Jeff Whittle

Nationwide Trends of Severe Sepsis in the 21st Century (2000–2007)

BACKGROUND Severe sepsis is common and often fatal. The expanding armamentarium of evidence-based therapies has improved the outcomes of persons with this disease. However, the existing national estimates of the frequency and outcomes of severe sepsis were made before many of the recent therapeutic advances. Therefore, it is important to study the outcomes of this disease in an aging US population with rising comorbidities. METHODS We used the Healthcare Costs and Utilization Projects Nationwide Inpatient Sample (NIS) to estimate the frequency and outcomes of severe sepsis hospitalizations between 2000 and 2007. We identified hospitalizations for severe sepsis using International Classification of Diseases, Ninth Revision, Clinical Modification codes indicating the presence of sepsis and organ system failure. Using weights from NIS, we estimated the number of hospitalizations for severe sepsis in each year. We combined these with census data to determine the number of severe sepsis hospitalizations per 100,000 persons. We used discharge status to identify in-hospital mortality and compared mortality rates in 2000 with those in 2007 after adjusting for demographics, number of organ systems failing, and presence of comorbid conditions. RESULTS The number of severe sepsis hospitalizations per 100,000 persons increased from 143 in 2000 to 343 in 2007. The mean number of organ system failures during admission increased from 1.6 to 1.9 (P < .001). The mean length of hospital stay decreased from 17.3 to 14.9 days. The mortality rate decreased from 39% to 27%. However, more admissions ended with discharge to a long-term care facility in 2007 than in 2000 (35% vs 27%, P < .001). CONCLUSIONS An increasing number of admissions for severe sepsis combined with declining mortality rates contribute to more individuals surviving to hospital discharge. Importantly, this leads to more survivors being discharged to skilled nursing facilities and home with in-home care. Increased attention to this phenomenon is warranted.

Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years: A Randomized Clinical Trial

IMPORTANCE The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain. OBJECTIVE To evaluate the effects of intensive (<120 mm Hg) compared with standard (<140 mm Hg) SBP targets in persons aged 75 years or older with hypertension but without diabetes. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015. INTERVENTIONS Participants were randomized to an SBP target of less than 120 mm Hg (intensive treatment group, n = 1317) or an SBP target of less than 140 mm Hg (standard treatment group, n = 1319). MAIN OUTCOMES AND MEASURES The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome. RESULTS Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 [95% CI, 0.49-0.91]). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 [95% CI, 0.89-1.11]). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 [95% CI, 0.97-3.09]), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 [95% CI, 0.76-2.00]), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 [95% CI, 0.99-2.33]), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 [95% CI, 0.98-2.04]), and 4.9% vs 5.5% for injurious falls (HR, 0.91 [95% CI, 0.65-1.29]). CONCLUSIONS AND RELEVANCE Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01206062.

Clinical Importance of HIV and Depressive Symptoms Among Veterans with HIV Infection

OBJECTIVE: To compare the clinical importance (association with illness severity and survival) of depressive and HIV symptoms among veterans with HIV infection.DESIGN: Cross-sectional study; survival analysis.SETTING: Infectious Disease Clinics at 3 VA Medical Centers.PARTICIPANTS: HIV-infected patients (N=881) and their health care providers from June 1999 through July 2000.MEASUREMENTS AND MAIN RESULTS: Depressive symptoms were assessed using the 10-item Centers for Epidemiologic Studies Depression Scale (CES-D). Patient baseline survey included an HIV Symptom Index measuring the frequency and bother of 20 common symptoms. Providers were surveyed on patients’ illness severity, and survival data were obtained from VA death records. Of 881 patients, 46% had significant depressive symptoms (CES-D ≥10). Increasing depression symptom severity was associated with increasing HIV symptom frequency (P<.001) and bother (P<.001). Multiple regression results revealed that having moderate or severe depressive symptoms was not associated with provider-reported illness severity or survival. However, HIV symptoms were significantly associated with provider-reported illness severity (P<.01) and survival (P=.05), after adjusting for moderate and severe depressive symptoms, CD4 cell count/mm3, viral load, age, race, and antiretroviral use.CONCLUSIONS: Depression, while common in this sample, was not associated with illness severity or mortality after adjusting for HIV symptoms. HIV symptoms are associated with severity of illness and survival regardless of patients’ severity of depressive symptoms. This suggests that equal medical consideration should be given to HIV symptoms presented by HIV-infected patients regardless of their depression status, rather than automatically attributing medical complaints to depression.

Computers in the exam room : Differences in physician-patient interaction may be due to physician experience

BackgroundThe use of electronic medical records can improve the technical quality of care, but requires a computer in the exam room. This could adversely affect interpersonal aspects of care, particularly when physicians are inexperienced users of exam room computers.ObjectiveTo determine whether physician experience modifies the impact of exam room computers on the physician–patient interaction.DesignCross-sectional surveys of patients and physicians.Setting and ParticipantsOne hundred fifty five adults seen for scheduled visits by 11 faculty internists and 12 internal medicine residents in a VA primary care clinic.MeasurementsPhysician and patient assessment of the effect of the computer on the clinical encounter.Main ResultsPatients seeing residents, compared to those seeing faculty, were more likely to agree that the computer adversely affected the amount of time the physician spent talking to (34% vs 15%, P = 0.01), looking at (45% vs 24%, P = 0.02), and examining them (32% vs 13%, P = 0.009). Moreover, they were more likely to agree that the computer made the visit feel less personal (20% vs 5%, P = 0.017). Few patients thought the computer interfered with their relationship with their physicians (8% vs 8%). Residents were more likely than faculty to report these same adverse effects, but these differences were smaller and not statistically significant.ConclusionPatients seen by residents more often agreed that exam room computers decreased the amount of interpersonal contact. More research is needed to elucidate key tasks and behaviors that facilitate doctor–patient communication in such a setting.

Visit-to-Visit Variability of Blood Pressure and Coronary Heart Disease, Stroke, Heart Failure, and Mortality: A Cohort Study

Context It is not clear whether variability in a patients outpatient blood pressure (BP) measurements has prognostic importance. Contribution Patients with greater visit-to-visit variability in BP readings had an increased risk for cardiovascular events and mortality, which was independent of their overall degree of BP control. Implication Further studies are warranted to assess whether reducing visit-to-visit BP variations will alter the risk for adverse cardiovascular outcomes. The prognostic value of blood pressure (BP) is mainly based on measurements obtained in a clinical setting, typically from a few visits (1). Until recently, variability of BP across outpatient visits was dismissed as random fluctuation around a patients true underlying BP (2, 3). Although some studies have reported associations between higher visit-to-visit variability (VVV) of systolic BP (SBP) and an increased risk for stroke and coronary heart disease (CHD), other analyses have failed to show such associations (410). The method applied in estimating VVV of BP varied widely across previous studies. In addition, studies have used as few as 3 visits and as many as 56 visits to estimate the VVV of BP, and the time between visits has ranged from 2 days to as long as 4 years (5, 11, 12). These factors not only influence VVV of BP but could also affect the strength of its association with cardiovascular disease (CVD) outcomes (4, 13). To address the inconsistent findings from previous studies, we did a secondary data analysis of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) to examine whether VVV of BP is associated with CVD and mortality events. ALLHAT provides the opportunity to evaluate the association between VVV of BP and major clinical outcomes in a large and diverse population with hypertension in which visits were conducted at set time intervals, BP was measured by following a standardized protocol, and outcomes were evaluated over several years of follow-up. Methods Study Design We did a cohort study as a secondary analysis using data from ALLHAT. Figure 1 shows the timeline for assessment of VVV of BP and outcome events within ALLHAT. The primary exposure of interest, VVV of SBP, was ascertained at the 7 study visits conducted between 6 and 28 months after randomization. We studied 4 outcomes: fatal CHD or nonfatal myocardial infarction (MI), all-cause mortality, stroke, and heart failure. Participants were followed from their 28-month visit until the occurrence of an outcome event or the end of active ALLHAT follow-up (October 2001 to March 2002). Participants who had an event before their 28-month visit were excluded from all analyses. Figure 1. Study design evaluating the association between VVV of BP and cardiovascular outcomes and all-cause mortality in ALLHAT. ALLHAT = Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; BP = blood pressure; DBP = diastolic blood pressure; SBP = systolic blood pressure; VVV = visit-to-visit variability. * Participants were followed for a mean of 2.7 to 2.9 y (maximum, 5.7 y) depending on the outcome after assessment of VVV of BP. ALLHAT was a multicenter, double-blind, randomized clinical trial sponsored by the National Heart, Lung, and Blood Institute of the National Institutes of Health. A complete description of the rationale and design of ALLHAT has been previously published (14). In brief, ALLHAT was designed to determine whether treatment initiated with a calcium-channel blocker (amlodipine), angiotensin-converting enzyme inhibitor (lisinopril), or -blocker (doxazosin)each compared with treatment initiated with a diuretic (chlorthalidone)would lower major cardiovascular outcomes. The primary end point was incidence of fatal CHD or nonfatal MI. A total of 42418 hypertensive adults aged 55 years or older with 1 or more additional risk factor for CVD were enrolled at 623 clinical sites across the United States, Canada, Puerto Rico, and the U.S. Virgin Islands between February 1994 and January 1998. The doxazosin treatment group was discontinued in 2000 because of the small chance of finding a benefit on CHD outcomes and an increased risk for CVD than in the chlorthalidone group (15). The main results comparing participants randomly assigned to chlorthalidone, amlodipine, or lisinopril were published in December 2002 (16). The trial was approved by local institutional review boards, and all participants provided written informed consent. Our current analysis was approved by the Institutional Review Board at the University of Alabama at Birmingham. Study Visits, BP Measurements, and Calculation of VVV of BP To calculate intraindividual VVV of SBP and diastolic BP (DBP), we used data from 7 follow-up visits that occurred 6, 9, 12, 16, 20, 24, and 28 months after randomization. We chose to begin the assessment period at the 6-month follow-up visit to avoid confounding by the initial reduction in BP that occurred between randomization and this visit (SBP, 6 to 10 mm Hg; DBP, approximately 5 mm Hg) due to early medication titration. To increase the precision of estimates, we calculated VVV of BP for participants with BP measurements at 5, 6, or 7 visits conducted between month 6 and 28 after randomization. The VVV of BP was imputed for participants who attended fewer than 5 visits between months 6 and 28. To maximize follow-up time, we did not extend the assessment past the 28-month follow-up visit. At each follow-up visit, BP was measured twice by a trained observer by means of a standardized technique (17). Using the average BP at each visit, we defined VVV of BP by the intraindividual SD across visits. Average real variability (ARV) and SD independent of the mean (SDIM) were calculated as alternative metrics for VVV of BP (Appendix Figure) (18). The VVV of DBP was also calculated in secondary analyses. Appendix Figure. Formulas used to calculate VVV of BP metrics. ARV = average real variability; BP = blood pressure; SDIM = SD independent of the mean; VVV = visit-to-visit variability. Outcome Ascertainment We studied 4 outcomes, including fatal CHD or nonfatal MI, all-cause mortality, stroke, and heart failure. The event ascertainment process is detailed elsewhere (14, 16). Participants were followed from the end of the assessment period to the date of each outcome, their date of death, or the end of active ALLHAT follow-up (1 October 2001 through 31 March 2002). Covariate Information Covariates used for adjustment were selected a priori on the basis of their potential role as confounders. Baseline (before randomization) variables included age, sex, race/ethnicity, education, current cigarette smoking status, body mass index, use of aspirin, high-density lipoprotein cholesterol level less than 0.91 mmol/L (<35 mg/dL) (at 2 occasions in the 5 years before ALLHAT enrollment), total cholesterol level, estimated glomerular filtration rate (eGFR), diabetes, history of MI or stroke, documentation of other atherosclerotic CVD, history of revascularization, atrial fibrillation by electrocardiography, left ventricular hypertrophy (LVH), the presence of ST depression and T-wave inversion, and use of antihypertensive medication before ALLHAT randomization. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (19). Data collected at visits conducted 6 to 28 months after randomization were used to calculate mean SBP and DBP; pulse pressure; the use of antihypertensive medications beyond the randomization drug; changes in antihypertensive medication regimen (adding, stopping, or changing antihypertensive medications); use of statins; and low adherence, which is defined as a report of a participant receiving less than 80% of the randomization drug at any visit between months 6 and 28. Participants who reported taking 80% or more of their randomization drug at every visit between months 6 and 28 were considered to have high adherence. Statistical Analysis Because of limited follow-up available after the assessment period for participants randomly assigned to receive doxazosin, we restricted our analyses to the 33357 ALLHAT participants randomly assigned to receive chlorthalidone, amlodipine, or lisinopril. We excluded 7543 participants who had CVD events or died before the 28-month visit. We imputed VVV of BP for participants with fewer than 5 visits and BP measurements between months 6 and 28 of follow-up. In addition, missing data for covariates were imputed (Appendix Table 1). Imputation was performed with 10 data sets using chained equations. Appendix Table 1. Percentage of Missing Data for Participants Included in the Current Analyses Characteristics of participants included in the current analyses were calculated after participants were stratified into a quintile of SD of SBP. The KaplanMeier method was used to calculate the cumulative incidence of each outcome by quintile of SD of SBP. Cox proportional hazards regression was used to calculate multivariable-adjusted hazard ratios (HRs) for each outcome associated with a quintile of SD of SBP, with the lowest quintile serving as the reference. Four nested models were constructed. Model 1 included adjustment for age, race/ethnicity, sex, region of residence, and antihypertensive randomization assignment. Model 2 includes the variables in model 1 and additional adjustment for education, smoking status, body mass index, use of aspirin, low high-density lipoprotein cholesterol level, total cholesterol level, eGFR, diabetes, history of MI or stroke, history of other atherosclerotic CVD, history of coronary revascularization, atrial fibrillation by electrocardiography, major ST depression or T-wave inversion, LVH, use of antihypertensive medications before ALLHAT randomization, and statin use during the assessment period (months 6 through 28 of follow-up). Model 3 includes the variables in model 2 and additional adjustment for mean pulse pressure, medic

ACCURACY OF MEDICARE CLAIMS DATA FOR ESTIMATION OF CANCER INCIDENCE AND RESECTION RATES AMONG ELDERLY AMERICANS

To explore the reliability of Medicare Part A claims data for clinical and health services research related to the care of patients with cancer, the authors compared estimates of the incidence of and resection rates for cancer of the breast, colon, and lung derived from analysis of Medicare Part A data versus data from the National Cancer Institutes Surveillance, Epidemiology, and End Results (SEER) Program. Incidence rates of breast, colon, and lung cancer estimated from Medicare Part A data were within 6% of estimates derived from SEER data. Resection rates estimated from Medicare Part A data, in contrast, were 12% to 27% lower than resection rates based on SEER data. This discrepancy is not explained by variations in practice between regions participating in versus those not participating in the SEER registries but may be due to undercoding of surgical procedures in Medicare Part A data. This analysis suggests that Medicare data can provide useful insights into the care of patients with cancer, but research regarding inpatient procedures employed in management of cancer should be based on analysis of Medicare Parts A and B data combined.

Relationship of Provider Characteristics To Outcomes, Process, And Costs of Care for Community-acquired Pneumonia

OBJECTIVES The authors describe the relation of provider characteristics to processes, costs, and outcomes of medical care for elderly patients hospitalized for community-acquired pneumonia. METHODS Using Medicare claims data, Medicare beneficiaries discharged from Pennsylvania hospitals during 1990 with community-acquired pneumonia were identified. Claims data were used to ascertain mortality, readmissions, use of procedures and physician consultations, and the costs of care. The relationship of these measures to provider characteristics was analyzed using regression techniques to adjust for patient characteristics, including comorbidity and microbial etiology. RESULTS Among 22,294 pneumonia episodes studied, 30-day mortality was 17.0%. After adjusting for patient characteristics, 30-day mortality and readmission rates were unrelated to hospital teaching status or urban location or to physician specialty. Use of procedures and physician consultations was more common and costs were 11% higher among patients discharged from teaching hospitals compared with nonteaching hospitals. Similarly, costs were 15% higher at urban hospitals compared with rural hospitals. General internists and medical subspecialists used more procedures and had higher costs than family practitioners. CONCLUSIONS Processes and costs of care for community-acquired pneumonia varied by provider characteristics, but neither mortality nor readmission rates did. These differences cannot be explained by clinical variables in the database. Further studies should determine whether less costly patterns of care for pneumonia, and perhaps other conditions, could replace more costly ones without compromising patient outcomes.

Race, Presenting Signs and Symptoms, Use of Carotid Artery Imaging, and Appropriateness of Carotid Endarterectomy

BACKGROUND AND PURPOSE We sought to determine whether there are racial differences in use of carotid artery imaging after controlling for clinical factors and to ascertain racial differences in presenting signs and symptoms and overall appropriateness for carotid endarterectomy (CE). METHODS We performed a retrospective cohort study of 803 patients older than 45 years, hospitalized between 1991 and 1994 at any of 4 Veterans Affairs Medical Centers, with a discharge diagnosis of transient ischemic attack or ischemic stroke. Clinical data were abstracted from the medical record, including presenting symptoms, diagnostic test results, and use of surgical procedures. Appropriateness for CE was determined according to RAND criteria. RESULTS Black patients were more likely than white patients to present with stroke (78% versus 55%) but less likely to present with transient ischemic attack (22% versus 45%; P=0.001). There was no racial difference in medical comorbidity or preoperative risk. Black patients were less likely to have an imaging study of their carotid arteries (67% versus 79%; P=0.001). Race remained an independent predictor of imaging after adjustment for clinical factors (odds ratio=1.50; 95% CI, 1.06 to 2.13). Because of higher prevalence of significant carotid artery stenosis, whites were significantly more likely than blacks to be assessed as appropriate candidates for surgery with the use of RAND criteria (18% versus 4%; P=0.001). CONCLUSIONS Use of carotid artery imaging, a critical step in determining eligibility for CE, is influenced by the patients race after controlling for clinical presentation. Adjustment for appropriateness of CE reduces but does not eliminate the importance of race.

Racial/Ethnic Variations in Physician Recommendations for Cardiac Revascularization

OBJECTIVES We sought to examine whether physician recommendations for cardiac revascularization vary according to patient race. METHODS We studied patients scheduled for coronary angiography at 2 hospitals, one public and one private, between November 1997 and June 1999. Cardiologists were interviewed regarding their recommendations for cardiac resvacularization. RESULTS African American patients were less likely than Whites to be recommended for revascularization at the public hospital (adjusted odds ratio [OR] = 0.31; 95% confidence interval [CI] = 0.12, 0.77) but not at the private hospital (adjusted OR = 1.69; 95% CI = 0.69, 4.14). CONCLUSIONS Physician recommendations for cardiac revascularization vary by patient race. Further studies are needed to examine physician bias as a factor in racial disparities in cardiac care and outcomes.

Chronic Kidney Disease Is Associated with Angiographic Coronary Artery Disease

Background/Aims: Patients with chronic kidney disease (CKD) have a dramatically increased risk for cardiovascular mortality. Few prior studies have examined the independent association of CKD with coronary anatomy. Methods: We evaluated the relationship between CKD and severe coronary artery disease (CAD) in 261 male veterans with nuclear perfusion imaging tests suggesting coronary ischemia. We used chart review and patient and provider interviews to collect demographics, clinical characteristics, and coronary anatomy results. We defined CKD as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, based on the creatinine obtained prior to angiography. We defined significant coronary obstruction as at least one 70% or greater stenosis. We used logistic regression to determine whether CKD was independently associated with significant coronary obstruction. Results: The likelihood of CAD increased monotonically with decreasing eGFR, from 51% among patients with eGFR ≧90 ml/min/1.73 m2 to 84% in those with eGFR <30 ml/min/1.73 m2 (p = 0.0046). Patients with CKD were more likely than those without CKD to have at least one significant coronary obstruction (75.9 vs. 60.7%, p = 0.016). Patients with CKD also had more significant CAD, that is, were more likely to have three-vessel and/or left main disease than those without CKD (34.9 vs. 16.9%, p = 0.0035). In logistic regression analysis, controlling for demographics and comorbidity, CKD continued to be independently associated with the presence of significant CAD (p = 0.0071). Conclusion: CKD patients have a high prevalence of obstructive coronary disease, which may contribute to their high cardiovascular mortality.