Virological and care outcomes of community ART distribution: Experience with the PODI+ model in Kinshasa, Democratic Republic of the Congo.

INTRODUCTION: Differentiated service delivery models for HIV treatment can minimize unnecessary burdens on health systems and promote efficient delivery of antiretroviral therapy (ART). Under the PODI+ (poste de distribution communautaire) model, ART multi-month dispensation (MMD) was provided by lay workers (peers) in communities. We compared outcomes among clinically stable adults living with HIV receiving MMD via PODI+ or health facility (HF). METHODS: Clients receiving MMD at nine HFs and two PODI+ sites in Kinshasa were followed prospectively for one year (2018-2020). Medication possession ratio (MPR) was measured as proportion of total days with medication during the study through record abstraction at 3-month intervals. Viral load was assessed at enrollment and 12 months. We compared MPR and viral load suppression by arm and examined associations and potential confounders using unadjusted and adjusted odds ratios (AOR). Likert-style client satisfaction was collected during 12-month interviews and described by arm. RESULTS: Odds of maintaining viral load suppression at 12 months for PODI+ participants were two times that for HF participants. In adjusted models, PODI+ participants had 1.89 times the odds of being suppressed at 12 months compared to HF participants (95% CI: 1.10, 3.27). No significant differences in MPR were found between groups (OR: 0.86, 0.38-1.99). Older participants had significantly higher odds of MPR (AOR: 1.02, 95% CI: 1.01, 1.03) and viral suppression (AOR: 1.03, 95% CI: 1.00, 1.07). Satisfaction with services was ≥87% overall, but PODI+ participants rated time spent at site, provider attributes and other care aspects more favorably. CONCLUSIONS: Participants receiving MMD via peer-run community distribution points had similar MPR, but better virological outcomes and greater satisfaction with care than clinically similar participants receiving MMD through facilities. PODI+ could be a useful model for expansion to serve larger clinic populations from overburdened health facilities, particularly as policy shifts towards more inclusive MMD eligibility requirements.

Strengthening the Evidence: Similar Rates of Neural Tube Defects Among Deliveries Regardless of Maternal HIV Status and Dolutegravir Exposure in Hospital Birth Surveillance in Eswatini.

Birth defect surveillance in Eswatini in 2020-2021 identified 0.80% defects (197/24 599 live and stillborn infants). Neural tube defect (NTD) prevalence was 0.08%, 0.08%, and 0.15% for 4902 women on dolutegravir preconception, 17 285 HIV-negative women, and 1320 women on efavirenz preconception, respectively, more definitively refuting the dolutegravir preconception NTD safety signal.

Effectiveness of an integrated multilevel early child development intervention on caregiver knowledge and behavior: a quasi-experimental evaluation of the Malezi program in Tanzania.

BACKGROUND: The quality of caregiving and the parent-child relationship is critical for early child development (ECD) and has been shown to be modifiable. This study evaluated an ECD project in Tanzania, assessing the effectiveness of radio messaging (RM) alone and a combined radio messaging/video job aids/ECD (RMV-ECD) intervention. METHODS: This two-arm pre-post evaluation study enrolled a cohort of caregivers of children 0-24 months in four districts of Tabora region, following them for 9 months. ECD radio messages were broadcast on popular stations at least 10 times/day reaching all study districts. In two districts, community health workers (CHW), trained in UNICEF's Care for Child Development package, used ECD videos in home- and facility-based sessions with caregivers. We used McNemar's testing (pre-post pairs) within intervention group to describe how the intervention was associated with change in five outcomes: ECD knowledge, early stimulation, father engagement, responsive care, and environment safety. Logistic regression was used to describe the relative benefits of the combined intervention package (RMV-ECD) compared to radio messaging (RM). RESULTS: In the RMV-ECD arm, all outcomes at endline except environment safety significantly improved after the intervention with the largest change seen in ECD knowledge (35.8% increase, p < .0001) and the smallest in father engagement (6.7%, p = .015). In the RM arm, ECD knowledge (5.7%, p = .031) and environment safety (18.1%, p = <.0001) improved. High measures of parenting stress were associated with lower likelihood of having good ECD knowledge (AOR 0.50, 95%CI: 0.35, 0.71), father engagement (AOR 0.72, 95%CI: 0.52, 0.99) and responsive care (AOR 0.31, 95%CI: 0.18, 0.54). CONCLUSIONS: An intervention that includes mass media, educational video content and CHWs who counsel caregivers in their homes and health facilities was associated with significant improvements in ECD parenting knowledge and behaviors but a relationship with responsive care could not be established. The less costly mass media-only intervention was associated with improved parenting knowledge and household environment safety. Parenting interventions targeting young children could be improved by incorporating more messaging and caregiver coaching in managing parental stress. TRIAL REGISTRATION: NCT05244161 (17/02/2022); retrospectively registered with the US National Institutes of Health ClinicalTrials.gov.

Factors Associated with Transition of HIV Care Readiness Among Adolescents and Youth from a Specialty Pediatric HIV Clinic in the United States.

Transitioning from pediatric to adult services is known to be associated with worsening of health outcomes and decreased retention in care among adolescents and youth living with HIV (AYLHIV). We aimed to identify factors associated with HIV care transition readiness among AYLHIV in care at a pediatric HIV clinic in Washington, DC. This retrospective cohort study from June 2019 through January 2021 collected demographic and clinical characteristics from the clinic database. We adapted the Transition Readiness Assessment Questionnaire (TRAQ; scored 1-4; 1 being the lowest level of preparedness) to evaluate transition readiness over time. We analyzed data using two-sided unadjusted two-sample and paired t-tests and adjusted analysis of variance (ANOVA). We included 103 AYLHIV (50.49% female; 100% non-Hispanic Black/African American; mean age = 19.54 ± 2.78 years; 81.55% virally suppressed). Mean baseline TRAQ score (2.32 ± 0.78) was associated with age (p < 0.0001), gender (p = 0.033), mode of HIV transmission (p = 0.0005), viral suppression (p = 0.0033), and duration of HIV diagnosis (p = 0.012). AYLHIV diagnosed with HIV within the prior year experienced significantly greater mean improvement in transition readiness compared with those living with HIV for >10 years (p = 0.013). Adjusted for covariates, older age (p < 0.0001), undetectable viral load (p = 0.0008), and presence of mental health condition(s) (p = 0.020) were associated with higher TRAQ scores. Lower improvement in transition readiness among youth with a longer history of HIV suggests that AYLHIV with perinatally acquired HIV might require additional support than those with horizontally acquired HIV.

Adverse Pregnancy Outcomes Among HIV-positive Women in the Era of Universal Antiretroviral Therapy Remain Elevated Compared With HIV-negative Women.

BACKGROUND: Without treatment, HIV infection in pregnant women is associated with adverse pregnancy outcomes. We compared adverse pregnancy outcomes among HIV-positive women on antiretroviral therapy (ART) and HIV-negative women who enrolled for antenatal care in selected health facilities in Maseru district, Lesotho. METHODS: We enrolled a cohort of HIV-positive and HIV-negative women at their first antenatal visit and followed them through delivery. Study data on miscarriage, stillbirth, preterm birth, low birth weight and birth defects were collected through participant interviews and medical record abstraction. We used the Rao-Scott χ2 test and the t test to assess differences in characteristics and outcomes between HIV-positive and HIV-negative women and generalized estimating equations for multivariable analysis. RESULTS: A total of 614 HIV-positive and 390 HIV-negative pregnant women were enrolled in the study with delivery information on 571 (93.1%) and 352 (90.3%) respectively. In the delivery cohort, the median age at enrolment was 28 years for HIV-positive women and 23 years for HIV-negative women with median gestational ages of 20 and 21 weeks, respectively. A total of 149 singleton pregnancies had documented adverse pregnancy outcomes; 33 (9.6%) HIV-negative pregnancies and 116 (20.6%) HIV-positive pregnancies. Compared with their HIV-negative counterparts, HIV-positive women were more likely to experience an adverse pregnancy outcome, adjusted odds ratio (AOR) 2.6 [95% confidence interval (CI): 1.71-3.97]; an intrauterine death (miscarriage or stillbirth), AOR 2.64 [95% CI: 1.25-5.49]; or a low birth weight delivery, AOR 1.89 [95% CI: 1.16-3.09]. CONCLUSION: Adverse pregnancy outcomes remained 2-3 times higher among HIV-positive women compared with HIV-negative women despite universal ART.

Changes in cerebral tissue oxygenation and fractional oxygen extraction with gestational age and postnatal maturation in preterm infants.

OBJECTIVE: This study examined the correlation of cerebral tissue oxygen saturation (SctO2) and cerebral tissue fractional oxygen extraction (cFTOE) with gestational age (GA) and postnatal age over the first 28 days of life. STUDY DESIGN: Preterm infants with birth weight (BW) <1500 g were monitored with near-infrared spectroscopy (NIRS) during the first 28 days of life. SctO2 and cFTOE measurements were analyzed using a linear mixed model. RESULTS: A total of 70 preterm infants were included. Mean SctO2 decreased with increasing GA; SctO2 was 76.4% and 74.6% in the first 24 h for infants 24 and 28-week GA, respectively. For infants born at 24 and 28 it decreased to 52.9% and 58.4% at 28 days of life, respectively. cFTOE increased with increasing GA and postnatal age. CONCLUSIONS: There is an inverse relationship between SctO2 and gestational age and postnatal age but a direct relationship between cFTOE with GA and postnatal age.

Small-area spatial-temporal changes in pre-exposure prophylaxis (PrEP) use in the general population and among men who have sex with men in the United States between 2012 and 2018.

PURPOSE: Oral emtricitabine/tenofovir disoproxil fumarate was approved for use as pre-exposure prophylaxis (PrEP) by the U.S. Food and Drug Administration in 2012. We used national pharmacy data to examine trends of PrEP use in U.S. counties from 2012 to 2018. METHODS: Using multi-level small-area spatio-temporal modeling, we calculated the estimated annual percentage change (EAPC) in prevalence of PrEP use in the general population from 2012 to 2018. We also used a proxy measure for prevalence of PrEP use among men who have sex with men (MSM) to evaluate trends of use among MSM, the PrEP use-to-MSM ratio (PmR) or number of male PrEP users per 1000 MSM population. RESULTS: The prevalence of PrEP use and PmR increased (EAPC range: (+26.9%, +71.0%) and (+28.4%, +158.7%), respectively) in all counties with varying magnitude of increase. Counties of the Midwest and the upper South and upper West had the slowest increase in prevalence of PrEP use (EAPC range: (+26.9%; +52.9%)). Counties of the northern part of the South had the lowest PmR (EAPC range: (+28.4%; +76.0%)). Counties of the most populous core-based statistical areas had a relatively faster increase in population prevalence of PrEP use but slower increase in PmR. CONCLUSIONS: All counties in the U.S. have witnessed an increase in PrEP use with important geographic variabilities. Identifying areas with slow improvement in PrEP use, as well as "model counties" with the fastest pace of progress in PrEP coverage, is critical to inform local and state-level policies and program evaluation for PrEP scale up, particularly among MSM at higher risk for HIV.

Active pediatric HIV case finding in Kenya and Uganda: A look at missed opportunities along the prevention of mother-to-child transmission of HIV (PMTCT) cascade.

BACKGROUND: Children living with HIV remain undiagnosed due to missed opportunities along the prevention of mother-to-child HIV transmission cascade. This study addresses programmatic gaps in the cascade by describing pregnancy and HIV-related services received by mothers of children newly identified as HIV-positive through active case finding. METHODS: This was a prospective observational cohort (2017-2018) of HIV-positive children <15 years of age newly diagnosed at study facilities and/or surrounding communities in Kenya and Uganda. At enrollment, caregivers were interviewed about maternal and child health and HIV history. Child medical and laboratory information was abstracted at two months post-diagnosis. Descriptive summary statistics were calculated; associations between selected factors and child age at HIV diagnosis were evaluated using generalized estimating equations. RESULTS: 174 HIV-positive children (median age 2.4 years) were enrolled. Among maternal caregivers, 110/132 (83.3%) attended antenatal care and 60 (45.5%) reported testing HIV-negative in antenatal care. Of 41 and 56 women known to be HIV-positive during pregnancy and breastfeeding respectively, 17 (41.5%) and 15 (26.8%) did not receive antiretroviral drugs. Despite known maternal HIV-positive status during pregnancy, 39% of these children were not diagnosed until after two years of age; children were diagnosed at younger ages in Uganda (p = 0.0074) and if mother was the caregiver (p<0.0001). The most common HIV testing points identifying children were outpatient (44.3%) and maternal/child health departments (29.9%). Nearly all children initiated antiretroviral therapy within two weeks of diagnosis. CONCLUSIONS: Multiple missed opportunities for HIV prevention and delays in HIV testing of HIV-exposed children were identified in newly diagnosed children. Findings support critical prevention messaging and retesting of HIV-negative women during pregnancy and breastfeeding, strengthening HIV treatment initiation and follow-up systems and interventions to ensure HIV-positive women receive lifelong antiretroviral therapy throughout the cascade, and broader implementation of community case finding so children not engaged in care receive testing services.

Conventional early infant diagnosis in Lesotho from specimen collection to results usage to manage patients: Where are the bottlenecks?

INTRODUCTION: Early infant diagnosis is an important step in identifying children infected with HIV during the perinatal period or in utero. Multiple factors contribute to delayed antiretroviral treatment initiation for HIV-infected children, including delays in the early infant HIV diagnosis cascade. METHODS: We conducted a retrospective study to evaluate early infant diagnosis turnaround times in Lesotho. Trained staff reviewed records of HIV-exposed infants (aged-6-8 weeks) who received an HIV test during 2011. Study sites were drawn from Highlands, Foothills and Lowlands regions of Lesotho. Central laboratory database data were linked to facility and laboratory register information. Turnaround time geometric means (with 95% CI) were calculated and compared by region using linear mixed models. RESULTS: 1,187 individual infant records from 25 facilities were reviewed. Overall, early infant diagnosis turnaround time was 61.7 days (95%CI: 55.3-68.7). Mean time from specimen collection to district laboratory was 14 days (95%CI: 12.1-16.1); from district to central laboratory, 2 days (95%CI 0.8-5.2); results from central laboratory to district hospital, 23.3 days (95%CI: 18.7-29.0); from district hospital to health facility, 3.2 days (95%CI 1.9-5.5); and from health facility to caregiver, 10.4 days (95%CI, 7.9-13.5). Mean times from specimen transfer to the central laboratory and for result transfer from central laboratory to district hospital were significantly shorter in the Lowlands Region (0.9 and 16.2 days, respectively), compared to Highlands Region (6.0 [P = 0.030] and 34.3 days [P = 0.0099]. Turnaround time from blood draw to receipt of results was significantly shorter for HIV infected infants compared to HIV uninfected infants [p = 0.0036] at an average of 47.1 days (95%CI: 38.9-56.9) and 62 days (95%CI: 55.9-68.7) respectively. Of 47 HIV-infected infants, 36 were initiated on antiretroviral therapy at an average of 1.3 days (95%CI: 0.3, 5.7) after caregiver received the result. CONCLUSION: HIV-infected infants received results earlier and were rapidly initiated on antiretroviral therapy once the result was delivered to caregiver. However, average early infant diagnosis turnaround time was two months; the longest period of delay was transfer of results from central laboratory to district hospital. Turnaround time of results based on geographical regions or between hospitals and health centres varied but did not reach statistical significance.

Understanding Antiretroviral Treatment Adherence Among HIV-Positive Women at Four Postpartum Time Intervals: Qualitative Results from the Kabeho Study in Rwanda.

As lifelong antiretroviral therapy (ART) for pregnant women is implemented, it is important to understand the attitudes and norms affecting women's postpartum ART adherence. This is a qualitative cross-sectional study of HIV-positive postpartum women (n = 112) enrolled in a 2-year observational prospective cohort in Rwanda. Informed by the Theory of Reasoned Action (TRA), we conducted in-depth interviews with women whose children were 0-6, 7-12, 13-18, or 21-24 months of age to describe factors contributing to adherence and changes over time. Positive ART attitudes reported by women included mothers' health promotion, prevention of infant HIV infection, higher CD4 count, and improved physical appearance. Negative attitudes were few, but included side effects and the lifelong nature of treatment. Learning from people living with HIV (PLHIV) was identified as a norm facilitating adherence; ART adherence was inhibited by fear of disclosure or stigmatization in communities and clinics. Poor adherence behaviors were common immediately after HIV diagnosis, not necessarily during prevention of mother-to-child transmission (PMTCT). Women with older children, most of whom stopped breastfeeding by 13-18 months, reported more barriers and missed doses than women with younger children. The TRA was useful in identifying the collective influence of attitudes, norms, and intentions on behavior. Findings suggest that HIV-positive women are vulnerable to poor adherence following HIV diagnosis and around the time of breastfeeding cessation. Lifelong treatment adherence can be supported through PLHIV exemplifying long-term ART use, fewer and less stigmatizing clinic visits, and counseling messages highlighting the benefits of drugs on appearance and illness prevention and incorporating biological feedback.

24-month HIV-free survival among infants born to HIV-positive women enrolled in Option B+ program in Kigali, Rwanda: The Kabeho Study.

Lifelong antiretroviral therapy (ART) provision to all pregnant HIV-positive women ("Option B+") has been recommended by the World Health Organization since 2013, but there remain limited data on the effects of Option B+ on long-term HIV-free survival in breastfeeding HIV-exposed infants. The Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) study enrolled HIV-positive women from the third trimester of pregnancy to 2 weeks postpartum in 14 heath facilities implementing Option B+ in Kigali, Rwanda. Mother-child pairs in the longitudinal observational cohort were followed until 24 months postpartum, with HIV diagnostic testing at 6 weeks, and 9, 18 and 24 months. The Kaplan-Meier method was used to estimate HIV transmission, survival, and HIV-free survival through 24 months. We enrolled 608 HIV-positive women in 2013-2014; birth outcome data were available for 600 women and 597 live-born infants. By 6 weeks, 11 infants had died and 3 infants had confirmed HIV infection (0.5% transmission; 95% confidence interval [CI] 0.2-1.6). At 9 months, there were 9 additional deaths and 2 new infections (cumulative transmission 0.9%, 95% CI 0.4-2.2). At 18 months, there were 6 additional deaths and no new infant infections. At 24 months, there were no additional child deaths and 1 new infection (cumulative 2.2%, 95% CI 0.7-7.0), for an overall 24-month HIV-free survival of 93.2% (95% CI 89.5-95.6). Low transmission rates and high HIV-free survival at 24 months were achieved in breastfeeding infants of HIV-positive mothers receiving universal ART in urban health facilities in Rwanda, though vigilance on maintaining viral suppression for ART-experienced women is needed.

Assessing Very Early Infant Diagnosis Turnaround Times: Findings from a Birth Testing Pilot in Lesotho.

Very early infant diagnosis (VEID) (testing within two weeks of life), combined with rapid treatment initiation, could reduce early infant mortality. Our study evaluated turnaround time (TAT) to receipt of infants' HIV test results and ART initiation if HIV-infected, with and without birth testing availability. Data from facility records and national databases were collected for 12 facilities offering VEID, as part of an observational prospective cohort study, and 10 noncohort facilities. HIV-exposed infants born in January-June 2016 and any cohort infant diagnosed as HIV-infected at birth or six weeks were included. The median TAT from blood draw to caregiver result receipt was 76.5 days at birth and 63 and 70 days at six weeks at cohort and noncohort facilities, respectively. HIV-exposed infants tested at birth were approximately one month younger when their caregivers received results versus those tested at six weeks. Infants diagnosed at birth initiated ART about two months earlier (median 6.4 weeks old) than those identified at six weeks (median 14.8 weeks). However, the long TAT for testing at both birth and six weeks illustrates the prolonged process for specimen transport and result return that could compromise the effectiveness of adding VEID to existing overburdened EID systems.

Detectable Viral Load in Late Pregnancy among Women in the Rwanda Option B+ PMTCT Program: Enrollment Results from the Kabeho Study.

There are limited viral load (VL) data available from programs implementing "Option B+," lifelong antiretroviral treatment (ART) to all HIV-positive pregnant and postpartum women, in resource-limited settings. Extent of viral suppression from a prevention of mother-to-child transmission of HIV program in Rwanda was assessed among women enrolled in the Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) Study. ARV drug resistance testing was conducted on women with VL>2000 copies/ml. In April 2013-January 2014, 608 pregnant or early postpartum HIV-positive women were enrolled in 14 facilities. Factors associated with detectable enrollment VL (>20 copies/ml) were examined using generalized estimating equations. The most common antiretroviral regimen (56.7%, 344/607) was tenofovir/lamivudine/efavirenz. Median ART duration was 13.5 months (IQR 3.0-48.8); 76.1% of women were on ART at first antenatal visit. Half of women (315/603) had undetectable RNA-PCR VL and 84.6% (510) had <1,000 copies/ml. Detectable VL increased among those on ART > 36 months compared to those on ART 4-36 months (72/191, 37.7% versus 56/187, 29.9%), though the difference was not significant. The odds of having detectable enrollment VL decreased significantly as duration on ART at enrollment increased (AOR = 0.99, 95% CI: 0.9857, 0.9998, p = 0.043). There was a higher likelihood of detectable VL for women with lower gravidity (AOR = 0.90, 95% CI: 0.84, 0.97, p = 0.0039), no education (AOR = 2.25, (95% CI: 1.37, 3.70, p = 0.0004), nondisclosure to partner (AOR = 1.97, 95% CI: 1.21, 3.21, p = 0.0063) and side effects (AOR = 2.63, 95% CI: 1.72, 4.03, p<0.0001). ARV drug resistance mutations were detected in all of the eleven women on ART > 36 months with genotyping available. Most women were receiving ART at first antenatal visit, with relatively high viral suppression rates. Shorter ART duration was associated with higher VL, with a concerning increasing trend for higher viremia and drug resistance among women on ART for >3 years.

Retention of mothers and infants in the prevention of mother-to-child transmission of HIV programme is associated with individual and facility-level factors in Rwanda.

OBJECTIVES: Investigate levels of retention at specified time periods along the prevention of mother-to-child transmission (PMTCT) cascade among mother-infant pairs as well as individual- and facility-level factors associated with retention. METHODS: A retrospective cohort of HIV-positive pregnant women and their infants attending five health centres from November 2010 to February 2012 in the Option B programme in Rwanda was established. Data were collected from several health registers and patient follow-up files. Additionally, informant interviews were conducted to ascertain health facility characteristics. Generalized estimating equation methods and modelling were utilized to estimate the number of mothers attending each antenatal care visit and assess factors associated with retention. RESULTS: Data from 457 pregnant women and 462 infants were collected at five different health centres (three urban and two rural facilities). Retention at 30 days after registration and retention at 6 weeks, 3, 6, 9 and 12 months post-delivery were analyzed. Based on an analytical sample of 348, we found that 58% of women and 81% of infants were retained in care within the same health facility at 12 months post-delivery, respectively. However, for mother-infant paired mothers, retention at 12 months was 74% and 79% for their infants. Loss to facility occurred early, with 26% to 33% being lost within 30 days post-registration. In a multivariable model retention was associated with being married, adjusted relative risk (ARR): 1.26, (95% confidence intervals: 1.11, 1.43); antiretroviral therapy eligible, ARR: 1.39, (1.12, 1.73) and CD4 count per 50 mm(3), ARR: 1.02, (1.01, 1.03). CONCLUSIONS: These findings demonstrate varying retention levels among mother-infant pairs along the PMTCT cascade in addition to potential determinants of retention to such programmes. Unmarried, apparently healthy, HIV-positive pregnant women need additional support for programme retention. With the significantly increased workload resulting from lifelong antiretroviral treatment for all HIV-positive pregnant women, strategies need to be developed to identify, provide support and trace these women at risk of loss to follow-up. This study provides further evidence for the need for such a targeted supportive approach.

Male Pattern Baldness in Relation to Prostate Cancer-Specific Mortality: A Prospective Analysis in the NHANES I Epidemiologic Follow-up Study.

We used male pattern baldness as a proxy for long-term androgen exposure and investigated the association of dermatologist-assessed hair loss with prostate cancer-specific mortality in the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. From the baseline survey (1971-1974), we included 4,316 men who were 25-74 years of age and had no prior cancer diagnosis. We estimated hazard ratios and used Cox proportional hazards regressions with age as the time metric and baseline hazard stratified by baseline age. A hybrid framework was used to account for stratification and clustering of the sample design, with adjustment for the variables used to calculate sample weights. During follow-up (median, 21 years), 3,284 deaths occurred; prostate cancer was the underlying cause of 107. In multivariable models, compared with no balding, any baldness was associated with a 56% higher risk of fatal prostate cancer (hazard ratio = 1.56; 95% confidence interval: 1.02, 2.37), and moderate balding specifically was associated with an 83% higher risk (hazard ratio = 1.83; 95% confidence interval: 1.15, 2.92). Conversely, patterned hair loss was not statistically significantly associated with all-cause mortality. Our analysis suggests that patterned hair loss is associated with a higher risk of fatal prostate cancer and supports the hypothesis of overlapping pathophysiological mechanisms.

Hyperactivated mTOR and JAK2/STAT3 Pathways: Molecular Drivers and Potential Therapeutic Targets of Inflammatory and Invasive Ductal Breast Cancers After Neoadjuvant Chemotherapy.

INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive and rare cancer with a poor prognosis and a need for novel targeted therapeutic strategies. Preclinical IBC data showed strong activation of the phosphatidylinositide-3-kinase/mammalian target of rapamycin (mTOR) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways, and expression of inflammatory cytokines and tumor-associated macrophages (TAMs). PATIENTS AND METHODS: Archival tumor tissue from 3 disease types (IBC treated with neoadjuvant chemotherapy [NAC], n = 45; invasive ductal carcinoma [IDC] treated with NAC [n = 24; 'treated IDC'; and untreated IDC [n = 27; 'untreated IDC']) was analyzed for the expression of biomarkers phospho-S6 (pS6) (mTOR), phospho-JAK2 (pJAK2), pSTAT3, interleukin (IL)-6, CD68 (monocytes, macrophages), and CD163 (TAMs). Surrounding nontumor tissue was also analyzed. RESULTS: Biomarker levels and surrogate activity according to site-specific phosphorylation were shown in the tumor tissue of all 3 disease types but were greatest in IBC and treated IDC and least in untreated IDC for pS6, pJAK2, pSTAT3, and IL-6. Of 37 IBC patients with complete biomarker data available, 100% were pS6-positive and 95% were pJAK2-positive. In nontumor tissue, biomarker levels were observed in all groups but were generally greatest in untreated IDC and least in IBC, except for JAK2. CONCLUSION: IBC and treated IDC display similar levels of mTOR and JAK2 biomarker activation, which suggests a potential mechanism of resistance after NAC. Biomarker levels in surrounding nontumor tissue suggested that the stroma might be activated by chemotherapy and resembles the oncogenic tumor-promoting environment. Activation of pS6 and pJAK2 in IBC might support dual targeting of the mTOR and JAK/STAT pathways, and the need for prospective studies to investigate combined targeted therapies in IBC.

Pregnant and Postpartum Women's Experiences and Perspectives on the Acceptability and Feasibility of Copackaged Medicine for Antenatal Care and PMTCT in Lesotho.

Objective. To improve PMTCT and antenatal care-related service delivery, a pack with centrally prepackaged medicine was rolled out to all pregnant women in Lesotho in 2011. This study assessed acceptability and feasibility of this copackaging mechanism for drug delivery among pregnant and postpartum women. Methods. Acceptability and feasibility were assessed in a mixed method, cross-sectional study through structured interviews (SI) and semistructured interviews (SSI) conducted in 2012 and 2013. Results. 290 HIV-negative women and 437 HIV-positive women (n = 727) participated. Nearly all SI participants found prepackaged medicines acceptable, though modifications such as size reduction of the pack were suggested. Positive experiences included that the pack helped women take pills as instructed and contents promoted healthy pregnancies. Negative experiences included inadvertent pregnancy disclosure and discomfort carrying the pack in communities. Implementation was also feasible; 85.2% of SI participants reported adequate counseling time, though 37.8% felt pack use caused clinic delays. SSI participants reported improvement in service quality following pack introduction, due to more comprehensive counseling. Conclusions. A prepackaged drug delivery mechanism for ANC/PMTCT medicines was acceptable and feasible. Findings support continued use of this approach in Lesotho with improved design modifications to reflect the current PMTCT program of lifelong treatment for all HIV-positive pregnant women.

Parity and diabetes risk among hispanic women from Colombia: cross-sectional evidence.

OBJECTIVE: The association between parity and type 2 diabetes has been studied in developed countries and in Singapore and Chinese women but not in Hispanics. Herein we evaluated the association between parity (number of live births) with diabetes in a group of Hispanic postmenopausal women from Colombia. RESEARCH DESIGN AND METHODS: Herein we evaluated the association between parity and diabetes in a population of 1,795 women from Colombia. Women were divided in birth categories (0 [referent], 1 or 2, 3-5, 6 or > births). Medical history of diabetes and anthropometric characteristics were recorded. Logistic regressions were performed in order to find the association between parity and diabetes in bivariable and multivariable models after controlling for age, body mass index (BMI), waist hip ratio (WHR) and diabetes family history, among other variables. RESULTS: In our study, there was an association between parity and diabetes after adjusting for age, BMI and diabetes family history in the multiparous women groups when compared to the women with no births (Referent group) [1-2 births vs. referent OR 5.2 (95 CI 1.2-22.9), 3-5 births vs. referent OR 5.5 (1.3-23.0) and ≥6 births vs. referent OR 7.5 (1.8-31.8), respectively]. The association was maintained in two of the groups in the multivariable analysis [OR 5.0 (1.1-22.9) and 5.3 (1.2-23.5)], for 1 or 2 births and 6 or > births versus 0 births, respectively. Positive diabetes family history and WHR were also associated with an increased risk of diabetes [OR 4.6 (3.0-7.0) and 4.1 (2.0-8.1), respectively]. CONCLUSIONS: In postmenopausal Hispanic women, multiparity, as well as a positive family history of diabetes and a high waist-hip ratio were associated with higher diabetes risk.

Relationship between male pattern baldness and the risk of aggressive prostate cancer: an analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

PURPOSE: Male pattern baldness and prostate cancer appear to share common pathophysiologic mechanisms. However, results from previous studies that assess their relationship have been inconsistent. Therefore, we investigated the association of male pattern baldness at age 45 years with risks of overall and subtypes of prostate cancer in a large, prospective cohort­the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. METHODS: We included 39,070 men from the usual care and screening arms of the trial cohort who had no cancer diagnosis (excluding nonmelanoma skin cancer) at the start of follow-up and recalled their hair-loss patterns at age 45 years. Hazard ratios (HRs) and 95% CIs were estimated by using Cox proportional hazards regression models with age as the time metric. RESULTS: During follow-up (median, 2.78 years), 1,138 incident prostate cancer cases were diagnosed, 571 of which were aggressive (biopsy Gleason score ≥ 7, and/or clinical stage III or greater, and/or fatal). Compared with no baldness, frontal plus moderate vertex baldness at age 45 years was not significantly associated with overall (HR, 1.19; 95% CI, 0.98 to 1.45) or nonaggressive (HR, 0.97; 95% CI, 0.72 to 1.30) prostate cancer risk but was significantly associated with increased risk of aggressive prostate cancer (HR, 1.39; 95% CI, 1.07 to 1.80). Adjustment for covariates did not substantially alter these estimates. Other classes of baldness were not significantly associated with overall or subtypes of prostate cancer. CONCLUSION: Our analysis indicates that frontal plus moderate vertex baldness at age 45 years is associated with an increased risk of aggressive prostate cancer and supports the possibility of common pathophysiologic mechanisms.

True durability: HIV virologic suppression in an urban clinic and implications for timing of intensive adherence efforts and viral load monitoring.

Although the majority of HIV-infected patients who begin potent antiretroviral therapy should expect long-term virologic suppression, the realities in practice are less certain. Durability of viral suppression was examined to define the best timing of targeted adherence strategies and intensive viral load monitoring in an urban clinic population with multiple challenges to ART adherence. We examined the risk of viral rebound for patients who achieved two consecutive viral loads lower than the lower limit of quantification (LLOQ) within 390 days. For 791 patients with two viral loads below the LLOQ, viral rebound >LLOQ from the first viral load was 36.9 % (95 % CI 32.2-41.6) in the first year, 26.9 % (95 % CI 21.7-32.1) in the year following one year of viral suppression, and 24.6 % (95 % CI 18.4-30.9) in the year following 2 years of viral suppression. However, for patients with CD4 ≥300 cells/µl who had 3-6 years of virologic suppression, the risk of viral rebound was very low. At the population level, the risk of viral rebound in a complex urban clinic population is surprisingly high even out to 3 years. Intensified monitoring and adherence efforts should target this high risk period. Thereafter, confidence in truly durable virologic suppression is improved.