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Biomedical subjects

D C Perlman

Publications and source records attributed to D C Perlman.

At least 19 recordsLinked to original sources
PubMed1999

Doing a shotgun: a drug use practice and its relationship to sexual behaviors and infection risk.

There has been a rise in the frequency with which inhalational routes such as smoking are used for illicit drug use. A growing population of new inhalational drug users augments the pool of individuals at risk for transition to injection drug use. Further, illicit drug smoking has been implicated in the transmission of a variety of pathogens by the respiratory route, and crack smoking has been associated with an increased risk of HIV infection, particularly through the exchange of high-risk sex for drugs. Shotguns are an illicit drug smoking practice in which smoked drugs are exhaled or blown by one user into the mouth of another user. We conducted a series of ethnographic observations to attempt to characterize more fully the practice of shotgunning, the range of associated behaviors, and the settings and contexts in which this practice occurs. Shotguns may be seen as a form of drug use which has close ties to sexual behaviors, and which has both pragmatic and interpersonal motivations, combining in a single phenomenon the potential direct and indirect risk of disease transmission by sexual, blood borne and respiratory routes. These data support the need to develop and evaluate comprehensive risk reduction interventions, which take into consideration the relationships between interpersonal and sexual behaviors and specific forms of drug use.

Administration, Inhalation↗
PubMed1999

Knowledge of tuberculosis among drug users. Relationship to return rates for tuberculosis screening at a syringe exchange.

Tuberculosis is an important health issue among drug users. We sought to evaluate active drug users' (DUs) knowledge of tuberculosis (TB) and to assess the relationship between TB knowledge and attitudes and tuberculin skin test (TST) return rates at a syringe exchange program. DUs were recruited at a syringe exchange program in New York City, were interviewed and offered TSTs, and received $15.00 upon returning for TST reading. The questionnaire evaluated knowledge of TB transmission, prevention, and treatment. From March 13, 1995 to January 31, 1996, 610 of 650 (94%) of DUs approached agreed to participate. Of these, 80% had previous TSTs within the past 2 years and 20% were known to be HIV infected. Almost all knew that TB is contagious and more than two thirds knew that TB is treatable and that TB preventive therapy existed. However, fewer than half knew that HIV-related TB could be treated, 30% thought TB could be treated without a medical doctor, and the majority (70%) thought a reactive TST implied infectivity. The rate of return for TST reading was 93%. In multivariate analysis, those who knew that HIV-related TB was curable were more likely to return for TST reading (odds ratio 2.0; 95% confidence interval 1.04 to 3.95; p = .03). The high acceptance and return rates suggest that TB services can be incorporated into syringe exchange programs. However, several important gaps in TB knowledge existed in this population at high risk of TB, which may impact on adherence and which support the need for TB education for drug users.

Adult↗
PubMed1999

Predictors for multidrug-resistant tuberculosis among HIV-infected patients and response to specific drug regimens. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) and the AIDS Clinical Trials Group (ACTG), National Institutes for Health.

SETTING: Mortality associated with human immunodeficiency virus (HIV) related multidrug-resistant tuberculosis (MDR-TB) is reduced with effective early therapy. Identifying predictors of, and effective regimens for, MDR-TB is critical. OBJECTIVE: A multicenter prospective study was initiated to 1) determine the demographic, behavioral, clinical and geographic risk factors associated with the occurrence of MDR-TB among HIV-infected patients, and 2) to evaluate the overall survival and clinical response of MDR-TB patients treated with specific drug regimens. METHODS: Patients were prospectively evaluated for MDR-TB. Information included history of prior treatment for tuberculosis, close contact with a known case of MDR-TB, and residence in a facility with known or suspected MDR-TB transmission. Patients with known MDR-TB, or those suspected to be at high risk, were offered enrollment in a treatment pilot study. Study drugs included levofloxacin and at least two additional drugs to which the patient's isolate was known, or most likely, to be susceptible. Survival was the primary endpoint. RESULTS: Complete data are available for 156 HIV-infected patients with confirmed tuberculosis. Sixteen (10%) had MDR-TB. Only a history of prior tuberculosis treatment was associated with MDR-TB in multivariate analysis (OR = 4.4, P < 0.02). Twelve patients with MDR-TB enrolled in the treatment pilot had a median CD4 cell count of 51/mm3. The cumulative probability of survival at one year was 75% (95% CI 50.5-99.5) and at 18 months, 65.6% (95% CI 38.1-93.1). Toxicity requiring discontinuation of medications occurred in two patients. CONCLUSIONS: A history of treatment for tuberculosis was the only predictor for MDR-TB in a cohort of HIV-infected patients with tuberculosis. In addition, this prospective study supports the results of prior retrospective studies that effective treatment impacts on mortality. Current second-line treatment, including high dose levofloxacin, appears to be reasonably well tolerated.

AIDS-Related Opportunistic Infections↗
PubMed1998

Experience with a cross-study endpoint review committee for AIDS clinical trials. Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVES: To describe the methods and results of a standardized system for clinical endpoint determination for defining and reviewing endpoints in clinical trials for HIV-infected individuals. DESIGN: A system was developed utilizing standard definitions for the 24 diagnoses or clinical events that serve as trial endpoints and together define the combined endpoint 'progression of HIV disease. A common set of case report forms were used for all trials. Thus, an event of Pneumocystis carinii pneumonia (PCP), for example, for a subject co-enrolled in an antiretroviral trial and a PCP prophylaxis trial was only reported once. METHODS: A central committee was established to define clinical events and review endpoints across all studies. Events were classified according to established criteria for confirmed, probable and possible levels of certainty. RESULTS: This report describes the methods used to ascertain and review endpoints, and summarized 2299 clinical events for 8097 subjects enrolled in one or more of nine clinical trials. Data on the diagnostic certainty of events and agreement between site clinicians and the endpoint committee are presented. CONCLUSIONS: Uniform classification of endpoints across AIDS clinical trials can be accomplished by multicenter, multitrial organizations with standardized definitions and review of endpoint documentation. Our experience suggests that nurse coordinators reviewing all submitted endpoints for every trial are warranted and the need for external review by a clinical events committee may depend on the type of trial conducted.

AIDS-Related Opportunistic Infections↗
PubMed1998

Evaluation of an intensive intermittent-induction regimen and duration of short-course treatment for human immunodeficiency virus-related pulmonary tuberculosis. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) and the AIDS Clinical Trials Group (ACTG).

This study examined whether adding levofloxacin to a standard four-drug regimen improved the 8-week culture response and compared effectiveness of 9 versus 6 months of intermittent therapy for human immunodeficiency virus-related pansusceptible pulmonary tuberculosis. Patients were randomized to receive either four or five drugs, the fifth being levofloxacin. Patients who completed induction therapy were randomized to complete 9 versus 6 months of intermittent therapy with isoniazid and rifampin. In the randomized induction phase, 97.3% of patients in the four-drug group and 95.8% in the five-drug group had sputum culture conversion at 8 weeks (P = 1.00). In the continuation phase, one patient (2%) assigned to 9 months and two patients (3.9%) assigned to 6 months of therapy had treatment failure/relapse (P = 1.00). In conclusion, this study showed that levofloxacin added no benefit to a highly effective, largely intermittent, four-drug induction regimen. Both 9 and 6 months of intermittent therapy were associated with low treatment failure/relapse rates.

AIDS-Related Opportunistic Infections↗
PubMed1997

Widespread dissemination of a drug-susceptible strain of Mycobacterium tuberculosis.

In New York City, a large proportion of new tuberculosis cases has been caused by 1 drug-susceptible strain (called C strain) of Mycobacterium tuberculosis. Between 1991 and 1994, among >600 tuberculosis patients consecutively identified in four large hospitals in the city, 54 with C strain, 69 with non-C cluster pattern strains, and 42 with noncluster pattern strains were studied. Susceptibility to reactive nitrogen intermediates (RNI) of selected isolates was compared. In a case-control analysis, 51% of patients with C strain, 28% with non-C cluster strains (P < .05), and 14% with noncluster strains (P < .01) were found to be injection drug users. C strain but not 13 other unrelated isolates were resistant to RNI. Injection drug use may provide a selective pressure for an RNI-resistant tubercle bacillus to emerge, which may give the organism a biologic advantage and explain the widespread dissemination of C strain M. tuberculosis within the city.

Adolescent↗
PubMed1997

Variation of chest radiographic patterns in pulmonary tuberculosis by degree of human immunodeficiency virus-related immunosuppression. The Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). The AIDS Clinical Trials Group (ACTG).

Our aim was to evaluate the effect of human immunodeficiency virus (HIV) disease stage on chest radiographic (CXR) findings among patients with HIV-related pulmonary tuberculosis (TB). Data are from a prospective multicenter treatment trial for HIV-related TB. Baseline CXR findings and CD4+ lymphocyte counts were compared among patients with HIV-related TB. Data from published studies describing CXR findings in HIV-infected patients were reviewed and a pooled-data analysis was conducted. Of 135 patients with culture-confirmed HIV-related TB, 128 had both CXR and CD4+ lymphocyte data. CD4+ lymphocyte counts of < 200/mm3 (n = 98) were significantly associated with hilar/mediastinal adenopathy on CXR (30%, vs. 7% with counts > or = 200/mm3; P = .01); counts of > or = 200/mm3 (n = 30) more frequently were associated with cavitation (20% vs. 7%; P = .08). Analyses of these results, pooled with other published data, confirmed these findings. This study demonstrates associations of certain CXR findings with HIV disease stage. Knowledge of the degree of immunosuppression is important when evaluating CXR findings in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1997

Clinical features and outcomes of HIV-related cytomegalovirus pneumonia.

OBJECTIVE: To describe the characteristics and outcomes of HIV-infected patients with biopsy-proven cytomegalovirus (CMV) pneumonia. DESIGN: Retrospective study. SETTING: A 900-bed acute facility in New York City. PATIENTS: Eighteen HIV-infected patients with pathologically confirmed CMV inclusions in lung tissue without other pathogens and 36 control patients with biopsy-proven Pneumocystis carinii pneumonia (PCP) selected for comparisons by computer-generated random sequential numbers. MAIN OUTCOME MEASURES: Demographic, clinical, laboratory, radiological findings, and in-hospital mortality. RESULTS: Eighteen HIV-infected patients were found to have CMV lung infection alone. Pathologic findings were pneumonitis (n = 11); pneumonitis and pulmonary vasculitis (n = 1); and CMV inclusions alone (n = 6). All presented with respiratory symptoms (cough or dyspnea), 89% had fever, 83% had radiological abnormalities, and 56% had severe hypoxemia. The pulmonary presentation was similar except for higher lactate dehydrogenase (median, 449 versus 329 IU/l; P = 0.03) and presence of pleural effusions (33 versus 0%; P = 0.001) in CMV patients. Multivariate analysis showed that CD4 counts < or = 12 x 10(6)/l (odds ratio; 9.2; P = 0.029) and extrapulmonary CMV (odds ratio, 20.4; P = 0.039) were independently associated with CMV pneumonia. Seventeen patients received specific anti-CMV therapy for a mean of 22 +/- 13 days. In-hospital mortality was higher in patients with CMV pneumonia (odds ratio, 11.9; P = 0.002). The median time from admission to death was 31 days. CONCLUSIONS: CMV lung infection was seen in severely immunosuppressed HIV-positive patients and associated with clinical pneumonitis with high early mortality. Although the clinical features resemble PCP, the presence of extrapulmonary CMV disease should suggest the diagnosis of CMV pneumonia.

AIDS-Related Opportunistic Infections↗
PubMed1997

Susceptibility to levofloxacin of Myocobacterium tuberculosis isolates from patients with HIV-related tuberculosis and characterization of a strain with levofloxacin monoresistance. Community Programs for Clinical Research on AIDS 019 and the AIDS Clinical Trials Group 222 Protocol Team.

OBJECTIVE: To characterize the susceptibility to levofloxacin of clinical isolates of Mycobacterium tuberculosis (MTB) obtained from patients with HIV-related tuberculosis and to characterize the molecular genetics of levofloxacin resistance. DESIGN AND METHODS: Isolates from culture-positive patients in a United States multicenter trial of HIV-related TB were tested for susceptibility to levofloxacin by minimum inhibitory concentration (MIC) determinations in Bactec 7H12 broth. Automated sequencing of the resistance determining region of gyrA was performed. RESULTS: Of the 135 baseline MTB isolates tested, 134 (99%; 95% exact binomial confidence interval, 95.9-99.9%) were susceptible to levofloxacin with an MIC < or = 1.0 microg/ml. We identified a previously unrecognized mis-sense mutation occurring at codon 88 of gyrA in a levofloxacin mono-resistant MTB isolate obtained from a patient with AIDS who had received ofloxacin for 8 months prior to the diagnosis of tuberculosis. CONCLUSIONS: Clinical MTB isolates from HIV-infected patients were generally susceptible to levofloxacin. However, the identification of a clinical isolate with mono-resistance to levofloxacin highlights the need for circumspection in the use of fluoroquinolones in the setting of potential HIV-related tuberculosis and for monitoring of rates of resistance of MTB isolates to fluoroquinolones.

AIDS-Related Opportunistic Infections↗
PubMed1997

Implementation of universal directly observed therapy at a New York City hospital and evaluation of an out-patient directly observed therapy program.

SETTING: Directly observed therapy (DOT) program for tuberculosis (TB) at a New York City hospital. OBJECTIVE: To describe a specific TB DOT program model utilizing active prospective identification of inpatients, and identify factors associated with patient acceptance of voluntary DOT and with their retention in therapy. METHODS: Recruitment for DOT by daily surveillance of in-patients. DOT was offered as the patient's choice together with concrete services and incentives. On-site DOT was offered in an out-patient clinic. Outreach efforts were initiated when a patient missed one or more DOT visit. RESULTS: During the study period, 95% of 176 in-patients with TB were evaluated for DOT. Of the 137 who were eligible for DOT, 85% (95% confidence interval [CI], 77.5% to 90%) elected to receive DOT. Illicit drug use was independently associated with a higher likelihood of acceptance of DOT (odds ratio[OR], 4.88; 95% CI, 1.5-15.7). Among the 101 patients who received onsite DOT, illicit drug use (OR, 0.21; 95% CI, 0.08-0.6) and previous TB therapy (OR, 0.27; 95% CI, 0.27-0.7) were both independently associated with lower retention in therapy. However, with intensive case management, only 1% of this cohort was lost to follow-up and the overall treatment completion index was 98%. CONCLUSION: In-patient surveillance is a highly effective DOT recruitment strategy. A DOT model which elicits patient participation in discharge plans and offers incentives can yield a high rate of voluntary acceptance. Outpatient case management is a highly effective means of ensuring treatment completion, especially in those at risk for poor retention.

Adult↗
PubMed1995

Predictors and outcome of multidrug-resistant tuberculosis.

We identify early predictors of multidrug-resistant tuberculosis and describe improved clinical outcomes, including survival, for patients with human immunodeficiency virus (HIV)-related multidrug-resistant tuberculosis (MDR-TB) when they are prospectively identified and receive treatment under direct observation. Analysis by means of a Cox proportional hazards model revealed that failure to defervesce while receiving a standard four-drug antituberculous regimen was independently associated with multidrug resistance (P = .004). When patients with HIV-related MDR-TB were prospectively identified and treated with at least two agents that were active in vitro, 100% bacteriologic conversion and improved survival (> or = 4 months for 88% of patients and > or = 1 year for 59% of patients) were observed. For patients with HIV-related tuberculosis, poorer survival was associated with a CD4+ lymphocyte count of < 25 mm3 (P = .03); multidrug resistance was not a predictor of poor outcome (P = .82). These data suggest that patients with prolonged fever who are receiving antituberculous therapy may be an appropriate subgroup to target for broader empirical therapy. The findings also demonstrate that improved outcomes can be achieved with HIV-related MDR-TB when patients are prospectively identified and treated with agents that are active in vitro.

AIDS-Related Opportunistic Infections↗
PubMed1995

Tuberculosis in drug users.

The rise in tuberculosis (TB) has disproportionately affected specific populations. Historically, many patients with TB became iatrogenic opiate addicts through therapeutic use of these drugs for symptom control. Demographic trends reshaped the relationship between drug use and TB into one in which drug use became a risk factor for tuberculosis as a result of the overlap of epidemiological and social factors associated with both drug use and TB. The spread of human immunodeficiency virus infection has amplified the spread of TB among drug users. We review the epidemiology of TB in drug users as well as the factors relevant to screening and compliance in drug-using populations. Drug users constitute a high-risk group for whom screening, prevention of infection, diagnosis, and treatment pose particular challenges. The development of TB services capable of engaging drug users (those both in and out of drug treatment programs) has potential for disrupting a significant chain of rapid TB transmission.

AIDS-Related Opportunistic Infections↗
PubMed1994

Two-stage tuberculin skin testing in an HIV-infected population: a preliminary report.

To identify differences in purified protein derivative (PPD) tuberculin positivity rates and to assess the utility of sequential PPD testing among persons with HIV infection, we performed two sequential administrations of 5 tuberculin units of PPD in a group of persons with HIV infection. Eligible patients were skin-tested with the tuberculin using the Mantoux method. Patients who tested < 5 mm of induration were skin-tested seven days later along with Candida and mumps antigens. Of 37 tested patients, only 18 (49%) returned to have the first test read. Using a > or = 5 mm cutoff, 5 (28%) tested positive. Positivity varied markedly between patients with CD4+ cell counts under and at or over 400 cells/mm3 (0% vs. 56%). Among patients who had a reaction to the first test, the reaction was smaller in patients with CD4+ cell counts under 400 than in those with counts at or over 400 cells/mm3 (mean induration: 2.8 vs. 30.4 mm). Positivity was also less frequent in intravenous drug users than in nonusers (9% vs. 57%); these two groups did not differ with respect to CD4+ cell counts. Of the 13 patients who tested < 5 mm, only 8 (62%) kept their appointments to have the second test placed and read. Only 1 of these, a drug user with a CD4+ count of 6 cells/mm3, had a positive reaction with boosting from 4 mm on the first test to 10 mm on the second. These data indicate that PPD testing may be unreliable in screening for tuberculosis infection in persons with CD4+ counts < 400 cell/mm3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗