Developing a Workforce for Health in North Carolina: Planning for the Future.

Among the many trends influencing health and health care delivery over the next decade, three are particularly important: the transition to value-based care and increased focus on population health; the shift of care from acute to community-based settings; and addressing the vulnerability of rural health care systems in North Carolina.

High sensitivity of human leukocyte antigen-b*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients.

BACKGROUND: Although the human leukocyte antigen (HLA)-B*5701 is highly associated with a hypersensitivity reaction (HSR) to abacavir (ABC), variable sensitivities have been reported when clinical data alone have been used to define an ABC HSR. This study evaluated the sensitivity of detection of the HLA-B*5701 allele as a marker of ABC HSRs in both white and black patients, using skin patch testing to supplement clinical diagnosis. METHODS: White and black patients, identified through chart review, were classified as having received a diagnosis of an ABC HSR based on clinical findings only (a clinically suspected ABC HSR) or based on clinical findings and a positive skin patch test result (an immunologically confirmed [IC] ABC HSR). Control subjects were racially matched subjects who tolerated ABC for >/=12 weeks without experiencing an ABC HSR. Patients and control subjects were tested for the presence of HLA-B*5701. Sensitivity, specificity, and odds ratios for the detection of HLA-B*5701 as a marker for an ABC HSR were calculated for white and black participants. RESULTS: Forty-two (32.3%) of 130 white patients and 5 (7.2%) of 69 black patients who met the criteria for clinically suspected HSRs had IC HSRs. All 42 white patients with IC HSRs were HLA-B*5701 positive (sensitivity, 100%; odds ratio, 1945; 95% confidence interval, 110-34,352). Among all white patients with clinically suspected HSRs, sensitivity was 44% (57 of 130 patients tested positive for HLA-B*5701); specificity among white control subjects was 96%. Five of 5 black patients with IC HSRs were HLA-B*5701 positive (sensitivity, 100%; odds ratio, 900; 95% confidence interval, 38-21,045). Among black patients with clinically suspected HSRs, the sensitivity was 14% (10 of 69 tested positive for HLA-B*5701); specificity among black control subjects was 99%. CONCLUSIONS: Although IC ABC HSRs are uncommon in black persons, the 100% sensitivity of HLA-B*5701 as a marker for IC ABC HSRs in both US white and black patients suggests similar implications of the association between HLA-B*5701 positivity and risk of ABC HSRs in both races.

Short-term safety and tolerability of a once-daily fixed-dose abacavir-lamivudine combination versus twice-daily dosing of abacavir and lamivudine as separate components: findings from the ALOHA study.

STUDY OBJECTIVE: To evaluate the short-term (12 wks) safety and tolerability of a once-daily, fixed-dose abacavir-lamivudine combination versus twice-daily dosing of the separate components, both with background antiretroviral therapy. DESIGN: Phase IIIB, randomized, open-label, parallel-group, multicenter study. SETTING: One hundred forty-six human immunodeficiency virus (HIV) clinics. PATIENTS: Six hundred eighty antiretroviral therapy-naïve patients with HIV type 1 RNA greater than 1000 copies/ml at baseline. INTERVENTION: Patients were randomly assigned in a 2:1 manner to receive either abacavir 600 mg-lamivudine 300 mg once/day or abacavir 300 mg twice/day and lamivudine 150 mg twice/day. Subjects were stratified based on choice of third or fourth antiretroviral drug (nucleoside reverse transcriptase inhibitor [NRTI], NNRTI, or protease inhibitor), assigned before randomization. MEASUREMENTS AND MAIN RESULTS: The primary end point was occurrence of grades 2-4 adverse events and serious adverse events; abacavir hypersensitivity reactions were considered serious adverse events. Baseline characteristics were similar between the once-daily (455 patients) and twice-daily (225 patients) groups. The rates of all grades 2-4 adverse events were similar: once-daily 33% (150 patients), twice-daily 31% (69). A slightly larger proportion of patients in the twice-daily group experienced drug-related grades 2-4 adverse events: once-daily 10% (47), twice-daily 16% (36). Rates of all serious adverse events (once-daily 11% [49], twice-daily 10% [22]) and drug-related serious adverse events (once-daily 5% [21], twice-daily 8% [17]) were similar. The rate of suspected abacavir hypersensitivity reaction was 5.3% (once-daily 4.4% [20], twice-daily 7.1% [16]), with a higher rate for the NNRTI stratum of the twice-daily group (8.6% [10]) than in any other stratum (once-daily, NNRTI 4.3% [10]; twice-daily, protease inhibitor 5.6% [6]; once-daily, protease inhibitor 4.6% [10]). CONCLUSION: In the short-term, the rates of adverse events in the once-daily and twice-daily groups appeared to be similar. The rate of suspected abacavir hypersensitivity reaction in the once-daily group was lower than the rate in the twice-daily group.

HIV-associated thrombotic microangiopathy in the era of highly active antiretroviral therapy: an observational study.

The prevalence and predisposing factors of thrombotic microangiopathy (TMA) in the era of highly active antiretroviral therapy (HAART) were evaluated among patients in the Collaborations in Human Immunodeficiency Virus (HIV) Outcomes Research/US cohort. Of 6022 patients, 17 (0.3%) had TMA, with unadjusted incidences per 100 person-years of 0.079 for TMA, 0.009 for thrombotic thrombocytopenic purpura, and 0.069 for hemolytic-uremic syndrome. Compared with patients without TMA, patients with TMA had lower mean CD4(+) cell counts (197 vs. 439 cells/mm(3); P=.0009) and higher mean log(10) HIV-1 RNA levels (4.6 vs. 3.3 copies/mL; P=.0001) at last follow-up and a significantly greater incidence of acquired immune deficiency syndrome (82.4% vs. 55.3%; P=.025), Mycobacterium avium complex infection (17.6% vs. 3.3%; P=.018), hepatitis C (29.4% vs. 11.3%; P=.001), and death (41.2% vs. 7.4%; P<.0001). The prevalence of herpes and use of antiherpetics were slightly higher for patients with TMA, but unadjusted distributions were not statistically significant. TMA in a cohort surveyed after the introduction of HAART was rare and was associated with advanced HIV disease.

Bacterial vaginosis, vaginal fluid neutrophil defensins, and preterm birth.

OBJECTIVE: To examine the association between bacterial vaginosis, vaginal fluid neutrophil defensins, and preterm birth. METHODS: Vaginal fluid specimens were obtained at 24-29 weeks' gestation from 242 cases with preterm birth and 507 noncases sampled using a case-cohort study design. We tested for bacterial vaginosis by Gram staining and Nugent scores and assayed for neutrophil defensins by enzyme-linked immunosorbent assay. Bacterial vaginosis was studied as a categoric variable (negative, intermediate, and positive), whereas defensins were studied as a continuous, categoric (based on percentiles), and dichotomous measure (presence versus absence). Three gestational age cut points were used to define preterm birth. Modified Cox proportional hazard models were used to evaluate the associations between bacterial vaginosis, defensins, and degree (less than 32, less than 34, and less than 37 weeks) and type (premature rupture of membranes, preterm labor) of preterm birth. RESULTS: Elevated vaginal fluid neutrophil defensins were not associated with birth before 37 weeks. Compared with women who did not have measurable vaginal fluid defensins, women with higher defensin levels (0-2.8 micro g/mL, 2.8-8.2 micro g/mL, and greater than 8.2 micro g/mL) had a greater risk of delivering before 32 weeks. Hazard ratios adjusted for maternal race and vaginal bleeding during pregnancy and 95% confidence intervals for these defensin levels were 1.7 (0.4, 6.9), 2.4 (0.7, 7.9), and 3.1 (1.0, 9.8), respectively. Bacterial vaginosis status did not influence the association between defensins and preterm birth. CONCLUSION: Elevated concentrations of vaginal fluid neutrophil defensins at 24-29 weeks' gestation might predict preterm birth before 32 weeks.

Gastroschisis: the effect of labor and ruptured membranes on neonatal outcome.

OBJECTIVES: The purpose of this study was to examine the relationship between labor and ruptured membranes on the neonatal outcome of infants with gastroschisis. STUDY DESIGN: We reviewed the outcomes of 60 neonates who were prenatally diagnosed with gastroschisis and who were delivered at the University of North Carolina Hospitals between June 1989 and April 1999. RESULTS: The mean gestational age at delivery was 36 weeks. Four infants (7%) died in the neonatal period, and 19 infants (32%) had a major morbidity. No significant differences appeared in any of the neonatal outcomes when they were stratified by the presence or absence of labor and presence or absence of ruptured membranes. After being controlled for confounding variables, the risk of neonatal death or major neonatal morbidity because of exposure to either labor or ruptured membranes was no different than the risks caused by no labor or intact membranes, respectively. CONCLUSION: Labor and ruptured membranes do not appear to be associated with increased neonatal morbidity or mortality rates in neonates with gastroschisis.

Bacterial vaginosis and vaginal fluid defensins during pregnancy.

OBJECTIVE: The purpose of this study was to examine the association between Gram stain findings of vaginal fluid and the concentration of vaginal fluid neutrophil defensins. STUDY DESIGN: Vaginal fluid specimens obtained from 749 women at 24 to 29 weeks of gestation were tested for bacterial vaginosis and assayed for neutrophil defensins. Bacterial vaginosis was studied as a categoric variable (negative, intermediate, and positive), whereas defensins were examined as a continuous measure and dichotomized on the basis of presence versus absence and at the 90th percentile. Multiple linear and logistic regression models were used to assess the relationship between bacterial vaginosis and defensins. RESULTS: Women with intermediate bacterial vaginosis were more likely to have elevated vaginal fluid neutrophil defensins (>90th percentile) than women with normal vaginal flora (adjusted odds ratio, 2.3; 95% CI, 1.3, 4.2), whereas women with frank bacterial vaginosis were not (adjusted odds ratio, 1.3; 95% CI, 0.7, 2.6). Among women with any detectable defensin (69.5% of the study population), intermediate bacterial vaginosis was associated positively with defensin concentrations in multiple linear regression models (P =.007). Women with intermediate and frank bacterial vaginosis had 5.9 microg/mL and 2.2 microg/mL higher defensin concentrations, respectively, than women who did not have bacterial vaginosis. The presence of leukocytes in vaginal fluids was associated positively with defensin concentrations (P <.0001). CONCLUSION: Changes in vaginal microflora during mid pregnancy are associated with an increased concentration of vaginal fluid neutrophil defensins.

Paternal leukocyte alloimmunization as a treatment for hemolytic disease of the newborn in a rabbit model.

OBJECTIVE: The purpose of this study was to evaluate maternal alloimmunization to paternal leukocytes as a treatment for hemolytic disease of the fetus/newborn in a rabbit model. STUDY DESIGN: Twelve does and paired red blood cell-incompatible bucks underwent the experimental protocol. Fetal hematologic parameters that were obtained by ultrasound-guided intracardiac sampling were compared from unaffected, compatible litters; from affected, incompatible litters (after alloimmunization to red blood cell antigens); and from affected, incompatible litters after alloimmunization to paternal leukocytes. Generalized estimation equations were used for statistical analysis. A probability value of <.05 was considered significant. RESULTS: Six of 12 does had at least one affected litter after alloimmunization to paternal leukocytes. After an adjustment for the mating cycle, the fetuses of does that underwent white blood cell immunization exhibited higher hemoglobin and hematocrit levels (beta = 4.6, P <.001, and beta = 11.6, P =.006, respectively) compared with the fetuses of does that were immunized only to red blood cells. CONCLUSION: Maternal alloimmunization to paternal leukocytes decreases the severity of hemolytic disease and may play a role in the treatment of severe hemolytic disease of the newborn in humans.