Significance tests and the duplicity of binary decisions.

Presents a logical justification for the following statements and discusses their implications: It is duplicitous (misleading) to use significance tests for making binary (either/or) decisions regarding the validity of a theory; the binary choice between calling results significant or not significant should not govern the confidence placed in a theory, because such confidence cannot be gained in the either/or fashion characterizing deductive certainty. The implications include grounds for describing ways that effect size estimates become useful in making judgments about the value of theories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A model to predict survival following liver retransplantation

In the current era of critical-organ shortage, one of the most controversial questions facing transplantation teams is whether hepatic retransplantation, which has historically been associated with increased resource utilization and diminished survival, should be offered to a patient whose first allograft is failing. Retransplantation effectively denies access to orthotopic liver transplantation (OLT) to another candidate and further depletes an already-limited organ supply. The study group was comprised of 1,356 adults undergoing hepatic retransplantation in the United States between 1990 and 1996 as reported to the United Network for Organ Sharing (UNOS). We analyzed numerous donor and recipient variables and created Cox proportional-hazards models on 900 randomly chosen patients, validating the results on the remaining cohort. Five variables consistently provided significant predictive power and made up the final model: age, bilirubin, creatinine, UNOS status, and cause of graft failure. Although both hepatitis C seropositivity and donor age were significant by univariate and multivariate analyses, neither contributed independently to the estimation of prognosis when added to the final model. The final model was highly predictive of survival (whole model chi2 = 139.63). The risk scores for individual patients were calculated, and patients were assigned into low-, medium-, and high-risk groups (P <.00001). The low degree of uncertainty in the probability estimates as reflected by confidence intervals, even in our high-risk patients, underscores the applicability of our model as an adjunct to clinical judgment. We have developed and validated a model that uses five readily accessible "bedside" variables to accurately predict survival in patients undergoing liver retransplantation.     

Rationing: a transatlantic perspective

Despite the differing mechanisms of health care delivery and financing in the United Kingdom and the United States many of the issues faced by the two countries are similar, most notably the increasing financial pressures. In both countries there have been recent changes in the allocation of resources and the mechanisms of decision making. Different criteria for determining resource allocation have been tried in the two health care systems. These developments change long traditions of rationing decisions at the individual patient level in the US, and of centralised government decision making in the UK.     

Impact of sonography on the diagnosis and treatment of acute lower abdominal pain in children and young adults

OBJECTIVE: Our purpose was to evaluate the impact of sonographic data on clinical physicians' diagnostic confidence and their treatment of children and young adults with acute lower abdominal pain. SUBJECTS AND METHODS: Senior surgical and emergency department staff completed questionnaires before and after abdominal sonography was performed on 94 of 101 consecutive children and young adults with acute lower abdominal pain, pelvic pain, or both. Physicians who were unaware of sonographic data stated the most likely diagnosis and their level of confidence in their diagnosis and then formulated clinical plans. After they were given sonographic data, physicians again stated the most likely diagnosis, estimated their level of confidence, and formulated revised treatment plans. RESULTS: Sonographic data resulted in revised clinical diagnoses in 52% of the patients. Overall, the gain in diagnostic confidence for the entire study population was 33% (95% confidence interval [CI], 27-38%; p < .0001). The impact on the physicians' confidence was greater in those children and young adults whose diagnoses changed after sonography (mean increase in physicians' confidence, 48.3%; 95% CI, 47-75%). In patients whose diagnoses were not changed after sonography, the mean increase in physicians' confidence was 17.6% (95% CI, 11-24%; p < .0001 [analysis of variance]). Physicians used sonographic data to change initial treatment plans in 43 patients (46%). Of these 43 patients, a lower intensity of care was given to 30 patients (70%) and a higher intensity to 13 patients (30%). CONCLUSION: Sonographic data frequently changed initial clinical diagnoses, thus increasing diagnostic confidence and changing clinical treatment decisions in the setting of acute lower abdominal pain in children and young adults.     

Carrier screening for cystic fibrosis, Gaucher disease, and Tay-Sachs disease in the Ashkenazi Jewish population: the first 1000 cases at New York University Medical Center, New York, NY

BACKGROUND: Ovarian cancer patients have a poor prognosis. In Norway, however, the prognosis has improved steadily since the 1950s, the age-adjusted 5-year relative survival reaching 37% in 1989 93. The aim of the present study was to explore the prognosis of patients with epithelial ovarian cancer diagnosed during 1975-94 (the prepaclitaxel period) and treated at The Norwegian Radium Hospital. METHOD: Relative risks (RR) of dying and 95% confidence intervals (95% CI) were derived from multivariate Cox proportional hazards regression models. RESULTS: A total of 2,769 patients with epithelial ovarian cancer were included in the present study. Altogether 54% of the patients were diagnosed with advanced stage disease (stages III and IV), whereas 32% were diagnosed with stage I disease. The prognosis of the patients improved from the 1970s to the 1990s, mainly due to increased short-term survival. In multivariate survival analysis, the RR of dying decreased with period of diagnosis. An RR of 0.77 (95% CI=0.66-0.89) was seen in 1990-94 compared with 1975-79. CONCLUSION: The short-term survival of patients with epithelial ovarian cancer improved from the late 1970s to the early 1990s. However, no major improvement in the long-term survival was seen.     

Annual league tables of mortality in neonatal intensive care units: longitudinal study. International Neonatal Network and the Scottish Neonatal Consultants and Nurses Collaborative Study Group

OBJECTIVE: To assess whether crude league tables of mortality and league tables of risk adjusted mortality accurately reflect the performance of hospitals. DESIGN: Longitudinal study of mortality occurring in hospital. SETTING: 9 neonatal intensive care units in the United Kingdom. SUBJECTS: 2671 very low birth weight or preterm infants admitted to neonatal intensive care units between 1988 and 1994. MAIN OUTCOME MEASURES: Crude hospital mortality and hospital mortality adjusted using the clinical risk index for babies (CRIB) score. RESULTS: Hospitals had wide and overlapping confidence intervals when ranked by mortality in annual league tables; this made it impossible to discriminate between hospitals reliably. In most years there was no significant difference between hospitals, only random variation. The apparent performance of individual hospitals fluctuated substantially from year to year. CONCLUSIONS: Annual league tables are not reliable indicators of performance or best practice; they do not reflect consistent differences between hospitals. Any action prompted by the annual league tables would have been equally likely to have been beneficial, detrimental, or irrelevant. Mortality should be compared between groups of hospitals using specific criteria-such as differences in the volume of patients, staffing policy, training of staff, or aspects of clinical practice-after adjusting for risk. This will produce more reliable estimates with narrower confidence intervals, and more reliable and rapid conclusions.     

Repair of congenital tracheal stenosis with a free tracheal autograft

PURPOSE: This retrospective review was conducted to determine if delay in the start of radiotherapy after definitive breast surgery had any detrimental effect on local recurrence or disease-free survival in node-negative breast cancer patients. METHODS AND MATERIALS: A total of 568 patients with T1-T2, N0 breast cancer were treated with breast-conserving surgery and breast irradiation, without adjuvant systemic therapy between January 1, 1985 and December 31, 1992, at the London Regional Cancer Centre. Adjuvant breast irradiation consisted either of 50 Gy in 25 fractions or 40 Gy in 15 or 16 fractions, followed by a boost of 10 Gy or 12.5 Gy to the lumpectomy site. The time intervals from definitive breast surgery to breast irradiation used for analysis were 0-8 weeks (201 patients), > 8-12 weeks (235 patients), > 1216 weeks (91 patients), and > 16 weeks (41 patients). The time intervals of 0-12 weeks (436 patients) and > 12 weeks (132 patients) were also analyzed. Kaplan-Meier estimates of time to local recurrence and disease-free survival rates were calculated. The association between surgery-radiotherapy interval, age (< or = 40, > 40 years), tumor size (< or = 2, > 2cm), Scharf-Bloom-Richardson (SBR) grade, resection margins, lymphatic vessel invasion, extensive intraductal component, and local recurrence and disease-free survival were investigated using Cox regression techniques. RESULTS: Median follow-up was 63.5 months. Patients in all 4 time intervals were similar in terms of age and pathologic features. There was no statistically significant difference between the 4 groups in local recurrence or disease-free survival with surgery-radiotherapy interval (p = 0.189 and p = 0.413, respectively). The 5-year freedom from local relapse was 95.4%. The crude local recurrence rate was 6.9% (7.8% for 436 patients treated within 12 weeks (median follow-up 67 months) and 3.8% for 132 patients treated > 12 weeks from surgery (median follow-up 52 months). In a stepwise multivariable Cox regression model for disease-free survival, allowing for entry of known risk factors, tumour size (p < 0.001), grade (p < 0.001), and age (p = 0.048) entered the model, but the surgery-radiotherapy interval did not enter the model. CONCLUSION: This retrospective study suggests that delay in start of breast irradiation beyond 12 and up to 16 weeks does not increase the risk of recurrence in node-negative breast cancer patients. The certainty of these results are limited by the retrospective nature of this analysis and the lack of information concerning the late local failure rate.     

Meta-analysis of intravenous dipyridamole-thallium-201 imaging (1985 to 1994) and dobutamine echocardiography (1991 to 1994) for risk stratification before vascular surgery

OBJECTIVES: This study evaluated the prognostic value of abnormal test results with pharmacologic stress with regard to perioperative and long-term outcomes in a large population of candidates for vascular surgery. BACKGROUND: Although numerous studies have demonstrated the prognostic value of dipyridamole-thallium-201 myocardial perfusion and dobutamine echocardiography in vascular surgery candidates, a synopsis of predictive estimates is difficult because of individual study variability in pretest clinical risk, sample size and study design. METHODS: A systematic review of published reports on preoperative pharmacologic stress risk stratification from the MEDLINE data base (1985 to 1994) identified 10 reports on dipyridamole-thallium-201 myocardial perfusion (1,994 patients) and 5 on dobutamine stress echocardiography (446 patients). Random effects models were used to calculate summary odds ratios and 95% confidence intervals. RESULTS: Summary odds ratios for death or myocardial infarction and secondary cardiac end points were greater for dobutamine echocardiographic dyssynergy (14- to 27-fold) than for dipyridamole-thallium-201 redistribution (4-fold); wider confidence intervals were noted with dobutamine echocardiography. Pretest coronary disease probability was correlated with the positive predictive value of a reversible thallium-201 defect (r=0.70), increasing sixfold from low to high risk patient subsets. Cardiac event rates were low in patients without a history of coronary artery disease (1% in 176 patients) compared with patients with coronary disease and a normal or fixed-defect pattern (4.8% in 83 patients) and one or more thallium-201 redistribution abnormality (18.6% in 97 patients, p=0.0001). CONCLUSIONS: Meta-analysis of 15 studies demonstrated that the prognostic value of noninvasive stress imaging abnormalities for perioperative ischemic events is comparable between available techniques but that the accuracy varies with coronary artery disease prevalence.     

Results of radical prostatectomy in men with clinically localized prostate cancer

OBJECTIVE: To assess the results of radical prostatectomy in men with early prostate cancer. DESIGN: Retrospective, nonrandomized, multi-institutional pooled analysis. SETTING: Eight university medical centers in the United States and Europe. PATIENTS: A total of 2758 men with stage Tl and T2 prostatic cancer. MAIN OUTCOME MEASURES: Disease-specific and metastasis-free survival rates. RESULTS: Tumor grade was the most important preoperative factor in determining outcome. Disease-specific survival 10 years following surgery and associated 95% confidence intervals were 94% (range, 87%-98%), 80% (range, 74%-85%), and 77% (range, 65%-86%) for those men with grade 1, 2, and 3 tumors, respectively. Metastasis-free survival at 10 years was 87% (range, 78%-92%), 68% (range, 62%-73%), and 52% (range, 38%-64%) for patients with grade 1, 2, and 3 cancers, respectively. CONCLUSIONS: Radical prostatectomy leads to high 10-year disease-specific survival rates in men with all tumor grades. However, caution is needed in comparing these results with similar studies of alternative treatment strategies, such as watchful waiting, due to the inherent potential biases in uncontrolled trials. Nevertheless, these results offer the best currently available estimates of 10-year outcome of radical prostatectomy in men with clinically localized prostate cancer and may be useful in counseling patients with early malignancy.     

Quantitative spectral electroencephalography in predicting survival in patients with early Alzheimer disease

OBJECTIVE: To determine whether measures of quantitative spectral electroencephalography (EEG) can predict survival in patients with early Alzheimer disease. DESIGN: Prospective cohort study; median duration of follow-up was 4.4 years in survivors and 2.6 years in nonsurvivors. Cox proportional hazards models, with adjustment for age and sex were used to estimate relationships between EEG measures and survival. Log relative percentage values of EEG bands were used as predictors. SETTING: Outpatient university memory clinic. PARTICIPANTS: One hundred one consecutively referred patients with early probable Alzheimer disease according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria were studied with EEG at the time of diagnosis. The mean age of the patients was 79.2 years, which was higher than in previous EEG studies. MAIN OUTCOME MEASURE: Mortality. RESULTS: Fifty-one patients (50.5%) died during follow-up, with a median survival time in all patients of 4.1 years. The following EEG variables were significantly associated with increased risk of mortality: from parieto-occipital leads, higher theta (hazard ratio, 2.05; 95% confidence interval, 1.15-3.66; P<.05), lower alpha (hazard ratio, 0.43; 95% confidence interval, 0.25-0.76; P<.01), and lower beta (hazard ratio, 0.38; 95% confidence interval, 0.22-0.68; P<.001) activity; and from frontocentral leads, higher theta activity (hazard ratio, 2.07; 95% confidence interval, 1.17-3.66; P<.05). Stepwise Cox regression analysis showed that loss of parieto-occipital beta (P<.01) and alpha (P<.05) power were independent and significant predictors of mortality. Both beta (12.6-35.4 Hz) and alpha (7.5-12.5 Hz) activity remained significantly associated with mortality after adjustment for education, dementia severity, symptom duration, level of cognitive function, presence of extrapyramidal symptoms or hallucinations, presence of vascular risk factors, and presence of leukoaraiosis or local cortical atrophy. CONCLUSIONS: Decreases of beta and alpha activity on quantitative spectral EEG are independent predictors of mortality in patients with early Alzheimer disease. In the clinical context, the use of EEG technology for prediction of survival in individual patients remains to be determined.     

Delayed exercise rate response kinetics due to sensor cross-checking in a dual sensor rate adaptive pacing system: the importance of individual sensor programming

General practitioners (GPs) in the United Kingdom are central to the commissioning of health care services. A qualitative study of their views was therefore designed, which incorporated an in-depth (open) interview technique carried out on a 20% sample of all GPs (n = 100) in one United Kingdom Health District. The data from these interviews indicated that GPs were aware of, but had mixed feelings about the need for rationing. They expressed disquiet about the dilemma faced in rationing health care at the time of the consultation and readily associated issues of cost in their practice with rationing. Some of the currently adopted methods of rationing (waiting lists, co-payments and ability to pay) were commented upon. The respondents also made suggestions on how rationing could be carried out, which included: maximizing efficiency to reduce the need for rationing; using a third party committee to make rationing decisions, with a membership of clinicians, managers, and possibly public representatives, and; being explicit about how rationing is done. Fundholding brought rationing decisions to the fore, and worried most who discussed it in the context of rationing. The conclusion of this paper is that current implicit rationing policies in the National Health Service are flawed as they assume that GPs will ration health care at the time of the consultation. The involvement of GPs in the rationing process is important (particularly given the present expansion of GP fundholding), so there is a need for an alternative to the present system.     

Relationship between cancer patients' predictions of prognosis and their treatment preferences

CONTEXT: Previous studies have documented that cancer patients tend to overestimate the probability of long-term survival. If patient preferences about the trade-offs between the risks and benefits associated with alternative treatment strategies are based on inaccurate perceptions of prognosis, then treatment choices may not reflect each patient's true values. OBJECTIVE: To test the hypothesis that among terminally ill cancer patients an accurate understanding of prognosis is associated with a preference for therapy that focuses on comfort over attempts at life extension. DESIGN: Prospective cohort study. SETTING: Five teaching hospitals in the United States. PATIENTS: A total of 917 adults hospitalized with stage III or IV non-small cell lung cancer or colon cancer metastatic to liver in phases 1 and 2 of the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). MAIN OUTCOME MEASURES: Proportion of patients favoring life-extending therapy over therapy focusing on relief of pain and discomfort, patient and physician estimates of the probability of 6-month survival, and actual 6-month survival. RESULTS: Patients who thought they were going to live for at least 6 months were more likely (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.8-3.7) to favor life-extending therapy over comfort care compared with patients who thought there was at least a 10% chance that they would not live 6 months. This OR was highest (8.5; 95% CI, 3.0-24.0) among patients who estimated their 6-month survival probability at greater than 90% but whose physicians estimated it at 10% or less. Patients overestimated their chances of surviving 6 months, while physicians estimated prognosis quite accurately. Patients who preferred life-extending therapy were more likely to undergo aggressive treatment, but controlling for known prognostic factors, their 6-month survival was no better. CONCLUSIONS: Patients with metastatic colon and lung cancer overestimate their survival probabilities and these estimates may influence their preferences about medical therapies.     

Genetic susceptibility to pregnancy-related venous thromboembolism: roles of factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations

OBJECTIVE: This study's objective was to evaluate the association between venous thromboembolism during pregnancy and the postpartum period and the factor V Arg 506 Gln (factor V Leiden), the prothrombin G20210A, and methylenetetrahydrofolate reductase C677T polymorphisms. STUDY DESIGN: In this case-control study 42 case patients and 213 control subjects (parous age-matched women without history of thrombosis) were genotyped for all the polymorphisms. Moreover, antiphospholipid antibodies and protein C, protein S, and antithrombin III deficiencies were investigated in each case. RESULTS: Ten case patients (23.8%) and 4 control subjects (1.9%; odds ratio 16.3, 95% confidence interval 4.8-54.9) carried the factor V Leiden mutation; 13 case patients (31.0%) and 9 control subjects (4.2%; odds ratio 10.2, 95% confidence interval 4.0-25.9) were carriers of the prothrombin G20210A allele. Finally, 12 case patients (28.6%) and 34 control subjects (16.0%; odds ratio 2.1, 95% confidence interval 1.0-4.5) were homozygotes for methylenetetrahydrofolate reductase C677T. Overall, mutations were found in 25 case patients (59.5%) and 47 control patients (22.2%; odds ratio 5.2, 95% confidence interval 4.9-19.6). One patient carried the antithrombin III deficiency and 1 the protein S deficiency, whereas 2 women had a primary antiphospholipid syndrome. CONCLUSIONS: The significant risk estimates of having a pregnancy-related venous thromboembolism in the presence of the prothrombotic genetic risk factors analyzed suggest to screen for these mutations women with a personal history of thromboembolic events during pregnancy or the postpartum period.     

Treatment of intermediate risk rhabdomyosarcoma and undifferentiated sarcoma with alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide

Over 50% of patients with newly diagnosed rhabdomyosarcoma (RMS) are in the 'intermediate risk' group with a 3-year progression-free survival of approximately 65%. This group consists of stage 1, group III, non-orbit tumours; stage 2, group II and III; and all stage 3 patients utilising the Intergroup Rhabdomyosarcoma Study (IRS) staging system. The role of doxorubicin in the treatment of RMS has been controversial. Ifosfamide, both alone and in combination with etoposide, has significant activity in patients with RMS. The aim of this pilot study was to examine the efficacy and toxicity of a chemotherapy regimen of alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide for intermediate risk RMS. 30 patients with intermediate risk RMS or undifferentiated sarcoma (US) were treated with alternating cycles of vincristine/doxorubicin/cyclophosphamide (VDC) and etoposide/ifosfamide (EI) at planned intervals of 3 weeks. Local treatment of the tumour in most cases was performed after four cycles of chemotherapy, followed by an additional 10 cycles of chemotherapy. At a median follow-up of 37.5 months, the Kaplan-Meier estimate of 3-year event-free survival was 85% (95% confidence interval 72-99%). The overall survival at 3 years was 91% (95% confidence interval 80-100%). No patient died from toxicity. The most common toxicity was febrile neutropenia in 35% of VDC and 26% of EI cycles. No nephrotoxicity or cardiac toxicity was seen. No patient progressed prior to week 12 local therapy. Alternating cycles of VDC and EI are an effective treatment for patients with intermediate risk RMS and US. Toxicity is tolerable. Delaying local treatment until week 12 does not compromise outcome.     

The importance of local control in the conservative treatment of breast cancer

The purpose of this study was to examine the meaning of local control, especially on survival, in breast cancer patients treated by lumpectomy with or without radiotherapy. We analyzed the survival results of four major published randomized trials that compare conservation surgery with or without radiation using three different statistical approaches: p-values, confidence intervals, and Bayesian techniques. All four trials report statistically significant increased local control and improved survival for the irradiated patients. Survival based on p-values and confidence intervals shows statistical significance for long-term follow-up of the NSABP-B06 trial, but not for the other trials, probably because of small sample sizes and short follow-up. At 10 years, the overall survival rates for the NSABP-B06 were 65% and 71% for lumpectomy alone or with radiation respectively. Interpreted in a Bayesian framework, the expected advantage in 10-year survival was 6% (the mean of NSABP-B06 10-year survival) with an 83% probability that the 10-year survival difference may lie between 2% and 10%. An 85% probability that 3% of patients will survive at 10 years because of irradiation translates into a 30% reduction in annual odds of death several years after treatment in stage I good prognosis patients and 15% in stage I poor prognosis patients. Analysis of the randomized trials comparing lumpectomy with or without radiation indicate a clear improvement in survival for the irradiated patients associated with increased local control. Combination of improved survival with the reduced psychological and economic costs associated with local recurrence argues well for the inclusion of radiation for many breast cancer patients.     

Accurate confidence limits for quantiles under random censoring

In survival analysis, estimates of median survival times in homogeneous samples are often based on the Kaplan-Meier estimator of the survivor function. Confidence intervals for quantiles, such as median survival, are typically constructed via large sample theory or the bootstrap. The former has suspect accuracy for small sample sizes under moderate censoring and the latter is computationally intensive. In this paper, improvements on so-called test-based intervals and reflected intervals (cf., Slud, Byar, and Green, 1984, Biometrics 40, 587-600) are sought. Using the Edgeworth expansion for the distribution of the studentized Nelson-Aalen estimator derived in Strawderman and Wells (1997, Journal of the American Statistical Association 92), we propose a method for producing more accurate confidence intervals for quantiles with randomly censored data. The intervals are very simple to compute, and numerical results using simulated data show that our new test-based interval outperforms commonly used methods for computing confidence intervals for small sample sizes and/or heavy censoring, especially with regard to maintaining specified coverage.     

Evaluation of deoxyribonucleic acid ploidy and S-phase fraction as prognostic parameters in advanced epithelial ovarian carcinoma: a prospective study

OBJECTIVE: Our goal was to study the prognostic value of deoxyribonucleic acid ploidy and S-phase fraction in advanced ovarian carcinoma. STUDY DESIGN: Prognostic factors for corrected survival were evaluated in a prospective study including 169 patients with stage III and IV ovarian cancer treated between 1985 and 1990. RESULTS: A total of 79% of the tumors were deoxyribonucleic acid aneuploid. Deoxyribonucleic acid aneuploidy was associated with grade of differentiation. S-phase fraction could be calculated in all deoxyribonucleic acid euploid tumors and 76% of the deoxyribonucleic acid aneuploid tumors. By multivariate analysis deoxyribonucleic acid ploidy, histologic type and grade, age, International Federation of Gynecology and Obstetrics stage, and amount of residual tumor were independent prognostic variables for corrected survival. On the basis of Cox regression a relative risk for the individual patient could be calculated. CONCLUSION: Deoxyribonucleic acid ploidy gives additive prognostic information and is a useful parameter for dividing patients with advanced ovarian cancer into risk groups for treatment decisions.     

Race, resource use, and survival in seriously ill hospitalized adults. The SUPPORT Investigators

OBJECTIVE: To examine the association between patient race and hospital resource use. DESIGN: Prospective cohort study. SETTING: Five geographically diverse teaching hospitals. PATIENTS: Patients were 9,105 hospitalized adults with one of nine illnesses associated with an average 6-month mortality of 50%. MEASUREMENTS AND MAIN RESULTS: Measures of resource use included: a modified version of the Therapeutic Intervention Scoring System (TISS); performance of any of five procedures (operation, dialysis, pulmonary artery catheterization, endoscopy, and bronchoscopy); and hospital charges, adjusted by the Medicare cost-to-charge ratio per cost center at each participating hospital. The median patient age was 65; 79% were white, 16% African-American, 3% Hispanic, and 2% other races; 47% died within 6 months. After adjusting for other sociodemographic factors, severity of illness, functional status, and study site, African-Americans were less likely to receive any of five procedures on study day 1 and 3 (adjusted odds ratio [OR] 0.70; 95% confidence interval [CI] 0.60, 0.81). In addition, African-Americans had lower TISS scores on study day 1 and 3 (OR -1.8; 95% CI-1.3, -2.4) and lower estimated costs of hospitalization (OR (-)$2,805; 95% CI (-)$1,672, (-)$3,883). Results were similar after adjustment for patients' preferences and physicians' prognostic estimates. Differences in resource use were less marked after adjusting for the specialty of the attending physician but remained significant. In a subset analysis, cardiologists were less likely to care for African-Americans with congestive heart failure (p < .001), and cardiologists used more resources (p < .001). After adjustment for other sociodemographic factors, severity of illness, functional status, and study site, survival was slightly better for African-American patients (hazard ratio 0.91; 95% CI 0.84, 0.98) than for white or other race patients. CONCLUSIONS: Seriously ill African-Americans received less resource-intensive care than other patients after adjustment for other sociodemographic factors and for severity of illness. Some of these differences may be due to differential use of subspecialists. The observed differences in resource use were not associated with a survival advantage for white or other race patients.     

Is there a rationale for rationing chronic dialysis? A hospital based cohort study of factors affecting survival and morbidity

OBJECTIVES: To determine factors influencing survival and need for hospitalisation in patients needing dialysis, and to define the potential basis for rationing access to renal replacement therapy. DESIGN: Hospital based cohort study of all patients starting dialysis over a 4 year recruitment period (follow up 15-63 months). Groups were defined on the basis of age, comorbidity, functional status, and whether dialysis initiation was planned or unplanned. SETTING: Renal unit in a district general hospital, which acts as the main renal referral centre for four other such hospitals and serves a population of about 1.15 million people. SUBJECTS: 292 patients, mean age 61.3 years (18-92 years, SD 15.8), of whom 193 (66%) were male, and 59 (20%) were patients with diabetes. Dialysis initiation was planned in 163 (56%) patients and unplanned in 129 (44%). MAIN OUTCOME MEASURES: Overall survival, 1 year survival, and hospitalisation rate. RESULTS: Factors affecting survival in the Cox's proportional hazard model were Karnofsky performance score at presentation (hazard ratio 0.979, 95% confidence interval 0.972 to 0. 986), comorbidity severity score (1.240, 1.131 to 1.340), age (1.036, 1.018 to 1.054), and myeloma (2.15, 1.140 to 4.042). The Karnofsky performance score used 3 months before presentation was significant (0.970, 0.956 to 0.981), as was unplanned presentation in this model (1.796, 1.233 to 2.617). Using these factors, a high risk group of 26 patients was defined, with 19.2% 1 year survival. Denying dialysis to this group would save 3.2% of the total cost of the chronic programme but would sacrifice five long term survivors. Less rigorous definition of the high risk group would save more money but lose more long term survivors. CONCLUSIONS: Severity of comorbid conditions and functional capacity are more important than age in predicting survival and morbidity of patients on dialysis. Late referral for dialysis affects survival adversely. Denial of dialysis to patients in an extremely high risk group, defined by a new stratification based on logistic regression, would be of debatable benefit.     

Surgical adjuvant active specific immunotherapy for patients with stage III melanoma: the final analysis of data from a phase III, randomized, double-blind, multicenter vaccinia melanoma oncolysate trial

BACKGROUND: A phase III, randomized, double-blind, multicenter trial of active specific immunotherapy (ASI) using vaccinia melanoma oncolysate (VMO) was performed in patients with stage III (American Joint Commission on Cancer) melanoma to determine the efficacy of VMO to increase the disease-free interval (DFI) or overall survival (OS) in these patients. Two interim analyses of data from this trial were performed in May 1994 and June 1995. Although the results from these analyses showed no statistically significant improvement in DFI or OS in all patients using VMO, two subsets-men aged 44-57 years with one to five positive nodes and all patients with clinical stage I and pathologic stage II disease-showed an overall survival advantage with VMO therapy. A final analysis of data from this trial was performed in May 1996 and is reported here. The design of future melanoma vaccine trials is discussed based on information learned from this first randomized, multicenter trial of ASI therapy. STUDY DESIGN: A polyvalent VMO was prepared using melanoma cells derived from four melanoma cell lines and vaccinia vaccine virus (V). Patients were accrued from 11 United States institutions and were randomized by the Statistical Center at the University of Alabama, Birmingham. Two hundred fifty patients were randomized to treatment with either VMO (1 U containing 2 mg of total protein derived from 5 x 10(6) melanoma cells and 10(5.6) 50% tissue culture infectious dose of vaccinia virus) or control V (1 U containing 10(5.4) 50% tissue culture infectious dose of vaccinia virus) once a week for 13 weeks and then once every 2 weeks for a total of 12 months, or until recurrence. Patient data were collected by the Statistical Center and analyzed as of May 1996 for DFI and OS using Wilcoxon test and log-rank analysis. RESULTS: Two hundred seventeen patients were found to be eligible according to the inclusion criteria. Data from these patients were analyzed for DFI and OS after a median followup of 46.3 months (50.2 months for VMO and 41.3 months for V). This final analysis showed no statistically significant increase in either DFI (p = 0.61) or OS (p = 0.79) of patients treated with VMO (n = 104) compared with V (n = 113). At 2-, 3-, and 5-year intervals, 47.8%, 43.8%, and 41.7% of patients treated with VMO were disease-free, respectively, compared with 51.2%, 44.8%, and 40.4% of patients treated with V. At the same intervals, 70.0%, 60.0%, and 48.6% of patients treated with VMO survived, compared with 65.4%, 55.6%, and 48.2% of patients treated with V. In a retrospective subset analysis, male patients aged 44-57 years (n = 20) with one to five positive nodes showed 18.9%, 26.82%, and 21.3% improvement in survival at 2-, 3-, and 5-year intervals, respectively, after treatment with VMO when compared with V (n = 18) (p = 0.046). CONCLUSIONS: This study was a randomized, multicenter, placebo-controlled evaluation of an active specific immunotherapeutic agent to increase the DFI or OS of patients with stage III melanoma in a surgical adjuvant setting. In this trial, ASI with VMO when compared with V showed no difference in either DFI or OS. In a retrospective subset analysis, however, a subset of men with one to five positive nodes, between the ages of 44 and 57 years, showed a survival advantage with VMO. This result suggests that one must include a detailed subset analysis in the design of future trials of ASI for patients with American Joint Commission on Cancer stage III melanoma. An appropriate control arm also must be included in ASI trials.