Control of endemic methicillin-resistant Staphylococcus aureus: a cost-benefit analysis in an intensive care unit

Context  Despite the success of some countries in controlling endemic methicillin-resistant Staphylococcus aureus (MRSA), such programs have not been implemented for some hospitals with endemic infection because of concerns that these programs would be costly and of limited benefit. Objective  To compare the costs and benefits of an MRSA control program in an endemic setting. Design and Setting  Case-control study conducted at a medical intensive care unit (ICU) of a French university hospital with a 4% prevalence of MRSA carriage at ICU admission. Patients  Twenty-seven randomly selected patients who had ICU-acquired MRSA infection between January 1993 and June 1997, matched to 27 controls hospitalized during the same period without MRSA infection. Main Outcome Measures  Intensive care unit costs attributable to MRSA infection, computed from excess therapeutic intensity in cases using estimates from a cost model derived in the same ICU, were compared with costs of the control program, derived from time-motion study of nurses and physicians. The threshold for MRSA carriage that would make the control strategy dominant was determined; sensitivity analyses varied rates of MRSA transmission and ratio of infection to transmission, length of ICU stay, and costs of isolation precautions. Results  The mean cost attributable to MRSA infection was US $9275 (median, $5885; interquartile range, $1400-$16,720). Total costs of the control program ranged from $340 to $1480 per patient. A 14% reduction in MRSA infection rate resulted in the control program being beneficial. In sensitivity analyses, the control strategy was dominant for a prevalence of MRSA carriage on ICU admission ranging from 1% to 7%, depending on costs of control measures and MRSA transmission, for infection rates greater than 50% following transmission. Conclusions  In this example of a hospital with endemic MRSA infection, selective screening and isolation of carriers on ICU admission are beneficial compared with no isolation.      

The Medical Costs of Gunshot Injuries in the United States

Context  The cost of treating gunshot injuries imposes a financial burden on society. Estimates of such costs are relevant to evaluation of gun violence reduction programs and may help guide reimbursement policies. Objectives  To develop reliable US estimates of the medical costs of treating gunshot injuries and to present national estimates for the sources of payment for treating these injuries. Design and Setting  Cost analysis using E-coded discharge data from hospitals in Maryland for 1994-1995 and New York for 1994 and from emergency departments in South Carolina for 1997. Other sources of data included the National Electronic Injury Surveillance System for 1994 incidence of nonfatal gun injuries, the National Spinal Cord Injury Statistical Center database for 1988-1992 estimates of lifetime medical costs of gun injuries, and the 1994 Vital Statistics census for incidence of fatal gun injuries. Main Outcome Measures  Estimated national acute-care and follow-up treatment costs and payment sources for gunshot injuries. Results  At a mean medical cost per injury of about $17,000, the 134,445 (95% confidence interval [CI], 109,465-159,425) gunshot injuries in the United States in 1994 produced $2.3 billion (95% CI, $2.1 billion–$2.5 billion) in lifetime medical costs (in 1994 dollars, using a 3% real discount rate), of which $1.1 billion (49%) was paid by US taxpayers. Gunshot injuries due to assaults accounted for 74% of total costs. Conclusions  Gunshot injury costs represent a substantial burden to the medical care system. Nearly half this cost is borne by US taxpayers.      

Trends in length of stay, living setting, functional outcome, and mortality following medical rehabilitation

Context  Changes in reimbursement have reduced length of stay (LOS) for patients receiving inpatient medical rehabilitation. The impact of decreased LOS on functional status, living setting, and mortality is not known. Objective  To examine changes in LOS, functional status, living setting, and mortality in patients completing inpatient rehabilitation. Design  Retrospective cohort study from 1994 through 2001 using information submitted to the Uniform Data System for Medical Rehabilitation. Setting and Participants  Data were analyzed from 744 inpatient medical rehabilitation hospitals and centers located in 48 US states. A total of 148 807 patient records from 5 impairment groups (stroke, brain dysfunction, spinal cord dysfunction, other neurologic conditions, and orthopedic conditions) were examined. Patients’ mean age was 67.8 (SD, 15.8) years; the sample was 59% female and 81% non-Hispanic white. Main Outcome Measures  Discharge setting, follow-up living setting, change in functional status, and mortality. Results  Median LOS decreased from 20 to 12 days (P<.001) from 1994 to 2001. The proportional decrease in median LOS was greatest (42%) for patients with orthopedic conditions. Mean days to follow-up remained constant from 89 in 1994 to 90 in 2001. Functional status was clinically stable, while efficiency (functional status change divided by LOS) increased significantly (P<.001). Rates of discharge to home and living at home at follow-up remained stable, ranging from 81% to 93%. However, mortality at 80- to 180-day follow-up increased from less than 1% in 1994 to 4.7% in 2001. Conclusions  Length of stay for inpatient rehabilitation decreased substantially from 1994 to 2001. Effectiveness as measured by change in functional status did not change clinically, and living setting did not change. Efficiency for functional outcomes improved but mortality at follow-up increased.      

Cause-specific excess deaths associated with underweight, overweight, and obesity

Context  The association of body mass index (BMI) with cause-specific mortality has not been reported for the US population. Objective  To estimate cause-specific excess deaths associated with underweight (BMI <18.5), overweight (BMI 25-<30), and obesity (BMI 30). Design, Setting, and Participants  Cause-specific relative risks of mortality from the National Health and Nutrition Examination Survey (NHANES) I, 1971-1975; II, 1976-1980; and III, 1988-1994, with mortality follow-up through 2000 (571 042 person-years of follow-up) were combined with data on BMI and other covariates from NHANES 1999-2002 with underlying cause of death information for 2.3 million adults 25 years and older from 2004 vital statistics data for the United States. Main Outcome Measures  Cause-specific excess deaths in 2004 by BMI levels for categories of cardiovascular disease (CVD), cancer, and all other causes (noncancer, non-CVD causes). Results  Based on total follow-up, underweight was associated with significantly increased mortality from noncancer, non-CVD causes (23 455 excess deaths; 95% confidence interval [CI], 11 848 to 35 061) but not associated with cancer or CVD mortality. Overweight was associated with significantly decreased mortality from noncancer, non-CVD causes (–69 299 excess deaths; 95% CI, –100 702 to –37 897) but not associated with cancer or CVD mortality. Obesity was associated with significantly increased CVD mortality (112 159 excess deaths; 95% CI, 87 842 to 136 476) but not associated with cancer mortality or with noncancer, non-CVD mortality. In further analyses, overweight and obesity combined were associated with increased mortality from diabetes and kidney disease (61 248 excess deaths; 95% CI, 49 685 to 72 811) and decreased mortality from other noncancer, non-CVD causes (–105 572 excess deaths; 95% CI, –161 816 to –49 328). Obesity was associated with increased mortality from cancers considered obesity-related (13 839 excess deaths; 95% CI, 1920 to 25 758) but not associated with mortality from other cancers. Comparisons across surveys suggested a decrease in the association of obesity with CVD mortality over time. Conclusions  The BMI-mortality association varies by cause of death. These results help to clarify the associations of BMI with all-cause mortality.      

Trends in Unintentional Drowning: The Role of Alcohol and Medical Care

Context  During the last few decades, mortality from drowning has decreased in the United States for unknown reasons. It has been hypothesized that this decline may be due to decreased use of alcohol in and around water or improved medical treatment after a submersion. Objectives  To estimate changes in unintentional mortality due to submersion, estimate trends in drownings attributable to alcohol use, and assess the role of medical care in these mortality trends. Design  A 21-year longitudinal study of case findings, from January 1, 1975, through December 31, 1995. Setting and Participants  All residents of King County, Washington, who died unintentionally from submersion and 284 persons hospitalized for submersion who survived. Main Outcome Measures  Changes in submersion-related mortality incidence over time, proportion of this mortality that could be attributed to alcohol use, changes over time in the case-fatality rate of treated patients, and estimate of deaths prevented in 1995 compared with projected estimates had there been no change in incidence since 1975. Results  There were 539 deaths due to drowning in King County during 21 years. Mortality rates during this period declined by 59% (95% confidence interval [CI], -70% to -46%). The incidence of death attributable to alcohol use decreased by 81% (95% CI, -91% to -57%); this could account for 51% of deaths prevented in 1995. Among 249 comatose patients who received prehospital care, 205 died; the odds of survival decreased 40% over 21 years (P=.40). Among 101 comatose patients who were hospitalized, 63 died; the odds of survival decreased 29% (P=.75). The incidence of survival of comatose hospital patients decreased by 29% from 1975 to 1995 (95% CI, -78% to +125%). We found no evidence that trends in medical treatment prevented any deaths due to drowning in 1995. Conclusions  Drowning incidence in King County, Washington, declined because of a decrease in severe submersion episodes rather than an increase in success of medical interventions. Our data support the theory that less use of alcohol around water prevents some deaths. About half of the decrease was unexplained.      

Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain

Ricard Ferrer, MD; Antonio Artigas, MD, PhD; Mitchell M. Levy, MD, FCCM; Jesús Blanco, MD, PhD; Gumersindo González-Díaz, MD, PhD; José Garnacho-Montero, MD, PhD; Jordi Ibáñez, MD, PhD; Eduardo Palencia, MD, PhD; Manuel Quintana, MD; María Victoria de la Torre-Prados, MD, PhD; for the Edusepsis Study Group

JAMA. 2008;299(19):2294-2303.

Context  Concern exists that current guidelines for care of patients with severe sepsis and septic shock are followed variably, possibly due to a lack of adequate education.

Objective  To determine whether a national educational program based on the Surviving Sepsis Campaign guidelines affected processes of care and hospital mortality for severe sepsis.

Design, Setting, and Patients  Before and after design in 59 medical-surgical intensive care units (ICUs) located throughout Spain. All ICU patients were screened daily and enrolled if they fulfilled severe sepsis or septic shock criteria. A total of 854 patients were enrolled in the preintervention period (November-December 2005), 1465 patients during the postintervention period (March-June 2006), and 247 patients during the long-term follow-up period 1 year later (November-December 2006) in a subset of 23 ICUs.

Intervention  The educational program consisted of training physicians and nursing staff from the emergency department, wards, and ICU in the definition, recognition, and treatment of severe sepsis and septic shock as outlined in the guidelines. Treatment was organized in 2 bundles: a resuscitation bundle (6 tasks to begin immediately and be accomplished within 6 hours) and a management bundle (4 tasks to be completed within 24 hours).

Main Outcome Measures  Hospital mortality, differences in adherence to the bundles' process-of-care variables, ICU mortality, 28-day mortality, hospital length of stay, and ICU length of stay.

Results  Patients included before and after the intervention were similar in terms of age, sex, and Acute Physiology and Chronic Health Evaluation II score. At baseline, only 3 process-of-care measurements (blood cultures before antibiotics, early administration of broad-spectrum antibiotics, and mechanical ventilation with adequate inspiratory plateau pressure) we had compliance rates higher than 50%. Patients in the postintervention cohort had a lower risk of hospital mortality (44.0% vs 39.7%; P = .04). The compliance with process-of-care variables also improved after the intervention in the sepsis resuscitation bundle (5.3% [95% confidence interval [CI], 4%-7%] vs 10.0% [95% CI, 8%-12%]; P < .001) and in the sepsis management bundle (10.9% [95% CI, 9%-13%] vs 15.7% [95% CI, 14%-18%]; P = .001). Hospital length of stay and ICU length of stay did not change after the intervention. During long-term follow-up, compliance with the sepsis resuscitation bundle returned to baseline but compliance with the sepsis management bundle and mortality remained stable with respect to the postintervention period.

Conclusions  A national educational effort to promote bundles of care for severe sepsis and septic shock was associated with improved guideline compliance and lower hospital mortality. However, compliance rates were still low, and the improvement in the resuscitation bundle lapsed by 1 year.

     

E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators

Context  Knowledge and understanding of gram-negative sepsis have grown over the past 20 years, but the ability to treat severe sepsis successfully has not. Objective  To assess the efficacy and safety of E5 in the treatment of patients with severe gram-negative sepsis. Design  A multicenter, double-blind, randomized, placebo-controlled trial conducted at 136 US medical centers from April 1993 to April 1997, designed with 90% power to detect a 25% relative risk reduction, incorporating 2 planned interim analyses. Setting  Intensive care units at university medical centers, Veterans Affairs medical centers, and community hospitals. Patients  Adults aged 18 years or older, with signs and symptoms consistent with severe sepsis and documented or probable gram-negative infection. Intervention  Patients were assigned to receive 2 doses of either E5, a murine monoclonal antibody directed against endotoxin (n = 550; 2 mg/kg per day by intravenous infusion 24 hours apart) or placebo (n = 552). Main Outcome Measures  The primary end point was mortality at day 14; secondary end points were mortality at day 28, adverse event rates, and 14-day and 28-day mortality in the subgroup without shock at presentation. Results  The trial was stopped after the second interim analysis. A total of 1090 patients received study medication and 915 had gram-negative infection confirmed by culture. There were no statistically significant differences in mortality between the E5 and placebo groups at either day 14 (29.7% vs 31.1%; P = .67) or day 28 (38.5% vs 40.3%; P = .56). Patients presenting without shock had a slightly lower mortality when treated with E5 but the difference was not significant (28.9% vs 33.0% for the E5 and placebo groups, respectively, at day 28; P = .32). There was a similar profile of adverse event rates between E5 and placebo. Conclusions  Despite adequate sample size and high enrollment of patients with confirmed gram-negative sepsis, E5 did not improve short-term survival. Current study rationale and designs should be carefully reviewed before further large-scale studies of patients with sepsis are conducted.      

Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes

Context  Effective medical care assumes delivery of evidence-based medicines to appropriate patients with doses comparable to those studied. Objective  To investigate dosing of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and glycoprotein IIb/IIIa inhibitors, and the association between dosing and major outcomes. Design, Setting, and Participants  A prospective observational analysis in 387 US academic and nonacademic hospitals of 30 136 patients from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative Registry who had non–ST-segment elevation acute coronary syndromes (NSTE ACS) with chest pain and either positive electrocardiograms or cardiac biomarkers between January 1 and September 30, 2004. Main Outcome Measures  Excessive dosing of UFH, LMWH, and glycoprotein IIb/IIIa inhibitors and major clinical outcomes, including bleeding, in-hospital mortality, and length of stay. Results  A total of 3354 patients (42%) with NSTE ACS who were administered antithrombotic agents received at least 1 initial dose outside the recommended range. An excess dose was administered to 2934 patients (32.8%) treated with UFH, 1378 (13.8%) treated with LMWH, and 2784 (26.8%) treated with glycoprotein IIb/IIIa inhibitors. Factors associated with excess dosing included older age, as well as female sex, renal insufficiency, low body weight, diabetes mellitus, and congestive heart failure. Relative to those patients not administered excess dosages, patients with excess dosages of UFH, LMWH, and glycoprotein IIb/IIIa inhibitors either tended toward or had higher risks for major bleeding (adjusted odds ratio [OR], 1.08; 95% confidence interval [CI], 0.94-1.26; OR, 1.39; 95% CI, 1.11-1.74; and OR, 1.36; 95% CI, 1.10-1.68; respectively). Bleeding increased relative to the degree of excess dose and to the number of agents administered in excess (6.6% [237/3590] if neither heparin nor glycoprotein IIb/IIIa excess vs 22.2% [93/419] if both excess). Mortality and length of stay were also higher among those patients administered excess dosing. We estimated that 15% (400/2766) of major bleeding in this population may be attributable to excess dosing. Conclusions  Patients with NSTE ACS treated in the community often receive excess doses of antithrombotic therapy. Dosing errors occur more often in vulnerable populations and predict an increased risk of major bleeding.      

Excess deaths associated with underweight, overweight, and obesity

Context  As the prevalence of obesity increases in the United States, concern over the association of body weight with excess mortality has also increased. Objective  To estimate deaths associated with underweight (body mass index [BMI] <18.5), overweight (BMI 25 to <30), and obesity (BMI 30) in the United States in 2000. Design, Setting, and Participants  We estimated relative risks of mortality associated with different levels of BMI (calculated as weight in kilograms divided by the square of height in meters) from the nationally representative National Health and Nutrition Examination Survey (NHANES) I (1971-1975) and NHANES II (1976-1980), with follow-up through 1992, and from NHANES III (1988-1994), with follow-up through 2000. These relative risks were applied to the distribution of BMI and other covariates from NHANES 1999-2002 to estimate attributable fractions and number of excess deaths, adjusted for confounding factors and for effect modification by age. Main Outcome Measures  Number of excess deaths in 2000 associated with given BMI levels. Results  Relative to the normal weight category (BMI 18.5 to <25), obesity (BMI 30) was associated with 111 909 excess deaths (95% confidence interval [CI], 53 754-170 064) and underweight with 33 746 excess deaths (95% CI, 15 726-51 766). Overweight was not associated with excess mortality (–86 094 deaths; 95% CI, –161 223 to –10 966). The relative risks of mortality associated with obesity were lower in NHANES II and NHANES III than in NHANES I. Conclusions  Underweight and obesity, particularly higher levels of obesity, were associated with increased mortality relative to the normal weight category. The impact of obesity on mortality may have decreased over time, perhaps because of improvements in public health and medical care. These findings are consistent with the increases in life expectancy in the United States and the declining mortality rates from ischemic heart disease.      

Glucose control and mortality in critically ill patients

Context  Hyperglycemia is common in critically ill patients, even in those without diabetes mellitus. Aggressive glycemic control may reduce mortality in this population. However, the relationship between mortality, the control of hyperglycemia, and the administration of exogenous insulin is unclear. Objective  To determine whether blood glucose level or quantity of insulin administered is associated with reduced mortality in critically ill patients. Design, Setting, and Patients  Single-center, prospective, observational study of 531 patients (median age, 64 years) newly admitted over the first 6 months of 2002 to an adult intensive care unit (ICU) in a UK national referral center for cardiorespiratory surgery and medicine. Main Outcome Measures  The primary end point was intensive care unit (ICU) mortality. Secondary end points were hospital mortality, ICU and hospital length of stay, and predicted threshold glucose level associated with risk of death. Results  Of 531 patients admitted to the ICU, 523 underwent analysis of their glycemic control. Twenty-four–hour control of blood glucose levels was variable. Rates of ICU and hospital mortality were 5.2% and 5.7%, respectively; median lengths of stay were 1.8 (interquartile range, 0.9-3.7) days and 6 (interquartile range, 4.5-8.3) days, respectively. Multivariable logistic regression demonstrated that increased administration of insulin was positively and significantly associated with ICU mortality (odds ratio, 1.02 [95% confidence interval, 1.01-1.04] at a prevailing glucose level of 111-144 mg/dL [6.1-8.0 mmol/L] for a 1-IU/d increase), suggesting that mortality benefits are attributable to glycemic control rather than increased administration of insulin. Also, the regression models suggest that a mortality benefit accrues below a predicted threshold glucose level of 144 to 200 mg/dL (8.0-11.1 mmol/L), with a speculative upper limit of 145 mg/dL (8.0 mmol/L) for the target blood glucose level. Conclusions  Increased insulin administration is positively associated with death in the ICU regardless of the prevailing blood glucose level. Thus, control of glucose levels rather than of absolute levels of exogenous insulin appear to account for the mortality benefit associated with intensive insulin therapy demonstrated by others.      

Screening for proteinuria in US adults: a cost-effectiveness analysis

Context  Chronic kidney disease is a growing public health problem. Screening for early identification could improve health but could also lead to unnecessary harms and excess costs. Objective  To assess the value of periodic, population-based dipstick screening for early detection of urine protein in adults with neither hypertension nor diabetes and in adults with hypertension. Design, Setting, and Population  Cost-effectiveness analysis using a Markov decision analytic model to compare a strategy of annual screening with no screening (usual care) for proteinuria at age 50 years followed by treatment with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II-receptor blocker (ARB). Main Outcome Measure  Cost per quality-adjusted life-year (QALY). Results  For persons with neither hypertension nor diabetes, the cost-effectiveness ratio for screening vs no screening (usual care) was unfavorable ($282 818 per QALY; incremental cost of $616 and a gain of 0.0022 QALYs per person). However, screening such persons beginning at age 60 years yielded a more favorable ratio ($53 372 per QALY). For persons with hypertension, the ratio was highly favorable ($18 621 per QALY; incremental cost of $476 and a gain of 0.03 QALYs per person). Cost-effectiveness was mediated by both chronic kidney disease progression and death prevention benefits of ACE inhibitor and ARB therapy. Influential parameters that might make screening for the general population more cost-effective include a greater incidence of proteinuria, age at screening ($53 372 per QALY for persons beginning screening at age 60 years), or lower frequency of screening (every 10 years: $80 700 per QALY at age 50 years; $6195 per QALY at age 60 years; and $5486 per QALY at age 70 years). Conclusions  Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years.      

Noninvasive positive-pressure ventilation for postextubation respiratory distress: a randomized controlled trial

Context  Noninvasive positive-pressure ventilation (NPPV) has been demonstrated to be effective in preventing the need for endotracheal intubation in some patients who present with acute respiratory failure. It is also used for patients who develop acute respiratory distress after extubation, but there are no randomized controlled trials that address its effectiveness in this population. Objective  To determine the effectiveness of NPPV compared with standard medical therapy in preventing the need for endotracheal reintubation in high-risk patients who develop respiratory distress during the first 48 hours after extubation. Design  Randomized, controlled, unblinded study with concealed allocation conducted between August 1, 1996 and October 31, 1999. Setting  An intensive care unit (ICU) in an academic, tertiary care hospital in Ontario. Patients  Eighty-one patients with a history of cardiac or respiratory disease or who initially required ventilatory support for more than 2 days and who developed respiratory distress within 48 hours of extubation. Interventions  Patients were randomly assigned to receive standard medical therapy alone (supplemental oxygen to maintain oxygen saturation by pulse oximetry 95%; n = 42) or NPPV by face mask plus standard medical therapy (n = 39). Main Outcome Measures  Rates of reintubation, duration of mechanical ventilation, lengths of ICU and hospital stay, and hospital mortality. Results  Comparing the NPPV group with the standard-therapy group, there was no difference in the rate of reintubation (72% vs 69%; relative risk, 1.04; 95% confidence interval, 0.78-1.38) or hospital mortality (31% for both groups; relative risk, 0.99; 95% confidence interval, 0.52-1.91). Similarly, no difference was found in duration of mechanical ventilation or length of ICU or hospital stay. Conclusions  The addition of NPPV to standard medical therapy does not improve outcome in heterogeneous groups of patients who develop respiratory distress during the first 48 hours after extubation.      

Costs and funding for published medical education research

Context  The Institute of Medicine has called for increased rigor of education research and funding to support educational innovation. However, funding for medical education research is scarce. The costs of conducting studies in medical education and how such research is currently funded have not been systematically evaluated. Objectives  To determine how medical education research studies that were recently published were funded and to approximate the costs of conducting these studies. Design, Setting, and Participants  We conducted a cross-sectional survey of first authors of medical education studies published from September 1, 2002, to December 31, 2003. Original medical education research studies conducted at US institutions and published in 13 prominent peer-reviewed journals were included. Main Outcome Measures  For each study we measured duration, percentage of the authors’ total work commitment ("percentage effort") devoted to the study, resources used and their costs, attainment of funding, and the first author’s estimated cost of conducting the study. The cost of each study was calculated by multiplying the percentage effort of each author for the duration of the study by the national median salary for each author, according to specialty and academic rank, and then adding the costs of resources used. Results  Responses were received from authors of 243 (84%) of 290 identified medical education studies. The median calculated cost of conducting the 243 studies was $24 471 (interquartile range [IQR], $11 531-$63 808). The median authors’ estimate of study cost was $10 000 (IQR, $4000-$25 000). Some funding was obtained for 72 (29.6%) of the studies. Of studies that were funded, the median amount of funding was $15 000 (IQR, $5000-$66 500). The median calculated cost of funded studies was $37 315 (IQR, $18 731-$82 393). Private foundation grants were the most common funding source (n = 30 [41.7%]). Factors independently associated with attaining funding were training in grant writing (odds ratio, 2.05; 95% confidence interval, 1.11-3.79) and number of medical education studies published by the first author (odds ratio, 2.4; 95% confidence interval, 1.24-4.63). Conclusions  The majority of published medical education research is not formally funded, and the studies that do receive support are substantially underfunded. To realize the Institute of Medicine’s directive and to improve the quality of medical research, policy reform that increases funding for medical education scholarship will likely be required.      

Accuracy of data in abstracts of published research articles

Context  The section of a research article most likely to be read is the abstract, and therefore it is particularly important that the abstract reflect the article faithfully. Objective  To assess abstracts accompanying research articles published in 6 medical journals with respect to whether data in the abstract could be verified in the article itself. Design  Analysis of simple random samples of 44 articles and their accompanying abstracts published during 1 year (July 1, 1996-June 30, 1997) in each of 5 major general medical journals (Annals of Internal Medicine, BMJ, JAMA, Lancet, and New England Journal of Medicine) and a consecutive sample of 44 articles published during 15 months (July 1, 1996-August 15, 1997) in the CMAJ. Main Outcome Measure  Abstracts were considered deficient if they contained data that were either inconsistent with corresponding data in the article's body (including tables and figures) or not found in the body at all. Results  The proportion of deficient abstracts varied widely (18%-68%) and to a statistically significant degree (P<.001) among the 6 journals studied. Conclusions  Data in the abstract that are inconsistent with or absent from the article's body are common, even in large-circulation general medical journals.      

Off-pump vs conventional coronary artery bypass grafting: early and 1-year graft patency, cost, and quality-of-life outcomes: a randomized trial

Context  Previous trials of off-pump coronary artery bypass (OPCAB) have enrolled selected patients and have not rigorously evaluated long-term graft patency. A preliminary report showed OPCAB achieved improved inhospital outcomes, similar completeness of revascularization, and shorter lengths of stay compared with conventional coronary artery bypass grafting (CABG). Objective  To assess graft patency, clinical and quality-of-life outcomes, and cost among patients while in the hospital and at 1-year follow-up. Design, Setting, and Patients  Randomized controlled trial of patients unselected for coronary anatomy, ventricular function, or comorbidities between March 10, 2000, and August 20, 2001, at a US academic center. A total of 200 patients were enrolled; 3 patients were withdrawn after randomization for mitral valve repair or replacement. Follow-up was complete for 197 patients at 30 days; 185 at 1 year. Interventions  One surgical session consisting of elective OPCAB or CABG with cardiopulmonary bypass.The surgeon had extensive experience performing off-pump surgery; patients were subsequently managed by blinded protocols. Main Outcome Measures  Coronary angiography documented graft patency prior to hospital discharge and at 1 year; health-related quality of life; and cost of the index and subsequent hospitalization(s). Results  Graft patency was similar for OPCAB and conventional CABG with cardiopulmonary bypass at 30 days (absolute difference, 1.3%; 95% confidence interval [CI], –0.66% to 3.31%; P = .19) and at 1 year (absolute difference, –2.2%; 95% CI, –6.1% to 1.7%; P = .27). Rates of death, stroke, myocardial infarction, angina, and reintervention were similar at 30 days and 1 year. There were no significant differences in health-related quality of life. Mean total hospitalization cost per patient at hospital discharge was $2272 (95% CI, $755-$3732) less for OPCAB (P = .002) and $1955 (95% CI, –$766 to $4727) less at 1 year (P = .08). Conclusions  In this randomized single-surgeon trial among unselected patients with angiographic follow-up, OPCAB achieved similar graft patency in the hospital and at 1 year. Cardiac outcomes and health-related quality of life at 30 days and 1 year were similar and patients incurred a lower cost. OPCAB may provide complete revascularization that is durable and cost-effective.      

Relationship Between Low Cardiorespiratory Fitness and Mortality in Normal-Weight, Overweight, and Obese Men

Context  Recent guidelines for treatment of overweight and obesity include recommendations for risk stratification by disease conditions and cardiovascular disease (CVD) risk factors, but the role of physical inactivity is not prominent in these recommendations. Objective  To quantify the influence of low cardiorespiratory fitness, an objective marker of physical inactivity, on CVD and all-cause mortality in normal-weight, overweight, and obese men and compare low fitness with other mortality predictors. Design  Prospective observational data from the Aerobics Center Longitudinal Study. Setting  Preventive medicine clinic in Dallas, Tex. Participants  A total of 25,714 adult men (average age, 43.8 years [SD, 10.1 years]) who received a medical examination during 1970 to 1993, with mortality follow-up to December 31, 1994. Main Outcome Measures  Cardiovascular disease and all-cause mortality based on mortality predictors (baseline CVD, type 2 diabetes mellitus, high serum cholesterol level, hypertension, current cigarette smoking, and low cardiorespiratory fitness) stratified by body mass index. Results  During the study period, there were 1025 deaths (439 due to CVD) during 258,781 man-years of follow-up. Overweight and obese men with baseline CVD or CVD risk factors were at higher risk for all-cause and CVD mortality compared with normal-weight men without these predictors. Using normal-weight men without CVD as the referent, the strongest predictor of CVD death in obese men was baseline CVD (age- and examination year-adjusted relative risk [RR], 14.0; 95% confidence interval [CI], 9.4-20.8); RRs for obese men with diabetes mellitus, high cholesterol, hypertension, smoking, and low fitness were similar and ranged from 4.4 (95% CI, 2.7-7.1) for smoking to 5.0 (95% CI, 3.6-7.0) for low fitness. Relative risks for all-cause mortality in obese men ranged from 2.3 (95% CI, 1.7-2.9) for men with hypertension to 4.7 (95% CI, 3.6-6.1) for those with CVD at baseline. Relative risk for all-cause mortality in obese men with low fitness was 3.1 (95% CI, 2.5-3.8) and in obese men with diabetes mellitus 3.1 (95% CI, 2.3-4.2) and as slightly higher than the RRs for obese men who smoked or had high cholesterol levels. Low fitness was an independent predictor of mortality in all body mass index groups after adjustment for other mortality predictors. Approximately 50% (n = 1674)of obese men had low fitness, which led to a population-attributable risk of 39% for CVD mortality and 44% for all-cause mortality. Baseline CVD had population attributable risks of 51% and 27% for CVD and all-cause mortality, respectively. Conclusions  In this analysis, low cardiorespiratory fitness was a strong and independent predictor of CVD and all-cause mortality and of comparable importance with that of diabetes mellitus and other CVD risk factors.      

Preoperative intensive inspiratory muscle training to prevent postoperative pulmonary complications in high-risk patients undergoing CABG surgery: a randomized clinical trial

Context  Postoperative pulmonary complications (PPCs) after coronary artery bypass graft (CABG) surgery are a major source of morbidity and mortality, and increase length of hospital stay and resource utilization. The prehospitalization period before CABG surgery may be used to improve a patient's pulmonary condition. The efficacy of preoperative inspiratory muscle training (IMT) in reducing the incidence of PPCs in high-risk patients undergoing CABG surgery has not yet been determined. Objective  To evaluate the prophylactic efficacy of preoperative IMT on the incidence of PPCs in high-risk patients scheduled for elective CABG surgery. Design, Setting, and Patients  A single-blind, randomized clinical trial conducted at the University Medical Center Utrecht, Utrecht, the Netherlands, with enrollment between July 2002 and August 2005. Of 655 patients referred for elective CABG surgery, 299 (45.6%) met criteria for high risk of developing PPCs, of whom 279 were enrolled and followed up until discharge from hospital. Intervention  Patients were randomly assigned to receive either preoperative IMT (n = 140) or usual care (n = 139). Both groups received the same postoperative physical therapy. Main Outcome Measures  Incidence of PPCs, especially pneumonia, and duration of postoperative hospitalization. Results  Both groups were comparable at baseline. After CABG surgery, PPCs were present in 25 (18.0%) of 139 patients in the IMT group and 48 (35.0%) of 137 patients in the usual care group (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.30-0.92). Pneumonia occurred in 9 (6.5%) of 139 patients in the IMT group and in 22 (16.1%) of 137 patients in the usual care group (OR, 0.40; 95% CI, 0.19-0.84). Median duration of postoperative hospitalization was 7 days (range, 5-41 days) in the IMT group vs 8 days (range, 6-70 days) in the usual care group by Mann-Whitney U statistic (z = –2.42; P = .02). Conclusion  Preoperative IMT reduced the incidence of PPCs and duration of postoperative hospitalization in patients at high risk of developing a pulmonary complication undergoing CABG surgery. Trial Registration  isrctn.org Identifier: ISRCTN17691887      

Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project

Context  Dietary patterns and lifestyle factors are associated with mortality from all causes, coronary heart disease, cardiovascular diseases, and cancer, but few studies have investigated these factors in combination. Objective  To investigate the single and combined effect of Mediterranean diet, being physically active, moderate alcohol use, and nonsmoking on all-cause and cause-specific mortality in European elderly individuals. Design, Setting, and Participants  The Healthy Ageing: a Longitudinal study in Europe (HALE) population, comprising individuals enrolled in the Survey in Europe on Nutrition and the Elderly: a Concerned Action (SENECA) and the Finland, Italy, the Netherlands, Elderly (FINE) studies, includes 1507 apparently healthy men and 832 women, aged 70 to 90 years in 11 European countries. This cohort study was conducted between 1988 and 2000. Main Outcome Measures  Ten-year mortality from all causes, coronary heart disease, cardiovascular diseases, and cancer. Results  During follow-up, 935 participants died: 371 from cardiovascular diseases, 233 from cancer, and 145 from other causes; for 186, the cause of death was unknown. Adhering to a Mediterranean diet (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.68-0.88), moderate alcohol use (HR, 0.78; 95% CI, 0.67-0.91), physical activity (HR, 0.63; 95% CI, 0.55-0.72), and nonsmoking (HR, 0.65; 95% CI, 0.57-0.75) were associated with a lower risk of all-cause mortality (HRs controlled for age, sex, years of education, body mass index, study, and other factors). Similar results were observed for mortality from coronary heart disease, cardiovascular diseases, and cancer. The combination of 4 low risk factors lowered the all-cause mortality rate to 0.35 (95% CI, 0.28-0.44). In total, lack of adherence to this low-risk pattern was associated with a population attributable risk of 60% of all deaths, 64% of deaths from coronary heart disease, 61% from cardiovascular diseases, and 60% from cancer. Conclusion  Among individuals aged 70 to 90 years, adherence to a Mediterranean diet and healthful lifestyle is associated with a more than 50% lower rate of all-causes and cause-specific mortality.      

Cost-effectiveness of treatment for chronic hepatitis C infection in an evolving patient population

Context  Approximately 2.7 million US individuals are chronically infected with the hepatitis C virus (HCV). As public health campaigns are pursued, a growing number of treatment candidates are likely to have minimal evidence of liver damage. Objective  To examine the clinical benefits and cost-effectiveness of newer treatments for chronic hepatitis C infection in a population of asymptomatic, HCV sero-positive but otherwise healthy individuals. Design and Setting  Cost-effectiveness analysis using a Markov model of the natural history of HCV infection and impact of treatment. We used an epidemiologic model to derive a range of natural history parameters that were empirically calibrated to provide a good fit to observed data on both prevalence of HCV seropositivity and time trends in outcomes related to HCV infection. Patients  Cohorts of 40-year-old men and women with elevated levels of alanine aminotransferase, positive results on quantitative HCV RNA assays and serologic tests for antibody to HCV, and no histological evidence of fibrosis on liver biopsy. Interventions  Monotherapy with standard or pegylated interferon alfa-2b; combination therapy with standard or pegylated interferon plus ribavirin. Main Outcome Measures  Lifetime costs, life expectancy, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Results  The probability of patients with chronic HCV developing cirrhosis over a 30-year period ranged from 13% to 46% for men and from 1% to 29% for women. The incremental cost-effectiveness of combination therapy with pegylated interferon for men ranged from $26 000 to $64 000 per QALY for genotype 1 and from $10 000 to $28 000 per QALY for other genotypes; and for women ranged from $32 000 to $90 000 for genotype 1 and from $12 000 to $42 000 for other genotypes. Because the benefits of treatment were realized largely in the form of improvements in health-related quality of life, rather than prolonged survivorship, cost-effectiveness ratios expressed as dollars per year of life were substantially higher. Results were most sensitive to assumptions about the gains and decrements in health-related quality of life associated with treatment. Conclusions  While newer treatment options for hepatitis C appear to be reasonably cost-effective on average, these results vary widely across different patient subgroups and depend critically on quality-of-life assumptions. As the pool of persons eligible for treatment for HCV infection expands to the more general population, it will be imperative for patients and their physicians to consider these assumptions in making individual-level treatment decisions.