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Traumatic spine fractures can result in chronic pain, disability, and prolonged rehabilitation. The purpose of this study is to determine the long-term effects of traumatic spine fractures on patients' functional outcomes after nonoperative and operative management.Patients with traumatic spine fractures over a 5-year period were identified and stratified by management strategy (nonoperative and operative) and compared. Functional outcomes were measured using the Boston Activity Measure for PostAcute Care to assess basic mobility and daily activity. Multiple linear regression was used to identify predictors of functional outcome after traumatic spine fractures.In total, 488 patients were identified: 271 nonoperative and 217 operative. Follow-up was obtained in 168 (34%) patients: 95 nonoperative and 73 operative. Mean follow-up was 5.7 years (range 3-8 years). Mean Activity Measure for PostAcute Care scores in patients managed nonoperatively for basic mobility (68 vs 64, P = .09) and daily activity (69 vs 66, P = .26) were clinically similar to those managed operatively. Multiple linear regression identified increasing age as a predictor of decreased basic mobility (β = -0.50, P.0001, β = -0.17, P = .022) and daily activity (β = -0.58, P.0001, β = -0.35, P = .003) in nonoperative and operative groups, respectively. In nonoperative patients, thoracic spine fracture was predictive of both decreased basic mobility (β = -5.88, P = .041) and daily activity (β = -8.62, P = .043). In operative patients, lower extremity fractures (β = -8.86, P = .012), discharge location (β = -6.91, P = .003), and time to operative fixation (β = -0.77, P = .040) were associated with decreased basic mobility.All patients with traumatic spine fractures displayed mild to moderate functional impairment. Age, thoracic fractures, lower extremity fractures, discharge location, and time to operative fixation were associated with poor functional outcomes.

BackgroundEarly neurologic deterioration (END) following ischemic stroke is a serious event and is associated with poor outcomes. However, the incidence and predictors of END after stroke thrombectomy for emergent large vessel occlusion are largely unknown.MethodsThe baseline characteristics of patients enrolled in the COMPASS trial (NCT02466893) were analyzed. The primary outcome was worsening of ≥4 National Institutes of Health Stroke Scale (NIHSS) points 24 hours post thrombectomy (4+ END24) and the secondary outcome was deterioration of ≥2 points (2+ END24).ResultsAmong 270 patients, 27 (10%) developed 4+ END24and 42 (16%) had 2+ END24. Those with 4+ END24were older (76.4±12.9 vs 70.9±12.9 years; p=0.04), had a higher prevalence of hypertension (96% vs 69%; p=0.003), diabetes (41% vs 27%; p=0.13) and higher pretreatment systolic blood pressure (SBP) (170.4±32.6 vs 157.6±28.1 mmHg; p=0.03). More 4+ END24patients had failed reperfusion: Thrombolysis in Cerebral Infarction ≤2a (26% vs 8%; p=0.003). In unadjusted analysis, older patients and those with hypertension, diabetes, elevated SBP and failed reperfusion had higher odds of 4+ END24. In adjusted analysis, age increase by 5 years led to an increase in 4+ END24of 28%, diabetes increased odds of 2.6 and failed reperfusion increased odds of 4.5. In the multivariable analysis for the secondary outcome, age (OR 1.33; 95% CI 1.109 to 1.593), diabetes (OR 2.7; 95% CI 1.247 to 5.764) and failed reperfusion (OR 7.2; 95% CI 0.055 to 0.349) were also significant predictors of 2+ END24.ConclusionsOlder patients with acute ischemic stroke who have a history of diabetes or hypertension, with elevated pretreatment SBP and failed reperfusion are at a higher risk of END following stroke thrombectomy for emergent large vessel occlusion.

IntroductionWhile young women in South Africa may navigate both HIV infection and pregnancy risks, intrauterine contraceptive (IUC) use is low. Though IUCs have low failure rates, concerns exist about whether the IUC is an appropriate method choice for women living with HIV (WLHIV). In this qualitative study, we explore WLHIVs' experiences of using IUC and reasons for discontinuation.MethodsThis qualitative study included in-depth interviews (IDIs) with 17 WLHIV who electively discontinued their allocated IUC while participating in a randomized controlled trial comparing the safety of the levonorgestrel intrauterine system (LNG-IUS) and the copper intrauterine device (C-IUD) in Cape Town, South Africa. The transcripts were coded and emergent themes were grouped to examine women's experiences with IUC use and reasons for discontinuation, highlighting experiential differences between the two methods.ResultsWomen's experience with the allocated IUC related most commonly to bleeding and/or abdominal pain just after insertion. Most C-IUD discontinuers, but only one LNG-IUS discontinuer, complained of pain and/or increased bleeding as the main reason for removal. Three women (two LNG-IUS, one C-IUD) requested removal because they desired pregnancy, while two others discontinued due to fears the IUC was exacerbating non-gynecologic conditions (hypertension, diabetes). Generally, women acknowledged advantages of IUC use and many expressed their desire to continue use if not for the side effects.ConclusionsIn the South African context, IUC use for WLHIV should be promoted with specific counseling considerations. Both providers and potential users should receive specific information about potential menstrual-related side effects and countering common misperceptions to enable informed contraceptive decision-making.

Background Interventions for increasing the uptake of COVID-19 vaccination among Black young adults are central to ending the pandemic. Black young adults experience harms from structural forces, such as racism and stigma, that reduce receptivity to traditional public health messaging due to skepticism and distrust. As such, Black young adults continue to represent a priority population on which to focus efforts for promoting COVID-19 vaccine uptake. Objective In aims 1 and 2, the Tough Talks digital health intervention for HIV disclosure will be adapted to address COVID-19 vaccine hesitancy and tailored to the experiences of Black young adults in the southern United States (Tough Talks for COVID-19). In aim 3, the newly adapted Tough Talks for COVID-19 digital health intervention will be tested across the following three southern states: Alabama, Georgia, and North Carolina. Methods Our innovative digital health intervention study will include qualitative and quantitative assessments. A unique combination of methodological techniques, including web-based surveys, choose-your-own-adventures, digital storytelling, user acceptability testing, and community-based participatory approaches, will culminate in a 2-arm hybrid type 1 effectiveness implementation randomized controlled trial, wherein participants will be randomized to the Tough Talks for COVID-19 intervention arm or a standard-of-care control condition (N=360). Logistic regression will be used to determine the effect of the treatment arm on the probability of vaccination uptake (primary COVID-19 vaccine series or recommended boosters). Concurrently, the inner and outer contexts of implementation will be ascertained and catalogued to inform future scale-up. Florida State University’s institutional review board approved the study (STUDY00003617). Results Our study was funded at the end of April 2021. Aim 1 data collection concluded in early 2022. The entire study is expected to conclude in January 2025. Conclusions If effective, our digital health intervention will be poised for broad, rapid dissemination to reduce COVID-19 mortality among unvaccinated Black young adults in the southern United States. Our findings will have the potential to inform efforts that seek to address medical mistrust through participatory approaches. The lessons learned from the conduct of our study could be instrumental in improving health care engagement among Black young adults for several critical areas that disproportionately harm this community, such as tobacco control and diabetes prevention. Trial Registration ClinicalTrials.gov NCT05490329; https://clinicaltrials.gov/ct2/show/NCT05490329 International Registered Report Identifier (IRRID) DERR1-10.2196/41240

Biomedical, female-initiated HIV prevention methods can help reduce disproportionately high HIV rates among women in sub-Saharan Africa, but male partner resistance and intimate partner violence (IPV) may impact ability to ensure effective use. To support consistent use of the dapivirine vaginal ring (VR), we pilot-tested the impact of the CHARISMA relationship counseling intervention ("CHARISMA") with women enrolled in the multi-site open-label Microbicide Trials Network (MTN) 025/HOPE trial at the Wits Reproductive Health and HIV Research Institute (Wits RHI) site in Johannesburg, South Africa. Lay counselors used a 42-item tool with five subscales to assess relationships and IPV and provide tailored counseling at enrolment, followed by a booster counselling session at Month 1 and follow-up checks at Months 3 and 6. We evaluated potential impact by examining self-reported ring disclosure to partners, partner clinic attendance, self-reported incident social harms (SH) and IPV, and biomarkers of ring adherence at Wits RHI. We subsequently compared these outcomes at three comparator HOPE study sites using multivariable regression models. Comparator study sites were purposively selected as those most similar to Wits RHI for baseline characteristics identified a priori. At Wits RHI, 95 of 96 (99%) HOPE participants enrolled into the CHARISMA pilot study. Mean age was 30, 36.8% lived with a partner, and 85.3% received their partner's financial support. During the six months of pilot study follow-up, participants reported: ring use disclosure to partners at 72.7% visits; 4.3% partners attending the research clinic; one partner-related SH; and 9.5% experienced incident IPV. The mean level of dapivirine released from returned used rings was 3.4 mg (SD 1.56), suggesting moderate adherence. Participants in the CHARISMA pilot had high background prevalence and incidence of IPV but were nevertheless able to adhere to ring use, and some male partners came to the research clinic. In adjusted regression models, compared to Wits RHI, partner clinic attendance was lower at all comparator sites; and significantly so at Site A (aRR 0.12, 95% CI 0.00-0.98). Sites B and C had lower levels of dapivirine released (suggesting lower adherence), but this difference was not significant. Site B women were more likely to report ring disclosure to partners at FU visits (aRR 1.12, 95% CI 1.00-1.25). IPV reported during follow-up was significantly lower at Site B (aRR 0.20, 95% CI 0.04-0.98, p = 0.047). CHARISMA taught women skills to decide on levels of ring-use disclosure to partners or others; therefore it is difficult to interpret differences in ring disclosure to partners with other sites. Similarly, CHARISMA heightened participants' awareness of abuse, possibly increasing IPV reports. Testing CHARISMA under fully-powered controlled conditions will improve understanding of its impact on women's relationships and ability to use female-initiated HIV prevention methods.

Interactive stories are a relatively newer form of storytelling with great potential to correct misinformation while increasing self-efficacy, which is crucial to vaccine acceptance. To address COVID-19 vaccine hesitancy and medical mistrust in young Black adults (BYA), we sought to adapt a pre-existing application ("app"; Tough Talks) designed to address HIV disclosure decision-making through choose-your-own adventure (CYOA) narratives and other activities. The adapted app (Tough Talks - COVID) uses a similar approach to situate COVID-19 vaccination decision-making within social contexts and to encourage greater deliberation about decisions. To inform content for the CYOA narratives, we conducted an online survey that was used to elicit the behavioral, cognitive, and environmental determinants influencing COVID-19 vaccine hesitancy among 150 BYA (ages 18-29) in Georgia, Alabama, and North Carolina. The survey included scenario questions that were developed with input from a youth advisory board to understand responses to peer and family influences. In two scenarios that involved discussions with family and friends about vaccination status, most respondents chose to be honest about their vaccination status. However, vaccinated individuals perceived more social pressure and stigma about not being vaccinated than unvaccinated respondents who were not as motivated by social pressure. Personal choice/agency in the face of perceived vaccine risks was a more common theme for unvaccinated respondents. Results suggest that relying on changing social norms alone may not impact barriers to vaccination in unvaccinated young adults without also addressing other barriers to vaccination such as concerns about autonomy and vaccine safety. Based on these findings, CYOA narratives in the app were adapted to include discussions with family and friends but also to touch on themes of personal choice as well as other topics that influence behaviors besides norms such as safety, side effects, and risk of COVID-19 in an evolving pandemic.

Cancer survivors who have undergone hematopoietic cell transplantation (HCT) are at risk for myocardial dysfunction. Children who receive allogenic HCT encounter systemic inflammation resulting in tachycardia and hypertension. The effect of these abnormalities on myocardial function is not known. The aim of this study was to determine whether cardiac dysfunction early after HCT can be predicted by tachycardia or hypertension, within a retrospective single-center sample of pediatric HCT recipients. Early tachycardia or hypertension was defined as a majority of values taken from infusion date to 90 days post-infusion being abnormal. Ejection fraction

BACKGROUND Few studies have focused on attitudes towards novel coronavirus 2019 (COVID-19) vaccination among Black or African American young adults (BYA) in the Southern United States (US), despite high levels of infection in this population. OBJECTIVE To understand this gap, we conducted an online survey to explore beliefs and experiences related to COVID-19 vaccination among BYA (ages 18-29) in three southern states. METHODS We recruited 150 BYA to participate in an online survey as formative research for an intervention to address vaccine hesitancy/skepticism in Alabama, Georgia, and North Carolina between September 22, 2021, and November 18, 2021. Participants were recruited through social media ads on Facebook, Twitter, Instagram, and YouTube. Additionally, we distributed information about the survey through national organizations working with BYA, our community partners and network collaborations. We used validated measures from prior surveys on COVID-19 vaccination. RESULTS Less than half of vaccinated respondents planned to get a booster shot (47%, n=71) and 14% (n=28) had not received any doses of the COVID-19 vaccine. Half of unvaccinated respondents (50%, n=14) reported they wanted to wait longer before getting vaccinated. Motivators to get vaccinated were similar between unvaccinated and vaccinated respondents (e.g., if required, to protect the health of others); but the main motivator for those vaccinated was to protect one’s own health. Among unvaccinated individuals, reasons for not receiving the COVID-19 vaccine included concern about vaccine side effects (54%) and mistrust of vaccine safety (46%), of effectiveness (43%), and of the government’s involvement with vaccines (43%). Experiences of discrimination (40%) and mistrust of vaccines (36%) were common even among the vaccinated population. Among all respondents, those who said they would be motivated to get vaccinated if it was required for school, work, or travel, were more likely to endorse negative beliefs about vaccines compared to those motivated for other reasons. CONCLUSIONS Mistrust in COVID-19 vaccine safety and efficacy was common among this sample of BYA in the South, irrespective of vaccination status. Other motivators such as safety of family and community and vaccination requirements may be able to tip the scales towards a decision to be vaccinated among those who are initially hesitant. However, it is unclear how vaccine requirements among BYA in the South affect trust in government or healthcare in the long-term. Interventions that include young Black adults in vaccination messaging and programs may consider more proactively addressing trust and countering misinformation.

Background Women may need or seek male partner approval to safely and consistently use oral antiretroviral pre-exposure prophylaxis (PrEP) or vaginal microbicides. We developed CHARISMA, a counseling intervention to support women’s relationships and their ability to consistently use HIV prevention products. Methods In a pilot study with 95 female participants in Johannesburg, South Africa, lay counselors implemented CHARISMA, assessing participants’ relationship(s) with their male partner(s) and barriers or facilitators to HIV prevention method use, and then providing tailored, interactive counseling. We conducted study participant surveys and clinic staff interviews to evaluate CHARISMA’s feasibility and acceptability. Results The CHARISMA pilot study indicates that a two-session relationship counseling intervention with 6-month follow-up to support women’s ability to safely and effectively use vaginal microbicides was generally acceptable and feasible. Most participants thought CHARISMA was relevant, helpful, and about the right length, and that it had a positive impact on their relationships with their partners and their product use. Staff estimated that the intervention took 1.5–2 h to implement at enrollment and 45 min to an hour for the month 1 visit. They thought that overall CHARISMA was generally feasible to implement. Conclusions Findings from this study suggest several lessons learned that may be relevant to others developing interventions supporting women’s use of oral PrEP or vaginal microbicides. The use of lay counselors instead of nurses to deliver counseling appeared to be successful, but the counselors experienced significant stress from hearing about participants’ traumatic experiences and required emotional support to avoid burnout. Although staff and participants felt that having multiple intervention sessions over time was valuable, a similar level of intensity may not be feasible in other settings. Further research is needed to determine an intervention delivery mode and follow-up period that optimally balances participant needs and clinic resources. Male engagement was a challenge, as it has been in previous studies of vaginal microbicides. Alternative strategies to reach men that do not require them to come to the clinic or rely on their female partners may be more effective.

Introduction: Our research assessed associations between stigma-related variables and medical care ratings among clients with HIV in HIV Prevention Trials Network (HPTN) 078 who were men who have sex with men (MSM). Methods: Logistic regression explored care ratings, stigma, socio-demographics (N = 637). Qualitative thematic coding and themes explored stigmatizing experiences in different settings (N = 111). Results: Whites were twice as likely as African-Americans to report high care ratings ( P Conclusions: Providers can promote African American MSM client retention with more affirming healthcare provision, namely minimizing assumptions and addressing identities and client needs beyond just HIV care.

Successful navigation of the HIV care continuum is necessary to maintain viral suppression. We explored gender-stratified correlates of being virally unsuppressed in the Prevention for Positives (P4P) component of HPTN 065. The outcome of interest was unsuppressed viral load (> 40 copies/mL) among individuals already living with HIV. Correlates included medication adherence factors, social support and stigma. Logistic regression models were stratified by gender (N = 673). Men-specific correlates of being virally unsuppressed included opposite-sex partners, older age and HIV disclosure stigma. Women-specific correlates included time since diagnosis, and personal-level barriers to medication adherence. When more individuals knew about their HIV status, women had over twice the likelihood of being virally unsuppressed; no such association was seen among men. Additionally, higher levels of social support were not associated with viral suppression among women. Interventions should consider gender-specific approaches to engaging social support in de-stigmatization of HIV and promotion of medication adherence and subsequent viral suppression.

Background Despite international support for increasing access to contraceptives among adolescents, gaps in use still exist worldwide. Past research has identified barriers to use across all levels of the socioecological model including restrictive policies, a lack of youth friendly services, and knowledge gaps. This study was conducted to further identify influences on contraceptive use among adolescent girls in Nigeria in hopes of guiding future policies and programs. Methods In 2018, 12 focus group discussions (FGD) were conducted in three cities in Nigeria with young women ages 15–24 with the objective of determining what and who influence adolescents’ contraceptive seeking behaviors. A vignette structure was used to identify perceptions on injunctive and descriptive community norms that influence adolescent contraceptive behaviors. The FGDs were conducted by members of the University of Ibadan Centre for Population and Reproductive Health (CPRH) and analyzed by a researcher at the University of North Carolina-Chapel Hill’s Carolina Population Center using a thematic analysis approach. Results Participants identified community level resistance to sex and contraceptive use among unmarried adolescents though also acknowledged that these adolescent behaviors are still occurring despite established norms. Concerns about side effects and the preservation of fertility were frequently attached to contraceptive use and pointed to as a reason for community resistance to contraceptive use among this population. Participants saw peers, parents and partners as influencers on a girl’s decision to seek a method, though each were believed to play a different role in that decision. Conclusion The findings show that that despite barriers created by established injunctive norms, young women with a supportive social network can access contraceptive methods despite these barriers. By harnessing the influence of peers, partners and parents, the Nigerian family planning efforts can strive to improve the health and well-being of young people.

Adherence to care and antiretroviral therapy is challenging, especially for people living with HIV (PLWH) with additional co-occurring risk factors. Case management interventions, including motivational interviewing (MI), show promise to improve HIV treatment adherence, but few studies have examined how such interventions are delivered to or experienced by PLWH who have been reengaged in care. We conducted qualitative interviews with six case managers and 110 PLWH exiting from a randomized study (HPTN 078) who received a MI-based case management intervention in addition to standard patient-navigation services, or standard services only. Our study provided greater insight into the main findings from HPTN 078, including an in-depth description of the multiple barriers to adherence faced by this largely “out-of-care” population, as well as a more nuanced understanding of the benefits and challenges of implementing MI. A blend of MI plus more intensive interventions may be needed for PLWH facing multiple structural barriers.

The management of diabetes, like many other chronic conditions, depends on effective primary care engagement. Patients with diabetes without a usual source of care have a higher risk of uncontrolled disease, hospitalizations, and early death. Our objective was to study the effect of a brief intervention to help patients in medically underserved areas obtain rapid primary care follow-up appointments following hospitalization. We performed a pilot pragmatic randomized controlled trial of adult patients with uncontrolled diabetes who had been admitted to one of three hospitals in the Memphis, TN, area. The enhanced usual care arm received a list of primary care clinics, whereas the intervention group had an appointment made for them preceding their index discharge. Patients in both groups were evaluated for primary care appointment attendance within seven and fourteen days of index discharge. In addition, we examined barriers patients encounter to receiving rapid primary care follow-up using a secret shopper approach to assess wait times when calling primary care offices. Twelve patients were enrolled with six in each trial arm. Baseline demographics, access to medical care, and health literacy were similar across the groups. Primary care follow-up was also similar across the groups; no improvements in follow-up rates were seen in the group receiving assistance with making appointments. Identified barriers to making primary care follow-up appointments included inability to schedule an urgent appointment, long hold times when calling doctor's offices and lack of transportation. Additionally, hold times when calling primary care offices were found to be excessively long in the medically underserved areas studied. The study demonstrates the feasibility of providing patient assistance with scheduling rapid primary care follow-up appointments at the time of discharge and the potential to improve care transitions and access to primary care among patients living in medically underserved areas. Larger pragmatic trials are needed to further test alternative approaches for insuring rapid primary care follow-up in vulnerable patients with ambulatory care-sensitive chronic conditions.

Evidence for a cerebellar role during cardiopulmonary challenges has long been established, but studies of cerebellar involvement in eupneic breathing have been inconclusive. Here we investigated temporal aspects of eupneic respiration in the Atoh1-En1/2 mouse model of cerebellar neuropathology. Atoh1-En1/2 conditional knockout mice have conditional loss of the developmental patterning genes Engrailed1 and 2 in excitatory cerebellar nuclear neurons, which leads to loss of a subset of medial and intermediate excitatory cerebellar nuclear neurons. A sample of three Atoh1-derived extracerebellar nuclei showed no cell loss in the conditional knockout compared to control mice. We measured eupneic respiration in mutant animals and control littermates using whole-body unrestrained plethysmography and compared the average respiratory rate, coefficient of variation, and the CV2, a measure of intrinsic rhythmicity. Linear regression analyses revealed that Atoh1-En1/2 conditional knockouts have decreased overall variability (p = 0.021; b = -0.045) and increased intrinsic rhythmicity compared to their control littermates (p 0.001; b = -0.037), but we found no effect of genotype on average respiratory rate (p = 0.064). Analysis also revealed modestly decreased respiratory rates (p = 0.025; b = -0.82), increased coefficient of variation (p = 0.0036; b = 0.060), and increased CV2 in female animals, independent of genotype (p = 0.024; b = 0.026). These results suggest a cerebellar involvement in eupneic breathing by controlling rhythmicity. We argue that the cerebellar involvement in controlling the CV2 of respiration is indicative of an involvement of coordinating respiration with other orofacial rhythms, such as swallowing.

OBJECTIVES To describe an innovative health information technology (HIT) model for supporting community-wide health improvement through multiprovider collaboration in a regional population health registry and practice-based research network (PBRN). STUDY DESIGN Case study. METHODS We describe the HIT data structure and governance of the Diabetes Wellness and Prevention Coalition (DWPC) Registry and PBRN based in Memphis, Tennessee. The population served and their characteristics were assessed for all adult patients with at least 1 encounter in a participating health care delivery system from January 1, 2013, to March 31, 2019. Disparities in access and health care utilization were assessed by residential zip code. RESULTS The DWPC Registry is a chronic disease and population health data warehouse designed to facilitate chronic disease surveillance and tracking of processes and outcomes of care in medically underserved areas of the mid-South. The Registry primarily focuses on obesity-associated chronic conditions such as diabetes, hypertension, hyperlipidemia, and chronic kidney disease. It combines patient data from 7 regional health systems, which include 6 adult hospitals and more than 50 outpatient practices, covering 462,223 adults with 2,032,425 clinic visits and 602,679 hospitalizations and/or emergency department visits from January 1, 2013, to March 31, 2019. The most prevalent chronic conditions include obesity (37.2%), hypertension (34.4%), overweight (26.4%), hyperlipidemia (18.0%), and type 2 diabetes (14.0%). The Registry provides quarterly practice improvement reports to participating clinics, facilitates surveillance of and outreach to patients with unmet health needs, and supports a pragmatic clinical trial and multiple cohort studies. CONCLUSIONS Regional registries and PBRNs are powerful tools that can support real-world quality improvement and population health efforts to reduce disparities and improve equity in chronic disease care in medically underserved communities across the United States.

HPTN 065 utilized financial incentives to promote viral suppression among HIV-positive participants. Exit interviews were conducted in a sub-study of participants in Washington, DC and Bronx, NY. The present analyses explored lived experiences of social ties and stigma as individuals navigated the HIV care continuum, including gender differences in lived experiences. Using viral load data and informed by stages-of-change theory, participants were categorized into "Low-Adherers (n = 13)", "Action (n = 29)" and "Maintenance (n = 31)" stages. Secondary analyses of qualitative data were informed by grounded theory, and instances of social ties and stigma discussed by participants were quantified with descriptive statistics. Participants (N = 73) were mostly male (64%), African American (58%), with yearly income under $10,000 (52%). Low-adherers identified fewer, and sometimes more combative social ties than those in other adherence stages. Maintainers identified supportive ties as motivation for medication adherence (68%) but relied less on them for motivation than individuals in other adherence stages. Low-adherers described current experiences of stigma related to being diagnosed with HIV more than other adherence stages (23%). Individuals in Action reported stigma related to disclosing their HIV status to others (52%), while individuals in Maintenance mostly stigmatized others engaging in "risky" behaviors (32%). Findings suggest that women may perceive greater HIV stigma than men, perceive less supportive social ties, and were the majority of Low-adherers. Gender-informed approaches can facilitate community de-stigmatization of HIV, as African American women may be at greater risk of negative HIV health outcomes.

PURPOSE: Clinical trials are necessary to test HIV-prevention strategies among adolescent girls and young women in sub-Saharan Africa. Psychosocial risk factors that increase girls’ and young women’s vulnerability for HIV may also impact their experiences in clinical trials. A better understanding of psychosocial risks among girls and young women enrolled in HIV-prevention research is needed. This analysis explores depression and sexual trauma among adolescent girls and young women enrolled in a mock microbicide trial in Tanzania. METHODS: We collected cross-sectional data from 135 HIV-negative adolescent girls and young women between 15–21 in Dar es Salaam, Tanzania enrolled in a mock microbicide trial. Depression, sexual behavior, and sexual trauma were measured. Sexual trauma and demographic variables were entered into a multivariate binomial logistic regression model predicting depression. FINDINGS: Overall, 27% of participants had moderate-to-severe depression. The most commonly endorsed items were anhedonia (lack of interest/pleasure) and low mood, which were reported by 78% of participants. Thoughts of suicide or self-harm were endorsed by 17% of participants. Coerced/forced first sex was reported by 42% of participants. Participants reporting coerced/forced first sex had 3.16 times the likelihood of moderate-to-severe depression. CONCLUSIONS: Depression and coerced/forced sex were common among participants in an HIV-prevention mock clinical trial in Tanzania. When enrolling adolescent girls and young women in HIV-prevention trials in sub-Saharan Africa, our research suggests the need for a trauma-informed approach, referrals for trauma and depression, and interventions that address the impact of depression and trauma on HIV prevention, clinical trial adherence, and clinical outcomes.

Consistent use of oral pre-exposure prophylaxis (PrEP) has been a challenge among women, particularly when in relationships with lack of partner support or intimate partner violence (IPV).We conducted a randomized controlled trial (RCT) of an empowerment counseling intervention called "CHARISMA" delivered to women within a PrEP demonstration project in Johannesburg, South Africa. The trial tested the effectiveness of CHARISMA to increase PrEP adherence; decrease social harms and IPV; and improve partnership dynamics (eg, communication, disclosure and support) compared with those who received the standard of care counselling support and referrals. Four hundred seven HIV-seronegative, nonpregnant women aged 18-45 years were enrolled for 6 months of PrEP use, with 203 randomized (1:1) to the intervention. All participants reporting IPV received counseling and referrals that followed the WHO five-step Listen, Inquire, Validate, Enhance Safety, and Support approach.This RCT did not identify statistically significant differences between study arms for PrEP adherence or relationship dynamics, with the exception of an increase in PrEP disclosure among intervention arm women. In our study, we cannot determine whether the lack of detectable findings may have been because of lack of intervention effect, strength of standard of care services, low risk in the study population, or other factors.Addressing IPV and relationship dynamics remain important factors influencing HIV risk, and addressing these within the context of PrEP delivery is an important synergistic opportunity. CHARISMA was highly acceptable to participants, and further adaptation and testing of the intervention to other populations and settings will augment the evidence base.

Background Despite high rates of novel COVID-19, acceptance of COVID-19 vaccination is low among Black adults. In response, we developed a digital health intervention (Tough Talks-COVID) that includes digital stories created in a workshop we held with young Black adults. Objective Our formative research using digital storytelling workshops asked 3 research questions: (1) What issues did participants have in conceptualizing their stories, and what themes emerged from the stories they created? (2) What issues did participants have related to production techniques, and which techniques were utilized in stories? and (3) Overall, how did participants evaluate their workshop experience? Methods Participants were workshop-eligible if they were vaccine-accepting based on a baseline survey fielded in late 2021. Final participants (N=11) completed a consent process, all 3 workshops, and a media release form for their digital story. The first 2 workshops provided background information and hands-on digital storytelling skills from pre- to postproduction. The third workshop served as a screening and feedback session for participants’ final videos. Qualitative and quantitative feedback elements were incorporated into all 3 sessions. Results Digital stories addressed one or more of 4 broad themes: (1) COVID-19 vulnerability, (2) community connections, (3) addressing vaccine hesitancy, and (4) countering vaccine misinformation. Participants incorporated an array of technical approaches, including unique creative elements such as cartoon images and instant messaging tools to convey social interactions around COVID-19 decision-making. Most (9/11, 82%) strongly agreed the digital storytelling workshops were delivered as expected; 10 of 11 agreed (n=5) or strongly agreed (n=5) that they had some ideas about what story to tell by the end of the first workshop, and most (8/11, 73%) strongly agreed they had narrowed down their ideas by workshop two. Of the participants, 9 felt they would very likely (n=6) or likely (n=3) use digital storytelling techniques for personal use in the future, and even more were very likely (n=7) to use the techniques for professional use. Conclusions Our study is one of the first to incorporate digital storytelling as a central component to a digital health intervention and the only one to do so with exclusive focus on young Black adults. Our emphasis on digital storytelling was shown to be highly acceptable. Similar approaches, including careful consideration of the ethical challenges of community-based participatory approaches, are applicable to other populations experiencing both COVID-19 inequities and marginalization, such as other age demographics and people of color.

Growing evidence highlights an association between an imbalance in the composition and abundance of bacteria in the breast tissue (referred as microbial dysbiosis) and breast cancer in women. However, studies on the breast tissue microbiome have not been conducted in non-Hispanic Black (NHB) women. We investigated normal and breast cancer tissue microbiota from NHB and non-Hispanic White (NHW) women to identify distinct microbial signatures by race, stage, or tumor subtype. Using 16S rRNA gene sequencing, we observed that phylum Proteobacteria was most abundant in normal (n = 8), normal adjacent to tumor (normal pairs, n = 11), and breast tumors from NHB and NHW women (n = 64), with fewer Firmicutes, Bacteroidetes, and Actinobacteria. Breast tissues from NHB women had a higher abundance of genus Ralstonia compared to NHW tumors, which could explain a portion of the breast cancer racial disparities. Analysis of tumor subtype revealed enrichment of family Streptococcaceae in TNBC. A higher abundance of genus Bosea (phylum Proteobacteria) increased with stage. This is the first study to identify racial differences in the breast tissue microbiota between NHB and NHW women. Further studies on the breast cancer microbiome are necessary to help us understand risk, underlying mechanisms, and identify potential microbial targets.

Summary Given the range of pre‐exposure prophylaxis (PrEP) products currently being tested to prevent HIV in women, a standardized Acceptability and Use of PrEP Products Among Women Tool may facilitate comparisons of product acceptability and use across different geographies, trials, and users. We conducted three rounds of cognitive interviewing over 2 months in 2016, with 28 South African women who had experience participating in a range of PrEP product trials. The final instrument contained 41 items, including five new items that improved construct validity and 22 items modified for clarity. Changes were made due to unclear wording, difficulty answering, participant embarrassment, low response variability, and administrative formatting. Cognitive interviewing provided a means to address issues that would have inhibited this tool's ability to accurately collect data otherwise. This rapid, low‐cost study provided valuable insight into participants' understanding of questions and demonstrated the utility of cognitive interviewing in international clinical trials.

Researchers and advocates have increasingly called for adolescent participation in clinical trials for new HIV prevention products, particularly adolescent girls in areas most affected by the epidemic. However, recent trials have highlighted the challenges for young women and adolescents to be able to effectively use new products that require daily dosing. This analysis provides a highly relevant context for this challenging environment by examining community members acceptability of adolescent girls' participation in clinical trials for new HIV prevention products. We conducted 41 in-depth interviews in Dar es Salaam, Tanzania and Pune, India with 22 key informants (KIs). Cultural perspectives on adolescent sexuality varied between countries, with KIs in Tanzania more readily acknowledging adolescent girls' sexual activity than KIs in India. KIs in both countries felt strongly adolescents must be well-informed about research concepts prior to participation, and emphasis should be given to preventative misconception. Despite concern in both countries that the trials might be seen as encouraging sexual behavior, KIs in Tanzania overwhelmingly supported adolescent inclusion, whereas KIs in India were more cautious. Involving adolescent girls in clinical trials for new HIV prevention products is potentially acceptable, although meaningful community engagement will be necessary.

Background Combined Internal Medicine/Pediatrics (Med/Peds) residencies rely on categorical program data to predict pass rates for the American Board of Internal Medicine Certifying Exam (ABIM-CE) and the American Board of Pediatrics Certifying Exam (ABP-CE). There is insufficient literature describing what best predicts a Med/Peds resident passing board exams. In this study, we aimed to determine how standardized test scores predict performance on ABIM-CE and ABP-CE for Med/Peds residents. Methodology We analyzed prior exam scores for 91/96 (95%) residents in a Med/Peds program from 2008 to 2017. Scores from the United States Medical Licensing Examination (USMLE) Steps 1 and 2 Clinical Knowledge (CK) and In-Training Exams in Internal Medicine (ITE-IM) and Pediatrics (ITE-P) were analyzed with the corresponding ABIM-CE and ABP-CE first-time scores. Linear and logistic regression were applied to predict board scores/passage. Results USMLE 1 and 2 CK, ITE-IM, and ITE-P scores had a linear relationship with both ABIM-CE and ABP-CE scores. In the linear regression, adjusted R2 values showed low-to-moderate predictive ability (R2 = 0.11-0.35), with the highest predictor of ABIM-CE and ABP-CE being USMLE Step 1 (0.35) and Postgraduate Year 1 (PGY-1) ITE-IM (0.33), respectively. Logistic regression showed odds ratios of passing board certifications ranging from 1.05 to 1.53 per point increase on the prior exam score. The PGY-3 ITE-IM was the best predictor of passing both certifying exams. Conclusions In one Med/Peds program, USMLE Steps 1 and 2 and all ITE-IM and ITE-P scores predicted certifying exam scores and passage. This provides Med/Peds-specific data to allow individualized resident counseling and guide programmatic improvements targeted to board performance.

Objective Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes (T1D). In established T1D patients, DKA is frequently a result of insulin omission or inadequate insulin administration during illness or stress. Ethnic minorities and patients with lower socioeconomic status are affected disproportionately. We hypothesized that implementation of intensive sick day rules with frequent reinforcement would reduce hospitalizations secondary to DKA in T1D youth irrespective of their demographics. Methods Intensive sick day rules were implemented beginning January 2016. All T1D patients seen in the pediatric endocrinology clinic or hospital between January 1st 2015 through December 31st 2017 were included for chart review. Categorical variables were analyzed with Chi-square test. For the continuous variables, t test was used. Episodes of DKA per 100 patients were compared using the trends test over the three-year period. Patients who had DKA in 2015 were analyzed as a subgroup. Results The frequency of DKA episodes per 100 patient years for 2015 was 19.1, for 2016 was 15.2 and was 12.4 for 2017. This decrease was statistically significant (p=0.006). The decline was also statistically significant for the subgroup of patients who developed DKA in 2015 and followed longitudinally. The decline was not uniform across all patient groups and DKA episodes remained associated with African- American race, Medicaid insurance status and higher HbA1c throughout the years. Conclusion Implementation of intensive sick day rules led to a decrease in total number of DKA admissions in our population with T1D youth. However, this intervention did not reduce the health disparity in this population and African-Americans on Medicaid insurance continued to form the disproportionate majority of admissions with DKA. This study highlights the need for further research into interventions that can improve outcomes across racial and socio-economic barriers.

Women's concerns about contraceptive-induced menstrual changes can lead to method discontinuation and nonuse, contributing to unmet need for contraception. Research on women's perceptions of amenorrhea related to longer acting methods and in low-income countries is limited.Data were from nationally representative household surveys and focus group discussions with women of reproductive age conducted in Burkina Faso and Uganda in 2016-2017. Bivariate cross-tabulations and multivariate logistic regression analyses were used to examine sociodemographic and reproductive characteristics associated with women's attitudes about contraceptive-induced amenorrhea (n=2,673 for Burkina Faso and 2,281 for Uganda); menstrual health determinants were also examined for Burkina Faso. Qualitative data from focus group discussions were analyzed to understand reasons behind women's attitudes and how they influence contraceptive decision making.Sixty-five percent of women in Burkina Faso and 40% in Uganda reported they would choose a method that caused amenorrhea during use. In Burkina Faso, the predicted probability of accepting amenorrhea was higher for women aged 15-19 (compared with older women), living in rural areas, married and cohabiting (compared with never married), currently using a contraceptive method (compared with never users) and from Mossi households (compared with Gourmantché); menstrual health practices were not associated with amenorrhea acceptability. In Uganda, the least wealthy women had the highest predicted probability of accepting amenorrhea (51%). Qualitative analysis revealed a variety of reasons for women's attitudes about amenorrhea and differences by country, but the relationship between these attitudes and contraceptive decision making was similar across countries.Addressing misconceptions about contraception and menstruation may result in more informed method decision making.Contexto: Las preocupaciones de las mujeres acerca de los cambios menstruales inducidos por los anticonceptivos pueden conducir a la interrupción y el abandono del método, lo cual contribuye a la necesidad insatisfecha de anticoncepción. La investigación sobre la percepción de la amenorrea por parte de las mujeres sobre los métodos de acción más prolongada y en los países de bajos ingresos es limitada. Métodos: Los datos provienen de encuestas representativas de hogares a nivel nacional y discusiones de grupos focales con mujeres en edad reproductiva realizadas en Burkina Faso y Uganda entre 2016 y 2017. Se utilizaron tabulaciones cruzadas bivariadas y análisis de regresión logística multivariada para examinar las características sociodemográficas y reproductivas asociadas con las actitudes de las mujeres con respecto a la amenorrea inducida por anticonceptivos (n = 2,673 para Burkina Faso y 2,281 para Uganda); también se examinaron los determinantes de la salud menstrual en Burkina Faso. Se analizaron datos cualitativos de discusiones de los grupos focales para comprender las razones que determinan las actitudes de las mujeres y cómo influyen en la toma de decisiones sobre anticonceptivos. Resultados: El 65% de las mujeres en Burkina Faso y el 40% en Uganda informaron que elegirían un método que les causara amenorrea durante su uso. En Burkina Faso, la probabilidad predicha de aceptar la amenorrea fue mayor para las mujeres de 15 a 19 años (en comparación con las mujeres mayores), que vivían en zonas rurales, que estaban casadas y cohabitaban (en comparación con las que nunca se habían casado), que actualmente usaban un método anticonceptivo (en comparación con las mujeres que nunca lo habían usado) y de hogares Mossi (en comparación con Gourmantché). Las prácticas de salud menstrual no se asociaron con la aceptabilidad de la amenorrea. En Uganda, las mujeres menos ricas tuvieron la probabilidad más alta de aceptar amenorrea (51%). El análisis cualitativo reveló una variedad de razones con respecto a las actitudes de las mujeres sobre la amenorrea y las diferencias por país, pero la relación entre estas actitudes y la toma de decisiones sobre anticonceptivos fue similar en todos los países. Conclusiones: El abordaje de los conceptos erróneos sobre la anticoncepción y la menstruación podría resultar en una toma de decisiones más informada sobre los métodos anticonceptivos.Contexte: Les inquiétudes des femmes à l'égard des changements menstruels induits par la contraception peuvent conduire à l'arrêt ou à la non-utilisation de la méthode et contribuer ainsi au besoin non satisfait de contraception. La recherche sur les perceptions des femmes de l'aménorrhée liée aux méthodes à durée d'action prolongée et dans les pays à revenu faible est limitée. Méthodes: Les données sont extraites d'enquêtes de ménage nationalement représentatives et de discussions de groupe avec des femmes en âge de procréer, menées au Burkina Faso et en Ouganda en 2016-2017. Les caractéristiques sociodémographiques et reproductives associées aux attitudes des femmes concernant l'aménorrhée induite par la contraception (n=2 673 pour le Burkina Faso et 2 281 pour l'Ouganda) ont été examinées en tableaux croisés bivariés et par analyses de régression logistique multivariée. Les déterminants de la santé menstruelle ont aussi été examinés pour le Burkina Faso. L'analyse des données qualitatives obtenues des discussions de groupe a permis de cerner les raisons à la base des attitudes des femmes et leur influence sur les décisions contraceptives prises. Résultats: Soixante-cinq pour cent des femmes burkinabè et 40% de leurs homologues ougandaises ont déclaré qu'elles choisiraient une méthode dont la pratique causerait l'aménorrhée. Au Burkina Faso, la probabilité prédite d'acceptation de l'aménorrhée s'est avérée supérieure pour les femmes âgées de 15 à 19 ans (par rapport à leurs aînées), vivant en milieu rural, mariées ou en union (par rapport à celles qui n'avaient jamais été mariées), pratiquant actuellement la contraception (par rapport à celles qui ne l'avaient jamais pratiquée) et d'origine Mossi (par rapport à Gourmantché). Les pratiques de santé menstruelle n‘étaient pas associées à l'acceptabilité de l'aménorrhée. En Ouganda, les femmes les moins riches sont associées à la plus haute probabilité prédite d'acceptation de l'aménorrhée (51%). L'analyse qualitative a révélé diverses raisons à la base des attitudes des femmes à l‘égard de l'aménorrhée ainsi que certaines différences suivant le pays, mais la relation entre ces attitudes et la décision contraceptive s'est avérée similaire dans les deux pays. Conclusions: La résolution des idées fausses concernant la contraception et la menstruation pourrait conduire à une prise de décision mieux éclairée dans le choix des méthodes.

Cancer survivors who have undergone hematopoietic cell transplantation (HCT) are at risk for myocardial dysfunction. Children who receive allogenic HCT encounter systemic inflammation resulting in tachycardia and hypertension. The effect of these abnormalities on myocardial function is not known. The aim of this study was to determine whether cardiac dysfunction early after HCT can be predicted by tachycardia or hypertension, within a retrospective single-center sample of pediatric HCT recipients. Early tachycardia or hypertension was defined as a majority of values taken from infusion date to 90 days post-infusion being abnormal. Ejection fraction53% determined systolic dysfunction. A composite score of accepted pediatric diastolic abnormalities determined diastolic dysfunction. Among 80 subjects (median age 8 years), early tachycardia, systolic dysfunction, and diastolic dysfunction were present in 64%, 25%, and 48% of the sample, respectively. In multivariable models, early tachycardia was an independent predictor of early systolic dysfunction (OR = 12.6 [1.4-112.8], p = 0.024) and diastolic dysfunction (OR = 3.9 [1.3-11.5], p = 0.013). Tachycardia and cardiac dysfunction are common and associated with one another in the early period after pediatric HCT. Future studies may elucidate the role of tachycardia and myocardial dysfunction early after HCT as important predictors of future cardiovascular dysfunction.

Introduction Oral, vaginal and other pre-exposure prophylaxis (PrEP) products for HIV prevention are in various stages of development. Low adherence poses a serious challenge to successful evaluation in trials. In a previous study, we developed tools to screen for general adherence and specifically monitor intravaginal ring adherence within the context of HIV prevention clinical trials. This study aimed to further validate the screening tool and to adapt and provide initial psychometric validation for an oral pill monitoring tool. Materials and methods We administered a cross-sectional survey between June and October 2018 at a trial site located near Cape Town, South Africa, and another in Thika, Kenya, with 193 women who had experience using daily oral pills. We fit confirmatory factor analysis models on the screening tool items to assess our previously-hypothesized subscale structure. We conducted an exploratory factor analysis of oral PrEP monitoring items to determine the underlying subscale structure. We then assessed the construct validity of each tool by comparing subscales against each other within the current sample and against our original sample, from a study conducted in four sites in South Africa, including Cape Town. Results The screening tool structure showed moderate evidence of construct validity. As a whole, the tool performed in a similar way to the original sample. The monitoring tool items, which were revised to assess perceptions about and experiences using daily oral PrEP, factored into five subscales that showed moderate to good reliability. Four of the five subscales had a similar structure overall to the vaginal ring monitoring tool from which they were adapted. Conclusions Accurate measurement of HIV-prevention product adherence is of critical importance to the assessment of product efficacy and safety in clinical trials, and the support of safe and effective product use in non-trial settings. In this study, we provide further validation for these measures, demonstrating the screening tool’s utility in additional populations and adapting the monitoring tool’s utility for different HIV-prevention products.

In HIV prevention trials, male partners have influenced women’s ability to adhere to investigational products, including antiretroviral (ARV) containing vaginal rings. Validated scales can be useful tools to systematically measure complex constructs, such as those related to male partner engagement. Although multiple scales exist to assess physical, psychological and sexual violence within intimate relationships, fewer scales focus on supportive behaviors within these relationships. Our intervention involved development of a Healthy Relationship Assessment Tool (HEART) that assessed both positive and negative aspects of male partner involvement in women’s HIV prevention. We identified and refined 127 potential items, representing intimate partner violence, agency and social support. A structured survey, including potential items and other sociodemographic and behavioral variables was administered to former microbicide trial and non-trial participants. We conducted an exploratory factor analysis (EFA) to identify a reduced set of constructs and items to screen women who might experience social harms or benefits from vaginal ring use. We examined associations between constructs and with other survey variables to assess content and construct validity. In a subset of 10 women who participated in the survey and qualitative interviews, we used qualitative data to predict survey scores. We retained five constructs with theoretical relevance and good-to-strong reliability for the tool, including: Traditional Values; Partner Support; Partner Abuse & Control; Partner Resistance to HIV Prevention; and HIV Prevention Readiness. Predicted associations between HEART constructs, and correspondence between participants’ qualitative data and HEART scores were generally correct, while those between constructs and other sociodemographic variables were more mixed. Initial validation of the HEART tool was promising. The tool will be used during the CHARISMA pilot study at the Johannesburg MTN 025/HOPE site and validated as part of a randomized controlled trial of CHARISMA within a PrEP demonstration project. Beyond clinical trial settings, HEART could assist PrEP or antiretroviral treatment (ART) providers with an easy-to-administer tool to identify risk and tailor risk reduction, empowerment and adherence counseling for microbicides, PrEP or ART related services.

African-American men who have sex with men (MSM) with HIV are more likely to have unsuppressed viral load than other racial/ethnic groups. HPTN 065 Study, completed in 2015, consisted of five interconnected study components conducted at clinics in Bronx, New York and Washington, D.C. Participants completed surveys with questions related to socio-demographic factors and individual-level HIV medication adherence barriers, such as forgetting doses or fear of taking medications in front of others. Descriptive analyses and ordinal logistic regression with robust standard errors were conducted. Fifty-seven per cent of participants (N = 359) were African-American (57.1%) and roughly 40% had no more than a high school education. Mean age was 48 years. Overall, MSM with viral load suppression identified fewer individual-level barriers to adherence (p < .01) and individuals with depressive symptoms identified a greater number of barriers to adherence (p < .01). Compared to African-Americans, white MSM had a lower likelihood of identifying barriers to adherence (p < .05). Findings suggest that individual-level barriers to HIV medication adherence are common among MSM, irrespective of time since diagnosis and viral suppression. Race-specific interventions which address intersectional stigma are needed to improve health outcomes among African-American MSM, who bear much of the burden of poor HIV outcomes in the United States.

Pragmatic clinical trials are commonly used in patient-centered outcomes research to assess heterogeneity of treatment effects. Patient-Centered Outcomes Research Institute (PCORI) methodology standards for assessing heterogeneity of treatment effects are extremely rigorous, but their implementation in real-world settings can be difficult. Predicting recruitment effectiveness and subgroup characteristics is often challenging and may require mid-stream revision of projected group and subgroup sizes. Yet, little real-world data are available to demonstrate methodologically valid approaches to address situations where such revisions are necessary. These data were used for mid-stream revision of group and subgroup sizes in the Management of Diabetes in Everyday Life (MODEL) clinical trial. The planned number of randomized participants retained over the one-year study period was reduced from 800 to 581 due to recruitment difficulties among potential participants residing in rural areas. Prospective power analyses are based on the revised target of 581 participants retained and the proportions of 167 participants with various key baseline characteristics, who had been randomized in MODEL by January 2018, as reported to the Patient Center Outcomes Research Institute (PCORI) and the MODEL Data Safety and Monitoring Committee. Power calculations are based on two-sided t-tests with type-I error rates of 0.05 and the assumption that effect sizes will range from small (standardized difference = 0.36) to medium (= 0.50). The primary outcome variables are how many days in the previous week participants 1) ate healthy meals, 2) participated in at least 30 minutes of physical activity, and 3) took medications as prescribed. The POWER procedure of SAS 9.4 was used for all analyses. These data, along with the approach, can assist statisticians as they plan future pragmatic clinical trials evaluating heterogeneity of treatment effects. These data can help inform investigators, conducting patient-centered outcomes research, as they define subgroups for either confirmatory analyses for testing heterogeneity of treatment effects or for exploratory analyses where estimation of confidence bounds may be useful for generating future hypotheses. (This work was supported through a Patient-Centered Outcomes Research Institute (PCORI) Project Program Award (SC15-1503-28336), www.ClinicalTrials.gov and Identifier: NCT02957513 [1] .)

Background: Daily oral TDF/FTC is protective against HIV infection when used for pre-exposure prophylaxis (PrEP). However, daily adherence to oral PrEP is difficult for many; therefore, finding alternative PrEP strategies remains a priority. HPTN 076 evaluated the long-acting injectable form of rilpivirine (RPV), known as RPV LA for safety, pharmacokinetics and acceptability. Methods: HPTN 076 (NTC 02165202) was a phase 2, double-blind, 2:1 randomized trial comparing the safety of 1200mg RPV LA (LA) to placebo (P). The study included a 28-day oral run-in phase of daily, self- administered oral RPV (25 mg), with directly observed oral dosing about six times. Of 136 enrolled sexually active, HIV-uninfected, low HIV-risk African (100) and US (36) adult women, injectable product was administered in two gluteal, intramuscular (IM) injections once every eight weeks to 122 participants following the oral run-in phase. A maximum of six injection time points occurred over a 48-week period. Acceptability, safety, tolerability and pharmacokinetic (PK) data were collected throughout the study. This paper includes primary endpoint data collected up to the week 52 post enrollment. Findings: The median age of the enrolled population was 31 years (IQR: 25,38), median weight 75 kg (IQR: 64, 89), median body mass index (BMI) 30 (IQR: 27, 35), 46% married, 94% Black and 60% unemployed. A total of 122 (80 LA, 42 P) women received at least one injection and 98 (64 LA, 34 P) received all six injections. During the injection phase, three women withdrew from the study (2 LA, 1 P) and 16 women discontinued study product (10 LA, 6 P). Fourteen women (11 LA and 3 P) discontinued oral study product and did not enter the injection phase. Study product discontinuations were not significantly different between the two arms throughout. Of the product discontinuations in the injection phase, 8% in LA and 5% in P arm were due to adverse events (AEs), including one randomized to the P arm with prolonged QTc interval on EKG. The proportion of women who experienced Grade 2 or higher AEs during the injection phase as the primary outcome was not significantly different between the two arms [73.8%, 95% CI: (63.2%, 82.1%) for LA and 73.8%, 95% CI: (58.9%, 84.7%), p>0.99]. Transient Grade ≥2 liver abnormalities occurred in 14% of women in the LA arm compared with 12% in P arm. Three LA women (4%) developed Grade 3 injection site reactions compared with none in P arm. In participants who received at least 1 injection, the geometric mean of overall RPV trough concentrations (Ctrough) was 62.2 ng/mL. In participants who received all six injections, the geometric mean of CTrough through the injection phase and after the last injection were 72.8 ng/mL and 100.9 ng/mL, respectively. At week 52 (eight weeks after last injection), the geometric mean of RPV Ctrough was 75.0 ng/mL. At the last injection visit (Week 44), 80 % of women who answered acceptability questions strongly agreed that they would think about using- and 68% that they would definitely use a PrEP injectable in the future. Interpretation: RPV LA IM injections every eight weeks in African and US women were safe and acceptable. Overall, despite more injection site reactions and pain in the participants receiving RPV LA the injections were well tolerated. Data from this study support the further development of injectable PrEP agents. Keyword: RPV LA as Pre exposure prophylaxis

Long-acting injectable PrEP could offer an alternative to daily oral PrEP, improve adherence and protection, if found acceptable, safe and effective. HPTN 077 evaluated injectable cabotegravir safety, tolerability and pharmacokinetics among HIV-uninfected males and females in sequentially-enrolled cohorts of two dosing strategies. We compared acceptability of product attributes, prevention preferences and future interest in injectable PrEP (FIIP) by region, sex-at-birth, arm and cohort and used multivariable analysis to identify FIIP determinants. Baseline injectable PrEP preferences were higher in non-U.S. sites and increased in both regions over time. In multivariable models, FIIP was most strongly associated with acceptability of product attributes, was higher in non-U.S. sites and more altruistic participants. Treatment arm and report of pain were not associated with FIIP. Injectable acceptability was highest in non-U.S. sites. Preferences for injectable versus other PrEP methods were higher among U.S. males than females, but higher among males and females in non-U.S. settings. Electronic supplementary material The online version of this article (10.1007/s10461-020-02808-2) contains supplementary material, which is available to authorized users.

Although significant progress has been made in improving breast cancer survival, disparities among racial, ethnic, and underserved groups still exist. The goal of this investigation is to quantify racial disparities in the context of breast cancer care, examining the outcomes of recurrence and mortality in the city of Memphis. Patients with a biopsy-proven diagnosis of breast cancer from January 1, 2002, through December 31, 2012, were obtained from the tumor registry. Black patients were more likely to have advanced (II, III, or IV) clinical stage of breast cancer at diagnosis versus white patients. Black breast cancer patients had a two times higher odds of recurrence (95% confidence interval: 1.4, 3.0) after adjusting for race and clinical stage. Black breast cancer patients were 1.5 times more likely to die (95% confidence interval: 1.2, 1.8), after adjusting for race; age at diagnosis; clinical stage; ER, PR, HER2 status; and recurrence. Black women with stages 0, I, II, and III breast cancer all had a statistically significant longer median time from diagnosis to surgery than white women. Black patients were more likely to have advanced clinical stages of breast cancer at diagnosis versus white patients on a citywide level in Memphis. Black breast cancer patients have higher odds of recurrence and mortality when compared with white breast cancer patients, after adjusting for appropriate demographic and clinical attributes. More work is needed to develop, evaluate, and disseminate interventions to decrease inequities in timeliness of care for breast cancer patients.

Black women are more likely to be diagnosed with late-stage breast cancer than white women and have the lowest probability of cause-specific survival. Obesity is associated with increased breast cancer risk and deaths in black women. Insulin-resistant obesity features chronic systemic and local inflammation of fat, which has been linked to breast cancer outcomes. The breast also consists of a mucosal immune system that provides a complex mechanical barrier and an inherent defense against pathogens. Growing evidence shows that an imbalance in the microbiome due to inflammation may give rise to cancer development. However, there is a lack of data on the role of the microbiome in breast tumors from black women. Using a global metabolomics approach, we investigated normal (n= 24) and breast cancer (n=27) tissue from black and white women to identify microbial metabolites and metabolomic signatures that differ by breast tumor subtype and obesity status. Principal component analysis and hierarchical clustering of the global metabolite profiling data revealed separation between the metabolic signatures of normal and breast tumor tissue. Random forest analysis also revealed a unique biochemical signature in normal versus breast tumors by obesity status and breast tumor subtype, including triple negative breast tumors. Our data show that obesity associates with a unique set of metabolic pathways that facilitate the handling of inflammation, protein catabolism and tissue remodeling, and energy metabolism, which may be regulated by microbial processing in breast tumor tissue. Citation Format: Athena Starlard-Davenport, Alana Smith, Elizabeth Tolley, Lu Lu. Metabolomic analysis reveals unique biochemical signatures associated with microbial dysbiosis, inflammation and energy metabolism in breast tissues of obese and nonobese black and white breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2341.