Recent Research

Nonprofit versus for-profit hospitals, corticosteroids in septic shock, pretreatment with P2Y12 inhibitors, and more.

Conversion to for-profit affects a hospital's bottom line, but not care

Hospitals that converted from nonprofit to for-profit between 2003 and 2010 improved their financial margins without any apparent effects on the care they provided, a recent study found.

The retrospective cohort study included 237 hospitals that converted to for-profit (and over a million of their Medicare patients) compared with 631 matched control hospitals (with over 4 million Medicare patients). The hospitals were compared on financial performance measures, quality process measures, mortality rates, Medicare volume, and patient population in the 2 years prior to conversion and 2 years after, with the conversion year excluded. Results were published in the Oct. 22/29, 2014, Journal of the American Medical Association.

Before conversion, the hospitals that would convert had lower total margins than the nonconverting hospitals (−1.2% vs. 1.7%). They were also more likely to be small or medium in size, to be located in the South, to be in an urban or suburban location, and to be a nonteaching institution. After conversion, they improved their margins more than controls (2.2% improvement vs. 0.4%; P=0.007). Over the course of the study, both groups of hospitals improved their process quality metrics by similar amounts. The converting hospitals were also similar to controls in their trends in mortality rates, annual Medicare volume, Disproportionate Share Hospital Index, and proportions of patients who were on Medicaid or black or Hispanic.

Because there were no significant differences in all of the studied markers, it's unclear how the converting hospitals were able to improve their finances, the study authors said. Possibilities include cutting costs or getting better payments from private payers. Similar studies conducted in the 1990s found that converting hospitals did change in their quality of care and patient makeup. The lack of difference found in this study may be a result of more rewarding and publicizing of quality or increased regulatory attention in recent years, the authors speculated.

An accompanying editorial suggested another explanation for the improved finances of the converting hospitals: Costs, such as debt, may have been shifted from the hospital to another level in the organization. The results of the study can be taken as a reassuring sign that conversion to for-profit status doesn't harm care or as a bad sign that improving a hospital's financial performance does not improve its outcomes, the editorialist noted.

Corticosteroids associated with survival only in sickest septic shock patients

Low-dose corticosteroids may have improved mortality in the sickest septic shock patients but didn't help and may have harmed less sick patients, a recent study found.

The retrospective study included 6,663 patients with septic shock treated at 28 ICUs in the United States, Canada, and Saudi Arabia between 1996 and 2007. Intravenous, low-dose corticosteroid treatment was provided to 1,838 patients within 48 hours of diagnosis, and their outcomes were compared to a matched group of patients who did not receive corticosteroids. Results were published in the November 2014 Critical Care Medicine.

Overall, the patients had similar 30-day mortality rates: 35.5% in the steroid group versus 34.9% in controls. But the subgroup of patients with an Acute Physiology and Chronic Health Evaluation (APACHE) II score of 30 or more had lower mortality associated with steroid use: 50.6% versus 55.8% (hazard ratio, 0.81; P=0.02). In patients with an APACHE II score of 24 or lower, there was a nonsignificant trend toward higher ICU, hospital, and 30-day mortality with steroids. In the patients as a whole, steroid therapy wasn't associated with any significant difference in ICU or hospital mortality or time on the ventilator or pressors.

It's uncertain why sicker patients would disproportionately benefit from corticosteroids, the study authors said. The results suggest that future randomized trials of low-dose corticosteroids for septic shock should focus on this patient group, they concluded. The study should only be considered hypothesis-generating, because it was limited by its retrospective nature, particularly the attempt to avoid survival bias by excluding patients who died within 48 hours of diagnosis.

The study is part of yet another pendulum swing in expert thinking about corticosteroids for sepsis, according to an accompanying editorial. It confirms some interpretations of the most recent large randomized trials that sicker patients may benefit from corticosteroid therapy while no overall effect is seen. Now the key challenge is to identify which sepsis patients would benefit from corticosteroids and when, the editorialist concluded.

Pretreatment with P2Y12 receptor inhibitors does not appear beneficial in non-ST elevation ACS

Patients with non-ST elevation acute coronary syndrome (ACS) do not appear to benefit from pretreatment with P2Y12 inhibitors, according to a recent study.

Researchers performed a systematic review and meta-analysis of randomized, placebo-controlled trials and observational studies published from August 2001 to March 2014 to compare the effect of P2Y12 pretreatment and no pretreatment on the safety and efficacy of treatment for non-ST elevation ACS. Studies were included if more than 50% of patients had non-ST elevation ACS and if both all-cause mortality and major bleeding were reported. Data were analyzed in a random-effect model that examined all patients regardless of their management strategy as well as only patients who had percutaneous coronary intervention (PCI). The study results were published online Oct. 24, 2014, by The BMJ.

A total of 7 studies met the inclusion criteria: 4 randomized, controlled trials, 1 observational analysis from a randomized, controlled trial, and 3 observational studies. All of the studies examined thienopyridines (clopidogrel in 6 studies and prasugrel in 1 study). Overall, 32,283 patients with non-ST elevation ACS were included, and of these, 18,711 were from randomized, controlled trials. Fifty-five percent of patients had PCI.

Pretreatment with a P2Y12 inhibitor did not appear to be associated with a significantly lower risk for death among all patients (odds ratio, 0.90; 95% CI, 0.75 to 1.07; P=0.24) or among patients from randomized, controlled trials (odds ratio, 0.90; 95% CI, 0.71 to 1.14; P=0.39). Findings were similar in the subgroup of patients who had PCI. A significantly elevated risk for major bleeding was seen with a P2Y12 inhibitor in all patients, in patients undergoing PCI, and in patients from randomized, controlled trials. The analysis of all patients found a reduction in major adverse cardiovascular events, due mainly to 2 older studies of clopidogrel, but no significant difference in risk for such events was seen in PCI patients.

The authors noted that they did not analyze individual-patient data and that confounding by indication could not be ruled out, among other limitations. However, they concluded that according to their findings, pretreatment with thienopyridines in patients with non-ST elevation ACS does not appear to decrease mortality risk. “The reduction of ischemic endpoints is modest and counterbalanced by an increase in major bleeding, no matter the final management strategy with or without PCI,” they wrote. “The concept of systematic and immediate pretreatment with P2Y12 antagonists in patients admitted with non-ST elevation ACS needs to be reconsidered.”

Lowering blood pressure doesn't appear to improve outcome immediately after acute stroke

Lowering blood pressure in the first few days after an acute stroke does not appear to improve functional outcome, according to a recent study.

Researchers performed a multicenter, partial-factorial trial to examine outcomes in patients who received medications to lower blood pressure after an acute stroke. Patients who were admitted to the hospital with acute ischemic or hemorrhagic stroke and elevated systolic blood pressure, defined as 140 to 220 mm Hg, were randomly assigned to receive 7 days of transdermal glyceryl trinitrate, 5 mg/d, begun within 48 hours of stroke onset, or no transdermal glyceryl trinitrate. In addition, a subset of patients who had been taking antihypertensive drugs before they had their stroke was also randomly assigned to continue them or stop them. The study's primary outcome was patients' function at 90 days as assessed by the modified Rankin Scale.

Results were published online Oct. 22, 2014, by Lancet.

A total of 4,011 patients were enrolled in the study from July 20, 2001, to Oct. 14, 2013, 2,000 in the transdermal glyceryl trinitrate group and 2,011 in the control group. Patients were enrolled at 173 sites in 23 countries. Of the 4,011 patients, 2,097 were already taking antihypertensive drugs; 1,053 patients were assigned to continue them, and 1,044 were assigned to stop them.

Patients' mean blood pressure was 167 mm Hg/90 mm Hg at baseline and was significantly lower on hospital day 1 in the intervention group compared with the control group (difference, −7.0 mm Hg/−3.5 mm Hg; P<0.0001 for both). Mean blood pressure was also significantly lower on day 7 in the patients who continued their antihypertensive medications than in those who stopped them (difference, −9.5 mm Hg/−5.0 mm Hg; P<0.0001 for both). Despite differences in blood pressure, however, functional outcome at day 90 showed no significant differences for either of the comparisons (adjusted common odds ratio, 1.01 for worse outcome in the treatment versus the comparison group [P=0.83] and 1.05 [P=0.55] for continuing versus stopping antihypertensive drugs).

The authors noted that because manufacturers could not supply placebo patches, glyceryl trinitrate was administered in a single-blind manner. In addition, they pointed out that the trial began before such interventions as stroke units, thrombolytic agents, and statins were more available and that some patients may have been taking antihypertensive drugs for reasons besides lowering blood pressure, among other limitations. However, they concluded that their trial showed no benefit to lowering blood pressure with glyceryl trinitrate in patients with elevated blood pressure after an acute stroke and offered no evidence for continuing prestroke antihypertensive drugs after hospital admission.

“The main implication for practice is that it seems reasonable to withhold blood pressure-lowering drugs until patients with an acute stroke are medically and neurologically stable, and have suitable oral or enteral access to allow safe drug reintroduction,” the authors wrote. “Nevertheless, post-acute blood pressure control is important to reduce the risk of subsequent vascular events and drugs will need to be restarted.”

3-minute assessment for CAM-defined delirium may improve diagnosis

A 3-minute assessment for delirium as defined by the Confusion Assessment Method (CAM) may help improve recognition of the disorder, according to a recent study.

Researchers derived the assessment, called 3D-CAM, by identifying 20 items that best operationalized the 4 diagnostic features of CAM. For prospective validation, trained research assistants at 4 general medicine units administered 3D-CAM assessments to 201 inpatients 75 years of age or older. Clinicians independently performed extensive assessments that included interviews with patients and families and medical record reviews. An expert panel then examined these data to determine the presence or absence of delirium and dementia; this was the reference standard. The researchers compared the 3D-CAM diagnosis of delirium with the reference standard for all patients and for patients with and without dementia. Results appeared in the Oct. 21, 2014, Annals of Internal Medicine.

Patients in the prospective validation study had a mean age of 84 years, and 28% had dementia at baseline, according to the expert panel. The reference standard assessment found that 21% of patients had delirium, and of these, 88% had hypoactive or normal psychomotor features. The median time to administer the 3D-CAM was 3 minutes (interquartile range, 2 to 5 minutes).

Twenty-four percent of patients were found to have delirium, according to the 3D-CAM. The 3D-CAM had a sensitivity of 95% (95% CI, 84% to 99%) and a specificity of 94% (95% CI, 90% to 97%) in all patients and also performed well in subgroups of patients with and without dementia (sensitivity, 96% [95% CI, 82% to 100%] and 93% [95% CI, 66% to 100%], respectively; specificity, 86% [95% CI, 67% to 96%] and 96% [95% CI, 91% to 99%], respectively).

The authors noted that the study was performed in only 1 medical center in only medical patients and was based on a single hospital day. However, they concluded that the 3D-CAM was “a brief, highly reproducible, and valid method for diagnosing delirium using the CAM algorithm,” with high sensitivity and specificity compared to the reference standard. “Given these characteristics, the 3D-CAM could be an important component of future efforts to improve systematic case-finding of delirium in high-risk older adults,” the authors wrote. “Further research will focus on developing the optimal strategies for translating the 3D-CAM into routine care and determining whether improved detection of delirium can result in improved outcomes for vulnerable hospitalized older persons.”

Transfusion at lower hemoglobin threshold appears as safe as higher threshold for septic shock patients

Septic shock patients who underwent transfusion at a lower hemoglobin threshold received fewer transfusions and had similar mortality at 90 days as those who underwent transfusion at a higher threshold, a recent study found.

Researchers randomized 998 patients with septic shock and a hemoglobin concentration of 9 g/dL or less to receive 1 unit of leukoreduced cells at 1 of 2 thresholds. At the lower threshold, the patient's hemoglobin level was 7 g/dL or less; at the higher threshold, the hemoglobin level was 9 g/dL or less. Patients came from 32 general ICUs in Denmark, Sweden, Norway, and Finland and underwent randomization between Dec. 3, 2011, and Dec. 26, 2013. The main outcome was death by 90 days after randomization. Secondary outcomes included use of life support, serious adverse reactions in the ICU, and ischemic events. Results were published in the Oct. 9, 2014, New England Journal of Medicine.

A total of 1,545 blood transfusions were given in the lower-threshold group compared to 3,088 transfusions in the higher-threshold group (P<0.001). The median cumulative number of transfusions after randomization was 1 unit in the lower-threshold group versus 4 in the other (P<0.001). While 36% of patients in the lower-threshold group had no transfusion in the ICU, only 1.2% of the higher-threshold group had no transfusion (P<0.001). At 90 days, death rates between groups didn't differ (43% in the lower-threshold group vs. 45% in the higher-threshold group, P=0.44). The numbers of patients who required life support or had severe adverse reactions or ischemic events were similar in the 2 intervention groups.

Similar results were seen in subgroups of patients who were older, had greater disease severity, and/or had chronic cardiovascular disease, the researchers noted. Patients with acute myocardial infarction were excluded from this trial, they warned, so research is still needed to assess the safety of lower hemoglobin thresholds for transfusion in this patient subgroup. Study limitations include that the researchers and patients weren't blind to their group assignments and that the trial had limited power to detect differences in certain subgroup analyses and secondary outcomes. Strengths are that the results are generalizable because patients were recruited from academic and community hospitals, most patients who were screened were included, and routine practice was maintained other than the hemoglobin thresholds for transfusion, they wrote.

Early goal-directed therapy didn't reduce death compared to usual care for ED patients with early septic shock

Providing early goal-directed therapy (EGDT) to ED patients with early septic shock didn't reduce 90-day mortality compared to usual care, a recent study found.

Researchers randomly assigned 1,600 patients treated between 2008 and 2014 at 51 centers—mostly in Australia and New Zealand—to receive either EGDT or usual care for 6 hours. Patients presented to the ED with suspected or confirmed infection, 2 or more criteria for a systemic inflammatory response, and evidence of refractory hypotension or hypoperfusion (lactate ≥4). Patients in the usual care group had treatment decisions made by their clinical team. EGDT patient care was provided by a study team trained in EGDT delivery, with resuscitation following the original EGDT algorithm and a central venous catheter capable of continuous SCVO2 measurement inserted within an hour after randomization. The main outcome was all-cause death within 90 days of randomization.

Patients in the EGDT group received a larger mean volume of IV fluids in the first 6 hours after randomization than the usual care group (1,964 mL vs. 1,713 mL) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusion (13.6% vs. 7%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all). At 90 days, the death rates didn't differ significantly between groups (18.6% in the EGDT group vs. 18.8% in the usual care group). There were also no significant differences in 28-day or in-hospital mortality, duration of organ support, or length of hospital stay between groups. Results were published in the Oct. 16, 2014, New England Journal of Medicine.

Adherence to the EGDT algorithm therapies was high among clinicians, the researchers noted, and the potential confounder of time to administration of antimicrobials was addressed in advance by requiring that all such drugs be administered before randomization. “There was no trend suggesting an effect of EGDT in any unadjusted or adjusted estimates of mortality, and subgroup analyses did not indicate that the benefit from EGDT increased with the severity of illness,” they wrote. “Our findings suggest that the value of incorporating EGDT into international guidelines as a standard of care is questionable.”

Postop antibiotics may not be needed for cholecystectomy patients with acute calculous cholecystitis

Postoperative antibiotics don't appear to lower the rate of infection in patients who undergo cholecystectomy for acute calculous cholecystitis, a recent study found.

Researchers randomly assigned 414 patients who had mild or moderate acute calculous cholecystitis to either continue their preoperative antibiotic regimen or to receive no antibiotics after cholecystectomy. The antibiotic regimen was 2 grams of amoxicillin plus clavulanic acid 3 times a day for 5 days. The main outcomes were the proportion of patients who developed postoperative surgical site or distant site infections within 4 weeks of surgery. The study was conducted between May 2010 and August 2012 at 17 French medical centers. Results were published in the July 9, 2014, Journal of the American Medical Association.

Using imputed intention-to-treat analysis, postop infection rates were 17% in the nontreatment group (n=35) and 15% in the treatment group (n=31), for an absolute difference of 1.93% (95% confidence interval [CI], −8.98% to 5.12%). Using the noninferiority margin of 11% established for the trial, the researchers concluded that no postoperative antibiotic treatment was not associated with worse outcomes compared to antibiotic treatment. In per protocol analysis of 338 patients, both groups had a postop infection rate of 13%. Length of stay and readmission rates were similar between the 2 groups.

The Infectious Diseases Society of America and other groups recommend treating patients with amoxicillin plus clavulanic acid or sulbactam after cholecystectomy for noncomplicated acute calculous cholecystitis, but this study found no benefit to doing so, the authors noted. Indeed, reducing unnecessary antibiotic use will save money and help lower antibiotic resistance. “In 2010, 37,499 cholecystectomies for acute calculous cholecystitis were performed in France, and 90 percent of these were for grades I and II [mild or moderate] acute calculous cholecystitis. Supposing that these patients did not really need postoperative antibiotics (which are generally prescribed for 5 days), we estimate that many days of antibiotic treatment could be avoided each year,” the authors wrote.

An editorialist noted that the study was limited in that it lacked blinding but added that the researchers took other steps to minimize bias. He concluded that the results support not administering postoperative antibiotics to this patient population.

Early hospital-initiated rehab for chronic respiratory disease shows no benefit versus usual care

Patients hospitalized for chronic respiratory disease did not appear to benefit from early rehab started during their hospital stay versus usual care, according to a recent study.

Researchers at 2 affiliated teaching hospitals in the United Kingdom performed a prospective, randomized, controlled trial to determine whether early rehab during acute admission for chronic respiratory disease exacerbations would improve outcomes and reduce risk for readmission. Patients with an exacerbation of chronic respiratory disease were assigned within 48 hours of hospital admission to receive early rehab or usual care. Early rehab involved a 6-week intervention that included prescribed aerobic, resistance, and neuromuscular electrical stimulation training, along with information on self-management and education. Usual care included physiotherapy (airway clearance, mobility assessment and supervision, and smoking cessation advice) and nutritional status assessment, along with outpatient pulmonary rehab offered 3 months after hospital discharge. The study's primary outcome measure was readmission rate at 12 months; secondary outcome measures were number of hospital days, mortality rate, physical performance, and health status. The study results were published online by The BMJ on July 8, 2014.

One hundred ninety-six patients were assigned to the early rehab group, and 193 were assigned to the usual care group. Mean age was approximately 71 years, and 45% and 44% of patients in each group, respectively, were men. Most of the patients (82%) had chronic obstructive pulmonary disease as their primary diagnosis. A total of 233 patients (60%) had at least 1 readmission in the year after their index admission, 62% of the early rehab group (122 of 196 patients) and 58% of the usual care group (111 of 193 patients), with no significant between-group difference (hazard ratio, 1.1; 95% CI, 0.86 to 1.43; P=0.4). Mortality rate appeared to increase in the intervention group at 1 year (odds ratio, 1.74; 95% CI, 1.05 to 2.88; P=0.03). Both groups demonstrated significant improvement in physical performance and health status after hospital discharge, and no significant between-group difference in these outcomes was noted at 1 year.

The authors noted that they included patients with various chronic respiratory diseases and that their results apply only to patients with fewer than 5 hospital admissions in the previous 12 months. However, they concluded that early rehab during hospital admission for acute exacerbation of chronic respiratory disease does not reduce readmission risk or improve physical outcomes over the next year compared with usual care. “The lack of impact on physical function and readmissions and the observation of an increased mortality at 12 months in the intervention group indicate caution before implementing such programmes during the immediate recovery from acute illness,” the authors wrote.