Background Human immunodeficiency virus (HIV) is the strongest known risk factor for tuberculosis (TB) through its impairment of T-cell immunity. Tuberculosis preventive treatment (TPT) is recommended for people living with HIV (PLHIV) by the World Health Organization, as it significantly reduces the risk of developing TB disease. We conducted a systematic review and meta-analysis of modeling studies to summarize projected costs, risks, benefits, and impacts of TPT use among PLHIV on TB-related outcomes. Methods and findings We searched MEDLINE, Embase, and Web of Science from inception until December 31, 2020. Two reviewers independently screened titles, abstracts, and full texts; extracted data; and assessed quality. Extracted data were summarized using descriptive analysis. We performed quantile regression and random effects meta-analysis to describe trends in cost, effectiveness, and cost-effectiveness outcomes across studies and identified key determinants of these outcomes. Our search identified 6,615 titles; 61 full texts were included in the final review. Of the 61 included studies, 31 reported both cost and effectiveness outcomes. A total of 41 were set in low- and middle-income countries (LMICs), while 12 were set in high-income countries (HICs); 2 were set in both. Most studies considered isoniazid (INH)-based regimens 6 to 2 months long (n = 45), or longer than 12 months (n = 11). Model parameters and assumptions varied widely between studies. Despite this, all studies found that providing TPT to PLHIV was predicted to be effective at averting TB disease. No TPT regimen was substantially more effective at averting TB disease than any other. The cost of providing TPT and subsequent downstream costs (e.g. post-TPT health systems costs) were estimated to be less than $1,500 (2020 USD) per person in 85% of studies that reported cost outcomes (n = 36), regardless of study setting. All cost-effectiveness analyses concluded that providing TPT to PLHIV was potentially cost-effective compared to not providing TPT. In quantitative analyses, country income classification, consideration of antiretroviral therapy (ART) use, and TPT regimen use significantly impacted cost-effectiveness. Studies evaluating TPT in HICs suggested that TPT may be more effective at preventing TB disease than studies evaluating TPT in LMICs; pooled incremental net monetary benefit, given a willingness-to-pay threshold of country-level per capita gross domestic product (GDP), was $271 in LMICs (95% confidence interval [CI] −$81 to $622, p = 0.12) and was $2,568 in HICs (−$32,115 to $37,251, p = 0.52). Similarly, TPT appeared to be more effective at averting TB disease in HICs; pooled percent reduction in active TB incidence was 20% (13% to 27%, p < 0.001) in LMICs and 37% (−34% to 100%, p = 0.13) in HICs. Key limitations of this review included the heterogeneity of input parameters and assumptions from included studies, which limited pooling of effect estimates, inconsistent reporting of model parameters, which limited sample sizes of quantitative analyses, and database bias toward English publications. Conclusions The body of literature related to modeling TPT among PLHIV is large and heterogeneous, making comparisons across studies difficult. Despite this variability, all studies in all settings concluded that providing TPT to PLHIV is potentially effective and cost-effective for preventing TB disease.

Objective:Elucidate brain activity differences between patients with tinnitus and controls.Study Design:Cross-sectional cohort study.Setting:Outpatient Otolaryngology clinic.Patients:Three cohorts; 8 controls, 12 with subjective idiopathic tinnitus (tinnitus without hearing loss), and 12 with both tinnitus and hearing loss.Intervention:An auditory oddball identification task was performed in fMRI scanner.Main Outcome Measures:Task performance and Tinnitus Handicap Inventory (THI) scores were recorded. Brain activation maps were generated comparing deviant and standard tones as well as at rest. One-way and two-way T-contrasts were generated in addition to multiple regression modeling which identified significant brain regions predicting tinnitus, disease severity, duration, and task performance.Results:Task performance worsened in tinnitus patients with increased auditory workload, in terms of additional hearing loss. THI score and grade correlated with false alarms. The limbic system, heschel's gyrus, angular gyrus and cerebellum have a significant effect on both brain behavior in patients with tinnitus, and predictability of tinnitus and its behavioral implications.Conclusion:Increased auditory workload resulted in poorer task performance. Moreover, it is possible to predict auditory task performance in patients with tinnitus by looking at the activity of specific regions of interest. Heschl's gyrus, angular gyrus, cerebellar, and limbic system activity are important contributors to neurological activity associated with tinnitus. Finally, predictive modeling may influence further research surrounding tinnitus treatment.

Polygenic risk scores aggregate an individual’s burden of risk alleles to estimate overall genetic risk for a specific trait or disease. Polygenic risk scores derived from Genome-Wide Association Studies of European populations perform poorly for other ancestral groups. Given the potential for future clinical utility, underperformance of polygenic risk score prediction in South Asian populations has the potential to reinforce health inequalities. To determine whether European-derived polygenic risk scores underperform at Multiple Sclerosis prediction in a South Asian population compared with a European-ancestry cohort, we used data from two longitudinal genetic cohort studies: Genes & Health (2015-), a study of ∼50,000 British-Bangladeshi and British-Pakistani individuals, and UK Biobank (2006-), which is comprised of ∼500,000 predominantly White British individuals. We compared individuals with and without Multiple Sclerosis in both studies (Genes and Health: NCases=42, NControl=40,490; UK Biobank: NCases=2091, NControl=374,866). Polygenic risk scores were calculated using clumping-and-thresholding with risk allele effect sizes from the largest Multiple Sclerosis Genome-Wide Association Study to date. Scores were calculated with and without the Major Histocompatibility Complex region, the most influential locus in determining Multiple Sclerosis risk. Polygenic risk scire prediction was evaluated using Nagelkerke’s pseudo-R2 metric adjusted for case ascertainment, age, sex, and the first four genetic principal components. We found that, as expected, European-derived polygenic risk scores perform poorly in the Genes and Health cohort, explaining 1.1% (including the Major Histocompatibility Complex) and 1.5% (excluding the Major Histocompatibility Complex) of disease risk. In contrast, Multiple Sclerosis polygenic risk scores explained 4.8% (including the Major Histocompatibility Complex) and 2.8% (excluding the Major Histocompatibility Complex) of disease risk in European-ancestry UK Biobank participants. These findings suggest that polygenic risk score prediction of Multiple Sclerosis based on European Genome-Wide Association Study results is less accurate in a South Asian population. Genetic studies of ancestrally-diverse populations are required to ensure that polygenic risk scores can be useful across ancestries.

No abstract