HIV-1 seroprevalence among childbearing women in northern Thailand: monitoring a rapidly evolving epidemic.

OBJECTIVES: To describe trends in prevalence of HIV-1 infection among women giving birth at Chiang Rai Hospital (CRH) and to assess risk factors associated with HIV infection in this population. DESIGN: Analysis of hospital registry data for all deliveries at CRH from 1990 to mid-1997. METHODS: From 1990 to mid-1997, women giving birth at CRH were tested for HIV-1 infection using enzyme immunoassay (EIA); positive sera were confirmed using a different manufacturer's EIA. Demographic and clinical data were abstracted from delivery-ward log books. RESULTS: Data from 40723 deliveries indicated that overall HIV-1 seroprevalence increased sharply, from 1.3% in 1990 to a peak of 6.4% in 1994, and then declined to 4.6% in the first 6 months of 1997. Prevalence was highest, at 7.0%, among young (age < or = 24 years) primigravidas, compared with 2.4% among older (age > or = 25 years) multigravidas. When we controlled for age, prevalence declined 40% from 1994 to 1997 among young primigravidas (95% confidence interval for percentage reduction, 16-57). Amongst older multigravid women, prevalence was consistently lower but increased steadily from 2.7% in 1994 to 3.4% in 1997. CONCLUSIONS: A rapid rise in HIV prevalence in childbearing women was followed by a sharp decline among young primigravidas. In each year, the prevalence was highest among young primigravidas. They may be the best subgroup of pregnant women for monitoring HIV epidemic trends, but they also represent a challenging prevention priority that will require its own targeted interventions.

Clinical assessment of HIV-associated lipodystrophy in an ambulatory population.

OBJECTIVE: To identify clinical factors associated with prevalence of fat atrophy (lipoatrophy) and fat accumulation (lipoaccumulation) in HIV-1 infected patients. DESIGN: Evaluation of HIV-1 infected patients seen for routine care between 1 October and 31 December 1998 in the eight HIV Outpatient Study (HOPS) clinics. SETTING: Eight clinics specializing in the care of HIV-1 infected patients. PATIENTS: A total of 1077 patients were evaluated for signs of fat maldistribution. INTERVENTIONS: A standardized set of questions and specific clinical signs were assessed. Demographic, clinical and pharmacological data for each patient were also included in the analysis. MAIN OUTCOME MEASURES: Demographic, immunologic, virologic, clinical, laboratory, and drug treatment factors were assessed in stratified and multivariate analyses for their relationship to the presence and severity of fat accumulation and atrophy. RESULTS: Independent factors for moderate/severe lipoatrophy for 171 patients were increasing age, any use of stavudine, use of indinavir for longer than 2 years, body mass index (BMI) loss, and measures of duration and severity of HIV disease. Independent risk factors for moderate/severe fat accumulation for 104 patients were increasing age, BMI gain, measures of amount and duration of immune recovery, and duration of antiretroviral therapy (ART). The number of non-drug risk factors substantially increased the likelihood of lipoatrophy. If non-drug risk factors were absent, lipoatrophy was unusual regardless of the duration of drug use. CONCLUSIONS: HIV-associated lipodystrophy is associated with several host, disease, and drug factors. While prevalence of lipoatrophy increased with the use of stavudine and indinavir, and lipoaccumulation was associated with duration of ART, other non-drug factors were strongly associated with both fat atrophy and accumulation.

Pregnancy, breast feeding, and oral contraceptives and the risk of epithelial ovarian cancer.

To quantify the effects of cumulative months of pregnancy, breast feeding, and oral contraceptive use on the risk of developing epithelial ovarian cancer, the authors used data collected for the Cancer and Steroid Hormone Study--a multicenter, population-based, case-control study. Detailed reproductive histories were obtained from 436 women aged 20-54 with epithelial ovarian cancer newly diagnosed between December 1980 and December 1982, and from 3833 women aged 20-54 selected at random from the same geographic areas. Estimated relative risks of epithelial ovarian cancer were 0.6 (95% confidence interval (CI) 0.5-0.8) for women who had ever been pregnant, 0.6 (95% CI 0.5-0.8) for women who had ever breast fed, and 0.5 (95% CI 0.5-0.7) for women who had ever used oral contraceptives. Logistic regression analysis revealed a strong trend in decreasing risk of epithelial ovarian cancer with increasing cumulative months of pregnancy; this effect was less pronounced in women aged 50-54 than in younger women. In contrast, a marked reduction in risk was associated with ever having breast fed or used oral contraceptives, while the decrease in risk from additional months of either of these exposures was less than that for pregnancy.

The interruption of transmission of indigenous measles in the United States during 1993.

BACKGROUND: The United States has a goal to eliminate all indigenous cases of measles by the year 2000. Initial interruption of indigenous measles transmission would be expected during a period of very low measles incidence as occurred during late 1993. METHODS: Indigenous measles cases (i.e. cases acquired in the United States and not traceable to any imported case) from 1993 were investigated to determine their source of infection. The probability of sustained undetected measles transmission between isolated indigenous cases was estimated. RESULTS: Of the 312 measles cases reported for 1993, only 25 (8%) occurred after September 19. Of these only 4 cases (16%) could be classified as indigenous. The estimated probability that any of these 4 cases resulted from indigenous measles transmission in theirs or any adjoining counties was 0.05 or less. CONCLUSIONS: Interruption of indigenous measles transmission appears to have occurred for the first time throughout the United States in 1993. This event provides strong support for the current national strategy for measles elimination. However, complete elimination of indigenous measles will require maintaining high population immunity to prevent spread from imported cases and attaining global measles control to prevent the importation of measles.

The incidence of Kawasaki syndrome in West Coast health maintenance organizations.

BACKGROUND: Kawasaki syndrome (KS) causes an acute vasculitis of unknown etiology. It is a leading cause of acquired heart disease of children in Japan and the United States. METHODS: We examined the incidence of KS in a well-defined population group of children < or =6 years of age, using data collected through the Vaccine Safety Datalink (VSD) project. The VSD database contains information on >1 million children enrolled in four West Coast health maintenance organizations (HMOs). RESULTS: During 1993 through 1996 a total of 234 physician-diagnosed KS patients were reported in the 4 HMOs; 152 (65.0%) were boys and 195 (83.3%) were <5 years of age. The incidence of KS among children <5 years of age in the HMOs ranged from 9.0 to 19.1 per 100,000 person years. KS incidence was higher among boys in 3 of the sites. In the 2 sites with the highest number of KS patients, a seasonal occurrence of KS in winter and early spring was observed. Overall 226 (96.6%) of the KS patients were reported to have been hospitalized; hospitalization rates for children <5 years of age ranged from 9.0 to 16.8 per 100,000 person years. CONCLUSIONS: The incidence of KS in the HMOs was similar to that reported in other population-based studies in the United States and higher than estimates for Australia and several European countries.

Epidemiology of diarrheal disease among children enrolled in four West Coast health maintenance organizations. Vaccine Safety Datalink Team.

BACKGROUND: We used information from the Vaccine Safety Datalink (VSD) about approximately 1 million children enrolled in four health maintenance organizations to assess the morbidity from diarrhea and estimate the disease burden of rotavirus. METHODS: We examined trends of diarrhea-associated hospitalizations and emergency room (ER) visits among VSD children ages 1 month through 4 years during October, 1992, through September, 1994 (two rotavirus seasons) and estimated the morbidity from rotavirus on the basis of characteristic patterns of age and seasonality. RESULTS: Overall diarrhea was associated with 6.3% of hospitalizations and 4% of ER visits. During a child's first 5 years of life, we estimated that 1 in 57 was hospitalized and 1 in 21 required an ER visit because of diarrhea. Each year the number of diarrhea-associated hospitalizations and ER visits was greatest in winter among children ages 4 to 23 months and peaked in November in California and during February in Oregon and Washington. The winter seasonality of diarrhea-associated hospitalizations reflected the trends for diarrhea of presumed noninfectious and viral etiologies, which together accounted for most (92.9%) hospitalizations. CONCLUSIONS: Diarrhea is an important cause of morbidity among VSD children. The epidemiologic patterns of diarrhea-associated hospitalizations and ER visits resembled those reported previously for rotavirus diarrhea, suggesting that rotavirus may be a major contributor to the overall morbidity from diarrhea. Enhanced surveillance by screening for rotavirus in a sample of children with diarrhea will permit a more accurate assessment of the disease burden of this pathogen and the cost effectiveness of a rotavirus immunization program.

Another look at the black-white gap in gestation-specific perinatal mortality.

In the US, black infants born near or at term experience higher mortality than white infants. To extend our understanding of black-white differences in the relative advantages of growth (measured by birthweight) for gestational age, we compared race-specific rates of perinatal mortality by deviation in grams from the median birthweight for four categories of gestation (35-36, 37-38, 39-41, and 42-43 weeks). We also used race-specific standards to examine the difference between the median birthweight and the optimum birthweight (i.e. birthweight with the lowest mortality). The data, which were derived from vital records for singletons delivered in the US from 1983-1984, comprised 24,626 fetal and neonatal deaths among 5,157,197 white infants and 5973 fetal and neonatal deaths among 926,678 black infants. At all deviations from the median birthweight, black infants had relatively better survival at 35-36 weeks of gestation. This advantage was reversed among infants with gestations of 39-41 and 42-43 weeks. The optimum birthweight for black infants with gestations greater than or equal to 37 weeks was closer to their median birthweight than was that for white infants. For black infants with gestations of 39-41 weeks, the optimum birthweight was 187g (95% confidence interval (CI): 150-234) greater than the median birthweight (3289g); for comparable white infants the optimum birthweight was 397g (95% CI: 366-431) greater than the median birthweight (3487g). To reduce the black-white gap in perinatal mortality, we need a better understanding of aetiological relations between gestation, growth, and mortality.

Older maternal age and infant mortality in the United States.

We used data from the National Infant Mortality Surveillance project to examine the effect of older maternal age on infant mortality for the 1980 United States birth cohort. The 1,579,854 births and 14,591 deaths of singletons who were black or white and whose mothers were 25-49 years of age were included. Direct standardization was used to calculate birth-weight-adjusted relative risks of neonatal and postneonatal mortality, using the birth weights of infants with maternal age 25-29 as the standard. We found that the risk of infant mortality was nearly equal for infants born to mothers 25-29 and 30-34 years of age; infants born to mothers 35-39 years of age were at a slightly elevated (18% higher) risk, and those born to mothers 40-49 years of age were at a much more elevated (69% higher) risk. Among whites, the higher neonatal mortality associated with a maternal age of 35-39 was mostly due to an increased prevalence of low birth weight; among blacks, it was due to higher birth-weight-specific risks. Neither white nor black postneonatal mortality risks were much elevated until a maternal age of 40-49, and this last elevation was mostly due to higher birth-weight-specific risks. These findings suggest that infertility and fetal mortality aside, and considering only the effect on infant mortality, it is relatively safe for women to postpone childbearing into their middle, and perhaps late, thirties.

Preterm delivery among black and white enlisted women in the United States Army.

OBJECTIVE: To examine black-white differences in preterm delivery in a healthy population who had unrestricted access to prenatal care. METHODS: We conducted a retrospective cohort study of 842 black and 1026 white enlisted servicewomen who delivered a singleton infant of 20 or more weeks' gestation from July 1, 1987 through September 30, 1990 at four Army Medical Centers in the United States. Data were collected by reviewing maternal and newborn records. We used logistic and proportional hazards regression models to analyze outcomes defined by length of gestation, cause of preterm delivery, and jointly by length and cause. RESULTS: Black enlisted women had a cumulative probability of preterm delivery (13.5%) that was higher than that for white enlisted women (10.5%) (hazard ratio 1.31, 95% confidence interval [CI] 1.002-1.70). However, the ratio of black-to-white hazards was not uniform. Black-white differences were small and nonsignificant from 33-36 weeks' gestation, when most preterm deliveries occur. The differences were also small and nonsignificant for deliveries related to spontaneous rupture of membranes or idiopathic preterm labor, the most common causes of preterm delivery. The black-to-white hazard ratios were greatest for all deliveries before 33 weeks' gestation and for medically indicated preterm deliveries. CONCLUSIONS: Efforts to reduce black-white differences in preterm delivery must go beyond providing prenatal care and eliminating recreational drug use. Future studies should consider black-white differences in environments during the mother's own development and in psychosocial and physical stresses during pregnancy.

Postneonatal deaths from infections and injuries: race, maternal risk, and age at death.

Most infants with birthweights greater than or equal to 2,500 g who survive the first 27 days of life have a reasonable opportunity to grow into healthy children. However, some of these infants succumb to two potentially preventable causes of death: infections and injuries. Although the relationship between maternal attributes and risk of death from these causes has been described, little is known about how maternal attributes relate to postneonatal age at death. To examine this relationship, we analyzed postneonatal deaths from infections and injuries among 3,116,391 white and 638,915 black neonatal survivors with birthweights greater than or equal to 2,500 g. We grouped postneonates by maternal race and risk status. Infants of mothers greater than or equal to 20 years of age who started prenatal care in the first trimester were considered low risk; all others were high risk. For each category of infection death (respiratory, central nervous system, and other bacterial--including sepsis), neither race nor maternal risk status was related to age at death. The same was true for three categories of injury death (motor vehicle, fire, and homicide), but not for injury deaths in the category of choking, drowning, or suffocation. Among blacks, these deaths occurred at younger ages, regardless of maternal risk status. Thus, efforts to prevent deaths from choking, drowning, or suffocation among blacks should focus on early infancy.

Young maternal age and infant mortality: the role of low birth weight.

In 1980, there were 562,330 babies born in the United States to teenage mothers (19 years of age or younger). The offspring of teenage mothers have long been known to be at increased risk of infant mortality, largely because of their high prevalence of low birth weight (less than 2,500 grams). We used data from the National Infant Mortality Surveillance (NIMS) project to examine the effect of young maternal age and low birth weight on infant mortality among infants born in 1980 to U.S. residents. This analysis was restricted to single-delivery babies who were either black or white, who were born to mothers ages 10-29 years, and who were born in one of 48 States or the District of Columbia. Included were 2,527,813 births and 28,499 deaths (data from Maine and Texas were excluded for technical reasons). Direct standardization was used to calculate the relative risks, adjusted for birth weight, of neonatal mortality (less than 28 days of life) and postneonatal mortality (28 days to less than 1 year of life) by race and maternal age. There was a strong association between young maternal age and high infant mortality and between young maternal age and a high prevalence of low birth weight. Neonatal mortality declined steadily with increasing maternal age. After adjusting for birth weight, the race-specific relative risks for babies born to mothers less than 16 years of age were still elevated from 11 to 40 percent, compared with babies born to mothers 25-29 years of age. Otherwise, all the relative risks were nearly equal to 1. By contrast, most of the association between young maternal age and postneonatal mortality persisted after birth weight adjustment in all maternal age groups.These results suggest that the prevention of neonatal mortality and, to a lesser extent, postneonatal mortality among babies born to teenagers depends on preventing low birth weight. The prevention of postneonatal mortality may depend more on other factors, such as assisting teenagers with better parenting. Finally, although there maybe few biological reasons to postpone childbearing,teenage childbearing continues to place the mother and her baby at a social disadvantage.

Large sample confidence intervals for regression standardized risks, risk ratios, and risk differences.

Several methods have been proposed for standardizing risks, risk ratios, and risk differences based on the results of logistic regression. These methods provide an alternative to direct standardization, a particularly useful approach when there are many covariates. In this paper, methods for calculating approximate confidence limits for these standardized measures are presented. A simple example, in which published data are used, illustrates the techniques and allows comparison with confidence limits calculated from the directly standardized risk ratio.

Identification of nonfatal family and intimate assault incidents in police data.

We examined different strategies for identifying nonfatal family and intimate assaults (FIAs) in police data. Police most often classify such incidents in the "assault" category, but they also use other crime categories. We estimated that, during 1984, 3300 FIAs (or 837 per 100,000 population) occurred in Atlanta. Of those, 77% were classified as assaults; 23% were classified in nonassault categories. Research measuring the magnitude of FIAs should take into account incidents classified in nonassault crime categories.

Are race and length of gestation related to age at death in the sudden infant death syndrome?

Although race and preterm delivery are known to be associated with sudden infant death syndrome (SIDS), the relationships between age at death from SIDS and these factors have not been well described. To examine these relationships, we used linked infant birth and death records for the cohort of 1,204,375 White and 283,776 Black postneonates who were born from 1979 to 1981 in five states: California, Georgia, Missouri, South Carolina and Tennessee. Deaths attributable to SIDS occurred to 1404 White postneonates and to 696 Black postneonates. Although postneonatal SIDS rate among Black infants was twice that of White infants, the relative risk was smaller among infants with gestations of less than 35 weeks. For White postneonates, the median postneonatal age at death sharply declined for gestations from 28-29 weeks to 36-37 weeks and levelled off for longer gestations. For Black postneonates, the results do not support an association between length of gestation and age at death. The findings suggest that practitioners investigating approaches to avert SIDS need to maintain their interventions to an older age among White preterm infants. Researchers investigating the causes of SIDS need to consider the relationship between length of gestation and age at death from SIDS as well as possible developmental differences between White and Black preterm infants.

Survival of hemophilic males with acquired immunodeficiency syndrome with and without risk factors for AIDS other than hemophilia.

Between January 1, 1981, and June 30, 1990, 1,514 hemophilia-associated acquired immunodeficiency syndrome (AIDS) cases in males were diagnosed in the United States. In 1,394, hemophilia was reported as the sole risk factor. For an additional 120, other risk factors were reported: of 101 of these, 40 had homosexual/bisexual activity, 53 had a history of intravenous drug use, and 8 had both of these risk factors. We examined the demographic data and the survival data of two principal groups: males for whom hemophilia was the sole reported risk factor for human immunodeficiency virus (HIV) exposure, and hemophilic males for whom homosexual/bisexual activity, intravenous drug use, or both of these additional risk factors were reported. The survival curves showed marginal differences between the hemophilia-only and the multiple risk groups; the median survival times were 13.1 and 14.6 months, with the cumulative probability of survival at 1 year as 52.7% and 54.0%, respectively. Kaposi's sarcoma was among AIDS indicator diseases more commonly found in the multiple risk factor group. Pneumocystis carinii pneumonia was the sole reported diagnosis indicative of AIDS for 34.4% of those in the hemophilia-only group, compared with 20.8% of those with multiple risk factors. The principal demographic difference between the two groups was the age distribution; those in the multiple risk factor group were primarily between 20 and 44 years of age. Restricting the analysis to those between 20 and 44 years resulted in a slightly longer survival time in the hemophilia-only group and no appreciable difference between the disease distributions and survival curves of the two groups.

Electrohydrodynamic effects in continuous flow electrophoresis.

We demonstrate experimentally and theoretically the importance of electrohydrodynamic (EHD) flows in continuous-flow electrophoresis (CFE) separations. These flows are associated with variations in the conductivity or dielectric constant, and are quadratic in the field strength. They appear to be the main cause of extraneous and undesired flows in CFE which have degraded separation performance and have until now not been explained. We discuss the importance of EHD flows relative to other effects. We also describe possible techniques for reducing the associated degradation of CFE separations.

Stiripentol in acute/chronic efficacy tests in monkey model.

Acute and chronic efficacy tests of stiripentol (4,4-dimethyl-1-[3,4-(methylenedioxy)-phenyl]-1-penten-3-ol) were conducted in alumina-gel rhesus monkeys. In the acute study (n = 6), discrete serial seizures precipitated by 150 mg/kg of 4-deoxypyridoxine hydrochloride were challenged by intravenous administration of stiripentol and the data compared with those obtained with valproate similarly tested in other monkeys (reported here) and with those from four other standard anticonvulsants (phenytoin, carbamazepine, phenobarbital, and diazepam--data published previously). In the acute challenge (Study 1), stiripentol performed comparably to valproate by delaying the onset of seizures but not eliminating them as did the other four drugs. In two separate chronic studies (at different doses, n = 6 each), stiripentol was given every 4 h by gastric catheter for 4 weeks, preceded and followed by 4 weeks of baseline. In these studies, stiripentol significantly reduced EEG interictal spike rates at mean plasma concentrations from 20 to 27 micrograms/ml in Study 2 and 11 to 14 micrograms/ml in Study 3. From these results, and those evinced in other studies, it appears that stiripentol should be evaluated for absence epilepsy and possible synergistic effects in polytherapy.

The postponement of neonatal deaths into the postneonatal period: evidence from Massachusetts.

Part of the slow decline in the postneonatal mortality rate and the rapid decline in the neonatal mortality rate during the 1970s may have been due to a postponement of some neonatal deaths into the postneonatal period. The authors hypothesized that any such postponement should be accompanied by a lack of decline, or even an increase, in late neonatal and postneonatal mortality rates among low birth weight babies and babies dying of conditions originating in the perinatal period. To examine this theory, the authors used vital records data to compare infant mortality rates in Massachusetts during 1970-1972 with rates during 1978-1980. Log-linear hazard models were used to calculate death rates, while controlling for changes in maternal age, race, education, and prior reproductive history. The authors found that babies of birth weight under 1,500 g had no decline in late neonatal mortality rates and babies of birth weight under 2,500 g had no decline in postneonatal mortality rates. Babies of birth weight 500-999 g had an increased postneonatal mortality rate (rate ratio = 2.4; 95% confidence limits = 1.0-5.4). These unimproved or increased death rates were due in part to conditions originating in the perinatal period. The authors conclude that, although infant mortality rates have declined, this postponement was real, and that efforts to monitor infant mortality will benefit from its routine quantification.

Weapon involvement and injury outcomes in family and intimate assaults.

OBJECTIVE: To compare the risk of death and the risk of nonfatal injury during firearm-associated family and intimate assaults (FIAs) with the risks during non-firearm-associated FIAs. DESIGN: Records review of police incident reports of FIAs that occurred in 1984. Victim outcomes (death, nonfatal injury, no injury) and weapon involvement were examined for incidents involving only one perpetrator. SETTING: City of Atlanta, Ga, within Fulton County. PARTICIPANTS: Stratified sample (n = 142) of victims of nonfatal FIAs, drawn from seven nonfatal crime categories, plus all fatal victims (n = 23) of FIAs. MAIN OUTCOME MEASURES: Risk of death (vs nonfatal injury or no injury) during FIAs involving firearms, relative to other types of weapons; risk of nonfatal injury (vs all other outcomes, including death) during FIAs involving firearms, relative to other types of weapons. RESULTS: Firearm-associated FIAs were 3.0 times (95% confidence interval, 0.9 to 10.0) more likely to result in death than FIAs involving knives or other cutting instruments and 23.4 times (95% confidence interval, 7.0 to 78.6) more likely to result in death than FIAs involving other weapons or bodily force. Overall, firearm-associated FIAs were 12.0 times (95% confidence interval, 4.6 to 31.5) more likely to result in death than non-firearm-associated FIAs. CONCLUSIONS: Strategies for limiting the number of deaths and injuries resulting from FIAs include reducing the access of potential FIA assailants to firearms, modifying firearm lethality through redesign, and establishing programs for primary prevention of violence among intimates.

Ukraine, 1992: first assessment of diphtheria vaccine effectiveness during the recent resurgence of diphtheria in the Former Soviet Union.

A case-control study in Ukraine provided the first data on the field effectiveness of Russian-produced vaccine during the 1990 diphtheria resurgence in the former Soviet Union. For each of 262 diphtheria cases <15 years of age who were reported from January through October 1992, 2 controls, matched by age and clinic, were selected. The effectiveness of three doses of diphtheria vaccine was 98.2% (95% confidence interval: 90.3-99.9). Among controls, 84% had received three or more vaccinations by 2 years of age. These results suggest that the following five hypothesized causes of the outbreak appeared unlikely: appearance of a new "mutant" diphtheria strain, low potency of the Russian-produced diphtheria vaccine, inadequate cold chain, poor host immunogenicity due to radiation exposure from Chernobyl, and low routine childhood vaccination coverage. It is concluded that initial priority for scarce resources for controlling this outbreak should be placed on vaccination of persons susceptible to diphtheria (e.g., adults) rather than revaccination of children.