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Biomedical subjects

W D Johnson

Publications and source records attributed to W D Johnson.

At least 37 records · Page 2Linked to original sources

IS1245 genotypic analysis of Mycobacterium avium isolates from patients in Brazil.

OBJECTIVE: Disseminated Mycobacterium avium infection is an emerging opportunistic disease among patients with acquired immunodeficiency syndrome (AIDS) in Brazil. The mode of transmission of M. avium in a developing country setting needs to be better characterized. METHODS: Mycobacterium avium strain collections in São Paulo and Rio de Janeiro were analyzed according to the strains' IS1245 DNA gel electrophoretic migration patterns. Medical records of the patients from whom M. avium isolates were available were reviewed, and their demographic characteristics were stratified according to the isolates' IS1245 DNA fingerprint patterns. RESULTS: Of 105 patients, 33 (31%) with M. avium isolated between 1990 and 1994 had strains having IS1245 patterns identical in patterns seen in isolates from two or more patients (designated as cluster pattern strains). Cluster pattern strains were isolated from 21 (39%) of 54 patients with disseminated infection (defined as infection due to M. avium isolated from a sterile site in an adult patient). Six of the cluster pattern strains were isolated only from sterile sites. In São Paulo, cluster pattern strains were significantly more likely to be isolated from patients with disseminated disease. CONCLUSIONS: These preliminary observations suggest that in large cities of Brazil, a high proportion (at least 39%) of disseminated M. avium infections in patients with AIDS results from a recent transmission. Some strains of M. avium may be more likely to cause disseminated disease than others after an infection.

AIDS-Related Opportunistic Infections↗

The natural history of human immunodeficiency virus 1 infection in Haitian infants.

OBJECTIVES: The current study followed HIV-infected women through pregnancy and their infants through the first 2 years of life to determine the rate of vertical transmission of HIV infection from Haitian women, factors in maternal health and obstetrical history that might influence such transmission and the natural history of HIV infection in their affected offspring. STUDY DESIGN: The medical histories of 81 infants born of HIV-infected women and of a control group of 88 infants born to uninfected women were documented with close clinical and serologic follow-up. In addition to standard tests for persistence of HIV antibodies, the use of acid-dissociated p24 assays enabled us to assign some additional infants to the HIV-infected cohort. RESULTS: Transmission could be documented in 27% of infants born to HIV-infected women. Excess early deaths occurred in infants of HIV-infected women in Port-au-Prince with 60% of infected infants dead by 6 months of age. This is a more accelerated mortality than that in a group of 42 HIV-infected infants born of Haitian mothers living in Miami where 10% were dead at 6 months. Clinically, in 6 of 19 deaths in HIV-infected children in Haiti, failure to thrive and gastroenteritis lead to a systemic infection manifested as meningitis, sepsis or pneumonia as the immediate cause of death. CONCLUSIONS: Early mortality attributable to perinatally acquired AIDS was identified in Haiti. The comparison of data from Miami and Port-au-Prince suggests that environmental exposures in developing countries may be more operative in this early mortality than viral strain or maternal host factors, both of which might be expected to be similar between the two groups of Haitian ethnicity.

Adult↗

Hypothesis testing and confidence interval construction in 2 x 2 tables of correlated proportions.

The 2 x 2 table is an invaluable tool for displaying bivariate binary data. It is easy to find examples of correlated binary response in biopharmaceutical experiments and clinical research and analysis of these data is a current research topic. The most common hypothesis tested for 2 x 2 tables of correlated proportions is that of homogeneity of the marginal proportions or, equivalently, the hypothesis of table symmetry. The 2 x 2 table of correlated proportions is rich with information and we present a survey of some of the analyses relevant for these data. Using asymptotic theory, we develop estimators of relevant parameters and associated test statistics that are of interest. We discuss interval estimation using arguments proposed by Quesenberry and Hurst (1) and Goodman (2). These interval estimators do not rely on estimation of the covariance matrix and are not necessarily equivalent to those obtained using modified chi-square statistics.

Analysis of Variance↗

On the singularity of the covariance matrix for estimates of multinomial proportions.

It is well known that the covariance matrix for the multinomial distribution is singular and, therefore, does not have a unique inverse. If, however, any row and corresponding column are removed, the reduced matrix is nonsingular and the unique inverse has a closed form. We elucidate some of the properties of the multinomial covariance matrix and its reduced forms. We state and prove a theorem that gives insight into the singularity and its removal. Based on these results, we establish that the covariance matrix for the multinomial distribution is positive semidefinite and that the reduced matrix is positive definite. In addition, we show that the determinant of the reduced matrix is invariant to the particular row and column that are removed. Goodness-of-fit statistics, including Pearson's chi-square, and justification of the degrees of freedom follow from the multivariate central limit theorem once the singularity is removed.

Analysis of Variance↗

The role of betamethasone in the treatment of acute exudative pharyngitis.

OBJECTIVE: To compare betamethasone with placebo as an adjuvant to antibiotic therapy in the treatment of acute exudative pharyngitis. METHODS: The study was a randomized, doubled-blind, placebo-controlled, single-center, parallel, outpatient clinical trial. After consent was obtained, each patient was asked to rate his or her pain on a 10-cm numbered visual analog scale (VAS; 0-10). All of the patients received injectable benzathine penicillin. If allergic to penicillin, they were started on a 10-day course of polyenteric-coated erythromycin (PCE). Each patient was randomized to receive either i.m. betamethasone or i.m. placebo. All patients were contacted by telephone at 24 and 48 hours by one of the study investigators and asked to rate their pain based on another VAS. If their pain was not resolved by 48 hours, they were called again daily between the third and seventh days after the initial visit to determine the time of pain resolution. RESULTS: A total of 92 patients were enrolled in the study, with 46 randomized to receive placebo and 46 to receive betamethasone. Eight patients were excluded from the statistical analysis because of inability to obtain follow-up. Demographic comparison showed that gender distributions, ages, mean initial pain scores, mean times to the first and second follow-up calls, and treatment regimens were similar in the 2 groups. There were significantly better pain scores for the betamethasone group at first follow-up (p = 0.0005), at second follow-up (p = 0.004), and in number of hours until relief of pain (p = 0.004). When only those patients with a positive culture for a streptococcus species were analyzed, there also were significant reductions in pain score at the first (p = 0.006) and second (p = 0.02) follow-up visits. CONCLUSION: Pain relief was greater and more rapid in patients treated with betamethasone as an adjuvant therapy in acute exudative pharyngitis.

Acute Disease↗

Confidence intervals for differences in correlated binary proportions.

An experiment to assess the efficacy of a particular treatment or process often produces dichotomous responses, either favourable or unfavourable. When we administer the treatment on two occasions to the same subjects, we often use McNemar's test to investigate the hypothesis of no difference in the proportions on the two occasions, that is, the hypothesis of marginal homogeneity. A disadvantage in using McNemar's statistic is that we estimate the variance of the sample difference under the restriction that the marginal proportions are equal. A competitor to McNemar's statistic is a Wald statistic that uses an unrestricted estimator of the variance. Because the Wald statistic tends to reject too often in small samples, we investigate an adjusted form that is useful for constructing confidence intervals. Quesenberry and Hurst and Goodman discussed methods of construction that we adapt for constructing confidence intervals for the differences in correlated proportions. We empirically compare the coverage probabilities and average interval lengths for the competing methods through simulation and give recommendations based on the simulation results.

Analysis of Variance↗

The validity and power of tests for equality of two correlated proportions.

With measurements taken on subjects over time, on matched pairs of subjects or on clusters of subjects, the data often contain pairs of correlated dichotomous responses. McNemar's test is perhaps the best known test to compare two correlated binomial proportions. The salient feature of McNemar's test is that we compute the variance of the contrast estimator under the restriction that the null hypothesis is true. Wald's test, on the other hand, does not require that restriction. As a consequence, Wald's statistic is always greater in magnitude than McNemar's statistic when the marginal proportions are unequal, but there is a problem with the validity of both McNemar's test and Wald's test with small to moderate samples. There have been various modifications suggested for McNemar's test to improve its performance. We propose a modified Wald's test that is valid in small to moderate samples and maintains good power. We also evaluate the performance of McNemar's test and Wald's test with and without modifications to enhance validity as well as the performance of the large sample likelihood ratio test and an exact test of the equality of correlated binomial proportions. In a smaller study, we compare the behaviour of a test based on the James-Stein estimator of the common odds ratio proposed by Liang and Zeger to McNemar's test and Wald's test.

Child↗

A SAS macro for constructing simultaneous confidence intervals for multinomial proportions.

Quesenberry and Hurst (1964), Goodman (1965) and Fitzpatrick and Scott (1987) proposed simultaneous construction of confidence intervals for multinomial proportions, however. statistical computing packages do not generally give one the option of specifying the type of construction to be used. We have written a SAS macro using PROC IML that takes multinomial cell counts as input and returns simultaneous confidence intervals with the user-specified coverage probability. Two main features of the macro are its ease of use and its flexibility in allowing the user to choose among six methods of constructing confidence intervals for multinomial proportions. Based on simulation May and Johnson (1997) recommended the intervals proposed by Goodman (1965) in most practical applications.

Binomial Distribution↗

Infectious considerations in the world traveler.

Travel-associated dermatoses are among the six most frequent medical problems encountered by international travelers. Skin disorders caused by parasites previously confined to the tropics are seen with increasing frequency by physicians in nonendemic areas. Cutaneous manifestations may provide important clues to the underlying infection. This article describes the epidemiology, assessment, and management of important parasitoses with cutaneous involvement.

Asia↗

A comparison of susceptibility results of the Bacteroides fragilis group and other anaerobes by traditional MIC results and statistical methods.

Antimicrobial susceptibility is compared by MIC values reflecting activity by weight and/or percentage of strains resistant. This study establishes these parameters in vitro in the traditional fashion and extends analysis statistically for various groups of anaerobic bacteria. Mode MIC, MIC50, MIC90 values and percentage of strains resistant indicated comparable activity for most of the beta-lactams. Geometric and arithmetic MICs suggested ceftizoxime to be the most active beta-lactam. Statistical analysis of all log2 values showed that metronidazole was the most active followed by clindamycin and that ceftizoxime was significantly more active than cefotaxime, piperacillin, ceftriaxone or cefoxitin.

Bacteria, Anaerobic↗

Clinical manifestations of human immunodeficiency virus infection in Haitian children.

OBJECTIVE: This study was designed to describe the characteristics of HIV-1 infection in children in Haiti and to assess its impact on morbidity and mortality. BACKGROUND: Throughout the developing world the female-to-male ratio of HIV-1 infection approaches 1:1, leading to a tremendous burden of vertically transmitted HIV-1 infection. The frequency of transmission, progression of disease and AIDS-defining clinical illnesses are not as well-described in this setting as in the industrial world. METHODS: Children were identified as being HIV-1-seropositive from case findings among family members of individuals presenting for screening at the GHESKIO Centers in Port-au-Prince, Haiti. Children who were seronegative from the same population were also enrolled and both groups were followed at regular intervals. The clinical course and illnesses associated with HIV infection were documented. RESULTS: Rapid progression to symptomatic disease and death was seen and a battery of physical findings enabled a clinician over time to assign with high sensitivity and specificity the diagnosis of AIDS to a child. Although many findings are similar, the presentation of HIV-1 infection in Haiti differed in significant ways from observations in the industrial world. In particular signs of malnutrition, failure to thrive and tuberculosis were more common in the Haitian population. CONCLUSION: Pediatric HIV-1 infection in Haiti differs significantly from the illness in the industrial world. Early mortality poses a particular difficulty in diagnosing and ascribing mortality to HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

Testing for treatment effect in the presence of regression toward the mean.

We are often faced with the statistical problem of evaluating the effect of a treatment in the extreme of a population. This requires taking measurements on truncated random variables and, hence, it becomes necessary to take proper account of the effect of regression toward the mean. The usual statistical procedures are inappropriate for testing treatment effect in the presence of regression toward the mean. Likelihood ratio and score tests based on truncated distributions should provide valid statistical inferences in these situations. We conducted simulation studies to investigate the properties of these methods and found that the likelihood ratio test performs well even when the sample size is moderate, whereas the score test does not seem to control the nominal significance level. We compared the likelihood ratio test to a regression-based t-test, assuming the mean of the baseline distribution to be known, and found the likelihood ratio test more powerful. In the case where the baseline mean is unknown, we also investigated Wald's test and compared it with the likelihood ratio test and score test with respect to validity and power using simulation. Wald's test and the score test do not control the nominal significance level unless the sample size is extremely large. Overall, the likelihood ratio test has the best performance among all the methods studied. The proposed likelihood ratio test is illustrated using an example of a cholesterol study.

Biometry↗

Tuberculosis and HIV infection among female inmates in São Paulo, Brazil: a prospective cohort study.

Prison populations are at increased risk of both human immunodeficiency virus (HIV) and Mycobacterium tuberculosis infections, but among female inmates information on such risks remains scarce, especially in developing countries. Between October 1992 and November 1993, 350 women incarcerated at a prison in São Paulo, Brazil, were prospectively evaluated for HIV and M. tuberculosis infection and disease. Among them, 87 (25%) were HIV seropositive, and 20 (5.7%) had tuberculosis (TB). During the incarceration period, the purified protein derivative test conversion rate was 29% for HIV-positive and 32% for HIV-negative women. However, the incidence of TB was 9.9 per 100 person-years for HIV-positive and 0.7 per 100 person-years of incarceration for HIV-negative women (p < 0.0001). A multivariate analysis indicated that HIV infection (p < 0.0001) and incarceration time < 12 months (p < 0.05) were each associated with TB. These findings indicate that new transmissions of M. tuberculosis infection are common among female inmates and that HIV-infected women are more likely to acquire active disease during the first 12 months of incarceration. Because of their role in childbearing and care female inmates are an important potential source of transmission of M. tuberculosis, and new strategies to control the spread of TB in prisons need to be developed.

Adolescent↗

Heterosexual transmission of HIV in Haiti.

BACKGROUND: Despite the importance of human immunodeficiency virus (HIV) transmission through heterosexual contact, the incidence of HIV infection in heterosexual cohorts has not been well studied, particularly in the developing world. OBJECTIVE: To 1) determine the incidence of HIV infection in discordant heterosexual couples (couples in which one partner had HIV infection and the other did not) in Haiti and 2) assess risk factors for and methods of preventing HIV infection. DESIGN: Prospective study. SETTING: National Institute for Laboratory Research, Portau-Prince, Haiti. PARTICIPANTS: 475 HIV-infected patients and their noninfected regular sex partners. MEASUREMENTS: Patients and their partners were evaluated at 3- to 6-month intervals for HIV infection, sexually transmitted diseases, and sexual practices. The efficacy of counseling and provision of free condoms was also evaluated. RESULTS: Among the 177 couples who remained sexually active during the prospective study period, 20 seroconversions to HIV positivity occurred, for an incidence rate of 5.4 per 100 person-years (95% CI, 5.16 to 5.64 per 100 person-years). Thirty-eight couples (21.5%) discontinued sexual activity during the study. Only 1 seroconversion occurred among the 42 sexually active couples (23.7% of the 177 sexually active couples) who always used condoms. In contrast, the incidence in sexually active couples who infrequently used or did not use condoms was 6.8 per 100 person-years (CI, 6.49 to 7.14 per 100 person-years). Transmission of HIV was associated with genital ulcer disease, syphilis, and vaginal or penile discharge in the HIV-negative partner and with syphilis in the HIV-infected partner. CONCLUSION: Counseling and the provision of free condoms contributed to the institution of safe sex practices or abstinence in 45% of discordant heterosexual couples. However, 55% of couples reported that they continued to have unprotected sex, resulting in an incidence of HIV infection of 6.8 per 100 person-years.

Condoms↗

Exceptional chemopreventive activity of low-dose dehydroepiandrosterone in the rat mammary gland.

To determine if the chemopreventive activity of dehydroepiandrosterone (DHEA) in the rat mammary gland can be dissociated from its toxicity, two studies were conducted in which low doses of DHEA were administered alone and in combination with other agents to rats treated with N-methyl-N-nitrosourea. Beginning 1 week prior to administration of 35 mg N-methyl-N-nitrosourea per kg body weight, groups of 20 female Sprague-Dawley rates were fed AIN-76A diet supplemented with DHEA alone (800 or 400 mg/kg diet), DHEA + tamoxifen (80 or 40 microgram/kg diet), DHEA + carbenoxolone (3500 or 1750 mg/kg diet), or DHEA + tamoxifen + carbenoxolone. When administered alone at either 800 or 400 mg/kg diet, DHEA reduced mammary cancer incidence from >70% in dietary controls to 0%; mammary cancer incidence from >70% in dietary controls to 0%; mammary cancer incidence in all DHEA combination regimens was also < or = 5%. The dose levels of DHEA used induced no toxicity or alteration in body weight gain. These results indicate that dietary supplementation with low doses of DHEA has chemopreventive efficacy greater than or equal to that of endocrine ablation. This protection may be mediated by the induction of differentiation in the mammary parenchyma.

Animals↗