Swiss HIV Cohort Study

The Brier score is a widely used metric in epidemiological and clinical research for evaluating the accuracy of probabilistic predictions for binary outcomes, such as disease occurrence, treatment response, and screening performance. Despite its popularity, the Brier score is frequently misunderstood, leading to flawed interpretation of prediction models and potentially misguided public health and clinical decisions. This study aims to didactically clarify common misconceptions about realised Brier scores and to provide practical, statistically rigorous guidance for its correct interpretation in epidemiologic and public health prediction models. We analytically examined its statistical properties and conducted simulation studies across diverse scenarios, varying the distribution of true outcome probabilities, prediction accuracy, sample size, and event prevalence. Five prevalent misconceptions were identified, including the mistaken belief that a Brier score of zero indicates a perfect model. Analytic arguments and simulations demonstrated that even perfectly specified models yield non-zero Brier scores under realistic conditions. The Brier score was shown to reflect not only prediction accuracy but also the underlying distribution of true risks and random variation in outcomes. Comparisons across different populations or disease settings can therefore be misleading, and the Brier score does not directly measure calibration. We recommend restricting comparisons to the same population and complementing the Brier score with calibration metrics and measures of clinical or public health utility. Adopting these practices will improve the validity and interpretability of risk prediction in epidemiologic research and enhance decision-making in population health.

We identified determinants of SARS-CoV-2 mRNA vaccine antibody response in people with HIV (PWH). Antibody response was higher among PWH less than 60 years, with CD4+ cell count superior to 350 cells/μl and vaccinated with mRNA-1273 by Moderna compared with BNT162b2 by Pfizer-BioNTech. Preinfection with SARS-CoV-2 boosted the antibody response and smokers had an overall lower antibody response. Elderly PWH and those with low CD4+ cell count should be prioritized for booster vaccinations.

BackgroundPost-transplant lymphoproliferative disease (PTLD) is a well-recognized complication after transplant. This study aimed to develop and independently validate a risk score to predict PTLD among solid organ transplant (SOT) recipients (kidney, liver, lung and heart). MethodsPoisson regression identified predictors of PTLD with the best fitting model selected for the risk score, where each predictor contributed with a risk coefficient to the risk score, dividing patients in high vs low risk of having a PTLD. ResultsFor both cohorts, most of the patients were male, aged more than 16 years old, kidney recipients and with a low-risk pre-transplant Epstein-Barr Virus (EBV) IgG donor/recipient serostatus. The derivation cohort consisted of 2546 SOT transplanted at Rigshospitalet, Copenhagen between 2004-2019; 57 developed PTLD. Predictors of PTLD were high-risk pre-transplant Epstein-Barr Virus (EBV) IgG donor/recipient serostatus, and current plasma EBV DNA positive, abnormal hemoglobin and C-reactive protein levels. A positive EBV DNA was the strongest parameter for the PTLD risk score (figure 1), although the model was able to predict the risk of PTLD cases in both EBV positive and EBV negative individuals. Individuals in the high-risk group had almost 7 times higher incidence of PTLD compared to the low risk group (table 1). In the validation cohort of 1611 SOT recipients between 2008-2018 from University Hospital of Zürich, 24 developed PTLD. A similar seven times higher risk of PTLD was observed in the high-risk group compared to the low risk group (table 1). The discriminatory ability was also similar in derivation (Harrell’s C-statistic of 0.82 95%CI (0.76-0.88) and validation (0.82, 95% CI:0.72-0.92) cohorts.An explanation about how the risk for PTLD is calculated for the SOT recipients; in this example the risk of developing PTLD is calculated in the next 180 daysPerformance of the PTLD score in the derivation and validation cohorts (low-risk group: score<=17 points; high-risk group: score>17 points)ConclusionThe risk score had a good discriminatory ability in both cohorts and helped to identify patients with higher risk of developing PTLD, so they can be monitored more often. This is the first risk-score developed and externally validated to predict risk of PTLD among SOT recipients.DisclosuresAll Authors: No reported disclosures

Living donor renal transplantation is widely performed in Switzerland with a superior long-term outcome and lower waiting time compared with deceased renal transplantation. However the chances of receiving a living donor kidney transplant are not the same for all transplant candidates. The current study aimed to identify psychosocial and demographic characteristics that predict lower access to living kidney donation in Switzerland. The study was a nationwide multicentre study nested within the Swiss Transplant Cohort Study. Pre-transplant demographic, psychosocial and health characteristics of 1126 deceased and 859 living renal transplant recipients were compared using logistic regression analysis. Transplant candidates with higher age (odds ratio [OR] per 10 years 0.67, 95% confidence interval [CI] 0.60&ndash;0.74), lower education (OR 0.46, 95% CI 0.36&ndash;0.59), a work capacity of less than 50% (OR 0.48, 95% CI 0.35&ndash;0.66), single or formerly married (OR 0.38, 95% CI 0.26&ndash;0.53 / OR 0.37, 95% CI 0.26&ndash;0.53) or with a higher hospital depression score (OR per 5 points 0.61, 95% CI 0.50&ndash;0.74) were less likely to receive an allograft from a living donor. In some regions of Switzerland candidates were more likely to undergo living transplantation than in other regions. No association was found with gender or income. Interventions to increase access to kidney transplantation from living donors should target transplant candidates of older age, lower education, lower working capacity and not living in a committed relationship. The observed regional differences suggest that additional determinants of living donation may play a role such as population and health professional attitudes toward living donation.

Only 10% of HIV positive individuals in Pakistan are receiving anti-retroviral therapy (ART) and the dropout rate from HIV treatment is extremely high. This short report attempts to highlight the risk of ART resistance. Pakistan National AIDS Control Programme's website reports 15,390 HIV positive persons receiving ART out of which 4,697 (30.5%) are people who inject drugs (PWIDs) among whom HIV prevalence is reported to be 38.4%. In the two large provinces of the country (Punjab and Sindh) with more than 90% burden of HIV, ART was initiated in 2,807 patients between April and September 2018, out of these 37% were lost to follow up. Many patients have cited issues related to quality of service at the ART centres as one of the reasons to not revisiting the treatment centres. HIV planners in Pakistan urgently need to make a new strategy and improve not only the quality of services but also increase the number of HIV positive persons receiving ART.

Interventions to prevent childhood obesity targeting school age children have mostly reported limited effectiveness, suggesting such prevention programs may need to start at an earlier age, but evidence has been scarce. We reported a pilot study aiming to demonstrate the feasibility of a multifaceted intervention for preschool children and to provide a preliminary assessment of the effectiveness. This nonrandomized controlled trial recruited children aged 3 to 6 years from 6 kindergartens in Guangzhou, China. Based on the preference of the School and Parents Committees, 4 kindergartens (648 children) received a 3-component intervention (training of kindergarten staff, initiating healthy curriculum for children, and close collaboration between families and kindergartens) over 12 months, while the other 2 kindergartens (336 children), serving as controls, received routine health care provision. Outcome measures were the changes in BMI z score between baseline and the end of 12 months, and the prevalence of postintervention children who were overweight or obese. By 12 months, children within the intervention group had a smaller BMI z score increase (0.24) compared to the control (0.41), with a difference of -0.31 (95% CI -0.47 to -0.15). The prevalence of overweight or obesity was also lower among the intervention group at the end of the study (OR: 0.43, 95% CI 0.19 to 0.96), adjusted for baseline status. Our results indicated a multicomponent health behavior intervention might be effective in reducing the prevalence of obesity, but the longer term effects will need confirmation from randomized controlled trials.

CD4+ T cell repopulation of the gut is rarely achieved in HIV-1-infected individuals who are receiving clinically effective antiretroviral therapy. Alterations in the integrity of the mucosal barrier have been indicated as a cause for chronic immune activation and disease progression. In this study, we present evidence that persistent immune activation causes impairment of lymphocytes to respond to chemotactic stimuli, thus preventing their trafficking from the blood stream to peripheral organs. CCR6+ and CXCR3+ Th cells accumulate in the blood of aviremic HIV-1-infected patients on long-term antiretroviral therapy, and their frequency in the circulation positively correlates to levels of soluble CD14 in plasma, a marker of chronic immune activation. Th cells show an impaired response to chemotactic stimuli both in humans and in the pathogenic model of SIV infection, and this defect is due to hyperactivation of cofilin and inefficient actin polymerization. Taking advantage of a murine model of chronic immune activation, we demonstrate that cytoskeleton remodeling, induced by okadaic acid, restores lymphocyte migration in response to chemokines, both in vitro and in vivo. This study calls for novel pharmacological approaches in those pathological conditions characterized by persistent immune activation and loss of trafficking of T cell subsets to niches that sustain their maturation and activities.

Plasma HIV viral load is related to declining CD4 lymphocytes. The extent to which CD8 cells, in addition to RNA viral load, predict the depletion of CD4 cells is not well characterized so far. We examine if CD8 cell count is a prognostic factor for CD4 cell counts during an HIV infection.A longitudinal analysis is conducted using data from the Swiss HIV cohort study collected between January 2000 and October 2014. Linear mixed regression models were applied to observations from HIV-1-infected treatment naive patients (NAIVE) and cART-treated patients to predict the short-term evolution of CD4 cell counts. For each subgroup, it was quantified to which extent CD8 cell counts or CD4/CD8 ratios are prognostic factors for disease progression.In both subgroups, 2500 NAIVE and 8902 cART patients, past CD4 cells are positively (P < 0.0001) and past viral load is negatively (P < 0.0001) associated with the outcome. Including additionally past CD8 cell counts improves the fit significantly (P < 0.0001) and increases the marginal explained variation 31.7% to 40.7% for the NAIVE and from 44.1% to 50.7% for the cART group. The past CD4/CD8 ratio (instead of the past CD8 level) is positively associated with the outcome, increasing the explained variation further to 41.8% for NAIVE and 51.9% for cART.