Recent Research

Beta-blockers and mortality in afib and sepsis, corticosteroids in CAP, dual versus triple antiplatelet therapy, and more.


Lower mortality may be associated with beta-blockers versus other drugs in patients with afib and sepsis

For patients with atrial fibrillation and sepsis, beta-blockers may be associated with lower mortality than calcium-channel blockers, digoxin, or amiodarone, a recent study found.

The study examined current clinical practice patterns and compared the effectiveness of different treatment strategies for afib among a large cohort of patients hospitalized with sepsis. Results were published online on Aug. 13 by CHEST.

Using enhanced billing data from about 20% of U.S. hospitals, researchers retrospectively analyzed 39,693 patients with afib and sepsis who received intravenous rate or rhythm control to treat afib. They found that hospitals most commonly selected calcium channel-blockers as the initial afib treatment (14,202 patients [36%]), followed by beta-blockers (11,290 patients [28%]), digoxin (7,937 patients [20%]), and amiodarone (6,264 patients [16%]). In this cohort, 49% were women, 76% were white, and mean age was 77 years.

In propensity-matched analyses, researchers found beta-blockers to be associated with lower hospital mortality when compared with calcium-channel blockers (18,720 patients; relative risk, 0.92; 95% CI, 0.86 to 0.97), digoxin (13,994 patients; relative risk, 0.79; 95% CI, 0.75 to 0.85), and amiodarone (5,378 patients; relative risk, 0.64; 95% CI, 0.61 to 0.69). They found similar results among subgroups with new onset or pre-existing afib, heart failure, vasopressor-dependent shock, or hypertension.

Selection of afib treatment during sepsis varied because of hospital factors, such as geographic location, hospital teaching status, and physician specialty, as well as patient clinical characteristics, according to the study, and about 10% of this variation was unexplained. “Practice pattern variation in [afib] treatment selection suggests lack of a current ‘standard of care’ for treating [afib] during sepsis,” the study authors wrote.

The authors also listed limitations to their study, such as how they used enhanced administrative data that lacked detailed sequence of events from chart review. They also stated that their effect estimates could be influenced by unmeasured confounding by disease severity or unmeasured clinical factors. Given these and several more limitations, the authors wrote that their findings should be considered “hypothesis-generating” and support the need for future clinical trials to explore the optimal treatment of afib during sepsis.

Admission for suicidal behavior associated with suicide, all-cause mortality within a year

Patients who received more intensive treatment at the hospital after harming themselves were more likely to die within the next year, suggesting that clinicians were accurately identifying at-risk patients, a study found.

The prospective cohort study included 38,415 British patients seen at 5 emergency departments for self-harm between 2000 and 2010. Within a year of presentation, 0.7% had committed suicide and 2.2% had died from any cause. Researchers examined 4 management options for these patients—psychosocial assessment, medical admission, psychiatric admission, and referral for mental health follow-up—for any association with 1-year mortality rates. In adjusted numbers, psychiatric admission was associated with the highest risk of suicide (hazard ratio [HR], 2.35; 95% CI, 1.59 to 3.45) and all-cause mortality (HR, 2.35; 95% CI, 2.04 to 2.72).

Adjustment for variables including sex, age, method of self-harm, and history of self-harm or psychiatric treatment reduced the association between the interventions and mortality. After adjustment, the HR for all-cause mortality was 1.06 for psychosocial assessment, 1.29 for medical admission, 1.28 for mental health referral, and 0.88 for psychiatric admission. For suicide, the HRs were 1.35, 1.41, 1.48, and 1.12, respectively.

The unadjusted associations are reassuring, suggesting that hospital clinicians are directing the highest-risk patients to more intensive treatment, the study authors concluded. Also, the change in hazard ratios between unadjusted and adjusted all-cause mortality for psychiatric admissions (decreased from 2.35 to 0.88) could indicate a beneficial effect for these patients, but the finding should be interpreted with caution. The results were published in The Lancet Psychiatry on Aug. 6.

An accompanying comment offered suggestions on how to reduce postdischarge risk of suicide: “attention to general medical as well as psychiatric needs of patients following self-harm; enhanced communication among clinicians involved in a patient's current and future care; discharge with secure aftercare plan with specific appointments, and ideally, contact with the responsible aftercare clinicians before discharge; and involvement of social support by family members or friends.”

Corticosteroids may improve outcomes in inpatients with community-acquired pneumonia

Patients hospitalized with community-acquired pneumonia (CAP) may benefit from systemic corticosteroid therapy, according to a recent study.

Researchers performed a systematic review and meta-analysis to look at the effect of adjunctive corticosteroid therapy on the outcomes of mortality, morbidity, and duration of hospitalization in patients hospitalized with CAP. Randomized trials published through May 24, 2015, that randomly assigned adults with CAP to receive oral or IV corticosteroids compared with placebo or no treatment were included. Included studies also needed to report on at least 1 of the following: duration of hospitalization, time to clinical stability, all-cause mortality, need for mechanical ventilation, need for ICU admission, or development of acute respiratory distress syndrome (ARDS). The study was published online by Annals of Internal Medicine on Aug. 11.

Thirteen randomized, controlled trials were included in the analysis. Most patients were men in their early 60s. Most of the trials were conducted in Europe, and 1 of 13 was pharma-funded. Sample sizes ranged from 30 to 784 patients, while follow-up ranged from in-hospital to 60 days from trial enrollment. The researchers found with moderate certainly that use of adjunctive corticosteroids was associated with possible reductions in all-cause mortality (12 trials; 1,974 patients; risk ratio [RR], 0.67 [95% CI, 0.45 to 1.01]; risk difference [RD], 2.8%), need for mechanical ventilation (5 trials; 1,060 patients; RR, 0.45 [95% CI, 0.26 to 0.79]; RD, 5.0%), and ARDS (4 trials; 945 patients; RR, 0.24 [95% CI, 0.10 to 0.56]; RD, 6.2%).

In addition, such therapy appeared with high certainty to decrease time to clinical stability (5 trials; 1,180 patients; mean difference, −1.22 days [95% CI, −2.08 to −0.35 days]) and hospitalization duration (6 trials; 1,499 patients; mean difference, −1.00 day [95% CI, −1.79 to −0.21 days]). There was high certainty that hyperglycemia requiring treatment occurred more often when adjunctive corticosteroids were administered (6 trials; 1,534 patients; RR, 1.49 [95% CI, 1.01 to 2.19]; RD, 3.5%), but this relationship was not seen for gastrointestinal hemorrhage.

The authors noted that their study was not able to determine optimal agent and dose for corticosteroids, that their results do not apply to patients who were excluded from the analyzed trials (for example, pregnant patients), that their findings in outcomes with small event sizes (i.e., need for mechanical ventilation, ICU admission, and ARDS) should be interpreted with caution, and that publication bias could not be ruled out. However, they concluded that systemic corticosteroid therapy could reduce mortality by approximately 3%, mechanical ventilation by approximately 5%, and hospital stay by approximately 1 day in hospitalized patients with CAP.

“Larger pragmatic trials could improve certainty associated with several important outcomes, including mortality, need for mechanical ventilation, ARDS, gastrointestinal bleeding, and neuropsychiatric disturbance,” the authors wrote. “Decision makers should seriously consider the use of corticosteroids in patients hospitalized with CAP, particularly in those who are more severely affected.”

The authors of an accompanying editorial said they believed the current meta-analysis supported the use of corticosteroids in patients with CAP, and they advocated the use of biomarkers, such as C-reactive protein levels, to determine systemic inflammation. They called for future studies that would consider host inflammatory response, potential interactions between corticosteroids and other treatments (such as macrolides), and additional end points besides mortality, including clinical failure.

Dual antiplatelet therapy may be safer than triple therapy in older patients with acute MI, afib

Treatment with dual antiplatelet therapy (DAPT) appears to be safer than DAPT plus warfarin (triple therapy) in older patients with acute myocardial infarction (MI) and atrial fibrillation who underwent coronary stenting, according to a recent study.

Researchers used linked data from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get with the Guidelines and Medicare administrative claims to examine patients 65 years of age or older who had acute MI and afib and underwent percutaneous coronary intervention (PCI) with stenting. The goal of the study was to determine appropriate antithrombotic therapy in this population by comparing those taking DAPT with those taking triple therapy. Major cardiac events (MACE) at 2 years, defined as death or readmission for MI or stroke, was the primary effectiveness outcome, while readmission for bleeding was the primary safety outcome.

In addition, in a sensitivity analysis, the authors looked at data from a Medicare Part D prescription claims database to determine persistence of warfarin and P2Y12 inhibitors at 90 days after discharge, as well as warfarin initiation after discharge. The study results were published Aug. 11 by the Journal of the American College of Cardiology.

Of the 4,959 patients included in the study, 1,370 (27.6%) were discharged from the hospital on triple therapy and 3,589 (72.4%) were discharged on DAPT. Patients prescribed triple therapy at discharge were more likely to be men and to have a history of PCI or coronary artery bypass grafting, prior stroke, and recent afib or atrial flutter. In addition, they were often taking warfarin before admission. Patients discharged on DAPT, meanwhile, were more likely to have had a major bleeding event during their hospitalization.

Two years after discharge, unadjusted cumulative incidence rates of MACE were 32.6% in the triple therapy group and 32.7% in the DAPT group (P=0.99), and rates for individual MACE components were also similar between groups. The adjusted hazard ratio for MACE in those receiving triple therapy versus DAPT was 0.99 (95% CI, 0.86 to 1.16), but risks for bleeding and intracranial hemorrhage were significantly higher in the triple therapy group (adjusted hazard ratios, 1.61 [95% CI, 1.31 to 1.97] and 2.04 [95% CI, 1.25 to 3.34], respectively). Among the 1,591 patients in the sensitivity analysis who were covered by Medicare Part D, 442 (27.8%) were discharged on warfarin and 1,149 (72.2%) were discharged on DAPT only. At 90 days, 93.2% of those discharged on warfarin continued to take warfarin and 94.7% of those discharged on DAPT continued to take a P2Y12 inhibitor, according to prescription claims data.

The authors noted that their study was observational, that their primary analysis was intention-to-treat, and that they had no data on novel oral anticoagulants due to the study time frame, among other limitations. However, they concluded that older patients with acute MI and afib who have undergone PCI appear to have a higher risk for major bleeding, both early and long-term, with triple therapy versus DAPT.

The authors of an accompanying editorial comment noted that the study found a lack of association between triple therapy and MACE risk but a significant association between triple therapy and bleeding risk. “Although the question of whether triple therapy is beneficial for MACE remains troublingly uncertain, the data are convincing for bleeding,” the editorialists wrote. They noted that while the idea of less therapy has appeal, recent investigations have focused instead on which new agents can be incorporated into triple therapy.

“Thus, the clinical dilemma remains: what do we do with patients who have concurrent indications for [oral anticoagulation] and DAPT?” the editorialists asked. Although the data are not perfect, “they do paint a convincing picture of uncertain benefit for MACE and convincing harm with bleeding,” they wrote. “Can we replace ‘more’ with a better alternative? Unfortunately, the answer to date is ‘not yet.’”

Colchicine treatment associated with reduced inflammation after STEMI

Colchicine may provide anti-inflammatory benefits to patients with ST-elevation myocardial infarction (STEMI), a small pilot study found.

The study included 151 Greek patients who presented with STEMI, 12 hours or less from the onset of chest pain, between July 2013 and March 2015. In addition to standard treatment (including primary percutaneous coronary intervention), 77 of the patients were given colchicine (a loading dose of 1.5 mg followed by 0.5 mg 1 hour later and then 0.5 mg twice daily for 5 days) while the other 74 received a placebo on the same schedule. Results were published in Circulation on Aug. 11.

The primary outcome was area under the curve of creatine kinase-MB (CK-MB) concentration, which was 3,144 ng-hours/mL in the colchicine group, compared to 6,184 ng-hours/mL in the controls (P<0.001). Sixty patients also underwent cardiac magnetic resonance imaging with late gadolinium enhancement (MRI-LGE) 6 to 9 days after STEMI. In this subset, the indexed MRI-LGE-defined infarct size was smaller in the colchicine group than controls (18.3 mL/1.73 m2 vs. 23.2 mL/1.73 m2; P=0.019).

The groups also showed difference in markers of inflammatory response. The highest neutrophil count measured during hospitalization was 7,543 cells/µL in the colchicine group compared to 8,922 cells/µL in controls (P=0.008), and C-reactive protein levels showed a similar pattern (maximum of 42.9 mg/L in the colchicine group vs. 63.8 mg/L in controls; P=0.019). The study authors concluded that colchicine treatment in STEMI patients was associated with smaller infarct size, although they cautioned that “further clinical trials are necessary to draw secure conclusions, especially considering the fact that the present study was not powered to assess clinical endpoints.”

The observed effect is biologically plausible, since inflammation has been shown to be associated with adverse results of STEMI and colchicine is known to have anti-inflammatory properties. The drug has also been shown to be safe in cardiovascular disease, the authors noted. However, the study did find a wide distribution of infarct sizes among treated patients, which could suggest that colchicine's effects are heterogeneous or could result from study patients' premature discontinuation of the drug.

More hand-hygiene strategies produce better results for hospitals, review finds

Hand-hygiene interventions in hospitals effectively increase compliance in health care workers, and more intensive approaches make for better results, according to a recent analysis.

A systematic review of 41 relevant studies published from 1980 to 2014 analyzed myriad intervention approaches, which were mostly bundled interventions involving several components. The most common bundled intervention was WHO-5, a 2005 hand hygiene campaign by the World Health Organization, according to the study, published online on July 28 by The BMJ.

The WHO-5 involves 5 components: system change, education and training, feedback, workplace reminders, and institutional safety climate. The researchers used network meta-analysis to compare the effectiveness of 4 strategies: no promotion of hand hygiene, single-component interventions, WHO-5, and WHO-5 plus other components, such as incentives, goal setting, or accountability (WHO-5+). Reported costs of the interventions ranged from $225 to $4,669 per 1,000 bed-days, according to the study.

The likelihood that intervention strategies promoted hand hygiene increased with the number of interventions. Compared with no intervention, mean odds ratios for improved hand hygiene were 4.30 (95% credible interval [CrI], 0.43 to 46.57) for a single intervention (system change or education); 6.51 (95% CrI, 1.58 to 31.91) for WHO-5; and 11.83 (95% CrI, 2.67 to 53.79) for WHO-5+.

Although 19 studies reported clinical or microbiological outcomes along with the hand-hygiene outcomes, most had too many limitations, according to the review. However, the researchers were able to glean insight from a couple of single-center studies. One found that increased use of alcohol hand rub was associated with a reduced incidence of health care-associated infections (P≤0.001) and health care-associated methicillin-resistant Staphylococcus aureus (MRSA) infection (P=0.02). Another study linked use of 1 L of alcohol hand rub per 100 patient-days to a reduction in MRSA of 0.03 clinical isolates per 100 patient-days (P≤0.001).

More evidence is needed to link better hand hygiene with a reduction in health care-associated infections, the outcome that matters most, according to an accompanying editorial. And despite wide acknowledgement that appropriate hand hygiene protects patients and clinicians from these infections, adherence to guidelines is “unacceptably poor,” the editorialist wrote.

The study's authors noted several limitations, such as how details on intervention implementation varied substantially; how direct observation of compliance can induce an increase in compliance unrelated to the intervention (the Hawthorne effect); and how the novelty of an intervention can influence improvements.

More broad-spectrum antibiotics used for nosocomial pneumonia, with no clear match to pathogens

There was a substantial increase in use of broad-spectrum antibiotics in patients with health care-associated pneumonia (HCAP) from 2006 to 2010, without any apparent increase in infections due to the pathogens requiring these drugs, a study found.

In 2005, the Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) recommended empiric coverage of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. The recommendations were updated in 2007 to emphasize that patients with risk factors for HCAP should be treated with broad-spectrum antibiotics.

Amid concerns that the HCAP risk factors are too broad and are driving excessive antibiotic use, researchers looked at hospitalizations for pneumonia at Veterans Affairs medical centers. They calculated sensitivity, specificity, and diagnostic odds ratio (DOR) by measuring annual trends in antibiotic selection; initial blood or respiratory cultures positive for MRSA, Pseudomonas aeruginosa, and Acinetobacter species; and alignment between antibiotic coverage and culture results for MRSA and P. aeruginosa.

Results appeared online July 29 at Clinical Infectious Diseases. Of 2.4 million hospitalizations at 128 facilities, 95,511 hospitalizations (3.9%) were for pneumonia. The proportion of hospitalizations for pneumonia remained stable over time, in contrast to an increase in sepsis diagnoses, the study reported.

Initial use of vancomycin increased from 16% in 2006 to 31% in 2010, and piperacillin-tazobactam increased from 16% to 27%. Initial use of ceftriaxone decreased from 39% to 33%, and azithromycin decreased from 39% to 36%. Macrolides, of which 99.5% were azithromycin, decreased from 39.5% to 36.0%. These decreases were statistically significant (P≤0.001 for all comparisons).

The proportion of culture-positive MRSA hospitalizations decreased (2.5% to 2.0%, P<0.001). There was no change for P. aeruginosa (1.9% to 2.0%, P=0.14) or Acinetobacter species (0.2% to 0.2%, P=0.17). Sensitivity increased for MRSA and P. aeruginosa (46% to 65% and 54% to 63%, P<0.001) while specificity decreased (85% to 69% and 76% to 68%, P<0.001), with no significant changes in DOR (4.6 to 4.1 [P=0.57] and 3.7 to 3.2 [P=0.95], respectively).

Researchers suggested that the shift toward broad-spectrum antibiotics reflects a change in the threshold for treatment rather than a response to increased prevalence or ability to identify patients at risk for resistant organisms. They added that the guidelines drove increased recognition for HCAP risk factors and likely modified clinicians' perception of risk.

“Clinicians continue to be challenged by the dilemma of whether to use broad-spectrum antibiotics in the treatment of pneumonia,” researchers wrote. “Unnecessary use of broad-spectrum antibiotics carries substantial risk, both to the individual patient and to public health. So does under-treatment of resistant pathogens. Given the raised awareness of antimicrobial resistance brought forth by practice guidelines, it is not surprising that providers at the VA, as in other systems, have lowered their threshold since their dissemination. Our study suggests, however, that even with an increased caliber of the shotgun, we are still missing the mark.”

An editorial offered a take-home lesson for hospitals. “Each hospital needs to routinely look at their microbiology data and after discussion with all stakeholders, determine which patients should be treated with broad-spectrum antibiotics versus CAP-guideline concordant therapy. Without these discussions we will be facing even larger problems due to MDR [multidrug-resistant] infections in the future,” the editorial said.

Mortality, hospitalizations, and end-of-life care improving, Medicare analysis finds

Mortality and hospitalizations have been declining among Medicare beneficiaries, in part due to quality improvement efforts, a recent study found, while another highlighted flaws in CMS's effort to reduce hospital-acquired conditions.

The first study was a cross-sectional analysis of 68 million Medicare beneficiaries age 65 years and over between 1999 and 2013. Their rate of all-cause mortality dropped from 5.30% in 1999 to 4.45% in 2013 (difference, 0.85 percentage points; 95% CI, 0.83 to 0.87). The researchers found other improvements among the 60 million fee-for-service beneficiaries (on whom more data were available): Hospitalizations dropped from 35,274 per 100,000 person-years to 26,930 per 100,000 person-years, and inpatient spending per beneficiary dropped from $3,290 to $2,801.

The study also looked at hospitalizations in the last 6 months of life and found that they dropped from 131.1 per 100 deaths to 102.9 per 100 deaths, with 56.8% of these patients at the end of life having at least 1 hospitalization in 2013 compared to 70.5% in 1999. Inflation-adjusted inpatient expenditure per death was $15,312 in 1999, $17,423 in 2009, and $13,388 in 2013. These findings may be due to increasing recognition of the importance of hospice and patient-centered care at the end of life, the study authors said.

There are a number of possible explanations for the drop in mortality and hospitalizations, including national quality improvement initiatives and process measures, the authors said. Increases in exercise and decreases in smoking could also have contributed, as well as medical advances, including targeted cancer therapies, statins, and coronary revascularization. Shifting of care to the outpatient setting could also have contributed to the reduction in hospitalizations, although it does not appear to be entirely responsible, the authors said.

The other study compared hospital characteristics with penalties issued by CMS under the fiscal year 2015 Hospital-Acquired Condition (HAC) Reduction Program. Twenty-two percent of the 3,284 participating hospitals were penalized, and they were more likely to be hospitals accredited by The Joint Commission, major teaching institutions, and safety-net hospitals and to have higher severity case-mixes compared with those that weren't penalized. Researchers also created a hospital quality score (based on volume, accreditations, and offering of advanced care services) and found that 67.3% of the highest-scoring hospitals faced HAC penalties compared to 12.6% of the lowest-scoring ones (P<0.001 for trend).

“These paradoxical findings suggest that the approach for assessing hospital penalties in the HAC Reduction Program merits reconsideration to ensure it is achieving the intended goals,” the authors said. Possible explanations for the findings include surveillance bias, inadequate risk adjustment, and aspects of the measurement system that benefit smaller hospitals, they noted, recommending that the HAC penalties be revised to target hospitals with higher than expected adverse event rates rather than those in the bottom quartile.

Both studies were published in the July 28 Journal of the American Medical Association.