer (Odocoileus virginianus). Risk-assessment efforts in Michigan have been initiated on farms to minimize interactions of cattle with wildlife hosts but research on M. bovis on cattle farms has not investigated the spatial context of disease epidemiology. To incorporate spatially explicit data, initial likelihood of infection probabilities for cattle farms tested for M. bovis, prevalence of M. bovis in white-tailed deer, deer density, and environmental variables for each farm were modeled in a Bayesian hierarchical framework. We used geo-referenced locations of 762 cattle farms that have been tested for M. bovis, white-tailed deer prevalence, and several environmental variables that may lead to long-term survival and viability of M. bovis on farms and surrounding habitats (i.e., soil type, habitat type). Bayesian hierarchical analyses identified deer prevalence and proportion of sandy soil within our sampling grid as the most supported model. Analysis of cattle farms tested for M. bovis identified that for every 1% increase in sandy soil resulted in an increase in odds of infection by 4%. Our analysis revealed that the influence of prevalence of M. bovis in white-tailed deer was still a concern even after considerable efforts to prevent cattle interactions with white-tailed deer through on-farm mitigation and reduction in the deer population. Cattle farms test positive for M. bovis annually in our study area suggesting that the potential for an environmental source either on farms or in the surrounding landscape may contributing to new or re-infections with M. bovis. Our research provides an initial assessment of potential environmental factors that could be incorporated into additional modeling efforts as more knowledge of deer herd factors and cattle farm prevalence is documented. [ABSTRACT FROM AUTHOR]

Socioeconomic status has a robust positive relationship with several health outcomes at the individual and population levels, but in the case of HIV prevalence, income inequality may be a better predictor than absolute level of income. Most studies showing a relationship between income inequality and HIV have used entire countries as the unit of analysis. In this study, we examine the association between income inequality at the community level and HIV prevalence in a sample of persons who inject drugs (PWID) in a concentrated epidemic setting. We recruited PWID and non-PWID community participants in Thai Nguyen, Vietnam, and administered a cross-sectional questionnaire; PWID were tested for HIV. We used ecologic regression to model HIV burden in our PWID study population on GINI indices of inequality calculated from total reported incomes of non-PWID community members in each commune. We also modeled HIV burden on interaction terms between GINI index and median commune income, and finally used a multi-level model to control for community level inequality and individual level income. HIV burden among PWID was significantly correlated with the commune GINI coefficient (r = 0.53, p = 0.002). HIV burden was also associated with GINI coefficient (β = 0.082, p = 0.008) and with median commune income (β = −0.018, p = 0.023) in ecological regression. In the multi-level model, higher GINI coefficient at the community level was associated with higher odds of individual HIV infection in PWID (OR = 1.46 per 0.01, p = 0.003) while higher personal income was associated with reduced odds of infection (OR = 0.98 per $10, p = 0.022). This study demonstrates a context where income inequality is associated with HIV prevalence at the community level in a concentrated epidemic. It further suggests that community level socioeconomic factors, both contextual and compositional, could be indirect determinants of HIV infection in PWID. [ABSTRACT FROM AUTHOR]

Objective: We examined the association between occupational lifting during pregnancy and risk of fetal death and preterm birth using a job exposure matrix (JEM). Methods: For 68,086 occupationally active women in the Danish National Birth Cohort, interview information on occupational lifting was collected around gestational week 16. We established a JEM based on information from women, who were still pregnant when interviewed. The JEM provided mean total loads lifted per day within homogeneous exposure groups as informed by job and industry codes. All women were assigned an exposure estimate from the JEM. We used Cox regression models with gestational age as underlying time variable and adjustment for covariates. Results: We observed 2,717 fetal deaths and 3,128 preterm births within the study cohort. No exposure-response relation was observed for fetal death, but for women with a prior fetal death, we found a hazard ratio (HR) of 2.87 (95% CI 1.37, 6.01) for stillbirth (fetal death ≥22 completed gestational weeks) among those who lifted >200 kg/day. For preterm birth, we found an exposure-response relation for primigravid women, reaching a HR of 1.43 (95% CI 1.13, 1.80) for total loads >200 kg per day. These findings correspond to an excess fraction of 11% for stillbirth and 10% for preterm birth. Conclusion: We found an increased risk of stillbirth among women with a prior fetal death, who lifted >200 kg/day, and an exposure-response relationship between occupational lifting and preterm birth among primigravid women. The study adds to a large body of prospective studies on occupational lifting and adverse pregnancy outcomes by refined exposure assessment. [ABSTRACT FROM AUTHOR]

Background: Internet-based biosurveillance systems have been developed to detect health threats using information available on the Internet, but system performance has not been assessed relative to end-user needs and perspectives. Method and Findings: Infectious disease events from the French Institute for Public Health Surveillance (InVS) weekly international epidemiological bulletin published in 2010 were used to construct the gold-standard official dataset. Data from six biosurveillance systems were used to detect raw signals (infectious disease events from informal Internet sources): Argus, BioCaster, GPHIN, HealthMap, MedISys and ProMED-mail. Crude detection rates (C-DR), crude sensitivity rates (C-Se) and intrinsic sensitivity rates (I-Se) were calculated from multivariable regressions to evaluate the systems’ performance (events detected compared to the gold-standard) 472 raw signals (Internet disease reports) related to the 86 events included in the gold-standard data set were retrieved from the six systems. 84 events were detected before their publication in the gold-standard. The type of sources utilised by the systems varied significantly (p<0001). I-Se varied significantly from 43% to 71% (p = 0001) whereas other indicators were similar (C-DR: p = 020; C-Se, p = 013). I-Se was significantly associated with individual systems, types of system, languages, regions of occurrence, and types of infectious disease. Conversely, no statistical difference of C-DR was observed after adjustment for other variables. Conclusion: Although differences could result from a biosurveillance system's conceptual design, findings suggest that the combined expertise amongst systems enhances early detection performance for detection of infectious diseases. While all systems showed similar early detection performance, systems including human moderation were found to have a 53% higher I-Se (p = 00001) after adjustment for other variables. Overall, the use of moderation, sources, languages, regions of occurrence, and types of cases were found to influence system performance. [ABSTRACT FROM AUTHOR]

Background: Sequential cohort design (SCD) applying matching for propensity scores (PS) in accrual periods has been proposed to mitigate bias caused by channeling when calendar time is a proxy for strong confounders. We studied the channeling of patients according to atorvastatin and simvastatin initiation in Finland, starting from the market introduction of atorvastatin in 1998, and explored the SCD PS approach to analyzing the comparative effectiveness of atorvastatin versus simvastatin in the prevention of cardiovascular events (CVE). Methods: Initiators of atorvastatin or simvastatin use in the 45–75-year age range in 1998–2006 were characterized by their propensity of receiving atorvastatin over simvastatin, as estimated for 17 six-month periods. Atorvastatin (10 mg) and simvastatin (20 mg) initiators were matched 1∶1 on the PS, as estimated for the whole cohort and within each period. Cox regression models were fitted conventionally, and also for the PS matched cohort and the periodically PS matched cohort, to estimate the hazard ratios (HR) for CVEs. Findings: Atorvastatin (10 mg) was associated with a 11%–12% lower incidence of CVE in comparison with simvastatin (20 mg). The HR estimates were the same for a conventional Cox model (0.88, 95% confidence interval 0.85–0.91), for the analysis in which the PS was used to match across all periods and the Cox model was adjusted for strong confounders (0.89, 0.85–0.92), and for the analysis in which PS matching was applied within sequential periods (0.88, 0.84–0.92). The HR from a traditional PS matched analysis was 0.80 (0.77–0.83). Conclusions: The SCD PS approach produced effect estimates similar to those obtained in matching for PS within the whole cohort and adjusting the outcome model for strong confounders, but at the cost of efficiency. A traditional PS matched analysis without further adjustment in the outcome model produced estimates further away from unity. [ABSTRACT FROM AUTHOR]

Background: Physical inactivity, ambient air pollution and obesity are modifiable risk factors for non-communicable diseases, with the first accounting for 10% of premature deaths worldwide. Although community level interventions may target each simultaneously, research on the relationship between these risk factors is lacking. Objectives: After comparing spatial interpolation methods to determine the best predictor for particulate matter (PM2.5; PM10) and ozone (O3) exposures throughout the U.S., we evaluated the cross-sectional association of ambient air pollution with leisure-time physical inactivity among adults. Methods: In this cross-sectional study, we assessed leisure-time physical inactivity using individual self-reported survey data from the Centers for Disease Control and Prevention's 2011 Behavioral Risk Factor Surveillance System. These data were combined with county-level U.S. Environmental Protection Agency air pollution exposure estimates using two interpolation methods (Inverse Distance Weighting and Empirical Bayesian Kriging). Finally, we evaluated whether those exposed to higher levels of air pollution were less active by performing logistic regression, adjusting for demographic and behavioral risk factors, and after stratifying by body weight category. Results: With Empirical Bayesian Kriging air pollution values, we estimated a statistically significant 16–35% relative increase in the odds of leisure-time physical inactivity per exposure class increase of PM2.5 in the fully adjusted model across the normal weight respondents (p-value<0.0001). Evidence suggested a relationship between the increasing dose of PM2.5 exposure and the increasing odds of physical inactivity. Conclusions: In a nationally representative, cross-sectional sample, increased community level air pollution is associated with reduced leisure-time physical activity particularly among the normal weight. Although our design precludes a causal inference, these results provide additional evidence that air pollution should be investigated as an environmental determinant of inactivity. [ABSTRACT FROM AUTHOR]

Aims: Hepatic steatosis has been related to insulin resistance and increased diabetes risk. We assessed whether combination of diabetes risk factors, evaluated by the Finnish Diabetes Risk Score, was associated with risk of hepatic steatosis in an apparently healthy Chinese population. Research Design and Methods: The study samples were from a community-based health examination survey in central China. In total 1,780 men and women (18–64 y) were included in the final analyses. Hepatic steatosis was diagnosed by ultrasonography. We created combination of diabetes risk factors score on basis of age, Body Mass Index, waist circumference, physical activity at least 4 h a week, daily consumption of fruits, berries or vegetables, history of antihypertensive drug treatment, history of high blood glucose. The total risk score is a simple sum of the individual weights, and values range from 0 to 20. Results: Hepatic steatosis was present 18% in the total population. In multivariate models, the odds ratios of hepatic steatosis were 1.20 (95%CI 1.15–1.25) in men and 1.25 (95%CI 1.14–1.37) in women by each unit increase in the combination of diabetes risk factors score, after adjustment for blood pressure, liver enzymes, plasma lipids, and fasting glucose. The area under the receiver operating characteristic curve for hepatic steatosis was 0.78 (95%CI 0.76–0.80), 0.76 in men (95%CI 0.74–0.78) and 0.83 (95%CI 0.79–0.87) in women. Conclusions: Our data suggest that combination of major diabetes risk factors was significantly related to risk of hepatic steatosis in Chinese adults. [ABSTRACT FROM AUTHOR]

Although there are great changes of dietary in the past few decades in China, few are known about the aluminium exposure in Chinese diet. The aim of this study is to systematically evaluate the dietary aluminium intake level in residents of Shenzhen, China. A total of 853 persons from 244 household were investigated their diet by three days food records. Finally, 149 kinds of foods in 17 food groups were selected to be the most consumed foods. From them, 1399 food samples were collected from market to test aluminium concentration. High aluminium levels were found in jellyfish (median, 527.5 mg/kg), fried twisted cruller (median, 466.0 mg/kg), shell (median, 107.1 mg/kg). The Shenzhen residents' average dietary aluminium exposure was estimated at 1.263 mg/kg bw/week which is lower than the PTWI (provisional tolerable weekly intake). But 0–2 and 3–13 age groups have the highest aluminium intake exceeding the PTWI (3.356 mg/kg bw/week and 3.248 mg/kg bw/week) than other age groups. And the main dietary aluminium exposure sources are fried twisted cruller, leaf vegetables and bean products. Our study suggested that even three decades rapid economy development, children in Shenzhen still have high dietary aluminium exposure risk. How to control high dietary aluminium exposure still is a great public health challenge in Shenzhen, China. [ABSTRACT FROM AUTHOR]

Background: The high burden of HIV infections among female sex workers (FSW) in sub-Saharan Africa has been long recognised, but effective preventive interventions have largely not been taken to scale. We undertook a national geographical mapping exercise in 2011/2012 to assess the locations and population size of FSW in Kenya, to facilitate targeted HIV prevention services for this population. Methods and Findings: We used a geographical mapping approach, consisting of interviews with secondary key informants to identify “hot” spots frequented by FSW, their operational dynamics and the estimated numbers of FSW in those spots. This was followed by validation of the estimates through interviews with FSW at each spot identified. The mapping covered Nairobi, the capital city of Kenya, and 50 other major urban centres. In total, 11,609 secondary key informant interviews were conducted to identify FSW spots. Further, a total of 6,360 FSW were interviewed for spot validation purposes. A total of 10,670 spots where FSW congregate were identified. The estimated FSW population in all the towns mapped was 103,298 (range 77,878 to 128, 717). Size estimates in the towns mapped were extended to smaller towns that were not mapped, using a statistical model. The national urban FSW population estimate was 138,420 (range 107, 552 to 169, 288), covering all towns of over 5,000 population. We estimated that approximately 5% of the urban female population of reproductive age in Kenya could be sex workers, which is consistent with previous estimates from other sub-Saharan African countries. Conclusions: This study provides the first national level data on the size of the FSW population in Kenya. These data can be used to enhance HIV prevention programme planning and implementation for FSW, to form the basis for impact evaluations, and to improve programme coverage by directing efforts to locations with the greatest need. [ABSTRACT FROM AUTHOR]

Characterizing the force of infection (FOI) is an essential part of planning cost effective control strategies for zoonotic diseases. Echinococcus multilocularis is the causative agent of alveolar echinococcosis in humans, a serious disease with a high fatality rate and an increasing global spread. Red foxes are high prevalence hosts of E. multilocularis. Through a mathematical modelling approach, using field data collected from in and around the city of Zurich, Switzerland, we find compelling evidence that the FOI is periodic with highly variable amplitude, and, while this amplitude is similar across habitat types, the mean FOI differs markedly between urban and periurban habitats suggesting a considerable risk differential. The FOI, during an annual cycle, ranges from (0.1,0.8) insults (95% CI) in urban habitat in the summer to (9.4, 9.7) (95% CI) in periurban (rural) habitat in winter. Such large temporal and spatial variations in FOI suggest that control strategies are optimal when tailored to local FOI dynamics. [ABSTRACT FROM AUTHOR]

Background: Variability in patients' postoperative pain experience and response to treatment challenges effective pain management. Variability in pain reflects individual differences in inhibitory pain modulation and psychological sensitivity, which in turn may be clinically relevant for the disposition to acquire pain. The aim of this study was to investigate the effects of conditioned pain modulation and situational pain catastrophizing on postoperative pain and pain persistency. Methods: Preoperatively, 42 healthy males undergoing funnel chest surgery completed the Spielberger's State-Trait Anxiety Inventory and Beck's Depression Inventory before undergoing a sequential conditioned pain modulation paradigm. Subsequently, the Pain Catastrophizing Scale was introduced and patients were instructed to reference the conditioning pain while answering. Ratings of movement-evoked pain and consumption of morphine equivalents were obtained during postoperative days 2–5. Pain was reevaluated at six months postoperatively. Results: Patients reporting persistent pain at six months follow-up (n = 15) were not significantly different from pain-free patients (n = 16) concerning preoperative conditioned pain modulation response (Z = 1.0, P = 0.3) or level of catastrophizing (Z = 0.4, P = 1.0). In the acute postoperative phase, situational pain catastrophizing predicted movement-evoked pain, independently of anxiety and depression (β = 1.0, P = 0.007) whereas conditioned pain modulation predicted morphine consumption (β = −0.005, P = 0.001). Conclusions: Preoperative conditioned pain modulation and situational pain catastrophizing were not associated with the development of persistent postoperative pain following funnel chest repair. Secondary outcome analyses indicated that conditioned pain modulation predicted morphine consumption and situational pain catastrophizing predicted movement-evoked pain intensity in the acute postoperative phase. These findings may have important implications for developing strategies to treat or prevent acute postoperative pain in selected patients. Pain may be predicted and the malfunctioning pain inhibition mechanism as tested with CPM may be treated with suitable drugs augmenting descending inhibition. [ABSTRACT FROM AUTHOR]

Objective: Development and validation of a selective and sensitive LCMS method for the determination of methotrexate polyglutamates in dried blood spots (DBS). Methods: DBS samples [spiked or patient samples] were prepared by applying blood to Guthrie cards which was then dried at room temperature. The method utilised 6-mm disks punched from the DBS samples (equivalent to approximately 12 µl of whole blood). The simple treatment procedure was based on protein precipitation using perchloric acid followed by solid phase extraction using MAX cartridges. The extracted sample was chromatographed using a reversed phase system involving an Atlantis T3-C18 column (3 µm, 2.1×150 mm) preceded by Atlantis guard column of matching chemistry. Analytes were subjected to LCMS analysis using positive electrospray ionization. Key Results: The method was linear over the range 5–400 nmol/L. The limits of detection and quantification were 1.6 and 5 nmol/L for individual polyglutamates and 1.5 and 4.5 nmol/L for total polyglutamates, respectively. The method has been applied successfully to the determination of DBS finger-prick samples from 47 paediatric patients and results confirmed with concentrations measured in matched RBC samples using conventional HPLC-UV technique. Conclusions and Clinical Relevance: The methodology has a potential for application in a range of clinical studies (e.g. pharmacokinetic evaluations or medication adherence assessment) since it is minimally invasive and easy to perform, potentially allowing parents to take blood samples at home. The feasibility of using DBS sampling can be of major value for future clinical trials or clinical care in paediatric rheumatology. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have demonstrated sulpiride to be significantly more effective than haloperidol, risperidone and olanzapine in schizophrenic treatment; however, only limited information is available on the potential risks associated with sulpiride treatment. This study attempts to provide information on the potential risks of sulpiride treatment of schizophrenia, especially with regard to unexpected adverse effects. Materials and Methods: Patients with schizophrenia aged 18 and older, newly prescribed with a single antipsychotic medication from the National Health Insurance Research Database of Taiwan in the period from 2003 to 2010 were included. A within-subject comparison method, prescription sequence symmetry analysis (PSSA) was employed to efficiently identify potential causal relationships while controlling for potential selection bias. Results: A total of 5,750 patients, with a mean age of 39, approximately half of whom were male, constituted the study cohort. The PSSA found that sulpiride was associated with EPS (adjusted SR, 1.73; 95% CI, 1.46–2.06) and hyperprolactinemia (12.04; 1.59–91.2). In comparison, EPS caused by haloperidol has a magnitude of 1.99 when analyzed with PSSA, and hyperprolactinemia caused by amisulpride has a magnitude of 8.05, respectively. Another finding was the unexpected increase in the use of stomatological corticosteroids, emollient laxatives, dermatological preparations of corticosteroids, quinolone antibacterials, and topical products for joint and muscular pain, after initiation of sulpiride treatment. Conclusions: We found sulpiride to be associated with an increased risk of EPS and hyperprolactinemia, and the potential risk could be as high as that induced by haloperidol and amisulpride, respectively. Additionally, our study provides grounds for future investigations into the associations between sulpiride and the increased use of additional drugs for managing adverse effects, including stomatological, dermatological, and musculoskeletal or joint side effects, constipation, and pneumonia. [ABSTRACT FROM AUTHOR]

Background: Most maternal deaths occur in developing countries and most maternal deaths are avoidable. China has made a great effort to reduce MMR by three quarters to meet the fifth Millennium Development Goal (MDG5). Methods: This retrospective study reviewed and analyzed maternal death data in Wuhan from 2001 to 2012. Joinpoint regression and multivariate Poisson regression was conducted using the log-linear model to measure the association of the number of maternal deaths with time, cause of death, where the death occurred, and cognitive factors including knowledge, attitude, resource, and management stratified. Results: The MMR declined from 33.41 per 100,000 live births in 2001 to 10.63 per 100,000 live births in 2012, with a total decline of 68.18% and an average annual decline of 9.89%. From 2001–2012, the four major causes of maternal death were obstetric hemorrhage (35.16%), pregnancy complications (28.57%), amniotic fluid embolism (16.48%) and gestational hypertension (8.79%). Multivariate Poisson regression showed on average the MMR decreased by.17% each year from 2001–2006 and stayed stagnant since 2007–2012. Conclusions: With the reduction in MMR in obstetric death (e.g. obstetric hemorrhage), there had been a remarkable reduction in MMR in Wuhan in 2001–2012, which may be due to (1) the improvement in the obstetric quality of perinatal care service on prevention and treatment of obstetric hemorrhage and emergency care skills, and (2) the improvement in the maternal health management and quality of prenatal care. Interventions to further reduce the MMR include several efforts such as the following: (1) designing community-based interventions, (2) providing subsidies to rural women and/hospitals for hospital delivery, (3) screening for pregnancy complications, and (4) establishing an emergency rescue system for critically ill pregnant women. [ABSTRACT FROM AUTHOR]

Background: Little is known about patterns of physical activity engaged in by youth after they immigrate to a new country. This study aims to investigate relationships between immigrant generation and ethnicity with physical activity, and to determine if the relationship between immigrant generation and physical activity was modified by ethnicity. Methods: The data sources were Cycle 6 (2009–2010) of the Canadian Health Behaviour in School-Aged Children Study and the 2006 Canada Census of Population. Participants (weighted n = 23,124) were young people from grades 6–10 in 436 schools. Students were asked where they were born, how long ago they moved to Canada, their ethnicity, and how many days a week they accumulated at least 60 minutes of moderate-to-vigorous physical activity (MVPA). Results: Youth born outside of Canada were less likely to be active than peers born in Canada; 11% vs 15% reported 7 days/week of at least 60 minutes of MVPA (p = .001). MVPA increased with time since immigration. Compared to Canadian-born youth, youth who immigrated within the last 1–2 years were less likely to get sufficient MVPA on 4–6 days/week (odds ratio: 0.66, 95% confidence interval: 0.53–0.82) and 7 days/week (0.62; 0.43–0.89). East and South-East Asian youth were less active, regardless of time since immigration: 4–6 days/week (0.67; 0.58–0.79) and 7 days/week (0.37; 0.29–0.48). Conclusion: Time since immigration and ethnicity were associated with MVPA among Canadian youth. Mechanisms by which these differences occur need to be uncovered in order to identify barriers to physical activity participation among youth. [ABSTRACT FROM AUTHOR]

Globally, incidence of Neisseria gonorrhoeae infection is once again the highest of the bacterial sexually transmitted infections. The bacterium can produce serious complications in those infected, and emerging resistance to third generation cephalosporins could usher in an era of potentially untreatable gonorrhea. This research aimed to identify risk factors for antibiotic resistant gonorrhea infection among clients at a Shanghai sexually transmitted infection clinic over two time periods, 2004–2005 and 2008–2011. Demographic and risk factor behavior data, and biological samples for antimicrobial resistance analysis, were collected. Statistical models were built to identify risk factors associated with probable resistance to ceftriaxone and resistance to penicillin and tetracycline. High levels of ciprofloxacin resistance (98%) in our sample precluded examining its risk factors; all isolates were susceptible to spectinomycin. Overall (P<0.001), chromosomal (P<0.001), and plasmid-mediated (P = 0.01) penicillin resistance decreased from the first to second period of the study. For tetracycline, chromosomal resistance decreased (P = 0.01) and plasmid-mediated resistance increased (P<0.001) between the first and second periods of study. In multi-level multivariable regression models, male gender (P = 0.03) and older age (P = 0.01) were associated with increased minimum inhibitory concentrations to ceftriaxone. Male gender (P = 0.03) and alcohol use (P = 0.02) were associated with increased odds of overall tetracycline resistance. Male gender was associated with increased odds of chromosomally-mediated tetracycline resistance (P = 0.04), and alcohol use was associated with increased odds of plasmid-mediated tetracycline resistance (P = 0.02). Additionally, individuals in middle-salary categories were found to have lower odds of plasmid-mediated resistance to tetracycline compared with those in the lowest salary category (P≤0.02). This study is one of the first to use multilevel analysis to consider the association between risk factors for gonorrhea infections and mechanisms of resistance to individual antibiotics. Such information is urgently needed to combat the growing threat of untreatable gonorrhea. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B is regarded as a serious public health issue in Lao People's Democratic Republic (Lao PDR), a Southeast Asian country. However, disease epidemiology among the general population is not well known, and thus a nationwide cross-sectional survey for hepatitis B surface antigen (HBsAg) prevalence in children and their mothers was conducted. Methods and findings: We applied three-stage cluster sampling using probability proportionate to size. After randomly selecting child (5 to 9 years old) and mother (15 to 45 years old) pairs from the selected villages, questionnaires and HBsAg rapid tests were conducted. Data from 965 child and mother pairs were analyzed. Multivariate logistic regression analyses were used to investigate the independent association of individual background characteristics for the odds of being HBsAg positive. In total, 17 children and 27 mothers were HBsAg positive. HBsAg prevalence was estimated to be 1.7% (95% confidence interval: 0.8%-2.6%) in children, and 2.9% (95% confidence interval: 1.7%–4.2%) in their mothers after taking sampling design and weight of each sample into account. Mother's infection status was positively associated with HBsAg positivity in children (p<0.001), whereas other potential risk factors, such as ethnicity, proximity to health centers, and history of surgery, were not. There were no significant associations between mother's HBsAg status and history of surgery, and other sociodemographic factors. Conclusions: Despite the slow implementation of the hepatitis B vaccination program, HBsAg prevalence among children and their mothers was not high in Lao PDR compared to reports from neighboring countries. The reasons for the differences in prevalence among these countries are unclear. We recommend that prevalence surveys be conducted in populations born before and after the implementation of a hepatitis B vaccination program to better understand the epidemiology of hepatitis B. [ABSTRACT FROM AUTHOR]

Molluscum contagiosum virus (MCV) is a significant but underreported skin pathogen for children and adults. Seroprevalence studies can help establish burden of disease. Enzyme linked immunosorbent assay (ELISA) based studies have been published for Australian and Japanese populations and the results indicate seroprevalences between 6 and 22 percent in healthy individuals, respectively. To investigate seroprevalence in Europe, we have developed a recombinant ELISA using a truncated MCV virion surface protein MC084 (V123-R230) expressed in E. coli. The ELISA was found to be sensitive and specific, with low inter- and intra-assay variability. Sera from 289 German adults and children aged 0–40 years (median age 21 years) were analysed for antibodies against MC084 by direct binding ELISA. The overall seropositivity rate was found to be 14.8%. The seropositivity rate was low in children below the age of one (4.5%), peaked in children aged 2–10 years (25%), and fell again in older populations (11–40 years; 12.5%). Ten out of 33 healthy UK individuals (30.3%; median age 27 years) had detectable MC084 antibodies. MCV seroconversion was more common in dermatological and autoimmune disorders, than in immunocompromised patients or in patients with multiple sclerosis. Overall MCV seroprevalence is 2.1 fold higher in females than in males in a UK serum collection. German seroprevalences determined in the MC084 ELISA (14.8%) are at least three times higher than incidence of MC in a comparable Swiss population (4.9%). While results are not strictly comparable, this is lower than Australian seroprevalence in a virion based ELISA (n = 357; 23%; 1999), but higher than the seroprevalence reported in a Japanese study using an N-terminal truncation of MC133 (n = 108, 6%; 2000. We report the first large scale serological survey of MC in Europe (n = 393) and the first MCV ELISA based on viral antigen expressed in E. coli. [ABSTRACT FROM AUTHOR]

Introduction: Findings regarding the association between overweight and all-cause mortality range from significantly lower to higher risk, compared with body-mass-index (BMI) within the “normal” range. Methods: We examined empirically potential methodological explanations for these apparently conflicting results using questionnaire and linked mortality data from 246,314 individuals aged ≥45 years in the Australian 45 and Up Study (11,127 deaths; median follow-up 3.9 years). Hazard ratios (HR) for all-cause mortality associated with BMI were modelled according to different methods of accounting for illness at baseline, finer versus broader gradations of BMI and choice of reference group, adjusting for potential confounders. Results: In analyses using the broad World Health Organization (WHO) categories, the all-cause mortality HR was significantly lower in the overweight category (25.0–29.99 kg/m2), than the normal weight (18.5–24.99 kg/m2) category. However, in analyses accounting for baseline illness, which excluded those with pre-existing illness at baseline, ever-smokers and the first 2 years of follow up, absolute age-standardised mortality rates varied up to two-fold between finer BMI categories within the WHO normal weight category; rates were lowest at 22.5–24.99 kg/m2 and mortality HRs increased steadily for BMI above (ptrend<0.02) and below (ptrend<0.003) this reference category. Hence, the breadth of the BMI categories used and whether or not baseline illness is accounted for explain the apparent discrepancies between reported BMI-mortality associations. Conclusion: Using fine BMI categories and the category with the lowest absolute rates as the reference group and accounting for the potential confounding effects of baseline illness is likely to yield the most reliable risk estimates for establishing the independent relationship of BMI to all-cause mortality. These results and those of other studies indicate that a BMI of 22.5–24.99 kg/m2, not the broad “overweight” category of 25–29.99 kg/m2, was associated with the most favourable mortality risk. [ABSTRACT FROM AUTHOR]