Rachel A. Cohen

Implementing Asthma Guidelines Using Practice Facilitation and Local Learning Collaboratives: A Randomized Controlled Trial

PURPOSE Guideline implementation in primary care has proven difficult. Although external assistance through performance feedback, academic detailing, practice facilitation (PF), and learning collaboratives seems to help, the best combination of interventions has not been determined. METHODS In a cluster randomized trial, we compared the independent and combined effectiveness of PF and local learning collaboratives (LLCs), combined with performance feedback and academic detailing, with performance feedback and academic detailing alone on implementation of the National Heart, Lung and Blood Institute’s Asthma Guidelines. The study was conducted in 3 primary care practice-based research networks. Medical records of patients with asthma seen during pre- and postintervention periods were abstracted to determine adherence to 6 guideline recommendations. McNemar’s test and multivariate modeling were used to evaluate the impact of the interventions. RESULTS Across 43 practices, 1,016 patients met inclusion criteria. Overall, adherence to all 6 recommendations increased (P ≤.002). Examination of improvement by study arm in unadjusted analyses showed that practices in the control arm significantly improved adherence to 2 of 6 recommendations, whereas practices in the PF arm improved in 3, practices in the LLCs improved in 4, and practices in the PF + LLC arm improved in 5 of 6 recommendations. In multivariate modeling, PF practices significantly improved assessment of asthma severity (odds ratio [OR] = 2.5, 95% CI, 1.7–3.8) and assessment of asthma level of control (OR = 2.3, 95% CI, 1.5–3.5) compared with control practices. Practices assigned to LLCs did not improve significantly more than control practices for any recommendation. CONCLUSIONS Addition of PF to performance feedback and academic detailing was helpful to practices attempting to improve adherence to asthma guidelines.

Supporting Better Science in Primary Care: A Description of Practice-based Research Networks (PBRNs) in 2011

Background: Bound by a shared commitment to improving medical care through systematic inquiry, practice-based research networks (PBRNs) provide a basic laboratory for primary care research and dissemination. Methods: Data from US primary care PBRNs were collected as part of the 2011 Agency for Healthcare Research and Quality PBRN registration process. Data addressed PBRN characteristics, research activities, and perceived strengths and weaknesses. Results: One hundred forty-three primary care PBRNs were registered with the resource center in 2011, including 131 that were identified as either eligible for Agency for Healthcare Research and Quality recognition (n = 121) or as developing (n = 10). These PBRNs included 12,981 practices with more than 63,000 individual members providing care to approximately 47.5 million people. PBRNs had an average of 482 individual members (median, 170) from 101 practices (median, 32). Conclusions: PBRNs are growing in experience and research capacity. With member practices serving approximately 15% of the US population, PBRNs are adopting more advanced study designs, disseminating and implementing practice change, and participating in clinical trials. PBRNs provide valuable capacity for investigating questions of importance to clinical practice, disseminating results, and implementing evidence-based strategies. PBRNs are well positioned to support the emerging public health role of primary care providers and provide an essential component of a learning health care system.

The NICHD International Site Development Initiative perinatal cohorts (2002–09)

70provided by the protocol, and initiation and manage-ment of ARV treatment or prophylaxis were decidedby individual site investigators as per ARV availability,Published by Oxford University Press on behalf of the International Epidemiological Association 2011 International Journal of Epidemiology 2011;1–8doi:10.1093/ije/dyr024

Prevalence and predictors of elevated aspartate aminotransferase-to- platelet ratio index in latin American perinatally HIV-infected children

Background: Chronic liver disease has emerged as an important problem in adults with longstanding HIV infection, but data are lacking for children. We characterized elevated aspartate aminotransferase-to-platelet ratio index (APRI), a marker of possible liver fibrosis, in perinatally HIV-infected children. Methods: The National Institute of Child Health and Human Development International Site Development Initiative enrolled HIV-infected children (ages 0.1–20.1 years) from 5 Latin American countries in an observational cohort from 2002 to 2009. Twice yearly visits included medical history, physical examination and laboratory evaluations. The prevalence (95% confidence interval) of APRI > 1.5 was calculated, and associations with demographic, HIV-related and liver-related variables were investigated in bivariate analyses. Results: APRI was available for 1012 of 1032 children. APRI was >1.5 in 32 (3.2%, 95% confidence interval: 2.2%–4.4%) including 2 of 4 participants with hepatitis B virus infection. Factors significantly associated with APRI > 1.5 (P < 0.01 compared with APRI ⩽ 1.5) included country, younger age, past or current hepatitis B virus, higher alanine aminotransferase, lower total cholesterol, higher log10 current viral load, lower current CD4 count, lower nadir CD4 count, use of hepatotoxic nonantiretroviral (ARV) medications and no prior ARV use. Rates of APRI > 1.5 varied significantly by current ARV regimen (P = 0.0002), from 8.0% for no ARV to 3.2% for non–protease inhibitor regimens to 1.5% for protease inhibitor–based regimens. Conclusions: Elevated APRI occurred in approximately 3% of perinatally HIV-infected children. Protease inhibitor–based ARVs appeared protective whereas inadequate HIV control appeared to increase risk of elevated APRI. Additional investigations are needed to better assess potential subclinical, chronic liver disease in HIV-infected children.

Leveraging practice-based research networks to accelerate implementation and diffusion of chronic kidney disease guidelines in primary care practices: a prospective cohort study

BackgroundFour practice-based research networks (PBRNs) participated in a study to determine whether networks could increase dissemination, implementation, and diffusion of evidence-based treatment guidelines for chronic kidney disease by leveraging early adopter practices.MethodsMotivated practices from four PBRNs received baseline and periodic performance feedback, academic detailing, and weekly practice facilitation for 6 months during wave I of the study. Each wave I practice then recruited two additional practices (wave II), which received performance feedback and academic detailing and participated in monthly local learning collaboratives led by the wave I clinicians. They received only monthly practice facilitation. The primary outcomes were adherence to primary care-relevant process-of-care recommendations from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative Guidelines. Performance was determined retrospectively by medical records abstraction. Practice priority, change capacity, and care process content were measured before and after the interventions.ResultsFollowing the intervention, wave I practices increased the use of ACEIs/ARBs, discontinuation of NSAIDs, testing for anemia, and testing and/or treatment for vitamin D deficiency. Most were able to recruit two additional practices for wave II, and wave II practices also increased their use of ACEIs/ARBs and testing and/or treatment of vitamin D deficiency.ConclusionsWith some assistance, early adopter practices can facilitate the diffusion of evidence-based approaches to other practices. PBRNs are well-positioned to replicate this process for other evidence-based innovations.

Missed opportunities for prevention of mother‐to‐child transmission of HIV‐1 in the NISDI Perinatal and LILAC cohorts

To evaluate cases of mother‐to‐child transmission of HIV‐1 at multiple sites in Latin America and the Caribbean in terms of missed opportunities for prevention.

Mode of delivery and neonatal respiratory morbidity among HIV-exposed newborns in Latin America and the Caribbean: NISDI Perinatal-LILAC Studies.

To evaluate respiratory morbidity (RM) in HIV‐exposed newborns according to mode of delivery.

Lipid levels in the second year of life among HIV-infected and HIV-exposed uninfected Latin American children

Background:Dyslipidemia is observed among older children and adults with HIV. We examined nonfasting cholesterol and triglycerides in two groups of 12–23-month-old Latin American children – HIV-infected vs. HIV-exposed but uninfected (HEU). Methods:HIV-infected and HEU children in Latin America and Jamaica were enrolled in an observational cohort. Eligibility for this analysis required having cholesterol and triglyceride results available during the second year of life. Results:HIV-infected (n = 83) children were slightly older at the time of lipid testing than the HEU (n = 681). Forty percent of the HIV-infected children were on protease inhibitor-based antiretroviral therapy (ART); 41% were not on ART. There was no statistically significant difference in mean cholesterol concentrations (mg/dl) by HIV status; however, the HIV-infected children had higher mean triglyceride concentrations. The prevalence of high cholesterol (>200 mg/dl) and high triglycerides (>110 mg/dl) was higher among the HIV-infected vs. HEU. Among the HIV-infected children, mean cholesterol and triglyceride concentrations varied by ART. Children receiving no ART had a significantly lower mean cholesterol concentration. Those receiving protease inhibitor-containing ART had a significantly higher mean triglyceride concentration compared to the other two antiretroviral regimen groups. Conclusion:A greater proportion of HIV-infected children at 12–23 months have hyperlipidemia when compared to HEU children, with the highest triglyceride concentrations observed among those receiving protease inhibitor-containing ART, and the lowest cholesterol levels among those not receiving ART. Implications of these findings will require continued follow-up of HIV-infected children who initiate therapy early in life.

Altered Natural Killer Cell Function in HIV-Exposed Uninfected Infants

Objectives HIV-exposed uninfected (HEU) infants have higher rates of severe and fatal infections compared with HIV-unexposed (HUU) infants, likely due to immune perturbations. We hypothesized that alterations in natural killer (NK) cell activity might occur in HEU infants and predispose them to severe infections. Design Case–control study using cryopreserved peripheral blood mononuclear cells (PBMCs) at birth and 6 months from HEU infants enrolled from 2002 to 2009 and HUU infants enrolled from 2011 to 2013. Methods NK cell phenotype and function were assessed by flow cytometry after 20-h incubation with and without K562 cells. Results The proportion of NK cells among PBMCs was lower at birth in 12 HEU vs. 22 HUU (1.68 vs. 10.30%, p < 0.0001) and at 6 months in 52 HEU vs. 72 HUU (3.09 vs. 4.65%, p = 0.0005). At birth, HEU NK cells demonstrated increased killing of K562 target cells (p < 0.0001) and increased expression of CD107a (21.65 vs. 12.70%, p = 0.047), but these differences resolved by 6 months. Stimulated HEU NK cells produced less interferon (IFN)γ at birth (0.77 vs. 2.64%, p = 0.008) and at 6 months (4.12 vs. 8.39%, p = 0.001), and showed reduced perforin staining at 6 months (66.95 vs. 77.30%, p = 0.0008). Analysis of cell culture supernatants indicated that lower NK cell activity in HEU was associated with reduced interleukin (IL)-12, IL-15, and IL-18. Addition of recombinant human IL-12 to stimulated HEU PBMCs restored IFNγ production to that seen in stimulated HUU cultures. Conclusion NK cell proportion, phenotype, and function are altered in HEU infants. NK cell cytotoxicity and degranulation are increased in HEU at birth, but HEU NK cells have reduced IFNγ and perforin production, suggesting an adequate initial response, but decreased functional reserve. NK cell function improved with addition of exogenous IL-12, implicating impaired production of IL-12 by accessory cells. Alterations in NK cell and accessory cell function may contribute to the increased susceptibility to infection in HEU infants.

Excess respiratory viral infections and low antibody responses among HIV-exposed, uninfected infants

Objective: HIV-exposed uninfected (HEUs) infants have frequent severe infection, hospitalization, and death. We performed a serologic investigation to determine the role of common childhood respiratory pathogens in the excess incidence of infections in HEUs. Design: Prospective cohort study of mother–infant pairs. Methods: Among 247 HEUs and 88 HIV-unexposed uninfected (HUU) infant–mother pairs, we measured maternal antibodies to respiratory syncytial virus (RSV) and pneumococcus (PNC 1, 5, 6B, 14); infant antibodies to RSV, influenza A (flu), parainfluenza viruses (1, 2, 3), and PNC 1, 5, 6B, and 14 were measured at 0 and 6 months, and antitetanus antibodies at 6 months. Results: HIV-infected mothers had higher RSV and lower PNC antibody concentrations at delivery than uninfected mothers. Transplacental transfer of maternal antibodies, particularly for RSV, was lower in HEUs compared with HUUs. At birth, HEUs had higher concentrations of anti-RSV antibodies than HUUs, but lower antibodies to the other respiratory agents. At 6 months, HEUs had significantly higher proportions of seroconversions and higher antibody concentrations against parainfluenza viruses 1, 2, and 3. There were no significant differences in seroconversions to flu and RSV, but antibody concentrations to RSV were six-fold lower in HEUs versus HUUs at 6 months. Antibody responses to at least two doses of tetanus vaccine were also six-fold lower in HEUs compared with HUUs. Conclusion: Six-month-old HEUs had a higher incidence of respiratory viral infections than HUUs. In addition to the low passive protection from maternal antibodies, low antibody responses of HEUs may contribute to increased morbidity and mortality.