Jeremy Weedon

Distinct Risk Factors for Intrauterine and Intrapartum Human Immunodeficiency Virus Transmission and Consequences for Disease Progression in Infected Children

Predictors and prognosis of intrauterine and intrapartum human immunodeficiency virus (HIV) transmission were investigated among 432 children of HIV-infected women in the Perinatal AIDS Collaborative Transmission Study. Timing of transmission was inferred from polymerase chain reaction or viral culture within 2 days of birth. Proportions of infections due to intrauterine transmission were similar among women using (29%) or not using zidovudine (30%). Preterm delivery was strongly associated with intrapartum transmission (relative risk, 3.7; 95% confidence interval [CI], 2.2-6.1), particularly among infants delivered longer after membrane rupture, but was not associated with intrauterine transmission. Progression to AIDS or death increased 2.5-fold (95% CI, 1.1-5.8) among intrauterine infected children, adjusting for preterm delivery, and maternal CD4 cell count. Early transmission appears unlikely to explain instances of zidovudine failure. Preterm infants may be more vulnerable to HIV acquisition at delivery, especially if membrane rupture is prolonged. Intrauterine infection does not appear to increase risk of preterm delivery.

Association of Human Immunodeficiency Virus (HIV) Load Early in Life with Disease Progression among HIV-Infected Infants

The utility of RNA virus load to predict progression of human immunodeficiency virus (HIV)-1 disease was assessed in 89 HIV-1-infected children. Of 22 virus load values during week 1 of life, 17 were below the detection threshold. Geometric mean virus load increased to approximately 7 x 10(5) copies/mL by week 4, was sustained throughout the first 6 months of life, and then declined to 1.6 x 10(5) copies/mL during the third year. Samples from week 1 of life had little predictive value, but virus load during days 7-30 strongly predicted progression to CDC-3 classification or death (P = .024; risk ratio = 1.6), and virus load during months 2-3 predicted progression to CDC-C or death within the first 6 months of life (P = .002, risk ratio = 11). Virus load was highly associated with imminent vulnerability to CDC-C or death (P = .002) during the first 18 months of life. Except for values from the first week of life, virus load at any age through 18 months is strongly associated with risk of HIV disease progression.

Survival outcomes with the use of surgery in limited-stage small cell lung cancer: should its role be re-evaluated?

Although chemotherapy and radiation therapy currently are recommended in limited‐stage small cell lung cancer (L‐SCLC), several small series have reported favorable survival outcomes in patients who underwent surgical resection. The authors of this report used a US population‐based database to determine survival outcomes of patients who underwent surgery.

Meta-analysis of the association of platelet glycoprotein IIIa PlA1/A2 polymorphism with myocardial infarction

This meta-analysis examined all the published reports up to October 1999 that studied the association between PlA2 polymorphism of platelet glycoprotein IIIa gene and myocardial infarction. The PlA2 polymorphism was not found to be associated with an increased risk of myocardial infarction, either overall or in selected subgroups, which were patients with premature disease onset (age < or = 60 years), first acute myocardial infarction, and patients who were men, women, and exclusively Caucasian.

Red cell distribution width (RDW) as a predictor of long-term mortality in patients undergoing percutaneous coronary intervention

Red cell distribution width (RDW) has been shown to be an independent predictor of mortality in patients with coronary artery disease and in patients with heart failure. The current study evaluated the prognostic utility of RDW in patients undergoing percutaneous coronary intervention (PCI). We evaluated 859 patients who underwent PCI during January 2003 to August 2005. After a median follow up of four (interquartile range 3.1 to 4.4) years, there were a total of 95 (11%) deaths. RDW was analysed as a categorical variable with empirically determined cut points of 13.3 and 15.7 (low RDW <13.3, medium RDW > or = 13.3 to <15.7, high RDW > or = 15.7) based on differences in hazard ratio (HR) for death among RDW deciles. In univariate analysis, higher RDW was a significant predictor of mortality (p < 0.001). In multivariate analysis there was a significant two-way interaction between RDW and haemoglobin (Hgb). RDW was not an independent predictor of mortality in patients with Hgb <10.4. However, among patients with Hgb >10.4, high RDW was a strong and independent predictor of mortality. For patients with Hgb > or = 10.4 to <12.7, HR for death in patients with high RDW relative to low RDW was 5.2 (95% confidence intervals [CI]: 2.0-13.3). For patients with Hgb > or = 12.7, HR for death in patients with high RDW relative to low RDW was 8.6 (CI:2.8-28.6). Higher RDW was a strong and independent predictor of long-term mortality in patients undergoing PCI who were not anaemic at baseline.

Aging cohort of perinatally human immunodeficiency virus-infected children in New York City

BACKGROUND New York City (NYC) pediatricians are now caring for fewer HIV-infected infants and more school age children and adolescents than earlier in the epidemic. METHODS Clinical, laboratory and demographic data were abstracted from medical records at 10 NYC centers participating in the CDC Pediatric Spectrum of HIV Disease project. Pediatric AIDS cases and HIV-related deaths reported to the NYC Department of Health were examined. RESULTS Median age of HIV-infected children in care increased from 3 years in 1989 to 1991 to 6 years in 1995 to 1998. The number of HIV-infected women giving birth in NYC declined 50% from 1990 to 1997 (1630 to 831); increasing numbers were identified prenatally (14% in 1989; 78% after 1995); and most received prenatal zidovudine prophylaxis (73% in 1997). Estimated perinatal transmission decreased to 10% by 1997. Improved identification of seropositive status in infants was associated with an increased proportion of infected infants receiving Pneumocystis carinii pneumonia (PCP) prophylaxis, 84% in 1997. AIDS free survival was longer for children born 1995 to 1998 than for those born before 1995, P = 0.004. In 1998 among children with advanced immunosuppression (CDC category 3), 66% were prescribed 3 or more antiretroviral medicines and 88% received PCP prophylaxis. Citywide AIDS cases and HIV-related deaths fell precipitously beginning in 1996. CONCLUSIONS Based on the observations of this study, the cohort of NYC HIV-infected children in care is aging, associated with a decline in new HIV infections, high rates of PCP prophylaxis and increased time to AIDS. Falling HIV-related deaths citywide support these observations.

Prospective study of bone mineral density changes in aging men with or at risk for HIV infection.

Objective:To investigate rates and predictors of change in bone mineral density (BMD) in a cohort of aging men with or at risk for HIV infection. Design:A prospective cohort study among 230 HIV-infected and 159 HIV-uninfected men aged at least 49 years. Methods:Longitudinal analyses of annual change in BMD at the femoral neck, total hip, and lumbar spine. Results:At baseline, 46% of men had normal BMD, 42% had osteopenia, and 12% had osteoporosis. Of those men with normal BMD, 14% progressed to osteopenia and 86% continued to have normal BMD. Of the men initially with osteopenia, 12% progressed to osteoporosis and 83% continued to have osteopenia. Osteopenia incidence per 100 person-years at risk was 2.6 for HIV-uninfected men and 7.2 for HIV-infected men; osteoporosis incidence was 2.2 per 100 person-years at risk among men with osteopenia, regardless of HIV status. In multivariable analysis of annual change in BMD at the femoral neck, we found a significant interaction between heroin use and AIDS diagnosis, such that the greatest bone loss occurred with both AIDS and heroin use (adjusted predicted mean annual bone loss 0.0196 g/cm2). Hepatitis C virus seropositivity was also associated with femoral neck bone loss (P = 0.04). The interaction between AIDS and heroin use also was associated with bone loss at the total hip, as was current methadone use (P < 0.01). Conclusion:We found an association of heroin use and AIDS with BMD change, suggesting that heroin users with AIDS may be at particular risk for bone loss.

Circulating vitamin D correlates with serum antimüllerian hormone levels in late-reproductive-aged women: Women's Interagency HIV Study

OBJECTIVE To study the correlation between circulating 25-hydroxyvitamin D (25OH-D) levels and serum antimüllerian hormone (AMH) in women enrolled in the Womens Interagency HIV Study. DESIGN Cross-sectional study. SETTING None. PATIENT(S) All premenopausal women (n = 388) with regular menstrual cycles were included and subdivided into three groups: group 1 with age <35 years (n = 128), group 2 with age 35-39 years (n = 119), and group 3 with age ≥40 years (n = 141). INTERVENTION(S) Serum for 25OH-D, AMH, fasting glucose and insulin, and creatinine levels. MAIN OUTCOME MEASURE(S) Correlation between 25OH-D and AMH before and after adjusting for HIV status, body mass index, race, smoking, illicit drug use, glucose and insulin levels, estimated glomerular filtration rate, and geographic site of participation. RESULT(S) After adjusting for all covariates, the regression slope in all participants for total 25OH-D predicting log(10)AMH for 25-year-olds (youngest participant) was -0.001 (SE = 0.008); and for 45-year-olds (oldest participant) the corresponding slope was +0.011 (SE = 0.005). Fasting insulin level was negatively correlated with serum AMH. The regression slope for the correlation between 25OH-D and AMH in group 1 was +0.002 (SE = 0.006); in group 2 was +0.006 (SE = 0.005); and in group 3 was +0.011 (SE = 0.005). There was no association between HIV and AMH. CONCLUSION(S) A novel relationship is reported between circulating 25OH-D and AMH in women aged ≥40 years, suggesting that 25OH-D deficiency might be associated with lower ovarian reserve in late-reproductive-aged women.

Human immunodeficiency virus-infected adolescents: a descriptive study of older children in New York City, Los Angeles County, Massachusetts and Washington, DC.

Background. Children infected with HIV are entering adolescence with challenging and changing medical and social needs. Through chart review we describe certain medical and social characteristics of adolescents who acquired HIV as children. Methods. HIV‐infected children 12 years of age and older in 1995 were monitored through the Pediatric Spectrum of HIV Disease study from four US sites. In addition to standard 6‐month medical chart reviews, a special chart abstraction in 1997 collected available psychosocial and sexual history information. Results. A total of 131 adolescents HIV‐infected as children were studied: 52 infected perinatally; 44 infected through a contaminated blood transfusion; 30 through receipt of contaminated blood products for hemophilia; and 5 with unknown transmission mode. Mean age at last medical contact was 15.5 years, 67% were Hispanic or African‐American, 12% were employed, 66% attended regular school, 66% knew their HIV status and 48% (8% for the perinatally infected) lived with their biologic mother. Information on sexual activity showed that 18% had sexual relations, 28% did not and for 53% sexual activity was not recorded in the medical chart. Four percent used illicit drugs, which along with sexual activity showed a positive association with age. Forty‐two percent had an AIDS‐defining opportunistic infection, and 56% had a recent CD4+ lymphocyte count <200 cells/&mgr;l. Conclusions. Adolescents in this study represent a heterogeneous group of surviving HIV‐infected children some of whom are sexually active and potential sources of HIV transmission. Clinicians who treat HIV‐infected and high risk adolescents face the challenges of providing care and prevention services appropriate to adolescent development.

Predictors of H1N1 vaccination in pregnancy

The purpose of this review was to determine factors that influence a pregnant womans acceptance of the H1N1 vaccine with the use of the Health Belief Model (HBM). A self-administered questionnaire based on the HBM was used in a cross-sectional study of postpartum women during the 2009 H1N1 epidemic. Overall, 212 postpartum women were approached and agreed to participate; of these women, 25.5% had received an H1N1 vaccination. Perceived barriers to vaccination (P = .001) and perceived severity of infection (P = .018) were independent predictors of vaccination. The total predictive utility of the full model that incorporated HBM dimensions, age, race, care provider, and education level was moderate (area under the curve, -0.86). The addressing of perceived barriers (such as fear of side-effects), an explanation of the safety of the vaccine for the fetus, and the stressing of complications that are associated with H1N1 infection in pregnancy may increase the rate of vaccination.