Marcia A. Testa

The Effects of Antihypertensive Therapy on the Quality of Life

We conducted a multicenter randomized double-blind clinical trial among 626 men with mild to moderate hypertension to determine the effects of captopril, methyldopa, and propranolol on their quality of life. Hydrochlorothiazide was added if needed to control blood pressure. After a 24-week treatment period, all three groups had similar blood-pressure control, although fewer patients taking propranolol required hydrochlorothiazide. Patients taking captopril alone or in combination with a diuretic were least likely to withdraw from treatment because of adverse effects (8 percent vs. 20 percent for methyldopa and 13 percent for propranolol). The treatment groups were similar in scores for sleep dysfunction, visual memory, and social participation. However, patients taking captopril, as compared with patients taking methyldopa, scored significantly higher (P less than 0.05 to less than 0.01) on measures of general well-being, had fewer side effects, and had better scores for work performance, visual-motor functioning, and measures of life satisfaction. Patients taking propranolol also reported better work performance than patients taking methyldopa. Patients taking captopril reported fewer side effects and less sexual dysfunction than those taking propranolol and had greater improvement (P less than 0.05 to less than 0.01) on measures of general well-being. Our findings show that antihypertensive agents have different effects on the quality of life and that these can be meaningfully assessed with available psychosocial measures.

Discontinuation of Antihyperlipidemic Drugs — Do Rates Reported in Clinical Trials Reflect Rates in Primary Care Settings?

BACKGROUND Discontinuation rates for drugs used to treat chronic conditions may affect the success of therapy. However, the discontinuation rates reported in clinical trials may not reflect those in primary care settings. METHODS We conducted a cohort study using computerized research files and medical records on 2369 new users of antihyperlipidemic therapy at two health maintenance organizations (HMOs) from 1988 through 1990. The rates of drug discontinuation in these primary care settings were compared with the rates reported in clinical trials published from 1975 through 1993, located with the Medline data base. RESULTS In the HMOs, the one-year probability of drug discontinuation was 41 percent for bile acid sequestrants (95 percent confidence interval, 38 to 44 percent), 46 percent for niacin (95 percent confidence interval, 42 to 51 percent), 15 percent for lovastatin (95 percent confidence interval, 11 to 19 percent), and 37 percent for gemfibrozil (95 percent confidence interval, 31 to 43 percent). For the bile acid sequestrants, niacin, and gemfibrozil, the risks of discontinuation were substantially higher in the HMOs than in randomized clinical trials, in which the summary estimates of this risk were 31 percent, 4 percent, and 15 percent, respectively, for trials of one year or longer. The rates of discontinuation in open-label studies were similar to those in the HMOs. CONCLUSIONS The discontinuation rates reported in randomized clinical trials may not reflect the rates actually observed in primary care settings. The effectiveness and tolerability of antihyperlipidemic medications should be studied further in populations that typically use the agents.

Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection

BACKGROUND Reduced doses of cytotoxic chemotherapy or standard-dose therapy plus a myeloid colony-stimulating factor decreases hematologic toxicity and its complications in patients with non-Hodgkins lymphoma associated with infection with the human immunodeficiency virus (HIV). However, the effect of reducing the doses of cytotoxic chemotherapeutic agents on clinical outcome is not known. METHODS We randomly assigned 198 HIV-seropositive patients with previously untreated, aggressive non-Hodgkins lymphoma to receive standard-dose therapy with methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) along with granulocyte-macrophage colony-stimulating factor (GM-CSF; n=94) or reduced-dose m-BACOD with GM-CSF administered only as indicated (n=98). RESULTS A complete response was achieved in 39 of the 94 assessable patients assigned to low-dose therapy (41 percent) and in 42 of the 81 assessable patients assigned to standard-dose therapy (52 percent, P= 0.56). There were no significant differences in overall or disease-free survival; median survival times were 35 weeks for patients receiving low-dose therapy and 31 weeks for those receiving standard-dose therapy (risk ratio for death in the standard-dose group=1.17; 95 percent confidence interval, 0.84 to 1.63; P=0.25). Toxic effects of chemotherapy rated grade 3 or higher occurred in 66 of 94 patients assigned to standard-dose therapy (70 percent) and 50 of 98 patients assigned to low-dose treatment (51 percent, P=0.008). Hematologic toxicity accounted for the difference. CONCLUSIONS As compared with treatment with standard doses of cytotoxic chemotherapy (m-BACOD), reduced doses caused significantly fewer hematologic toxic effects yet had similar efficacy in patients with HIV-related lymphoma. Dose-modified chemotherapy should be considered for most HIV-infected patients with lymphoma.

Quality of Life and Antihypertensive Therapy in Men -- A Comparison of Captopril with Enalapril

Background We conducted a multicenter trial comparing two angiotensin-converting-enzyme inhibitors to determine whether effects on quality of life during antihypertensive therapy are uniform within this pharmacologic class of agents, and to relate the effects of the drugs on quality of life to objective adverse events, such as the loss of a job or the death of a spouse. Methods After a four-week washout period when they received placebo, 379 men with mild-to-moderately-severe hypertension were randomly assigned to receive captopril (25 to 50 mg twice daily, with or without hydrochlorothiazide) or enalapril (5 to 20 mg per day, with or without hydrochlorothiazide) for 24 weeks. Blood pressure, quality of life, and life events were monitored. Differences between treatments were evaluated by calibrating measures of quality of life with objective life events. Results Throughout the treatment period, no differences were found in blood pressure, frequency of withdrawal of patients from the study, or major side ...

AIDS-related Kaposi's sarcoma: prospective validation of the AIDS Clinical Trials Group staging classification. AIDS Clinical Trials Group Oncology Committee.

PURPOSE To prospectively validate the AIDS Clinical Trials Group (ACTG) staging classification for AIDS-associated Kaposis sarcoma (KS). PATIENTS AND METHODS Two hundred ninety-four consecutive patients enrolled in eight ACTG therapeutic trials for AIDS-associated KS were staged prospectively according to tumor extent (T), severity of immunosuppression (I), and other systemic human immunodeficiency virus type 1 (HIV-1)-associated illness (S) and were observed for survival. Patients were classified as good risk (subscript 0) or poor risk (subscript 1) for each variable according to published ACTG criteria. Univariate and multivariate analyses were used to evaluate the associations between TIS variables and survival; additional analyses were conducted to improve the predictive value of the staging system. RESULTS Survival was significantly shorter for patients in the poor-risk category for each of the TIS variables. Respective median survivals for patients in the good- and poor-risk categories were 27 and 15 months for T (P < .001); 40 and 13 months for I (P < .001) when I0 included CD4 counts > or = 200/microL and 22 and 16 months for S (P = .04). Multivariate analysis indicated that severity of immunosuppression gave the most predictive information but also showed that T provided significant additional predictive information in patients whose immune function was least impaired. Refined Cox models using a CD4 count of 150/microL rather than 200/microL to distinguish I0 and I1 yielded a simplified model with better fit to the observed data. CONCLUSION The ACTG TIS classification predicts survival in patients with AIDS-associated KS; CD4 count and tumor stage provide the most predictive information. However, a lower CD4 count than the one originally proposed provides better discrimination between prognostic groups.

Prognostic value of the electroencephalogram in neonatal asphyxia

In order to determine whether an EEG early in the course of asphyxia neonatorum is of any more value than the neurological examination in predicting outcome we reviewed case histories of 38 infants with asphyxia neonatorum. The EEG background activity was valuable in predicting outcome. Normal and maturationally delayed EEGs were associated with normal outcomes while low voltage, electrocerebral inactivity and burst suppression EEGs were highly correlated with severe neurological sequelae. Epileptiform activity was not as predictive of outcome as background activity. Although initial normal neurological examinations were associated with normal developmental and neurological outcomes, moderately and severely abnormal infants had more variable courses. A single EEG done early in the course of asphyxia neonatorum is a more sensitive predictor of outcome than the neurological examination.

Factors influencing medication adherence beliefs and self-efficacy in persons naive to antiretroviral therapy: a multicenter, cross-sectional study.

It is widely recognized that adherence to antiretroviral therapy is critical to long-term treatment success, yet rates of adherence to antiretroviral medications are frequently subtherapeutic. Beliefs about antiretroviral therapy and psychosocial characteristics of HIV-positive persons naive to therapy may influence early experience with antiretroviral medication adherence and therefore could be important when designing programs to improve adherence to antiretroviral therapy. As part of a multicenter AIDS Clinical Trial Group (ACTG 384) study, 980 antiretroviral-naive subjects (82% male, 47% White, median age 36 years, and median CD4 cell count 278 cells/mm3) completed a self-administered questionnaire prior to random treatment assignment of initial antiretroviral medications. Measures of symptom distress, general health and well-being, and personal and situational factors including demographic characteristics, social support, self-efficacy, depression, stress, and current adherence to (nonantiretroviral) medications were recorded. Associations among variables were explored using correlation and regression analyses. Beliefs about the importance of antiretroviral adherence and ability to take antiretroviral medications as directed (adherence self-efficacy) were generally positive. Fifty-six percent of the participants were “extremely sure” of their ability to take all medications as directed and 48% were “extremely sure” that antiretroviral nonadherence would cause resistance, but only 37% were as sure that antiretroviral therapy would benefit their health. Less-positive beliefs about antiretroviral therapy adherence were associated with greater stress, depression, and symptom distress. More-positive beliefs about antiretroviral therapy adherence were associated with better scores on health perception, functional health, social–emotional–cognitive function, social support, role function, younger age, and higher education (r values = 0.09–0.24, all p < .001). Among the subset of 325 participants reporting current use of medications (nonantiretrovirals) during the prior month, depression was the strongest correlate of nonadherence (r = 0.33, p < .001). The most common reasons for nonadherence to the medications were “simply forgot” (33%), “away from home” (27%), and “busy” (26%). In conclusion, in a large, multicenter survey, personal and situational factors, such as depression, stress, and lower education, were associated with less certainty about the potential for antiretroviral therapy effectiveness and ones perceived ability to adhere to therapy. Findings from these analyses suggest a role for baseline screening for adherence predictors and focused interventions to address modifiable factors placing persons at high risk for poor adherence prior to antiretroviral treatment initiation

Higher survival rates among younger patients after pediatric intensive care unit cardiac arrests.

BACKGROUND. Age is an important determinant of outcome from adult cardiac arrests but has not been identified previously as an important factor in pediatric cardiac arrests except among premature infants. Chest compressions can result in more effective blood flow during cardiac arrest in an infant than an older child or adult because of increased chest wall compliance. We, therefore, hypothesized that survival from cardiac arrest would be better among infants than older children. METHODS. We evaluated 464 pediatric ICU arrests from the National Registry of Cardiopulmonary Resuscitation from 2000 to 2002. NICU cardiac arrests were excluded. Data from each arrest include >200 variables describing facility, patient, prearrest, arrest intervention, outcome, and quality improvement data. Age was categorized as newborn (<1 month; N = 62), infant (1 month to <1 year; N = 105), younger child (1 year to <8 years; N = 90), and older child (8 years to <21 years; N = 207). Multivariable logistic regression was performed to examine the association between age and survival. RESULTS. Overall survival was 22%, with 27% of newborns, 36% of infants, 19% of younger children and 16% of older children surviving to hospital discharge. Newborns and infants demonstrated double and triple the odds of surviving to hospital discharge from a cardiac arrest in an intensive care setting when compared with older children. When potential confounders were controlled, newborns increased their advantage to almost fivefold, while infants maintained their survival advantage to older children. CONCLUSIONS. Survival from pediatric ICU cardiac arrest is age dependent. Newborns and infants have better survival rates even after adjusting for potential confounding variables.

Evaluation of the Quality of Life Associated with Zidovudine Treatment in Asymptomatic Human Immunodeficiency Virus Infection

BACKGROUND Zidovudine therapy is recommended for asymptomatic patients infected with the human immunodeficiency virus (HIV) who have fewer than 500 CD4+ cells per cubic millimeter. An analysis of the quality of life associated with therapy that integrated both the effects of adverse events and the benefits of delayed disease progression might influence this recommendation. METHODS We applied a survival analysis adjusted for the quality of life to data from a randomized trial conducted by the AIDS Clinical Trials Group. The trial compared treatment with 500 mg of zidovudine per day, 1500 mg of zidovudine per day, and placebo (Protocol 019) in 1338 asymptomatic HIV-infected patients. RESULTS The average time with neither a progression of disease nor an adverse event (symptom or laboratory finding) was 15.7, 15.6, and 14.8 months for patients receiving placebo, 500 mg of zidovudine, and 1500 mg of zidovudine, respectively. The incidence of severe symptoms was 13.8 percent in the placebo group, 15.2 percent in the 500-mg group, and 19.9 percent in the 1500-mg group (P = 0.038). After 18 months, the 500-mg group gained an average of 0.5 months without disease progression, as compared with the placebo group, but had severe adverse events an average of 0.6 months sooner. The 500-mg group had more quality-of-life--adjusted time than the placebo group only if the time lived after the progression of disease was considered by a patient to have less value than the time after the occurrence of a severe symptom. CONCLUSIONS For asymptomatic patients treated with 500 mg of zidovudine, a reduction in the quality of life due to severe side effects of therapy approximately equals the increase in the quality of life associated with a delay in the progression of HIV disease.

Prognostic factors in the treatment of human immunodeficiency virus-associated non-Hodgkin's lymphoma: analysis of AIDS Clinical Trials Group protocol 142--low-dose versus standard-dose m-BACOD plus granulocyte-macrophage colony-stimulating factor. National Institute of Allergy and Infectious Diseases.

PURPOSE The overall results of chemotherapy in human immunodeficiency virus (HIV)-associated non-Hodgkins lymphoma (NHL) have been poor. To define a subgroup of patients who may have a better outcome, an analysis of prognostic factors was performed of patients treated in AIDS Clinical Trials Group (ACTG) protocol 142, a phase III randomized trial of low-dose versus standard-dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) plus granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of patients with newly diagnosed HIV-associated NHL. MATERIALS AND METHODS The following baseline variables were included as potential predictors of survival among 192 patients who received treatment: age; intravenous drug use (IVDU); specific type of sexual contact as risk factors (homosexual, bisexual, or heterosexual contact); prior AIDS diagnosis; CD4 cell count; serum lactic acid dehydrogenase (LDH); histology; Karnofsky performance status (KPS); stage; B symptoms; race (white/nonwhite); nodal involvement; extranodal involvement; number of extranodal sites; specific sites: bone marrow, liver, kidney, lung, or gastrointestinal tract; and treatment arm (standard-dose m-BACOD/low-dose m-BACOD). RESULTS Age greater than 35 years, IVDU, stages III/IV, and CD4 cell counts less than 100/microL were adverse prognostic factors in multivariate analyses using the Cox proportional hazards model. The median overall survival for patients with none or one of the adverse factors was 46 weeks, with two was 44 weeks, and with three or four was 18 weeks. At 144 weeks, 29.5% of patients with none or one, 16.9% with two, and 0% with three or four factors were alive (P < .001). CONCLUSION Long-term survival can be achieved in approximately one third of patients with HIV-associated NHL with favorable characteristics.