The SUPPORT Principal Investigators
Objectives.--To improve end-of-life decision making and reduce the frequency of a mechanically supported, painful, and prolonged process of dying.
Design.--A 2-year prospective observational study (phase I) with 4301 patients followed by a 2-year controlled clinical trial (phase II) with 4804 patients and their physicians randomized by specialty group to the intervention group (n=2652) or control group (n=2152).
Setting.--Five teaching hospitals in the United States.
Patients.--A total of 9105 adults hospitalized with one or more of nine life-threatening diagnoses; an overall 6-month mortality rate of 47%.
Intervention.--Physicians in the intervention group received estimates of the likelihood of 6-month survival for every day up to 6 months, outcomes of cardiopulmonary resuscitation (CPR), and functional disability at 2 months. A specially trained nurse had multiple contacts with the patient, family, physician, and hospital staff to elicit preferences, improve understanding of outcomes, encourage attention to pain control, and facilitate advance care planning and patient-physician communication.
Results.--The phase I observation documented shortcomings in communication, frequency of aggressive treatment, and the characteristics of hospital death: only 47% of physicians knew when their patients preferred to avoid CPR; 46% of do-not-resuscitate (DNR) orders were written within 2 days of death; 38% of patients who died spent at least 10 days in an intensive care unit (ICU); and for 50% of conscious patients who died in the hospital, family members reported moderate to severe pain at least half the time. During the phase II intervention, patients experienced no improvement in patient-physician communication (eg, 37% of control patients and 40% of intervention patients discussed CPR preferences) or in the five targeted outcomes, ie, incidence or timing of written DNR orders (adjusted ratio, 1.02; 95% confidence interval [CI], 0.90 to 1.15), physicians' knowledge of their patients' preferences not to be resuscitated (adjusted ratio, 1.22; 95% CI, 0.99 to 1.49), number of days spent in an ICU, receiving mechanical ventilation, or comatose before death (adjusted ratio, 0.97; 95% CI, 0.87 to 1.07), or level of reported pain (adjusted ratio, 1.15; 95% CI, 1.00 to 1.33). The intervention also did not reduce use of hospital resources (adjusted ratio, 1.05; 95% CI, 0.99 to 1.12).
Conclusions.--The phase I observation of SUPPORT confirmed substantial shortcomings in care for seriously ill hospitalized adults. The phase II intervention failed to improve care or patient outcomes. Enhancing opportunities for more patient-physician communication, although advocated as the major method for improving patient outcomes, may be inadequate to change established practices. To improve the experience of seriously ill and dying patients, greater individual and societal commitment and more proactive and forceful measures may be needed.
(JAMA. 1995;274:1591-1598)
Scott A. Optenberg, DrPH; Ian M. Thompson, MD; Paul Friedrichs, MD; Barbara Wojcik, PhD; Catherine R. Stein, MS; Barnett Kramer, MD
Objective.--To evaluate long-term survival of black and white prostate cancer patients in an equal-access medical care system to help distinguish biological from medical and social explanations of mortality differences.
Design and Setting.--Retrospective study of US Department of Defense tumor registry patients with prostate cancer. Ethnicity, age, diagnosis, staging, risk factors, treatment, and survival end points were extracted.
Patients.--Prostate cancer patients (N=1606; 7.5% black, 92.5% white) who were active-duty personnel, dependents, or retirees eligible for care in the military medical system.
Main Outcome Measures.--Racial differences in tumor stage and grade, risk factors, recurrence, and treatment wait time (time between initial diagnosis and initial treatment); influence of stage, grade, treatment, wait time, age, and race on survival.
Results.--No differences were found in behavioral risk factors or tumor grade or size, but blacks entered active treatment (P<.001) and exhibited a higher relative risk of cancer (P=.01) in younger age groups, presented with higher stage (P<.001), and demonstrated increased progression in distant metastatic disease (P=.01). No significant differences were detected in overall wait time. When adjusted for stage, no difference was found in type of treatment. Overall, stage, grade, and age were found to affect survival (P=.04 to P<.001), but race did not. When analyzed by stage, blacks demonstrated a clear trend of longer survival for distant metastatic disease (P=.04 to P=.06). This trend was confirmed using Kaplan-Meier estimates (P=.04, likelihood ratio).
Conclusions.--This analysis suggests that in an equal-access medical care system there are no stage-specific differences in treatment between black and white prostate cancer patients. Survival among blacks is similar to that among whites and may surpass it for high-stage disease.
(JAMA. 1995;274:1599-1605)
Laura-Mae Baldwin, MD, MPH; L. Gary Hart, PhD; Michael Lloyd, ARM; Meredith Fordyce, MA; Roger A. Rosenblatt, MD, MPH
Objective.--To test the hypothesis that physicians with greater malpractice claims exposure, either through personal experience or in their practice environment, will use more prenatal resources and have a higher cesarean delivery rate than physicians with lesser claims exposure.
Design.--Retrospective cohort study using county malpractice defendant rate data from the Washington State Physicians Insurance and Exchange Association and prenatal care, delivery method, and self-reported obstetric suit experience data from the Content of Obstetrical Care Study database.
Setting.--Washington State obstetric practices.
Participants.--Stratified random samples of obstetrician-gynecologists and family physicians.
Main Outcome Measures.--The rates of obstetric ultrasound use, referral and consultation, prenatal care resource use, and cesarean delivery.
Results.--After controlling for patient, physician, and sociodemographic characteristics, we found no difference in prenatal resource use or cesarean delivery rate for low-risk patients between physicians with more and less exposure to malpractice claims.
Conclusions.--This study does not support an association between the malpractice experience or exposure of individual physicians and an increase in the use of prenatal resources or cesarean deliveries for the care of low-risk obstetric patients.
(JAMA. 1995;274:1606-1610)
Tim I. Edeki, MD, PhD; Huabing He, PharmD; Alastair J. J. Wood, MD
Objective.--To determine whether the effects of topically administered timolol in an individual would be dependent on the presence or absence in that individual of the P-450 enzyme CYP2D6 and whether the effects of topically administered timolol would be increased and its metabolism decreased by the oral administration of quinidine, a known inhibitor of CYP2D6.
Design.--Single-blind randomized crossover comparison of topical timolol, placebo, and the effects of inhibition of timolol metabolism by oral quinidine.
Setting.--Clinical research center of an academic medical center.
Participants.--Eight male extensive metabolizers (EMs) and five male poor metabolizers (PMs) of debrisoquin.
Intervention.--Two drops of 0.5% timolol or artificial tears were administered into each nostril in random order, and placebo or 50 mg of quinidine was administered orally to the EMs in random order, followed 30 minutes later by either the timolol or placebo drops.
Main Outcome Measurement.--Plasma timolol concentrations were measured by high-pressure liquid chromatography, while the extent of beta-blockade was determined by the suppression of exercise-induced rise in heart rate.
Results.--The exercise heart rate was reduced following timolol eye drops compared with placebo in both EMs (P<.001) and PMs (P<.001) with significantly greater heart rate reduction (P=.01) and higher plasma timolol concentration in PMs compared with EMs (P =.03). Administration of quinidine with timolol eye drops to EMs resulted in a further significant reduction in heart rate (P =.02) and increase in plasma timolol concentration (P =.04).
Conclusions.--An individual's debrisoquin phenotype is an important determinant of beta-blockade following timolol eye drops, and metabolism of timolol is inhibited and beta-blockade increased by coadministration of oral quinidine. Clinicians should be aware of the potential for drug interactions that occur when orally administered drugs inhibit the metabolism of a topically administered drug.
(JAMA. 1995;274:1611-1613)
Scott M. Silvers, Neil B. Hampson, MD
Objective.--To describe the case characteristics of a series of patients poisoned with carbon monoxide (CO) while boating for recreation.
Design.-- Cases of patients referred for treatment of CO poisoning with hyperbaric oxygen were reviewed. Those cases that occurred during recreational boating were selected for analysis.
Setting.--A private, urban, tertiary care center studied from July 1984 to June 1994.
Patients.--Thirty-nine patients ranging in age from 6 months to 69 years who were poisoned in 27 separate incidents.
Main Outcome Measures.-- Characteristics of the poisoning incidents were assessed at initial patient presentation, immediately following treatment, and with follow-up telephone interviews.
Results.-- Of 512 patients treated for acute unintentional CO poisoning, 39 cases (8%) occurred in 27 incidents related to recreational boating activities. Individuals typically lost consciousness as a result of the poisoning. Most cases occurred aboard a boat that was older than 10 years, had an enclosable cabin, was longer than 22 feet, was powered by a gasoline engine, and was without a CO detector on board.
Conclusions.-- Carbon monoxide poisoning is a serious hazard associated with recreational boating. The installation of CO detectors aboard boat types typically associated with this syndrome should be strongly encouraged.
(JAMA. 1995;274:1614-1616)
Mark L. Wolraich, MD; David B. Wilson, PhD; J. Wade White, MD
Objective.--To examine the effects of sugar on the behavior or cognition of children by using meta-analytic techniques on reported studies.
Data Sources.--Studies were identified through a literature search of the MEDLINE and PsychINFO databases and the authors' files using sugar, sucrose, and attention deficit disorder as the search terms.
Study Selection.--Studies were required to (1) intervene by having the subjects consume a known quantity of sugar; (2) use a placebo (artificial sweetener) condition; (3) blind the subjects, parents, and research staff to the conditions; and (4) report statistics that could be used to compute the dependent measures effect sizes.
Data Extraction.--Variables included publication year, study setting, subject type and number, gender, age, sugar and placebo type and dose, prior dietary condition, measurement construct, means and SDs for the sugar and placebo conditions, and direction of effect.
Data Synthesis.--Sixteen reports met the inclusion criteria for a total of 23 within-subject design studies. The weighted mean effect size and related statistics for each of the 14 measurement constructs revealed that although the range for these means was from - 0.14 for direct observations and up to +0.30 for academic tests, the 95% confidence interval for all 14 mean effect sizes included 0.
Conclusion.--The meta-analytic synthesis of the studies to date found that sugar does not affect the behavior or cognitive performance of children. The strong belief of parents may be due to expectancy and common association. However, a small effect of sugar or effects on subsets of children cannot be ruled out.
(JAMA. 1995;274:1617-1621)
Ronald A. Schoenenberger, MD, MPH; Milenko J. Tanasijevic, MD; Ashish Jha; David W. Bates, MD, MSc
Objectives.--To develop explicit, reliable appropriateness criteria for antiepileptic drug level monitoring and to assess the appropriateness of monitoring in one tertiary care institution.
Design.--Appropriateness criteria derived from the literature and through expert opinion were used to evaluate a stratified random sample of antiepileptic drug level determinations obtained from chart review.
Setting.--Tertiary care center performing more than 10 000 antiepileptic drug level determinations per year.
Patients.--A total of 330 inpatients in whom antiepileptic drug levels were measured a total of 855 times.
Methods.--Drug levels were assessed at least 200 times for each of four antiepileptic drugs (phenytoin, carbamazepine, phenobarbital, and valproic acid).
Main Outcome Measures.--The proportion of antiepileptic drug levels with an appropriate indication and, of those, the proportion sampled appropriately.
Results.-- Overall, 27% (95% confidence interval, 24% to 30%) of levels had an appropriate indication. Interrater agreement for appropriateness was substantial (kappa=0.61). There was no significant difference in the appropriateness rate among the four drugs (range, 25% to 29%). Of the 624 antiepileptic drug level determinations considered inappropriate (73%), only four (0.6%) were more than 20% higher than the upper limit of normal, and none of the four patients had clinical signs of drug toxicity. A median of six levels (range, one through 69) was determined per patient, and the median interval between level determinations was 24 hours. Of the 27% of level determinations with an appropriate indication, 51% were sampled correctly, resulting in an overall appropriateness rate of 14%.
Conclusions.-- Only 27% of antiepileptic drug level determinations had an appropriate indication, and half of these were not sampled correctly. Routine daily monitoring without pharmacological justification accounted for most of the inappropriate drug level determinations. Efforts to decrease inappropriate monitoring may result in substantial cost reductions without missing important clinical results.
(JAMA. 1995;274:1622-1626)
American College of Medical Genetics/American Society of Human Genetics Working Group on ApoE and Alzheimer Disease
Objective.--To evaluate the published data on the association between apolipoprotein E genotype (APOE) and Alzheimer disease (AD) and determine whether the data support the use of genetic testing for diagnosis or prediction of disease. This statement is intended for neurologists, psychiatrists, geneticists, primary care providers, diagnostic laboratories, and the public.
Participants.--The joint American College of Medical Genetics (ACMG) and American Society of Human Genetics (ASHG) Test and Technology Transfer Committee developed a 10-member ACMG/ASHG Working Group to assess available data on the association of AD with APOE alleles. To ensure inclusion of clinical specialists primarily involved with AD patients and families, the American Academy of Neurology (AAN) and the American Psychiatric Association (APA) appointed liaisons to the Working Group.
Evidence.--Peer-reviewed journal publications obtained from an Index Medicus search or known to members of the Working Group were the source of data on which the statement is based.
Consensus Process.--Following discussions with all members of the Working Group, a draft statement was prepared by the chair and circulated among all members until a consensus was reached. The consensus draft was sequentially reviewed and endorsed by the appropriate scientific and executive committees of the ACMG, ASHG, AAN, APA, and the National Institutes of Health-Department of Education Working Group on Ethical, Legal, and Social Implications of Human Genome Research. In some instances, suggestions from these committees were incorporated into the final statement.
Conclusions.--There is general consensus that APOE epsilon4 is strongly associated with AD and that when present may represent an important risk factor for the disease. However, at the present time it is not recommended for use in routine clinical diagnosis nor should it be used for predictive testing. Studies to date indicate that the APOE genotype alone does not provide sufficient sensitivity or specificity to allow genotyping to be used as a diagnostic test. Because AD develops in the absence of APOE epsilon4 and because many with APOE epsilon4 seem to escape disease, genotyping is also not recommended for use as a predictive genetic test. The results of a collaborative study under way will clarify some of these issues. Whether APOE genotypes have other uses in the management of AD will become apparent over the next few years.
(JAMA. 1995;274:1627-1629)