Sugar-sweetened beverage consumption and age at menarche in a prospective study of US girls.

STUDY QUESTION: Is sugar-sweetened beverage (SSB) consumption associated with age at menarche? SUMMARY ANSWER: More frequent SSB consumption was associated with earlier menarche in a population of US girls. WHAT IS KNOWN ALREADY: SSB consumption is associated with metabolic changes that could potentially impact menarcheal timing, but direct associations with age at menarche have yet to be investigated. STUDY DESIGN, SIZE, DURATION: The Growing up Today Study, a prospective cohort study of 16 875 children of Nurses' Health Study II participants residing in all 50 US states. This analysis followed 5583 girls, aged 9-14 years and premenarcheal at baseline, between 1996 and 2001. During 10 555 person-years of follow-up, 94% (n = 5227) of girls reported their age at menarche, and 3% (n = 159) remained premenarcheal in 2001; 4% (n = 197) of eligible girls were censored, primarily for missing age at menarche. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cumulative updated SSB consumption (composed of non-carbonated fruit drinks, sugar-sweetened soda and iced tea) was calculated using annual Youth/Adolescent Food Frequency Questionnaires from 1996 to 1998. Age at menarche was self-reported annually. The association between SSB consumption and age at menarche was assessed using Cox proportional hazards regression. MAIN RESULTS AND THE ROLE OF CHANCE: More frequent SSB consumption predicted earlier menarche. At any given age between 9 and 18.5 years, premenarcheal girls who reported consuming >1.5 servings of SSBs per day were, on average, 24% more likely [95% confidence interval (CI): 13, 36%; P-trend: <0.001] to attain menarche in the next month relative to girls consuming ≤2 servings of SSBs weekly, adjusting for potential confounders including height, but not BMI (considered an intermediate). Correspondingly, girls consuming >1.5 SSBs daily had an estimated 2.7-month earlier menarche (95% CI: -4.1, -1.3 months) relative to those consuming ≤2 SSBs weekly. The frequency of non-carbonated fruit drink (P-trend: 0.03) and sugar-sweetened soda (P-trend: 0.001), but not iced tea (P-trend: 0.49), consumption also predicted earlier menarche. The effect of SSB consumption on age at menarche was observed in every tertile of baseline BMI. Diet soda and fruit juice consumption were not associated with age at menarche. LIMITATIONS, REASONS FOR CAUTION: Although we adjusted for a variety of suspected confounders, residual confounding is possible. We did not measure SSB consumption during early childhood, which may be an important window of exposure. WIDER IMPLICATIONS OF THE FINDINGS: More frequent SSB consumption may predict earlier menarche through mechanisms other than increased BMI. Our findings provide further support for public health efforts to reduce SSB consumption. STUDY FUNDING/COMPETING INTERESTS: The Growing up Today Study is supported by grant R03 CA 106238. J.L.C. was supported by the Breast Cancer Research Foundation; Training Grant T32ES007069 in Environmental Epidemiology from the National Institute of Environmental Health Sciences, National Institutes of Health; and Training Grant T32HD060454 in Reproductive, Perinatal and Pediatric Epidemiology from the National Institute of Child Health and Human Development, National Institutes of Health. A.L.F. is supported by the American Cancer Society, Research Scholar Grant in Cancer Control. K.B.M. was supported in part by the National Cancer Institute at the National Institutes of Health (Public Health Service grants R01CA158313 and R03CA170952). There are no conflicts of interest to declare.

Clinical malaria diagnosis in pregnancy in relation to early perinatal mother-to-child transmission of HIV: a prospective cohort study.

OBJECTIVES: We prospectively investigated fever symptoms and maternal diagnosis of malaria in pregnancy (MIP) in relation to child HIV infection among 2368 pregnant HIV-positive women and their infants, followed up from pregnancy until 6 weeks post-delivery in Tanzania. METHODS: Doctors clinically diagnosed and treated MIP and fever symptoms during prenatal health care. Child HIV status was determined via DNA polymerase chain reaction (PCR). Multivariable logistic regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for HIV mother-to-child transmission (MTCT) by the 6th week of life. RESULTS: Mean gestational age at enrolment was 22.2 weeks. During follow-up, 16.6% of mothers had at least one MIP diagnosis, 15.9% reported fever symptoms and 8.7% had both fever and MIP diagnosis. Eleven per cent of HIV-exposed infants were HIV-positive by 6 weeks. The RR of HIV MTCT was statistically similar for infants whose mothers were ever vs. never clinically diagnosed with MIP (RR 1.24; 95% CI 0.94-1.64), were diagnosed with one vs. no clinical MIP episodes (RR 1.07; 95% CI 0.77-1.48) and had ever vs. never reported fever symptoms (RR 1.04; 95% CI 0.78-1.38) in pregnancy. However, the HIV MTCT risk increased by 29% (95% CI 4-58%) per MIP episode. Infants of women with at least two vs. no MIP diagnoses were 2.1 times more likely to be HIV infected by 6 weeks old (95% CI 1.31-3.45). CONCLUSIONS: Clinical MIP diagnosis, but not fevers, in HIV-positive pregnant women was associated with an elevated risk of early HIV MTCT, suggesting that malaria prevention and treatment in pregnant HIV-positive women may enhance the effectiveness of HIV prevention in MTCT programmes in this setting. Future studies using a laboratory-confirmed diagnosis of malaria are needed to confirm this association.

PREDICTORS OF INCIDENT TUBERCULOSIS IN HIV-EXPOSED CHILDREN IN TANZANIA.

OBJECTIVE: To examine the predictors of tuberculosis infection in HIV-exposed children. DESIGN: A longitudinal cohort study nested within a randomised controlled trial. SETTING: Antenatal clinics in Dar-es-Salaam, Tanzania. SUBJECTS: Children born to 875 HIV-infected women in Tanzania. RESULTS: A total of 82 children developed tuberculosis during the follow-up period. In multivariate analyses, HIV infection was associated with a six-fold increase in risk of tuberculosis. Breastfeeding duration, child mid-upper arm circumference, and maternal CD4 T-cell counts were inversely related to risk of tuberculosis. In HIV-infected children, greater number of people eating at the same household meal and child CD8 T-cell counts were associated with increased risk of tuberculosis; higher maternal lymphocyte counts, increased duration of breastfeeding, and lower vitamin E levels were associated with reduced risk of tuberculosis. In HIV-uninfected children, breastfeeding duration and increased child mid-upper arm circumference were associated with reduced risk of tuberculosis. CONCLUSION: Breastfeeding duration, HIV status, maternal and child nutritional and immunological status were important predictors of child tuberculosis. Appropriate infant feeding and nutritional interventions could represent important adjuncts to prevent tuberculosis in children born to HIV-infected women in sub-Saharan Africa.

Lipid-soluble vitamins A, D, and E in HIV-infected pregnant women in Tanzania.

BACKGROUND/OBJECTIVES: There is limited published research examining lipid-soluble vitamins in human immunodeficiency virus (HIV)-infected pregnant women, particularly in resource-limited settings. SUBJECTS/METHODS: This is an observational analysis of 1078 HIV-infected pregnant women enrolled in a trial of vitamin supplementation in Tanzania. Baseline data on sociodemographic and anthropometric characteristics, clinical signs and symptoms, and laboratory parameters were used to identify correlates of low plasma vitamin A (<0.7 micromol/l), vitamin D (<80 nmol/l) and vitamin E (<9.7 micromol/l) status. Binomial regression was used to estimate risk ratios and 95% confidence intervals. RESULTS: Approximately 35, 39 and 51% of the women had low levels of vitamins A, D and E, respectively. Severe anemia (hemoglobin <85 g/l; P<0.01), plasma vitamin E (P=0.02), selenium (P=0.01) and vitamin D (P=0.02) concentrations were significant correlates of low vitamin A status in multivariate models. Erythrocyte Sedimentation Rate (ESR) was independently related to low vitamin A status in a nonlinear manner (P=0.01). The correlates of low vitamin D status were CD8 cell count (P=0.01), high ESR (ESR >81 mm/h; P<0.01), gestational age at enrollment (nonlinear; P=0.03) and plasma vitamins A (P=0.02) and E (P=0.01). For low vitamin E status, the correlates were money spent on food per household per day (P<0.01), plasma vitamin A concentration (nonlinear; P<0.01) and a gestational age <16 weeks at enrollment (P<0.01). CONCLUSIONS: Low concentrations of lipid-soluble vitamins are widely prevalent among HIV-infected women in Tanzania and are correlated with other nutritional insufficiencies. Identifying HIV-infected persons at greater risk of poor nutritional status and infections may help inform design and implementation of appropriate interventions.

The use of total lymphocyte count as a surrogate for low CD4+ T lymphocyte cell counts among HIV-1-infected women in Tanzania.

BACKGROUND: Human Immunodeficiency Virus type 1 (HIV-1) infection leads to a progressive decline in CD4+ T-lymphocyte (CD4) cells. Initiation of prophylaxis against Opportunistic infections in adults (CD4% used for children) and antiretroviral therapy is usually based on CD4 cell counts, but CD4 cell counts measurement is not affordable in most African countries. OBJECTIVE: To examine whether total lymphocyte counts (TLC) may be used as proxies for low CD4 cell counts. DESIGN: Cross-sectional at baseline when women were pregnant and at least six months postpartum. METHODS: 1,078 HIV-1-infected pregnant women from Dar es Salaam, Tanzania were enrolled in a randomized clinical trial. A series of receiver operator characteristic (ROC) curves were created at baseline and at least 6 months postpartum and among women in WHO Stage 3 and above. The sensitivity and specificity of TLC and hemoglobin in predicting an absolute CD4 count < 200 cells/mm3 were determined for various clinically relevant cut points. RESULTS: TLC was not a good predictor of low CD4 cell counts during pregnancy or at least six months postpartum as exhibited by low ROC Area Under the Curve (AUCs) of .57 and .62 respectively. No other variable had the ability to predict CD4 < 200 cells/mm3. CONCLUSIONS: The use of TLC as a proxy for the estimation of low CD4 cell counts in a population of HIV-1-infected adults from sub-Saharan Africa was not substantiated. Inexpensive methods to quantify CD4 cell counts in Africa are needed.

Point and interval estimates of partial population attributable risks in cohort studies: examples and software.

The concept of the population attributable risk (PAR) percent has found widespread application in public health research. This quantity describes the proportion of a disease which could be prevented if a specific exposure were to be eliminated from a target population. We present methods for obtaining point and interval estimates of partial PARs, where the impact on disease burden for some presumably modifiable determinants is estimated in, and applied to, a cohort study. When the disease is multifactorial, the partial PAR must, in general, be used to quantify the proportion of disease which can be prevented if a specific exposure or group of exposures is eliminated from a target population, while the distribution of other modifiable and non-modifiable risk factors is unchanged. The methods are illustrated in a study of risk factors for bladder cancer incidence (Michaud DS et al., New England J Med 340 (1999) 1390). A user-friendly SAS macro implementing the methods described in this paper is available via the worldwide web.

Socio-economic and demographic factors associated with prevalence of HIV infection among pregnant women in Dar es Salaam, Tanzania.

BACKGROUND: HIV/AIDS epidemic has become generalised in low resource settings in sub-Saharan Africa where 90% of all maternal-foetal transmission of HIV infection occurs. Global effort to scale-up pMTCT is underway, however, mechanisms to maximise screening of HIV- 1 positive women for Nevirapine treatment and other interventions, are not clear. OBJECTIVE: To identify socioeconomic and demographic characteristics associated with the prevalence of HIV- 1 infection among Tanzanian women. DESIGN: Cross-sectional study. SETTING: Four antenatal clinics in Dar es Salaam. RESULTS: HIV prevalence rate was 13.1 (95% confidence interval (CI): 12.7% - 13.5%) and it increased with increasing maternal age. Older age than 25, mid-arm circumference less than 25cm, geographic location, working in a public house, and partner's occupation were independently associated with higher prevalence of infection. Women in monogamous marriages were 77% less likely to be HIV infected compared to women with no regular partner. Similarly, women with more than five persons per household, and those who spent less on food had a significantly lower HIV prevalence. CONCLUSION: HIV infection is sufficiently widespread among women in Dar es Salaam suggesting that screening based on socioeconomic and demographic characteristics would miss a large proportion of the positives. There is need to increase facilities for counselling and testing using an opt-out approach for testing in all antenatal clinics in the city.

Determinants of low birth weight among HIV-infected pregnant women in Tanzania.

BACKGROUND: Low birth weight (LBW) increases the risk of infant death, but little is known about its causes among HIV-infected populations in sub-Saharan Africa. OBJECTIVE: We assessed sociodemographic, nutritional, immunologic, parasitic, and infant risk factors for birth weight, LBW, and small-for-gestational-age (SGA) status in a cohort of 822 HIV-positive women enrolled in a clinical trial of vitamin supplementation and pregnancy outcomes in Dar es Salaam, Tanzania. DESIGN: Women were enrolled at prenatal care clinics during their second trimester, at which time blood, stool, urine, and genital specimens were collected, and anthropometric measurements and sociodemographic data were recorded. Birth weight was measured at hospital delivery. RESULTS: The mean (+/-SD) birth weight was 3015 +/- 508 g, 11.1% of newborns weighed <2500 g (LBW), and 11.5% were SGA. In multivariate analyses, maternal weight at enrollment and a low CD8 cell count were inversely associated with LBW. Advanced-stage HIV disease, previous history of preterm birth, Plasmodium falciparum malaria, and any helmintic infection were associated with higher risk of LBW. The intestinal parasites Entamoeba histolytica and Strongyloides stercoralis were predictors of LBW despite their low prevalence in the cohort. In a multivariate-adjusted linear regression model, BMI, midupper arm circumference, a CD4 cell count <200 x 10(6) cells/L (200 cells/mm(3)), primiparity, maternal literacy, and infant HIV infection at birth were significantly associated with birth weight in addition to risk factors included in the LBW model. Determinants of SGA included maternal weight, low serum vitamin E concentration, candidiasis, malaria, and infant HIV infection at birth. CONCLUSION: Prevention of HIV disease progression and vertical transmission, improved nutritional status, and better management of malaria and intestinal parasitic infections are likely to reduce the incidence of LBW in Tanzania.

HIV-1 LTR subtype and perinatal transmission.

Multiple subtypes of HIV-1 have been identified; however, there is little data on the relative transmissibility of viruses belonging to different subtypes. A matched case-control study addressed whether viruses with different long terminal repeat (LTR) subtypes were transmitted equally from mother to infant. The LTR subtype was determined for 45 matched cases and controls who participated in a clinical trial in Tanzania. HIV-1 subtypes A, C, and D and intersubtype recombinant sequences were identified. Exact matched logistic regression analysis showed that viruses containing subtype A or intersubtype recombinant LTRs were 3.2 and 4.8 times more likely to be transmitted from mother to infant than viruses with subtype D LTRs. Viruses containing subtype C LTRs were 6.1 times more likely to be transmitted than those with subtype D LTRs. These differences in transmission were independent of maternal CD4 at enrollment. Thus, it appears that HIV-1 subtype may be associated with differing rates of perinatal transmission in Tanzania.

Differences in perinatal transmission among human immunodeficiency virus type 1 genotypes.

OBJECTIVE: To determine whether genotypes from human immunodeficiency virus type 1 (HIV-1) subtypes A, C, or D or intersubtype recombinants have the same probability of being transmitted from mother to child. METHODS: We determined the HIV-1 genetic subtype and maternal risk factors of 51 matched transmitting and nontransmitting mothers from Tanzania. The HIV-1 gag (p24-p7) and env (C2-C5) nucleotide sequences were used for genotype classification, and matched logistic regression analysis was used to assess differences among genotypes. RESULTS: Mothers infected with HIV-1 subtype A (odds ratio, 3.8; 95% CI, 0.8-24.7%), HIV-1 subtype C (odds ratio, 5.1; 95% CI, 1.3-30.8%), or HIV-1 intersubtype recombinant viruses (odds ratio, 5.3; 95% CI, 1.2-33.4%) were more likely to transmit HIV-1 to their infants than mothers infected with HIV-1 subtype D. Lower CD4 cell counts at enrollment were associated with transmission, but CD4 cell counts within each genotype did not explain differences in transmission among HIV-1 genotypes. CONCLUSION: We have shown that HIV-1 genotypes might be associated with differential risk for vertical transmission. These findings provide the first evidence that HIV-1 genetic subtypes may play a role in rates of vertical transmission in an African setting.

The association between maternal HIV-1 infection and pregnancy outcomes in Dar es Salaam, Tanzania.

OBJECTIVE: To examine the association between maternal HIV infection and pregnancy outcomes controlling for potential confounding factors among a cohort of HIV-uninfected and HIV-infected pregnant women in Dar es Salaam, Tanzania. DESIGN: Prospective cohort study. METHODS: A cohort of 1,078 HIV-infected and 502 HIV-uninfected pregnant women between 12 and 27 weeks of gestation were enrolled and followed up until delivery. Multiple regression models were used to compare the risk of adverse pregnancy outcomes among HIV-uninfected women with those among HIV-infected women overall, and separately among asymptomatic or symptomatic HIV-infected women. RESULTS: No significant differences between HIV-uninfected women and HIV-infected women were observed in risks of fetal loss or low birthweight or in the weight, head circumference and gestational age of infants at birth. HIV-infected women were more likely to have severe immature infants (<34 weeks) than HIV-uninfected women (multivariate RR 1.54 [95% CI 0.90-2.48]; P= 0.05). There was a significantly higher risk of low birthweight (RR 2.29, 95% CI 1.34-3.92; P = 0.03) and prematurity (<37 weeks) (RR 1.93, 95% CI 1.35-2.77; P = 0.0003) among symptomatic HIV-infected women when compared with HIV-uninfected women. CONCLUSION: HIV-infected women, particularly those whoare symptomatic, are at a higher risk of adverse pregnancy outcomes.

Vitamin A supplements and diarrheal and respiratory tract infections among children in Dar es Salaam, Tanzania.

OBJECTIVE: To determine the effect of vitamin A supplementation on the risk of diarrhea and of acute respiratory infection. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Dar-es-Salaam, Tanzania. SUBJECTS: Six hundred eighty-seven children, 6 to 60 months old, hospitalized with pneumonia, who received vitamin A or placebo at baseline and at 4 and 8 months after discharge from hospital. MAIN OUTCOME VARIABLES: Incidence and duration of episodes of diarrhea and respiratory tract infections during the year after discharge from the hospital. RESULTS: Relative to those receiving placebo, children receiving vitamin A had a significantly smaller risk of severe watery diarrhea (multivariate odds ratio = 0.56, 95% CI = 0.32-0.99, P =.04) but a higher risk of cough and rapid respiratory rate (multivariate odds ratio = 1.67, 95% CI = 1.17-2.36, P =.004). Vitamin A supplementation was also associated with increased risk of acute diarrhea among normally nourished children or children with stunted growth but was relatively protective among children with wasting disease (P value for interaction =.01). The apparently increased risk of respiratory tract infection was limited to children who were seronegative for human immunodeficiency virus (HIV) (P value for interaction =.07). CONCLUSIONS: Vitamin A supplements provide a low-cost intervention against morbidity in HIV-infected and undernourished children. Supplements may also have serious non-lethal adverse outcomes in well-nourished individuals. Whether these apparent detrimental effects of vitamin A are transient or long-term needs to be examined.

Randomized trial of vitamin supplements in relation to vertical transmission of HIV-1 in Tanzania.

BACKGROUND: Observational studies suggest that poor nutritional status among HIV-infected pregnant women is associated with a higher risk of vertical transmission of HIV. METHODS: We randomized 1083 pregnant women infected with HIV-1 in a double-blind, placebo-controlled trial to examine the effects of supplements of vitamin A and/or multivitamins (excluding vitamin A) using a 2-x-2 factorial design. We report the effects of the supplements on HIV infection defined using polymerase chain reaction (PCR), or death up to 6 weeks postpartum. RESULTS: Of babies in the multivitamin arm 38, (10.1%) were HIV-positive at birth compared with 24 (6.6%) in the no-multivitamin arm (relative risk [RR] = 1.54; 95% CI, 0.94-2.51; p = .08). Of babies born to mothers in the vitamin A arm, 38 (10.0%) were HIV-positive at birth compared with 24 (6.7%) in the no-vitamin A arm (RR, 1.49; 95% CI, 0.91-2.43; p = 0.11). Neither multivitamins nor vitamin A had an effect on HIV status at 6 weeks among those who were HIV-negative at birth (RR = 1.04; 95% CI, 0.65-1.66; p = 0.88) and (RR = 1.30; 95% CI, 0.80-2.09; p = .29, respectively). Similarly, neither supplement was associated with being either HIV-infected or dead at birth (RR, 0.98; 95% CI, 0.76-1.27; p = .89 and RR, 1.01; 95% CI, 0.78-1.31; p = .95, respectively. A beneficial effect of multivitamins on birth weight was limited to babies who were HIV-negative at birth; babies in the multivitamin arm weighed +94 g more compared with those in the no-multivitamin arm (p = .02). Among babies who were HIV-positive at birth, the corresponding difference was -31 g (p = .82). CONCLUSIONS: Vitamin A and multivitamins did not affect the risk of vertical transmission of HIV in utero nor during the intrapartum and early breastfeeding periods. Multivitamins resulted in a significant improvement in birth weight of babies who were HIV-negative at birth but had no effect among those who were HIV-positive. The effect of vitamin supplements on HIV transmission through breastfeeding and on clinical progression of HIV disease is yet to be ascertained.

Increased intraocular pressure and visual field defects in high resistance wind instrument players.

OBJECTIVE: In this twofold study, part 1 aimed to determine whether the playing of high resistance wind instruments elevates intraocular pressure (IOP) and if so, to investigate the mechanism of IOP elevation and whether its magnitude differs while playing high resistance versus low resistance instruments. The purpose of part 2 was to evaluate whether high resistance players have a greater incidence of glaucomatous changes than other musicians. DESIGN: Three case reports and a cross-sectional study. PARTICIPANTS: Two players of high resistance instruments and one player of high and low resistance wind instruments participated in part 1 of the study. Nine high resistance wind players, 12 low resistance wind players, and 24 nonwind players were recruited among professional musicians in the Boston area to participate in part 2. INTERVENTION: In part 1, IOP and uveal thickness changes were measured by pneumatonometry and ultrasound biomicroscopy in two participants playing their high resistance wind instruments (trumpet and oboe) and in a third participant playing both high (trumpet) and low (clarinet and saxaphone) resistance instruments. Each musician in part 2 underwent medical and musical history, measurement of IOP, Humphrey visual field testing, slit-lamp examination, gonioscopy, and dilated examination. MAIN OUTCOME MEASURES: Intraocular pressure and uveal thickness changes, and visual field loss and optic nerve head appearance were the main parameters measured in part 1 and part 2, respectively. RESULTS: In part 1, pneumatonometry showed IOP elevation dependent on the force of blowing, and ultrasound biomicroscopy revealed uveal thickening associated with IOP elevation. The magnitude of IOP elevation was dependent on the amount of expiratory resistance provided by the particular instrument. Part 2 showed that life hours of high resistance wind instrument playing had a significant relationship to abnormal visual field (P = 0.03) and corrected pattern standard deviation (CPSD) scores (P = 0.007) in univariate logistic regression and univariate linear regression, respectively. A 0.011-unit increase in CPSD for each 1000 life hours of high resistance wind playing was found. CONCLUSIONS: High and low resistance wind musicians experience a transient rise in their IOP while playing their instruments as a result least in part of uveal engorgement. The magnitude of IOP increase is greater in high resistance wind players versus low resistance wind players. High resistance wind musicians had a small but significantly greater incidence of visual field loss (abnormal fields and increased CPSD scores) than other musicians, which was related to life hours of playing. The cumulative effects of long-term intermittent IOP elevation during high resistance wind instrument playing may result in glaucomatous damage, which could be misdiagnosed as normal-tension glaucoma.

Effects of long-acting versus short-acting calcium channel blockers among older survivors of acute myocardial infarction.

OBJECTIVE: Recent studies have highlighted the potentially harmful effects of short-acting calcium channel blockers, especially of the dihydropyridine type, in patients with coronary heart disease. Some have argued that long-acting calcium channel blockers are safer, but few outcome data exist. The objective of the study was to compare the occurrence of adverse outcomes among recipients of long-acting versus short-acting calcium channel blockers, with dihydropyridines and non-dihydropyridines compared separately. SETTING: The New Jersey Medicare population. DESIGN: A retrospective cohort study using linked Medicare and drug claims data. PARTICIPANTS: Older survivors of acute myocardial infarction (MI) occurring in 1989 and 1990. Eligible subjects had survived at least 30 days after the MI, participated in Medicare and a drug benefits program, and were prescribed a single type of either a long-acting or a short-acting calcium channel blocker within 90 days after the MI. MEASUREMENTS: The two outcome measures were rates of all-cause mortality and cardiac rehospitalization. Using separate Cox regression models for dihydropyridines (nifedipine, nicardipine) and non-dihydropyridines (diltiazem, verapamil), we examined these outcomes for recipients of long-acting compared with short-acting calcium channel blockers. RESULTS: Of the 833 patients eligible for the study, 160 were prescribed long-acting and 673 short-acting calcium channel blockers. Clinical characteristics of long-acting and short-acting users were comparable. During 2 years of follow-up, 221 deaths and 300 rehospitalizations occurred. Controlling for age, sex, race, and indicators of disease severity and comorbidity, the relative risk of dying for recipients of long-acting, compared with short-acting, dihydropyridines was .42 (95% confidence interval (CI), 0.21-0.86). For cardiac rehospitalization, the relative risk was 0.57 (95% CI, 0.34-0.94). For the long-acting versus short-acting nondihydropyridines, the adjusted relative risk of dying was 1.43 (95% CI, 0.88-2.32), and for cardiac rehospitalization, .65 (95% CI, 0.40-1.05). CONCLUSION: Use of long-acting dihydropyridine calcium channel blockers after acute MI was associated with substantially lower rates of cardiac rehospitalization and death compared with use of their short-acting counterparts. More data are needed to address the possibility that long-acting, compared with short-acting, non-dihydropyridines could decrease rehospitalization rates but increase mortality.

Evaluation of focal defects of the nerve fiber layer using optical coherence tomography.

OBJECTIVE: To analyze glaucomatous eyes with known focal defects of the nerve fiber layer (NFL), relating optical coherence tomography (OCT) findings to clinical examination, NFL and stereoscopic optic nerve head (ONH) photography, and Humphrey 24-2 visual fields. DESIGN: Cross-sectional prevalence study. PARTICIPANTS: The authors followed 19 patients in the study group and 14 patients in the control group. INTERVENTION: Imaging with OCT was performed circumferentially around the ONH with a circle diameter of 3.4 mm using an internal fixation technique. One hundred OCT scan points taken within 2.5 seconds were analyzed. MAIN OUTCOME MEASURES: Measurements of NFL thickness using OCT were performed. RESULTS: In most eyes with focal NFL defects, OCTs showed significant thinning of the NFL in areas closely corresponding to focal defects visible on clinical examination, to red-free photographs, and to defects on the Humphrey visual fields. Optical coherence tomography enabled the detection of focal defects in the NFL with a sensitivity of 65% and a specificity of 81%. CONCLUSION: Analysis of NFL thickness in eyes with focal defects showed good structural and functional correlation with clinical parameters. Optical coherence tomography contributes to the identification of focal defects in the NFL that occur in early stages of glaucoma.

A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virus-infected and uninfected children in Tanzania.

OBJECTIVES: To determine whether vitamin A supplements result in reduced mortality among HIV-infected and uninfected children. DESIGN: Randomized, double blind, placebo-controlled trial. METHODS: Starting in April, 1993, we randomized 687 children age 6 months to 5 years who were admitted to the hospital with pneumonia. Children who were severely malnourished or had clinical signs of vitamin A deficiency were excluded. At baseline children received placebo or 400 000 IU (or half that for infants) of vitamin A, in addition to standard treatment for pneumonia. They received further doses of the same regimen 4 and 8 months after hospital discharge. Sera from children were tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot tests. For positive children <15 months of age, HIV infection was confirmed by amplified heat-denatured HIV-p24 antigen assays with confirmatory neutralization assays. HIV status was ascertained for 648 of 687 enrolled children. The mean duration of follow-up was 24.4 months (SD = 12.1). RESULTS: Of 648 children 58 (9%) were HIV-infected. Compared with uninfected children, all-cause mortality was higher among HIV-infected children, as was mortality caused by pneumonia or diarrhea (P < 0.001 for each). Overall vitamin A supplements resulted in a 49% reduction in mortality [relative risk (RR), 0.51; 95% confidence interval (CI), 0.29 to 0.90, P = 0.02]. Vitamin A supplements reduced all-cause mortality by 63% among HIV-infected children (RR 0.37; CI 0.14 to 0.95, P = 0.04) and by 42% among uninfected children (RR 0.58, CI 0.28 to 1.19, P = 0.14). Vitamin A supplements were also associated with a 68% reduction in AIDS-related deaths (P = 0.05) and a 92% reduction in diarrhea-related deaths (P = 0.01). CONCLUSION: Vitamin A deficiency, which is common among children in many developing countries, is particularly severe among HIV-infected children. Our findings indicate that vitamin A supplements, a low cost intervention, reduce mortality of HIV-infected children.

Vitamin A supplementation and severity of pneumonia in children admitted to the hospital in Dar es Salaam, Tanzania.

Vitamin A deficiency and acute lower respiratory tract infections coexist as important public health problems in many developing countries. We carried out a randomized, double-blind, placebo-controlled trial to examine whether large doses of vitamin A given to Tanzanian children who are admitted to the hospital with nonmeasles pneumonia would reduce the severity of respiratory disease. Six hundred eighty-seven children were randomly assigned to receive either placebo or vitamin A [200 000 IU (60 mg retinol equivalents) for children > 1 y of age and 100000 IU (30 mg retinol equivalents) for infants] on the day of admission and another dose on the following day. Of the 346 children in the vitamin A group, 13 died in the hospital, compared with 8 of 341 children in the placebo group; the relative mortality was 1.63 (95% CI: 0.67, 3.97; P = 0.28). The mean number of days of hospitalization was the same in both groups (4.2 d). There were no differences between the vitamin A and placebo groups in the duration of hospital stay when examined within categories of children stratified by age, sex, breast-feeding status, nutritional status at baseline, or quartile of dietary vitamin A intake in the 4 mo before admission to the hospital. There were also no differences in the mean number of days of fever, rapid respiratory rate, or hypoxia, whether these endpoints were examined in the total number of subjects or in a subset with more severe clinical conditions at baseline. Large doses of vitamin A had no protective effect on the course of pneumonia in hospitalized Tanzanian children.

Laser trabeculoplasty: how little is enough?

BACKGROUND AND OBJECTIVE: The optimal number of laser applications for argon laser trabeculoplasty in patients with primary open-angle glaucoma has not been established. The purpose of this study was to determine the fewest number of burns necessary for clinically effective intraocular pressure reduction for these patients. PATIENTS AND METHODS: Using a prospective, randomized, collaborative study, the authors examined the relationship between the number of laser trabeculoplasty burns and intraocular pressure for patients with primary open-angle glaucoma. A total of 122 patients received either 50 burns to half of the trabecular meshwork (group 1) or 35 burns to one third of the trabecular meshwork (group 2). RESULTS: The mean baseline intraocular pressures were similar between group 1 (22.3 +/- 4.1 mm Hg [mean +/- SD]) and group 2 (22.8 +/- 5.0 mm Hg) (P = .58). Intraocular pressure reduction at 9 to 12 months, although significant in both groups (group 1: 4.4 +/- 3.0 mm Hg, P < .0001; group 2: 3.9 +/- 5.1 mm Hg, P < .0001), did not differ significantly between the two groups (P = .63). CONCLUSION: This study demonstrated that 35 burns may be as clinically effective as 50 burns in reducing the intraocular pressure in primary open-angle glaucoma patients.

Adverse outcomes of underuse of beta-blockers in elderly survivors of acute myocardial infarction.

OBJECTIVES: To study determinants and adverse outcomes (mortality and rehospitalization) of beta-blocker underuse in elderly patients with myocardial infarction; and whether the relative risks (RRs) of survival associated with beta-blocker use were comparable to those reported in the large randomized controlled trials (RCTs). SETTING: New Jersey Medicare population. DESIGN: Retrospective cohort design using linked Medicare and drug claims data from 1987 to 1992. PATIENTS: Statewide cohort of 5332 elderly 30-day acute myocardial infarction (AMI) survivors with prescription drug coverage, of whom 3737 were eligible for beta-blockers. MAIN OUTCOME MEASURES: beta-Blocker and calcium channel blocker use in the first 90 days after discharge and mortality rates and cardiac hospital readmissions over the 2-year period after discharge, controlling for sociodemographic and baseline risk variables. RESULTS: Only 21% of eligible patients received beta-blocker therapy; this rate remained unchanged from 1987 to 1991. Patients were almost 3 times more likely to receive a new prescription for a calcium channel blocker than for a new beta-blocker after their AMIs. Advanced age and calcium channel blocker use predicted underuse of beta-blockers. Controlling for other predictors of survival, the mortality rate among beta-blocker recipients was 43% less than that for nonrecipients (RR=0.57; 95% confidence interval [CI], 0.47-0.69). Effects on mortality were substantial in all age strata (65-74 years, 75-84 years, and > or = 85 years) and consistent with the results for elderly subgroups of 2 large RCTs. beta-Blocker recipients were rehospitalized 22% less often than nonrecipients (RR=0.78; 95% CI, 0.67-0.90). Use of a calcium channel blocker instead of a beta-blocker was associated with a doubled risk of death (RR= 1.98; 95% CI, 1.44-2.72), not because calcium channel blockers had a demonstrable adverse effect, but because they were substitutes for beta-blockers. CONCLUSIONS: beta-Blockers are underused in elderly AMI survivors, leading to measurable adverse outcomes. These data suggest that the survival benefits of beta-blockade after an AMI may extend to eligible patients older than 75 years, a group that has been excluded from RCTs.