Duty hours, infective endocarditis

Summaries from ACP Hospitalist Weekly.

Patient safety, resident sleep do not appear to differ with flexible vs. standard duty hours

Patient safety outcomes and resident sleep loss do not appear to be affected by flexible or standard duty hours, according to two recent studies from a randomized clinical trial.

The iCOMPARE (Individualized Comparative Effectiveness of Models Optimizing Patient Safety and Resident Education) trial assessed patient safety and resident sleep and alertness at 63 U.S. internal medicine residency programs during the 2015-2016 academic year. The programs were randomly assigned to follow the Accreditation Council for Graduate Medical Education (ACGME)'s standard 2011 duty-hour policies mandating 16-hour shifts and an 80-hour workweek, or flexible policies, where an 80-hour workweek was maintained but no limits were placed on shift length or mandatory time off between shifts. A study reporting the effects on patient safety and a study reporting on sleep and alertness outcomes were published March 7 by the New England Journal of Medicine. iCOMPARE was funded by the National Heart, Lung, and Blood Institute and by ACGME.

Thirty-two programs were assigned to the flexible group, and 31 were assigned to the standard group. In the first study, the primary outcome was the change in unadjusted 30-day mortality before and during the trial year, according to Medicare claims, while changes in five other measures of patient safety and risk-adjusted outcomes were the secondary outcome measures. The prespecified noninferiority margin was 1 percentage point for differences in changes between the flexible and standard programs. Patients in the flexible programs had a noninferior change in mortality versus those in the standard programs (12.5% in the trial year and 12.6% in the pretrial year vs. 12.2% in the trial year vs. 12.7% in the pretrial year, respectively). Unadjusted rate of readmission at seven days, other indicators of patient safety, and Medicare payments were also within the noninferiority margin, while 30-day readmissions and prolonged hospital stay were not. Findings were similar for risk-adjusted measures, the study authors said.

In the second study, sleep duration and morning sleepiness and alertness were compared for noninferiority between 205 interns in six flexible programs and 193 interns in six standard programs. The outcome measures included sleep duration as measured with actigraphy, the Karolinska Sleepiness Scale, and a Psychomotor Vigilance Test. Data were obtained over 14 days for both groups. Average sleep time per 24 hours was 6.85 hours for residents in flexible programs and 7.03 for those in standard programs. Sleep duration and Karolinska Sleepiness Scale score were both noninferior in the flexible group versus the standard group, while noninferiority was not established between groups for alertness.

The iCOMPARE investigators wrote that the first trial “suggests that allowing program directors the discretion to make their own schedules without continuous duty-hour limits did not result in worse patient outcomes” and that the second trial indicates that intern sleep duration and sleepiness were noninferior in flexible versus standard programs, while results for alertness did not meet prespecified criteria for noninferiority. An accompanying editorial said that based on the results from these studies and previous research on duty hours, “We can confidently say that working flexible hours, still within the 80-hour constraints, does not result in higher patient mortality than working standard hours.” In addition, the trial shows that interns don't seem to get more or less sleep with either type of schedule, the editorialists said.

The editorialists also noted that the patient voice has been “conspicuously absent” in duty-hour research and that the effect on patients of duty-hour changes and other changes in health care delivery, such as hospitalist care and the implementation of electronic health records, is worthy of further attention. “This cultural shift is certainly not attributable to work-hour restrictions alone,” the editorialists wrote. “But as we move beyond the question of how many consecutive hours our most junior doctors can safely work, we will continue to ask how we might design a system capable of fostering the morale of its workforce, while simultaneously sustaining the relationships that remain fundamental to the well-being of both patients and their doctors.”

Studies analyze rise in infective endocarditis hospitalizations related to drug use

Hospitalizations for strokes related to opioid use and infective endocarditis increased significantly between 2008 and 2015, a study found.

Researchers identified hospitalizations from 1993 through 2015 for opioid use, infective endocarditis, and stroke (defined as ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage) and calculated their frequency among the U.S. population using data from the National Inpatient Sample, ICD-9-CM codes, and the U.S. Census. Results were published online on Jan. 30 by Stroke and appeared in the March issue.

From 1993 through 2015, there were 5,283 hospitalizations for stroke associated with infective endocarditis and opioid use (mean patient age, 41.2 years; 34.2% women; 57.6% non-Hispanic white). The rate of such hospitalizations increased from 2.4 per 10 million U.S. residents in 1993 (95% CI, 0.5 to 4.3) to 18.8 per 10 million in 2015 (95% CI, 14.4 to 23.3). The rate did not significantly change between 1993 and 2008 (annual percentage change, 1.9%; 95% CI, −2.2% to 6.1%), but from 2008 to 2015, it significantly increased (annual percentage change, 20.3%; 95% CI, 10.5% to 30.9%). Non-Hispanic white patients in the Northeastern and Southern U.S. had the greatest increases in the rate of hospitalization for stroke associated with infective endocarditis and opioid use.

The authors noted limitations of the study, such as potential misclassification of diagnoses in administrative claims data and a lack of access to granular clinical information (e.g., cause, severity, and location of stroke). “These novel findings indicate that increasing opioid abuse in the United States is not only causing more social/occupational dysfunction, cardiac complications, and premature mortality but may also be increasing the population burden of permanent functional disability as a result of stroke,” they wrote.

In another study, researchers analyzed recent trends in hospitalizations for infective endocarditis and injection drug use and characterized patients' clinical outcomes and 30-day readmissions using the National Readmissions Database from January 2010 to September 2015. They stratified patients by injection drug use status and surgical versus medical management. Results were published Feb. 5 by the Journal of the American College of Cardiology.

The survey-weighted sample contained 96,344 (77.8%) cases of infective endocarditis not related to injection drug use and 27,432 (22.2%) cases related to injection drug use. From 2010 through 2015, the proportion of infective endocarditis cases related to injection drug use increased from 15.3% to 29.1% (P<0.001). Compared to nonrelated cases, cases related to injection drug use at index hospitalization were associated with less mortality (6.8% vs. 9.6%; P<0.001) due to younger age, but similar risk of 30-day readmission (23.8% vs. 22.9%; P=0.077).

Compared with medically managed cases of infective endocarditis unrelated to injection drug use, medically managed patients with injection drug use had longer length of stay (β=1.36 d; 95% CI, 0.71 to 2.01 d), lower costs (β=−$4,427; 95% CI, −$7,093 to −$1,761), and more readmissions for endocarditis (18.1% vs. 5.6%; P<0.001), septicemia (14.0% vs. 7.3%; P< 0.001), and drug abuse (4.3% vs. 0.7%; P< 0.001). Compared to surgically managed patients with unrelated infective endocarditis, those with surgically managed infective endocarditis related to drug use had longer lengths of stay (β=4.26 d; 95% CI, 2.73 to 5.80 d) and more readmissions for septicemia (15.6% vs. 5.2%; P<0.001) and drug abuse (7.3% vs. 0.9%; P< 0.001).

Limitations of the study include its retrospective nature, potential coding errors within the National Readmissions Database, and a lack of detailed data, the study authors said. Although patients with infective endocarditis related to injection drug use seem to have lower mortality, their long-term mortality remains unknown, an accompanying editorial noted. Future studies should assess the benefit of surgery in this population, particularly in the subgroup of those with persistent drug use, the editorialists said.

“[I]ncreased focus on addiction treatment and social support following hospital discharge is mandatory to reduce the risk of recurrent endocarditis,” they wrote.

More medications in advanced illness can lower quality of life, increase symptom burden

Among adults with advanced illness, taking more medications is associated with higher symptom burden and lower quality of life, a study found.

To evaluate associations between polypharmacy, symptom burden, and quality of life in patients with advanced, life-limiting illness (defined as clinician-estimated survival of one month to one year), and recent deterioration in functional status, researchers conducted a secondary analysis of baseline data from a trial of statin discontinuation. Polypharmacy was assessed by determining the number of non-statin medications taken regularly or as needed. Symptom burden was assessed by using the Edmonton Symptom Assessment Scale (range, 0 to 90, with higher scores indicating greater symptom burden), while quality of life was assessed by using the McGill Quality of Life Questionnaire (range, 0 to 10, with higher scores indicating better quality of life). Results of the study were published by the Journal of General Internal Medicine on Feb. 4 and appeared in the April issue.

Image by Getty Images
Image by Getty Images

Three hundred seventy-two participants were included in the study. Of these, 47% were age 75 years or older and 35% were enrolled in hospice. Fifty-two percent had a cancer diagnosis. The most common noncancer diagnoses were chronic obstructive pulmonary disease, congestive heart failure, and dementia. The mean symptom score was 27.0, with higher scores associated with higher polypharmacy. The mean quality-of-life score was 7.0, with worse total quality of life associated with higher polypharmacy. The average number of non-statin medications was 11.6; one-third of participants took 14 or more medications.

In adjusted models, higher polypharmacy was associated with higher symptom burden, and this association remained significant in fully adjusted linear regression models, implying that each additional medication was associated with a higher symptom burden of 0.81 point on the Edmonton Symptom Assessment Scale, the authors noted. Higher polypharmacy was also associated with lower quality of life in unadjusted linear regression models. This association remained significant in adjusted analyses, implying that every additional medication was associated with lower quality of life by 0.06 point on the McGill Quality of Life Questionnaire. Adjusting for symptom burden weakened the association between polypharmacy and quality of life without a significant interaction, which suggests that the decrease in quality of life associated with polypharmacy may be related to medication-associated symptoms, the authors said.

Attention to medication-related symptoms and shared decision-making regarding deprescribing are warranted because polypharmacy may be particularly burdensome near the end of life, as patients accumulate medications to treat and prevent multiple diseases, the authors concluded.

“Efforts to alleviate the burden of polypharmacy and improve quality of life for patients with advanced, life-limiting illness will require clinician and patient education, accompanied by patient-centered decision-making. All clinicians caring for older and/or seriously ill patients should learn targeted approaches to deprescribing, and these approaches should be employed routinely,” they wrote.

Early norepinephrine was associated with faster control of septic shock

Patients with sepsis and hypotension were more likely to have their shock controlled within six hours if they received early norepinephrine therapy, according to a recent study.

The single-center trial included 310 patients diagnosed with sepsis with hypotension at a hospital in Thailand. They were randomized to either early norepinephrine (4 mg mixed with 250 mL of 5% dextrose in water) or placebo. If mean arterial blood pressure didn't reach 65 mm Hg after the patient had received at least 30 mL/kg of fluid and the study drug infusion, open-label vasopressors were permitted when no attenuation of shock was observed.

The study's primary outcome was shock control by six hours after diagnosis (defined as mean arterial blood pressure >65 mm Hg and either urine flow >0.5 mL/kg/h for two consecutive hours or serum lactate level decreased >10% from baseline). Results were published by the American Journal of Respiratory and Critical Care Medicine on Feb. 1 and appeared in the May issue.

Patients in the early norepinephrine group received the drug a median of 93 minutes after arrival at the ED, compared to 192 minutes in the standard therapy group (P<0.001). Significantly more of them achieved shock control by six hours (118 of 155 [76.1%] vs. 75 of 155 [48.4%]; P<0.001). Early norepinephrine was also associated with lower incidence of cardiogenic pulmonary edema (14.4% vs. 27.7%; P=0.004) and new-onset arrhythmia (11% vs. 20%; P=0.03). The rate of 28-day mortality was 15.5% in the early norepinephrine group and 21.9% in the standard treatment group, a nonsignificant difference (P=0.15).

The authors believe this to be the first study to assess the benefit of early norepinephrine for sepsis-related hypotension that looked at surrogate, short-term, shock control endpoints. They noted that the studied endpoints measure restoration of both macro- and microcirculation. The study had a number of limitations, including the inability to mask the effect of the norepinephrine, lack of control over the fluid resuscitation rates, and uncertain generalizability outside this single center.

“Further studies are needed to confirm these findings before this approach can be introduced in clinical resuscitation practice,” the authors said. Such research should investigate the effect of early norepinephrine on organ dysfunction and on mortality, which was not a prespecified outcome of this trial.

Antibiotic use common during asthma hospitalizations, associated with longer stay

Antibiotics did not improve outcomes in adult patients who were hospitalized for an asthma exacerbation and received systemic corticosteroids, a study found.

Image by Getty Images
Image by Getty Images

The retrospective cohort study included 19,811 adults hospitalized for an asthma exacerbation and treated with systemic corticosteroids in any of 542 U.S. acute care hospitals from Jan. 1, 2015, through Dec. 31, 2016. Almost half of the patients (44.4%) had antibiotics started during the first two days of hospitalization and prescribed for a minimum of two days. Outcomes were compared by whether patients did or didn't receive antibiotics, and results were published by JAMA Internal Medicine on Jan. 28.

Patients who received antibiotics were older (median age, 48 vs. 45 years), were more likely to be white (48.6% vs. 40.9%), and were more likely to smoke (6.6% vs. 5.3%) than those who didn't, as well as having a higher rate of comorbidities (e.g., 6.2% with congestive heart failure vs 5.8%). The study's primary outcome, hospital length of stay, was significantly longer in the antibiotic group (median, 4 days vs. 3 days; ratio in a propensity-scored matched analysis, 1.29 [95% CI, 1.27 to 1.31]). The groups had similar rates of treatment failure within 30 days (defined as initiation of mechanical ventilation, transfer to the ICU after hospital day 2, in-hospital mortality, or readmission for asthma): 5.4% with antibiotics versus 5.8% without. Hospital costs were higher in the patients treated with antibiotics.

“These findings are novel, reflect the experience of unselected patients cared for in routine settings, and lend strong support to current guidelines that recommend against the use of antibiotics in the absence of concomitant infection. In addition, the findings highlight the need for future research to improve antimicrobial stewardship in the setting of asthma,” the authors said. They noted that biomarkers for guiding antibiotic therapy, such as procalcitonin, may be helpful in this area.

Limitations of the study include the possibility of residual confounding by indication, although the authors said they conducted robust statistical and sensitivity analyses to try to avoid this problem. Because the study was observational, the results do not demonstrate causality. The data set also lacked physiological measures of disease severity.

Atrial fibrillation common, increasing among COPD patients

Atrial fibrillation is common among patients hospitalized for an exacerbation of chronic obstructive pulmonary disease (COPD) and became more so between 2003 and 2014, a study found.

The retrospective analysis used the 2003-2014 Nationwide Inpatient Sample to identify adults with a primary diagnosis of COPD who received home oxygen and were hospitalized for a COPD exacerbation. Out of the 1,345,270 patients included, 18.2% (n=244,488) had atrial fibrillation. The prevalence of atrial fibrillation among the COPD patients increased significantly over the study period, from 12.9% in 2003 to 21.3% in 2014 (P<0.0001). Prevalence varied by age, sex, race, income, insurance type, and hospital region. Older age, female sex, white race, high income, and large hospital size were associated with increased odds of atrial fibrillation. Results were published by CHEST on Jan. 23 and appeared in the May issue.

In-hospital mortality was higher among patients with atrial fibrillation (3.5% vs. 1.7%), but from 2003 to 2014, it decreased more among patients with atrial fibrillation than those without (from 6.1% to 2.9% vs. from 2.1% to 1.5%). Having atrial fibrillation was also associated with increased risk of other adverse outcomes, including acute respiratory failure (odds ratio [OR], 1.09; 95% CI, 1.06 to 1.12), invasive mechanical ventilation (OR, 1.37; 95% CI, 1.29 to 1.47), noninvasive mechanical ventilation (OR, 1.14; 95% CI, 1.09 to 1.18), acute kidney injury (OR, 1.09; 95% CI, 1.04 to 1.13), sepsis (OR, 1.23; 95% CI, 1.10 to 1.37), and stroke (OR, 1.80; 95% CI, 1.40 to 2.32). The presence of atrial fibrillation was also associated with higher costs and longer length of stay.

“This high [atrial fibrillation] prevalence highlights the enormous burden of [atrial fibrillation] among this population in the US. Furthermore, the increasing [atrial fibrillation] prevalence in hospital encounters with end-stage COPD represents a growing challenge in the US,” said the study authors. They offered a number of possible explanations for the increasing prevalence, including the aging population, improving diagnostics, decreasing mortality from atrial fibrillation, and rising prevalence of risk factors. The observed decline in mortality among patients with COPD and atrial fibrillation is encouraging, but better management strategies for these patients are still needed, the authors said.

The study was limited by potential for coding inaccuracies and confounding, as well as the inability to distinguish index admissions from readmissions, which might have inflated the estimates of atrial fibrillation prevalence.

OPAT used for endocarditis more than guidelines recommend

Many more patients receive outpatient parenteral antibiotic treatment (OPAT) for infective endocarditis than guidelines recommend, without any apparent negative effect on outcomes, a study found.

The retrospective analysis included 2,000 consecutive patients seen in 25 Spanish hospitals for infective endocarditis from 2008 to 2012. Intravenous drug users were excluded. A total of 429 patients (21.5%) received OPAT. Only 21.7% of the patients who received OPAT met the Infectious Diseases Society of America's (IDSA) 2001 criteria to be treated as an outpatient. A similar proportion of the patients who were treated in the hospital (23.3%) met OPAT criteria. Results were published by Clinical Infectious Diseases on Jan. 14.

Of the patients who received OPAT, 57% had native-valve infective endocarditis, 27% had prosthetic-valve infective endocarditis, and 19% had pacemaker/defibrillator infective endocarditis. The most common microorganisms were viridans group streptococci (18.6%), Staphylococcus aureus (15.6%), and coagulase-negative staphylococci (14.5%). The median length of antibiotic treatment was 42 days, and 44% of patients underwent cardiac surgery.

The one-year mortality rate was 7.7% in OPAT patients and 12.5% in hospitalized patients. Rates of readmission within three months and relapse were similar between groups (10.9% vs. 10.0% and 1.4% vs. 3.2%, respectively). One-year mortality risk was associated with Charlson score (odds ratio [OR], 1.21; 95% CI, 1.04 to 1.42) and cardiac surgery (OR, 0.24; 95% CI, 0.09 to 0.63). Aortic valve involvement was the only predictor of readmission within a year (OR, 0.47; 95% CI, 0.22 to 0.98). Whether a patient met OPAT criteria did not predict mortality or readmission.

This is not the first study to show that OPAT is used more broadly than guidelines recommend, said the authors. They called for revision of the IDSA guidelines, but also more research comparing OPAT and hospital treatment. “However, as a general rule, it seems reasonable to consider as candidates for OPAT all patients with endocarditis not caused by difficult-to-treat microorganisms requiring complex antibiotic combinations and not presenting clinical, echocardiographic, or post-surgical complications that have not resolved shortly after onset,” the authors said. That recommendation applies only when an appropriate OPAT program and sufficient outpatient support for the patient are available, they noted.

Limitations of the study include that it couldn't match patients between settings, that there was heterogeneity among participating centers, and that referral bias was possible. In addition, epidemiological aspects (like bacteria prevalence) make it uncertain whether the results can be extrapolated to other geographic areas. An accompanying editorial noted that deviations from IDSA criteria common among the patients receiving OPAT included recent cardiac surgery (44.3%), heart failure (29%), severe aortic regurgitation (13.8%), and central nervous system emboli (8.4%).