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Effect of misonidazole dose on survival in patients with stage IIIB-IVA squamous cell carcinoma of the uterine cervix: an RTOG randomized trial.

Between August 1980 and November 1984, 120 patients with FIGO Stage IIIB or IVA squamous cell carcinoma of the uterine cervix were randomized to receive radiation therapy (RT) (46 Gy pelvis + 10 Gy parametrial boost) followed by intracavitary or external boost to the primary +/- misonidazole (MISO) (400 mg/M2 2-4 hours prior to RT daily, maximum 12 gm/M2). The median at 24-28 hr misonidazole plasma level was 20 micrograms/ml 2-6 hr and 3.5 micrograms/ml. Approximately 60% of the patients on RT + MISO received 100% of expected total Misonidazole dose; peripheral neurologic toxicity was reported for nine patients receiving misonidazole (8 with mild and 1 with moderate paresthesia or pain). Time-dependent regression analyses found that actual cumulative misonidazole dose was not related to duration of survival from start of treatment (p = 0.5). MISO dose expressed as a percent of expected dose was marginally related to increased survival measured from 14 weeks on on study (p = 0.1). No improvement in survival was observed with the addition of misonidazole to RT (64% of the patients on RT alone were alive at 18 months versus 54% of those on RT + MISO).

Carcinoma, Squamous Cell↗

Replicating the chronic disease score (CDS) from automated pharmacy data.

Michael Von Korff and colleagues at the Center for Health Studies, Group Health Cooperative (GHC) of Puget Sound created a measure of chronic disease status (CDS) using automated outpatient pharmacy data. They reported the measure appeared to provide a stable and valid measure of health status. The availability of such a measure could become a new tool for a variety of applications, including screening, resource allocation, and quality assurance. The measure was replicated for its reliability and construct and predictive validity in the KPNW membership using automated pharmacy data. Reliability and validity were tested using correlation and regression techniques. The CDS showed test-retest reliability over time. It showed construct validity with the RAND-36 instrument and the BSI-8 depression screener. It showed predictive validity with health care visits and hospitalizations. The results were similar to those at GHC. The findings indicated that the CDS can serve, with certain precautions, as a readily accessible low cost measure of health status.

Chronic Disease↗

Technical efficiency in the use of health care resources: a comparison of OECD countries.

Our paper analyzes technical efficiency in the production of aggregate health outcomes of reduced infant mortality and increased life expectancy, using Organization for Economic Cooperation and Development (OECD) health data. Application of data envelopment analysis (DEA) reveals that some countries achieve relative efficiency advantages, including those with good health outcomes (Japan, Sweden, Norway, and Canada) and those with modest health outcomes (Mexico and Turkey). We conclude the USA may learn from countries more economical in their allocation of healthcare resources that more is not necessarily better. Specifically, we find that the USA can substantially reduce inputs while maintaining the current level of life expectancy.

Cross-Cultural Comparison↗

Ex vivo adenoviral-mediated gene transfer to lung isografts during cold preservation.

BACKGROUND: Although whole-organ gene transfer has been reported in heart and liver transplant models, it has not been well characterized in lung grafts. The aim of this study was to determine the feasibility of ex vivo gene transfer to rat lung isografts during cold preservation using an adenoviral vector. METHODS: F344 rats, divided into four groups, underwent orthotopic left lung transplantation. In group I, lung grafts were flushed with adenovirus carrying the beta-galactosidase gene. After storage at 10 degrees C, grafts were implanted in recipient animals. Group II underwent the same procedure but graft storage was at 4 degrees C. Groups III (10 degrees C) and IV (4 degrees C) served as controls. On postoperative day 5, recipients were sacrificed, and native and transplanted lungs were examined. RESULTS: In group I, all animals showed successful, albeit patchy, gene expression. This occurred in 2 of 4 animals in group II, the other 2 showing no expression. Transduced cells were consistent morphologically with endothelial cells and pneumocytes. A minimal mononuclear inflammatory infiltrate was present. Control groups showed no transduction. CONCLUSIONS: It is feasible to perform ex vivo adenoviral-mediated gene transfer to rat lung isografts during cold preservation.

Adenoviridae↗

Comparative effects of ticrynafen and hydrochlorothiazide in the treatment of hypertension.

Two dose levels of ticrynafen, a new uricosuric diuretic, and of hydrochlorothiazide were randomly assigned, double-blind to 240 men with initial diastolic blood pressures in the range of 95 to 114 mm Hg. A dose of 500 mg of ticrynafen once daily exerted an antihypertensive effect comparable to that of 50 or 100 mg of hydrochlorothiazide. Whereas serum uric acid levels rose in patients treated with hydrochlorothiazide, they fell markedly in those receiving ticrynafen. Otherwise, both diuretics produced similar chemical changes in serum. Patients tolerated ticrynafen as well as they did hydrochlorothiazide over a period of six months of observation, and there was no evidence of serious toxicity or loss of therapeutic effect with ticrynafen. This antihypertensive agent, in appropriate doses, appears to be as effective and well tolerated as hydrochlorothiazide, and in addition ticrynafen prevents hyperuricemia.

Blood Pressure↗

What has bioethics to offer the developing countries.

My paper consists of three parts. In the first part I try to explain the intellectual basis of bioethics in developing countries. In the second part I describe the bioethical dilemmas facing these countries. In the third part I shall discuss the changes that have to be made in bioethics if it is to take root in these countries, and thereby help them to improve the human existence.

Bioethical Issues↗

Propranolol in schizophrenia. I. Comparison of propranolol, chlorpromazine and placebo.

Fifty-three hospitalized chronic schizophrenic patients were treated with either propranolol, chlorpromazine or placebo in a double-blind randomized trials for up to three months. Propranolol in a usual dose of 640 mg/day, produced marked cardiovascular effects but no improvement in schizophrenic symptomatology relative to placebo. The effects of chlorpromazine were small and inconsistent.

Blood Pressure↗

Vincristine and prednisone prolong the survival of patients receiving intravenous or oral melphalan for multiple myeloma: Cancer and Leukemia Group B experience.

A total of 589 patients with previously untreated multiple myeloma were randomized to receive daily oral melphalan, pulse-dose intravenous (IV) melphalan, carmustine (BCNU), or lomustine (CCNU). All patients received an initial tapering course of prednisone (Pred). During week 22 (day 154), patients were randomized to receive or not to receive additional therapy with vincristine (VCR) (1 mg/m2) and prednisone (0.6 mg/kg/d for seven days) at 8-week intervals. The influence of VCR/Pred was determined in 302 patients who remained on study beyond 22 weeks after initial therapy. VCR/Pred converted a significant percentage of nonresponders to responders in patients treated with melphalan (55% v 19%, P = .002), but not in patients treated with a nitrosourea (48% v 23%, P = .06). Survival beyond week 22 was significantly longer following the addition of VCR/Pred in patients receiving melphalan (median, 35.3 months v 27.0 months; P = .003) but not in patients receiving BCNU or CCNU (median, 28.1 months v 26.2 months; P = .91). These differences were seen both for oral and IV melphalan. A trend for beneficial effect of VCR/Pred was definitely seen in the good-risk patients (P = .03) but only suggestive for poor-risk patients (P = .12). Following adjustment for VCR/Pred effects, there were no differences in the survival of patients receiving any of the four initial treatments.

Antineoplastic Combined Chemotherapy Protocols↗

Neurosurgery in the United States: a log-diary study.

The Division of Research in Medical Education and of the University of Southern California, with the cooperation and assistance of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons, has conducted a national study of the professional activities of neurological surgeons in the United States. One of a series of 24 surveys of medical and surgical specialties, the survey obtained information on patient workloads, the allocation of physician time, the characteristics of patients and the circumstances under which they were seen, patient diagnoses, and the care that was provided--including whether an operation was performed. This paper provides a selection of the findings deemed most relevant to manpower issues in neurosurgery. A later paper will examine regional differences in patient care, including the frequency with which selected surgical procedures are used for different clinical conditions.

Commission on Professional and Hospital Activities↗

Stop-smoking program using nicotine reduction therapy and behavior modification for heavy smokers.

One hundred eighteen volunteers were studied in a hospital-based smoking cessation program in which nicotine polacrilex (Nicorette) was used as an adjunct to behavioral modification (group support). The "success" rate of 40% to 47% at 1 year was chemically verified. The regimen for using the nicotine polacrilex was "within labeling" but decidedly different from the regimen used in most smoking cessation programs involving this product.

Adult↗

Home transport and wastage: environmentally relevant household activities in the life cycle of food.

In environmental systems analysis of food production systems, the consumer phase (home transport, cooking, storing, and wastage) is an important contributor to the total life-cycle environmental impact. However, households are the least investigated part of the food chain. Information gathering about households involves difficulties; the number of households is large, and food-related activities are embedded in other household activities. In cooperation between researchers from environmental systems analysis and consumer research, Swedish households were surveyed by questionnaire, diary, and interviews. Data on home transport of food and wastage were collected. The average weekly driving distance was 28 to 63 km per household, depending on how trips made in conjunction with other errands are allocated. The wastage of prepared food ranged between 0 and 34% for different food categories, and wastage from storing between 0 and 164% (more food was discarded, e.g. by cleaning out a cupboard, than consumed). In both cases dairy products scored highest.

Activities of Daily Living↗

Effect of corn processing on degradable intake protein requirement of finishing cattle.

Three finishing trials were conducted to determine effect of corn processing on degradable intake protein requirement (DIP) of feedlot cattle. In Trial 1, 252 steers were fed 90% concentrate, high-moisture corn-based diets that contained 0, 0.4, 0.8, or 1.2% urea (DM basis) to provide dietary DIP values of 7.0, 8.2, 9.3, and 10.5% of DM, respectively. Nonlinear analysis predicted maximal feed efficiency at 10.2% dietary DIP (95% confidence interval was 9.9 to 13.3%). In Trial 2, 264 steers were fed 90% concentrate, steam-flaked corn-based diets that contained 0, 0.4, 0.8, 1.2, 1.6, or 2.0% urea (DM basis) to provide dietary DIP values of 4.7, 5.8, 7.0, 8.2, 9.3, and 10.5% of DM, respectively. Nonlinear analysis predicted maximal feed efficiency at 7.1% dietary DIP (95% confidence interval was 7.0 to 7.2%). In Trial 3, 90 individually-fed steers were fed 90% concentrate, dry-rolled, high-moisture, or steam-flaked corn-based diets. Urea was factored across diets at 0, 0.5, 1.0, or 2.0% of DM to provide dietary DIP values of 4.8. 6.3, 7.8, 9.2, and 10.7% for dry-rolled, 6.7,8.1,9.6, 11.1, and 12.5% for high-moisture, and 4.7, 6.1, 7.6, 9.0, and 10.5% for steam-flaked corn-based diets, respectively. For the dry-rolled corn-based diet, nonlinear analysis could not predict a requirement because feed efficiency was not improved beyond the first increment of dietary DIP, suggesting that the DIP requirement was met at 6.3% of DM. For the high-moisture corn-based diet, nonlinear analysis predicted maximal feed efficiency at 10.0% dietary DIP (95% confidence interval was 9.2 to 11.3%). For the steam-flaked corn based diet, nonlinear analysis predicted maximal feed efficiency at 9.5% dietary DIP (95% confidence interval was 9.2 to 9.5%). Our estimate of the DIP requirement for dry-rolled corn-based diets (6.3%) agrees well with past research and predicted values. Our estimate of the DIP requirement for high-moisture corn-based diets (10.1%) was very consistent between trials and higher than predicted. Our estimates of the DIP requirement for steam-flaked corn-based diets varied from 7.1 to 9.5%, with an average of 8.3% of dietary DM.

Animal Feed↗

Randomized, double-blind, cross-over study comparing prochlorperazine and lorazepam with high-dose metoclopramide and lorazepam for the control of emesis in patients receiving cytotoxic chemotherapy.

To further define optimal combinations of antiemetics, high-dose metoclopramide and lorazepam (M+L) were compared with prochlorperazine and lorazepam (P+L) in a randomized, double-blind, cross-over study. Both patient and observer assessments were documented in 66 patients receiving cisplatin and noncisplatin chemotherapy. M+L significantly reduced the severity of vomiting (P = 0.01), duration of vomiting (P = 0.05), and number of vomiting episodes (P = 0.003). Comparing the severity or duration of nausea, M+L and P+L were not significantly different. M+L significantly reduced severity of vomiting (P = 0.005) and number of vomiting episodes (P = 0.03) in the cisplatin subset. The number of vomiting episodes was also reduced in the noncisplatin subset (P = 0.03). When asked to nominate a preferred regimen, 41% of patients preferred P+L, 35% preferred M+L, and 24% rated them equally. M+L was associated with significantly more anxiety and less sedation than P+L. Patient assessments produced similar results to observer assessments but gave a broader understanding of our patients' tolerance to chemotherapy. M+L is a superior regimen in controlling vomiting induced by chemotherapy.

Adult↗

Early hospital discharge of preterm very low birth weight infants.

OBJECTIVE: The objective of this study was to investigate whether early discharge from the hospital was feasible for selected very low birth weight (VLBW) infants. STUDY DESIGN: A randomized clinical trial of discharge of VLBW infants from the neonatal intensive care unit at 1300 gm versus 1800 gm was done comparing weight gain and incidence of infection. Forty-three VLBW infants treated in the neonatal intensive care unit and follow-up clinics of the Hospital Universitario del Valle, Cali, Colombia, were entered into the study at 1300 to 1350 gm when they met behavioral criteria for discharge and the family home was approved. RESULTS: There were no differences in weight gain or incidence of infection in the home group compared with the hospital group. A significant saving in hospital days and hospital costs was realized for the home group. Family cooperation was heightened in the home group. CONCLUSIONS: Early discharge from the hospital at weights as low as 1300 to 1350 gm is safe for the VLBW infant when properly selected on the basis of behavioral criteria and environmental approval. The potential savings in hospital costs should be considered when resources are allocated for continued support for these infants.

Age Distribution↗

Correlation between level of heparinization and patency of the infarct-related coronary artery after treatment of acute myocardial infarction with alteplase (rt-PA).

BACKGROUND AND OBJECTIVES: The conjunctive use of intravenous heparin may influence the efficacy of alteplase for coronary thrombolysis in patients with acute myocardial infarction. In this study we examined the relation between the level of intravenous anticoagulation with heparin and sustained coronary artery patency in a subgroup of patients of the European Cooperative Study Group (ECSG) trial. METHODS: In the ECSG trial, patients treated with alteplase and aspirin were randomized to concomitant fixed doses of intravenous heparin (a bolus dose of 5,000 U followed by a continuous infusion of 1,000 U/h or placebo). The current study group comprised 149 of 324 ECSG patients allocated to heparin therapy and 132 of 320 ECSG patients allocated to placebo administration who had both an interpretable coronary angiogram obtained within 6 days of treatment and sufficient plasma samples to assess the level of anticoagulation. Activated partial thromboplastin times, fibrinogen and D-dimer levels were determined on plasma samples at baseline and at 45 min and 3, 12, 24 and 36 h after the start of alteplase administration. RESULTS: The coronary artery patency rate was higher in patients allocated to heparin therapy than in those allocated to placebo (80% and 71%, respectively, p = 0.05). Patients allocated to heparin were classified into three subgroups: 48 patients (32%) with all activated partial thromboplastin times at least twice their own baseline value (optimal anticoagulation), 40 patients (27%) with the lowest activated partial thromboplastin time at 3, 12, 24 or 36 h between 130% and 200% of the baseline value (suboptimal anticoagulation) and 61 patients with at least one activated partial thromboplastin time less than 130% of baseline (inadequate anticoagulation). In the heparin group, coronary artery patency correlated with the level of anticoagulation: 90%, 80% and 72%, respectively, in patients with optimal, suboptimal and inadequate anticoagulation (p = 0.02, optimal vs. inadequate anticoagulation). Heparin administration was associated with a smaller reduction in fibrinogen and a smaller increase in D-dimer level during and after alteplase administration. No correlation was found between fibrinogen or D-dimer levels and coronary artery patency. No intracerebral hemorrhage occurred in these patients; however, bleeding was more frequent in the subgroup with optimal anticoagulation (p = 0.05). CONCLUSIONS: Intense anticoagulation with intravenous heparin enhances coronary artery patency after alteplase treatment of acute myocardial infarction.

Adult↗