Mediation Analysis for Censored Survival Data under an Accelerated Failure Time Model

Recent advances in causal mediation analysis have formalized conditions for estimating direct and indirect effects in various contexts. These approaches have been extended to a number of models for survival outcomes including accelerated failure time (AFT) models which are widely used in a broad range of health applications given their intuitive interpretation. In this setting, it has been suggested that under standard assumptions, the “difference” and “product” methods produce equivalent estimates of the indirect effect of exposure on the survival outcome. We formally show that these two methods may produce substantially different estimates in the presence of censoring or truncation, due to a form of model misspecification. Specifically, we establish that while the product method remains valid under standard assumptions in the presence of independent censoring, the difference method can be biased in the presence of such censoring whenever the error distribution of the AFT model fails to be collapsible upon marginalizing over the mediator. This will invariably be the case for most choices of mediator and outcome error distributions. A notable exception arises in case of normal mediator-normal outcome where we show consistency of both difference and product estimators in the presence of independent censoring. These results are confirmed in simulation studies and two data applications

Heritability of fetal hemoglobin, white cell count, and other clinical traits from a sickle cell disease family cohort

Sickle cell disease (SCD) is the most common monogenic disorder in the world. Notably, there is extensive clinical heterogeneity in SCD that cannot be fully accounted for by known factors, and in particular, the extent to which the phenotypic diversity of SCD can be explained by genetic variation has not been reliably quantified. Here, in a family-based cohort of 449 patients with SCD and 755 relatives, we first show that 5 known modifiers affect 11 adverse outcomes in SCD to varying degrees. We then utilize a restricted maximum likelihood procedure to estimate the heritability of 20 hematologic traits, including fetal hemoglobin (HbF) and white blood cell count (WBC), in the clinically relevant context of inheritance from healthy carriers to SCD patients. We report novel estimations of heritability for HbF at 31.6% (±5.4%) and WBC at 41.2% (±6.8%) in our cohort. Finally, we demonstrate shared genetic bases between HbF, WBC, and other hematologic traits, but surprisingly little overlap between HbF and WBC themselves. In total, our analyses show that HbF and WBC have significant heritable components among individuals with SCD and their relatives, demonstrating the value of using family-based studies to better understand modifiers of SCD

Improving health facility delivery rates in Zanzibar, Tanzania through a large-scale digital community health volunteer programme: a process evaluation.

The utilization of community health worker (CHW) programmes to improve maternal and neonatal health outcomes has become widely applied in low- and middle-income countries. While current research has focused on discerning the effect of these interventions, documenting the process of implementing, scaling and sustaining these programmes has been largely ignored. Here, we focused on the implementation of the Safer Deliveries CHW programme in Zanzibar, a programme designed to address high rates of maternal and neonatal mortality by increasing rates of health facility delivery and postnatal care visits. The programme was implemented and brought to scale in 10 of 11 districts in Zanzibar over the course of 3 years by D-tree International and the Zanzibar Ministry of Health. As the programme utilized a mobile app to support CHWs during their visits, a rich data resource comprised of 133 481 pregnancy and postpartum home visits from 41 653 women and 436 CHWs was collected, enabling the evaluation of numerous measures related to intervention fidelity and health outcomes. Utilizing the framework of Steckler et al., we completed a formal process evaluation of the primary intervention, CHW home visits to women during their pregnancy and postpartum period. Our in-depth analysis and discussion will serve as a model for process evaluations of similar CHW programmes and will hopefully encourage future implementers to report analogous measures of programme performance

Protocol for the "four steps to control your fatigue (4-STEPS)" randomised controlled trial: a self-regulation based physical activity intervention for patients with unexplained chronic fatigue

<p>Abstract</p> <p>Background</p> <p>Unexplained Chronic Fatigue is a medical condition characterized by the presence of persistent, severe and debilitating medically unexplained fatigue, leading to impaired functioning and lower quality of life. Research suggests that physical activity can contribute to the reduction of fatigue and other somatic symptoms and can thus significantly improve physical functioning and quality of life in these patients. Based on the self-regulation (SR) theory of behaviour change, we developed a brief physical activity program for patients suffering from unexplained chronic fatigue which focuses on the training of self-regulation skills, the "4-STEPS to control your fatigue" program.</p> <p>Methods/Design</p> <p>This is a multi-centre, randomised controlled trial (RCT) that will be carried out in local primary care centres and at the Portuguese Fibromyalgia and Chronic Fatigue Syndrome Patients Association. Patients aged between 18 and 65 and fulfilling operationalized criteria for Idiopathic Chronic Fatigue (ICF) and Chronic Fatigue Syndrome (CFS) will be recruited and randomly allocated to standard care (SC) or standard care plus a self-regulation based physical activity program (4-STEPS). Patients will be assessed at baseline, after the intervention (3 months) and at 12 months follow-up. The primary outcome is fatigue severity.</p> <p>Discussion</p> <p>The results of the RCT will provide information about the effectiveness of a brief self-regulation intervention for promoting physical activity in patients with unexplained chronic fatigue. If the program proves to be effective, it may be considered as an adjunctive treatment for these patients.</p> <p>Trial Registration</p> <p>ISRCTN: <a href="http://www.anzctr.org.au/ISRCTN70763996.aspx">ISRCTN70763996</a></p

Evaluation of the implementation of a community health worker-led COVID-19 contact tracing intervention in Chiapas, Mexico, from March 2020 to December 2021

BACKGROUND: Mexico is one of the countries with the greatest excess death due to COVID-19. Chiapas, the poorest state in the country, has been particularly affected. Faced with an exacerbated shortage of health professionals, medical supplies, and infrastructure to respond to the pandemic, the non-governmental organization Compañeros En Salud (CES) implemented a COVID-19 infection prevention and control program to limit the impact of the pandemic in the region. We evaluated CES's implementation of a community health worker (CHW)-led contact tracing intervention in eight rural communities in Chiapas. METHODS: Our retrospective observational study used operational data collected during the contract tracing intervention from March 2020 to December 2021. We evaluated three outcomes: contact tracing coverage, defined as the proportion of named contacts that were located by CHWs, successful completion of contact tracing, and incidence of suspected COVID-19 among contacts. We described how these outcomes changed over time as the intervention evolved. In addition, we assessed associations between these three main outcomes and demographic characteristics of contacts and intervention period (pre vs. post March 2021) using univariate and multivariate logistic regression. RESULTS: From a roster of 2,177 named contacts, 1,187 (54.5%) received at least one home visit by a CHW and 560 (25.7%) had successful completion of contact tracing according to intervention guidelines. Of 560 contacts with complete contact tracing, 93 (16.6%) became suspected COVID-19 cases. We observed significant associations between sex and coverage (p = 0.006), sex and complete contact tracing (p = 0.049), community of residence and both coverage and complete contact tracing (p < 0.001), and intervention period and both coverage and complete contact tracing (p < 0.001). CONCLUSIONS: Our analysis highlights the promises and the challenges of implementing CHW-led COVID-19 contact tracing programs. To optimize implementation, we recommend using digital tools for data collection with a human-centered design, conducting regular data quality assessments, providing CHWs with sufficient technical knowledge of the data collection system, supervising CHWs to ensure contact tracing guidelines are followed, involving communities in the design and implementation of the intervention, and addressing community member needs and concerns surrounding stigmatization arising from lack of privacy

Childhood immunization during the COVID-19 pandemic: experiences in Haiti, Lesotho, Liberia and Malawi

OBJECTIVE: To examine changes in vaccination of children younger than 1 year during the coronavirus disease 2019 (COVID-19) pandemic (March 2020-August 2021) in Haiti, Lesotho, Liberia and Malawi. METHODS: We used data from health management information systems on vaccination of children aged 12 months or younger in districts supported by Partners In Health. We used data from January 2016 to February 2020 and a linear model with negative binomial distribution to estimate the expected immunization counts for March 2020-August 2021 with 95% prediction intervals, assuming no pandemic. We compared these expected levels with observed values and estimated the immunization deficits or excesses during the pandemic months. FINDINGS: Baseline vaccination counts varied substantially by country, with Lesotho having the lowest count and Haiti the highest. We observed declines in vaccination administration early in the COVID-19 pandemic in Haiti, Lesotho and Liberia. Continued declines largely corresponded to high rates of COVID-19 infection and discrete stock-outs. By August 2021, vaccination levels had returned to close to or above expected levels in Haiti, Liberia and Lesotho; in Malawi levels remained below expected. CONCLUSION: Patterns of childhood immunization coverage varied by country over the course of the pandemic, with significantly lower than expected vaccination levels seen in one country during subsequent COVID-19 waves. Governments and health-care stakeholders should monitor vaccine coverage closely and consider interventions, such as community outreach, to avoid or combat the disruptions in childhood vaccination