Parametric assumptions equate to hidden observations: comparing the efficiency of nonparametric and parametric models for estimating time to AIDS or death in a cohort of HIV-positive women

Abstract Background When conducting a survival analysis, researchers might consider two broad classes of models: nonparametric models and parametric models. While nonparametric models are more flexible because they make few assumptions regarding the shape of the data distribution, parametric models are more efficient. Here we sought to make concrete the difference in efficiency between these two model types using effective sample size. Methods We compared cumulative risk of AIDS or death estimated using four survival models – nonparametric, generalized gamma, Weibull, and exponential – and data from 1164 HIV patients who were alive and AIDS-free in 1995. We added pseudo-observations to the sample until the spread of the 95% confidence limits for the nonparametric model became less than that for the parametric models. Results We found the 3-parameter generalized gamma to be a good fit to the nonparametric risk curve, but the 1-parameter exponential both underestimated and overestimated the risk at different times. Using two year-risk as an example, we had to add 354, 593, and 3960 observations for the nonparametric model to be as efficient as the generalized gamma, Weibull, and exponential models, respectively. Conclusions These added observations represent the hidden observations underlying the efficiency gained through parametric model form assumptions. If the model is correctly specified, the efficiency gain may be justified, as appeared to be the case for the generalized gamma model. Otherwise, precision will be improved, but at the cost of specification bias, as was the case for the exponential model

Transportability without positivity: a synthesis of statistical and simulation modeling

When estimating an effect of an action with a randomized or observational study, that study is often not a random sample of the desired target population. Instead, estimates from that study can be transported to the target population. However, transportability methods generally rely on a positivity assumption, such that all relevant covariate patterns in the target population are also observed in the study sample. Strict eligibility criteria, particularly in the context of randomized trials, may lead to violations of this assumption. Two common approaches to address positivity violations are restricting the target population and restricting the relevant covariate set. As neither of these restrictions are ideal, we instead propose a synthesis of statistical and simulation models to address positivity violations. We propose corresponding g-computation and inverse probability weighting estimators. The restriction and synthesis approaches to addressing positivity violations are contrasted with a simulation experiment and an illustrative example in the context of sexually transmitted infection testing uptake. In both cases, the proposed synthesis approach accurately addressed the original research question when paired with a thoughtfully selected simulation model. Neither of the restriction approaches were able to accurately address the motivating question. As public health decisions must often be made with imperfect target population information, model synthesis is a viable approach given a combination of empirical data and external information based on the best available knowledge

Cancer Incidence Among US Medicare ESRD Patients Receiving Hemodialysis, 1996-2009

Patients with end-stage renal disease (ESRD) receiving dialysis have been reported to have increased risk of cancer. However, contemporary cancer burden estimates in this population are sparse and do not account for the high competing risk of death characteristic of dialysis patients

“Do you think your main partner has other sex partners?” A simple question provides insight into sexual risk in Jamaica

To estimate the association between a simple measure of sexual partner concurrency and sexually transmitted infection (STI) we conducted a cross-sectional population-based household survey (n=1795) and targeted surveys of people at venues where people meet sexual partners (n=1580) to ask about sexual behavior. Persons interviewed at venues were tested for HIV, gonorrhoea, chlamydia, gonorrhea, and trichomoniasis. We compared the association between STI and reporting a partner had other partners. More women than men reported their main partner had other partners. Thirteen percent of all women in the population-based survey and 14.4% in the targeted survey reported having one partner in the past 12 months and that partner had additional partners. STI prevalence was significantly associated with reporting a partner had other partners (36.8% vs 30.2%; prevalence ratio [PR]1.2; 95% CI 1.1,1.4). Construction of complete sexual networks is costly and not routinely feasible. We recommend adding a question to cross-sectional surveys used to monitor sexual behavior about whether the respondent believes his or her partner has other sexual partners. Although subject to bias, the question was useful in Jamaica to identify a group of women with only one sexual partner at increased risk of infection

Community-facility linkage models and maternal and infant health outcomes in Malawi’s PMTCT/ART program: a cohort study

Background: In sub-Saharan Africa, 3 community-facility linkage (CFL) models—Expert Clients, Community Health Workers (CHWs), and Mentor Mothers—have been widely implemented to support pregnant and breastfeeding women (PBFW) living with HIV and their infants to access and sustain care for prevention of mother-to-child transmission of HIV (PMTCT), yet their comparative impact under real-world conditions is poorly understood. Methods and findings: We sought to estimate the effects of CFL models on a primary outcome of maternal loss to follow-up (LTFU), and secondary outcomes of maternal longitudinal viral suppression and infant “poor outcome” (encompassing documented HIV-positive test result, LTFU, or death), in Malawi’s PMTCT/ART program. We sampled 30 of 42 high-volume health facilities (“sites”) in 5 Malawi districts for study inclusion. At each site, we reviewed medical records for all newly HIV-diagnosed PBFW entering the PMTCT program between July 1, 2016 and June 30, 2017, and, for pregnancies resulting in live births, their HIV-exposed infants, yielding 2,589 potentially eligible mother–infant pairs. Of these, 2,049 (79.1%) had an available HIV treatment record and formed the study cohort. A randomly selected subset of 817 (40.0%) cohort members underwent a field survey, consisting of a questionnaire and HIV biomarker assessment. Survey responses and biomarker results were used to impute CFL model exposure, maternal viral load, and early infant diagnosis (EID) outcomes for those missing these measures to enrich data in the larger cohort. We applied sampling weights in all statistical analyses to account for the differing proportions of facilities sampled by district. Of the 2,049 mother–infant pairs analyzed, 62.2% enrolled in PMTCT at a primary health center, at which time 43.7% of PBFW were ≤24 years old, and 778 (38.0%) received the Expert Client model, 640 (31.2%) the CHW model, 345 (16.8%) the Mentor Mother model, 192 (9.4%) ≥2 models, and 94 (4.6%) no model. Maternal LTFU varied by model, with LTFU being more likely among Mentor Mother model recipients (adjusted hazard ratio [aHR]: 1.45; 95% confidence interval [CI]: 1.14, 1.84; p = 0.003) than Expert Client recipients. Over 2 years from HIV diagnosis, PBFW supported by CHWs spent 14.3% (95% CI: 2.6%, 26.1%; p = 0.02) more days in an optimal state of antiretroviral therapy (ART) retention with viral suppression than women supported by Expert Clients. Infants receiving the Mentor Mother model (aHR: 1.24, 95% CI: 1.01, 1.52; p = 0.04) and ≥2 models (aHR: 1.44, 95% CI: 1.20, 1.74; p < 0.001) were more likely to undergo EID testing by age 6 months than infants supported by Expert Clients. Infants receiving the CHW and Mentor Mother models were 1.15 (95% CI: 0.80, 1.67; p = 0.44) and 0.84 (95% CI: 0.50, 1.42; p = 0.51) times as likely, respectively, to experience a poor outcome by 1 year than those supported by Expert Clients, but not significantly so. Study limitations include possible residual confounding, which may lead to inaccurate conclusions about the impacts of CFL models, uncertain generalizability of findings to other settings, and missing infant medical record data that limited the precision of infant outcome measurement. Conclusions: In this descriptive study, we observed widespread reach of CFL models in Malawi, with favorable maternal outcomes in the CHW model and greater infant EID testing uptake in the Mentor Mother model. Our findings point to important differences in maternal and infant HIV outcomes by CFL model along the PMTCT continuum and suggest future opportunities to identify key features of CFL models driving these outcome differences

A comparison of respondent-driven and venue-based sampling of female sex workers in Liuzhou, China

ObjectivesTo compare two methods for sampling female sex workers (FSWs) for bio-behavioural surveillance. We compared the populations of sex workers recruited by the venue-based Priorities for Local AIDS Control Efforts (PLACE) method and a concurrently implemented network-based sampling method, respondent-driven sampling (RDS), in Liuzhou, China.MethodsFor the PLACE protocol, all female workers at a stratified random sample of venues identified as places where people meet new sexual partners were interviewed and tested for syphilis. Female workers who reported sex work in the past 4 weeks were categorised as FSWs. RDS used peer recruitment and chain referral to obtain a sample of FSWs. Data were collected between October 2009 and January 2010. We compared the socio-demographic characteristics and the percentage with a positive syphilis test of FSWs recruited by PLACE and RDS.ResultsThe prevalence of a positive syphilis test was 24% among FSWs recruited by PLACE and 8.5% among those recruited by RDS and tested (prevalence ratio 3.3; 95% CI 1.5 to 7.2). Socio-demographic characteristics (age, residence and monthly income) also varied by sampling method. PLACE recruited fewer FSWs than RDS (161 vs 583), was more labour-intensive and had difficulty gaining access to some venues. RDS was more likely to recruit from areas near the RDS office and from large low prevalence entertainment venues.ConclusionsSurveillance protocols using different sampling methods can obtain different estimates of prevalence and population characteristics. Venue-based and network-based methods each have strengths and limitations reflecting differences in design and assumptions. We recommend that more research be conducted on measuring bias in bio-behavioural surveillance

Clinic presentation delay and tuberculosis treatment outcomes in the Lake Victoria region of East Africa: A multi-site prospective cohort study

In the Lake Victoria region of East Africa, little is known about delays between tuberculosis (TB) symptom onset and presentation at a clinic. Associations between clinic presentation delay and TB treatment outcomes are also poorly understood. In 2019, we abstracted data from routine TB treatment records for all adults (n = 776) initiating TB treatment in a 6-month period across 12 health facilities near Lake Victoria. We interviewed 301 cohort members and assessed whether they experienced a clinic presentation delay longer than 6 weeks. We investigated potential clinical and demographic correlates of clinic presentation delay and examined the association between clinic presentation delay and an unfavorable TB treatment outcome (death, loss to follow-up, or treatment failure). Clinic presentation delay was common, occurring among an estimated 54.7% (95% CI: 48.9%, 61.2%) of cohort members, though no specific correlates were identified. Clinic presentation delay was slightly associated with unfavorable TB treatment outcomes. The 180-day risk of an unfavorable outcome was 14.2% (95% CI: 8.0%, 20.4%) among those with clinic presentation delay, compared to 12.7% (95% CI: 5.1%, 20.3%) among those presenting earlier. Multi-level community-based interventions may be necessary to reduce clinic presentation delays in communities near Lake Victoria

Clinic presentation delay and tuberculosis treatment outcomes in the Lake Victoria region of East Africa: A multi-site prospective cohort study

In the Lake Victoria region of East Africa, little is known about delays between tuberculosis (TB) symptom onset and presentation at a clinic. Associations between clinic presentation delay and TB treatment outcomes are also poorly understood. In 2019, we abstracted data from routine TB treatment records for all adults (n = 776) initiating TB treatment in a 6-month period across 12 health facilities near Lake Victoria. We interviewed 301 cohort members and assessed whether they experienced a clinic presentation delay longer than 6 weeks. We investigated potential clinical and demographic correlates of clinic presentation delay and examined the association between clinic presentation delay and an unfavorable TB treatment outcome (death, loss to follow-up, or treatment failure). Clinic presentation delay was common, occurring among an estimated 54.7% (95% CI: 48.9%, 61.2%) of cohort members, though no specific correlates were identified. Clinic presentation delay was slightly associated with unfavorable TB treatment outcomes. The 180-day risk of an unfavorable outcome was 14.2% (95% CI: 8.0%, 20.4%) among those with clinic presentation delay, compared to 12.7% (95% CI: 5.1%, 20.3%) among those presenting earlier. Multi-level community-based interventions may be necessary to reduce clinic presentation delays in communities near Lake Victoria

Geographic mobility and treatment outcomes among people in care for tuberculosis in the Lake Victoria region of East Africa: A multi-site prospective cohort study

Geographic mobility may disrupt continuity of care and contribute to poor clinical outcomes among people receiving treatment for tuberculosis (TB). This may occur especially where health services are not well coordinated across international borders, particularly in lower and middle income country settings. In this work, we describe mobility and the relationship between mobility and unfavorable TB treatment outcomes (i.e., death, loss to follow-up, or treatment failure) among a cohort of adults who initiated TB treatment at one of 12 health facilities near Lake Victoria. We abstracted data from health facility records for all 776 adults initiating TB treatment during a 6-month period at the selected facilities in Kenya, Tanzania, and Uganda. We interviewed 301 cohort members to assess overnight travel outside one’s residential district/sub-county. In our analyses, we estimated the proportion of cohort members traveling in 2 and 6 months following initiation of TB treatment, explored correlates of mobility, and examined the association between mobility and an unfavorable TB treatment outcome. We estimated that 40.7% (95% CI: 33.3%, 49.6%) of people on treatment for TB traveled overnight at least once in the 6 months following treatment initiation. Mobility was more common among people who worked in the fishing industry and among those with extra-pulmonary TB. Mobility was not strongly associated with other characteristics examined, however, suggesting that efforts to improve TB care for mobile populations should be broad ranging. We found that in this cohort, people who were mobile were not at increased risk of an unfavorable TB treatment outcome. Findings from this study can help inform development and implementation of mobility-competent health services for people with TB in East Africa

SARS-CoV-2 infection in central North Carolina: Protocol for a population-based longitudinal cohort study and preliminary participant results

Public health surveillance systems likely underestimate the true prevalence and incidence of SARS-CoV-2 infection due to limited access to testing and the high proportion of subclinical infections in community-based settings. This ongoing prospective, observational study aimed to generate accurate estimates of the prevalence and incidence of, and risk factors for, SARS-CoV-2 infection among residents of a central North Carolina county. From this cohort, we collected survey data and nasal swabs every two weeks and venous blood specimens every month. Nasal swabs were tested for the presence of SARS-CoV-2 virus (evidence of active infection), and serum specimens for SARS-CoV-2-specific antibodies (evidence of prior infection). As of June 23, 2021, we have enrolled a total of 153 participants from a county with an estimated 76,285 total residents. The anticipated study duration is at least 24 months, pending the evolution of the pandemic. Study data are being shared on a monthly basis with North Carolina state health authorities and future analyses aim to compare study data to state-wide metrics over time. Overall, the use of a probability-based sampling design and a well-characterized cohort will enable collection of critical data that can be used in planning and policy decisions for North Carolina and may be informative for other states with similar demographic characteristics