Benefits of screening for latent Mycobacterium tuberculosis infection.

BACKGROUND: The benefits of screening for latent Mycobacterium tuberculosis infection are unknown for most people, because screening has not been studied in clinical trials and preventive therapy has not been tested in all risk groups for whom it is recommended. METHOD: A MEDLINE search was performed to determine tuberculosis risk. A Markov model was used to analyze tuberculin skin test screening and preventive therapy for 3-year-old and 30-year-old persons with positive test results. Outcome measures were lifetime and 10-year tuberculosis risk, including spread to others, life expectancy extension, and number needed to screen and number needed to treat to prevent 1 case and 1 death during 10 years. RESULTS: The benefits of screening and preventive therapy outweigh the risks for all groups tested, although the benefits range from large to small. The number needed to screen to prevent 1 case is 10 to 6888, and the number needed to treat is 2 to 179. Persons with human immunodeficiency virus infection, intravenous drug abuse, or end-stage renal disease treated with transplantation and children exposed to high-risk adults have the highest tuberculosis rates and the lowest number needed to screen and number needed to treat to prevent cases and deaths. The range of risks found in the literature for some risk groups, such as persons with silicosis, leukemia or lymphoma, end-stage renal disease treated with dialysis, or prolonged corticosteroid therapy, is wide and, as a result, the benefits of screening are uncertain. CONCLUSIONS: The benefits of screening and preventive therapy vary widely, although the benefits outweigh the risks for all risk groups. The benefits are large for some risk groups and uncertain for others.

Tuberculosis susceptibility patterns, predictors of multidrug resistance, and implications for initial therapeutic regimens at a New York City hospital.

BACKGROUND: Multidrug resistance has complicated tuberculosis therapy. We studied antibiotic susceptibilities of Mycobacterium tuberculosis and predictors of multidrug resistance to assist in determining initial drug regimens. METHODS: We conducted a case-control study based on chart review of patients with and without multidrug-resistant tuberculosis, including outpatients and inpatients with culture-proved tuberculosis seen at a large New York, NY, hospital during 1991 and 1992. Patient characteristics studied included serologic findings for human immunodeficiency virus and the presence of the acquired immunodeficiency syndrome. Descriptive analysis considered potential initial drug regimens. A theoretically effective regimen was assumed to contain at least two drugs to which an isolate was susceptible. RESULTS: For 172 patients, 28.5% of isolates were resistant to isoniazid, at least 20.9% to rifampin, 15.7% to ethambutol, 8.1% to pyrazinamide, 18.6% to streptomycin, 9.9% to ethionamide, 8.1% to kanamycin, and none to capreomycin, cycloserine, and ciprofloxacin; 18.6% were resistant to both isoniazid and rifampin. Chart review of 159 patients showed that acquired immunodeficiency syndrome, human immunodeficiency virus seropositivity, female gender, residence in the Bronx, and race were associated with multidrug resistance. The four-drug regimen of isoniazid, rifampin, ethambutol, and pyrazinamide was theoretically effective for 81% to 85% of patients. No subset of patients would have a markedly better theoretical benefit from that regimen. Only five- or six-drug regimens that used the combinations of capreomycin plus ciprofloxacin, capreomycin plus cycloserine, ciprofloxacin plus cycloserine, or all three drugs together theoretically offered significantly higher effectiveness. CONCLUSIONS: Tuberculosis isolates at our hospital have a high frequency of multidrug resistance. Only five- or six-drug regimens are theoretically adequate as initial therapy for our patients.

A model for physicians' therapeutic decision making.

We explored physician's cognitive processes when making therapeutic decisions in a complex situation in which more than one treatment option is acceptable. Eighteen internists were presented with three hypothetical cases of patients with coronary artery disease and were asked to explain their treatment decisions. Based on process tracing, we characterized their method of therapeutic decision making. We found that physicians use a three-stage process that we call focal composite analysis: (1) selection of a few facts (focal points) and evaluation of each fact individually with respect to treatment options; (2) reassessment of the value of the focal points with respect to each other and unification of the case; and (3) summation of the values of the focal points to make the final decision. Using this model, we predicted physicians' actual treatment decisions in 96% of the hypothetical cases. Further analysis revealed a wide variety of focal points chosen overall, with most physicians choosing different focal points in each case. Of a total of 32 focal points chosen in three cases, only two focal points were predictors of the physicians' actual treatment choices. We conclude that in the complex problem considered here physicians use a staged process of choosing and evaluating information to make therapeutic choices.

Lumbar puncture in asymptomatic late syphilis. An analysis of the benefits and risks.

We evaluated the treatment of asymptomatic patients with untreated syphilis of more than one year's duration (asymptomatic late syphilis) using a decision-analysis model. Two strategies were compared: treatment with 7.2 million units of penicillin G benzathine, or performing a lumbar puncture to test for asymptomatic neurosyphilis followed by penicillin and management based on cerebrospinal fluid analysis. Estimates of probabilities of disease prevalence, test sensitivity, and cure and complication rates were derived from published studies. Both strategies resulted in a cure rate of at least 99.7% using the best estimates. Although the strategy using lumbar puncture results in a 0.2% higher cure rate, its rate of complications (0.3%) exceeds its marginal benefit. We conclude that a lumbar puncture offers little additional benefit and may increase morbidity in patients with asymptomatic late syphilis.

Cost-effectiveness of cytomegalovirus (CMV) disease prevention in patients with AIDS: oral ganciclovir and CMV polymerase chain reaction testing.

OBJECTIVE: To perform a cost-effectiveness analysis of strategies to prevent cytomegalovirus (CMV) disease. METHOD: Markov model and published data. PATIENTS: Hypothetical HIV-infected patients with CD4 cell counts < or = 50 x 10(6)/l and positive CMV serologies. INTERVENTIONS: Oral ganciclovir daily versus plasma CMV DNA polymerase chain reaction (PCR) testing every 3 months with oral ganciclovir for patients with positive tests. OUTCOME MEASURES: The number of CMV disease cases prevented by the interventions, life expectancy, disease-free life expectancy, and the cost to extend life by 1 year. RESULTS: Oral ganciclovir preventive therapy reduces the lifetime number of CMV disease cases by 50 per 1000 cohort, extends life expectancy by 5 days and disease-free life expectancy by 18 days, and costs US$ 1,762,517 per year of life extended. Periodic PCR testing reduces the lifetime number of CMV disease cases by eight per 1000 cohort, extends life expectancy by 1 day and disease-free life expectancy by 3 days, and costs US$ 495,158 per year of life extended. The prevention strategies could be acceptably cost effective only under a combination of optimistic assumptions and reduced costs. CONCLUSIONS: Oral ganciclovir preventive therapy and periodic plasma testing for CMV PCR with oral ganciclovir for those with positive tests result in small benefits at great cost. They are not cost-effective prevention strategies for persons with advanced HIV infection and positive CMV serologies.

Tuberculosis preventive therapy for HIV-infected people in sub-Saharan Africa is cost-effective.

OBJECTIVE: Since antiretroviral therapy is largely unavailable to HIV-infected patients in developing countries and recent clinical trials have shown that tuberculosis (TB) preventive therapy can reduce TB and HIV-associated morbidity and mortality, we studied the effectiveness and cost-effectiveness of TB preventive therapy for HIV-infected persons in sub-Saharan Africa. METHODS: A Markov model that used results of clinical trials of TB preventive therapy in sub-Saharan Africa and literature-derived medical care costs was used to evaluate three preventive therapy regimens in HIV-infected, tuberculin-positive patients in Uganda: (1) daily isoniazid (INH) for 6 months, (2) daily INH and rifampin (RIF) for 3 months, and (3) twice-weekly RIF and pyrazinamide (PZA) for 2 months. RESULTS: All three regimens extend life expectancy and reduce the number of TB cases. When only medical care costs are considered, all three preventive therapy regimens cost more than not providing preventive therapy to extend life and prevent active tuberculosis. When medical care and social costs are considered together, 6-months of daily INH treatment will save money relative to no preventive therapy and when the costs associated with treating secondary infections are included, all three preventive therapy regimens are less expensive than no preventive therapy. With the inclusion of secondary infection costs, 6 months of daily INH results in savings of $24.16 per person. CONCLUSIONS: TB preventive therapy taken by HIV-infected tuberculin reactors in sub-Saharan Africa results in extended life-expectancy, reduction of the incidence of TB and monetary savings in medical care and social costs. TB control policy in sub-Saharan Africa should include preventive therapy.

Influenza and pneumococcal vaccination of HIV-infected patients: a policy analysis.

OBJECTIVE: To analyze the policy of vaccinating human immunodeficiency virus (HIV)-infected young adults against influenza and pneumococcal infections. METHODS: Transition state model of clinical immune deterioration of HIV infection, published data, and experts' estimates for the uncertain variables. Outcome measures are the number of influenza and pneumococcal infection hospitalizations and deaths prevented over 10 years and cost-effectiveness ratios. PATIENTS: Hypothetical cohort of HIV-infected 30-year-old patients. RESULTS: Although pneumococcal vaccine effectiveness diminishes with advanced HIV disease, the risks of pneumococcal infection rise substantially. Pneumococcal vaccination was therefore found to be a reasonable prevention strategy at all HIV disease stages: few vaccinations are needed to prevent hospitalizations and deaths, and the vaccination strategy is cost-effective. By contrast, influenza incidence is low among young adults, and HIV-related immunodeficiency increases influenza risks only minimally. Because the vaccine is administered yearly, many more vaccinations must be administered and fewer hospitalizations and deaths are prevented than with pneumococcal vaccination. The costs to extend life expectancy are high, and beyond the costs of other prevention strategies for persons with moderate to severe immunodeficiency. CONCLUSIONS: Pneumococcal vaccination is a reasonable prevention strategy for HIV-infected patients at all stages of immunodeficiency. Fewer hospitalizations and deaths are prevented by influenza vaccination, making it a far less cost-effective prevention strategy than pneumococcal vaccination.

Survival of elderly patients with transfusion-related acquired immunodeficiency syndrome.

OBJECTIVE: To determine the influences of age and risk group on the survival of AIDS patients. We concentrated on transfusion because it is the commonest risk factor for AIDS in patients over 70 years of age. DESIGN: Survival curve regression analysis. PARTICIPANTS: Patients aged 13 years and over with AIDS acquired through transfusion, and patients 65 years or older with AIDS as a result of intravenous drug use (IVDU). Data were obtained from the New York City Department of Health. MAIN OUTCOME: The patients were divided into four groups, ages 13-40 years, 41-64 years, and 65 years and over with AIDS as a result of transfusion, and 65 years and older with AIDS as a result of IVDU. The survivals of the three transfusion-related AIDS groups were compared, as were the 65 years-and-over groups with AIDS as a result of transfusion or IVDU. AIDS-defining diagnoses between those over and under 65 years with AIDS as a result of transfusion were also compared. RESULTS: The median survival for the three transfusion-related AIDS groups were 273 days, 58 days, and 60 days, respectively. There was a significant association between shorter survival and increasing age. This was largely due to the longer survival of the patients aged 13-40 years. There was no difference in AIDS-defining diagnosis between those over and under 65 years with transfusion-related AIDS. The survival curves of the elderly with AIDS as a result of transfusion or IVDU were not different. CONCLUSION: Age over 40 years is an independent risk factor for poor survival among transfusion-related AIDS patients. Among the elderly, patients with transfusion-related AIDS have similar survivals to patients with IVDU-related AIDS.

Community participation in New York City: success or failure?

This paper describes the planning efforts of a community agency that was ultimately unsuccessful in converting two primary care centers from the traditional fee-for-service Medicaid reimbursement system to a per-capita prepaid Medicaid reimbursement system. We analyze how the community agency prepared its plan, the barriers it encountered in trying to implement a demonstration project, the ambiguous messages community organizations receive from policy-makers, and the role the Mount Sinai School of Medicine played in the conversion effort.

Tuberculin screening: cost-effectiveness analysis of various testing schedules.

Because there is no tuberculin screening schedule currently recommended for adults, we used a Markov process in a cost-effectiveness analysis to determine an optimal strategy. We simulated the prognosis of a cohort of black 20-year-olds to evaluate the effects of various screening schedules with intradermal tuberculin and administration of isoniazid prophylaxis to those with positive results. The schedule with the lowest cost-effectiveness ratio is a single screening at 50 years of age, which costs $41,672 per quality-adjusted life year (QALY) gained. The cost-effectiveness ratio is nearly the same for all schedules involving a single screening between 30 and 70 years of age. Repeated screening strategies are less cost effective. Sensitivity analysis shows that the range of acceptable screening strategies changes significantly under alternate assumptions about the mortality from isoniazid hepatitis. However, screening at 50 years of age remains nearly optimal under the alternatives considered. Altering the values of other parameters generally produced only small changes. Tuberculin screening at 50 years of age should be added to primary care preventive practices because the strategy is as cost effective as standard health interventions and is robust to alternative assumptions. If further research confirms the base case assumptions about isoniazid toxicity, consideration should be given to increasing screening to every 10 years, which would produce a larger health benefit, albeit at substantially higher cost.

Tuberculosis prevention: cost-effectiveness analysis of isoniazid chemoprophylaxis.

Isoniazid chemoprophylaxis is not recommended for all persons infected with tubercle bacilli. Because of the small but significant risk of isoniazid hepatotoxicity, chemoprophylaxis is reserved for only those at the highest risk of tuberculosis activation. To evaluate this policy, we performed a cost-effectiveness analysis of isoniazid chemoprophylaxis for two populations with positive tuberculin skin tests: recent tuberculin converters, who are at high risk for activation, and older tuberculin reactors, who have a low risk for activation and for whom chemoprophylaxis is not now recommended. The cost-effectiveness ratios found were stable, despite wide variations in model assumptions and probability estimates. For high-risk tuberculin reactors, chemoprophylaxis resulted in net medical care monetary savings, extended life expectancy, and fewer fatal illnesses. For low-risk tuberculin reactors, chemoprophylaxis resulted in positive, but small, health effects. Because the cost to gain these positive effects were also small, the resulting cost-effectiveness ratios were reasonable and in the realm of accepted prevention strategies: $12,625 to gain one year of life and $35,011 to avert one death. These findings suggest that the current policy is too restrictive and that many in the large population of low-risk tuberculin reactors should be considered for isoniazid chemoprophylaxis.

Completing tuberculosis prophylaxis in jail: targeting treatment and comparison of rifampin/pyrazinamide with isoniazid regimens.

SETTING: A county jail. OBJECTIVE: To characterize the treatment of latent tuberculosis infection and the impact on treatment completion of the 2-month rifampin and pyrazinamide regimen as compared to the traditional 6- to 12-month isoniazid regimen among persons incarcerated at a county correctional facility. DESIGN: Retrospective review of tuberculosis records from January 1998 to December 2000. RESULTS: Of 2127 inmates who were tuberculin skin test positive, 146 were started on treatment. This was generally limited to those expected to remain incarcerated long enough to complete the course of treatment. Completion rates were 88% (67/76) for the 2-month and 74% (51/69) for the 6- to 12-month courses (P = 0.03), and 82% overall. The two regimens were similarly tolerated, but inmates on isoniazid were more likely to be released (despite longer projected incarceration) and not complete treatment once in the community. Thirty-seven per cent of persons for whom treatment was not indicated by the previous guidelines should have had treatment by the new guidelines. CONCLUSION: The 2-month rifampin/pyrazinamide regimen had a higher completion rate than the longer isoniazid regimen, without additional toxicity, and allowed more patients to be treated. Latent tuberculosis treatment targeted to those able to complete the regimen in jail yields high completion rates.

Building an effective doctor-patient relationship: from patient satisfaction to patient participation.

In this paper, the authors argue that patient satisfaction is an insufficient measure of the quality of the doctor-patient relationship. While shown to have a salutary effect on patient anxiety concerning illness and treatment, the only other significant outcome associated with levels of satisfaction is utilization behavior. This is not surprising, the authors argue, since prevailing conceptualizations of patient satisfaction fail to incorporate measures of patient participation in the therapeutic process. Evidence suggests that by encouraging patients to take an active role in their health care physicians can increase the effectiveness of their therapeutic activities. A method for involving patients is through incorporating their preferences into the physician's decision-making processes. An example of physician decision making which incorporates patient preferences is provided.

KIE: Patient satisfaction is rejected as a sufficient measure of the quality and effectiveness of the physician patient relationship. Satisfaction appears to be correlated with passive acquiescence to treatment but not with commitment to health promoting behavior. Physicians are urged to involve patients in an informed decision making process by eliciting and including patient preferences in a health program that incorporates an active patient role. The authors suggest a preliminary, "utility value" model of clinical decision analysis to be used in conditions of uncertainty when the outcomes of care may be risky or costly. The model, which requires the physician to elicit the patient's ranking of potential outcomes of treatment options, integrates the probability of an event's occurrence with that event's outcome value.

Anticoagulation clinics and the monitoring of anticoagulant therapy.

Patients attending an anticoagulation clinic were studied to delineate predisposing risk factors for bleeding and thromboembolic episodes. Seventy-three patients were observed for a total of 921.8 patient-treatment months. The mean duration of treatment was 12.6 months (range 3-36 months). No major bleed occurred (a bleed which caused discontinuation of therapy, hospitalization or death). Thirty-two patients had minor bleeding episodes (0.42 bleeds per patient-year of treatment). The average prothrombin time ratio during the third to the sixth month of therapy was predictive of the bleeding risk. There was no association between bleeding and age, sex, indication for anticoagulation therapy or associated illnesses. Four thromboembolic episodes occurred (0.05 per patient-year of treatment), 3 arterial and 1 venous. At the time of the one venous thromboembolic event the prothrombin time ratio was subtherapeutic. In all 3 patients with arterial thromboembolism the mean 3- to 6-month prothrombin time ratio was less than or equal to the lower limit of the recommended range of 1.6-2.5. In our study prothrombin time ratios of 1.3-1.5 for venous thromboembolic disease and 1.6-2.5 for arterial thromboembolic disease were not associated with thromboembolism or major bleeding. Anticoagulation clinics facilitate the close monitoring of patients on oral anticoagulant therapy.

The epidemiology of HIV infection and AIDS in east and central Harlem, NY.

This report describes the AIDS epidemic in East and Central Harlem, among the hardest-hit communities in the nation. Information was obtained from two New York State mandatory reporting programs: anonymous HIV antibody testing of newborns, and physician and hospital reports of AIDS cases to city and county public health departments. One of 30 babies born in East Harlem and one of 46 newborns in Central Harlem are seropositive. The cumulative rate of reported AIDS cases in these communities is 10-15 times the national rate, and together, the communities reported 1.3% of all AIDS cases in the nation, although they have only 0.1% of the nation's population; 2.2% of all childhood AIDS cases have been reported from East and Central Harlem. Women, minorities, and injection drug users comprise a higher proportion of the cases than in the city, the state, and the nation. The consequences of the epidemic in these communities are enormous, including profound stresses on community institutions and exacerbation of the resurgence of tuberculosis.

The underreporting of disease and physicians' knowledge of reporting requirements.

Previous studies of underreporting of disease have mainly addressed the attitudes of physicians toward reporting of communicable disease to public health agencies and have not examined adequately the physicians' knowledge of the reporting system as a cause of underreporting. To investigate, the authors designed a questionnaire and distributed it to 345 physicians at two hospitals. One hundred and sixty-nine questionnaires, which examined knowledge of reporting requirements and reasons for not complying with those requirements during 1978-81, were returned (a 49 percent response rate). Most of the respondents knew that reporting is required, but their knowledge in specific areas, such as which diseases are reportable, varied greatly. The number of physicians who knew which diseases they are required to report ranged from a low of 63 physicians (37 percent) for trachoma to 163 (96 percent) for syphilis. Of the 169 physicians, only 50 believed they knew how to report reportable diseases, and only 40 of them knew the correct procedures. Thirty-six percent of the 169 physicians indicated that they had not reported any cases at all during 1978-81. On the average, physicians recalled reporting 28 percent of their reportable cases. When they indicated why they had not complied with reporting requirements, the physicians chose reasons that reflected a lack of knowledge of the reporting system. The most common reasons were "did not know how to report" and "did not know it was a reportable disease." The results suggest that a major factor in physician underreporting is a lack of knowledge of the morbidity reporting system.