The Opioid Analgesic Reduction Study (OARS) Pilot: A Double-Blind Randomized Multicenter Trial.

BACKGROUND: With addiction rates and opioid deaths increasing, health care providers are obligated to help stem the opioid crisis. As limited studies examine the comparative effectiveness of fixed-dose combination nonopioid analgesia to opioid-containing analgesia, a comparative effectiveness study was planned and refined by conducting a pilot study. METHODS: The Opioid Analgesic Reduction Study (OARS) pilot, a stratified, randomized, multisite, double-blind clinical trial, was designed to test technology and procedures to be used in the full OARS trial. Participants engaged in the full protocol, enabling the collection of OARS outcome data. Eligible participants reporting to 1 of 5 sites for partial or full bony impacted mandibular third molar extraction were stratified by biologic sex and randomized to 1 of 2 treatment groups, OPIOID or NONOPIOID. OPIOID participants were provided 20 doses of hydrocodone 5 mg/acetaminophen 300 mg. NONOPIOID participants were provided 20 doses of ibuprofen 400 mg/acetaminophen 500 mg. OARS outcomes data, including pain experience, adverse effects, sleep quality, pain interference, overall satisfaction, and remaining opioid tablets available for diversion, were collected via surveys, electronic medication bottles, eDiary, and activity/sleep monitor. RESULTS: Fifty-three participants were randomized with 50 completing the OARS pilot protocol. Across all outcome pain domains, in all but 1 time period, NONOPIOID was better in managing pain than OPIOID (P < 0.05 level). Other outcomes suggest less pain interference, less adverse events, better sleep quality, better overall satisfaction, and fewer opioid-containing tablets available for diversion. DISCUSSION: Results suggest patients requiring impacted mandibular third molar extraction would benefit from fixed-dose combination nonopioid analgesia. KNOWLEDGE TRANSFER STATEMENT: Study results suggest fixed-dose nonopioid combination ibuprofen 400 mg/acetaminophen 500 mg is superior to opioid-containing analgesic (hydrocodone 5 mg/acetaminophen 500 mg). This knowledge should inform surgeons and patients in the selection of postsurgical analgesia.

Prevalence of HIV-1 and oral lesions in pregnant women in rural Malawi.

OBJECTIVE: Whether oral lesions were associated with human immunodeficiency virus-type 1 (HIV-1) status in a cohort of pregnant Malawian women was studied. STUDY DESIGN: Six hundred thirty-eight women participated in a randomized prospective study at 3 prenatal clinics in a rural area of southern Malawi. Oral examinations, followed by collection of oral fluid specimens with an HIV-1 oral specimen collection device, were performed. The specimens were tested for antibodies against HIV-1. RESULTS: Sixty-one oral lesions were found in 60 participants. While traditional HIV-1 associated lesions were rare, benign migratory glossitis was unexpectedly common (6%). Oral hairy leukoplakia was significantly more common among women who were HIV-1 positive than among women who were HIV-1 negative. An HIV-1 prevalence rate of 21.8% was estimated among the women, with the highest rate of HIV-1 infection (34.1%) among women aged 25 to 29 years. CONCLUSION: Stratifying lesions showed a small number of oral hairy leukoplakia to be markers for HIV-1. A high seroprevalence was found in this rural cohort, but there were unexpectedly few oral lesions. The relatively few oral lesions diagnosed may indicate a recent infection with HIV.

Incubation period of HIV-1 in perinatally infected children. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVES: To estimate the distribution of the incubation period of HIV-1 among perinatally infected children and to test the hypothesis that this distribution has been changing over time. DESIGN: An analysis of 190 perinatally HIV-1-infected children born between 1986 and 1997 in eight medical centers in New York City to women enrolled in a prospective cohort study. METHODS: Non-parametric Kaplan-Meier method and parametric survival analysis. RESULTS: Using the Kaplan-Meier method it was estimated that among perinatally HIV-1-infected children, 48% [95% confidence interval (CI), 41-56] developed AIDS by 3 years of age after which the rate was less than 3% per year. Using a parametric survival analysis for extrapolation, it was predicted that 33% (95% CI, 23-43) would remain AIDS-free at 13 years of age. Median age at onset of AIDS was estimated to be 4.1 years (95% CI, 1.9-6.4) by parametric survival analysis. The year of birth was significantly associated with AIDS-free survival, suggesting an increase in the time to AIDS over the years. This association remained significant (P=0.03) after adjustment for those maternal characteristics that have also changed over time: timing of enrollment (prepartum versus postpartum), zidovudine, alcohol, and hard drug (heroin, cocaine or methadone) use during pregnancy. CONCLUSIONS: Although a substantial proportion of perinatally HIV-1-infected children develop AIDS very early in life, a significant and increasing percentage of them are expected to survive into adolescence without developing AIDS. Further research is needed to determine the factors associated with the lengthening survival to AIDS.

Learning disability, school achievement, and grade retention among children with cleft: a two-center study.

OBJECTIVE: This study examined the prevalence of learning disability (LD), level of school achievement; and prevalence of grade retention by type of cleft and gender at two craniofacial centers. SETTING: The setting included two university-based craniofacial centers. DESIGN/PATIENTS: Participants included 84 consecutively evaluated patients from one center who were matched by cleft type, age, and gender with 84 patients evaluated at the second center. OUTCOMES: The outcomes included learning disability, school achievement, and grade retention. RESULTS: The results revealed that 46% of subjects with cleft had LD, 47% had deficient educational progress, and 27% had repeated a grade (excluding kindergarten) in school. Males with cleft palate only (CPO) had a significantly higher rate of LD than any other subject group. Males with CPO and females with cleft lip and palate (CLP) were more likely to repeat a grade in school than were females with CPO and males with CLP. CONCLUSIONS: Children with cleft are at risk for learning disability, low school achievement, and grade retention.

Timing of maternal-infant HIV transmission: associations between intrapartum factors and early polymerase chain reaction results. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To investigate the hypothesis that labour and delivery events, perinatal characteristics, and maternal factors are only associated with intrapartum HIV transmission, and not with intrauterine HIV transmission. METHODS: In the New York City Perinatal HIV Transmission Collaborative Study 276 infants of HIV-infected women were followed prospectively and had results of early polymerase chain reaction (PCR) tests available. Among infected children, intrauterine infection was presumed if HIV DNA was detected by PCR in samples collected from children aged < or = 3 days, and intrapartum infection was presumed if HIV DNA was not detected in these early samples. The proportion of infants with presumed intrauterine and intrapartum infections were compared by selected intrapartum, perinatal and maternal characteristics. RESULTS: Presumed intrapartum infection was found in 7% of infants delivered by Cesarean section and, among infants delivered vaginally, those with longer duration of membrane rupture (> 4 h) were significantly more likely to have presumed intrapartum HIV infection (22%) than those with shorter duration (9%; P = 0.02). There were no differences in presumed intrauterine HIV infection by mode of delivery or longer duration of membrane rupture. Infants born preterm and small for gestational age had significantly higher risks of presumed intrapartum infection, but only those who were small for gestational age had higher risks of intrauterine infection. CONCLUSION: Our results support the notion that selected intrapartum conditions, long duration of membrane rupture prior to delivery in particular, are independent risk factors for maternal-infant transmission, and suggest that preterm infants may be especially vulnerable to intrapartum HIV exposure.

The effect of maternal viral load on the risk of perinatal transmission of HIV-1. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the effect of maternal viral load at delivery on the risk of perinatal transmission of HIV-1. DESIGN: A nested case-control study within a prospectively followed cohort of HIV-1-infected pregnant women and their infants. SETTING: The multicenter New York City Perinatal HIV Transmission Collaborative Study. PARTICIPANTS: Fifty-one women who gave birth to HIV-1 infected infants were frequency-matched within CD4+ cell count quintiles with 54 non-transmitting mothers. MAIN OUTCOME MEASURES: Maternal quantity of HIV-1 viral RNA was assayed in plasma obtained near delivery using the nucleic acid sequence-based amplification assay system. RESULTS: Viral RNA was detected in 73 (70%) out of 105 women and the median viral load was 16,000 RNA copies/ml in transmitters and 6,600 in non-transmitters (P < 0.01). When adjusted for maternal CD4+ count near delivery, women with measurable viral load were nearly sixfold more likely to transmit HIV-1 than women with viral load below detection [adjusted odds ratio (AOR), 5.8; 95% confidence interval (CI), 2.2 15.5]. The odds ratio for perinatal transmission of log10 viral load, adjusted for CD4 count was 2.7 (95% CI, 1.5-5.1). When stratified by the stage of HIV-1 disease, the only group with significant association between log10 viral load and transmission were AIDS-free women with CD4+ count > 500 x 10(6)/l (AOR, 9.1; 95% CI, 2.6-31.5). CONCLUSIONS: High maternal viral load increases the likelihood of perinatal transmission of HIV-1 in women without AIDS and advanced immunosuppression. HIV-1 infected pregnant women without advanced disease, shown by others to have the lowest risk of perinatal transmission, may benefit the most from efforts to identify and decrease viral load at delivery.

Prospective study of human immunodeficiency virus 1-related disease among 512 infants born to infected women in New York City. The New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the incidence of HIV-1-related clinical findings, mortality and predictors of death in a cohort of HIV-exposed infants followed from birth. METHODS: Data were collected approximately bimonthly during the first and second year of life and used in Kaplan-Meier and Cox proportional hazards survival analyses to predict time to the development of symptoms and death. RESULTS: One hundred sixteen infected and 396 uninfected infants were followed for a median of 26 months at 7 New York City hospitals from 1986 to 1995. Two or more nonspecific HIV-related symptoms, AIDS or death occurred in 83% of infected children by the first year. Fifty infected infants (43%) developed AIDS and 19 (38%) of these had Pneumocystis carinii pneumonia. Estimated median age at AIDS/death was 30 months and 64% of infected children remained alive and AIDS-free at 1 year. Estimated infant mortality among infected children was 160/1000 live births, and median survival after AIDS was 21 months; 55% of infected children survived > 12 months after diagnosis of AIDS. P. carinii pneumonia was the most common cause of death. Although birth CD4 values did not predict AIDS or death, CD4 counts as early as 6 months of age were highly correlated with both. Thirteen (68%) of 19 infants who remained AIDS-free up to 3 to 6 months of age with CD4 count < or = 1500 cells/microliters subsequently developed AIDS vs. 18 (30%) of 61 with CD4 count > 1500 (P = 0.0001). CONCLUSIONS: Most HIV-1-infected infants develop disease in the first year of life. AIDS or death can be predicted by a threshold CD4 count of 1500 cells/microliters at 3 to 6 months of age.

Heterosexual behavior during pregnancy and perinatal transmission of HIV-1. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the relationship between maternal heterosexual activity during pregnancy and perinatal transmission of HIV-1. DESIGN: A retrospective analysis of 175 New York City HIV-1-seropositive women enrolled during pregnancy or immediately post-partum from 1986 to 1994 in a prospective cohort study. METHODS: Frequency of heterosexual intercourse and condom use during pregnancy was determined from self-report measures. Unprotected intercourse was defined as follows: 'none', consistent condom use or abstinence; 'moderate', inconsistent condom use and fewer than 80 episodes of intercourse; and 'high', inconsistent condom use and 80 or more episodes. RESULTS: The rate of perinatal HIV-1 transmission was 9.1% (four out of 44) among women with no unprotected intercourse during pregnancy, 22.2% (20 out of 90) among those with moderate frequency, and 39.0% (16 out of 41) among those with high frequency (P < 0.01). The relative risk (RR) of perinatal transmission was higher among women with moderate [RR, 2.4; 95% confidence interval (Cl), 0.9-6.7] and high frequency of unprotected sexual intercourse (RR, 4.3; 95% Cl, 1.6-11.8) compared with women with no unprotected sexual intercourse. When potential covariates (maternal injecting drug use, CD4 lymphocyte count, AIDS, zidovudine use, pelvic inflammatory disease or sexually transmitted disease during pregnancy, delivery mode, and extreme prematurity) were included in a logistic regression model (n = 128), the rate of perinatal transmission remained significantly higher among women with any unprotected sexual intercourse during pregnancy. CONCLUSIONS: Data suggest that unprotected sexual intercourse during pregnancy influences perinatal HIV-1 transmission.

Benefit of primary prophylaxis before 18 months of age in reducing the incidence of Pneumocystis carinii pneumonia and early death in a cohort of 112 human immunodeficiency virus-infected infants. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the effectiveness of primary prophylaxis in preventing Pneumocystis carinii pneumonia (PCP) in children with perinatally acquired human immunodeficiency virus 1 (HIV-1) infection. METHODS: We conducted a retrospective analysis of a cohort of infants followed from birth at six metropolitan hospitals and one outpatient clinic for pregnant, drug-using women in New York City. Outcomes measured were histologically confirmed PCP and/or death. The potential confounding effect of the infant's stage of illness, as determined by CD4 count, was controlled by including all CD4 determinations as time-dependant covariates in a Cox proportional hazards analysis. Cases were censored at PCP onset, death, loss to follow-up, and 18 months of age. RESULTS: One hundred twelve HIV-infected children were enrolled at birth between 1986 and 1993. Sixty of these were tracked beyond 18 months of age; of the others, 21 died before this age, 4 were considered lost to follow-up, and 27 had not reached 18 months of age at the last visit. Only 3 cases (4%) of confirmed PCP occurred among the 70 children who received primary PCP prophylaxis before 18 months of age, compared with 12 cases (28%) among 42 children not receiving PCP prophylaxis at any point before 18 months of age. The Kaplan-Meier estimated incidence of PCP in the first year among children not receiving prophylaxis was 25% (95% confidence interval [CI], 12 to 39). Using Cox methods, the unadjusted risk of PCP among infants not receiving prophylaxis, relative to those receiving it, was 4.1 (95% CI, 1.1 to 15); the relative risk was 4.4 (95% CI, 1.2 to 17) adjusting for the percentage of CD4-positive lymphocytes and 5.1 (95% CI, 1.3 to 20) adjusting for the absolute number of CD4-positive cells. Eight of 26 deaths were caused by PCP, and the likelihood of early death was significantly diminished if PCP prophylaxis was given (relative risk controlling for absolute CD4 cells, 2.57; 95% CI, 1.1 to 6.1). CONCLUSIONS: We report evidence that primary antimicrobial PCP prophylaxis is highly effective in decreasing the frequency of PCP and early death in infants with perinatal HIV infection. These findings support the revised National Pediatric HIV Resource Center and Centers for Disease Control and Prevention guidelines for PCP prophylaxis in children.

Comparison of methods of estimating the mother-to-child transmission rate of human immunodeficiency virus type 1 (HIV-1). New York City Perinatal HIV Transmission Collaborative Study Group.

Four methods of estimating mother-to-child transmission rates of human immunodeficiency virus type 1 (HIV-1), based on the 1992 Ghent workshop, were compared in a multicenter New York City prospective cohort study in 1986-1992. Of 833 infants born to women at risk of HIV-1 infection, 388 were born HIV-1 seropositive and 445 were HIV-1 seronegative. The four methods, the Antibody Only, Indirect, Direct, and Virologic Methods, yielded transmission rate estimates of 19-25%, classifying 59-89% of the cohort. Estimation based on persistence of HIV-1 antibody and clinical assessment yielded transmission rates similar to those methods that incorporated virologic testing.

Neonatal predictors of infection status and early death among 332 infants at risk of HIV-1 infection monitored prospectively from birth. New York City Perinatal HIV Transmission Collaborative Study Group.

BACKGROUND AND METHODS: Differences in newborn outcome measures for human immunodeficiency virus (HIV)-1-infected and HIV-1-exposed but uninfected infants have been found in several studies, but not in others. Eighty-four infected and 248 uninfected children born to HIV-1-seropositive mothers followed prospectively in a multicenter, perinatal HIV-1 transmission cohort study were compared for differences in maternal demographics, health status, and newborn outcome measures, including delivery complications, physical examination findings, neonatal complications, and laboratory results. RESULTS: Mothers of HIV-1-infected infants were more likely than those of uninfected infants to have acquired immunodeficiency syndrome (AIDS) diagnosed through 2 weeks postpartum (21% vs 11%, P = .04); the transmission rate for the 38 women with AIDs was 37% compared with 22% for the 245 women without AIDS. Two of 27 (7%) women receiving zidovudine during pregnancy had infected infants compared with 73 (27%) of 275 women who did not receive zidovudine (P = .033). Mean gestational age was significantly lower among HIV-1-infected (37 weeks) than among uninfected infants (38 weeks; P < .001). Infected infants had significantly higher rates of prematurity (gestational age less than 37 weeks) (33% vs 19%, P = .01) and extreme prematurity (gestational age less than 34 weeks) (18% vs 6%, P = .001) than uninfected infants. Infection was associated with lower birth weight (2533 g vs 2862 g, P < .001) and smaller head circumference (32.0 cm vs 33.1 cm, P = .001). HIV-1-infected infants were significantly more likely to be small for gestational age (26% vs 16%, P = .04) and low birth weight (less than 2500 g) (45% vs 29%, P = .006) than infants who were uninfected. Twenty-two (26%) HIV-1-infected children died during a median follow-up of 27.6 months (range 1.9 to 98.3 months). Prematurity was predictive of survival: by Kaplan-Meier, an estimated 55% (95% confidence interval, 31% to 72%) of preterm infected children survived to 24 months compared with 84% (95% confidence interval, 70% to 92%) of full-term infected children (P = .005). CONCLUSION: Infants born to women with AIDS are at higher risk for HIV-1 infection than are infants born to HIV-1-infected women with AIDS not yet diagnosed. Women receiving zidovudine appear less likely to transmit HIV-1 to their infants. Significantly higher rates of prematurity and intrauterine growth retardation were found among HIV-1-infected infants than among those in the uninfected, HIV-1-exposed control group. Prematurity was associated with shortened survival in HIV-1-infected infants. Measures of intrauterine growth and gestation appear to be important predictors of HIV-1 infection status for seropositive infants and of prognosis for the infected infant.

Efficacy of antenatal zidovudine in reducing perinatal transmission of human immunodeficiency virus type 1. The New York City Perinatal HIV Transmission Collaborative Study Group.

New York City women (321) enrolled during 1986-1993 in an observational cohort study were analyzed retrospectively to determine the effectiveness of antenatal zidovudine in reducing perinatal transmission of human immunodeficiency virus type 1 (HIV-1) in women with various CD4+ lymphocyte counts (< 200, 200-499, > 499/microL). When CD4+ lymphocyte level was controlled for, women prescribed zidovudine during pregnancy were less likely to transmit HIV-1 to their infants (adjusted odds ratio, 0.36; 95% confidence interval, 0.14-0.92). There was no conclusive evidence that efficacy of zidovudine depended on CD4+ lymphocyte level, suggesting that women with severe CD4+ cell depression, who are at highest risk of transmitting HIV-1, may also benefit from zidovudine. Antenatal zidovudine treatment alone may substantially lower the risk of perinatal HIV-1 transmission. These data are consistent with the results of AIDS Clinical Trial Group protocol 076 and suggest that a substantial portion of zidovudine's protective effect may occur when used during the antenatal period.