Coordinating centers and multi-practice-based research network (PBRN) research.

Practice-based research networks (PBRNs) have emerged as laboratories in which to address important primary care challenges. In 2011, the Agency for Healthcare Research and Quality's PBRN database included more than 130 networks, most regional and some national, with member practices in every state. Regional networks may have certain advantages over national networks with respect to practice recruitment and project quality control because of closer relationships and shorter distances. However, national networks often can achieve larger numbers of practices with greater diversity, resulting in broader generalizability of results. Increasingly, regional networks are collaborating on multinetwork projects, but this creates significant study coordination challenges. A potential solution is to incorporate PBRN coordinating centers similar to those used in many National Institutes of Health and industry-sponsored multi-center clinical trials. In this article, we discuss the potential functions of a coordinating center in multi-region PBRN studies based on our experience with 2 recent studies.

Longitudinal antiretroviral adherence among adolescents infected with human immunodeficiency virus.

OBJECTIVES: To longitudinally follow a cohort of adolescents with human immunodeficiency virus (HIV) and to investigate long-term antiretroviral therapy adherence and factors associated with adherence. DESIGN, SETTING, AND PATIENTS: Adolescents infected with HIV (N = 231; mean age, 18.4 years; 72.7% female; 74.9% African American) from 13 cities throughout the United States were assessed at 3-month intervals. MAIN OUTCOME MEASURES: Self-reported adherence measures were validated by comparison with HIV-1 RNA viral load, and behavioral factors that may be associated with antiretroviral therapy adherence were assessed. RESULTS: At the initial visit, approximately 69% of the adolescents reported being adherent to antiretroviral therapy. Adolescents in the later HIV disease stage were less likely to be adherent compared with those in the earlier disease stage. Less alcohol use and being in school were associated with adherence by adolescents on weekends and over the preceding month. Longitudinal adherence was investigated among 65 subjects initially adherent with available information for at least 4 consecutive visits. The median time to nonadherence was 12 months, and failure to maintain adherence was significantly associated with younger age and depression. Among adolescents who attained an undetectable viral load, only about 50% maintained an undetectable viral load for the year. CONCLUSIONS: These findings indicate an urgent need for better interventions to assist adolescents with HIV in adhering to their medication regimens. Adolescents with advanced disease are likely to need more intervention. New treatments recently found effective for adolescent depression may assist in improving adherence for a majority of adolescents with HIV.

Long-term mortality in the United States cohort of pituitary-derived growth hormone recipients.

OBJECTIVE: Patients who received pituitary-derived growth hormone (GH) are at excess risk of mortality from Creutzfeldt-Jakob disease. We investigated whether they were at increased risk of death from other conditions, particularly preventable conditions. STUDY DESIGN: A cohort (N=6107) from known US pituitary-derived GH recipients (treated 1963-1985) was studied. Deaths were identified by reports from physicians and parents and the National Death Index. Rates were compared with the expected rates for the US population standardized for race, age, and sex. RESULTS: There were 433 deaths versus 114 expected (relative risk [RR], 3.8; 95% confidence interval [CI], 3.4-4.2; P<.0001) from 1963 through 1996. Risk was increased in subjects with GH deficiency caused by any tumor (RR, 10.4; 95% CI, 9.1-12.0; P<.0001). Surprisingly, subjects with hypoglycemia treated within the first 6 months of life were at extremely high risk (RR, 18.3; 95% CI, 9.2-32.8; P<.0001), as were all subjects with adrenal insufficiency (RR, 7.1; 95% CI, 6.2-8.2; P<.0001). A quarter of all deaths were sudden and unexpected. Of the 26 cases of Creutzfeldt-Jakob disease, four cases have died since 2000. CONCLUSIONS: The death rate in pituitary-derived GH recipients was almost four times the expected rate. Replacing pituitary-derived GH with recombinant GH has eliminated only the risk of Creutzfeldt-Jakob disease. Hypoglycemia and adrenal insufficiency accounted for far more mortality than Creutzfeldt-Jakob disease. The large number of potentially preventable deaths in patients with adrenal insufficiency and hypoglycemia underscores the importance of early intervention when infection occurs in patients with adrenal insufficiency, and aggressive treatment of panhypopituitarism.

Barriers to HAART adherence among human immunodeficiency virus-infected adolescents.

OBJECTIVES: To investigate the barriers to highly active antiretrovial therapy (HAART) adherence among human immunodeficiency virus (HIV)-infected adolescents and to explore the association of barriers and nonadherence. DESIGN: Structured interviews were conducted to determine the barriers associated with adherence; principal component factor analysis was performed on scores of the 19 barrier variables. SETTING: Human immunodeficiency virus-infected adolescents were recruited from 13 US cities into the REACH (Reaching for Excellence in Adolescent Care and Health) Project, the first large-scale disease progression study of HIV-positive adolescents infected through sexual behavior or injection drug use. PATIENTS: Human immunodeficiency virus-infected adolescents in the REACH cohort who were prescribed HAART (N = 114) were included in the analyses. MAIN OUTCOME MEASURES: The main outcome measures were self-report of adherence and barriers to adherence and viral load (HIV-1 RNA level in plasma). RESULTS: Viral load was significantly associated with self-report of adherence to HAART (P =.02). Only 28.3% of adolescents reported taking all of their prescribed antiretroviral medications in the previous month. Factor analysis of the barriers to adherence indicates there are 2 factors accounting for the largest proportion of the variance: (1) medication-related adverse effects (both physical and psychological) and (2) complications in day-to-day routines. CONCLUSIONS: Adherence was tied closely with daily routine, which supports the assumption that working closely with adolescents to improve their organizational skills may be necessary to improve adherence. Patient-level intervention, provider-level intervention, and health care system modification may all be necessary to improve HIV-infected adolescents' adherence to HAART.

Utility of cervicography in HIV-infected and uninfected adolescents.

PURPOSE: To compare cytology with cervicography in HIV-infected and uninfected adolescent females. METHODS: At the time of analysis, 334 girls aged 13-19 years from 13 U.S. cities were participating in a prospective study of HIV infection. All subjects had cytology and a Cervigram (cervicography) performed at two consecutive visits 6 months apart, referred to as visit (V) 1 and 2. Cervigrams were sent to the parent company for diagnosis and were categorized as: "negative" or "positive" (compatible with low-grade or high-grade squamous intraepithelial lesions [SIL]). Cytology was considered abnormal if the subject had SIL at either V1 or V2. Sensitivity, specificity, and positive predictive value (PPV) of the Cervigram were calculated compared with repeat Papanicolaou (Pap) smears. RESULTS: Two consecutive adequate Pap smears were available for analysis in 200 adolescents; 51% (95% CI, 43-59) of the 142 HIV-positive youth and 19% (95% CI, 9-29) of the 58 HIV-negative youth had SIL on at least one Pap smear (p < .001). A positive Cervigram was observed in 44% (95% CI, 36-53) of the HIV-infected group and 29% (95% CI, 17-41) of the HIV-uninfected group (p =.06). For the HIV-infected group, the sensitivity, specificity, and PPV of the Cervigram to detect SIL were 58% (95% CI, 45-71), 69% (95%CI, 57-80), and 64% (95%CI, 52-77), respectively. For the HIV-uninfected group, the sensitivity, specificity, and PPV were 64% (95% CI, 31-89), 80% (95% CI, 65-90), and 44% (95% CI, 19-68), respectively. The combined sensitivity, using both the Pap smear and Cervigram result from V1 to detect SIL, was 82% (95% CI, 71-91 for HIV+ and 48-98 for HIV-) in both groups. However, the PPV based the performance of the Cervigram in Pap smear-negative women as 33% (95% CI, 17-53) and 15% (95% CI, 2-45) for the HIV-infected and uninfected group, respectively (p = not significant [ns]). CONCLUSIONS: Although the sensitivity of a single Pap smear increased significantly when the Cervigram was used as an adjunct, the low PPV in both HIV-infected and uninfected groups, suggests that cervicography has a limited utility for precancer and cervical cancer screening in high-risk adolescent populations.

Human papillomavirus infection and abnormal cytology of the anus in HIV-infected and uninfected adolescents.

OBJECTIVE: To examine the prevalence of and risk for anal human papillomavirus (HPV) infection and abnormal anal cytology in sexually active adolescents. DESIGN: Prevalence data from adolescents aged 13-18 years with and without HIV infection and with a history of high-risk sexual behavior. METHODS: HPV DNA was detected using amplification techniques. Abnormal anal cytology was defined as atypical squamous cell of undetermined significance or worse. RESULTS: Prevalence of anal HPV infection was similar in HIV-infected [28/58 (48%)] and uninfected [9/25 (36%)] boys (P = 0.3). but greater in HIV-infected [59/183 (59%)] than in uninfected [11/82 (13%)] girls (P < 0.001). Perianal warts were a risk for anal HPV in both boys [odds ratio (OR), 15.5; 95% confidence interval (CI), 1.6-149] and girls (OR, 9.9; 95% CI, 1.9-51.3). In subjects without anal warts, HIV infection was significant for girls (OR, 2.3; 95% CI, 1.1-4.9) and homosexual/bisexual orientation was significant for boys (OR, 5.2; 95% CI, 1.3-20.6). Abnormal anal cytology was more common among boys [32/77 (41.6%)] than girls [38/230 (16.5%)] (P < 0.001) and in addition to anal HPV, independent risk factors were positive HIV status in boys (OR, 6.5; 95% CI, 1.5-11.9) and number of partners within the past 3 months in girls (OR, 4.2; 95% CI, 1.5-11.9). CONCLUSIONS: Strong risk factors for abnormal anal cytology were HIV infection and anal HPV in boys and anal HPV and higher number of sexual partners for girls. The results suggest that anal cytology screening should be considered in HIV infected homosexual/bisexual males.