Methylation markers for anal cancer screening: A repeated cross-sectional analysis of people living with HIV, 2015-2016.

People living with HIV (PLWH) are at highest risk of anal cancer and will benefit from optimized screening for early disease detection. We compared host DNA methylation markers in high-grade squamous intraepithelial lesions (HSIL) versus samples negative for intraepithelial lesions (NILM) or low-grade intraepithelial lesions (LSIL) in PLWH. We recruited PLWH identifying as male aged ≥18 years undergoing high-resolution anoscopy (HRA) in Seattle, Washington, 2015-2016. Anal brush samples were collected for HPV detection, genotyping, and pyrosequencing methylation (host genes ASCL1, PAX1, FMN2, and ATP10A); clinical data were abstracted from medical records. We assessed associations between methylation and presence and extent of HSIL using generalized estimating equation logistic regression, adjusting for age, CD4 count and HIV viral load. Marker panels using HPV DNA and methylation were also evaluated to predict prevalent HSIL. We analyzed 125 samples from 85 participants (mean age 50.1; standard deviation 11.0 years). ASCL1 (adjusted odds ratio [aOR] per 1 unit increase mean percent methylation: 1.07, 95% CI: 1.01-1.13) and FMN2 (aOR per 1 unit increase mean percent methylation: 1.14, 95% CI: 1.08-1.20) methylation were significantly associated with HSIL versus NILM/LSIL. ASCL1 (aOR: 1.06, 95% CI: 1.01-1.11) and FMN2 (aOR: 1.13, 95% CI: 1.08-1.17) methylation were positively associated with increasing HSIL extent. A panel combining methylation (ASCL1 and FMN2) and HPV DNA (HPV16, HPV18, and HPV31) demonstrated best balance of sensitivity (78.2%) and specificity (73.9%) for HSIL detection compared with methylation or HPV alone. Increasing levels of DNA methylation of ASCL1 and FMN2 were positively associated with HSIL detection in PLWH. Host gene methylation testing shows promise for HSIL screening and triage.

Effect of Human Immunodeficiency Virus Infection on Human Papillomavirus Clearance Among Women in Senegal, West Africa.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) is associated with development of invasive cervical cancer. METHODS: Longitudinal data was collected from 174 Senegalese women. We employed marginal Cox proportional hazards models to examine the effect of human immunodeficiency virus (HIV) status (HIV positive vs HIV negative) and HIV type (HIV-1 vs HIV-2 vs dual HIV-1/HIV-2) on clearance of type-specific HPV infection. Analyses were stratified by incident versus prevalent HPV infection. RESULTS: Incident HPV infections in HIV-positive women were less likely to clear than those in HIV-negative women (adjusted hazard ratio [HR] = 0.60; 95% confidence interval [CI], .38-.94). Among HIV-positive women, HIV-2-infected women and HIV-1/2 dually infected women were more likely to clear HPV incident infections than HIV-1-infected women (HR = 1.66; 95% CI, .95-2.92 and HR = 2.17; 95% CI, 1.12-4.22, respectively). Incident HPV infections in HIV-positive women with CD4 cell count ≤500 cells/µL were less likely to clear than those in HIV-positive women with CD4 cell count >500 cells/µL (HR = 0.65; 95% CI, .42-1.01). No significant associations were observed for prevalent HPV infections. CONCLUSIONS: HIV infection reduced the likelihood of clearance of incident HPV infection. Furthermore, among HIV-positive women, low CD4 cell count and dual HIV infection were each associated with reduced likelihood of clearance.

Age-specific burden of cervical cancer associated with HIV: A global analysis with a focus on sub-Saharan Africa.

HIV substantially worsens human papillomavirus (HPV) carcinogenicity and contributes to an important population excess of cervical cancer, particularly in sub-Saharan Africa (SSA). We estimated HIV- and age-stratified cervical cancer burden at a country, regional and global level in 2020. Proportions of cervical cancer (a) diagnosed in women living with HIV (WLHIV), and (b) attributable to HIV, were calculated using age-specific estimates of HIV prevalence (UNAIDS) and relative risk. These proportions were validated against empirical data and applied to age-specific cervical cancer incidence (GLOBOCAN 2020). HIV was most important in SSA, where 24.9% of cervical cancers were diagnosed in WLHIV, and 20.4% were attributable to HIV (vs 1.3% and 1.1%, respectively, in the rest of the world). In all world regions, contribution of HIV to cervical cancer was far higher in younger women (as seen also in empirical series). For example, in Southern Africa, where more than half of cervical cancers were diagnosed in WLHIV, the HIV-attributable fraction decreased from 86% in women ≤34 years to only 12% in women ≥55 years. The absolute burden of HIV-attributable cervical cancer (approximately 28 000 cases globally) also shifted toward younger women: in Southern Africa, 63% of 5341 HIV-attributable cervical cancer occurred in women <45 years old, compared to only 17% of 6901 non-HIV-attributable cervical cancer. Improved quantification of cervical cancer burden by age and HIV status can inform cervical cancer prevention efforts in SSA, including prediction of the impact of WLHIV-targeted vs general population approaches to cervical screening, and impact of HIV prevention.

Food insecurity predicts loss to follow-up among people living with HIV in Senegal, West Africa.

The goals of this study were to assess retention on antiretroviral therapy (ART) and to identify predictors of loss to follow-up (LTFU) among people living with HIV (PLHIV) in Senegal. HIV-positive individuals presenting for initiation of ART in Dakar and Ziguinchor were enrolled and followed for 12 months. Data were collected using interviews, clinical evaluations, laboratory analyses, chart review, and active patient tracing. Of the 207 individuals enrolled, 70% were female, 32% had no formal education, and 28% were severely food insecure. At the end of the follow-up period, 58% were retained on ART, 15% were deceased, 4% had transferred care, 5% had migrated, and 16% were lost to follow-up. Enrollment in Ziguinchor (OR 2.71 [1.01-7.22]) and severe food insecurity (OR 2.55 [1.09-5.96]) were predictive of LTFU. Sex, age, CD4 count, BMI <18.5, country of birth, marital status, number of children, household size, education, consultation with traditional healers, transportation time, and transportation cost were not associated with LTFU. The strongest predictor of severe food insecurity was lack of formal education (OR 2.75 [1.30-5.80]). Addressing the upstream drivers of food insecurity and implementing strategies to enhance food security for PLHIV may be effective approaches to reduce LTFU and strengthen the HIV care cascade in the region.

Morbidity and rehospitalization postpartum among women with epilepsy and their infants: A population-based study.

OBJECTIVE: We compared the relative occurrence of selected pregnancy outcomes and postpartum rehospitalizations among women with and without epilepsy and their infants. Using linked vital-hospital discharge records of women with deliveries in Washington State 1987-2014, comparisons were made overall, by epilepsy type, and by time periods related to antiepileptic drug (AED) marketing changes. METHODS: This population-based retrospective cohort study identified women with, and without epilepsy per diagnosis codes in the hospital discharge record from among all deliveries during 1987-2014 to examine maternal and infant outcomes, rehospitalization and mortality <2 years postpartum. Relative risks (RRs) and 95 % confidence intervals (CI) overall, and by epilepsy type were calculated using Poisson regression. We assessed the validity of epilepsy identification based on diagnosis codes by conducting a medical chart review for a sample of women. RESULTS: Women with epilepsy had increased risks of preeclampsia (RR 1.23; 95 % CI 1.08-1.41) and gestational diabetes (RR 1.18; 95 % CI 1.02-1.36). Their infants had increased malformation (RR 1.23; 95 % C: 1.08-1.42) and small for gestational age (SGA, RR 1.39; 95 % CI 1.25-1.54) risks, and were nearly three times as likely to not be breastfed. Affected mothers (RR 5.25; 95 % CI 2.46-11.23) and their infants (RR 1.64, 95 % CI 1.41-1.89) required more ICU admissions during the delivery hospitalizations, and more postpartum rehospitalization, with greatest risk in the first six months. Maternal mortality < 2 years after delivery was increased (RR 7.11; 95 % CI 2.47-20.49). Increased risks were observed for all epilepsy subtypes for nearly all outcomes examined. Risks of preterm delivery and low birthweight increased over time (p <.05). Suggestive, but not statistically significant temporal decreases in risks of gestational diabetes and malformations and increased risk of preterm labor were noted. We observed high sensitivity of diagnosis codes for identifying pregnant women with epilepsy. CONCLUSION: These population-based results emphasize the need for frequent postpartum monitoring of women with epilepsy. Increases in risks of low birthweight and preterm delivery over time are of concern. Possible temporal changes in other outcomes warrant further investigation.

Enteric Permeability, Systemic Inflammation, and Post-Discharge Growth Among a Cohort of Hospitalized Children in Kenya and Pakistan.

OBJECTIVES: To determine whether gut permeability is associated with post-discharge growth and systemic inflammation among hospitalized children in low- and middle-income countries. METHODS: Children aged 2-23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent lactulose-rhamnose ratio (LRR) permeability testing and were compared to age-matched children from their home communities. Linear mixed effect models estimated the associations between LRR among discharged children with change in length-for-age (LAZ) and weight-for-age z score (WAZ) at 45, 90, and 180 days after discharge. Linear regression tested if relationships between LRR, systemic inflammation [C-reative protein (CRP), Cluster of Differentiation 14 (CD14), Tumour Necrosis Factor Alpha (TNFα), Interleukin-6 (IL-6)], and enterocyte damage [Intestinal Fatty-Acid Binding protein (I-FABP)] differed between the hospitalized and community groups. RESULTS: One hundred thirty-seven hospitalized and 84 community participants were included. The hospitalized group had higher log-LRR [0.43, 95% confidence interval (CI): 0.15-0.71, P = 0.003] than the community children. Adjustment for weight-for-length z score at discharge attenuated this association (0.31, 95% CI: 0.00-0.62, P = 0.049). LRR was not associated with changes in WAZ or LAZ in the post-discharge period. Associations between LRR and CRP (interaction P = 0.036), TNFα ( P = 0.017), CD14 ( P = 0.078), and IL-6 ( P = 0.243) differed between community and hospitalized groups. LRR was associated with TNFα ( P = 0.004) and approached significance with CD14 ( P = 0.078) and IL-6 ( P = 0.062) in community children, but there was no evidence of these associations among hospitalized children. CONCLUSIONS: Although increased enteric permeability is more prevalent among children being discharged from hospital compared to children in the community, it does not appear to be an important determinant of systemic inflammation or post-discharge growth among hospitalized children.

Long-term Experience and Outcomes of Programmatic Antiretroviral Therapy for Human Immunodeficiency Virus Type 2 Infection in Senegal, West Africa.

BACKGROUND: Programmatic treatment outcome data for people living with human immunodeficiency virus type 2 (HIV-2) in West Africa, where the virus is most prevalent, are scarce. METHODS: Adults with HIV-2 initiating or receiving antiretroviral therapy (ART) through the Senegalese national AIDS program were invited to participate in this prospective, longitudinal observational cohort study. We analyzed HIV-2 viral loads, CD4 cell counts, antiretroviral drug resistance, loss to follow-up, and mortality. We also examined changes in treatment guidelines over time and assessed progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets for HIV-2. RESULTS: We enrolled 291 participants at 2 sites for 926.0 person-years of follow-up over 13 years. Median follow-up time was 2.2 years per participant. There were 21 deaths reported (7.2%), and 117 individuals (40.2%) were lost to follow-up, including 43 (14.7%) who had an initial visit but never returned for follow-up. CD4 counts and HIV-2 viral suppression (< 50 copies/mL) at enrollment increased over calendar time. Over the study period, 76.7% of plasma viral loads for participants receiving ART were suppressed, and median CD4 gain was 84 cells/µL in participants' first 2 years on study. Since the UNAIDS 90-90-90 strategy was published, 88.1% of viral loads were suppressed. Fifteen percent of patients experienced virologic failure with no known resistance mutations, while 56% had evidence of multiclass drug resistance. CONCLUSIONS: Participants in the Senegalese national AIDS program are initiating ART earlier in the course of disease, and more modern therapeutic regimens have improved outcomes among those receiving therapy. Despite these achievements, HIV-2 treatment remains suboptimal, and significant challenges to improving care remain.

The association between three key social determinants of health and life dissatisfaction: A 2017 behavioral risk factor surveillance system analysis.

Poor health outcomes disproportionately impact certain populations in the United States owing to the inequitable distribution of social determinants of health (SDOH). Using the 2017 Behavioral Risk Factor Surveillance System (BRFSS), we estimated the association of three adverse SDOH (housing insecurity, food insecurity, and financial instability) with life dissatisfaction. Participants were from Wisconsin, Minnesota, and Ohio, the only states that included the SDOH and Emotional Support and Life Satisfaction modules (n = 25,850). Six percent of respondents reported life dissatisfaction. Those who reported housing insecurity (Prevalence difference (PD) = 14.2 per 100, 95% CI [7.6, 20.7]), food insecurity (PD = 10.9 [7.1, 14.7]), and financial instability (PD = 5.6 [4.9, 6.3]) had higher prevalence of life dissatisfaction. The differences in prevalence of life dissatisfaction, comparing those with and without an adverse SDOH, decreased with increased emotional support (for housing insecurity, food insecurity, and financial instability, respectively: low support, PD = 30.2 [11.6, 48.8], 22.1 [11.6, 32.6], 16.4 [12.0, 20.8]; high support, PD = 4.8 [-2.9, 12.6], 4.8 [0.0, 9.7], 1.7 [1.1, 2.3]). Participants with frequent mental distress (FMD) had greater prevalence differences than those without FMD (for housing insecurity, food insecurity, and financial instability, respectively: with FMD, PD = 15.4 [7.5, 23.3], 10.7 [4.7, 16.7], 14.4 [9.6, 19.3]; without FMD, PD = 6.1 [-0.5, 12.5], 5.3 [1.6, 9.0], 2.5 [2.0, 3.0]). Social determinants may not only influence physical health but also have an impact on psychological well-being. This impact may be altered by levels of emotional support and FMD.

Firearm ownership and access to healthcare in the U.S.: A cross-sectional analysis of six states.

Provider-led firearm storage counseling is a form of firearm suicide prevention intervention. Little research examines whether barriers to healthcare access for at-risk individuals limit this intervention's impact. This study explores the relationship between household firearm presence/storage practices and healthcare access/utilization using a cross-sectional analysis of the 2017 Behavioral Risk Factor Surveillance System (BRFSS), which included state-representative data from six states that completed the Firearm Safety and Healthcare Access Modules: California, Idaho, Kansas, Oregon, Texas, and Utah. Exposures were household firearm presence and firearm storage practices. Outcomes were lacking health insurance, not having a healthcare provider, inability to afford care, and no recent routine checkup. Logistic regression models adjusted for age, sex, education, employment, children in the household, and state of residency. Our analysis included 31,888 individuals; 31.1% reported a household firearm. Compared to those in firearm-owning households, those in non-firearm-owning households had higher odds of being uninsured (aOR 1.99, 95%CI 1.60-2.48), not having a provider (aOR 1.40, 95%CI 1.18-1.67), and reporting cost as a barrier to care (aOR 1.37, 95%CI 1.13-1.67). Among firearm-owning households, those with firearms stored loaded and unlocked had higher odds of lacking a personal healthcare provider (aOR 1.52, 95%CI 1.07-2.15) compared to individuals in homes where firearms were stored unloaded. Results indicate that while individuals in firearm-owning households are more likely than non-firearm owning households to have healthcare access, those in homes with the riskiest firearm storage practices had less access. Provider-led counseling may have limited reach for individuals in homes with risky firearm storage practices.

Risk of non-syndromic orofacial clefts by maternal rural-urban residence and race/ethnicity: A population-based case-control study in Washington State 1989-2014.

BACKGROUND: Orofacial clefts (OFC) have multifactorial aetiology. Established risk factors explain a small proportion of cases. OBJECTIVES: To evaluate OFC risk by maternal rural residence and race/ethnicity, and test whether these associations changed after US-mandated folic acid fortification. METHODS: This population-based case-control study included all non-syndromic OFC cases among Washington State singleton livebirths between 1989-2014 and birth year-matched controls. Data sources included birth certificates and hospital records. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for OFC by maternal rural-urban residence (adjusted for maternal race/ethnicity) and by maternal race/ethnicity. We evaluated additive and multiplicative effect measure modification by time of folic acid fortification (before vs. after). Probabilistic quantitative bias analysis accounted for potential differential case ascertainment for infants born to Black mothers. RESULTS: The overall non-syndromic OFC birth prevalence was 1.0 per 1000 livebirths (n = 2136 cases). Among controls (n = 25 826), 76% of mothers were urban residents and 72% were of White race/ethnicity. OFC risk was slightly higher for infants born to rural than to urban mothers, adjusting for race/ethnicity (OR 1.12, 95% CI 1.01, 1.25). The association was similar before and after US-mandated folic acid fortification. Compared with infants born to White mothers, OFC risk was higher for American Indian mothers (OR 1.73, 95% CI 1.35, 2.23) and lower for Black (OR 0.62, 95% CI 0.48, 0.81), Hispanic (OR 0.75, 95% CI 0.64, 0.87), and Asian/Pacific Islander (API) mothers (OR 0.87, 95% CI 0.74, 1.02). Bias analysis suggests the observed difference for Black mothers may be explained by selection bias. Post-fortification, the association of OFC with maternal API race/ethnicity decreased and with maternal Black race/ethnicity increased relative to maternal White race/ethnicity. CONCLUSIONS: Infants born to rural mothers and to American Indian mothers in Washington State during 1989-2014 were at higher OFC risk before and after US-mandated folic acid fortification.

The impact of food insecurity on HIV outcomes in Senegal, West Africa: a prospective longitudinal study.

BACKGROUND: Understanding the impact of food insecurity on HIV outcomes is critical for the development and implementation of effective, evidence-based interventions to address food insecurity and improve the HIV care cascade. We conducted a prospective, longitudinal study to determine the impact of food insecurity on HIV outcomes in Senegal, West Africa. METHODS: HIV-infected individuals presenting for care and initiation of ART through the Senegalese National AIDS program in Dakar and Ziguinchor were eligible for enrollment. Data were collected using interviews, clinical evaluations, laboratory analyses, and chart review at enrollment, month 6, and month 12. Logistic regression was used to determine the association between food insecurity and HIV outcomes. RESULTS: Among the 207 participants in this study, 70% were female and the median age was 37 years. The majority (69%) were food insecure at enrollment, 29% were severely food insecure, and 38% were undernourished. Nearly a third (32%) had no formal education, 23% practiced agriculture, and 40% owned livestock. The median daily food expenditure per person was $0.58. The median round trip transportation time to clinic was 90 min (IQR 30-240). The median cost of transportation to clinic was $1.74. At month 12, 69% were food insecure, 23% were severely food insecure, and 14% were undernourished. At month 12, 43% had not disclosed their HIV status; food insecurity was associated with non-disclosure of HIV-status due to fear of stigmatization and feelings of shame. Severe food insecurity was a strong predictor of loss to follow-up (OR 3.13 [1.08-9.06]) and persistent severe food insecurity was associated with virologic failure (OR 5.14 [1.01-26.29]) and poor adherence to ART 8.00 [1.11-57.57]. Poor nutritional status was associated with poor immunologic recovery (OR 4.24 [1.56-11.47]), virologic failure (OR 3.39 [1.13-10.21]), and death (OR 3.35 [1.40-8.03]). CONCLUSION: Severity and duration of food insecurity are important factors in understanding the relationship between food insecurity and HIV outcomes. Our findings highlight the importance of nutritional status, socioeconomic opportunity, and self-stigmatization in the complex pathway between food insecurity and HIV outcomes. Interdisciplinary, multisectoral efforts are needed to develop and implement effective interventions to address food insecurity among people living with HIV.

Association Between Consumption of Sugar-Sweetened Beverages and 100% Fruit Juice With Poor Mental Health Among US Adults in 11 US States and the District of Columbia.

INTRODUCTION: Excess sugar consumption is linked to several mental health conditions. Sugar-sweetened beverages (SSBs) and 100% fruit juice contain similar amounts of sugar per serving, yet prior studies examining sugary beverages and mental health are limited to SSBs. Of those, few have assessed potential modifiers such as sex. METHODS: We examined the association between daily consumption of fruit juice and SSBs with poor mental health by using data from the 2017 Behavioral Risk Factor Surveillance System. We used Poisson regression models with clustered-robust standard errors to measure the association between SSB and fruit juice consumption (none, >0 to <1, and ≥1 times per day) and experiencing 14 or more days of poor mental health in the past month, adjusting for sociodemographic characteristics. We used an F test of joint significance to assess effect modification by sex for SSB and fruit juice analyses. RESULTS: Consuming SSBs 1 or more times per day versus consuming none was associated with a 26% greater prevalence of poor mental health (95% CI, 1.11-1.43). Associations for consuming >0 to <1 times per day compared with consuming none were not significant. We found no evidence of an association between fruit juice consumption and mental health, nor evidence of effect modification by sex in the SSB and fruit juice analyses. CONCLUSION: Consuming SSBs 1 or more times per day was significantly associated with poor mental health whereas 100% fruit juice consumption was not. Future studies should examine alternative cut-points of fruit juice by using prospective designs.

Association of Arthritis and Antihypertensive Medication Use Among Individuals With Hypertension: A Cross-Sectional Analysis of the 2017 Behavioral Risk Factor Surveillance System.

BACKGROUND: The aim of this study was to assess whether arthritis is associated with lower antihypertensive medication (AHM) use among those with hypertension and whether this relationship differs by age or cardiovascular (CV) comorbidity. METHODS: The data were from the 2017 Behavioral Risk Factor Surveillance System. We employed survey weights to account for the complex sampling design and nonresponse bias. We used generalized linear models to estimate unadjusted and adjusted prevalence ratios (PRs) and 95% confidence intervals comparing AHM use among those with severe or mild arthritis to those without arthritis, stratified by age, sex, and CV comorbidity. RESULTS: Among 173,098 adults with hypertension, 26.0% had severe arthritis and 22.3% had mild arthritis. Compared with those without arthritis, individuals with mild or severe arthritis were older, predominantly female, with lower income and more comorbidities. After adjustment for sex, race, inability to afford medications, and CV comorbidity, the prevalence ratios for AHM use were stronger for younger versus older age groups. Associations did not differ significantly by sex or CV comorbidity. Associations were similar for mild and severe arthritis, compared with no arthritis. CONCLUSIONS: Among individuals with hypertension, those with arthritis had significantly higher prevalences of AHM use compared with those without arthritis. Higher prevalences of AHM use were seen with older age categories, although a stronger association of arthritis and AHM use was found in younger age groups. Future studies on hypertension management in arthritis should examine these relationships more closely.

Projected impact and cost-effectiveness of community-based versus targeted azithromycin administration strategies for reducing child mortality in sub-Saharan Africa.

BACKGROUND: Trials of mass drug administration (MDA) of azithromycin (AZM) report reductions in child mortality in sub-Saharan Africa (SSA). AZM targeted to high-risk children may preserve benefit while minimizing antibiotic exposure. We modeled the cost-effectiveness of MDA to children 1-59 months of age, MDA to children 1-5 months of age, AZM administered at hospital discharge, and the combination of MDA and post-discharge AZM. METHODS AND FINDINGS: Models employed a payer perspective with a 1-year time horizon. Cost-effectiveness was presented as cost per DALY averted and death averted, with probabilistic sensitivity analyses. The model included parameters for macrolide resistance, adverse events, hospitalization, and mortality sourced from published data. Assuming a base-case 1.64% mortality risk among children 1-59 months old, 3.1% among children 1-5 months old, 4.4% mortality risk post-discharge, and 13.5% mortality reduction per trial data, post-discharge AZM would avert ~45,000 deaths, at a cost of $2.84/DALY (95% uncertainty interval [UI]: 1.71-5.57) averted. MDA to only children 1-5 months old would avert ~186,000 deaths at a cost of $4.89/DALY averted (95% UI: 2.88-11.42), MDA to all under-5 children would avert ~267,000 deaths a cost of $14.26/DALY averted (95% UI: 8.72-27.08). Cost-effectiveness decreased with presumed diminished efficacy due to macrolide resistance. CONCLUSIONS: Targeting AZM to children at highest risk of death may be an antibiotic-sparing and cost-effective, or even cost-saving, strategy to reduce child mortality. However, targeted AZM averts fewer absolute deaths and may not reach all children who would benefit. Any AZM administration decision must consider implications for antibiotic resistance.

Perspectives on the Future of Epidemiology: A Framework for Training.

Over the past century, the field of epidemiology has evolved and adapted to changing public health needs. Challenges include newly emerging public health concerns across broad and diverse content areas, new methods, and vast data sources. We recognize the need to engage and educate the next generation of epidemiologists and prepare them to tackle these issues of the 21st century. In this commentary, we suggest a skeleton framework upon which departments of epidemiology should build their curriculum. We propose domains that include applied epidemiology, biological and social determinants of health, communication, creativity and ability to collaborate and lead, statistical methods, and study design. We believe all students should gain skills across these domains to tackle the challenges posed to us. The aim is to train smart thinkers, not technicians, to embrace challenges and move the expanding field of epidemiology forward.

Association Between Chronic Hepatitis C Virus Infection and Myocardial Infarction Among People Living With HIV in the United States.

Hepatitis C virus (HCV) infection is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic type 1 MI (T1MI) and supply-demand mismatch type 2 MI (T2MI). We examined the association between HCV and MI among patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems, a US multicenter clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Third Universal Definition of Myocardial Infarction. We estimated the association between chronic HCV (RNA+) and time to MI while adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics, and history of injecting drug use. Among 23,407 PLWH aged ≥18 years, there were 336 T1MIs and 330 T2MIs during a median of 4.7 years of follow-up between 1998 and 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR) = 1.46, 95% confidence interval (CI): 1.09, 1.97) but not T1MI (aHR = 0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR = 2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research.

Trends in Reported Sexual Behavior and Y-Chromosomal DNA Detection Among Female Sex Workers in the Senegal Preexposure Prophylaxis Demonstration Project.

BACKGROUND: Preexposure prophylaxis (PrEP) can reduce HIV acquisition among female sex workers (FSWs). However, changes in condomless sex frequency after PrEP initiation could reduce PrEP effectiveness when PrEP adherence is suboptimal as well as increase the risk of acquiring other sexually transmitted infections. Objective measures of condomless sex may be more accurate for determining changes in sexual behavior than self-reported measures. METHODS: We longitudinally measured self-reported condom use, number of clients, and presence of Y-chromosomal DNA (Yc-DNA) in vaginal swabs among 267 FSWs accessing PrEP at 4 clinics in Senegal between 2015 and 2016. We assessed trends in sexual behavior over time since PrEP initiation using generalized estimating equations and evaluated predictors of Yc-DNA detection. RESULTS: We found no increase in self-reported condomless sex with clients (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.89-1.00), main partners (OR, 0.99; 95% CI, 0.96-1.02), or Yc-DNA detection (OR, 0.99; 95% CI, 0.90-1.08) over time since initiation. Y-chromosomal DNA was detected in 34 (22%) of 154 swabs tested and in 15 (26%) of 58 swabs from FSW reporting consistent condom use among both clients and main partners. Self-reported condom use with clients or main partners did not predict Yc-DNA detection. CONCLUSIONS: In a FSW PrEP demonstration project in Senegal, we found no evidence of risk compensation among FSWs on PrEP as measured by self-reported behavior or through Yc-DNA detection. Y-chromosomal DNA detection was frequently detected among FSWs reporting consistent condom use, highlighting limitations of self-reported sexual behavioral measures.

Sexual Self-Efficacy and Entitlement to Pleasure: The Association of the Female Sexual Subjectivity Inventory with Sexual Risk Taking and Experience of Orgasm.

Young women's understanding of their own sexuality has increasingly been acknowledged as an important component of their sexual health. The Female Sexual Subjectivity Inventory (FSSI) was developed to measure five distinct factors of young women's experiences of sexual pleasure and empowerment. No studies have explicitly evaluated the association between FSSI scores and clinical sexual health outcomes. We conducted a cross-sectional survey of women to assess the association between FSSI factors and the occurrence of three clinical sexual health outcomes in the prior 12 months: acquisition of an STI, unwanted pregnancy, or taking emergency contraception (Plan B). We also assessed the association between FSSI scores and self-reported orgasm frequency during partnered sexual activity. We used multivariate logistic regression models to estimate associations. Finally, we used the FSSI scale in a novel way to identify a population of women who are discordant on their levels of entitlement to pleasure from a partner and self-efficacy in achieving sexual pleasure. We did not find any statistically significant associations between mean score on any of the FSSI factors and clinical sexual health outcomes of interest in the prior year. We found that all FSSI factors except Sexual Self-Reflection were positively associated with increased orgasm frequency. Our study underscores the validity of the FSSI as a measure to assess psychosocial constructs relevant to young women's ability to experience sexual pleasure with a partner and introduces a novel way to use the scale to assess the development of women's sexual subjectivity.

Female genital mutilation and noninvasive cervical abnormalities and invasive cervical cancer in Senegal, West Africa: A retrospective study.

Female genital mutilation or cutting (FGM/C) is a traditional practice that affects a significant portion of women in sub-Saharan Africa, Egypt, areas of the Middle East and some countries in Asia. While clinical and epidemiological studies have established a close association between inflammation and carcinogenesis, particularly in epithelial cancers, the relationship between FGM/C and cervical cancer is not well known. We performed a secondary analysis using combined data from six research studies conducted in and around Dakar, Senegal from 1994 to 2012. Study subjects included both asymptomatic women who presented to outpatient clinics but were screened for cervical cancer, and women with cancer symptoms who were referred for cervical cancer treatment. We used unconditional logistic regression to estimate adjusted pooled odds ratios (ORs) and 95% confidence intervals (CI) for associations between FGM/C and (1) Invasive cervical cancer (ICC) and (2) noninvasive cervical abnormalities. After adjusting for confounding, women with ICC were 2.50 times more likely to have undergone FGM/C than women without cervical abnormalities (95% CI, 1.28-4.91). Restricting to HPV-positive women increased the strength of the association (OR = 4.23; 95% CI 1.73-10.32). No significant associations between FGM/C and noninvasive cervical abnormalities were observed, except in commercial sex workers with FGM/C (OR = 2.01; 95% CI 1.19-3.40). The potential increased risk for ICC suggested by our study warrants further examination. Study results may impact cancer prevention efforts in populations where FGM/C is practiced and draw awareness to the additional health risks associated with FGM/C.

Prevalence, predictors, and management of advanced HIV disease among individuals initiating ART in Senegal, West Africa.

BACKGROUND: The WHO guidelines for the management of advanced HIV disease recommend a package of care consisting of rapid initiation of antiretroviral therapy (ART), enhanced screening and diagnosis of tuberculosis (TB) and cryptococcal meningitis, co-trimoxazole prophylaxis, isoniazid preventive therapy (IPT), fluconazole pre-emptive therapy, and adherence support. The goals of this study were to determine the prevalence of advanced HIV disease among individuals initiating ART in Senegal, to identify predictors of advanced disease, and to evaluate adherence to the WHO guidelines. METHODS: This study was conducted among HIV-positive individuals initiating ART in Dakar and Ziguinchor, Senegal. Clinical evaluations, laboratory analyses, questionnaires and chart review were conducted. Logistic regression was used to identify predictors of advanced disease. RESULTS: A total of 198 subjects were enrolled; 70% were female. The majority of subjects (71%) had advanced HIV disease, defined by the WHO as a CD4 count < 200 cells/mm3 or clinical stage 3 or 4. The median CD4 count was 185 cells/mm3. The strongest predictors of advanced disease were age ≥ 35 (OR 5.80, 95%CI 2.35-14.30) and having sought care from a traditional healer (OR 3.86, 95%CI 1.17-12.78). Approximately one third of subjects initiated ART within 7 days of diagnosis. Co-trimoxazole prophylaxis was provided to 65% of subjects with CD4 counts ≤350 cells/mm3 or stage 3 or 4 disease. TB symptom screening was available for 166 subjects; 54% reported TB symptoms. Among those with TB symptoms, 39% underwent diagnostic evaluation. Among those eligible for IPT, one subject received isoniazid. No subjects underwent CrAg screening or received fluconazole to prevent cryptococcal meningitis. CONCLUSIONS: This is the first study to report an association between seeking care from a traditional healer and presentation with WHO defined advanced disease in sub-Saharan Africa. Given the widespread use of traditional healers in sub-Saharan Africa, future studies to further explore this finding are indicated. Although the majority of individuals in this study presented with advanced disease and warranted management according to WHO guidelines, there were numerous missed opportunities to prevent HIV-associated morbidity and mortality. Programmatic evaluation is needed to identify barriers to implementation of the WHO guidelines and enhanced funding for operational research is indicated.