The utility of verbal autopsies for identifying HIV-1-related deaths in Haitian children.

OBJECTIVE: To determine whether deaths among Haitian infants born to HIV-1-seronegative women could be distinguished from deaths among children born to HIV-1-seropositive women using the verbal autopsy technique. METHODS: Mothers of 315 Haitian children who died were interviewed about events leading to the child's death. Three physicians independently reviewed interview data and determined the probable cause of death without knowledge of maternal HIV-1 status or hospital records. The underlying causes of death assigned to the infants were analyzed to determine whether maternal HIV status could be predicted. RESULTS: There was good agreement among the physicians (kappa = 0.62) and 90% agreement between hospital records and the verbal autopsy diagnosis. Compared with children born to HIV-1-seronegative women, deaths in children born to HIV-1-seropositive mothers were more likely to be ascribed to a presumptive diagnosis of AIDS (37 versus 21%; P = 0.01). The sensitivity and specificity of verbal autopsies for identifying deaths associated with maternal HIV-1 infection ranged from 37 to 59% and from 69 to 79%, respectively, depending on the classification system used. The predictive positive value of a death believed to be consistent with pediatric HIV-1 infection was 26-30% and the predictive negative value was 85-90%. CONCLUSION: Verbal autopsies may be useful for distinguishing certain causes of death, but have limited utility for distinguishing deaths associated with maternal HIV-1 infection from deaths among children born to HIV-1-seronegative women.

HIV-1 in Haitian women 1982-1988. The Cite Soleil/JHU AIDS Project Team.

Pregnant Haitian women (n = 4,474) residing in a periurban slum were interviewed to identify risk factors for sexually transmitted diseases and sera were tested to identify antibodies to HIV-1 and syphilis. The seroprevalence rates for antibodies to HIV-1 increased from 8.9% in 1986 to 9.9% in 1987 and 10.3% in 1988. Sera obtained in 1982 from 533 mothers of young infants in the same community revealed that 7.8% were HIV-1 seropositive. Of women pregnant for the first time in 1986-1988, 6.6% were HIV-1 seropositive and 6.0% had a positive VDRL. The highest seropositivity rates (greater than 15%) were noted in women 20 to 29 years of age with a history of two or more sexual partners in the year prior to pregnancy. Factors independently associated with HIV-1 seropositivity in pregnant women by logistic regression analysis included being unmarried, age 20-29 years, having had more than one sex partner in the year prior to pregnancy, a positive serologic test for syphilis, and smoking. A dose-response effect was noted in the association between HIV-1 seropositivity and smoking. The association between smoking and HIV-1 infections could be confounded by unrecognized behavioral factors or due to a biologic effect of smoking. The continuing high HIV-1 seropositivity rates in pregnant women indicate that current preventive measures are insufficient and increased control efforts are urgently needed.

Childhood survival in Haiti: protective effect of measles vaccination.

To evaluate the impact of measles vaccination on survival of children residing in a periurban slum in Haiti, a total-population survey was conducted 2.5 years after completion of a one-time study of the serologic response to measles vaccine administered in the same population. Pregnancy histories from the 16,400 women in the population revealed that 1499 children had been born during a 7-month interval that would have made them eligible for participation in the measles vaccine program. Of these children, 1381 (92.1%) survived to 9 months of age, the median age that measles vaccine had been administered. Seventy-three infants had died between 9 and 39 months of age. Mortality of infants who were seronegative before receiving measles vaccine was significantly lower (P = .0013) than that of unvaccinated infants (3/235 vs 70/1056, respectively). Other factors positively associated with survival between 9 and 39 months of age included socioeconomic status (P = .0002), maternal literacy (P = .0020), maternal knowledge and use of oral rehydration solution (P = .0002), and an interval of greater than 24 months to the birth of the next younger sibling (P = .0012). Multivariate stepwise logistic regression analysis was used to evaluate the independent association of measles vaccination by adjusting for other factors that also correlated with survival and that might have been associated with maternal seeking of vaccinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Response to desipramine treatment in adolescent depression: a fixed-dose, placebo-controlled trial.

OBJECTIVE: To determine the efficacy and tolerability of the tricyclic antidepressant desipramine (DMI) in the treatment of DSM-III-R-diagnosed major depressive disorder in adolescents. METHOD: Sixty adolescents (42 female, 18 male; aged 15 to 19 years) diagnosed with major depressive disorder using clinical interview and Schedule for Affective Disorders and Schizophrenia for School-Age Children were randomized to receive either DMI (200 mg daily in divided doses) or placebo for six consecutive weeks following a 1-week placebo period. Treatment outcome was determined using the Hamilton Depression Rating Scale and the Beck Depression Inventory. Tolerability was determined using a symptom side effects scale. In addition, a variety of laboratory and cardiovascular monitoring was performed. RESULTS: No significant differences in treatment outcome between DMI- and placebo-treated groups were determined. Neither DMI, nor its metabolite 2-hydroxy-DMI, nor their ratio, was positively correlated to treatment outcome. The DMI group endorsed more side effects but there were no significant between-group differences in any laboratory, electrocardiographic, or other cardiovascular parameters apart from heart rate, which was increased in the DMI-treated group (p = .03). CONCLUSIONS: Given the findings of this study and our review of previously published reports of tricyclic antidepressant treatment in this population, the routine use of short-term (6 weeks) DMI in the treatment of adolescent depression is not supported by the data on hand. Further investigations into what constitutes optimal psychopharmacological treatment of adolescent depression are warranted.

An open naturalistic trial of fluoxetine in adolescents and young adults with treatment-resistant major depression.

ABSTRACT Fifteen adolescents and young adults (ages 16-24) with a DSM-III-R diagnosis of major depression, who failed to respond to prior treatment with tricyclic antidepressants, were treated in an open trial using fluoxetine. Of the 11 patients who completed a 6-7 week trial, 64% showed a therapeutic response (>/=50% change) on the Hamilton Depression Rating Scale (HDRS), and 73% showed a positive response when rated by the Clinical Global Impression Scale (CGI). Side effects generally were mild, and the most common were tremor, dry mouth, nausea, sweating, and decreased appetite. Sweating, drowsiness, dry mouth, tremor, and alopecia appeared more commonly than in adult studies. One patient became manic, and none showed an increase in suicidal ideation. A starting dose of 20 mg daily often was tolerated poorly, and patients generally did better with 5-10 mg daily for the first week. Some patients appeared to exhibit antidepressant responses on 5-10 mg daily. These preliminary data suggest that fluoxetine, in doses ranging from 5 to 40 mg daily, when used in combination with psychosocial treatments, may be an effective antidepressant in adolescents or young adults who have not previously responded to adequate tricyclic therapy. Double-blind placebo-controlled studies are needed to evaluate the potential efficacy of fluoxetine in treating major depression in adolescents and young adults.

Factors associated with poor nutritional status among community dwelling Lebanese elderly subjects living in rural areas: results of the AMEL study.

OBJECTIVES: This study aimed to assess the nutritional status, measured by MNA, and its association with socio-demographic indicators and health related characteristics of a representative sample of community dwelling elderly subjects. DESIGN: Cross-sectional study. SETTING: Community dwelling elderly individuals living in rural communities in Lebanon. PARTICIPANTS: 1200 elderly individuals aged 65 years or more. MEASUREMENTS: Socio-demographic indicators and health related characteristics were recorded during a standardized interview. Nutritional status was assessed through Mini Nutritional Assessment (MNA). The 5-item GDS score and the WHO-5-A score were used to assess mood, whereas Mini Mental Status (MMS) was applied to evaluate cognitive status. RESULTS: The prevalence of malnutrition and risk of malnutrition was 8.0% respective 29.1% of the study sample. Malnutrition was significantly more frequent in elderly subjects aged more than 85 years, in females, widowed and illiterate people. Moreover, participants who reported lower financial status were more often malnourished or at risk of malnutrition. Regarding health status, poor nutritional status was more common among those reporting more than three chronic diseases, taking more than three drugs daily, suffering from chronic pain and those who had worse oral health status. Also, depressive disorders and cognitive dysfunction were significantly related to malnutrition. After multivariate analysis following variables remained independently associated to malnutrition: living in the governorate of Nabatieh (ORa 2.30, 95% CI 1.35 -3.93), reporting higher income (ORa 0.77, 95% CI 0.61-0.97), higher number of comorbidities (ORa 1.22, 95% CI 1.12-1.32), chronic pain (ORa 1.72, 95% CI 1.24-2.39), and depressive disorders (ORa 1.66, 95% CI 1.47-1.88). On the other hand, better cognitive functioning was strongly associated with decreased nutritional risk (ORa 0.27, 95%CI 0.17-0.43). CONCLUSION: Our results highlighted the close relationship between health status and malnutrition. The identification of potential predictive factors may allow better prevention and management of malnutrition in elderly people.

Diffusion of peroxynitrite into the human platelet inhibits cyclooxygenase via nitration of tyrosine residues.

Peroxynitrite (ONOO(-)), a reactive oxidant produced by the reaction between nitric oxide and superoxide, was found to diffuse into the platelet cytosol and inhibit arachidonic acid-induced platelet aggregations with IC(50) value of 5.8 +/- 1.2 microM. A fluorescence assay established that ONOO(-) diffused into the platelet cytosol in a manner that was inhibited (50-70%) by 4, 4'-diisothiocyanatostilbene-2,2'-disulfonic acid, an inhibitor of HCO(3)(-)/Cl(-) anion exchanger. Treatment of platelets with (-)-epigallocatechin gallate (2 microM), a tea polyphenol and inhibitor of tyrosine nitration, abolished the inhibitory effect of ONOO(-) on arachidonate-induced aggregations by 88%. ONOO(-) (50-300 microM), added to platelets 1 min before arachidonic acid, inhibited (20-100%) formation of platelet cyclooxygenase (COX) products thromboxane A(2) and 12-hydroxyheptadecatrienoic acid. Interestingly, simultaneous addition of ONOO(-) and arachidonic acid stimulated eicosanoid production by 20 to 60%. The inhibition of thromboxane A(2) generation correlated with the 5- to 10-fold increase in the 3-nitrotyrosine levels of the platelet COX. Experiments with purified COX-1 and COX-2 also showed 9-fold increase of 3-nitrotyrosine levels, which correlated with decreased (93-98%) production of prostaglandin H(2) when ONOO(-) (50 microM) was added 1 min before arachidonic acid. However, the addition of ONOO(-) (50-100 microM) simultaneously with arachidonic acid increased prostaglandin H(2) formation by 30 to 60%. Thus, the inhibitory effect of ONOO(-) involved nitration of COX tyrosine residues, whereas the stimulatory effect was likely to be a result of ONOO(-) functioning as a peroxide activator of eicosanoid signaling. Increasing doses of ONOO(-) not only inhibited platelet COX but also induced formation of unique eicosanoids: iso-prostaglandin F(2alpha), epoxyhydroxyeicosatrienoic acid, and trans-arachidonic acids, suggesting that OH and NO(2) radicals were generated from ONOO(-) in platelets. Formation of ONOO(-) from NO and superoxide may function as a platelet hormone-like COX regulatory mechanism in inflammatory processes in which large amounts of these molecules are produced.

Response to desipramine treatment in adolescent major depression.

Thirty adolescents (ages 15-20) who met DSM-III-R criteria for major depressive disorder completed a double-blind, placebo-controlled, 6-week, fixed-dose (200 mg daily) study of desipramine (DMI). Thirty-three percent of the placebo group and 50 percent of the DMI group improved (greater than or equal to 50% change on the Hamilton Rating Scale for Depression). Subjective reports of adverse effects did not significantly differentiate the two groups. Major adverse effects, necessitating study discontinuation, occurred solely in the DMI group.

Premorbid and postmorbid school functioning in bipolar adolescents: description and suggested academic interventions.

OBJECTIVE: This study was designed to describe and evaluate the manner in which changes in school functioning are associated with bipolar affective disorder (BAD) in adolescence. METHOD: Pre- and post-illness onset school functioning data were collected from a sample of 44 adolescents with a DSM-III-R diagnosis of BAD. A variety of assessment measures were used, including personal interview, a review of school history and formal academic testing. RESULTS: Our findings reveal an overall profile of generally good to excellent premorbid school functioning in most adolescent onset bipolar patients, which subsequently shows marked deterioration along several dimensions (work effort, academic achievement, peer relationships and extracurricular involvement) following BAD onset. CONCLUSIONS: Onset of bipolar illness in adolescence negatively impacts on the teenager's ability to function effectively in the school environment. Specific program modifications are required in order to optimize the bipolar teenager's success at school. These are identified and discussed.

Acute water shortage and health problems in Haiti.

During a severe drought Port-au-Prince, Haiti, lost hydroelectric power for 10 weeks. This led to water shortages in areas of the city dependent on water supplied from electrically driven pumps. In a study of the impact of water restriction on disease, 400 families were randomly selected from two urban areas differentially affected by the water shortage. Disease in children was found to be related to quantity of water used, socioeconomic status, employment of head of household, and family size. The methods used in this study are recommended for the investigation of the relationship between water quantity and health.

Transmission of HIV-1 infections from mothers to infants in Haiti. Impact on childhood mortality and malnutrition. The CDS/JHU AIDS Project Team.

Of 4588 pregnant women in a high-risk Haitian population, 443 (9.7%) were serologically positive for the human immunodeficiency virus type 1 (HIV-1). Infants born to women who were HIV-1 seropositive were more likely to be premature, of low birth weight, and malnourished at 3 and 6 months of age than were infants born to women who were HIV-1 seronegative. Increased mortality was observed in infants born to women who were HIV-1 seropositive by 3 months of age. At 12 months of age, 23.4% of the infants born to women who were HIV-1 seropositive had died compared with 10.8% of the infants born to women who were HIV-1 seronegative; at 24 months of age, the mortality rates were 31.3% and 14.2%, respectively. Maternal HIV-1 infections resulted in an 11.7% increase in the overall infant mortality rate in this population. The estimated mother-to-infant HIV-1 transmission rate in these breast-fed infants was 25%, similar to the rates reported for non-breast-fed populations in the United States and Europe.

Response to measles vaccine in Haitian infants 6 to 12 months old. Influence of maternal antibodies, malnutrition, and concurrent illnesses.

To study the factors affecting the serologic response to measles vaccination, we evaluated 595 Haitian infants from 6 through 12 months of age, and their mothers, at the beginning of an immunization program. Thirty-four per cent of the infants had preexisting serologic evidence of measles infections by 11 months of age. Among infants more than nine months of age, those who had had measles had a significantly lower nutritional status than those who had not (P less than 0.01). After vaccination, seroconversion rates increased from 45 per cent at 6 months to 100 per cent at 12 months. The lowest rate of vaccine failure compatible with acceptably low rates of natural infections could be achieved by vaccination after eight months of age. Infants born to mothers with low levels of antibody to measles (hemagglutination-inhibition antibody titers less than 1:40) were significantly more likely to have had natural measles (P less than 0.01) or to have seroconversion after vaccination (P less than 0.001) at 6 to 10 months of age than were infants born to mothers with higher of age than were infants born to mothers with higher titers. Malnutrition and acute infections did not affect seroconversion rates. These data support the World Health Organization recommendation to administer measles vaccine in under-developed countries as soon after nine months of age as possible, regardless of nutritional status or the presence of minor illnesses.