Cash Transfers and HIV/HSV-2 Prevalence: A Replication of a Cluster Randomized Trial in Malawi

INTRODUCTION: In this paper we perform a replication analysis of Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial by Sarah Baird and others published in The Lancet in 2012. The original study was a two-year cluster randomized intervention trial of never married girls aged 13-22 in Malawi. Enumeration areas were randomized to either an intervention involving cash transfer (conditional or unconditional of school enrollment) or control. The study included 1708 Malawian girls, who were enrolled at baseline and had biological testing for HIV and herpes simplex virus type 2 (HSV-2) at 18 months. The original findings showed that in the cohort of girls enrolled in school at baseline, the intervention had an effect on school enrollment, sexual outcomes, and HIV and HSV-2 prevalence. However, in the baseline school dropout cohort, the original study showed no intervention effect on HIV and HSV-2 prevalence. METHODS: We performed a replication of the study to investigate the consistency and robustness of key results reported. A pre-specified replication plan was approved and published online. Cleaned data was obtained from the original authors. A pure replication was conducted by reading the methods section and reproducing the results and tables found in the original paper. Robustness of the results were examined with alternative analysis methods in a measurement and estimation analysis (MEA) approach. A theory of change analysis was performed testing a causal pathway, the effect of intervention on HIV awareness, and whether the intervention effect depended on the wealth of the individual. RESULTS: The pure replication found that other than a few minor discrepancies, the original study was well replicated. However, the randomization and sampling weights could not be verified due to the lack of access to raw data and a detailed sample selection plan. Therefore, we are unable to determine how sampling influenced the results, which could be highly dependent on the sample. In MEA it was found that the intervention effect on HIV prevalence in the baseline schoolgirls cohort was somewhat sensitive to model choice, with a non-significant intervention effect for HIV depending on the statistical model used. The intervention effect on HSV-2 prevalence was more robust in terms of statistical significance, however, the odds ratios and confidence intervals differed from the original result by more than 10%. A theory of change analysis showed no effect of intervention on HIV awareness. In a causal pathway analysis, several variables were partial mediators, or potential mediators, indicating that the intervention could be working through its effect on school enrollment or selected sexual behaviors. CONCLUSIONS: The effect of intervention on HIV prevalence in the baseline schoolgirls was sensitive to the model choice; however, HSV-2 prevalence results were confirmed. We recommend that the results from the original published analysis indicating the impact of cash transfers on HIV prevalence be treated with caution

Establishing an Institution-Wide Graduate Medical Education Research Collaborative to Promote Scholarly Activities among House Officers

Background: House officers’ ability to participate in research and quality improvement projects can be hindered by barriers, including lack of time, mentoring, and resources. Objective: Create a collaborative for house officers that provides readily accessible resources in study design as well as data collection, analysis, interpretation, and presentation. Methods: In 2017, we established a collaborative comprised of biostatisticians and an Associate Dean for Graduate Medical Research, providing a trove of experience in research and quality improvement. We worked closely with the Institutional Review Board and Electronic Health Records Core to simplify the process for house officers to utilize these research resources. The collaborative has weekly small group meetings to discuss new projects/updates and monthly large group meetings where house officers can present their ideas for additional feedback from peers and additional faculty. These formats are flexible, which allows us to tailor our assistance to the needs of each individual project. Results: In the first year since establishing the collaborative, we have received 51 project concepts from 44 house officers. Of the projects needing assistance (n=44), 100% were discussed in one of our weekly meetings and received assistance from the collaborative, and 34% presented at our large monthly meeting. A year into the collaborative, 20% of projects are either in the data analysis phase or have already been presented. Conclusion: As evidenced by the number of projects we received in our first year, there is a significant benefit for this type of collaborative resource to support and stimulate successful scholarly activity in house officers

Abnormal T Cell Frequencies, Including Cytomegalovirus-Associated Expansions, Distinguish Seroconverted Subjects at Risk for Type 1 Diabetes

We analyzed T cell subsets from cryopreserved PBMC obtained from the TrialNet Pathway to Prevention archives. We compared subjects who had previously seroconverted for one or more autoantibodies with non-seroconverted, autoantibody negative individuals. We observed a reduced frequency of MAIT cells among seroconverted subjects. Seroconverted subjects also possessed decreased frequencies of CCR4-expressing CD4 T cells, including a regulatory-like subset. Interestingly, we found an elevation of CD57+, CD28-, CD127-, CD27- CD8 T cells (SLEC) among seroconverted subjects that was most pronounced among those that progressed to disease. The frequency of these SLEC was strongly correlated with CMV IgG abundance among seroconverted subjects, associated with IA-2 levels, and most elevated among CMV+ seroconverted subjects who progressed to disease. Combined, our data indicate discrete, yet profound T cell alterations are associated with islet autoimmunity among at-risk subjects

Bupropion and Nicotine Patch as Smoking Cessation Aids in Alcoholics

This is a double blind placebo controlled study of sustained release bupropion as a smoking cessation aid in alcoholics undergoing treatment for their alcoholism. Participants (N=58) were enrolled within one week of entry into alcohol treatment from community and Veterans Affairs Substance Use Disorder programs. All participants received nicotine patch and were invited to attend a smoking cessation lecture and group. Cigarette smoking and alcohol outcomes were measured at six months. Bupropion when added to nicotine patch did not improve smoking outcomes. One-third of participants on bupropion reported discontinuing the drug during weeks 1-4. Participants reported cigarette outcomes with nicotine patch which are similar to those seen in the general population. All study participants significantly reduced cigarette use. Co-morbid affective disorder or antipersonality disorder did not affect outcomes. Alcohol outcomes were improved in those who discontinued cigarettes

A multiple testing approach to the regularisation of large sample correlation matrices

This paper proposes a regularisation method for the estimation of large covariance matrices that uses insights from the multiple testing (MT) literature. The approach tests the statistical significance of individual pair-wise correlations and sets to zero those elements that are not statistically significant, taking account of the multiple testing nature of the problem. The effective p-values of the tests are set as a decreasing function of N (the cross section dimension), the rate of which is governed by the nature of dependence of the underlying observations, and the relative expansion rates of N and T (the time dimension). In this respect, the method specifies the appropriate thresholding parameter to be used under Gaussian and non-Gaussian settings. The MT estimator of the sample correlation matrix is shown to be consistent in the spectral and Frobenius norms, and in terms of support recovery, so long as the true covariance matrix is sparse. The performance of the proposed MT estimator is compared to a number of other estimators in the literature using Monte Carlo experiments. It is shown that the MT estimator performs well and tends to outperform the other estimators, particularly when N is larger than T