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Biomedical subjects

D L Cohn

Publications and source records attributed to D L Cohn.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1998

Comparison of health status, socioeconomic characteristics, and knowledge and use of HIV-related resources between HIV-infected women and men.

OBJECTIVES: The authors compared socioeconomic characteristics, and knowledge and use of human immunodeficiency virus (HIV)-related resources and health status measures between HIV-infected women and men registered within the Denver Health and Hospitals health care system. METHODS: Data collected through two Centers for Disease Control-funded surveillance initiatives (Adult Spectrum of Disease and Supplement to HIV/AIDS Surveillance) were linked. Health status measures were obtained using the Medical Outcomes Study (MOS-20) questionnaire. To compare health status measures between genders, men were matched to women based on disease stage, intravenous drug use, race, years of education, employment status, and age. RESULTS: Among all patients interviewed (n = 419), women (n = 52) were more likely to be minority, uneducated, intravenous drug users, and at earlier stages of HIV-disease than men (n = 367). Employment status was not significantly different. Knowledge of available services was generally good among both genders. Women received public assistance and had health insurance (Medicaid) more often than men. Women used support services, social work, and shelter assistance less often than men. The matched pairs analysis (n = 46 pairs) showed no significant differences between genders in physical and social function, mental health, pain, or general health perceptions; however, role function was better in women than in men (P<0.02). CONCLUSIONS: When controlling for factors that may influence health and access to health care, HIV disease generally impacts the health status of both genders similarly. Women scored higher in role function which may reflect family caretakers' responsibilities. Although knowledge of HIV-related resources was similar by gender, men made contact more often suggesting areas for enhanced outreach toward women.

Adolescent↗
PubMed1998

Sex hustling, injection drug use, and non-gay identification by men who have sex with men. Associations with high-risk sexual behaviors and condom use.

OBJECTIVE: To explore differences in demographic characteristies, risk practices, and preventive behaviors among subgroups of men who have sex with men (MSM), including gay- and non-gay-identified MSM, MSM who inject drugs, and those engaging in sex hustling. DESIGN: A secondary analysis of cross-sectional data collected through interviewer-administered questionnaires in a purposive sample of MSM. SETTING: Gay bars, bath houses, adult video arcades, and out-door crusing areas in Denver and Long Beach. PARTICIPANTS: Men who reported oral or anal sex with another man in the past year with oversampling of non-gay-identified MSM. RESULTS: Of 1,290 MSM, 417 (32%) did not gay-identify, 86 (7%) were drug injectors, and 117 (9%) were hustlers. Of drug-injecting MSM, 55% reported sex hustling and 40% of hustlers reported injection drug use. Hustling was associated with higher number of partners, more frequent anal sex with men and women, and less frequent condom use during anal sex with occasional male partners. Hustlers and drug-injecting MSM used condoms less consistently during vaginal intercourse with female partners than did other MSM. CONCLUSIONS: Among MSM, subgroups at particularly high risk for HIV can be identified. Although these subgroups may be relatively small, they may be important epidemiologic links to the larger MSM and heterosexual communities and warrant focused behavioral interventions to prevent the further spread of HIV.

Adult↗
PubMed1998

The use of restriction fragment length polymorphism (RFLP) analysis for epidemiological studies of tuberculosis in developing countries.

DNA fingerprinting, of which restriction fragment length polymorphism (RFLP) typing is the most common method used, has permitted novel investigations of the epidemiology and pathogenesis of tuberculosis. The use of IS6110, an insertion sequence which is present in Mycobacterium tuberculosis, is generally considered to be the standard RFLP method, but other molecular typing techniques may be used as adjuncts in selected circumstances. A number of epidemiologic studies using RFLP typing have been done in both industrialized and developing countries. The major findings include the confirmation or identification of chains of transmission (of both drug-sensitive and drug-resistant strains of tuberculosis), distribution of strain clusters within populations, differentiation of relapse from exogenous reinfection, better understanding of the pathogenesis of tuberculosis, identification of laboratory cross-contamination, and insight into the molecular evolution of the species. For developing countries, where the burden of tuberculosis is greatest, three major areas of investigation for the use of RFLP analysis in epidemiologic studies of tuberculosis have been identified: 1) community transmission, 2) nosocomial transmission, and 3) human immunodeficiency virus (HIV)-related tuberculosis. Elements of protocols are suggested which can be used by investigators to perform well-designed epidemiologic studies which will be relevant to developing countries and which are likely to have an impact on control programmes in these settings.

AIDS-Related Opportunistic Infections↗
PubMed1997

Early manifestations of disseminated Mycobacterium avium complex disease: a prospective evaluation.

A nested case-control study was conducted in two trials of prophylaxis for Mycobacterium avium complex (MAC) infection to describe the specific signs, symptoms, and laboratory abnormalities of MAC disease in AIDS. Patients had < or =200/mm3 CD4 cells and a prior AIDS-defining illness. Of 571 patients, 102 (17.9%) developed MAC bacteremia during a mean follow-up of 256 days. Among cases of MAC disease, 90 were compared with 180 matched controls. Patients with MAC disease were more likely than controls to have lower weights (66.3 vs. 71.1 kg, P = .001) and Karnofsky scores (74.3 vs. 84.4, P < .001); a higher proportion had fever (48% vs. 26%, P = .003), abdominal pain (23% vs. 13%, P =.05), decreased hemoglobin levels (10.9 vs. 12.1 g/dL, P < .001), and elevated alkaline phosphatase (203 vs. 138 U/L, P=.04) and lactate dehydrogenase (334 vs. 280 U/L, P = .02) levels. Characteristics of MAC disease that occurred before bacteremia were weight loss (3 months prior), fever (2 months), and anemia and elevated lactate dehydrogenase (1 month). These data suggest that patients have symptomatic MAC disease for several months prior to the occurrence of bacteremia.

Adult↗
PubMed1997

Drug-resistant tuberculosis: review of the worldwide situation and the WHO/IUATLD Global Surveillance Project. International Union Against Tuberculosis and Lung Disease.

The emergence of strains of Mycobacterium tuberculosis that are resistant to antimycobacterial agents is a worldwide problem whose global magnitude is not well described. We reviewed and tabulated 63 surveys of resistance to antituberculous drugs that were performed between 1985 and 1994. Rates of primary resistance to isoniazid, administered as a single agent, ranged from 0 to 16.9% (median rate, 4.1%); to streptomycin, 0.1%-23.5% (median, 3.5%); to rifampin, 0-3.0% (median, 0.2%); and to ethambutol, 0-4.2% (median, 0.1%). The rates of acquired resistance to these agents, which were higher than those of primary resistance, were as follows: isoniazid, 4.0%-53.7% (median rate, 10.6%); streptomycin, 0-19.4% (median, 4.9%); rifampin 0-14.5% (median, 2.4%); and ethambutol, 0-13.7% (median, 1.8%). The highest rates of multidrug-resistant tuberculosis have been reported in Nepal (48.0%), Gujarat, India (33.8%), New York City, (30.1%), Bolivia (15.3%), and Korea (14.5%). The WHO (World Health Organization) and the IUATLD (International Union Against Tuberculosis and Lung Disease) have established a global project of drug resistance surveillance that is based on standard epidemiological methods and quality control through an extensive network of reference laboratories. Accurate drug resistance surveillance data can be used to assess and improve national tuberculosis programs.

Antitubercular Agents↗
PubMed1997

Geographic and seasonal variation in Mycobacterium avium bacteremia among North American patients with AIDS.

Analysis of geographic risk was performed for Mycobacterium avium complex (MAC) bacteremia among North American patients with AIDS. Monthly mycobacterial blood cultures were taken from patients who were placebo recipients in a prospective evaluation of MAC prophylaxis. Of 571 patients, 102 (17.9%) acquired MAC bacteremia during an average follow-up of 256 days. The area with the highest risk for MAC was the South Central region (27.9%; P < 0.02), whereas the area with the lowest risk was Canada (11.3%; P = 0.12). When the southern states were combined and compared with the northern states and Canada, the incidence of MAC bacteremia was higher in the southern states (21.6% versus 14.0%, P < 0.03). Proportional hazards analysis was performed for the difference between the North and South and controlled for baseline CD4 cell count. In this analysis, time to MAC was significantly longer in the North (hazard ratio = 0.587, 95% confidence interval 0.390 to 0.883, P = 0.01). Although overall variation in seasonality was not marked, there was a significant decrease in cases in the North during the summer months (P < 0.01). We conclude that geographic location is a risk factor for MAC bacteremia in patients with advanced AIDS, with decreased risk in northern North America.

AIDS-Related Opportunistic Infections↗
PubMed1997

Use of the bacille Calmette-Guérin vaccination for the prevention of tuberculosis: renewed interest in an old vaccine.

The reemergence of tuberculosis, including the impact of HIV infection and multidrug-resistant tuberculosis, have renewed interest in the bacille Calmette-Guérin (BCG) vaccine. During the past 7 decades, numerous studies have shown variable efficacy of BCG vaccination, ranging from 0% to 80%. The BCG vaccine is more likely to prevent disseminated forms of tuberculosis in children than pulmonary tuberculosis in adolescents or adults. Bacille Calmette-Guérin vaccination is recommended in asymptomatic children with or at risk for HIV infection, but it rarely may cause disseminated BCG infection and should not be used in persons with symptomatic HIV infection or AIDS. In healthcare workers with exposure to Mycobacterium tuberculosis, including multidrug-resistant tuberculosis, BCG vaccination generally is not recommended. Revaccination with BCG does not confer more benefit than initial vaccination, and repeat vaccinations should be discontinued. With recent advances in technology and a better understanding of the immunopathogenesis of tuberculosis, efforts to develop a more potent and specific vaccine need to be pursued. If a more effective vaccine against tuberculosis is developed, vaccination can be expected to have an additional impact on global tuberculosis control in conjunction with current strategies of case detection, treatment of disease, and preventive therapy.

AIDS-Related Opportunistic Infections↗
PubMed1997

Noncompliance with directly observed therapy for tuberculosis. Epidemiology and effect on the outcome of treatment.

STUDY OBJECTIVES: To describe the epidemiology and clinical consequences of noncompliance with directly observed therapy (DOT) for treatment of tuberculosis. DESIGN: Retrospective review. SETTING: An urban tuberculosis control program that emphasizes DOT. PATIENTS: All patients treated with outpatient DOT from 1984 to 1994. MEASUREMENTS AND RESULTS: We defined noncompliance as follows: (1) missing > or = 2 consecutive weeks of DOT; (2) prolongation of treatment > 30 days due to sporadic missed doses; or (3) incarceration for presenting a threat to public health. Poor outcomes of therapy were defined as a microbiologic or clinical failure of initial therapy, relapse, or death due to tuberculosis. Fifty-two of 294 patients (18%) who received outpatient DOT fulfilled one or more criteria for noncompliance. Using multivariate logistic regression, risk factors for noncompliance were alcohol abuse (odds ratio, 3.0; 95% confidence interval, 1.2 to 7.5; p = 0.02) and homelessness (odds ratio, 3.2; 95% confidence interval, 1.5 to 7.2; p = 0.004). Noncompliant patients had poor outcomes from the initial course of therapy more often than compliant patients: 17 of 52 (32.7%) vs 8 of 242 (3.3%); relative risk was 9.9; 95% confidence interval was 4.5 to 21.7 (p < 0.001). CONCLUSIONS: In an urban tuberculosis control program, noncompliance with DOT was common and was closely associated with alcoholism and homelessness. Noncompliance was associated with a 10-fold increase in the occurrence of poor outcomes from treatment and accounted for most treatment failures. Innovative programs are needed to deal with alcoholism and homelessness in patients with tuberculosis.

Adult↗
PubMed1997

Short-term incarceration for the management of noncompliance with tuberculosis treatment.

STUDY OBJECTIVES: To review the use of incarceration for noncompliance with tuberculosis treatment. DESIGN: Retrospective review. SETTING: An urban tuberculosis control program. PATIENTS: Patients treated for active tuberculosis. MEASUREMENTS AND RESULTS: We reviewed the legal basis and practical application of quarantine for active tuberculosis, including the use of incarceration for noncompliance. The records of patients treated at the Denver Metro Tuberculosis Clinic during 1984 to 1994 were reviewed to identify patients who were incarcerated and to evaluate the effectiveness of this intervention. Of 424 cases of tuberculosis, 20 patients (4.7%) were incarcerated for noncompliance; an additional 21 patients (5.0%) were lost to follow-up prior to completing therapy. Incarcerated patients were predominantly men who were born in the United States and had a history of homelessness and alcohol abuse. The median duration of the initial incarceration was 20 days (range, 7 to 51 days). Of the 17 patients released prior to completing therapy, 13 (76%) were compliant with outpatient, directly observed therapy after one or two short-term incarcerations (<60 days); only three patients were incarcerated for the duration of treatment. Overall, 18 of 20 incarcerated patients (90%) were successfully treated. CONCLUSIONS: Approximately 5% of the patients treated through our program were incarcerated for noncompliance; an additional 5% were unavailable for follow-up and would have been candidates for incarceration if found. Homelessness and alcoholism were closely associated with the use of incarceration. Short-term incarceration followed by outpatient, directly observed therapy was relatively successful in the management of this difficult patient population.

Adult↗
PubMed1997

A cost-effectiveness analysis of directly observed therapy vs self-administered therapy for treatment of tuberculosis.

STUDY OBJECTIVES: To compare the costs and effectiveness of directly observed therapy (DOT) vs self-administered therapy (SAT) for the treatment of active tuberculosis. DESIGN: Decision analysis. SETTING: We used published rates for failure of therapy, relapse, and acquired multidrug resistance during the initial treatment of drug-susceptible tuberculosis cases using DOT or SAT. We estimated costs of tuberculosis treatment at an urban tuberculosis control program, a municipal hospital, and a hospital specializing in treating drug-resistant tuberculosis. OUTCOME MEASURES: The average cost per patient to cure drug-susceptible tuberculosis, including the cost of treating failures of initial treatment. RESULTS: The direct costs of initial therapy with DOT and SAT were similar ($1,206 vs $1,221 per patient, respectively), although DOT was more expensive when patient time costs were included. When the costs of relapse and failure were included in the model, DOT was less expensive than SAT, whether considering outpatient costs only ($1,405 vs $2,314 per patient treated), outpatient plus inpatient costs ($2,785 vs $10,529 per patient treated), or outpatient, inpatient, and patients' time costs ($3,999 vs $12,167 per patient treated). Threshold analysis demonstrated that DOT was less expensive than SAT through a wide range of cost estimates and clinical event rates. CONCLUSION: Despite its greater initial cost, DOT is a more cost-effective strategy than SAT because it achieves a higher cure rate after initial therapy, and thereby decreases treatment costs associated with failure of therapy and acquired drug resistance. This cost-effectiveness analysis supports the widespread implementation of DOT.

Antitubercular Agents↗
PubMed1997

Prevention strategies for Mycobacterium avium-intracellulare complex (MAC) infection. A review of recent studies in patients with AIDS.

In patients with AIDS, disseminated Mycobacterium avium-intracellulare complex (MAC) infection is a common bacterial infection and is associated with considerable morbidity and mortality. In placebo-controlled studies, rifabutin, clarithromycin and azithromycin (administered as single agents) have been shown to prevent the development of MAC bacteraemia in patients with advanced HIV disease. Clarithromycin also conferred a survival benefit over placebo, but this was not initially observed with either rifabutin or azithromycin. Subsequently, the efficacy of single agent therapy was compared with that of combination treatment as prophylaxis against the development of disseminated MAC. In the AIDS Clinical Trials Group (ACTG) 196/Community Programs for Clinical Research on AIDS (CPCRA) 009 study, clarithromycin monotherapy and clarithromycin and rifabutin combination therapy regimens were both more effective than rifabutin monotherapy in reducing the incidence of MAC bacteraemia. However, the combination regimen was generally not well tolerated. In the California Consortium Treatment Group (CCTG)/Multiple Opportunistic Prevention Prophylactic Strategy (MOPPS) study, azithromycin plus rifabutin was significantly more effective than either agent administered alone, and azithromycin was more effective than rifabutin. However, azithromycin (alone or in combination with rifabutin) caused frequent gastrointestinal adverse events. Emergence of resistance in those failing prophylaxis appeared to be higher with clarithromycin than with azithromycin or rifabutin. The use of the combination regimen of clarithromycin plus rifabutin did not reduce the selection of clarithromycin-resistant isolates. Several issues need to be considered in the choice of MAC prophylaxis for the individual patient. On the basis of efficacy and potential drug interactions with protease inhibitors, clarithromycin or azithromycin is preferred to rifabutin. However, rifabutin is less likely to result in the emergence of resistance than the macrolides, and is likely to prevent tuberculosis, whereas azithromycin and clarithromycin will prevent some bacterial infections. Combination therapy for prophylaxis is not indicated in most situations.

AIDS-Related Opportunistic Infections↗
PubMed1997

A retrospective comparison of clarithromycin versus rifampin in combination treatment for disseminated Mycobacterium avium complex disease in AIDS: clarithromycin decreases transfusion requirements.

SETTING: Urban county medical center. OBJECTIVE: To compare clinical outcomes associated with two treatment regimens for AIDS-associated disseminated Mycobacterium avium complex (DMAC). From 1989 to mid-1992, patients were treated with rifampin, ethambutol, and clofazimine; in mid-1992 clarithromycin replaced rifampin. DESIGN: A retrospective review of patients with DMAC; the main outcome measures assessed were toxicity associated with DMAC treatment, transfusions after the diagnosis of DMAC, and survival. RESULTS: 88 patients received the rifampin-based regimen and 86 were treated with the clarithromycin-based regimen. Drug-related adverse events were recorded less frequently with clarithromycin treatment (21% vs. 42%, P = 0.005), and additional antimycobacterial agents were used less often (28% vs. 44%, P = 0.04). In a multivariate logistic regression model, severe anemia at the time of DMAC diagnosis was associated with transfusion-dependence (relative risk [RR] 5.6, 95% confidence interval [CI] 2.2, 13.8, P < 0.001) and clarithromycin treatment was inversely associated with transfusion dependence (RR 0.4, 95% CI 0.1, 0.98, P = 0.04). In a multivariate Cox regression model including other factors affecting survival, clarithromycin treatment did not confer a survival advantage (P = 0.74). CONCLUSIONS: The clarithromycin-containing regimen was better tolerated and was associated with substantially lower transfusion requirements than the rifampin-based regimen; survival was not affected.

AIDS-Related Opportunistic Infections↗
PubMed1996

The impact of human immunodeficiency virus infection on drug-resistant tuberculosis.

Infection with human immunodeficiency virus (HIV) has been associated with increased rates of single- and multidrug-resistant (MDR) tuberculosis in the New York City area. In order to examine the relationship of HIV infection to drug-resistant tuberculosis in other selected regions of the United States, we established a registry of cases of culture-proven tuberculosis. Data were collected from sites participating in an NIH-funded, community-based HIV clinical trials group. All cases of tuberculosis, regardless of HIV status, which occurred between January 1992 and June 1994 were recorded. Overall, 1,373 cases of tuberculosis were evaluated, including 425 from the New York City area, and 948 from seven other metropolitan areas. The overall prevalence of resistance to one or more drugs was 20.4%, and 5.6% of isolates were resistant to both isoniazid and rifampin (MDR). In the New York City area, HIV-infected patients were significantly more likely than persons not known to be HIV-infected, to have resistance to at least one drug (37% versus 19%) and MDR (19% versus 6%). In other geographic areas, overall drug resistance was 16%, and only 2.2% of isolates were MDR. In multiple logistic regression analyses, HIV infection was shown to be a risk factor for drug-resistant tuberculosis, independent of geographic location, history of prior therapy, age, and race. We concluded that HIV infection is associated with increased rates of resistance to antituberculosis drugs in both the New York City area and other geographic areas. MDR tuberculosis is occurring predominantly in the New York City area and is highly correlated with HIV infection.

Adolescent↗
PubMed1996

Building a peer network for a community level HIV prevention program among injecting drug users in Denver.

As part of a multi-site Centers for Disease Control and Prevention-funded initiative, a community-level HIV prevention project targeting injection drug users was implemented in the FivePoints community in Denver, Colorado. The protocol for the initiative included the use of peer networks to conduct outreach and disseminate intervention materials to injecting drug users. Since April 1993, project staff established a peer network of 119 participants who distribute approximately 3,000 materials per month.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Increasing the use of bleach and condoms among injecting drug users in Denver: outcomes of a targeted, community-level HIV prevention program.

OBJECTIVE: To evaluate the impact of an HIV risk-reduction program among injecting drug users (IDU) in Denver, Colorado. DESIGN: A targeted, community-level intervention study with multiple, time-phased, cross-sectional measurements assessing HIV high-risk behaviors among IDU in intervention and comparison sites. SETTING: Neighborhoods with high IDU prevalence in Denver, Colorado (intervention site) and Long Beach, California (non-intervention comparison site). PARTICIPANTS: Street-recruited IDU who had injected drugs in the previous 30 days and shared injection equipment in the previous 60 days to evaluate the use of bleach to clean injection equipment; or had sexual intercourse in the previous 30 days, to evaluate condom use. INTERVENTION: A prevention program in which peer volunteers were recruited and trained to distribute and discuss intervention kits that included condoms, bleach bottles and role model stories. MAIN OUTCOME MEASURES: Multiple cross-sectional surveys were conducted in the intervention and comparison sites to assess the impact of the intervention on the consistent use of bleach before sharing injection equipment and the consistent use of condoms for vaginal intercourse with steady and occasional partners. RESULTS: Between February 1991 and December 1993, 1997 IDU were interviewed, 890 at the intervention site and 1107 at the comparison site. In contrast to the comparison site, subjects from the intervention site reported significant increases in consistent use of bleach [odds ratio (OR), 2.6; 95% confidence interval (CI), 1.3-5.1; P < 0.001], and consistent use of condoms with occasional partners (OR, 13.6; 95% CI, 3.2-58.0; P < 0.001). CONCLUSION: This targeted, peer-based intervention was associated with significant HIV risk reduction among IDU in Denver and may be useful in other communities at risk for HIV infection.

Adult↗
PubMed1995

Treatment of multidrug-resistant tuberculosis.

Recent outbreaks of multi-drug-resistant tuberculosis (MDR-TB) have resulted in significant morbidity and mortality in patients with AIDS. The poor outcomes are attributable to delayed diagnoses, slow reporting of antimycobacterial susceptibility results, inadequate treatment regimens and profound immunosuppression. There are no prospective clinical trials which have evaluated the optimal treatment of MDR-TB. A retrospective study has shown that in immunocompetent patients with secondary MDR-TB, only 56% responded to prolonged courses of multiple drug regimens, and 22% died of TB. In patients with AIDS, even fewer patients respond, with median survivals of 2-4 months. In general, better responses have been associated with in vitro susceptibility of patients' isolates. If possible, patients with MDR-TB should receive at least three drugs to which their isolates are susceptible for at least 24 months; these regimens are likely to include ethambutol, pyrazinamide, a quinolone, and an aminoglycoside. Selected patients benefit from surgical intervention combined with aggressive chemotherapy. MDR-TB is best prevented by directly observed therapy of patients with susceptible organisms and rigorous infection control practices in areas of high incidence of MDR-TB. Effective treatment regimens for MDR-TB await the development of novel compounds which have better in vitro activity against MDR-TB than currently available drugs.

AIDS-Related Opportunistic Infections↗