Antibiotic use and risk of ischemic stroke in the elderly.

PURPOSE: To determine whether treating infections with antibiotics that have antichlamydial activity decreases the risk of ischemic stroke in the elderly. SUBJECTS: We analyzed data from 199 553 subjects 65 years and older in a health care claims database who had continuous health and pharmacy coverage for at least 2 years between January 1, 1991, and September 30, 1997. Using proportional hazards models with time-dependent covariates for prior antibiotic prescription and adjusting for cardiovascular risk factors, we determined the associations between antibiotic use and first claim for ischemic stroke (n = 7,335) during the observation period. RESULTS: Rates of stroke (per 1,000 person-years) were 6.64 for macrolides, 9.27 for quinolones, 7.49 for tetracyclines, 6.88 for penicillins, 7.97 for cephalosporins, 8.58 for trimethoprim-sulfamethoxazole, and 7.29 for subjects with no antibiotic claims. The adjusted hazard ratios (HR) were 0.94 (95% confidence interval [CI]: 0.87 to 1.01) for macrolides, 1.04 (95% CI: 0.91 to 1.18) for tetracyclines, 1.02 (95% CI: 0.95 to 1.08) for penicillins, and 1.00 (95% CI: 0.82 to 1.22) for trimethoprim-sulfamethoxazole. Subjects with claims for quinolone antibiotics (HR = 1.17; 95% CI: 1.09 to 1.26) and cephalosporins (HR = 1.09; 95% CI: 1.02 to 1.16) had a slightly higher risk of stroke. CONCLUSION: Exposures to short courses of antibiotics are not associated with lower risk of ischemic stroke in patients aged 65 years and older.

Neighborhood poverty and the resurgence of tuberculosis in New York City, 1984-1992.

OBJECTIVES: The resurgence of tuberculosis (TB) in NewYork City has been attributed to AIDS and immigration; however, the role of poverty in the epidemic is unclear. We assessed the relation between neighborhood poverty and TB at the height of the epidemic and longitudinally from 1984 through 1992. METHODS: Census block groups were used as proxies for neighborhoods. For each neighborhood, we calculated TB and AIDS incidence in 1984 and 1992 with data from the Bureaus of Tuberculosis Control and AIDS Surveillance and obtained poverty rates from the census. RESULTS: For 1992, 3,343 TB cases were mapped to 5,482 neighborhoods, yielding a mean incidence of 46.5 per 100,000. Neighborhood poverty was associated with TB (relative risk = 1.33; 95% confidence interval = 1.30, 1.36 per 10% increase in poverty). This association persisted after adjustment for AIDS, proportion foreign born, and race/ethnicity. Neighborhoods with declining income from 1980 to 1990 had larger increases in TB incidence than did neighborhoods with increasing income. CONCLUSIONS: Leading up to and at the height of the TB epidemic in New York City, neighborhood poverty was strongly associated with TB incidence. Public health interventions should target impoverished areas.

An analysis of cardiac mortality in patients with new-onset end-stage renal disease in New York State.

End-stage renal disease (ESRD) is associated with an overall one-year mortality of 23.5% in the US, of which cardiac causes constitute 50% of all deaths. Data on incident ESRD patients were obtained from the Health Care Financing Administration's 2728 and 2746 forms by special request from the ESRD Network of New York. 4,948 ESRD patients, who started dialysis in New York State from April 1, 1995, through April 1, 1996, were assessed to identify risk factors present at the initiation of dialysis that predict cardiac death. 899 deaths were registered during the 19-month-follow-up period, 50% of which were from cardiac causes. Using the Cox-proportional hazards model, the increasing age category, white race, the presence of one or more vascular co-morbid conditions, and the presence of diabetes and one or more cardiac co-morbid conditions significantly predicted cardiac death (p < 0.05). Diabetes increased the risk for cardiac death by 48% for those patients without any cardiac co-morbidities (RR = 1.48, p < 0.0082). In contrast with results observed in the general population, gender, serum albumin and body mass index were not significant predictors of cardiac death. In identifying risk factors present at the initiation ofdialysis that predict cardiac death, this study highlights factors that may be modified prior to dialysis initiation in order to improve life expectancy and mortality rates and decrease health care costs for the ESRD population.

Changes in liver function tests after laparoscopic cholecystectomy: not so rare, not always ominous.

The incidental findings of increased alanine aminotransferase (ALT) and aspartate amino transferase (AST) after uneventful laparoscopic cholecystectomy (LC) prompted us to investigate the incidence and the clinical significance of this phenomenon. Changes in liver function test after LC (n = 55) were compared with those after OC (n = 16). Liver function tests were obtained preoperatively and postoperatively on days 1, 2, and 7. All of the patients fulfilled the selection criteria: normal preoperative liver function test and no endoscopic retrograde cholangiopancreatography, common bile duct exploration, or postoperative biliary complications (injury, infection, or obstruction). Converted cholecystectomies were also excluded. During LC, the intra-abdominal pressure was maintained within the conventional range of 14 to 15 mm Hg. ALT had doubled in the first 48 hours from the preoperative mean in 58.2 per cent in LC patients versus only 6.3 per cent in the OC group. AST doubled from the preoperative mean value in 38.2 per cent in the LC group versus only 6.3 per cent in the OC group. By the 7th postoperative day, the enzymes returned to the preoperative values in both the LC and the OC group. In many instances, a significant increase in ALT and AST blood levels occurred after uneventful LC. The phenomenon is transient as these enzymes returned to normal value within 7 days. These changes are clinically silent in patients with a normal liver function.

A health information network for managing innercity tuberculosis: bridging clinical care, public health, and home care.

The purpose of this study was to use a health information network and innovative technology to coordinate tuberculosis care. An innercity medical center, a local health department, and a home care nurse service in northern Manhattan were used. The organizations were linked with computer networks. An automated decision support system with a natural language processor was used to detect tuberculosis cases and report them to the health department, and to select patients for respiratory isolation. Educational materials were placed on the World Wide Web and a Web-based kiosk. Home care nurses were outfitted with wireless pen-based computers, and data were relayed to the medical center. Automated tuberculosis case reporting resulted in time savings but not improved accuracy. Automated rules resulted in significant improvements in respiratory isolation. Kiosk educational materials were well-used. Wireless computing led to better access to information for both nurses and physicians, but not to reduction of workload. The key success element was recognition of critical priorities. It is concluded that innovative technology can facilitate the coordination of clinical care, public health, and home care.

Association between coronary heart disease and cancers of the breast, prostate, and colon.

Coronary heart disease (CHD) and cancers of the breast, prostate, and colon are more common in industrialized countries than in the developing world, and to some degree, these conditions appear to share risk factors. To investigate whether there is an association between these cancers and a prior history of CHD, a hospital-based case-control study was conducted at Columbia-Presbyterian Medical Center in New York. The study was based on 252 breast cancer cases, 256 colorectal cancer cases, and 322 benign surgical controls, all of whom underwent biopsy or surgery between January 1989 and December 1992, and on 319 prostate cancer cases and 189 benign prostatic hypertrophy controls diagnosed between January 1984 and December 1986 (prior to widespread use of prostate-specific antigen screening). Medical records were reviewed on each, focusing on the preoperative anesthesia and surgical clearances. No association was found between a history of CHD and breast or colorectal cancer, but an elevated risk was found for prostate cancer (odds ratio, 2.00; 95% confidence interval, 1.18-3.39), using unconditional logistic regression with adjustment for appropriate confounders. No association was found between cigarette smoking and any of the three cancers. Aspirin use was protective for colorectal cancer (odds ratio, 0.35; 95% confidence interval, 0.17-0.73) but had no association with breast or prostate cancer. The study suggests that individuals with CHD are at elevated risk for prostate cancer but not breast or colorectal cancer. Etiological risk factors associated with CHD should be investigated with regard to prostate cancer. Patients with CHD may represent a high-risk group for prostate cancer and potential future targets for prostate cancer screening interventions.

Global surveillance for antituberculosis-drug resistance, 1994-1997. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance.

BACKGROUND: Drug-resistant tuberculosis threatens efforts to control the disease. This report describes the prevalence of resistance to four first-line drugs in 35 countries participating in the World Health Organization-International Union against Tuberculosis and Lung Disease Global Project on Anti-Tuberculosis Drug Resistance Surveillance between 1994 and 1997. METHODS: The data are from cross-sectional surveys and surveillance reports. Participating countries followed guidelines to ensure the use of representative samples, accurate histories of treatment, standardized laboratory methods, and common definitions. A network of reference laboratories provided quality assurance. The median number of patients studied in each country or region was 555 (range, 59 to 14,344). RESULTS: Among patients with no prior treatment, a median of 9.9 percent of Mycobacterium tuberculosis strains were resistant to at least one drug (range, 2 to 41 percent); resistance to isoniazid (7.3 percent) or streptomycin (6.5 percent) was more common than resistance to rifampin (1.8 percent) or ethambutol (1.0 percent). The prevalence of primary multidrug resistance was 1.4 percent (range, 0 to 14.4 percent). Among patients with histories of treatment for one month or more [corrected], the prevalence of resistance to any of the four drugs was 36.0 percent (range, 5.3 to 100 percent), and the prevalence of multidrug resistance was 13 percent (range, 0 to 54 percent). The overall prevalences were 12.6 percent for resistance to any of the four drugs [corrected] (range, 2.3 to 42.4 percent) and 2.2 percent for multidrug resistance (range, 0 to 22.1 percent). Particularly high prevalences of multidrug resistance were found in the former Soviet Union, Asia, the Dominican Republic, and Argentina. CONCLUSIONS: Resistance to antituberculosis drugs was found in all 35 countries and regions surveyed, suggesting that it is a global problem.

Respiratory isolation of tuberculosis patients using clinical guidelines and an automated clinical decision support system.

OBJECTIVE: To evaluate a clinical guideline and an automated computer protocol for detection and respiratory isolation of tuberculosis (TB) patients. DESIGN: An automated computer protocol was tested on a retrospective cohort of adult culture-positive TB patients admitted from 1992 to 1993 to Columbia-Presbyterian Medical Center and evaluated prospectively from July 1995 until July 1996. SETTING: A large teaching hospital in New York City. PATIENTS: 171 adult patients admitted from 1992 to 1993 and 43 patients admitted between July 1995 and July 1996. INTERVENTIONS: The 1990 Centers for Disease Control and Prevention guidelines for preventing transmission of TB were adapted to formulate clinical guidelines to ensure early isolation of TB patients at Columbia-Presbyterian Medical Center. RESULTS: Implementation of a clinical respiratory isolation protocol resulted in a significant improvement in TB patient isolation rates, from 45 (51%) of 88 in 1992 to 62 (75%) of 83 in 1993 (P<.001). In testing automated protocols, the theoretical improvement would have identified an additional 27 patients not isolated by clinicians, making the overall isolation rate 134 (78%) of 171. For the prospective evaluation, 30 (70%) of 43 TB patients were isolated by clinicians adhering to the clinical protocol. Four additional patients were identified by the automated TB protocol, making the combined isolation rate 34 (79%) of 43. CONCLUSIONS: A clinical policy to isolate TB patients and suspected human immunodeficiency virus-infected patients with cough, fever, or radiographic abnormalities improved isolation of culture-documented TB patients from 1992 to 1993. Automated computer protocols were successful in identifying additional potentially infectious patients that clinicians failed to place on respiratory isolation. Clinical and automated protocols combined resulted in better isolation rates than a clinical protocol alone.

Run-in periods in randomized trials: implications for the application of results in clinical practice.

Prerandomization run-in periods are being used to select or exclude patients in an increasing number of clinical trials, but the implications of run-in periods for interpreting the results of clinical trials and applying these results in clinical practice have not been systematically examined. We analyzed illustrative examples of reports of clinical trials in which run-in periods were used to exclude noncompliant subjects, placebo responders, or subjects who could not tolerate or did not respond to active drug. The Physicians' Health Study exemplifies the use of a prerandomization run-in period to exclude subjects who are nonadherent, while recent trials of tacrine for Alzheimer disease and carvedilol for congestive heart failure typify the use of run-in periods to exclude patients who do not tolerate or do not respond to the study drug. The reported results of these studies are valid. However, because the reported results apply to subgroups of patients who cannot be defined readily based on demographic or clinical characteristics, the applicability of the results in clinical practice is diluted. Compared with results that would have been observed without the run-in period, the reported results overestimate the benefits and underestimate the risks of treatment, underestimate the number needed to treat, and yield a smaller P value. The Cardiac Arrhythmia Suppression Trial exemplifies the use of an active-drug run-in period that enhances clinical applicability by selecting a group of study subjects who closely resembled patients undergoing active clinical management for this problem. Run-in periods can dilute or enhance the clinical applicability of the results of a clinical trial, depending on the patient group to whom the results will be applied. Reports of clinical trials using run-in periods should indicate how this aspect of their design affects the application of the results to clinical practice.

Automated tuberculosis detection.

OBJECTIVE: To measure the accuracy of automated tuberculosis case detection. SETTING: An inner-city medical center. INTERVENTION: An electronic medical record and a clinical event monitor with a natural language processor were used to detect tuberculosis cases according to Centers for Disease Control criteria. MEASUREMENT: Cases identified by the automated system were compared to the local health department's tuberculosis registry, and positive predictive value and sensitivity were calculated. RESULTS: The best automated rule was based on tuberculosis cultures; it had a sensitivity of .89 (95% CI.75-.96) and a positive predictive value of .96 (.89-.99). All other rules had a positive predictive value less than .20. A rule based on chest radiographs had a sensitivity of .41 (.26-.57) and a positive predictive value of .03 (.02-.05), and rule the represented the overall Centers for Disease Control criteria had a sensitivity of .91 (.78-.97) and a positive predictive value of .15 (.12-.18). The culture-based rule was the most useful rule for automated case reporting to the health department, and the chest radiograph-based rule was the most useful rule for improving tuberculosis respiratory isolation compliance. CONCLUSIONS: Automated tuberculosis case detection is feasible and useful, although the predictive value of most of the clinical rules was low. The usefulness of an individual rule depends on the context in which it is used. The major challenge facing automated detection is the availability and accuracy of electronic clinical data.

The role of diabetes mellitus in the higher prevalence of tuberculosis among Hispanics.

OBJECTIVES: This research studied the relative contribution of diabetes mellitus to the increased prevalence of tuberculosis in Hispanics. METHODS: A case-control study was conducted involving all 5290 discharges from civilian hospitals in California during 1991 who had a diagnosis of tuberculosis, and 37,366 control subjects who had a primary discharge diagnosis of deep venous thrombosis, pulmonary embolism, or acute appendicitis. Risk of tuberculosis was estimated as the odds ratio (OR) across race/ethnicity, with adjustment for other factors. RESULTS: Diabetes mellitus was found to be an independent risk factor for tuberculosis. The association of diabetes and tuberculosis was higher among Hispanics (adjusted OR [ORadj] = 2.95: 95% confidence interval [CI] = 2.61, 3.33) than among non-Hispanic Whites (ORadj = 1.31: 95% CI = 1.19. 1.45): among non-Hispanic Blacks, diabetes was not found to be associated with tuberculosis (ORadj = 0.93: 95% CI = 0.78, 1.09). Among Hispanics aged 25 to 54, the estimated risk of tuberculosis attributable to diabetes (25.2%) was equivalent to that attributable to HIV infection (25.5%). CONCLUSIONS: Diabetes mellitus remains a significant risk factor for tuberculosis in the United States. The association is especially notable in middle-aged Hispanics.

Nonadherence in tuberculosis treatment: predictors and consequences in New York City.

BACKGROUND: Poor adherence to antituberculosis treatment is the most important obstacle to tuberculosis control. PURPOSE: To identify and analyze predictors and consequences of nonadherence to antituberculosis treatment. PATIENTS AND METHODS: Retrospective study of a citywide cohort of 184 patients with tuberculosis in New York City, newly diagnosed by culture in April 1991-before the strengthening of its control program-and followed up through 1994. Follow-up information was collected through the New York City tuberculosis registry. Nonadherence was defined as treatment default for at least 2 months. RESULTS: Eighty-eight of the 184 (48%) patients were nonadherent. Greater nonadherence was noted among blacks (unadjusted relative risk [RR] 3.0, 95% confidence interval [CI] 1.1 to 8.6, compared with whites), injection drug users (RR 1.5, 95% CI 1.1 to 2.0), homeless (RR 1.4, 95% CI 1.0 to 1.8), alcoholics (RR 1.4, 95% CI 1.0 to 1.9), and HIV-infected patients (RR 1.4, 95% CI 1.1 to 1.9); also, census-derived estimates of household income were lower among nonadherent patients (P = 0.018). In multivariate analysis, only injection drug use and homelessness predicted nonadherence, yet 46 (39%) of 117 patients who were neither homeless nor drug users were nonadherent. Nonadherent patients took longer to convert to negative culture (254 versus 64 days, P < 0.001), were more likely to acquire drug resistance (RR 5.6, 95% CI 0.7 to 44.2), required longer treatment regimens (560 versus 324 days, P < 0.0001), and were less likely to complete treatment (RR 0.5, 95% CI 0.4 to 0.7). There was no association between treatment adherence and all-cause mortality. CONCLUSIONS: In the absence of public health intervention, half the patients defaulted treatment for 2 months or longer. Although common among the homeless and injection drug users, the problem occurred frequently and unpredictably in other patients. Nonadherence may contribute to the spread of tuberculosis and the emergence of drug resistance, and may increase the cost of treatment. These data lend support to directly observed therapy in tuberculosis.

Association of apo E polymorphism with plasma lipid levels in a multiethnic elderly population.

Apolipoprotein E polymorphisms are important determinants of blood lipid levels and have been associated with longevity and atherosclerosis. However, information is limited on the effects of apo E variation on the lipids of nonwhite and elderly individuals. We tested the hypothesis that apo E polymorphisms are associated with plasma lipid levels in an elderly, multiethnic population. Cross-sectional data from 1068 noninstitutionalized individuals from northern Manhattan over the age of 64 who were not on a lipid-lowering diet or drug were analyzed. The ethnic distribution was 34% African-Americans, 47% Hispanics, and 19% non-Hispanic Caucasians. In the entire group, the most prevalent apo E allele was epsilon 3 (76%), followed by epsilon 4 (16%) and epsilon 2 (8%); epsilon 4 was more prevalent in African-Americans (21%) than in non-Hispanic Caucasians (12%) or Hispanics (14%). The apo epsilon 2 allele was the most important correlate of plasma lipids, but association varied across ethnoracial groups. After being adjusted for age, sex, obesity, diabetes mellitus, and alcohol intake, LDL cholesterol levels declined with each apo epsilon 2 allele by 8.8 mg/dL in Hispanics and by 25.6 and 18.1 mg/dL in non-Hispanic Caucasians and African-Americans, respectively (P < .001). No significant independent effect was noted for any apo E genotype on HDL cholesterol. Overall, there was a reduction in the total/HDL cholesterol ratio, per apo epsilon 2 allele, of 0.82 in non-Hispanic Caucasians and 0.43 and 0.48 in African-American and Hispanic individuals, respectively (P < .05). In a multivariate model, apo epsilon 4 did not significantly affect plasma lipid levels. Plasma triglyceride levels were inversely correlated with the number of apo epsilon 4 alleles (175, 159, and 143 mg/dL with 0, 1, and 2 alleles, respectively; P =.002), and this effect increased with age. Thus, in an elderly, multiethnic population, apolipoprotein E polymorphisms were important determinants of blood lipids, with differing effects depending on ethnicity. The presence of apo epsilon 2 was associated with lower LDL cholesterol levels and total/HDL cholesterol ratio, although apo epsilon genotype did not influence HDL cholesterol levels. Prospective studies are needed to test whether apo epsilon 2 protects against incident cardiovascular disease in the elderly.

The relationship between delayed or incomplete treatment and all-cause mortality in patients with tuberculosis.

OBJECTIVE: To analyze the factors associated with survival in patients with pulmonary and extrapulmonary tuberculosis in New York City. DESIGN: Observational study of a citywide cohort of tuberculosis cases. SETTING: New York City, April 1991, before the strengthening of its control program. PATIENTS: All 229 newly diagnosed cases of tuberculosis documented by culture in April 1991. Most patients (74%) were male, and the median age was 37 years (range, 1-89 years). In all, 89% belonged to minority groups. Human immunodeficiency virus (HIV) infection was present in 50% and multidrug resistance in 7% of the cases. Twenty-one patients (9%) were not treated. MAIN OUTCOME MEASURES: Follow-up information was collected through the New York City tuberculosis registry; death from any cause was verified through the National Death Index. RESULTS: Cumulative all-cause mortality by October 1994 was 44%; the median survival for those who died was 6.3 months (range, 0 days to 3 years). The most important baseline predictors of mortality, adjusted for baseline clinical and demographic factors, were acquired immunodeficiency syndrome (AIDS) (91% vs 11% in HIV-seronegative patients; Cox relative risk [RR], 7.8; 95% confidence interval [CI], 2.1-29.1), multidrug resistance (87% vs 39% in pansensitive cases; adjusted RR, 5.8; 95% CI, 2.3-14.5), and lack of treatment (81% vs 40%; adjusted RR, 3.1; 95% CI, 1.0-9.7). Also, 11 of 13 HIV-infected patients who started treatment after a 1-month delay died. Among 173 patients surviving the recommended treatment period, those who completed therapy (66%) had a lower subsequent mortality (20% vs 37%; RR, 0.5; 95% CI, 0.3-0.9). CONCLUSIONS: Mortality from tuberculosis was high, even among patients without multidrug resistance who were not known to be infected with HIV. Most HIV-seropositive patients with delayed therapy died. Multidrug resistance predicted higher mortality, and treatment completion was associated with improved subsequent patient survival.

The emergence of drug-resistant tuberculosis in New York City.

BACKGROUND: In the past decade the incidence of tuberculosis has increased nationwide and more than doubled in New York City, where there have been recent nosocomial outbreaks of multidrug-resistant tuberculosis. METHODS: We collected information on every patient in New York City with a positive culture for Mycobacterium tuberculosis during April 1991. Drug-susceptibility testing was performed at the Centers for Disease Control and Prevention. RESULTS: Of the 518 patients with positive cultures, 466 (90 percent) had isolates available for testing. Overall, 33 percent of these patients had isolates resistant to one or more antituberculosis drugs, 26 percent had isolates resistant to at least isoniazid, and 19 percent had isolates resistant to both isoniazid and rifampin. Of the 239 patients who had received antituberculosis therapy, 44 percent had isolates resistant to one or more drugs and 30 percent had isolates resistant to both isoniazid and rifampin. Among the patients who had never been treated, the proportion with resistance to one or more drugs increased from 10 percent in 1982 through 1984 to 23 percent in 1991 (P = 0.003). Patients who had never been treated and who were infected with the human immunodeficiency virus (HIV) or reported injection-drug use were more likely to have resistant isolates. Among patients with the acquired immunodeficiency syndrome, those with resistant isolates were more likely to die during follow-up through January 1992 (80 percent vs. 47 percent, P = 0.02). A history of antituberculosis therapy was the strongest predictor of the presence of resistant organisms (odds ratio, 2.7; P < 0.001). CONCLUSIONS: There has been a marked increase in drug-resistant tuberculosis in New York City. Previously treated patients, those infected with HIV, and injection-drug users are at increased risk for drug resistance. Measures to control and prevent drug-resistant tuberculosis are urgently needed.