The impact of ABCC11 polymorphisms on the risk of early-onset fluoropyrimidine toxicity.

A missense variant (c.1637C>T, T546M) in ABCC11 encoding the MRP8 (multidrug resistance protein 8), a transporter of 5-fluorodeoxyuridine monophosphate, has been associated with an increased risk of 5-fluorouracil-related severe leukopenia. To validate this association, we investigated the impact of the ABCC11 variants c.1637C>T, c.538G>A and c.395+1087C>T on the risk of early-onset fluoropyrimidine-related toxicity in 514 cancer patients. The ABCC11 variant c.1637C>T was strongly associated with severe leukopenia in patients carrying risk variants in DPYD, encoding the key fluoropyrimidine-metabolizing enzyme dihydropyrimidine dehydrogenase (odds ratio (OR): 71.0; 95% confidence interval (CI): 2.5-2004.8; Pc.1637C>T*DPYD=0.013). In contrast, in patients without DPYD risk variants, no association with leukopenia (OR: 0.95; 95% CI: 0.34-2.6) or overall fluoropyrimidine-related toxicity (OR: 1.02; 95% CI: 0.5-2.1) was observed. Our study thus suggests that c.1637C>T affects fluoropyrimidine toxicity to leukocytes particularly in patients with high drug exposure, for example, because of reduced fluoropyrimidine catabolism.

Palliative Care Quality Indicators for Patients with End-Stage Liver Disease Due to Cirrhosis.

BACKGROUND AND AIMS: There are guidelines for the medical management of cirrhosis and associated quality indicators (QIs), but QIs focusing on standards for palliative aspects of care are needed. METHODS: We convened a 9-member, multidisciplinary expert panel and used RAND/UCLA modified Delphi methods to develop palliative care quality indicators for patients with cirrhosis. Experts were provided with a report based on a systematic review of the literature that contained evidence concerning the proposed candidate QIs. Panelists rated QIs prior to a planned meeting using a standard 9-point RAND appropriateness scale. These ratings guided discussion during a day-long phone conference meeting, and final ratings were then provided by panel members. Final QI scores were computed and QIs with a final median score of greater than or equal to 7, and no disagreement was included in the final set. RESULTS: Among 28 candidate QIs, the panel rated 19 as valid measures of quality care. These 19 quality indicators cover care related to information and care planning (13) and supportive care (6). CONCLUSIONS: These QIs are evidence-based process measures of care that may be useful to improve the quality of palliative care. Research is needed to better understand the quality of palliative care provided to patients with cirrhosis.

Ivacaftor improves appearance of sinus disease on computerised tomography in cystic fibrosis patients with G551D mutation.

BACKGROUND: Most patients with Cystic fibrosis (CF) have chronic sinus disease which may require multiple sinus surgeries and antibiotic courses. Ivacaftor can improve lung function, lower sweat chloride levels and improve weight by targeting the primary defect, a faulty gene and its protein product, cystic fibrosis transmembrane conductance regulator (CFTR) in patients with the G551D mutation. Its role in improving sinus disease has not been evaluated. OBJECTIVE: The objective of this study was to evaluate efficacy of ivacaftor in improving CF related sinus disease. DESIGN: Observational study. PARTICIPANTS: Twelve patients with cystic fibrosis and a G551D-CFTR mutation. METHODS: Twelve patients with a G551D-CFTR mutation were monitored for at least one year before and after starting ivacaftor. OUTCOME MEASURES: Sinus disease progression was monitored by comparing computed tomography (CT) of sinuses before and at one year on therapy. Hospital admissions, pulmonary exacerbations, weight, BMI and lung function were also compared. RESULTS: Median age was 17 years (range 10-44). Weight, BMI, FEV1 significantly increased and sweat chloride significantly decreased by six months on ivacaftor therapy. CT of the sinuses in all patients improved. Seven patients had severe sinus disease, improved to moderate in three and mild in remaining four. Four patients had moderate disease which improved to mild in all. One patient had normal sinus CT before and after the therapy. CONCLUSIONS: Patients with CF and G551D mutation, within 6 months of starting ivacaftor had significant improvements in weight, BMI and mean % FEV1. Significant lessening of underlying sinus disease measured by CT scan was noted, suggesting a disease modifying effect.

[What is new in 2014 for the specialist in hospital internal medicine? The point of view of university hospital chief residents]. / L'année 2014 mise en perspective par les internistes hospitaliers.

The year 2014 was rich in significant advances in all areas of internal medicine. Many of them have an impact on our daily practice and on the way we manage one problem or another. From the use of the ultrasound for the diagnosis of pneumonia to the choice of the site of venous access and the type of line, and the increasing complexity of choosing an oral anticoagulant agent, this selection offers to the readers a brief overview of the major advances. The chief residents in the Service of internal medicine of the Lausanne University hospital are pleased to share their readings.

17-year follow-up of the rough-blasted threaded Weill cup in uncemented total hip arthroplasty.

INTRODUCTION: For uncemented hip arthroplasty, various cup designs are available. The threaded Weill acetabular component (Weill cup; Zimmer, Winterthur, Switzerland) has been used for more than 20 years, with poor results of the smooth threaded design. Our study was intended to assess the 17-year outcome of the rough-blasted option of the threaded Weill cup. MATERIALS AND METHODS: Between 1987 and 1988, a series of 86 rough-blasted threaded Weill cups were implanted in combination with the CLS Spotorno stem (Zimmer Ltd, Germany) The patients' mean age at the time of surgery was 50 years (range 19-67 years). 67 out of 86 hips (78%) were available for a follow-up at a mean of 17 years (range 16-18 years). Radiographs were available from 55 out of 63 unrevised hips (87%) and analyzed for radiolucency and PE wear. RESULTS: Two out of 86 cups (3%) were revised due to aseptic loosening and another two cups (3%) were awaiting revision for the same reason. Ten patients (10 cups, 12%) were lost to follow-up, and nine patients with nine cups (11%) had deceased without radiographic signs of cup failure. Cup survival with "revision or awaiting revision" as endpoint was 86% (95% CI 75-92%). No deep infections occurred, and no polyethylene insert was exchanged. The Harris hip score was excellent in 37 out of 67 clinically examined hips (55%), good in 18 hips (26%), satisfactory in 5 hips (8%) and moderate or poor in 5 hips (8%) and 2 hips (3%), respectively. CONCLUSION: The rough-blasted threaded Weill cup provides a good long-term performance in cementless total hip arthroplasty. The results compare favourably to the smooth threaded cup design.

Coronary heart disease in women: battle is won, but the war remains.

According to the most recent report of the US National Heart, Lung, and Blood Institute, mortality from coronary heart disease has declined in women from one in three to one in four. Due to massive campaigning efforts in educating the medical community and the general public, coronary heart disease has become increasingly recognized as a woman's disease. Indeed, it is the number one killer in women, exceeding cancer and infectious diseases. Numerous observational studies, clinical trials, and reports have indicated that there are gender-specific differences in the presentation, diagnosis, treatment, and outcomes of coronary heart disease. One common theme, not only in United States, but world-wide is the underutilization of known and validated medical and interventional therapies in women compared to men. Even though previously conducted large, randomized controlled trials had limited numbers of women, recent large scale cardiac trials in women have enabled the development of evidence-based guidelines for coronary heart disease diagnosis and management in women. Importantly, menopausal hormone therapy and antioxidant vitamin therapy do not protect post-menopausal women from coronary heart disease. Aggressive life-style and pharmacologic management of known coronary risk factors in women should be a top priority to improve coronary heart disease morbidity and mortality. Research data continue to emerge to fill the gaps of how gender affects atherosclerosis; in the meantime, continued patient and physician education to increase awareness of coronary heart disease may help to eliminate some of the gender-based disparities in the delivery of coronary care to women.

Direct digital lateral cephalometry: the effects of JPEG compression on image quality.

OBJECTIVES: This study used an aluminium test object to assess the effect of the Joint Photographics Expert Group (JPEG) compression algorithm, on direct digital cephalometric image quality. METHODS: The aluminium block of 15 steps, with 20 holes in each step was radiographed in a Planmeca Proline 2002 digital cephalometric machine with Dimaxis2 software. Six different JPEG compression ratios were used to capture the cephalometric images. These ratios were 60%, 70%, 80%, 90%, TOP QUALITY JPEG (TQJPEG 98%) and TIFF (uncompressed). The images were taken at 68 kV and 12 mA with a 7 s exposure. Six experienced observers viewed the monitor displayed images, which were presented randomly. This was repeated one month later. The number of holes detected by each observer was plotted against each compression ratio. Intra-observer and inter-observer reproducibility was calculated using the Mann-Whitney U-test. Differences between the compression ratios were assessed using a Kruskal-Wallis one-way analysis of variance. RESULTS: When comparing intra-observer reproducibility, it was found that there were only four of 36 comparisons that showed a statistically significant difference (Observer 1: 60% (P=0.004), TQJPEG (P=0.019); Observer 2: TIFF (P=0.005); Observer 3: 90% (P=0.007)). Statistically, there was no significant difference with inter-observer reproducibility. There was no statistically significant difference between the image quality obtained from each compression ratio. CONCLUSIONS: The results showed that JPEG compression does not have any effect on the perceptibility of landmarks in the aluminium test object used in this study.

From adrenoceptor mechanisms to clinical therapeutics: Raymond Ahlquist, Ph.D., 1914-1983.

Identification of two distinct types of adrenotropic receptors, alpha and beta, by Raymond Ahlquist provided the scientific basis that enabled the development of drugs to selectively block adrenoceptor function. These pharmacotherapeutic advances have improved the care of patients with coronary and hypertensive cardiovascular disease.

Renal insufficiency and cardiovascular events in postmenopausal women with coronary heart disease.

OBJECTIVES: This study sought to determine the independent association of renal insufficiency with cardiovascular risk among women with known coronary heart disease (CHD). BACKGROUND: Although patients with end-stage renal disease and proteinuria are at high risk for cardiovascular events, little is known about the cardiovascular risk associated with moderate renal insufficiency. METHODS: The Heart and Estrogen/progestin Replacement Study (HERS) was a clinical trial among 2,763 women with coronary disease who were randomized to conjugated estrogen plus progestins or identical placebo and followed for a mean of 4.1 years. Women were categorized as having normal renal function (creatinine < 1.2 mg/dl; n = 2,012), mild renal insufficiency (1.2 mg/dl to 1.4 mg/dl; n = 567) and moderate renal insufficiency (>1.4 mg/dl; n = 182). We examined the independent association of renal function with incident cardiovascular events including CHD death, nonfatal myocardial infarction, hospitalization for unstable angina, stroke and transient ischemic attacks. RESULTS: Compared with women with normal renal function, those with mild and moderate renal insufficiency were older, more likely to be black, have a history of hypertension and diabetes and have higher serum levels of triglycerides and lipoprotein(a). After multivariate adjustment, both mild (relative hazards [RH] = 1.24; 95% confidence interval [CI]: 1.0 to 1.5) and moderate renal insufficiency (RH = 1.57; 95% CI: 1.2 to 2.1) were independently associated with increased risk for cardiovascular events compared with women with normal renal function. CONCLUSIONS: Renal insufficiency is an independent risk factor for cardiovascular events in postmenopausal women with known coronary artery disease. Renal function may add helpful information to CHD risk stratification.

Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin.

The Coronary Drug Project was conducted between 1966 and 1975 to assess the long-term efficacy and safety of five lipid-influencing drugs in 8,341 men aged 30 to 64 years with electrocardiogram-documented previous myocardial infarction. The two estrogen regimens and dextrothyroxine were discontinued early because of adverse effects. No evidence of efficacy was found for the clofibrate treatment. Niacin treatment showed modest benefit in decreasing definite nonfatal recurrent myocardial infarction but did not decrease total mortality. With a mean follow-up of 15 years, nearly 9 years after termination of the trial, mortality from all causes in each of the drug groups, except for niacin, was similar to that in the placebo group. Mortality in the niacin group was 11% lower than in the placebo group (52.0 versus 58.2%; p = 0.0004). This late benefit of niacin, occurring after discontinuation of the drug, may be a result of a translation into a mortality benefit over subsequent years of the early favorable effect of niacin in decreasing nonfatal reinfarction or a result of the cholesterol-lowering effect of niacin, or both.

Percutaneous transluminal coronary angioplasty in women compared with men.

OBJECTIVES: This study compares in-hospital and long-term outcome after angioplasty in women and men. BACKGROUND: The recognition that coronary artery disease is the most common cause of death in women has increased interest in outcome studies of coronary artery disease in women. METHODS: Patients who had previous coronary revascularization and those who underwent angioplasty in the setting of acute myocardial infarction were excluded. Angioplasty was performed with standard methods. Clinical data were retrieved from a clinical data base and analyzed with standard statistical methods. RESULTS: There were 2,845 women and 7,940 men. The women were older (62 +/- 11 vs. 57 +/- 10 years) and had more hypertension (54.5% vs. 40.1%), diabetes (19.3% vs. 11.7%), grade III to IV angina (71.5% vs. 58.4%) and congestive failure (4.3% vs. 2.1%) than men (all p < 0.0001). More men had a previous myocardial infarction (35.4% vs. 31.0%) and were taller and weighed more (all p < 0.0001). The men had lower ejection fractions and more multivessel disease (31.0% vs. 25.2%) (both p < 0.0001). In women there was a trend toward more Q wave myocardial infarctions (1.1% vs. 0.75%, p = 0.10), and hospital mortality was higher (0.7% vs. 0.1%, p < 0.0001). Angina at follow-up was more common in women 40.2% vs. 26.7%, p < 0.0001). The multivariate correlates of in-hospital death were short stature, reduced ejection fraction and multivessel disease, with trends for older age and female gender. Five-year survival was 95% in men and 92% in women (p = 0.0002). However, female gender was not a multivariate correlate of long-term survival and was accounted for by other characteristics, primarily age. The multivariate correlates of long-term survival were older age, congestive failure, reduced ejection fraction, multivessel disease, diabetes, hypertension and a trend for severe angina. No difference between women and men was noted in long-term freedom from myocardial infarction. There were more additional procedures in men than in women. CONCLUSIONS: Despite higher in-hospital mortality, long-term mortality and clinical outcome were similar in both genders when age and body habitus were accounted for.

Patient characteristics associated with care by a cardiologist among adults hospitalized with severe congestive heart failure. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

OBJECTIVES: The goal of this study was to determine factors associated with receiving cardiologist care among patients with an acute exacerbation of congestive heart failure. BACKGROUND: Because cardiologist care for acute cardiovascular illness may improve care, barriers to specialty care could impact patient outcomes. METHODS: We studied 1,298 patients hospitalized with acute exacerbation of congestive heart failure who were cared for by cardiologists or generalist physicians. Using multivariable logistic models we determined factors independently associated with attending cardiologist care. RESULTS: Patients were less likely to receive care from a cardiologist if they were black (adjusted odds ratio [AOR] 0.53, 95% confidence interval [CI] 0.35, 0.80), had an income of less than $11,000 (AOR 0.65, 95% CI 0.45, 0.93) or were older than 80 years of age (AOR 0.23, 95% CI 0.12, 0.46). Patients were more likely to receive cardiologist care if they had college level education (AOR 1.89, 95% CI 1.02, 3.51), a history of myocardial infarction (AOR 1.59, 95% CI 1.17, 2.16), a serum sodium less than 133 on admission (AOR 1.96, 95% CI 1.30, 2.95) or a systolic blood pressure less than 90 on admission (AOR 1.97, 95% CI 1.20, 3.24). Patients who stated a desire for life extending care were also more likely to receive care from a cardiologist (AOR 1.40, 95% CI 1.04, 1.90). CONCLUSIONS: After adjusting for severity of illness and patient preferences for care, patient sociodemographic factors were strongly associated with receiving care from a cardiologist. Future investigations are required to determine whether these associations represent unmeasured preferences for care or inequities in our health care system.

Religiousness and spirituality among HIV-infected Americans.

PURPOSE: To describe the demographic and clinical factors associated with the importance of religiousness and spirituality among patients with human immunodeficiency virus (HIV) infection in the United States. METHODS: Longitudinal study of a nationally representative cohort of 2266 patients receiving care for HIV infection surveyed in 1996 and again in 1998. Measures included 12 items assessing religious affiliation and attendance, the importance of religion and spirituality in life, and religious and spiritual practices. Multi-item religiousness and spirituality scales were constructed. RESULTS: Eighty percent of respondents reported a religious affiliation. Sixty-five percent affirmed that religion and 85% that spirituality was "somewhat" or "very" important in their lives. A majority indicated that they "sometimes" or "often" rely on religious or spiritual means when making decisions (72%) or confronting problems (65%). Women, nonwhites, and older patients were more religious and spiritual. Residents of regions other than the western United States reported higher religiousness. High school graduates were more religious and spiritual than those with less education. Patients who did not report one of the risk factors assessed for HIV infection had higher religiousness scores than injection drug users (IDUs). Women, nonwhites other than Hispanics, patients older than 45 years of age compared to those between 18 and 34 years of age, and more educated patients reported higher spirituality. Clinical stage was not associated with religiousness or spirituality. CONCLUSIONS: A large majority of HIV-infected patients in the United States affirm the importance of religiousness and spirituality. These findings support a comprehensive, humanistic approach to the care of HIV-infected patients.

Prevalence of silent myocardial ischemia and arrhythmias in patients with coronary heart disease undergoing gastrointestinal tract endoscopic procedures.

BACKGROUND: Since the introduction of gastrointestinal tract endoscopic procedures, there has been concern about cardiovascular complications, especially in patients with coronary heart disease. Although, in general, these procedures are safe, previous studies have documented perturbations in blood pressure, heart documented perturbations in blood pressure, heart rate, and oxygen saturation, as well as the occurrence of arrhythmias and nonspecific ST-segment electrocardiographic changes during such procedures. No studies, however, have specifically addressed the prevalence of silent myocardial ischemia and arrhythmias in patients with well-established coronary heart disease. METHODS: During a 15-month period, 25 hospitalized patients with well-defined coronary heart disease underwent continuous ambulatory electrocardiographic recording during endoscopic procedures requiring intravenous sedation, as well as during a prolonged baseline period. All patients were considered clinically stable, although 92% were categorized as being at intermediate or high coronary risk by standard risk stratification criteria. Eleven patients (44%) had had previous myocardial infarction, and 68% reported a history of angina. RESULTS: Although 24% of patients had one or more episodes of electrocardiographic ischemia during the recording periods, no patient had evidence of ischemia exclusively during the endoscopic procedure. Arrhythmias were no more frequent during the endoscopic procedures than during a corresponding baseline period. Symptomatic angina or serious arrhythmias did not occur during the procedures. CONCLUSIONS: Our data suggest that endoscopic procedures in patients with stable but severe coronary heart disease, when performed with standard medications, monitoring, and techniques, rarely result in silent or symptomatic myocardial ischemia or serious arrhythmias. In addition, although asymptomatic minor arrhythmias are common during endoscopic procedures, their occurrence appears less frequent than during daily hospital life.

Sexual behavior of individuals infected with the human immunodeficiency virus. The need for intervention.

BACKGROUND: Public health efforts to stop the spread of the human immunodeficiency virus (HIV) emphasize behavior change among all persons at risk of infection. Yet efficient physician-based intervention might be targeted toward persons infected with HIV. To evaluate the need for intervention among HIV-infected persons attending a continuity clinic, we determined the prevalence of behaviors risky for new transmission of HIV and the characteristics of HIV-infected individuals participating in such behavior. METHODS: Cross-sectional structured survey of 227 HIV-infected patients attending an urban HIV continuity-of-care clinic. RESULTS: Nine percent of the subjects had vaginal, anal, or oral sex without a condom with an HIV-negative last sex partner (24% of whom were unaware that the subject was HIV infected) and an additional 13% with an HIV-status-unknown last sex partner (41% were unaware that the subject was HIV infected). Subjects used a condom for intercourse more often with a partner they knew to be HIV negative than HIV-status-unknown or HIV-positive (84% vs 59% vs 51%). Subjects with more lifetime male sexual partners were more likely to have had sex without a condom with an HIV-negative or HIV-status-unknown partner. CONCLUSION: The HIV-infected individuals in this clinic setting participate in a substantial amount of sexual behavior placing others at risk of new HIV infection. Physicians must address such behaviors, and programs specifically aimed at reducing such behavior should be a public health priority.

Outcomes of patients with do-not-resuscitate orders. Toward an understanding of what do-not-resuscitate orders mean and how they affect patients.

OBJECTIVES: To evaluate the outcomes of hospitalized patients with do-not-resuscitate (DNR) orders and to identify variables that may elucidate the high mortality of patients with DNR orders. METHODS: Among a nationally representative sample of Medicare patients hospitalized with congestive heart failure, acute myocardial infarction, pneumonia, cerebrovascular accident, or hip fracture, we retrospectively studied in-hospital and 180-day mortality and hospital lengths of stay for patients without DNR orders, with early (day 1 or 2) DNR orders, and with late (day 3 or later) DNR orders, before and after adjustment for sickness at hospital admission and patient and hospital characteristics. RESULTS: In-hospital mortality for patients with DNR orders exceeded that for patients without DNR orders before adjustment (59% vs 8%, P < .001), and after accounting for differences in sickness at admission and patient and hospital characteristics (40% vs 9%, P < .001). Sicker patients were assigned earlier DNR orders. Yet, patients with early DNR orders had a lower adjusted in-hospital mortality (31% vs 49%, P < .001) and shorter hospital stay (10 vs 18 days, P < .001) than did patients with late DNR orders. CONCLUSIONS: Hospitalized older patients with DNR orders have a much higher mortality than predicted by admission demographic and clinical characteristics. The differential association of early and late DNR orders with mortality indicates that DNR orders represent a heterogeneous group of interventions that may be a marker of unmeasured sickness and a determinant of quality of care. A better understanding of what the DNR order represents and its effect on patient care is needed to ensure optimal use.

Response to exercise in patients taking psychotropic drugs. Arrhythmias and the QT interval (QT wave peak).

Psychotropic drugs may prolong the QT interval, potentially predisposing to ventricular arrhythmias and/or sudden death. Exercise prescribed as therapy for depression may also prolong the QT interval and augment arrhythmia risk. To determine QT-interval (QT wave peak, or QTPK) response to exercise in patients receiving psychotropic drugs, treadmill exercise testing was performed on 20 mentally competent psychiatric inpatients clinically free of heart disease. Twenty-four-hour ambulatory ECGs were performed within one day of exercise testing to detect arrhythmias during routine daily activities. Exercise test results for psychiatric patients were compared with those of normal subjects receiving no medication. Separate regression lines relating heart rate of QTPK interval, calculated for each group, showed no significant difference. No serious arrhythmias occurred during routine daily activities or exercise. Patients without heart disease taking psychotropic drugs have appropriate QTPK-interval shortening with exercise.

Outcomes of acute exacerbation of severe congestive heart failure: quality of life, resource use, and survival. SUPPORT Investigators. The Study to Understand Prognosis and Preferences for Outcomes and Risks of Treatments.

BACKGROUND: Congestive heart failure (CHF) is a common disease with high health care costs and high mortality rates. Knowledge of the health-related quality of life outcomes of CHF may guide decision making and be useful in assessing new therapies for this population. METHODS: A prospective cohort study was conducted involving 1390 adult patients hospitalized with an acute exacerbation of severe CHF (New York Heart Association class III-IV). Demographic data and health-related quality of life were determined by interview; physiologic status and cost and intensity of care were determined from hospital charts. RESULTS: The median (25th, 75th percentiles) age of patients was 68.0 (58.2, 76.9) years; 61.7% were male. Survival was 93.4% at discharge from the index hospitalization, 72.9% at 180 days, and 61.5% at 1 year. Of patients interviewed at 180 days, the median health rating on a scale of 0 to 100 (0 indicates death; 100, excellent health) was 60 (interquartile range, 50-80), and 59.7% were independent in their activities of daily living. Overall quality of life was reported to be good, very good, or excellent in 58.2% at 180 days. Patients with worse functional capacity were more likely to die. Health perceptions among the patients with available interview data improved at 60 and 180 days after acute exacerbation of severe CHF. CONCLUSIONS: Patients hospitalized for acute exacerbation of severe CHF have a generally poor 6-month survival, but survivors retain relatively good functional status and have good health perceptions. Furthermore, health perceptions improve after the acute exacerbation.

Epidemiology of do-not-resuscitate orders. Disparity by age, diagnosis, gender, race, and functional impairment.

BACKGROUND: The relationship of do-not-resuscitate (DNR) orders to patient and hospital characteristics has not been well characterized. METHODS: This observational study of a nationally representative sample of 14,008 Medicare patients hospitalized with congestive heart failure, acute myocardial infarction, pneumonia, cerebrovascular accident, or hip fracture evaluated the relationship of DNR orders to patient sickness at admission, functional impairment, age, disease, race, gender, preadmission residence, insurance status, and hospital characteristics. RESULTS: Of the 14,008 patients, DNR orders were assigned to 11.6%. Patients with greater sickness at admission and functional impairment received more DNR orders (P < .001) but even among patients in the sickest quartile (with a 65% chance of death within 180 days), only 31% received DNR orders. The DNR orders were assigned more often to older patients after adjustment for sickness at admission and functional impairment (P < .001), and DNR order rates differed by diagnosis (P < .001). After adjustment for patient and hospital characteristics, DNR orders were assigned more often to women and patients with dementia or incontinence and were assigned less often to black patients, patients with Medicaid insurance, and patients in rural hospitals. CONCLUSIONS: Do-not-resuscitate orders are assigned more often to sicker patients but may be underused even among the most sick. Sickness at admission and functional impairment do not explain the increase in DNR orders with age or the disparity across diagnosis. Further evaluation is needed into whether variation in DNR order rates with age, diagnosis, race, gender, insurance status, and rural location represents differences in patient preferences or care compromising patient autonomy.

Depressed mood and survival in seriously ill hospitalized adults. The SUPPORT Investigators.

OBJECTIVES: To assess the relationship among depressed mood, physical functioning, and severity of illness and to determine the relationship between depressed mood and survival time, controlling for severity of illness, baseline functioning, and characteristics of patients. METHODS: Prospective cohort study of data for 3529 seriously ill hospitalized adults who received care at 5 tertiary care teaching hospitals and who completed a depressed mood assessment 7 to 11 days after admission to the study. The Profile of Mood States depression subscale was used to assess depressed mood. A stratified Cox proportional hazards model was used to assess the independent effect of depressed mood on survival time, adjusting for demographic characteristics of patients and health status. RESULTS: Greater magnitudes of depressed mood were associated with worse levels of physical functioning (r = 0.151; P < .001) and more severity of illness. Depressed mood was associated with reduced survival time after adjusting for patient demographics and health status (hazards ratio, 1.134; 95% confidence interval, 1.071-1.200; P < or = .001). CONCLUSION: Seriously ill patients should be assessed for the presence of depressed mood even if they have not been given a diagnosis of depression. Further study is needed to determine whether interventions aimed at relieving depressed mood may improve prognosis.