Jeffrey Glassroth

Bacterial Pneumonia in Persons Infected with the Human Immunodeficiency Virus

BACKGROUND Patients with human immunodeficiency virus (HIV) infection are at increased risk for bacterial pneumonia in addition to opportunistic infection. However, the risk factors for bacterial pneumonia and its incidence in this population are not well defined. METHODS In a multicenter, prospective, observational study, we monitored 1130 HIV-positive and 167 HIV-negative participating adults for up to 64 months for pulmonary disease. The HIV-positive group comprised 814 homosexual or bisexual men, 261 injection-drug users, and 55 female partners of HIV-infected men. RESULTS There were 237 episodes of bacterial pneumonia among the HIV-positive participants (rate, 5.5 per 100 person-years), as compared with 6 episodes among the HIV-negative participants (rate, 0.9 per 100 person-years; P < 0.001). The rate of bacterial pneumonia increased with decreasing CD4 lymphocyte counts (2.3, 6.8, and 10.8 episodes per 100 person-years in the strata with more than 500, 200 to 500, and fewer than 200 cells per cubic millimeter, respectively; P < or = 0.022 for each comparison). Injection-drug users had a higher rate of bacterial pneumonia than did homosexual or bisexual men or female partners. In the stratum with the fewest CD4 lymphocytes, cigarette smoking was associated with an increased rate of pneumonia. Mortality was almost four times higher among participants with an episode of pneumonia than among the others. Prophylaxis with trimethoprim-sulfamethoxazole was associated with a 67 percent reduction in confirmed episodes of bacterial pneumonia (P = 0.007). CONCLUSIONS Bacterial pneumonia is more frequent in HIV-positive persons than in seronegative controls, and the risk is highest among those with CD4 lymphocyte counts below 200 per cubic millimeter and among injection-drug users.

INCIDENCE OF TUBERCULOSIS IN THE UNITED STATES AMONG HIV-INFECTED PERSONS. THE PULMONARY COMPLICATIONS OF HIV INFECTION STUDY GROUP

Among opportunistic pathogens associated with the acquired immunodeficiency syndrome (AIDS), Mycobacterium tuberculosis is distinguished by its relative virulence and potential for person-to-person transmission. Persons infected with human immunodeficiency virus (HIV) are particularly susceptible to tuberculosis, both from the reactivation of latent infection and from new infection with rapid progression to active disease [1-4]. The annual incidence of tuberculosis in the United States was 8.7 per 100 000 persons in 1995 [5], but rates 1000-fold higher have been reported in some HIV-seropositive populations [6-14]. Most studies have been restricted by geography, HIV-risk group, or specific high-prevalence settings; such restrictions have resulted in an inaccurate assessment of the overall effect of the HIV epidemic on the incidence of tuberculosis in the United States [15, 16]. The Pulmonary Complications of HIV Infection Study (PCHIS) [17] prospectively followed HIV-seropositive patients who had demographic variables similar to those of patients with AIDS in the United States. Participants with asymptomatic or symptomatic HIV infection were recruited from sites in the eastern, midwestern, and western United States. A previous report on this cohort [18] identified determinants of delayed-type hypersensitivity response and risk factors for tuberculin reactivity. We examined the incidence of tuberculosis among patients enrolled in the PCHIS for a median observation period of approximately 4.5 years. Methods Patients and Study Design The PCHIS was a multicenter, prospective study of the frequency and spectrum of pulmonary disorders in persons infected with HIV. From November 1988 through February 1990, 1171 HIV-seropositive persons and 182 HIV-seronegative persons were enrolled at centers in six U.S. cities: New York; Newark, New Jersey; Detroit; Chicago; San Francisco; and Los Angeles. Participants were followed through 31 March 1994. We report on 1130 HIV-infected persons from the PCHIS who were followed past baseline. Participants were recruited to represent a range of severity of HIV disease. Approximately half of the participants at each center had CD4 lymphocyte counts of 400 cells/mm3 or more and no HIV-related symptoms, and half had CD4 lymphocyte counts of less than 400 cells/mm3 or symptomatic HIV infection. Both groups included persons from one of three HIV-transmission categories: homosexual men, male and female injection drug users, and women who had acquired HIV through heterosexual contact. Exclusion criteria were AIDS, as defined by the Centers for Disease Control and Prevention (CDC) [19]; acute pulmonary processes; use of immunosuppressive therapy in the past 6 months; and treatment of tuberculosis in the past 12 months. The study was approved by the institutional review board at each site, and participants gave informed consent. At baseline and at regular intervals, clinical monitoring (including T-lymphocyte subset analysis and chest roentgenography) was done, and participants were acutely evaluated if new pulmonary symptoms occurred. Centers used the same predetermined diagnostic algorithms that were initiated if specified criteria were met. Complete details of the study design have been described elsewhere [17]. Delayed hypersensitivity was tested at baseline and then annually using purified protein derivative (PPD) tuberculin at a strength of 5 TU per 0.1-mL dose and mumps antigen (Connaught Laboratories, Inc., Swiftwater, Pennsylvania). Tests were administered by intradermal injection of 0.1 mL of antigen by the Mantoux method and read by experienced nurses 48 to 72 hours later in most cases (the interval exceeded 4 days in 18 persons). A positive response to PPD was defined as an induration at least 5 mm in diameter. Any person who was not positive when first tested but who became positive on any subsequent test was considered to be a tuberculin converter. A positive response to mumps was defined as any degree of induration (>0 mm). The criteria for anergy was nonreactivity (0 mm) to both PPD and mumps antigen. Pulmonary tuberculosis was defined by the isolation of M. tuberculosis from a respiratory tract specimen or by improvement on chest radiography in response to specific multidrug antituberculous therapy. Patients who were diagnosed with extrapulmonary tuberculosis had clinically compatible disease and response to specific therapy, with or without the isolation of the organism from a site outside the lung. Patients who were considered to have both pulmonary and extrapulmonary tuberculosis met each set of criteria. These requirements are consistent with those of the CDC for reporting cases of tuberculosis [20], except that we did not require patients to be PPD positive if they had disease that was not mycobacteriologically confirmed. Statistical Analysis Tuberculosis rates were calculated as the number of cases divided by the number of years that patients were followed multiplied by 100. Except as noted below, the length of time that patients were followed was calculated for each person starting from enrollment and continuing until one of the following occurred: diagnosis of tuberculosis, death from any cause, the last study visit, or 31 March 1994. Statistical significance for comparison of rates was determined by tests for person-time data done on the basis of binomial distribution [21]. P values were determined by an exact test when sample sizes were insufficient and by an asymptotic test when sizes were sufficient. All tests were two-sided, and a P value of 0.05 was considered significant. Exact 95% CIs were calculated for rates by assuming the numerator to be a Poisson variable [22] and for rate ratios using a modified binomial model [21]. Adjusted rate ratios for comparisons among groups defined by demographic variables were calculated by using a Mantel-Haenszel type estimator for incidence-rate data with approximate 95% confidence limits based on the tests [21]. Seventy-three participants, including women who had acquired HIV through heterosexual contact and persons were not black, white, or Hispanic, were excluded from some calculations of adjusted rates because of small sample sizes. Distributions of time to death among patients with tuberculosis were estimated using the Kaplan-Meier method, and comparisons were made using the log-rank test. To calculate tuberculosis rates by immunologic status, we divided the time each participant was followed into the number of years during which CD4 lymphocyte counts were 200 cells/mm3 or greater and the number of years after CD4 lymphocyte counts were less than 200 cells/mm3. Time for these CD4 groups was then summed for all participants. Rates were calculated as the number of tuberculosis cases in each group divided by the number of years followed. One participant who did not have CD4 measurements was omitted from these calculations. Twenty-three participants who were never tested for PPD response were excluded from PPD conversion rates and calculations of tuberculosis rates by PPD status. Participants who were tested for PPD response at least once were classified into one of three groups: positive at entry, newly positive (converted), or negative. One hundred seventy-two of 1107 participants were assigned to groups on the basis of only one test. Baseline PPD status was assigned for 66 participants who were not tested at study entry by using the first reported test and time followed calculated from the date of that test. For participants who developed tuberculosis, only the results of PPD tests done before diagnosis were considered. Tuberculin converters were considered to be part of the negative group before becoming PPD positive and to be part of the newly positive group after converting. Persons who reported a history of isoniazid use or tuberculosis before the study or who received isoniazid for at least 6 months during follow-up were considered to have completed prophylactic therapy. All others were considered to have not been given prophylaxis. Time before completion of isoniazid therapy was included with time followed in the untreated group. Restricted tuberculosis rates were calculated by PPD status for those considered to have not received prophylaxis. Results Patient Characteristics at Baseline Overall, 1171 HIV-seropositive persons entered the study. Follow-up was completed for 1130 persons (96%), whose baseline characteristics are shown in Table 1. Approximately 1% of patients reported a history of tuberculosis, 8% reported a previous positive result on a PPD test, and 4% reported previous use of isoniazid. The median CD4 T-lymphocyte count among HIV-seropositive patients was 410 cells/mm3: Thirty-six percent of patients had counts of at least 500 cells/mm3, 44% had counts between 200 and 499 cells/mm3, and 19% had counts of less than 200 cells/mm3. At study entry, 6% of patients were PPD positive, 42% were reactive to mumps antigen, and 54% were anergic. A cross-sectional analysis of skin-test results at baseline in this cohort has been described in detail elsewhere [18]. Table 1. Baseline Characteristics of the Study Chart* Patient Follow-up The median duration of follow-up was 53 months. By the end of the study, 655 persons had survived after a median follow-up of 57 months (range, 31 to 64 months), 354 had died after a median follow-up of 31 months (range, 1 to 63 months), and 121 withdrew or were lost to follow-up after a median of 25 months (range, 1 to 61 months). Participants received PPD skin tests a median of three times, and 1107 (98%) participants were evaluated at least once. Sixty-six (6%) participants were PPD positive when first tested. Among the 1041 patients who were PPD negative at first testing, 29 subsequently became PPD positive (0.8 conversions per 100 person-years). During follow-up, isoniazid prophylaxis was prescribed for 110 persons (10%), but only 53 (5%) received therapy for 6 months or more. Inc

Tuberculin and Anergy Testing in HIV-Seropositive and HIV-Seronegative Persons

Human immunodeficiency virus (HIV) is playing a substantial role in the resurgence of tuberculosis in the United States. Particularly affected are people in urban areas, where there are large populations of HIV-infected persons [1-8]. Urban subpopulations with a high prevalence of HIV infection, such as intravenous drug users (a group already at increased risk for tuberculosis before the appearance of the acquired immunodeficiency syndrome [AIDS]), have the highest tuberculosis attack rates [3]. Unlike other AIDS-associated opportunistic pathogens, Mycobacterium tuberculosis is readily communicable among persons with all levels of immunity. Recently, tuberculosis outbreaks, some with multidrug-resistant strains, have occurred among HIV-positive patients with transmission to HIV-negative patients and health care workers [9-13]. Prevention strategies rely heavily on the use of tuberculin purified protein derivative (PPD) to identify persons harboring M. tuberculosis [14]. Anergy, a consequence of HIV infection, undermines these strategies in persons at the highest risk for tuberculosis infection and subsequent active disease [15-18]. A negative PPD test result in this setting could be attributable to a true lack of exposure to tuberculosis or simply to the incapacity of the patient to manifest an appropriate cell-mediated immune response. To reduce the measured prevalence of anergy and thereby increase the proportion of tuberculin nonreactors who can be considered truly PPD negative, the Centers for Disease Control and Prevention (CDC) has recommended the additional use of at least two delayed-type hypersensitivity control antigens (mumps antigen plus Candida antigen or tetanus toxoid) when screening HIV-infected patients. Thus, persons from populations with a prevalence of tuberculous infection of 10% or more and who are tuberculin negative but not anergic may be spared preventive therapy with isoniazid [19]. However, the ability of control antigens to predict the likelihood that a negative PPD test result is truly negative in this highly anergic population is unknown. To improve approaches to tuberculosis prophylaxis, more data are needed about the relations among delayed-type hypersensitivity responsiveness, the prevalence of tuberculosis, and the waning immunity associated with progressive HIV infection. In an ongoing multicenter study of the natural history of the pulmonary complications associated with HIV infection, we have been examining these factors prospectively in a cohort of 1353 persons in 6 U.S. geographic areas. Recently, we evaluated baseline delayed-type hypersensitivity responses in this cohort of HIV-seropositive and HIV-seronegative persons and identified variables associated with tuberculin reactivity and anergy. Methods Patients and Study Design The Pulmonary Complications of HIV Infection Study is a multicenter study designed to prospectively describe the frequency, types, and effect of pulmonary complications in HIV-infected persons, both before and after the development of AIDS. All diagnoses, treatments, and outcomes are recorded and monitored in a common database. Because our purpose was to evaluate longitudinally both the early and late pulmonary manifestations of HIV infection, each center attempted to recruit about 170 HIV-seropositive participants, half with CD4 lymphocyte counts of 400 cells/mm3 or more and no HIV-related symptoms and half with fewer than 400 CD4 cells/mm3 or symptomatic HIV-infection (defined by a temperature of 38 C or more for at least 2 weeks, involuntary weight loss of 10% or more from baseline, diarrhea of at least a 1-month duration, oral candidiasis, or oral hairy leukoplakia). Within each group, participants were drawn from one of three HIV transmission categories (homosexual men, male and female intravenous drug users, and women with heterosexually acquired HIV infection) to reflect their approximate distribution at each clinical site. About 30 HIV-seronegative homosexual men and intravenous drug users were also recruited at each site to serve as controls. Participants had to be willing and able to comply with the protocol and were required to give informed consent. The study was reviewed and approved by the institutional review board at each site. Exclusion criteria included Centers for Disease Control and Prevention (CDC)-defined AIDS [20], severe non-HIV-related disease likely to affect survival, lung disorders likely to interfere with the required evaluations, acute pulmonary processes, immunosuppressive therapies within the previous 6 months, and treatment for active tuberculosis within the past 12 months. From November 1988 through February 1990, we enrolled 1353 persons in the study, of whom 1171 were HIV seropositive and 182 were HIV seronegative. Human immunodeficiency virus serologic status was confirmed at study entry using a licensed enzyme-linked immunosorbent assay and a Western blot assay. Further baseline evaluation included a complete medical history, a physical examination, hematologic and biochemical studies, T-lymphocyte subset analysis, delayed-type hypersensitivity testing, a chest roentgenogram, and pulmonary function measurements. Measurement of Delayed-Type Hypersensitivity Response We tested delayed-type hypersensitivity with the following antigens: mumps antigen (Connaught Laboratories, Inc., Swiftwater, Pennsylvania); Dermatophytin 0 (Candida) at 1:100 dilution (Hollister-Stier, Spokane, Washington); Dermatophytin (trichophytin) at 1:100 dilution (Hollister-Stier); and tuberculin PPD at a strength of 5 tuberculin units per 0.1-mL dose (Connaught Laboratories, Ltd., Willowdale, Ontario, Canada). Tests were administered by intradermal injection of 0.1 mL of antigen (Mantoux method) and read by a trained observer 48 to 72 hours after application in most participants (the interval exceeded 4 days in 18 persons). Response was recorded as the greatest diameter of induration. We used the current standard operational criteria for a positive response: induration of at least 5 mm for all antigens except PPD, for which an induration of 10 mm was required among HIV-uninfected persons [19]. Anergy was defined as 0 mm of induration for all delayed-type hypersensitivity antigens administered in a given panel. Unless otherwise specified, a test battery of tuberculin PPD, mumps antigen, and Candida antigen was used to define anergy. At one site, however, the investigators did not distinguish between induration and erythema for the mumps, Candida, and trichophytin tests, documenting reactions to these antigens in terms of millimeters of erythema. When examined by zone diameter, their measurements were generally consistent with those from the other centers. Furthermore, the results of multivariate analyses with and without the data from this site were similar. Other investigators have shown a high degree of correlation between induration and erythema with these antigens [21]. Thus, for the purposes of our analysis, responses were recorded in millimeters of induration. Because trichophytin elicited a positive reaction in only 14.0% of those tested, it was dropped from the delayed-type hypersensitivity battery midway through the enrollment period. Although lot numbers varied, the skin tests used at the centers were supplied by the same manufacturers, with a single exception: At one site, investigators used a different Candida preparation. The Candida test results for this center (247 participants) were excluded from all analyses involving this antigen. Determination of Lymphocyte Subsets Lymphocyte subsets were determined for CD3, CD4, and CD8 receptor-bearing cells by the same laboratory at each site. All laboratories participated in the flow cytometry quality control program sponsored by the National Institute of Allergy and Infectious Diseases [22]. Statistical Analysis All analyses are based on data collected during the baseline evaluation. Statistical significance for comparisons of proportions was determined by chi-square or Fisher exact test [23]. For comparisons among nonindependent groups, repeated-measures analysis for categorical outcomes was used to determine statistical significance [24, 25]. Logistic regression models were used to study the relation between PPD positivity or anergy and potential risk factors [26]. Risk factors considered were HIV status; CD4 count among HIV-seropositive persons; intravenous drug use; race or ethnicity; a history of a positive PPD test result, tuberculosis, or BCG vaccination; age; gender; and socioeconomic status. Seventy-seven participants, including women with heterosexually acquired infection and persons who were not white, black, or Hispanic, were excluded from all multivariate analyses because of small sample sizes. Initial models included HIV status (positive or negative), intravenous drug use (presence or absence), race or ethnicity (white, black, or Hispanic), a history of a positive PPD test result, and age, as well as interaction terms, to determine whether the effect of HIV positivity varied among these groups or whether the effect of drug use varied by race. No statistically significant interactions were observed. All odds ratios presented were derived from subsequent models containing main effects only. A dichotomous variable indicating the 12% of the cohort who did not have a high school diploma was used as an index of socioeconomic status and was included in all final models. All tests were two sided. A P value of 0.05 was considered statistically significant. Ninety-five percent CIs are given when appropriate. Results Patient Characteristics During the 16-month enrollment period, 1171 HIV-seropositive and 182 HIV-seronegative persons entered the study. The two groups were similar with regard to age, sex, race, transmission category, and tuberculosis-associated history (Table 1). Of the 1165 men, 966 (82.9%) were homosexual; of the 188 women, 132 (70.2%) were intravenous drug users.

Alcohol consumption among HIV-infected patients

This prospective, cohort study analyzed the prevalence of alcoholism and patterns of alcohol intake over time in a cohort of HIV-infected patients, predominantly homosexual/bisexual men. One hundred eleven HIV-positive subjects were recruited from a comprehensive HIV clinic associated with a large Midwestern university hospital. Each participant completed the Michigan Alcoholism Screening Test (MAST) survey and a standardized quantity—frequency questionnaire on alcohol intake at enrollment. The quantity—frequency scale was repeated every six months for a total of 30 months. Forty-five of the 111 subjects (41%) met the criteria for alcoholism, as defined by a MAST score 5 or higher. There was a significant decrease in alcohol consumption over time, from 6.4 drinks/week in the initial time period to 3.9 drinks/week by the final time period (p<0.001).

Pulmonary disease caused by nontuberculous mycobacteria

The propensity of various nontuberculous mycobacteria to cause lung disease varies widely and is conditioned by host factors; infection is believed to occur from environmental sources. Nontuberculous mycobacteria pulmonary disease (PNTM) is increasing worldwide and Mycobacterium avium complex is the most common cause. PNTM usually occurs in one of three prototypical forms: hypersensitivity pneumonitis, cavitary tuberculosis-like disease or nodular bronchiectasis. PNTM has been linked in some patients to genetic variants of the cystic fibrosis transmembrane conductance regulator gene and a distinct patient phenotype. Interactions between PNTM and other comorbidities are also increasingly appreciated. Guidelines for diagnosis, emphasizing chest imaging and microbiology, have been published; speciation using molecular techniques is critical for accuracy and for treatment decisions. Clinical trials are lacking to inform treatment for many species and experience with M. avium complex and several others species serves as a guide instead. Use of multiple drugs for a period of at least 12 months following sputum conversion is the norm for most species. In vitro drug susceptibility results for many drugs may not correlate with clinical outcomes and such testing should be done on a selective basis.

Impact of Bacterial Pneumonia and Pneumocystis carinii Pneumonia on Human Immunodeficiency Virus Disease Progression

The course of pneumonia caused by pyogenic bacteria and Pneumocystis carinii was examined in a multicity cohort study of HIV infection. The median duration of survival among 150 individuals following initial bacterial pneumonia was 24 months, compared with 37 months among 299 human immunodeficiency virus (HIV)-infected control subjects matched by study site and CD4 lymphocyte count (P<.001). For 152 subjects with P. carinii pneumonia, median survival was 23 months, compared with 30 months for 280 matched control subjects (P = .002). Median durations of survival associated with the two types of pneumonia differed by only 47 days, despite a higher median CD4 lymphocyte count associated with bacterial pneumonia. These results suggest that both P. carinii pneumonia and bacterial pneumonia are associated with a significantly worse subsequent HIV disease course. The similarity of prognosis after one episode of bacterial pneumonia vs. an AIDS-defining opportunistic infection and the proportion of cases occurring in association with a CD4 lymphocyte count of >200 suggest that measures to prevent bacterial pneumonia should be emphasized.

Bacterial pneumonia associated with HIV-1 infection

Bacterial pneumonia remains an important cause of treatable morbidity among HIV-1-infected persons. These pneumonias occur at all CD4 counts but are especially common as the HIV-1 infection progresses. Bronchopneumonia should be considered particularly in the setting of segmental or lobar consolidation associated with productive cough and fever. S. pneumoniae remains the most common pathogen causing bronchopneumonia. Because of the high rate of bacteremia, diagnosis may be facilitated by blood cultures. Treatment is similar to management of HIV-1-seronegative persons, although drug resistance against some bacteria may be an emerging problem. Several opportunities exist for prevention, and these should be pursued vigorously.

Pulmonary complications of amiodarone toxicity

A MIODARONE HYDROCHLORIDE, a benzofurone derivative, has been used since 1969 for the control of cardiac arrhythmias in the United States. It appears to be uniquely effective for some patients with refractory ventricular arrhythmias. Although serum levels in the range of 1.0 to 2.5 pg/mL have been considered therapeutic,’ amiodarone concentrations in tissues such as fat, skin, and lung may be many times greater. A variety of side effects have been noted following use of this drug, including corneal microdeposits, alteration of thyroid function, dermatitis, pseudocyanotic skin discoloration, hepatic dysfunction, proximal muscle weakness, and peripheral neuropathy. Pulmonary complications were not appreciated until 1980, when the first report of suspected pulmonary toxicity appeared.2 Since then there have been a number of articles describing pulmonary toxicity due to this agent in Europe and the United States. The magnitude of the problem of pulmonary toxicity is difficult to determine. The literature is primarily one of case reports and the criteria used to make the clinical diagnosis of amiodarone pulmonary toxicity are imprecise and inconstant. There is no hallmark of this complication short of pulmonary histology, and lung biopsy has not been performed routinely. Patients receiving amiodarone commonly have a history of clinical conditions, including congestive heart failure, which may be difficult to distinguish from amiodarone lung toxicity. Furthermore, alterations in pulmonary function may occur in some amiodarone treated patients without other clinical manifestations of pulmonary toxicity. All of these factors make it difficult to estimate the incidence of clinically significant amiodarone pulmonary toxicity. Key features that should be used in defining this entity in future studies include: (1) biopsy evidence of alveolitis, (2) diffuse pulmonary infiltrates or infiltrates involving the upper lung zones, (?) dyspnea and cough, (4) exclusion of other conditions likely to produce the clinical picture including congestive heart failure, infection, and collagen vascular disease, and (5) improvement after stopping or decreasing the dose of amiodarone. With these provisos in mind, the best estimate of the incidence of clinically significant amiodarone pulmonary toxicity in the United States is 5% to 15%.3-‘2 It should be noted, however, that autopsy studies suggest this condition may be underdiagnosed.

Overall and cause-specific mortality in a cohort of home-/bisexual men, injecting drug users, and female partners of HIV-infected men

OBJECTIVE To study the overall and cause-specific HIV-related mortality in a cohort of HIV-seropositive subjects according to transmission category, race/ethnicity, sex and severity of immunosuppression. DESIGN A cohort of 1129 HIV-seropositive homo-/bisexual men, injecting drug users, and female partners of HIV-infected men were enrolled at six centers in San Francisco, Los Angeles, Chicago, Newark, Detroit and New York between 1 November 1988 and 1 November 1989. Subjects were evaluated every 6 months at least until 31 March 1994. METHODS The analyses of overall mortality for the subgroups of interest were performed with Kaplan-Meier plots and Cox proportional hazards models. Cause-specific analyses were performed on the primary cause of death using rates per 100 person-years of exposure. RESULTS AND CONCLUSIONS Baseline severity of immunosuppression is the strongest predictor of mortality. There were no statistically significant differences in overall HIV-related mortality among transmission categories, race/ethnicity groups or sexes. There were differences, however, in cause-specific mortality among the different risk groups.

Obtaining permission for an autopsy: Its importance for patients and physicians

This paper reviews the importance, benefits, and methods of increasing autopsy percentages. Its focus is on specific procedures for obtaining autopsy consent, particularly in terms of addressing the problems that most often interfere with obtaining permission for postmortem examination. Techniques for handling various misconceptions about autopsies are discussed. These guides for postmortem-related discussions with families will lead to improvement in overall physician performance and satisfaction.