Considering the implementation research-to-practice gap: An experimental evaluation of intervention-general methods for assessing and supporting intervention fidelity through coaching.

Implementation support through coaching-such as with embedded fidelity assessment, performance feedback, modeling, and alliance building-has been empirically supported as a way to increase and sustain interventionists' fidelity levels. However, education research consistently shows that practitioners struggle to monitor and improve interventionists' fidelity using implementation support strategies. One explanation for this type of implementation research-to-practice gap is that evidence-based coaching strategies have significant limitations with respect to their usability, feasibility, and adaptability. This study is the first to experimentally evaluate an evidence-based set of adaptable materials and procedures designed to assess and support the intervention fidelity of school-based interventions. Using a randomized multiple-baseline-across-participants design, we examined the extent to which these materials and procedures would influence intervention adherence and quality of an evidence-based reading intervention. Across all nine interventionist participants, data revealed that the implementation strategies meaningfully improved intervention adherence and quality, and high levels of intervention fidelity maintained 1 month after removing the support procedures. Findings are discussed with respect to how these materials and procedures address a critical need within school-based research and practice as well as how they may help to inform and address the implementation research-to-practice gap in education.

Exploration of the Complex Relationships Among Multilevel Predictors of PrEP Use Among Men Who Have Sex with Men in the United States.

To explore the relationships among individual-, social-, and contextual- (state-level characteristics, including LBGTQ + and racial inequality) level factors and PrEP use. A cross-sectional survey was conducted in 2015-2016 among a geographically diverse group of men who have sex with men (MSM). Survey data was linked to publicly available state-level data based on participant zip code. Multivariable multilevel logistic regression was used to explore the association between multilevel variables and PrEP use. Of 4165 HIV-negative MSM, 13.4% were taking PrEP. In the regression analysis, several demographic and behavioral factors were associated with higher odds of PrEP use. Importantly, after adjusting for individual- and social-level factors, residents of states with high LGBTQ + equality had significantly higher odds of taking PrEP (OR 1.57; 95% CI 1.119, 2.023) compared to low equality states. LGBTQ + inequality between states may hinder PrEP use. States may need to take proactive measures to reduce LGBTQ + inequality as this may negatively impact the ability to reach the federal administration's stated goal to end the HIV epidemic in the US.

Lessons for Patient Education Around Long-Acting Injectable PrEP: Findings from a Mixed-Method Study of Phase II Trial Participants.

This study aimed to identify patients' physical and psychosocial experiences of an investigational long-acting injectable PrEP product to aid in the development of patient and provider education materials. Twenty-eight participants of a Phase 2 safety, tolerability, and acceptability study of long-acting integrase inhibitor cabotegravir (CAB-LA) were interviewed on their physical and psychosocial experiences of the injections. Five themes emerged through a framework analysis on these interview transcripts: (1) injection-related pain is highly variable across individuals; (2) pain is more impactful after the injections than during; (3) patient anxiety is critical, but does not determine the experience of injections and decreases over time; (4) intimacy and awkwardness of gluteal injections impacts patients' experiences; (5) patient education and care strategies can mitigate the above factors. These findings can inform further sociobehavioral research within Phase 3 efficacy trials of CAB-LA, as well as patient education and provider guidance for future injectable PrEP products.

Chronic Hepatitis C Virus Infection and the Proinflammatory Effects of Injection Drug Use.

BACKGROUND: Chronic inflammation, as defined by persistent immune activation, is associated with adverse clinical outcomes. People who inject drugs (PWID) have evidence of persistent immune activation. Here, in a cohort of PWID with or without hepatitis C virus (HCV) infection, we sought to dissect out the contribution of chronic HCV infection (common in PWID) from the effects of injection drug use itself. METHODS: Four groups of study volunteers were recruited: group 1 comprised active PWID; group 2, individuals who ceased injecting drugs 1-2 months before recruitment; group 3, individuals who ceased injecting drugs 3-4 months before recruitment; and group 4, healthy volunteers. Soluble and cell-associated markers of immune activation were quantified. RESULTS: HCV-viremic PWID have elevated levels of immune activation when compared to healthy volunteers. Cessation of injection drug use results in a decline in immune activation in the absence of HCV viremia, while HCV-viremic individuals who previously were PWID continue to harbor elevated levels of immune activation, as defined by increased levels of soluble CD14 and tumor necrosis factor α and by the presence of CD38+HLA-DR+ CD4+ and CD8+ T cells. CONCLUSIONS: Immune activation, a well-defined surrogate of poor clinical outcome that is elevated in PWID, can regress to normal levels in former injection drug users who are HCV aviremic. Therefore, enhanced harm-reduction efforts should incorporate aggressive treatment of HCV infection. CLINICAL TRIALS REGISTRATION: NCT01831284.

Failure of many United States Department of Health Web sites to provide accurate information about the female condom.

Uptake of the female condom (FC) in the United States has historically been low; inadequate promotion may be one barrier faced by potential users. We performed a content analysis of state and municipal health department Web sites to describe how the FC is being promoted for pregnancy and disease prevention. We found that only a slim majority (60.8%) of health department Web sites mention the FC at all and those that do include numerous inaccuracies in their messaging. These inaccuracies may discourage uptake of the FC or have a detrimental impact on the experience when using the product for the first time.

A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge.

Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human immunodeficiency virus) rhesus macaque challenge model. We examined the pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera (depot medroxyprogesterone acetate), which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with GSK744 LA (50 mg/kg) monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were fivefold lower on average in cervical tissues than in rectal tissues. Eight female rhesus macaques were treated with GSK744 LA at week 0, and four female rhesus macaques served as controls. All animals received a high-dose challenge of SHIV162P3 at week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas viremia was detected 1 to 2 weeks after SHIV challenge in all control animals. The GSK744 LA-treated rhesus macaques were given a second administration of drug at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected six of eight female rhesus macaques against three high-dose SHIV challenges, whereas all control animals became infected after the first challenge (P = 0.0003, log-rank test). These results support further clinical development of GSK744 LA for PrEP.

Inconsistencies on U.S. Departments of Health Websites Regarding Anal Use of the Female Condom.

The female condom (FC) is FDA approved to prevent pregnancy and sexually transmitted infections during vaginal intercourse, but not for use during anal intercourse. Studies suggest that a sizeable proportion of men who have sex with men use the FC for anal intercourse despite lack of safety and efficacy information. We reviewed Department of Health (DOH) websites for U.S. states (n = 50) and major municipalities (population >500,000; n = 29) regarding anal use of the FC. Forty-eight (60.8 %) websites mentioned the FC, of which only 21 (45.8 %) mentioned anal use. Of those that mention anal use, 8 (38.1 %) supported, 13 (61.9 %) were neutral, and 1 (4.8 %) discouraged this use. Ten websites (47.6 %) provided instructions for anal use of the FC-ranging from removal of the inner ring, leaving the inner ring in place, and either option. In the absence of safety and efficacy data, U.S. DOH websites are providing different and often contradictory messages about the FC for anal sex.

High interest in a long-acting injectable formulation of pre-exposure prophylaxis for HIV in young men who have sex with men in NYC: a P18 cohort substudy.

OBJECTIVE: In the context of continued high rates of condomless anal intercourse and HIV-1 infection, young men who have sex with men (YMSM) need additional effective and desirable HIV prevention tools. This study reports on the willingness of a racially-ethnically diverse cohort of YMSM to use a new biomedical prevention approach, a long-acting injectable pre-exposure prophylaxis (LAI-PrEP) agent. METHODS: A cross-sectional study conducted between June-August 2013 recruited participants from an ongoing cohort study of YMSM in NYC. Participants included 197 YMSM, of whom 72.6% (n = 143) identified as men of color. Two outcomes were measured through computer-assisted self-interviews: 1) willingness to use long-acting injectable PrEP and 2) preference for route of administration of PrEP. In addition, concerns about perceived impacts of PrEP on health and risk behavior, access to health services, and stigma were investigated. RESULTS: Over 80% (n = 159/197, p<0.001) of participants stated they would be willing to use LAI-PrEP. With regards to preference for mode of delivery 79.2% (n = 156/197, p<0.001) stated they would prefer an injection administered every three months over a daily pill or neither one. CONCLUSIONS: This study is the first to explore acceptability of LAI-PrEP in the US. A significant majority of participants expressed willingness to use LAI and the majority preferred LAI-PrEP. LAI-PrEP holds great promise in that it could circumvent the adherence challenges associated with daily dosing, especially if nested within appropriate psycho-behavioral support. Medical providers whose patients include YMSM at high risk for HIV infection should note the positive attitudes toward PrEP, and specifically LAI-PrEP.

A randomized open-label study of 3- versus 5-drug combination antiretroviral therapy in newly HIV-1-infected individuals.

BACKGROUND: To understand whether combination antiretroviral therapy (cART) has been optimized, we asked whether 3-drug protease inhibitor (PI)-based cART intensified with raltegravir and maraviroc and initiated during early infection would improve outcomes when compared with similarly applied 3-drug PI-based cART. METHODS: Forty newly HIV-1-infected patients were randomized 1:2 to receive 3-drug (N = 14) or 5-drug (N = 26) therapy. The primary end point was the percent of subjects with undetectable plasma viremia using standard reverse transcriptase-polymerase chain reaction and the single copy assay after 48 weeks. Secondary end points included levels of cell-associated HIV-1 DNA and RNA and levels of infectious virus in resting CD4 T cells at week 96 and quantitative and qualitative immunologic responses. RESULTS: At 48 weeks, 34 subjects remained on study and are included in the as-treated analysis. Three of 11 (27.3%) in the 3-drug arm and 9 of 21 (42.9%) in the 5-drug arm had plasma HIV-1 RNA levels below detection by both standard reverse transcriptase-polymerase chain reaction and single copy assay (P = 0.46, Fisher exact test). No significant differences in absolute levels of proviral DNA or changes in cell-associated RNA were seen during 96 weeks of therapy. Mean levels of infectious HIV-1 in resting CD4 T cells at week 96 in 7 subjects treated with 3-drugs and 13 with 5-drugs were 0.67 and 0.71 infectious units per million, respectively (P = 0.81). No differences were seen in quantitative or qualitative immunologic determinations including markers of immune activation. CONCLUSIONS: Intensified 5-drug cART initiated during early infection fails to significantly further impact virologic or immunologic responses beyond those achieved with standard 3-drug PI-based cART.

The Himalayas: barrier and conduit for gene flow.

The Himalayan mountain range is strategically located at the crossroads of the major cultural centers in Asia, the Middle East and Europe. Although previous Y-chromosome studies indicate that the Himalayas served as a natural barrier for gene flow from the south to the Tibetan plateau, this region is believed to have played an important role as a corridor for human migrations between East and West Eurasia along the ancient Silk Road. To evaluate the effects of the Himalayan mountain range in shaping the maternal lineages of populations residing on either side of the cordillera, we analyzed mitochondrial DNA variation in 344 samples from three Nepalese collections (Newar, Kathmandu and Tamang) and a general population of Tibet. Our results revealed a predominantly East Asian-specific component in Tibet and Tamang, whereas Newar and Kathmandu are both characterized by a combination of East and South Central Asian lineages. Interestingly, Newar and Kathmandu harbor several deep-rooted Indian lineages, including M2, R5, and U2, whose coalescent times from this study (U2, >40 kya) and previous reports (M2 and R5, >50 kya) suggest that Nepal was inhabited during the initial peopling of South Central Asia. Comparisons with our previous Y-chromosome data indicate sex-biased migrations in Tamang and a founder effect and/or genetic drift in Tamang and Newar. Altogether, our results confirm that while the Himalayas acted as a geographic barrier for human movement from the Indian subcontinent to the Tibetan highland, it also served as a conduit for gene flow between Central and East Asia.

Participation in research involving novel sampling and study designs to identify acute HIV-1 infection among minority men who have sex with men.

HIV-1 infection disproportionally affects African-American and Latino men who have sex with men (MSM). Their inclusion in biomedical and behavioral research is critical to understanding and addressing HIV vulnerability. Using focus groups, we sought to understand the perceptions related to participating in biomedical research of acute/recent HIV-1 infection (AHI) using complex sampling and data collection methods to reach this hidden group at highest risk of acquiring and transmitting HIV. Given the potential impact of AHI on HIV transmission in MSM, it is important to understand this intersection for HIV prevention, care, and treatment purposes. The aim of this study was to understand how recruitment and data collection methods affect AHI research participation willingness particularly among MSM of color. Findings suggest that major barriers to research participation with complex sampling to identify AHI and intensive risk behavior collection such as diary methods are lack of anonymity, partner disclosure, and study fatigue. The authors explore implications for future study designs and development based on these findings.

Household exposure to pesticides and bladder exstrophy in a newborn baby boy: a case report and review of the literature.

INTRODUCTION: Bladder exstrophy is a rare urogenital abnormality. Other urogenital malformations have been associated with exposure to hormonal pesticide disruptors during critical developmental periods. This is the first report in the literature to associate household exposure to pesticides with bladder exstrophy. CASE PRESENTATION: We describe the pediatric environmental history of a newborn baby boy with isolated bladder exstrophy. In this case the pediatric environmental history includes the constitutional, genealogical, genetic and environmental factors related to bladder exstrophy, which revealed a cockroach infestation in the parents' home and the daily use of bug spray to kill them. The mother used one bottle of spray every 2 days (1000cc) and more in the summer, when the problem was worse. During gestational weeks 0-12, the mother intensively used a domestic pesticide consisting of a mixture of pyrethroids (cyfenothrin 0.5%, and tetramethrin 0.31%) and pyriproxyfen (0.01%). She described repeated episodes of mild to moderate poisoning that are associated with the use of household pesticides. The mother is a housewife and the father works as a fumigator of fruit fields and he reported gastrointestinal symptoms associated with the use of occupational pesticides. However, he did not believe he carried traces of these products into the home and his wife washed his work clothes separately. The pyrethroids and pyriproxyfen were detected in a urine sample obtained from the child 4 months after he was born. No other risk factors were identified. CONCLUSIONS: A detailed and carefully conducted pediatric environmental history, which includes information about home pesticide use, should be carried out for all children with bladder exstrophy. Domestic exposure to pesticides during critical developmental periods may have deleterious effects for the fetus.

Estimated intake levels of methylmercury in children, childbearing age and pregnant women in a Mediterranean region, Murcia, Spain.

Methylmercury (MeHg) is a bioaccumulable toxin in the trophic chain and a powerful neurotoxin during fetal and child development. Consumption of contaminated fish and shellfish is a principal environmental source of MeHg exposure. This study was designed to assess the Hg and estimated MeHg intake in vulnerable groups of the Murcia region, a Mediterranean part of Spain, compared with international regulations. A validated food frequency questionnaire was used to assess seafood consumptions in 320 children younger than 10 years, 301 women of childbearing age, and 537 pregnant women. Hg concentrations were measured in the most consumed fish products by cold vapor generation-atomic fluorescence spectrometry. The weekly intake of MeHg (microg/kg bw/week) was 2.60 (95% CI = 2.10-3.10) in children 1-5 years, 2.65 (95% CI = 2.26-3.03) in children 6-10 years, 0.98 (95% CI = 0.89-1.07) in women of childbearing age, and 0.88 (95% CI = 0.81-0.95) in pregnant women. The main exposure to MeHg, especially in young children, is related to intake of bluefin tuna and swordfish. Fifty-four percent of children aged 1-10 years, 10% of pregnant women, and 15% of women of childbearing age exceed the Joint Expert Committee on Food Additives provisional tolerable weekly intake of MeHg. In the Murcia region, where fish is a central component of the diet, the focus should be on educating vulnerable populations to reorient fish consumption in order to lower the amount of Hg incorporated with the diet as well as to reduce Hg emissions into the environment.

A randomized trial of bupropion and/or nicotine gum as maintenance treatment for preventing smoking relapse.

AIM: To investigate the efficacy of maintenance treatment with bupropion and/or nicotine gum for reducing smoking relapse. DESIGN, SETTING AND PARTICIPANTS: A 48-week study was conducted at a university-based smoking cessation clinic between February 2001 and October 2005. A total of 588 smokers received bupropion and nicotine patch in 8 weeks of open-label treatment (OLT); 289 abstainers during the last 4 weeks of OLT were randomized in double-blind placebo-controlled fashion to one of four arms for 16 weeks of maintenance treatment (MT) followed by 24 weeks of non-treatment follow-up (NTFU). INTERVENTION: Bupropion (300 mg/day) and 2 mg nicotine gum, used alone or combined, and comparable placebo pill and placebo gum. Behavioral counseling at all visits. OUTCOME: Time to relapse (TTR) from randomization. Relapse is defined as the first 7 consecutive days of smoking. Abstinence verified by carbon monoxide