In search of power and significance: issues in the design and analysis of stochastic cost-effectiveness studies in health care

Application of techniques such as cost-effectiveness analysis (CEA) is growing rapidly in health care. There are two general approaches to analysis: deterministic models based upon assumptions and secondary analysis of retrospective data, and prospective stochastic analyses in which the design of a clinical experiment such as randomised controlled trial is adapted to collect patient-specific data on costs and effects. An important methodological difference between these two approaches is in the quantification and analysis of uncertainty. Whereas the traditional CEA model utilizes sensitivity analysis, the mean-variance data on costs and effects from a prospective trial presents the opportunity to analyze cost-effectiveness using conventional inferential statistical methods. In this study we explored some of the implications of moving economic appraisal away from deterministic models and toward the experimental paradigm. Our specific focus was on the feasibility and desirability of constructing statistical tests of economic hypotheses and estimation of cost-effectiveness ratios with associated 95% confidence intervals. We show how relevant variances can be estimated for this task and discuss the implications for the design and analysis of prospective economic studies.     

Changing clinical practice. Prospective study of the impact of continuing medical education and quality assurance programs on use of prophylaxis for venous thromboembolism

OBJECTIVE: To determine the effect of continuing medical education (CME) with and without a quality assurance component (CME+QA) on physician practices in the prevention of venous thromboembolism. METHODS: A communitywide study was performed in 15 short-stay hospitals in central Massachusetts. The study population included 3158 patients in acute-care hospitals with multiple risk factors for venous thromboembolism. Study hospitals were randomly assigned to one of two educational strategies or to a control group that received no intervention. RESULTS: The proportion of patients at high risk for venous thromboembolism who received effective methods of prophylaxis increased significantly from 29% in 1986 to 52% in 1989 (P < .001). This increase was seen in all study groups: control hospitals, 40% to 51% (P < .001); CME hospitals, 21% to 49% (P < .0001); and CME+QA hospitals, 27% to 55% (P < .0001). The increase in prophylaxis use from 1986 to 1989 was significantly greater among patients cared for in hospitals whose physicians participated in a formal CME program (an increase of 28%) than in control hospitals (an increase of 11%) (P < .001). There was no significant difference in the use of prophylaxis in hospitals whose physicians received CME+QA interventions compared with hospitals whose physicians received CME interventions alone (identical increases of 28%). CONCLUSION: A formal CME program significantly increased the frequency with which physicians prescribed prophylaxis for venous thromboembolism. We believe the key factor in our CME interventions that motivated clinicians to change their practices was the provision of hospital-specific data demonstrating a compelling need for improvement. Despite the substantial investment by hospitals in QA, traditional QA intervention appeared to provide no additional benefit. Even after extensive CME/QA interventions, prophylaxis for venous thromboembolism remained underutilized, suggesting the need to develop new approaches to changing clinical practice.     

Intraperitoneal rupture of ectopic varices--a rare complication of portal hypertension

A 50 year old man presented with sudden abdominal pain, abdominal distension and shock. At emergency laparotomy a large amount of blood was found in the peritoneal cavity. There was micronodular cirrhosis of the liver and the spleen was enlarged. The bleeding was traced to distended veins in the right paracolic gutter which were oversewn and the abdomen closed. A coagulopathy was diagnosed and treatment including high dose aprotinin commenced. However, he continued to bleed and at a second laparotomy the area of previous haemorrhage was packed. Further deterioration continued until death 12 hours later. Intraperitoneal haemorrhage from ectopic varices is a rare occurrence. There is a high mortality rate usually due to an advanced coagulopathy. This is the first report of aprotinin being used in an attempt to treat this. On the basis of this report aprotinin would not seem to be of benefit for this condition.     

Interpreting hospital admissions data across the K?rner divide: the example of diabetes in the north western region

Hospital admission rates and hospital bed utilization rates are presented for all admissions assigned to diabetes mellitus as principal cause in the North Western Region from 1980/81 to 1990/91. Data are derived from Hospital Activity Analysis (1980/81-1986/87) and from the Regional Information System (1988/89-1990/91). Admission rates for all categories of diabetes combined showed little change until 1986/87 after which they rose progressively each year. Hospital bed utilization rates fell progressively from 1986/87 onwards, the number of bed days attributed to diabetes falling from 1.9% to 0.8% of the total for all causes. Most of the rise in admission rates from 1988/89 onwards was attributable to diabetes with ophthalmic complications (ICD 250.4). This was heavily influenced by the enumeration of day cases in the Regional Information System. When these are discounted, admission rates for the more recent years are stable. Diabetes without mention of complications (ICD 250.0) showed the most dramatic decline in its contribution to hospital bed utilization. This may be the result of increasing outpatient support from diabetes specialist nurses whose numbers increased in inverse proportion to the fall in bed utilization attributed to ICD 250.0.     

The routine use of radiography and arterial blood gases in the evaluation of blunt trauma in children

STUDY OBJECTIVE: To evaluate the usefulness of routine radiographs and arterial blood gases in children with blunt trauma. DESIGN: Retrospective chart review. TYPE OF PARTICIPANTS: Ninety patients who met triage criteria for our trauma team evaluation and who were less than 15 years old were evaluated. Patients with a Glasgow Coma Scale score (GCS) of 15 (lie, mild to moderately injured children) were the focus of this study. METHODS: Children seen from May 1991 through August 1992 had charts reviewed systematically and within 24 hours of emergency department evaluation. Standard radiologic evaluation, including cervical-spine, chest, and pelvic radiographs, as well as arterial blood gas analysis, were obtained. The severity of injury was graded according to the Modified Injury Severity Scale. RESULTS: The mean age of patients was 6.4 years, and the injuries observed were exclusively extremity fractures. The correlation between physical examination findings and radiologic evaluation was assessed. Forty-three patients had an abnormal physical examination (ie, gross deformity, limitation of motion, or pain), and 26 had a fracture identified on radiograph. Forty-seven patients had a normal physical examination and none had a fracture identified on radiograph (P < .001; sensitivity of positive signs and symptoms, 100%; false-negative findings, 0%). Four patients with abnormal blood gases are described. No patient had any vascular or solid organ injury identified. CONCLUSION: In children with a GCS score of 15, selected radiologic and laboratory tests based on clinical findings are recommended. Careful observation and repeat examinations by trained clinicians can select a group of children at low risk for occult injury.     

Sperm morphology as diagnosed by strict criteria: probing the impact of teratozoospermia on fertilization rate and pregnancy outcome in a large in vitro fertilization population

OBJECTIVE: To investigate the predictive value of sperm morphology assessed by strict criteria on IVF outcome. DESIGN: Retrospective analysis of all IVF cycles (January 1987 to December 1992). MAIN OUTCOME MEASURES: All patients were assigned to one of three groups based on sperm morphology: P-pattern (< 4% normal forms), G-pattern (4% to 14% normal forms), and N-pattern (> 14% normal forms). Morphology pattern was related to other semen characteristics and IVF outcome. RESULTS: Despite corrective measures at oocyte insemination, the fertilization rate was significantly different among the three morphology groups, P < G < N. N-pattern sperm produced a mean fertilization rate over 85% regardless of low motility or concentration. In a cohort study, P-pattern cycles produced a lower implantation rate and lower ongoing pregnancy rate, independent of the lower fertilization rate. CONCLUSIONS: Strict morphology is an excellent biomarker of sperm fertilizing capacity, independent of motility and concentration. P-pattern sperm may denote a poorer prognosis for establishing a pregnancy, even after a satisfactory fertilization rate is achieved.     

Role of neutrophil-endothelial cell adhesion in inflammatory disorders

Polymorphonuclear leukocytes are armed with an impressive arsenal of bactericidal agents that allow these cells to play a vital role in host defense against invading pathogens. However, these same agents can produce extensive cellular damage in host tissues when leukocytes are activated during inflammatory conditions. Recognition of this fact, when coupled with the observation that leukocyte adhesion to post-capillary venules is a critical first step in the inflammatory process, has led to the development of the concept that inhibition of neutrophil-endothelial cell adhesion (NECA) may represent a novel therapeutic strategy for the prevention of leukocyte-dependent injury in inflammatory conditions. Indeed, pharmacological or immunologic inhibition of NECA reduces cellular injury, dysfunction, and necrosis induced by ischemia/reperfusion, circulatory shock and resuscitation, organ transplantation, cardiopulmonary bypass, frostbite, and thermal trauma. NECA also appears to play an important role in the pathobiology of airway inflammation and asthma, pulmonary oxygen toxicity, arthritis, bacterial meningitis, and cerebral malaria. The aim of this review is to summarize the evidence implicating NECA in the pathogenesis of these inflammatory conditions.