INFERENCE FOR SURVIVAL CURVES WITH INFORMATIVELY COARSENED DISCRETE EVENT-TIME DATA: APPLICATION TO ALIVE

In many prospective studies, including AIDS Link to the Intravenous Experience (ALIVE), researchers are interested in comparing event-time distributions (e.g.,for human immunodeficiency virus seroconversion) between a small number of groups (e.g., risk behavior categories). However, these comparisons are complicated by participants missing visits or attending visits off schedule and seroconverting during this absence. Such data are interval-censored, or more generally,coarsened. Most analysis procedures rely on the assumption of non-informative censoring, a special case of coarsening at random that may produce biased results if not valid. Our goal is to perform inference for estimated survival functions across a small number of goups in the presence of informative coarsening. To do so, we propose methods for frequentist and Bayesian inference of ALIVE data utilizing information elicited from ALIVE scientists and an AIDS epidemiology expert about the visit compliance process

Effect of perioperative complications on excess mortality among women after coronary artery bypass: The israeli coronary artery bypass graft study (ISCAB)

AbstractBackground: Widely observed excess mortality among women after coronary artery bypass grafting is still largely unexplained, although case-mix factors have been identified. We evaluated the contribution of perioperative complications to the risk of 180-day mortality among women while adjusting for case-mix factors. Methods: This is part of a prospective, 1-year nationwide Israeli coronary artery bypass graft study of 1029 female and 3806 male patients. Deaths within 180 days were independently ascertained. Case-mix risk strata were obtained from a pooled Cox survival model (including all subjects and study variables) by using the adjusted coefficients corresponding to the case-mix factors within the model. Sex-specific mortality associated with perioperative complications was evaluated within the strata. In addition, sex-specific Cox models were constructed. Results: Higher mortality among women compared with that among men was significant within the pooled model (hazard ratio, 1.4; P =.038) and was evident early in the postoperative period. Women tended to cluster in the highest risk quartile compared with men (39.8% vs 20.9%, P <.001). However, although the incidence of perioperative complications was similar for the 2 sexes, the associated mortality for a given perioperative complication was higher among women. Sex-specific Cox models confirmed the above findings. For example, the hazard ratio for women with low postoperative hemoglobin was 6.9, whereas for men, the hazard ratio was 3.9. Conclusions: The role of perioperative factors in the excess mortality among women after coronary artery bypass grafting shifts the focus of attention from the selection of women for the operation to the in-hospital experience. Improving the outcome for women will entail efforts to prevent complications in the perioperative period.J Thorac Cardiovasc Surg 2002;123:517-2

Effectiveness of Highly Active Antiretroviral Therapy among Injection Drug Users with Late-Stage Human Immunodeficiency Virus Infection

Highly active antiretroviral therapy (HAART) has been shown to be effective in different populations, but data among injection drug users are limited. Human immunodeficiency virus-infected injection drug users recruited into the Acquired Immunodeficiency Syndrome Link to Intravenous Experiences (ALIVE) Study as early as 1988 were tested semiannually to identify their first CD4-positive T-lymphocyte cell count below 200/ll; they were followed for mortality through 2002. Visits were categorized into the pre-HAART (before mid-1996) and the HAART eras and further categorized by HAART use. Survival analysis with staggered entry was used to evaluate the effect of HAART on acquired immunodeficiency syndrome-related mortality, adjusting for other medications and demographic, clinical, and behavioral factors. Among 665 participants, 258 died during 2,402 person-years of follow-up. Compared with survival in the pre-HAART era, survival in the HAART era was shown by multivariate analysis to be improved for both those who did and did not receive HAART (relative hazards ~ 0.06 and 0.33, respectively; p < 0.001). Inferences were unchanged after restricting analyses to data starting with 1993 and considerations of leadtime bias and human immunodeficiency viral load. The annual CD4-positive T-lymphocyte cell decline was less in untreated HAART-era participants than in pre-HAART-era participants (-10/microliter vs. -37/microliter, respectively), suggesting that changing indications for treatment may have contributed to improved survival and that analyses restricted to the HAART era probably underestimate HAART effectiveness.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40266/2/Vlahov_Effectiveness of Highly Active Antiretroviral Therapy_2005.pd

The effect of HIV infection on overdose mortality

Objectives: To quantify the association of HIV infection with overdose mortality and explore the potential mechanisms. Design: A prospective cohort study. Methods: A total of 1927 actively injecting drug users who were HIV seronegative at baseline, of whom 308 later HIV seroconverted, were followed semi-annually for death from 1988 to 2001. Survival analyses using marginal structural and standard Cox models were used to evaluate the effect of HIV infection on the risk of overdose mortality. Results: Overdose death rates were higher in HIV-seropositive than HIV-seronegative drug users: 13.9 and 5.6 per 1000 person-years, respectively (P < 0.01). The hazard ratio (HR) was 2.54 [95% confidence interval (CI) 1.47, 4.38] for the marginal structural model and 2.06 (95% CI 1.25, 3.38) for the standard Cox model, both adjusted for demographics, drug injection characteristics, alcohol abuse, substance abuse treatment, and sexual orientation. Adjusting for possible time-varying mediators (i.e. drug use, medical conditions and healthcare access) in extended marginal structural models reduced the effect of HIV on overdose mortality by 30% (HR 1.82, 95% CI 1.01, 3.30). Abnormal liver function was associated with a higher risk of overdose mortality (HR 2.00, 95% CI 1.05, 3.84); adjustment for this further reduced the effect of HIV on overdose mortality. Conclusion: HIV infection was associated with a higher risk of overdose mortality. Drug use behavior, systematic disease and liver damage associated with HIV infection appeared to account for a substantial portion of this association. The data suggest a group to target with interventions to reduce overdose mortality rates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/40279/2/Wang_The Effect of HIV Infection on Overdose_2005.pd

Cancer of the cervix in Bulgaria : epidemiology of a crisis

Eastern Europe continues to have the highest rates of cancer of the uterine cervix (CUC) and human papillomavirus (HPV) infection in Europe.Aim: The aim of this study was to investigate CUC trends in Bulgaria in the context of a lack of a population-based screening program and a demographic crisis.Methodology: This was a retrospective study of 7861 CUC patients who were registered in the Bulgarian National Cancer Registry (BNCR) between 2013 and 2020 and followed up with until March 2022. We used descriptive statistics and modeling to assess temporal trends in new CUC incidence rates and identify factors associated with survival.Results: Bulgaria’s population has decreased by 11.5% between 2011 and 2021. The CUC incidence rate decreased from 29.5/100,000 in 2013 to 23.2/100,000 in 2020 but remains very high. The proportion of patients diagnosed in earlier stages of CUC has decreased over time. Up to 19% of patients with CUC in Bulgaria are diagnosed between the age of 35 and 44 years. The median survival was 101.5 months, with some improvement in later years (adjusted HR = 0.83 for 2017–2020).Conclusions: In countries with well-established population-based screening, CUC is nowadays considered a rare disease. However, it is not considered rare in Bulgaria. Population-based screening starting at an earlier age is the fastest way to improve outcomes.peer-reviewe

Multi-Level Considerations for Optimal Implementation of Long-Acting Injectable Antiretroviral Therapy to Treat People Living with HIV: Perspectives of Health Care Providers Participating in Phase 3 Trials

BACKGROUND: Long-acting injectable antiretroviral therapy (LA ART) has been shown to be non-inferior to daily oral ART, with high patient satisfaction and preference to oral standard of care in research to date, and has recently been approved for use in the United States and Europe. This study examined the perspectives of health care providers participating in LA ART clinical trials on potential barriers and solutions to LA ART roll-out into real world settings. METHODS: This analysis draws on two data sources: (1) open-ended questions embedded in a structured online survey of 329 health care providers participating in the ATLAS-2 M trial across 13 countries; and (2) in-depth interviews with 14 providers participating in FLAIR/ ATLAS/ATLAS-2 M trials in the United States and Spain. Both assessments explored provider views and clinic dynamics related to the introduction of LA ART and were analyzed using thematic content analysis. The Consolidated Framework for Implementation Research (CFIR) was drawn on as the conceptual framework underpinning development of a model depicting study findings. RESULTS: Barriers and proposed solutions to LA ART implementation were identified at the individual, clinic and health system levels. Provider perceptions of patient level barriers included challenges with adhering to frequent injection appointments and injection tolerability. Proposed solutions included patient education, having designated staff for clinic visit retention, and clinic flexibility with appointment scheduling. The main provider concern was identifying appropriate candidates for LA ART; proposed solutions focused on patient provider communication and decision making. Clinic level barriers included the need for additional skilled individuals to administer injections, shifts in workflow as demand increases and the logistics of cold-chain storage. Proposed solutions included staff hiring and training, strategic planning around workflow and logistics, and the possibility of offering injections in other settings, including the home. Health system level barriers included cost and approvals from national regulatory bodies. Potential solutions included governments subsidizing treatment, ensuring cost is competitive with oral ART, and offering co-pay assistance. CONCLUSIONS: Results suggest the importance of multi-level support systems to optimize patient-provider communication and treatment decision-making; clinic staffing, workflow, logistics protocols and infrastructure; and cost-related factors within a given health system

Study design and participant characteristics of a randomized controlled trial of directly administered antiretroviral therapy in opioid treatment programs

<p>Abstract</p> <p>Background</p> <p>HIV-infected drug users are at higher risk of non-adherence and poor treatment outcomes than HIV-infected non-drug users. Prior work from our group and others suggests that directly administered antiretroviral therapy (DAART) delivered in opioid treatment programs (OTPs) may increase rates of viral suppression.</p> <p>Methods/Design</p> <p>We are conducting a randomized trial comparing DAART to self-administered therapy (SAT) in 5 OTPs in Baltimore, Maryland. Participants and investigators are aware of treatment assignments. The DAART intervention is 12 months. The primary outcome is HIV RNA < 50 copies/mL at 3, 6, and 12 months. To assess persistence of any study arm differences that emerge during the active intervention, we are conducting an 18-month visit (6 months after the intervention concludes). We are collecting electronic adherence data for 2 months in both study arms. Of 457 individuals screened, a total of 107 participants were enrolled, with 56 and 51 randomly assigned to DAART and SAT, respectively. Participants were predominantly African American, approximately half were women, and the median age was 47 years. Active use of cocaine and other drugs was common at baseline. HIV disease stage was advanced in most participants. The median CD4 count at enrollment was 207 cells/mm³, 66 (62%) had a history of an AIDS-defining opportunistic condition, and 21 (20%) were antiretroviral naïve.</p> <p>Conclusions</p> <p>This paper describes the rationale, methods, and baseline characteristics of subjects enrolled in a randomized clinical trial comparing DAART to SAT in opioid treatment programs.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00279110">NCT00279110</a></p

Sensitivity Analysis Using Elicited Expert Information for Inference With Coarsened Data: Illustration of Censored Discrete Event Times in the AIDS Link to Intravenous Experience (ALIVE) Study

In this paper, the authors use the rubric of “coarsened data,” of which missing and censored data are special cases, to motivate the elicitation and use of expert information for performing sensitivity analyses of censored event-time data. Elicited information is important because observed data are insufficient to estimate how study participants with coarsened data compare with participants with uncoarsened data, and misspecifying this comparison may produce biased analysis results. In the presence of coarsening, performing a sensitivity analysis over a range of plausible assumptions is the best one can do. Here the authors illustrate an approach for eliciting expert information for use in sensitivity analyses to compare cumulative incidence functions of censored nonmortality outcomes. An example of such data is the AIDS Link to Intravenous Experience (ALIVE) Study, where the authors aim to estimate and compare cumulative incidence functions for human immunodeficiency virus between risk factor categories. The interval and right-censoring and censoring due to death found in the ALIVE data (1988–1998) are thought to be informative; thus, a sensitivity analysis is performed using information elicited from 2 ALIVE scientists and an expert in acquired immunodeficiency syndrome epidemiology about the relation between seroconversion and censoring

Use of Seroconversion Panels To Estimate Delay in Detection of Anti-Human Immunodeficiency Virus Antibodies by Enzyme-Linked Immunosorbent Assay of Pooled Compared to Singleton Serum Samples

The transfusion of unsafe blood worldwide accounts for 5 to 15% of new human immunodeficiency virus (HIV) infections, most of which occur in sub-Saharan Africa. While developed countries now apply PCR testing of pooled samples, some developing countries still do not have universal screening policies. More efficient low-cost procedures for the screening of pooled samples have the potential to encourage mass screening efforts in resource-poor settings. The aim of this study was to estimate the delay in the detection of HIV antibodies in pooled serum samples compared to that in singleton serum samples by enzyme-linked immunosorbent assay (ELISA) and to evaluate the risk of transfusion-transmitted HIV infection during the window period. Serial blood samples obtained from five HIV seroconversion panels were mixed with HIV-seronegative blood samples to create pools of 6, 12, 16, 24, 32, and 48 samples. The delay in detection of the first anti-HIV antibody-positive sample in tests with pooled samples was calculated for each pool size and compared to that obtained by testing of singleton samples and statistically evaluated by a robust log-linear regression analysis. The risk of a false-negative (FN) result caused by dilution was estimated by use of the incidence risk/window period model. The additional risk of transmission related to ELISA screening of pooled samples for HIV did not exceed 9% of the current risk of an FN result (estimated to be 1/1,067,000). The countries with virus prevalence rates in donors of less than 15% are expected to save up to 30% in the number of tests. ELISA screening of pooled samples could be considered in settings where the testing of blood supplies for HIV is not routinely done