Fatal toxic epidermal necrolysis during prophylaxis with pyrimethamine and sulfadoxine in a human immunodeficiency virus-infected person.

The combination of pyrimethamine and sulfadoxine (Fansidar) has been reported to cause severe skin reactions including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Recently, this drug combination has been used for prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. After two months of weekly prophylaxis with pyrimethamine and sulfadoxine, a 48-year-old homosexual man who was antibody positive for human immunodeficiency virus developed severe widespread erythema, blisters, and loss of skin in sheets, and subsequently died. To our knowledge, this is the first reported case of fatal toxic epidermal necrolysis occurring in a patient with acquired immunodeficiency syndrome-related complex. The lack of absolute safety of prophylaxis with pyrimethamine and sulfadoxine is emphasized in our case, and mandates cautious use and the consideration of less toxic prophylactic measures such as therapy with the recently introduced aerosolized pentamidine.

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.

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.

Infections associated with Hickman catheters in patients with acquired immunodeficiency syndrome.

PURPOSE: Hickman catheters are frequently used as convenient long-term venous access in patients with acquired immunodeficiency syndrome (AIDS). These patients seem to be at increased risk for bacterial infections of intravenous devices. The aim of our study was to determine the frequency of Hickman catheter infection in patients with AIDS as compared with that in other patients. PATIENTS AND METHODS: We analyzed the records of 69 patients who underwent 71 consecutive Hickman catheter placements during a one-year study period. RESULTS: Forty-six Hickman catheters were inserted in 44 patients with AIDS, and 25 Hickman catheters were placed in 25 other patients. There were 18 infections: 16 occurred in patients with AIDS, and two developed in the control group (p less than 0.05). The 16 infections in AIDS were as follows: five exit site, five septicemias, two tunnel, one septic phlebitis, and three probable Hickman catheter-related. Staphylococcus aureus was responsible for 14 cases (87%); Staphylococcus epidermidis was responsible for four cases (25%). Mean onset of infection was 32 days, but seven patients were diagnosed in the first eight days after Hickman catheter insertion. Fever occurred in all patients with early infection, leukopenia was present only in three; infusion of parenteral nutrition did not increase the risk. Two early infections were fatal. The rate of Hickman catheter infection in patients with AIDS was 0.47 per 100 catheter days, as compared with 0.09 in the control group. CONCLUSION: Our findings underscore the need for using Hickman catheters only when absolutely indicated in patients with AIDS, since the risk of serious infectious complications appears to be high.

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.

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.

High Staphylococcus aureus nasal carriage rate in patients with acquired immunodeficiency syndrome or AIDS-related complex.

Staphylococcus aureus has been reported to cause a high number of infections and septicemias, often related to intravenous catheters, in patients with acquired immunodeficiency syndrome (AIDS). Our objective was to assess the frequency of S. aureus nasal carriage among patients with AIDS or AIDS-related complex (ARC). The nasal carriage rate of S. aureus was determined within 24 hours of admission in 64 consecutively hospitalized patients with AIDS or ARC. Intravenous drug abusers were excluded. A control group of 64 patients with other diseases was also tested. Of 64 patients with AIDS or ARC, 35 (55%) were nasal carriers of S. aureus, compared with 18 (28%) of 64 control patients. Recent hospitalization did not influence carriage rate, nor did the recent use of antibiotics or zidovudine. The significant S. aureus carriage rate in patients with AIDS or ARC may contribute to the high incidence of intravenous catheter-related S. aureus infections in this population.

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.

Clinical features and management of severe dermatological reactions to drugs.

Cutaneous adverse drug reactions are a frequent occurrence and have been reported in more than 2% of hospitalised patients. Among the most commonly involved drugs are sulphonamides, penicillins, anticonvulsants and non-steroidal anti-inflammatory drugs. Two groups of mechanisms are involved in the pathogenesis of drug reactions: immunological, with all 4 types of hypersensitivity reactions described; and non-immunological, accounting for at least 75% of all drug reactions. Besides minor skin reactions like urticaria, maculopapular rash, fixed eruptions or erythema nodosum, which are generally self-limited, severe life-threatening manifestations also occur. Erythema multiforme is secondary to drugs in half the cases; the minor form is characterised by typical target and iris lesions and is usually benign. However, a much more severe condition, erythema multiforme major or Stevens-Johnson syndrome, is associated with mucosal, ocular and visceral involvement, and carries a mortality of 5 to 15% if untreated. Toxic epidermal necrolysis, which could represent an even more dramatic form of the same disease, is characterised by severe widespread erythema, blisters and loss of skin in sheets, with denudation of more than 10% of the body surface area. This entity is frequently due to drugs. Mortality is 25 to 70%, and 90% of the survivors will have sequelae. Exfoliative dermatitis is an erythematous scaling disease often produced by drugs and carrying significant mortality. Photodermatitis may at times present with severe eczematous features. For clinical and epidemiological reasons it is important to try to identify the culprit drug following an approach based on previous experience with the drug, timing of events, patient reaction to dechallenge, patient reaction to rechallenge (if feasible), alternative aetiological candidates, and drug concentration or evidence of overdose. Management of severe skin reactions to drugs should require admission to a burn unit, where patients should be placed in warmed air-fluidised beds, receive excellent nursing care, analgesics and tranquillisers. Peeling necrotic epidermis should be removed and denuded dermis covered with biological grafts or synthetic dressings. Fluid balance must be adequately maintained; nutritional support and careful monitoring of early signs of skin infections is mandatory to ensure immediate antimicrobial treatment. Ocular care must be excellent to avoid serious sight-threatening sequelae. Steroids are presently not recommended. With these therapeutic modalities, morbidity and mortality can be markedly decreased.

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.

House staff on-call scheduling: an intern's proposal.

House staff scheduling is currently one of the most important issues in graduate medical education. Proposals for regulation arose as a result of mistakes made by exhausted interns, and they involve doctors, hospitals, the public, and authorities. The New York State Department of Health recommendations include restricting work to less than 80 hours per week and shifts to less than 24 consecutive hours.

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.

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.

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.

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.