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Biomedical subjects

L B Reichman

Publications and source records attributed to L B Reichman.

At least 37 records · Page 2Linked to original sources

Incidence of tuberculosis in the United States among HIV-infected persons. The Pulmonary Complications of HIV Infection Study Group.

BACKGROUND: The resurgence of tuberculosis in the United States is largely linked to the human immunodeficiency virus (HIV) epidemic. Despite this link, the epidemiology of tuberculosis and preventive strategies in patients infected with HIV are not completely understood. OBJECTIVES: To determine the incidence and predictors of tuberculosis in HIV-infected persons. DESIGN: Prospective, multicenter cohort study. SETTING: Community-based cohort of persons with and without HIV infection at centers in the eastern, midwestern, and western United States. PARTICIPANTS: 1130 HIV-seropositive patients without AIDS who were followed for a median of 53 months (814 homosexual men, 261 injection drug users, and 55 women who had acquired HIV through heterosexual contact). MEASUREMENTS: Delayed hypersensitivity response to purified protein derivative (PPD) tuberculin and mumps antigen, CD4 T-lymphocyte counts, and frequency of tuberculosis. RESULTS: 31 HIV-seropositive patients developed tuberculosis (0.7 cases per 100 person-years [95% CI, 0.5 to 1.0]). The most important demographic risk factor was location (adjusted risk ratio for eastern compared with midwestern and western United States, 4.1 [CI, 2.0 to 8.4]). Tuberculosis occurred more frequently in persons with CD4 counts of less than 200 cells/mm3 (1.2 cases per 100 person-years [CI, 0.7 to 1.9]) than in those with higher counts (0.5 cases per 100 person-years [CI, 0.3 to 0.8]). The rate of tuberculosis was highest among tuberculin converters (5.4 cases per 100 person-years [CI, 1.1 to 15.7]), lower among patients who were PPD positive at first testing (4.5 cases per 100 person-years [CI, 1.6 to 9.7]), and lowest among patients who remained PPD negative (0.4 cases per 100 person-years [CI, 0.2 to 0.7]). Tuberculosis was not reported among persons who had PPD reactions of 1 to 4 mm. Compared with that of patients who tested positive for mumps, the risk for tuberculosis of those who tested negative was increased about sevenfold if they were PPD positive (P < 0.03) and fourfold if they were PPD negative (P < 0.02). CONCLUSIONS: Incidence of tuberculosis was higher in the eastern United States, in patients with CD4 counts of less than 200 cells/mm3, and in PPD-positive patients. Analysis of tuberculin reaction size supports the current interpretive criteria of the Centers for Disease Control and Prevention. Nonreactivity to mumps antigen indicated increased risk for tuberculosis independent of PPD response.

AIDS-Related Opportunistic Infections↗

Predictors of Pneumocystis carinii pneumonia in HIV-infected persons. Pulmonary Complications of HIV Infection Study Group.

The Pulmonary Complications of HIV Infection Study is a prospective, multicenter, observational study evaluating pulmonary disease among HIV-infected persons. For approximately 52 mo, 1,182 HIV-infected subjects were followed. All participants were evaluated for pulmonary disease on a predetermined schedule. There were 145 episodes of Pneumocystis carinii pneumonia (PCP). Low CD4 count correlated with risk of PCP (p < 0.0001); 79% had CD4 counts less than 100/microl and 95% had CD4 counts less than 200/microl. Subtle changes in diffusing capacity for carbon monoxide (DLCO) were associated with PCP. Univariate analysis identified recurrent undiagnosed fevers, night sweats, oropharyngeal thrush, and unintentional weight loss to be associated with risk among persons with CD4 counts above 200/microl. Subjects in whom CD4 counts declined to below 200/microl and who were not receiving preventive therapy were nine times more likely to develop PCP within 6 mo compared with subjects who received such therapy. A strong trend toward differences between the sexes was detected. Black subjects had less than one third the risk of developing PCP as did white subjects (p < 0.0001). There was no significant difference in risk by HIV transmission category, study site, frequency of follow-up, age, education, smoking history, or use of antiretroviral therapy. Multivariable analysis revealed low CD4 lymphocyte count (p < 0.0001), use of prophylaxis (p < 0.0001), racial differences (p < 0.0001), and declining DLCO (p = 0.015) to influence risk. Constitutional signs and symptoms indicate increased risk for PCP among HIV-infected persons with CD4 counts above 200/microl.

AIDS-Related Opportunistic Infections↗

Intensive care of patients with HIV infection: utilization, critical illnesses, and outcomes. Pulmonary Complications of HIV Infection Study Group.

To examine intensive care unit (ICU) admission rates and diagnoses of patients with HIV infection, and to determine the outcomes of different critical illnesses, we analyzed data derived from the 63 patients who were admitted to an ICU from among the 1,130 adults with HIV infection who did not have AIDS at the time of enrollment in a multicenter prospective study. Patients were admitted and treated according to the judgment of their physicians. During 4,298 patient-years of follow-up for the entire cohort, there were 1,320 hospital admissions, of which 68 (5%) included admission to an ICU. Twenty-five (40%) of the patients admitted to the ICU died during that admission. Twenty-four patients (38%) were admitted with a principal diagnosis of lung disease; 11 had Pneumocystis carinii pneumonia (PCP), one of whom was coinfected with Aspergillus fumigatus and Legionella pneumophilia, and six of them (55%) died. Four had bacterial pneumonia, two had pulmonary edema caused by renal failure, and one each had pulmonary tuberculosis, pulmonary Kaposi's sarcoma, pneumothorax, adult respiratory distress syndrome, severe pulmonary fibrosis, cytomegalovirus pneumonitis, and metastatic adenocarcinoma to the lungs. Eleven of these 14 patients (79%) died. Thirty-nine patients had 44 admissions for nonpulmonary diagnoses, including gastrointestinal disorders (14 admissions), cardiovascular disorders (nine), sepsis syndrome (six), neurologic disorders (four), monitoring and ICU nursing care during or after a procedure (four), metabolic disorders (three), trauma (two), drug overdose (one), and unknown reasons (one). Nine (23%) of these patients died. Twenty-eight patients underwent mechanical ventilation, and 16 (57%) died. Seven (25%) had PCP (five died), seven had other primary pulmonary diseases (six died), and 14 were placed on mechanical ventilation for nonpulmonary disorders (five died). Survival did not correlate with CD4 count determined within 6 mo of admission to the ICU. In conclusion, the range of indications for critical care in patients with HIV infection is diverse. PCP accounted for only 16% of the ICU admissions, and mechanical ventilation for PCP and other pulmonary disorders was associated with a high mortality rate. In contrast, mechanical ventilation for nonpulmonary disorders, and admission to the ICU for nonpulmonary diagnoses was associated with a more favorable outcome.

Adult↗

Respiratory disease trends in the Pulmonary Complications of HIV Infection Study cohort. Pulmonary Complications of HIV Infection Study Group.

We examined trends in the incidence of specific respiratory disorders in a multicenter cohort with progressive human immunodeficiency virus (HIV) disease during a 5-yr period. Individuals with a wide range of HIV disease severity belonging to three transmission categories were evaluated at regular intervals and for episodic respiratory symptoms using standard diagnostic algorithms. Yearly incidence rates of respiratory diagnoses were assessed in the cohort as a whole and according to CD4 count or HIV transmission category. The most frequent respiratory disorders were upper respiratory tract infections, but the incidence of lower respiratory tract infections increased as CD4 counts declined. Specific lower respiratory infections followed distinctive patterns according to study-entry CD4 count and transmission category. Acute bronchitis was the predominant lower respiratory infection of cohort members with entry CD4 counts > or = 200 cells/mm3. In cohort members with entry CD4 counts of 200 to 499 cells/mm3, the incidence of bacterial and Pneumocystis carinii pneumonia each increased an average of 40% per year. In members with entry CD4 counts < 200 cells/mm3, acute bronchitis, bacterial pneumonia, and P. carinii pneumonia occurred at high rates without discernible time trends, despite chemoprophylaxis in more than 80% after Year 1, and the rate of other pulmonary opportunistic infections increased over time. Each year, injecting drug users had a higher incidence of bacterial pneumonia than did homosexual men. The yearly rate of tuberculosis was < 3 episodes/100 person-yr in each entry CD4 and HIV-transmission group. We conclude that the time trends of HIV-associated respiratory disorders are determined by HIV disease stage and influenced by transmission category. Whereas acute bronchitis is prevalent during all stages of HIV infection, incidence rates of bacterial pneumonia and P. carinii pneumonia rise continuously during progression to advanced disease. In advanced disease, the incidence of acute bronchitis, bacterial pneumonia and P. carinii pneumonia is high despite widespread chemoprophylaxis.

AIDS-Related Opportunistic Infections↗

Nonspecific airway hyperresponsiveness in HIV disease. Pulmonary Complications of HIV Infection Study Group.

OBJECTIVES: HIV disease is frequently complicated by episodic acute bronchitis, suggesting the presence of chronic bronchial inflammation. To further examine this concept, we investigated the possible association of nonspecific airway hyperresponsiveness (AHR) and HIV disease. DESIGN: Methacholine inhalation challenge studies were performed on 66 HIV-seropositive and 8 HIV-seronegative members of the Pulmonary Complications of HIV Infection Study Cohort. AHR was defined as 20% or more decline in FEV1 from the postdiluent value after inhalation of 125 or less cumulative breath units. The prevalence of AHR in HIV-seropositive cohort members was compared with that in matched control subjects who had undergone methacholine challenge testing for two unrelated studies. Demographic, behavioral, and clinical features in HIV cohort members with and without AHR were contrasted. The relationship between AHR and the occurrence of episodic airway disease or symptoms suggestive of airway disease was examined. RESULTS: AHR was not more prevalent in HIV-seropositive cohort members than control subjects (19.3% vs 12.9%; p > 0.1). Within the cohort, AHR was detected more frequently in members with than without a history of asthma (60% vs 16%; p < 0.05). A greater proportion with than without AHR had 1 or more episode of pneumonia within 2 years (46% vs 9%; p < 0.01), 1 or more asthma episode during the study period (39% vs 1.9%; p < 0.001), or wheeze noted during clinic visits (62% vs 17%; p < 0.01). The proportion that experienced acute bronchitis did not differ in the two groups. CONCLUSIONS: This study suggest that HIV-infected persons do not have increased prevalence of nonspecific AHR. In HIV disease, AHR is associated asthma, but not episodic acute bronchitis. Thus, the possibility that airway injury without demonstrable AHR might complicate HIV disease remains.

Adult↗

Tuberculosis elimination--what's to stop us?

It is well recognized and has oft been stated that tuberculosis (TB) is the largest cause of death from a single infection worldwide; it infects fully one-third of the world's population, is fully 100% curable and 100% preventable and yet is nowhere near being eliminated in any area of the globe, including the most developed nations. The failure to eliminate this, possibly the most easily eliminatable of all scourges, must rank as one of mankind's most serious ongoing blunders. After all, we know the pathogenesis, we know the transmission, we know how to diagnose, treat and prevent almost all cases, yet TB killed more individuals in 1996 than it did when Robert Koch discovered the bacillus that causes TB more than a century ago. TB is different from almost any other disease in that cases of TB must be actively sought and treated to keep them from spreading to others. In most diseases the untreated case dies and harms nobody. In TB the untreated or improperly treated case becomes resistant and spreads drug-resistant TB until it is found and properly treated. We physicians love to blame our patients for noncompliance in taking drugs. However, our failure to deal with TB clearly and documentedly rests with a lack of compliance on several levels. TB will nerve be eliminated until this lack of compliance on all levels is addressed and corrected.

Health Knowledge, Attitudes, Practice↗

An incentive in tuberculosis preventive therapy for an inner city population.

SETTING: Measures known to improve adherence such as short course chemoprophylaxis and directly observed therapy can be enhanced to a significant extent/by the use of incentives. Adherence to tuberculosis therapy is influenced by several factors, including the health care system, complexity of therapeutic regimens and patient's characteristics. Individual factors that negatively influence patient's adherence are the most difficult to counter. Preventive tuberculosis therapy is doubly challenging because the benefit of treatment is not felt, while toxicity from the medication, when it occurs, is experienced immediately. Ingenious incentives therefore have to make it worth the patient's while. During a study on preventive regimens, a request for an incentive, Sustacal, was observed to help completion of preventive regimens. Components of individual TB programs may help in patient adherence; it is important for health care staff to identify these aspects and, if they are successful, utilize these as an incentive to complete treatment.

AIDS-Related Opportunistic Infections↗

Lack of usefulness of radiographic screening for pulmonary disease in asymptomatic HIV-infected adults. Pulmonary Complications of HIV Infection Study Group.

OBJECTIVE: To determine the use of chest radiographs in the screening of asymptomatic adults infected with the human immunodeficiency virus (HIV). METHODS: A prospective, multicenter study of the pulmonary complications of HIV infection in a community-based cohort of persons with and without HIV infection. The subjects included 1065 HIV-seropositive subjects without the acquired immunodeficiency syndrome at the time of enrollment: 790 homosexual men, 226 injection drug users, and 49 women with heterosexually acquired infection. Frontal and lateral chest radiographs were performed at 3-, 6-, and 12-month intervals, CD4 lymphocyte measurements at 3- and 6-month intervals, tuberculin and mumps skin tests at 12-month intervals, and medical histories and physical examinations at 3- and 6-month intervals. Pulmonary diagnoses that occurred within 2 months following each radiograph were analyzed and correlated with the radiographic results. RESULTS: Evaluable screening chest radiographs (5263) were performed in HIV-seropositive subjects while they were asymptomatic; of these, 5140 (98%) were classified as normal and 123 (2%) as abnormal. A new pulmonary diagnosis was identified within 2 months following a screening radiograph in 55 subjects. Only 11 of these subjects had abnormal radiographs; the sensitivity of the radiograph was 20%. The sensitivity was similarly low at baseline, within each transmission category, and in subjects whose CD4 lymphocyte counts were less than 0.2 x 10(9)/L (200/microL). The types of pulmonary diseases that occurred were similar in the subjects with normal and abnormal screening radiographs. CONCLUSION: Screening chest radiography in asymptomatic HIV-infected adults is unwarranted because the diagnostic yield is low.

AIDS-Related Opportunistic Infections↗

Multidrug resistance in the world: the present situation.

Tuberculosis (TB) is the leading cause of death attributable to a single infectious pathogen with one-third of the world population infected. In the USA, TB rates have fallen 3 years in succession after a sustained rise since 1985. More important are the multidrug-resistant tuberculosis (MDR-TB) cases, which are thought to be largely due to the breakdown in the delivery of health care in the USA in conjunction with HIV infection. In countries facing the HIV epidemic, the overlap of these two populations leads to a rapid acceleration of active TB and the emergence of MDR-TB. In the USA the most recent published survey (1991) revealed that 3.5% of strains were resistant to isoniazid and rifampin. Worldwide, MDR-TB is also thought to be highly prevalent, not only because of a breakdown in health infrastructure but also because of inappropriate prescription, lack of drug availability and the use of combination capsules in which the drugs are not bioavailable. Key points in therapy are to order susceptibility tests, obtain a complete drug history, treat with an adequate number of effective drugs and never, ever add a single drug to a failing regimen.

Anti-Infective Agents↗

Reliability of anergy skin testing in persons with HIV infection. The pulmonary Complications of HIV Infection Study Group.

Testing with antigens that elicit delayed-type cutaneous hypersensitivity reactions is commonly used to evaluate immune competence in persons infected with the human immunodeficiency virus; however, the reliability of such testing has not been determined. We performed serial testing with tuberculin, mumps, and Candida antigens in 491 HIV-infected persons and found that 30% of persons who initially had no reaction (0 mm) to any of the three antigens, and, thus, were considered to be anergic, had reaction to the mumps or Candida antigen when they were retested 12 months later. We also examined the results of mumps antigen tests in 50 subjects who had a negative tuberculin tests after an initial positive test. The mumps antigen test was positive in 39% of the subjects when the tuberculin test was falsely negative. We conclude that tests commonly used to define anergy cannot reliably identify the anergic state. Moreover, using the mumps antigen to aid in the interpretation of the tuberculin test will often lead to erroneous conclusions. These data indicate that the results of anergy testing should not be used to make individual patient decisions concerning preventive therapy for tuberculosis.

Administration, Cutaneous↗

Fixed-dose combinations of antituberculous medications to prevent drug resistance.

The treatment of tuberculosis requires at least two drugs to retard the development of drug resistance. Unfortunately, patients may take only one drug (monotherapy) when more than one is prescribed. Fixed-dose combinations with two or more antituberculous drugs in one capsule or tablet are available to prevent this. In the United States, these drugs are Rifamate (Marion Merrell Dow), which contains isoniazid plus rifampin, and Rifater (Marion Merrell Dow), which contains isoniazid plus rifampin and pyrazinamide. Because these preparations make monotherapy impossible, they are clearly preferable to individual drugs. In the United States in 1993, however, only 15% to 18% of rifampin was sold in the form of fixed-dose combinations. To correct this deficiency, fixed-dose combinations should be widely promoted and accepted as a primary way to prevent drug-resistant tuberculosis. There are two caveats regarding these preparations. First, many fixed-dose combinations, especially those in developing countries, achieve inadequate blood levels of one or more of the component drugs, especially rifampin. Our recommendations apply only to preparations with proven bioavailability. Second, because the name Rifamate is similar to the name rifampin, mistakes in prescribing and dispensing can result in the patient receiving rifampin alone when Rifamate is intended. A name change from Rifamate to a highly distinctive name such as Rif-Isoniazid is needed to prevent such occurrences.

Antitubercular Agents↗