David N. Rose

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 physicians decision-making processes. An example of physician decision making which incorporates patient preferences is provided.

Interpretation of the tuberculin skin test.

OBJECTIVE: To reinterpret epidemiologic information about the tuberculin test (purified protein derivative) in terms of modern approaches to test characteristics; to clarify why different outpoints of induration should be used to define a positive test in different populations; and to calculate test characteristics of the intermediate-strength tuberculin skin test, the probabilityMycobacterium tuberculosis infection at various induration sizes, the area under the receiver operating characteristic (ROC) curve, and optimal cutpoints for positivity.METHODS: Standard epidemiologic assumptions were used to distinguish M. tuberculosis-infected from -uninfected persons; also used were data from the U.S. Navy recruit and World Health Organization tuberculosis surveys; and Bayesian analysis.RESULTS: In the general U.S. population, the test’s sensitivity is 0.59 to 1.0, the specificity is 0.95 to 1.0, and the positive predictive value is 0.44 to 1.0, depending on the outpoint. Among tuberculosis patients, the sensitivity is nearly the same as in the general population; the positive predictive value is 1.0. The area under the ROC curve is 0.997. The probability ofM. tuberculosis infection at each induration size varies widely, depending on the prevalence. The optimal cutpoint varies from 2 mm to 16 mm and is dependent on prevalence and the purpose for testing.CONCLUSIONS: The operating characteristics of the tuberculin test are superior to those of nearly all commonly used screening and diagnostic tests. The tuberculin test has an excellent ability to distinguishM. tuberculosis-infected from -uninfected persons. Interpretation requires consideration of prevalence and the purpose for testing. These findings support the recommendation to use different cutpoints for various populations. Even more accurate information can be gotten by interpreting induration size as indicating a probability ofM. tuberculosis infection.

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

Short-Course Prophylaxis against Tuberculosis in HIV-Infected Persons: A Decision and Cost-Effectiveness Analysis

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.

Anticoagulation clinics and the monitoring of anticoagulant therapy

Infection with HIV is the most powerful risk factor for active tuberculosis in patients with latent Mycobacterium tuberculosis infection [1, 2]. Persons with both types of infections have an annual active tuberculosis rate of 3% to 16% and a lifetime active tuberculosis rate of 30% to 50% [1, 2]. Recent studies [3-6] indicate that active tuberculosis accelerates progression of HIV disease and increases HIV viral load 5- to 160-fold, and that M. tuberculosis upregulates HIV replication. Furthermore, HIV-infected patients with tuberculosis have lower rates of survival than HIV-infected patients who have not had tuberculosis, even when patients are matched by HIV disease stage and other risk factors for disease progression [7-10]. This may explain how tuberculosis prophylaxis in a clinical trial reduced the rate of opportunistic infections and overall mortality in addition to preventing active tuberculosis [11]. The Centers for Disease Control and Prevention and the American Thoracic Society recommend a 12-month regimen of isoniazid prophylaxis for HIV-infected patients [12-14]. Although prophylaxis has been proposed to reduce HIV-related tuberculosis in many countries, persistent difficulties in implementation and adherence, risk for isoniazid-associated hepatotoxicity, and unresolved questions about costs and benefits temper enthusiasm for its use [2]. After researchers found that some combination drug regimens were effective after several months in a murine model of tuberculosis and in patients with silicosis [15, 16], clinical trials were done to test short-course regimens in HIV-positive patients. The results of the trials indicate that some regimens are safe and effective [17-22]. My analysis addresses the following questions: How do the short-course prophylaxis regimens and the 12-month isoniazid regimen compare? Are the more expensive short-course regimens cost-effective? Methods A decision and cost-effectiveness analysis was done for hypothetical HIV-infected patients (CD4 count 200 cells/mm3) who have positive results on tuberculin skin tests. The currently recommended 12-month isoniazid regimen was compared with no prophylaxis and with six short-course prophylaxis regimens: isoniazid, 300 mg/d for 6 months; isoniazid, 600 mg or 800 mg (depending on the patients weight) twice weekly for 6 months; isoniazid, 300 mg/d, and rifampin, 600 mg/d, with and without pyrazinamide, 2000 mg/d for 3 months; rifampin, 450 mg or 600 mg, and pyrazinamide, 1500 mg, 2000 mg, or 2500 mg twice weekly for 2 months; and rifampin, 600 mg/d, and pyrazinamide, 20 mg/kg of body weight per day for 2 months. The outcome measures were expected 5-year survival rate, lifetime incidence of tuberculosis per cohort, life expectancy, and the cost to extend life by 1 quality-adjusted life-year (QALY). A Markov model [23] programmed on Microsoft Excel (Microsoft Corp., Redmond, Washington) was used to calculate the outcomes (Figure 1). In the first year, patients chose whether to receive prophylaxis. Those who chose prophylaxis risked a fatal adverse event with some regimens. (Nonfatal adverse events are included in the analysis and affect quality of life but not survival.) All patients risked developing tuberculosis, but this risk was decreased by prophylaxis. Regardless of whether tuberculosis occurred, patients risked death from any cause. In each subsequent year, patients who had not had tuberculosis risked active disease and all patients risked death from any cause. Figure 1. Decision tree for HIV-infected tuberculin reactors. Table 1 shows the assumptions and the range of values for each variable. Transition probabilities were calculated with the exponential transformation [23]. A base-case analysis was done, followed by a sensitivity analysis that tested the full range of values for each assumption one at a time and in combination. The cost-effectiveness analysis used a U.S. societal perspective, direct medical care costs only, quality adjustments, and a 3% annual discount rate. Costs were converted to 1997 U.S. dollars by using the medical care component of the consumer price index. Table 1. Assumptions and Sources Active Tuberculosis Observational studies and clinical trials of HIV-infected tuberculin reactors show annual rates of tuberculosis (including confirmed and clinically probable cases) of 3.4% to 16.2% [11, 17-1924, 33-38]. The base-case analysis used an annual rate of 6.7%, which was the median rate of the placebo groups of the clinical trials [11, 17-19]. Effectiveness of Prophylaxis Regimens The effectiveness of prophylaxis was taken from the results of six clinical trials [11, 17-22]. Incomplete adherence to the regimens was incorporated into this study through use of the intention-to-treat analyses of the clinical trials. Because the duration of effectiveness has not been studied, the base-case analysis used the assumption that effectiveness lasts for 3 years and diminishes to zero after 5 years. The 12-month regimen of daily isoniazid was tested in a clinical trial in Haiti by Pape and colleagues [11]. In 63 tuberculin reactors, the tuberculosis rate was 1.7% for patients receiving isoniazid plus vitamin B6 and 10.0% for those receiving vitamin B6 alone. A 6-month regimen of daily isoniazid was studied in three clinical trials. Wadhawan and colleagues [17] reported the results of a trial in Zambia in which isoniazid significantly reduced the tuberculosis rate. A smaller study by Hawken and associates in Kenya [18] followed patients for less than 2 years and found a rate reduction that was not statistically significant. Whalen and colleagues [19] conducted a large trial in Uganda and reported a statistically significant reduction in the tuberculosis rate (from 3.41% in the placebo group to 1.08% in the isoniazid group; relative risk [RR], 0.33 [95% CI, 0.14 to 0.77]) [19]. The effectiveness found in this trial was used in the base-case analysis, and the range of the CI was used in the sensitivity analysis. Whalen and colleagues [19] also studied two 3-month regimens: daily isoniazid and rifampin with and without pyrazinamide. The rate of tuberculosis in the group receiving the two-drug regimen was 1.32% (RR, 0.40 [CI, 0.18 to 0.86] compared with the placebo group). The rate in the group receiving the three-drug regimen was 1.73% (RR, 0.51 [CI, 0.24 to 1.08]; P = 0.08) compared with the placebo group. In a trial in Haiti, Halsey and colleagues [20] compared a 2-month regimen of twice-weekly rifampin and pyrazinamide with a 6-month regimen of twice-weekly isoniazid plus vitamin B6. In the 36 months after randomization, the rate of tuberculosis was 1.7% per year in the rifampin and pyrazinamide group and 1.8% per year in the isoniazid group, a difference that is not statistically significant. Because this trial did not include a placebo group, the base-case rate with no prophylaxis (6.7%) was used to calculate the effectiveness of these regimens compared with no prophylaxis. The effectiveness of a 2-month regimen of daily rifampin and pyrazinamide was taken from an international trial conducted by Gordin and colleagues [21, 22]. They reported a 1.2% rate of tuberculosis. Because the study did not have a placebo group (the comparison group received 12 months of isoniazid and also had a tuberculosis rate of 1.2%), the method mentioned above was used to calculate the effectiveness of the 2-month regimen compared with no prophylaxis. Adverse Effects of Prophylaxis Rates of adverse reactions to prophylaxis were taken from the same clinical trials [17-22]. The methods for recording and reporting these events differed substantially among studies; this made comparisons difficult. Thus, each rate was varied through a wide range in the sensitivity analysis. Although fatal isoniazid-associated hepatotoxicity was not reported in the clinical trials, risk for this event was included in the base-case analysis of regimens that contained isoniazid because its occurrence is well documented In the Haitian study reported by Pape and colleagues [11], isoniazid taken for 12 months caused no important adverse events. In contrast, 10.7% of the patients in the international trial done by Gordin and colleagues had adverse events [21, 22]. In other populations, clinical hepatitis occurred at rates of 0.5% to 6.9% and deaths occurred at a rate of 14 per 100 000 persons [25-28]. Because the standard protocol now includes monitoring for hepatitis, the mortality rate has decreased to 1 to 2 per 100 000 persons [13, 14, 28, 29]. The base-case analysis used the assumption that the rates of mild, moderate to severe, and fatal adverse events are 10.1%, 0.6%, and 0.002%, respectively. Adverse event rates for the 6-month regimen of daily isoniazid and the 3-month regimens of isoniazid and rifampin with and without pyrazinamide were taken from the Ugandan trial done by Whalen and colleagues [19]. For this analysis, the rates were based on the marginal rates above those of placebo recipients. The rate of fatal isoniazid-associated hepatotoxicity for all 3- and 6-month regimens that contained isoniazid was assumed to be half that for the 12-month regimen [26]. Adverse event rates for the 6-month regimen of twice-weekly isoniazid and the 2-month regimen of twice-weekly rifampin and pyrazinamide were taken from the Haitian trial done by Halsey and colleagues [20]. Adverse event rates were not reported in detail, but diarrhea and stomach pain were more common in the isoniazid group than in the rifampin and pyrazinamide group. Survival Survival rates for HIV-infected patients with and those without an episode of active tuberculosis were taken from a retrospective cohort study conducted at four U.S. medical centers [9]. Patients with tuberculosis were matched with controls without tuberculosis according to CD4 cell count and study site. The two groups were similar with respect to age, sex, ethnicity, previous incidence of opportunistic infection, and use of ant

Complications of surgery in HIV-infected patients.

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.

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

Surgical decision-making can be complex if a patient has HIV infection. HIV infection affects the differential diagnosis of surgical disease nutritional status and life expectancy. Some have suggested that HIV infection may also influence postoperative wound healing and complication rates. The results of surgery on HIV-infected patients have been reported as unacceptably poor or remarkably favorable. As a result some surgeons recommend medical management or conservative approaches for conditions that are usually treated more aggressively. Others have stated that HIV infection should have only minor influence on decision-making for many surgical conditions and therefore standard surgical approaches are appropriate. Does HIV infection affect postoperative complications? We reviewed the literature to describe postoperative complications and to determine whether the complication rate is higher in HIV-infected than in uninfected patients or in patients with advanced HIV disease. (excerpt)

Zidovudine prophylaxis for needlestick exposure to human immunodeficiency virus: a decision analysis.

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 ≤ 50 × 106/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

A medical school's involvement in the development of a community-based health center

1762 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

Preventive Treatment for Tuberculosis in Elderly Persons

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.