Margot R. Krauss

Maternal antiretroviral use during pregnancy and infant congenital anomalies: the NISDI perinatal study.

Background:We evaluated the association between maternal antiretrovirals (ARVs) during pregnancy and infant congenital anomalies (CAs), utilizing data from the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study. Methods:The study population consisted of first singleton pregnancies on study, ≥20 weeks gestation, among women enrolled in NISDI from Argentina and Brazil who delivered between September 2002 and October 2007. CAs were defined as any major structural or chromosomal abnormality, or a cluster of 2 or more minor abnormalities, according to the conventions of the Antiretroviral Pregnancy Registry. CAs were identified from fetal ultrasound, study visit, and death reports. Prevalence rates [number of CAs per 100 live births (LBs)] were calculated for specific ARVs, classes of ARVs, and overall exposure to ARVs. Results:Of 1229 women enrolled, 995 pregnancy outcomes (974 LBs) met the inclusion criteria. Of these, 60 infants (59 LBs and 1 stillbirth) had at least 1 CA. The overall prevalence of CAs (per 100 LBs) was 6.2 [95% confidence interval (CI) 4.6 to 7.7]. The prevalence of CAs after first trimester ARVs (6.2; 95% CI 3.1 to 9.3) was similar to that after second (6.8; 95% CI 4.5 to 9.0) or third trimester (4.3; 95% CI 1.5 to 7.2) exposure. The rate of CAs identified within 7 days of delivery was 2.36 (95% CI 1.4 to 3.3). Conclusions:The prevalence of CAs after first trimester exposure to ARVs was similar to that after second or third trimester exposure. Continued surveillance for CAs among children exposed to ARVs during gestation is needed.

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.

ELISA underestimates measles antibody seroprevalence in US military recruits

The prevalence of antibodies to measles, mumps, and rubella in US military recruits is of importance to public health leaders. We performed ELISA testing using a commercially available product on samples from 537 recruits obtained in 1998, of which 437 were positive (81%). We then performed a validation study in a subsample of the population using plaque reduction neutralization (PRN) to assess misclassification error. This resulted in a corrected estimate of the prevalence of immunity to measles of 96% (95% CI: 92-100%). The military vaccinates a percentage of recruits who are likely to be immune if more sensitive testing, such as PRN, was used.

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.

Hypertension, preeclampsia and eclampsia among HIV-infected pregnant women from Latin America and Caribbean countries

OBJECTIVES To evaluate the incidence of and risk factors for hypertensive disorders in a cohort of HIV-infected pregnant women. METHODS Hypertensive disorders (HD) including preeclampsia/eclampsia (PE/E) and pregnancy induced hypertension, and risk factors were evaluated in a cohort of HIV-infected pregnant women from Latin America and the Caribbean enrolled between 2002 and 2009. Only pregnant women enrolled for the first time in the study and delivered at ≥20 weeks gestation were analyzed. RESULTS HD were diagnosed in 73 (4.8%, 95% CI: 3.8%-6.0%) of 1513 patients; 35 (47.9%) had PE/E. HD was significantly increased among women with a gestational age-adjusted body mass index (gBMI) ≥25 kg/m(2) (OR = 3.1; 95% CI: 1.9-5.0), hemoglobin (Hg) ≥11 g/dL at delivery (OR = 2.1; 95% CI: 1.2-3.6) and age ≥35 years (OR = 1.8; 95% CI: 1.1-3.2). PE/E was increased among women with a gBMI ≥25 kg/m(2) (OR = 3.0; 95% CI: 1.5-6.0) and Hg ≥11 g/dL at delivery (OR = 2.8; 95% CI: 1.2-6.5). A previous history of PE/E increased the risk of PE/E 6.7 fold (95% CI: 1.8-25.5). HAART before conception was associated with PE/E (OR = 2.3; 95% CI: 1.1-4.9). CONCLUSIONS HIV-infected women, with a previous history of PE/E, a gBMI ≥25 kg/m(2), Hg at delivery ≥11 g/dL and in use of HAART before conception are at an increased risk of developing PE/E during pregnancy.

Tuberculosis in HIV-infected infants, children, and adolescents in Latin America

OBJECTIVE To evaluate the occurrence, clinical presentations and diagnostic methods for tuberculosis in a cohort of HIV-infected infants, children and adolescents from Latin America. METHODS A retrospective analysis of children with tuberculosis and HIV was performed within a prospective observational cohort study conducted at multiple clinical sites in Latin America. RESULTS Of 1114 HIV-infected infants, children, and adolescents followed from 2002 to 2011, 69 that could be classified as having confirmed or presumed tuberculosis were included in this case series; 52.2% (95% CI: 39.8-64.4%) had laboratory-confirmed tuberculosis, 15.9% (95% CI: 8.2-26.7%) had clinically confirmed disease and 31.9% (95% CI: 21.2-44.2%) had presumed tuberculosis. Sixty-six were perinatally HIV-infected. Thirty-two (61.5%) children had a history of contact with an adult tuberculosis case; however information on exposure to active tuberculosis was missing for 17 participants. At the time of tuberculosis diagnosis, 39 were receiving antiretroviral therapy. Sixteen of these cases may have represented immune reconstitution inflammatory syndrome. CONCLUSIONS Our study emphasizes the need for adequate contact tracing of adult tuberculosis cases and screening for HIV or tuberculosis in Latin American children diagnosed with either condition. Preventive strategies in tuberculosis-exposed, HIV-infected children should be optimized.

Undervaccination of perinatally HIV-infected and HIV-exposed uninfected children in Latin America and the Caribbean.

Background: Perinatally HIV-infected (PHIV) children may be at risk of undervaccination. Vaccination coverage rates among PHIV and HIV-exposed uninfected (HEU) children in Latin America and the Caribbean were compared. Methods: All PHIV and HEU children born from 2002 to 2007 who were enrolled in a multisite observational study conducted in Latin America and the Caribbean were included in this analysis. Children were classified as up to date if they had received the recommended number of doses of each vaccine at the appropriate intervals by 12 and 24 months of age. Fisher’s exact test was used to analyze the data. Covariates potentially associated with a child’s HIV status were considered in multivariable logistic regression modeling. Results: Of 1156 eligible children, 768 (66.4%) were HEU and 388 (33.6%) were PHIV. HEU children were significantly (P < 0.01) more likely to be up to date by 12 and 24 months of age for all vaccines examined. Statistically significant differences persisted when the analyses were limited to children enrolled before 12 months of age. Controlling for birth weight, sex, primary caregiver education and any use of tobacco, alcohol or illegal drugs during pregnancy did not contribute significantly to the logistic regression models. Conclusions: PHIV children were significantly less likely than HEU children to be up to date for their childhood vaccinations at 12 and 24 months of age, even when limited to children enrolled before 12 months of age. Strategies to increase vaccination rates in PHIV are needed.

Evaluation of viral load thresholds for predicting new World Health Organization stage 3 and 4 events in HIV-infected children receiving highly active antiretroviral therapy.

Background:This study evaluated a wide range of viral load (VL) thresholds to identify a cut-point that best predicts new clinical events in children on stable highly active antiretroviral therapy (HAART). Methods:Cox proportional hazards modeling was used to assess the adjusted risk for World Health Organization stage 3 or 4 clinical events (WHO events) as a function of time-varying CD4, VL, and hemoglobin values in a cohort study of Latin American children on HAART ≥6 months. Models were fit using different VL cut-points between 400 and 50,000 copies per milliliter, with model fit evaluated on the basis of the minimum Akaike information criterion value, a standard model fit statistic. Results:Models were based on 67 subjects with WHO events out of 550 subjects on study. The VL cut-points of >2600 and >32,000 copies per milliliter corresponded to the lowest Akaike information criterion values and were associated with the highest hazard ratios (2.0, P = 0.015; and 2.1, P = 0.0058, respectively) for WHO events. Conclusions:In HIV-infected Latin American children on stable HAART, 2 distinct VL thresholds (>2600 and >32,000 copies/mL) were identified for predicting children at significantly increased risk for HIV-related clinical illness, after accounting for CD4 level, hemoglobin level, and other significant factors.

Repeat pregnancy in women with HIV infection in Latin America and the Caribbean

Intended and unintended pregnancies occur frequently among human immunodeficiency virus (HIV)-infected women. We evaluated the occurrence of repeat pregnancy and characteristics associated with this outcome among HIV-infected women in Latin America and the Caribbean who were participating in the National Institute of Child Health and Human Development (NICHD) International Site Development Initiative (NISDI). Of the 1342 HIV-infected pregnant women enrolled in NISDI, 124 (9.2%) had one or more repeat pregnancies on study. Median time between the index delivery and date of conception of the subsequent pregnancy was 1.4 years (range 0.1–5.7). Younger age (odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.04–1.11 per one year decrease in age), hospitalization during the index pregnancy or up to six months post-partum [OR = 2.0, 95% CI: 1.2–3.4], and poor index pregnancy outcome (stillbirth or spontaneous/therapeutic abortion; OR = 3.4, 95% CI: 1.4–8.4) were associated with increased occurrence of repeat pregnancy in multivariable analysis. Among women with repeat pregnancies, the proportion receiving antiretroviral treatment (vs. prophylaxis) increased from 39.4% at the time of the index pregnancy to 81.8% at the time of the repeat pregnancy (p < 0.001). These results can help identify women most likely to benefit from reproductive counseling in order to assist with healthy pregnancy planning and prevention of unintended pregnancies.