Neonatal outcomes based on mode and intensity of delivery room resuscitation.

OBJECTIVE: To examine outcomes of neonates based on the mode and intensity of resuscitation received in the delivery room (DR). STUDY DESIGN: A retrospective study of 439 infants with birth weight ⩽1500 g receiving DR resuscitation at two hospital centers in Philadelphia, Pennsylvania. RESULTS: Of 439 infants, 22 (5%) received routine care, 188 (43%) received noninvasive positive pressure ventilation (PPV) and 229 (52%) received endotracheal tube (ETT) intubation in the DR. Adjusted odds for respiratory distress syndrome was associated with lower rates in infants requiring lower intensity of DR resuscitation (P<0.001). Noninvasive PPV vs ETT was associated with decreased odds of developing intraventricular hemorrhage and retinopathy of prematurity (P<0.05). Routine vs noninvasive PPV or ETT had decreased odds of developing bronchopulmonary dysplasia (P<0.05). CONCLUSION: Decreased intensity of DR resuscitation was associated with a decreased risk of specific morbidities.

Density of day cares in relation to reported pertussis incidence in Philadelphia.

OBJECTIVES: Reported pertussis incidence has increased markedly in recent years. In addition to the documented increase in under-immunization and waning immunity, the increase may be related to the more frequent use of child care services by parents over the last few decades. Additionally, clustering of outbreaks may be related to neighborhood characteristics not previously identified. STUDY DESIGN: We conducted a citywide case-control study of children in Philadelphia aged birth through six years, between 2001 and 2013. Cases were reported as probable pertussis diagnoses to the Health Department. Controls were sampled from the city's immunization information system and matched to the cases by date of birth. METHODS: Multilevel logistic regression was used to isolate the independent contributions of individual and neighborhood risk factors and the corresponding relative odds of pertussis. The density of day cares in each neighborhood served as the main exposure and reported incident cases of confirmed and probable pertussis was the main outcome. RESULTS: Between 2001 and 2013, 410 cases of confirmed and probable pertussis were included with four controls matched per case yielding a final sample of 2050 children from 45 Philadelphia neighborhoods. There was a 30% increase in the risk of pertussis based solely on the neighborhood where the children resided (median odds ratio 1.3, 95% credible interval 1.1, 1.6). The density of day cares in each neighborhood was unrelated to the distribution of pertussis cases. CONCLUSIONS: Pertussis clustering was observed at the neighborhood level in Philadelphia, but was unrelated to the neighborhood's day care density. From a Health Department perspective, the highest risk neighborhoods should be targeted for vaccine campaigns and further research to identify the etiologic risk factors.

Experiences of racial discrimination and relation to sexual risk for HIV among a sample of urban black and African American men.

This study aimed to examine racial discrimination and relation to sexual risk for HIV among a sample of urban black and African American men. Participants of this cross-sectional study were black and African American men (N = 703) between the ages of 18 and 65 years, recruited from four urban clinical sites in the northeast. Multivariate logistic regression models were used to analyze the relation of reported racial discrimination to the following: (1) sex trade involvement, (2) recent unprotected sex, and (3) reporting a number of sex partners in the past 12 months greater than the sample average. The majority of the sample (96%) reported racial discrimination. In adjusted analyses, men reporting high levels of discrimination were significantly more likely to report recent sex trade involvement (buying and/or selling) (adjusted odds ratio (AOR) range = 1.7-2.3), having recent unprotected vaginal sex with a female partner (AOR = 1.4, 95% confidence interval (CI), 1.1-2.0), and reporting more than four sex partners in the past year (AOR = 1.4, 95% CI, 1.1-1.9). Findings highlight the link between experiences of racial discrimination and men's sexual risk for HIV.

Experiences of racial discrimination & relation to violence perpetration and gang involvement among a sample of urban African American men.

OBJECTIVE: To examine racial discrimination and its relation to violence involvement among a sample of urban African American men. METHODS: Participants of this cross-sectional study were African American men (N = 703) between the ages of 18 and 65 years, recruited from four urban community health centers and two hospital-based clinics within an urban center in the Northeast. Multivariate logistic regression models were used to assess the relation of reported racial discrimination to recent perpetration of intimate partner violence (IPV), street violence involvement, and gang involvement. Racial discrimination was measured via 7 items assessing everyday and lifetime experiences of racial discrimination. RESULTS: In logistic regression models adjusted for age and homelessness, men reporting high levels of discrimination (scores above the sample median) were significantly more likely to report IPV perpetration (Adjusted Odds Ratio (AOR) = 1.9; 95% Confidence Interval (CI): 1.2-2.9) and street violence involvement (AOR = 1.5; 95% CI: 1.1-2.2) as compared to men reporting lower levels of discrimination. No relation was found between experiencing discrimination and gang involvement. CONCLUSIONS: Findings showcase the potential relevance of racial discrimination to efforts focused on reducing racial disparities related to violence.

The effect of homeopathically prepared thyroxine on highland frogs: influence of electromagnetic fields.

BACKGROUND: Previous experiments show that amphibian larvae are responsive to homeopathically prepared thyroxine. METHODS: We studied the effect of a highly diluted and agitated thyroxine solution exposed to various electromagnetic fields on metamorphosis in highland Rana temporaria. The devices tested were: microwave oven, mobile phone, airport X-ray, and a red light barcode scanner. Animals were treated either with homeopathically prepared thyroxine (10(-30) parts by weight, 10(-35) in the water in which the animals were kept), or analogously prepared blank solution, or analogously prepared thyroxine exposed to the electromagnetic field of one of the devices tested. Solutions were administered at 48h intervals according to a standardized protocol. RESULTS: Animals treated with the standard test solution thyroxine 10(-30) metamorphosed more slowly than the control animals, ie the effect of the homeopathically prepared thyroxine was opposed to the usual physiological effect of molecular thyroxine. The cumulative number of test animals that had reached the four-legged stage at defined points in time was smaller in the group treated with homeopathically prepared thyroxine at most of the points in time. This was found independently by all three research teams involved. In contrast, this effect did not occur when the thyroxine solution had been exposed to the field of the early model microwave oven, or mobile phone. There was no difference between aqueous or alcoholic solutions were used, and there was, if any, only a small protective effect from aluminum foil. Airport X-ray and red light barcode scanning did not diminish the effect of the homeopathic solution.

Beyond assumptions of negligible risk: sexually transmitted diseases and women who have sex with women.

OBJECTIVES: This study evaluated the association of female-female sexual behavior with sexually transmitted diseases (STDs). METHODS: Female participants (n = 286) were recruited from the Twin Cities Gay/Lesbian/Bisexual/Transgender Pride Festival. Logistic regression was used to examine the association between female-female sexual behavior and STDs. RESULTS: Women in all partner history groups, including 13% of women with only female partners, reported a history of STD. Increased sexual exposures with women predicted an increase in the likelihood of STDs after known risk factors had been controlled. Neither number of female partners nor number of exposures was associated with obtaining regular STD testing. CONCLUSIONS: The risk of STDs through female-female sexual exposure is not negligible. Nevertheless, patterns of STD testing do not reflect this risk.

The Minnesota DARE PLUS Project: creating community partnerships to prevent drug use and violence.

The research community has criticized Drug Abuse Resistance Education (D.A.R.E.) because the extant literature indicates a lack of evidence that the elementary school program prevents drug use. Yet D.A.R.E. continues to be the most widely implemented drug use prevention program in the United States and has considerable community support. To date, the junior high D.A.R.E. program has not been evaluated. The Minnesota DARE PLUS Project is a randomized trial of 24 schools and communities. During 1999-2001, students in eight schools will receive the junior high D.A.R.E. curriculum in 7th grade; eight schools also will receive the curriculum as well as additional parent involvement, peer leadership, and community components in the 7th and 8th grades; and eight schools will serve as controls. This article describes the background and conceptualization, the curriculum and additional intervention components, and the evaluation methods of the DARE PLUS Project.

HIV-1 genotypic zidovudine drug resistance and the risk of maternal--infant transmission in the women and infants transmission study. The Women and Infants Transmission Study Group.

OBJECTIVES: Although the treatment of pregnant women and their infants with zidovudine (ZDV) has been remarkably effective in preventing the perinatal transmission of human HIV-1, many potentially preventable infections still occur. To examine whether the risk of perinatal infection is increased among women who carry ZDV-resistant HIV-1, the role of genotypic ZDV resistance in perinatal transmission was evaluated. METHODS: The reverse transcriptase (RT) region of clinical isolates from culture supernatants of 142 HIV-1-infected women enrolled in the Women and Infants Transmission Study (WITS), who had been treated with ZDV during pregnancy was sequenced. Results from genotypic sequencing were linked to demographic, laboratory, and obstetrical databases, and the magnitude of association of having consensus drug-resistant HIV-1 RT mutations with transmission was estimated. RESULTS: Twenty-five per cent (34/142) of maternal isolates had at least one ZDV-associated resistance mutation. A lower CD4 cell percentage and count (P= 0.0001) and higher plasma HIV-1 RNA (P=0.006) were associated with having any ZDV resistance mutation at delivery. Having any RT resistance mutation [odds ratio (OR): 5.16; 95% confidence interval (CI): 1.40, 18.97; P=0 0.01], duration of ruptured membranes [OR: 1.13 (1.02, 1.26) per 4 h duration; P= 0.02], and total lymphocyte count [OR: 1.06 (1.01, 1.10) per 50 cells higher level; P=0.009] were independently associated with transmission in multivariate analysis. CONCLUSION: Maternal ZDV resistant virus was predictive of transmission, independent of viral load, in these mothers with moderately advanced HIV-1 disease, many of whom had been treated with ZDV before pregnancy.

Quantitative proviral DNA and antibody levels in the natural history of HTLV-I infection.

The pathogenesis of human T-cell lymphotropic virus type I (HTLV-I) in adult T-cell leukemia/lymphoma (ATL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is poorly understood. We prospectively followed up and evaluated the virologic correlates of infection in transfusion recipients after seroconversion, in asymptomatic carriers, and in ATL and HAM/TSP patients. Proviral DNA levels (copies/105 lymphocytes) were determined by real-time automated polymerase chain reaction and antibody titers by end-point dilution by use of an HTLV-I enzyme-linked immunoassay. In early infection, proviral load was initially elevated (median, 212 copies/105 lymphocytes at time 1) and later decreased (median, 99 copies at time 2, and 27 copies at time 3). Corresponding antibody titers were low at time 1 (1:2154), had significantly increased by time 2 (1:12312), and were stable by time 3 (1:4694). These viral markers were significantly lower in asymptomatic carriers than in HAM/TSP or ATL patients. Therefore, proviral load and antibody titers may be useful as predictive markers of disease among carriers.

A study of adult T-cell leukemia/lymphoma incidence in central Brooklyn.

Adult T-cell leukemia/lymphoma (ATL), a rare outcome of infection with human T-lymphotropic virus (HTLV-I), is endemic in central Brooklyn, which has a large Caribbean migrant population. Previous studies have suggested that HTLV-I prevalence in central Brooklyn may be similar to that recorded in the Caribbean islands. We established a pilot 1-year surveillance program to identify cases of ATL in 7 of 10 hospitals serving the residents of 18 zip codes of central Brooklyn with a combined population of 1,184,670. Of the 6,198 in-patient beds in the catchment area, approximately 83% were covered. Twelve incident cases of ATL were ascertained, all among persons of Afro-Caribbean descent, indicating an annual incidence in African-Americans in this community of approximately 3.2/100,000 person-years. Unexplained hypercalcemia was the most useful screening method, identifying 3 of 5 patients not referred for possible ATL by a local hematologist. The female:male ratio was 3:1. The age pattern was different from that reported in the Caribbean Basin and closer to the pattern seen in Japan. Our study supports evidence that HTLV-I infection and ATL are endemic in central Brooklyn and suggests that a more intensive surveillance program for this disease coupled with intervention efforts to reduce HTLV-I transmission are warranted.

Selective vertical transmission of HIV-1 antiretroviral resistance mutations.

OBJECTIVE: To examine the patterns of vertical transmission of zidovudine (ZDV) resistance mutations. DESIGN: HIV-1 reverse transcriptase codons 10-250 were sequenced from 24 pairs of ZDV-exposed women and their HIV-infected infants as part of the Women and Infants Transmission Study. METHODS: Viral RNA was extracted from tissue culture supernatants and sequenced using fluorescent dye-primer chemistry and an automated sequencer. RESULTS: For 17 of these pairs, maternal and infant sequences were identical to one another and lacking known ZDV resistance mutations. The remaining seven maternal sequences contained known mutations associated with ZDV resistance at reverse transcriptase codons 70, 210, 215 and 219. In each case where the maternal HIV isolate showed a pure mutant species, the infant sequence was identical. When the maternal sequence showed the presence of a sequence mixture at codon 70 or 219, the infant's virus showed only wild-type sequence even when the ZDV-resistant mutant was quantitatively dominant in the mother. The single maternal HIV isolate showing mixed sequence at codon positions 210 and 215 transmitted an unmixed mutant to the infant at both positions. When maternal mixtures were present at sites not associated with ZDV resistance, only the dominant species appeared in the infant. CONCLUSIONS: When maternal HIV isolates contained mixed wild-type and ZDV-resistant subpopulations, only a single component of the mixture could be detected in the infected infants. Resistance mutants without the codon 215 mutation were not transmitted from mixtures, even when the mutants formed the majority of circulating maternal virus. In perinatal HIV transmission, specific ZDV-resistant HIV genotypes circulating in the maternal virus pool may influence whether infection in the infant will be established by a wild-type or ZDV-resistant HIV strain.

The inter-relation of maternal immune competence, HIV-1 viral load, and nutritional status in preventing vertical transmission: an alternative to chemoprophylaxis?

As the human immunodeficiency virus (HIV) global pandemic moves towards the end of its second decade, women of reproductive age throughout the world have been shown to be increasingly at risk for acquiring HIV-1 infection. Recently, the focus for preventive measures has expanded to include preventing the perinatal transmission of HIV-1 to fetuses and newborns. This manuscript reviews the available literature that examines risk factors for perinatal transmission, immunopathogenesis of HIV-1 infection, and the role that antioxidant micronutrients play in modulating immune response to HIV-1 disease progression. The available information provides a compelling case for the design of studies that evaluate the extent to which maternal HIV-1 viremia and disease progression are modulated by her nutritional status. Should results from these studies confirm that antioxidant micronutrient status is inversely related to HIV-1 RNA load, particularly in economically vulnerable populations, carefully designed and executed supplementation trials would be warranted.

Statistical issues for HIV surrogate endpoints: point/counterpoint. An NIAID workshop.

This paper summarizes the proceedings of an NIAID-sponsored workshop on statistical issues for HIV surrogate endpoints. The workshop brought together statisticians and clinicians in an attempt to shed light on some unresolved issues in the use of HIV laboratory markers (such as HIV RNA and CD4+ cell counts) in the design and analysis of clinical studies and in patient management. Utilizing a debate format, the workshop explored a series of specific questions dealing with the relationship between markers and clinical endpoints, and the choice of endpoints and methods of analysis in clinical studies. This paper provides the position statements from the two debaters on each issue. Consensus conclusions, based on the presentations and discussion, are outlined. While not providing final answers, we hope that these discussions have helped clarify a number of issues, and will stimulate further consideration of some of the highlighted problems. These issues will be critical in the proper assessment and use of future therapies for HIV disease.

Undiagnosed adult T-cell leukemia/lymphoma in central Brooklyn, NY.

We present a case, identified by surveillance for adult T-cell leukemia/lymphoma (ATL), who had initial symptoms not specifically related to ATL, and who would not have been identified as having ATL otherwise. A 51-year-old Trinidadian black woman was hospitalized for abdominal pain, nausea, and vomiting. Hematology and clinical chemistry revealed leukocytosis (19,600/mm3), an elevated lymphocyte percent (63%), and hypercalcemia (19.4 mg/dl). The patient was serologically confirmed with HTLV-I-associated ATL. Lymphoma was diagnosed at autopsy. This case is representative of ATL, which along with HTLV-I infection, may be emerging public health problems in urban communities of the northeast and southeast United States.

Association between serum total cholesterol and HIV infection in a high-risk cohort of young men.

Low serum total cholesterol (TC) is associated with a variety of nonatherosclerotic diseases, but the association of TC with infectious disease has been little studied. In this study, we examined the relationship between serum TC and HIV infection in members of a large health maintenance organization in Northern California. The cohort consisted of 2446 unmarried young men 15 to 49 years of age at high risk of HIV infection, defined as self-reported history of sexually transmitted disease or liver disease. Baseline measurements were taken between 1979 and 1985, and subjects were passively followed for HIV infection until the end of 1993 (average length of follow-up, 7.7 years). From a multivariate-adjusted Cox regression, the rate ratio (RR) of HIV infection was 1.66 (95% CI = 1.07, 2.56) for men with serum TC levels <160 mg/dl compared with those with TC levels between 160 and 199 mg/dl. Similar excess risk of AIDS and AIDS-related death was observed. These findings suggest that low serum TC levels should be considered a marker of increased risk of HIV infection in men already at heightened risk of HIV infection.

Association of plasma human immunodeficiency virus type 1 RNA level with risk of clinical progression in patients with advanced infection. AIDS Clinical Trials Group (ACTG) 116B/117 Study Team. ACTG Virology Committee Resistance and HIV-1 RNA Working Groups.

Human immunodeficiency virus (HIV)-1 RNA level in plasma was evaluated as a surrogate marker for disease progression in a clinical trial of advanced HIV-1 infection. Baseline HIV-1 RNA level was an independent predictor of disease progression (relative hazard [RH] for each doubling of HIV-1 RNA level, 1.26; 95% confidence interval [CI], 1.03-1.54; P = .02), after adjusting for the week 4 change in HIV-1 RNA level, baseline CD4 cell count, syncytium-inducing phenotype, clinical status at study entry, and therapy randomization. A 50% reduction in HIV-1 RNA level was associated with a 27% decrease in the adjusted risk of disease progression during the study (RH, 0.73; 95% CI, 0.52-1.02; P = .07). The partial validation of HIV-1 RNA as a predictor for clinical end points has implications for the use of HIV-1 RNA in clinical trials and practice.

Prognostic value of plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in patients with advanced HIV-1 disease and with little or no prior zidovudine therapy. AIDS Clinical Trials Group Protocol 116A/116B/117 Team.

The association of plasma human immunodeficiency virus type 1 (HIV-1) RNA level at study entry and over time with clinical progression was evaluated in 187 patients from AIDS Clinical Trials Group protocol 116A who had little or no prior zidovudine treatment. Three-fold-higher HIV-1 RNA levels at study entry and 3-fold increases by week 8 were associated with progression (relative hazard [RH], 1.67; 95% confidence limits [CL], 1.20, 2.32; and RH, 1.45; CL, 1.02, 2.05, respectively). Having 3-fold-higher CD4 cell count at entry was independently associated with a 52% reduction in risk for progression (adjusted RH, 0.48; CL, 0.33, 0.70). When stratified by length of prior zidovudine therapy, RNA level was predictive in drug-naive patients (adjusted RH, 1.87; CL, 1.23, 2.85) but not predictive in patients with up to 16 weeks of prior therapy (adjusted RH, 1.11; CL, 0.70, 1.76). Analysis suggests that the acquisition of mutations at HIV-1 reverse transcriptase codons 215 and 74 is associated with subsequent increases in HIV-1 RNA level (relative risk, 7.00; CL, 0.86, 56.90).

Prevalence and clinical significance of zidovudine resistance mutations in human immunodeficiency virus isolated from patients after long-term zidovudine treatment. AIDS Clinical Trials Group 116B/117 Study Team and the Virology Committee Resistance Working Group.

Zidovudine resistance mutations at reverse transcriptase codons 215 or 41 were found in two-thirds of human immunodeficiency virus type 1 (HIV-1) isolates obtained at baseline from patients enrolled in an AIDS Clinical Trials Group (ACTG) protocol that compared didanosine with continued zidovudine in patients with > or = 16 weeks of previous zidovudine therapy (ACTG 116B/117). The combined presence of mutations at both codons 215 and 41 conferred an increased risk for progression (relative hazard, 1.82; 95% confidence interval [CI], 1.02-3.26) and an increased risk for death (RH, 5.42; 95% CI, 1.92-15.30) in analyses that controlled for other factors predictive of progression. However, the benefit of switching to didanosine compared with continued zidovudine therapy was independent of the presence of these mutations. Although this information is not helpful in determining when to alter therapy, detection of zidovudine resistance mutations provides prognostic information in patients with advanced HIV disease.