228 research outputs found

    Prediction-based classification for longitudinal biomarkers

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    Assessment of circulating CD4 count change over time in HIV-infected subjects on antiretroviral therapy (ART) is a central component of disease monitoring. The increasing number of HIV-infected subjects starting therapy and the limited capacity to support CD4 count testing within resource-limited settings have fueled interest in identifying correlates of CD4 count change such as total lymphocyte count, among others. The application of modeling techniques will be essential to this endeavor due to the typically nonlinear CD4 trajectory over time and the multiple input variables necessary for capturing CD4 variability. We propose a prediction-based classification approach that involves first stage modeling and subsequent classification based on clinically meaningful thresholds. This approach draws on existing analytical methods described in the receiver operating characteristic curve literature while presenting an extension for handling a continuous outcome. Application of this method to an independent test sample results in greater than 98% positive predictive value for CD4 count change. The prediction algorithm is derived based on a cohort of n=270n=270 HIV-1 infected individuals from the Royal Free Hospital, London who were followed for up to three years from initiation of ART. A test sample comprised of n=72n=72 individuals from Philadelphia and followed for a similar length of time is used for validation. Results suggest that this approach may be a useful tool for prioritizing limited laboratory resources for CD4 testing after subjects start antiretroviral therapy.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS326 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

    High-Risk Contexts for Violence Against Women: Using Latent Class Analysis to Understand Structural and Contextual Drivers of Intimate Partner Violence at the National Level

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    Introduction: Intimate partner violence (IPV) affects 1 in 3 women and poses a major human rights threat and public health burden, yet there is great variation in risk globally. Whilst individual risk factors are well-studied, less research has focussed on the structural and contextual drivers of IPV and how these co-occur to create contexts of high risk. Methods: We compiled IPV drivers from freely-accessible global country-level data sources and combined gender inequality, natural disasters, conflict, colonialism, socioeconomic development and inequality, homicide and social discrimination in a latent class analysis, and identified underlying 'risk contexts' based on fit statistics and theoretical plausibility (N=5,732 country-years; 190 countries). We used multinomial regression to compare risk contexts according to: proportion of population with disability, HIV/AIDS, refugee status, and mental health disorders; proportion of men with drug use disorders; men's alcohol consumption; and population median age (N=1,654-5,725 country-years). Finally, we compared prevalence of physical and/or sexual IPV experienced by women in the past 12 months across risk contexts (N=3,175 country-years). Results: Three distinct risk contexts were identified: 1) non-patriarchal egalitarian, low rates of homicide; 2) patriarchal post-colonial, high rates of homicide; 3) patriarchal post-colonial conflict and disaster-affected. Compared to non-patriarchal egalitarian contexts, patriarchal post-colonial contexts had a younger age distribution and a higher prevalence of drug use disorders, but a lower prevalence of mental health disorders and a smaller refugee population. IPV risk was highest in the two patriarchal post-colonial contexts and associated with country income classification. Conclusions: Whilst our findings support the importance of gender norms in shaping women's risk of experiencing IPV, they also point towards an association with a history of colonialism. To effectively address IPV for women in high prevalence contexts, structural interventions and policies are needed that address not only gender norms, but also broader structural inequalities arising from colonialism

    Parental leave in European Companies

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    Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

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    Background No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011. Methods Two definitions were evaluated; RP definition A: An average eGFR decline (slope) ≥5 ml/min/1.73 m2/year over four years of follow-up with ≥3 eGFR measurements/year, last eGFR <90 ml/min/1.73 m2 and an absolute decline ≥5 ml/min/1.73 m2/year in two consecutive years. RP definition B: An absolute annual decline ≥5 ml/min/1.73 m2/year in each year and last eGFR <90 ml/min/1.73 m2. Sensitivity analyses were performed considering two and three years' follow-up. The percentage with and without RP who went on to subsequently develop incident chronic kidney disease (CKD; 2 consecutive eGFRs <60 ml/min/1.73 m2 and 3 months apart) was calculated. Results 22,603 individuals had baseline eGFR ≥90 ml/min/1.73 m2. 108/3655 (3.0%) individuals with ≥4 years' follow-up and ≥3 measurements/year experienced RP under definition A; similar proportions were observed when considering follow-up periods of three (n=195/6375; 3.1%) and two years (n=355/10756; 3.3%). In contrast under RP definition B, greater proportions experienced RP when considering two years (n=476/10756; 4.4%) instead of three (n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years' follow-up. For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD. Conclusions Our results suggest using three years' follow-up and at least two eGFR measurements per year is most appropriate for a RP definition, as it allows inclusion of a reasonable number of individuals and is associated with the known risk factors. The definition does not necessarily identify all those that progress to incident CKD, however, it can be used alongside other renal measurements to early identify and assess those at risk of developing CKD. Future analyses will use this definition to identify other risk factors for RP, including the role of antiretrovirals

    UK-Wide Multicenter Evaluation of Second-line Therapies in Primary Biliary Cholangitis

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    Background &amp; aims: thirty-to-forty percent of patients with primary biliary cholangitis inadequately respond to ursodeoxycholic acid. Our aim was to assemble national, real-world data on the effectiveness of obeticholic acid (OCA) as a second-line treatment, alongside non-licensed therapy with fibric acid derivatives (bezafibrate or fenofibrate).Methods: this was a nationwide observational cohort study conducted from August 2017 until June 2021.Results: we accrued data from 457 patients; 349 treated with OCA and 108 with fibric acid derivatives. At baseline/pre-treatment, individuals in the OCA group manifest higher risk features compared with those taking fibric acid derivatives, evidenced by more elevated alkaline phosphatase values, and a larger proportion of individuals with cirrhosis, abnormal bilirubin, prior non-response to ursodeoxycholic acid, and elastography readings &gt;9.6kPa (P &lt; .05 for all). Overall, 259 patients (OCA) and 80 patients (fibric acid derivatives) completed 12 months of second-line therapy, yielding a dropout rate of 25.7% and 25.9%, respectively. At 12 months, the magnitude of alkaline phosphatase reduction was 29.5% and 56.7% in OCA and fibric acid groups (P &lt; .001). Conversely, 55.9% and 36.4% of patients normalized serum alanine transaminase and bilirubin in the OCA group (P &lt; .001). The proportion with normal alanine transaminase or bilirubin values in the fibric acid group was no different at 12 months compared with baseline. Twelve-month biochemical response rates were 70.6% with OCA and 80% under fibric acid treatment (P = .121). Response rates between treatment groups were no different on propensity-score matching or on sub-analysis of high-risk groups defined at baseline.Conclusion: across the population of patients with primary biliary cholangitis in the United Kingdom, rates of biochemical response and drug discontinuation appear similar under fibric acid and OCA treatment.</p
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