Laine J. Murphey, MD, PhD

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Healthcare-associated infections financially impact the U.S. system
2. No mortality benefit with treatment of single peripheral pulmonary emboli
3. Modified (shorter) IV acetylcysteine infusion reduces adverse effects
4. Comorbidities contribute to potentially avoidable hospital readmissions
5. Resident handoff bundle reduces medical errors and adverse events, improves handoff quality
6. Uncomplicated skin infections in the ambulatory setting commonly involve avoidable antibiotic exposure
7. Warfarin initiation in atrial fibrillation associated with increased short-term risk of stroke
8. Multifaceted discharge interventions reduce rates of pediatric readmission and post-hospital ED utilization
9. Sepsis diagnoses are common, but many septic patients in ED do not receive antibiotics
10. New oral anticoagulants safe, effective for atrial fibrillation treatment

Healthcare-Associated Infections Continue to Impact the U.S. Healthcare System Financially

Clinical question: What is the estimated cost of healthcare-associated infections (HAI) to the U.S. healthcare system?

Background: In spite of education efforts, HAIs occur frequently and contribute to high healthcare costs in the U.S. This study sought to estimate the costs of HAIs to the U.S. system using statistical analyses of published data.

Study design: Simulations of published data.

Setting: Published studies on five major HAIs.

Synopsis: Monte Carlo simulations based upon published point estimates were used to estimate per-case cost and confidence intervals, with extrapolation to total costs to the U.S. healthcare system. Overall, five major HAIs occur approximately 440,000 times annually and cost the healthcare system an estimated $9.78 billion (range $8.28 to $11.5 billion) in 2009.

Surgical site infections (36.0%) were the most common of the studied HAIs, with increased per-case cost of $20,785, equating to an estimated $3.30 billion annually (33.7% of total HAI costs). Clostridium difficile infection accounted for 30.3% of HAI but only 15.4% of costs ($1.51 billion). Central line-associated bloodstream infections were most costly per case ($45,814), with total costs of $1.85 billion (18.9% of costs). Ventilator-associated pneumonia accounted for $3.09 billion, or 31.7% of total costs. Catheter-associated urinary tract infection only represented 0.3% of total costs, or $27.9 million annually.

The authors suggest that changes in payment reform likely will drive hospitals to further invest in HAI reduction efforts.

Bottom line: HAIs remain frequent and expensive complications of hospitalization, in spite of improvement efforts to date.

Citation: Zimlichman E, Henderson D, Tamir O, et al. Health care-associated infections: a meta-analysis of costs and financial impact on the US health care system. JAMA Intern Med. 2013;173(22):2039-2046.

No Mortality Benefit with Treatment of Single Peripheral Pulmonary Emboli

Clinical question: Does treatment of single peripheral pulmonary emboli impact mortality and rates of post-discharge venous thromboembolism (VTE)?

Background: With the increase in CT pulmonary angiography (CTPA) use the past decade, there has been an increased rate of detection of peripheral filling defects. When confronted with a single peripheral filling defect (SPFD), clinicians face the dilemma of whether treatment is necessary, given the risks associated with anticoagulation.

Study design: Retrospective cohort.

Setting: Community teaching hospital in Norwalk, Conn.

Synopsis: A total of 4,906 CTPAs were screened, revealing 153 scans with an SPFD. Primary analysis included 134 patients 18 years or older. Of these patients, 61 (45.5%) received treatment with anticoagulation (n=51) or IVC filter alone (n=10).

This study revealed no difference in adjusted 90-day mortality between treated and untreated groups. No statistically significant difference was found in the rate of post-discharge VTE within 90 days.

Characteristics associated with treatment for SPFD were patient immobility, previous VTE, and radiology labeling the filling defect as a pulmonary embolus. It is important to note that none of the patients who had a normal second imaging study (e.g. V/Q scan or ultrasound) were treated; therefore, the use of secondary studies could mitigate some of the uncertainty around SPFD management, though this is not recommended in current diagnostic algorithms. Because this is a single-center study with a modest sample size, the comparability of findings to other centers might be limited. Larger studies are needed to help clarify these findings.

Bottom line: Treatment of SPFD was not associated with a difference in mortality or post-discharge VTE within 90 days.

Citation: Green O, Lempel J, Kolodziej A, et al. Treatment of single peripheral pulmonary emboli: patient outcomes and factors associated with decision to treat. J Hosp Med. 2014;9(1):42-47.

Modified IV Acetylcysteine Infusion Reduces Adverse Effects

Clinical question: Does a shorter regimen of IV acetylcysteine reduce adverse effects compared to the standard regimen?

Background: Acetaminophen poisoning is common, and recommended treatment is IV acetylcysteine; however, the standard regimen has many adverse effects, including vomiting and anaphylactoid reactions. Although studies have outlined these side effects, no published trials have compared their frequency to that of a shorter protocol.

Study design: Double-blinded, randomized controlled trial.

Setting: Three acute care hospitals in the United Kingdom.

Synopsis: Of 3,311 patients who presented with acetaminophen overdose, 222 underwent randomization to the standard (duration 20-25 hours) or modified (12 hours) acetylcysteine regimen, with or without pre-treatment with IV ondansetron 4 mg. The primary outcome of vomiting, retching, or need for rescue antiemetic treatment within two hours of acetylcysteine initiation was significantly less frequent in patients who received the shorter regimen, compared to those allocated to the standard regimen.

Specifically, the adjusted odds ratio was 0.26 with the modified regimen (97.5% CI, 0.13-0.52; P<0.0001). The primary outcome was significantly less in patients pre-treated with ondansetron compared to placebo (OR 0.41, 97.5% CI 0.2-0.8; P=0.003). Anaphylactic reactions were significantly reduced with the shorter protocol; no significant difference in hepatotoxicity was noted.

It is reasonable to infer that the shorter acetylcysteine regimen substantially reduces the frequency of vomiting and serious anaphylactoid reactions when compared with the standard schedule; however, hospitalists should note that this study was not powered to assess for non-inferiority of the shorter regimen with regard to prevention of acetaminophen’s hepatotoxic effects. Further studies are needed to confirm the efficacy and safety of the modified regimen before widespread adoption into clinical practice.

Bottom line: A shorter acetylcysteine regimen is associated with decreased occurrence of vomiting and anaphylactoid reactions compared to the standard protocol for treating acetaminophen toxicity. Additional research is needed to assess non-inferiority of this modified regimen for prevention of hepatotoxic effects.

Citation: Bateman DN, Dear JW, Thanacoody HK, et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomized controlled trial. Lancet. 2014;383(9918):697-704.

Comorbidities Contribute to Potentially Avoidable Hospital Readmissions

Clinical question: What is the role of comorbidities in 30-day potentially avoidable readmissions?

Background: Higher comorbidity burden has been associated with 30-day readmissions. This study evaluated the role of comorbidities in the 30-day rate of potentially avoidable readmissions from a tertiary-care medical center.

Study design: Retrospective cohort.

Setting: Tertiary-care teaching hospital and affiliated network.

Synopsis: Investigators tested the hypothesis that comorbidities significantly contribute to 30-day, potentially avoidable readmissions in a cohort of consecutively discharged medical patients at an academic medical center over a 12-month period. Out of a total of 10,731 discharges, there were 2,398 readmissions to hospitals in the same health system. Of those 2,398 readmissions, 858 (35.8%) were judged potentially avoidable using a validated algorithm. Frequently, the reason for readmission was not related to the index discharge diagnosis but to a complication of known comorbidities.

The authors identified the top five diagnoses for readmission as infection, neoplasm, heart failure, gastrointestinal disorder, and liver disorder. Among those patients who had a readmission diagnosis different from the index-case discharge diagnosis, the comorbidities of neoplastic disease, heart failure, and chronic kidney disease significantly contributed to readmission as compared to those without similar comorbidities.

Bottom line: The reason for readmission often is not related to the index hospitalization diagnosis but, rather, to comorbidities present at the index episode of care; thus, attention to management of comorbidities in the post-discharge period is important in circumventing potentially avoidable readmissions.

Citation: Donzé J, Lipsitz S, Bates DW, Schnipper JL. Causes and patterns of readmissions in patients with common comorbidities: retrospective cohort study. BMJ. 2013;347:F7171.

Resident Handoff Bundle Reduces Medical Errors and Adverse Events, Improves Handoff Quality

Clinical question: In a pediatric inpatient setting, is the use of a handoff program associated with improved patient safety measures and handoff quality?

Background: Sentinel events related to errors in communication are a significant patient safety dilemma and an impetus for ongoing efforts to improve handoffs in postgraduate medical education. Various strategies to be incorporated into the handoff process have been suggested in the literature, but research is limited with regard to the relationship between handoffs and patient safety.

Study design: Prospective, pre-post study.

Setting: Academic, pediatric hospital in an urban setting.

Synopsis: Overall, 1,255 patient admissions (642 pre-/613 post-handoff intervention) were evaluated on two inpatient units during the periods of July 2009-September 2009 (pre-intervention) and November 2009-January 2010 (post-intervention). The intervention was a handoff “bundle” consisting of a standardized communication and handoff training session, a verbal mnemonic to standardize handoffs, and a new unified resident-intern handoff structure in a private, quiet setting. A computerized handoff tool was also added in one unit. Primary outcomes were a comparison of the rate of medical errors per 100 admissions and rates of preventable adverse events before and after the intervention.

Implementation of the bundle resulted in a significant decrease in medical errors (18.3 from 33.8 per 100 admissions, P<0.001) and preventable adverse events (1.5 from 3.3 per 100 admissions, P=0.04). Secondary outcomes included reductions in omissions of key data in the written handoff (even greater in the group using the computerized tool) and increased percentage of time spent in direct patient care, with no change in handoff duration. Additionally, handoffs were more likely to occur in a quiet, private location.

Limitations included the potential for confounding in a pre-post intervention design, the difficulty in ascertaining the value of the individual components of the bundle, and the potential lack of generalizability.

Bottom line: In a pediatric hospital setting, a multifaceted handoff bundle is associated with improved handoff quality and reductions in medical errors and preventable adverse events.

Citation: Starmer AJ, Sectish TC, Simon DW, et al. Rates of medical errors and preventable adverse events among hospitalized children following implementation of a resident handoff bundle. JAMA. 2013;310(21):2262-2270.

Uncomplicated Skin Infections in Ambulatory Setting Commonly Involve Avoidable Antibiotic Exposure

Clinical question: What are the current prescribing practices for antibiotics used to treat skin and soft tissue infections in the outpatient setting?

Background: Uncomplicated skin and soft tissue infections are among the most frequent indications for outpatient antibiotic use. Because antibiotic use is associated with bacterial resistance and adverse events, understanding antibiotic prescribing practices is necessary to minimize these types of complications.

Study design: Retrospective cohort.

Setting: Ambulatory care setting in the Denver Health System.

Synopsis: Data from 364 adults and children who presented to an ambulatory setting with a primary diagnosis of skin and soft tissue infection were analyzed using a stepwise multivariate logistic regression in order to determine factors associated with avoidable antibiotic exposure. Among cellulitis cases, 61% of patients were prescribed antibiotics to treat methicillin-resistant Staphylococcus aureus. Avoidable antibiotic exposure occurred in 46% of cases, including use of antibiotics with broad Gram-negative activity (4%), combination therapy (12%), and treatment for ≥10 days (42%). Use of short-course, single-antibiotic treatment approaches consistent with national guidelines would have reduced prescribed antibiotic days by 19%, to 55%.

Bottom line: Avoidable antibiotic exposure frequently occurs in the treatment of uncomplicated skin infections; using short-course, single-antibiotic treatment strategies could significantly reduce total antibiotic use.

Citation: Hurley HJ, Knepper BC, Price CS, Mehler PS, Burman WJ, Jenkins TC. Avoidable antibiotic exposure for uncomplicated skin and soft tissue infections in the ambulatory care setting. Am J Med. 2013;126(12):1099-1106.

Warfarin Initiation in Atrial Fibrillation Associated with Increased Short-Term Risk of Stroke

Clinical question: Is the initiation of warfarin associated with an increased risk of ischemic stroke in patients with atrial fibrillation (Afib)?

Background: Two Afib trials of oral factor Xa inhibitors showed an increased risk of stroke when patients were transitioned to open label warfarin at the end of the study. Warfarin can, theoretically, lead to a transient hypercoagulable state upon treatment initiation, so further study is indicated to determine if the initiation of warfarin is associated with increased stroke risk among Afib patients.

Study design: Population-based, nested case-control.

Setting: UK Clinical Practice Research Datalink.

Synopsis: A cohort of 70,766 patients with newly diagnosed Afib was identified from a large primary care database. Conditional logistic regression was used to estimate adjusted rate ratios (RR) of stroke associated with warfarin monotherapy, classified according to time since initiation of treatment when compared to patients not on antithrombotic therapy.

Warfarin was associated with a 71% increased risk of stroke in the first 30 days of use (RR 1.71, 95% CI 1.39-2.12). Risk was highest in the first week of warfarin treatment, which is consistent with the known transient pro-coagulant effect of warfarin. Decreased risks were observed with warfarin initiation >30 days before the ischemic event (31-90 days: RR 0.50, 95% CI 0.34-0.75; >90 days: RR 0.55, 95% CI 0.50-0.61).

Limitations included the extraction of data from a database, which could lead to misclassification of diagnosis or therapy, and the observational nature of the study.

Bottom line: There may be an increased risk of ischemic stroke during the first 30 days of treatment with warfarin in patients with Afib.

Citation: Azoulay L, Dell-Aniello S, Simon T, Renoux C, Suissa S. Initiation of warfarin in patients with atrial fibrillation: early effects on ischaemic strokes [published online ahead of print December 18, 2013]. Eur Heart J.

Multifaceted Discharge Interventions Reduce Rates of Pediatric Readmission and Post-Hospital ED Utilization

Clinical question: Do interventions at discharge reduce the rate of readmissions and post-hospitalization ED visits among pediatric patients?

Background: Readmissions are a high-priority quality measure in both the adult and pediatric settings. Although a broadening body of literature is evaluating the impact of interventions on readmissions in adult populations, the literature does not contain a similar breadth of assessments of interventions in the pediatric setting.

Study design: Systematic review.

Setting: English-language articles studying pediatric inpatient discharge interventions.

Synopsis: A total of 1,296 unique articles were identified from PubMed and the Cumulative Index to Nursing and Allied Health Literature. Additional articles were identified on review of references, yielding 14 articles that met inclusion criteria. Included studies evaluated the effect of pediatric discharge interventions on the primary outcomes of hospital readmission or post-hospitalization ED visits. Interventions focused on three main patient populations: asthma, cancer, and prematurity.

Six studies demonstrated statistically significant reductions in readmissions and/or ED visits, while two studies actually demonstrated an increase in post-discharge utilization. All successful interventions began in the inpatient setting and were multifaceted, with four of six studies including an educational component and a post-discharge follow-up component.

While all of the studies evaluated sought to enhance the transitional care from the inpatient to outpatient setting, only the interventions that included one responsible party (individual or team) with expertise in the medical condition providing oversight and support were successful in reducing the specified outcomes. A significant limitation was that many of the studies identified were not sufficiently powered to detect either outcome of interest.

Bottom line: A multifaceted intervention involving educational and post-discharge follow-up components with an experienced individual or team supporting the transition is associated with a reduction in hospital readmissions and post-discharge ED utilization.

Citation: Auger KA, Kenyon CC, Feudtner C, Davis MM. Pediatric hospital discharge interventions to reduce subsequent utilization: a systematic review [published online ahead of print December 20, 2013]. J Hosp Med.

Sepsis Diagnoses Are Common in ED, but Many Septic Patients in the ED Do Not Receive Antibiotics

Clinical question: Has the frequency of sepsis rates, along with administration of antibiotics in U.S. emergency departments (EDs), changed over time?

Background: Prior studies reviewing discharge data from hospitals suggest an increase of sepsis over time; however, little epidemiological research has evaluated the diagnosis of sepsis and antibiotic use in ED settings.

Study design: Retrospective, four-stage probability sample.

Setting: National Hospital Ambulatory Medical Care Survey (NHAMCS).

Synopsis: The NHAMCS includes a sample of all U.S. ED visits, except federal, military, and VA hospitals. According to NHAMCS data, an estimated 1.3 billion visits by adults to U.S. EDs occurred from 1994-2009, or approximately 81 million visits per year. Explicit sepsis was defined by the presence of the following, with ICD-9 codes: septicemia (038), sepsis (995.91), severe sepsis (995.92), or septic shock (785.52). Implicit sepsis was defined as a code indicating infection plus a code indicting organ dysfunction.

In U.S. EDs, explicit sepsis did not become more prevalent from 1994-2009; however, implicitly diagnosed sepsis increased by 7% every two years. There were 260,000 explicit sepsis-related ED visits per year, or 1.23 visits per 1,000 U.S. population. In-hospital mortality was 17% and 9% for the explicit and implicit diagnosis groups, respectively. On review of the explicit sepsis group, only 61% of the patients were found to have received antibiotics in the ED. The rate did increase over the time studied, from 52% in 1994-1997 to 69% in 2006-2009.

The study was limited by the retrospective analysis of data not designed to track sepsis or antibiotic use.

Bottom Line: Explicitly recognized sepsis remained stable in the ED setting from 1994-2009, and early antibiotic use has improved during this time, but there is still much opportunity for improvement.

Citation: Filbin MR, Arias SA, Camargo CA Jr, Barche A, Pallin DJ. Sepsis visits and antibiotic utilization in the U.S. emergency departments. Crit Care Med. 2014;42(3):528-535.

New Oral Anticoagulants Safe and Effective for Atrial Fibrillation Treatment

Clinical question: Is there a difference in efficacy and safety among new oral anticoagulants compared to warfarin in subgroups of patients with atrial fibrillation (Afib)?

Background: Studies of new oral anticoagulants have demonstrated that these agents are at least as safe and effective as warfarin for prevention of stroke and systemic embolism in Afib. This study was designed to look at available phase 3 randomized trials, with the goal of subgroup analysis for both efficacy and bleeding risks.

Study design: Meta-analysis.

Setting: Phase 3 randomized controlled trials of patients with Afib.

Synopsis: The analysis included four trials of Afib patients randomized to receive warfarin or a novel oral anticoagulant (NOAC), including dabigatran, rivaroxaban, apixaban, and edoxaban. In total, 42,411 patients received an NOAC and 29,272 patients received warfarin. Separate analyses were performed for high-dose and low-dose NOACs.

The high-dose NOAC demonstrated a 19% reduction in stroke and systemic embolic events as compared to warfarin, largely due to the reduction of hemorrhagic strokes by the NOAC. The low-dose NOAC showed similar efficacy to warfarin for reduction of stroke and systemic embolic events, with an increase noted in the subset of ischemic stroke in low-dose NOAC. Both doses of NOAC demonstrated a significant reduction in all-cause mortality. NOAC showed a non-significant reduction in bleeding compared to warfarin; however, subset analysis demonstrated an increase in gastrointestinal bleeding with high-dose NOAC and a significant reduction in intracranial hemorrhage with low-dose NOAC.

A notable limitation of the study is that it only included clinical trials in the analysis.

Bottom line: In relation to stroke, systemic embolic events, and all-cause mortality, new oral anticoagulants showed a favorable efficacy and safety profile as compared to warfarin in Afib patients.

Citation: Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Healthcare-associated infections financially impact the U.S. system
2. No mortality benefit with treatment of single peripheral pulmonary emboli
3. Modified (shorter) IV acetylcysteine infusion reduces adverse effects
4. Comorbidities contribute to potentially avoidable hospital readmissions
5. Resident handoff bundle reduces medical errors and adverse events, improves handoff quality
6. Uncomplicated skin infections in the ambulatory setting commonly involve avoidable antibiotic exposure
7. Warfarin initiation in atrial fibrillation associated with increased short-term risk of stroke
8. Multifaceted discharge interventions reduce rates of pediatric readmission and post-hospital ED utilization
9. Sepsis diagnoses are common, but many septic patients in ED do not receive antibiotics
10. New oral anticoagulants safe, effective for atrial fibrillation treatment

Healthcare-Associated Infections Continue to Impact the U.S. Healthcare System Financially

Clinical question: What is the estimated cost of healthcare-associated infections (HAI) to the U.S. healthcare system?

Background: In spite of education efforts, HAIs occur frequently and contribute to high healthcare costs in the U.S. This study sought to estimate the costs of HAIs to the U.S. system using statistical analyses of published data.

Study design: Simulations of published data.

Setting: Published studies on five major HAIs.

Synopsis: Monte Carlo simulations based upon published point estimates were used to estimate per-case cost and confidence intervals, with extrapolation to total costs to the U.S. healthcare system. Overall, five major HAIs occur approximately 440,000 times annually and cost the healthcare system an estimated $9.78 billion (range $8.28 to $11.5 billion) in 2009.

Surgical site infections (36.0%) were the most common of the studied HAIs, with increased per-case cost of $20,785, equating to an estimated $3.30 billion annually (33.7% of total HAI costs). Clostridium difficile infection accounted for 30.3% of HAI but only 15.4% of costs ($1.51 billion). Central line-associated bloodstream infections were most costly per case ($45,814), with total costs of $1.85 billion (18.9% of costs). Ventilator-associated pneumonia accounted for $3.09 billion, or 31.7% of total costs. Catheter-associated urinary tract infection only represented 0.3% of total costs, or $27.9 million annually.

The authors suggest that changes in payment reform likely will drive hospitals to further invest in HAI reduction efforts.

Bottom line: HAIs remain frequent and expensive complications of hospitalization, in spite of improvement efforts to date.

Citation: Zimlichman E, Henderson D, Tamir O, et al. Health care-associated infections: a meta-analysis of costs and financial impact on the US health care system. JAMA Intern Med. 2013;173(22):2039-2046.

No Mortality Benefit with Treatment of Single Peripheral Pulmonary Emboli

Clinical question: Does treatment of single peripheral pulmonary emboli impact mortality and rates of post-discharge venous thromboembolism (VTE)?

Background: With the increase in CT pulmonary angiography (CTPA) use the past decade, there has been an increased rate of detection of peripheral filling defects. When confronted with a single peripheral filling defect (SPFD), clinicians face the dilemma of whether treatment is necessary, given the risks associated with anticoagulation.

Study design: Retrospective cohort.

Setting: Community teaching hospital in Norwalk, Conn.

Synopsis: A total of 4,906 CTPAs were screened, revealing 153 scans with an SPFD. Primary analysis included 134 patients 18 years or older. Of these patients, 61 (45.5%) received treatment with anticoagulation (n=51) or IVC filter alone (n=10).

This study revealed no difference in adjusted 90-day mortality between treated and untreated groups. No statistically significant difference was found in the rate of post-discharge VTE within 90 days.

Characteristics associated with treatment for SPFD were patient immobility, previous VTE, and radiology labeling the filling defect as a pulmonary embolus. It is important to note that none of the patients who had a normal second imaging study (e.g. V/Q scan or ultrasound) were treated; therefore, the use of secondary studies could mitigate some of the uncertainty around SPFD management, though this is not recommended in current diagnostic algorithms. Because this is a single-center study with a modest sample size, the comparability of findings to other centers might be limited. Larger studies are needed to help clarify these findings.

Bottom line: Treatment of SPFD was not associated with a difference in mortality or post-discharge VTE within 90 days.

Citation: Green O, Lempel J, Kolodziej A, et al. Treatment of single peripheral pulmonary emboli: patient outcomes and factors associated with decision to treat. J Hosp Med. 2014;9(1):42-47.

Modified IV Acetylcysteine Infusion Reduces Adverse Effects

Clinical question: Does a shorter regimen of IV acetylcysteine reduce adverse effects compared to the standard regimen?

Background: Acetaminophen poisoning is common, and recommended treatment is IV acetylcysteine; however, the standard regimen has many adverse effects, including vomiting and anaphylactoid reactions. Although studies have outlined these side effects, no published trials have compared their frequency to that of a shorter protocol.

Study design: Double-blinded, randomized controlled trial.

Setting: Three acute care hospitals in the United Kingdom.

Synopsis: Of 3,311 patients who presented with acetaminophen overdose, 222 underwent randomization to the standard (duration 20-25 hours) or modified (12 hours) acetylcysteine regimen, with or without pre-treatment with IV ondansetron 4 mg. The primary outcome of vomiting, retching, or need for rescue antiemetic treatment within two hours of acetylcysteine initiation was significantly less frequent in patients who received the shorter regimen, compared to those allocated to the standard regimen.

Specifically, the adjusted odds ratio was 0.26 with the modified regimen (97.5% CI, 0.13-0.52; P<0.0001). The primary outcome was significantly less in patients pre-treated with ondansetron compared to placebo (OR 0.41, 97.5% CI 0.2-0.8; P=0.003). Anaphylactic reactions were significantly reduced with the shorter protocol; no significant difference in hepatotoxicity was noted.

It is reasonable to infer that the shorter acetylcysteine regimen substantially reduces the frequency of vomiting and serious anaphylactoid reactions when compared with the standard schedule; however, hospitalists should note that this study was not powered to assess for non-inferiority of the shorter regimen with regard to prevention of acetaminophen’s hepatotoxic effects. Further studies are needed to confirm the efficacy and safety of the modified regimen before widespread adoption into clinical practice.

Bottom line: A shorter acetylcysteine regimen is associated with decreased occurrence of vomiting and anaphylactoid reactions compared to the standard protocol for treating acetaminophen toxicity. Additional research is needed to assess non-inferiority of this modified regimen for prevention of hepatotoxic effects.

Citation: Bateman DN, Dear JW, Thanacoody HK, et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomized controlled trial. Lancet. 2014;383(9918):697-704.

Comorbidities Contribute to Potentially Avoidable Hospital Readmissions

Clinical question: What is the role of comorbidities in 30-day potentially avoidable readmissions?

Background: Higher comorbidity burden has been associated with 30-day readmissions. This study evaluated the role of comorbidities in the 30-day rate of potentially avoidable readmissions from a tertiary-care medical center.

Study design: Retrospective cohort.

Setting: Tertiary-care teaching hospital and affiliated network.

Synopsis: Investigators tested the hypothesis that comorbidities significantly contribute to 30-day, potentially avoidable readmissions in a cohort of consecutively discharged medical patients at an academic medical center over a 12-month period. Out of a total of 10,731 discharges, there were 2,398 readmissions to hospitals in the same health system. Of those 2,398 readmissions, 858 (35.8%) were judged potentially avoidable using a validated algorithm. Frequently, the reason for readmission was not related to the index discharge diagnosis but to a complication of known comorbidities.

The authors identified the top five diagnoses for readmission as infection, neoplasm, heart failure, gastrointestinal disorder, and liver disorder. Among those patients who had a readmission diagnosis different from the index-case discharge diagnosis, the comorbidities of neoplastic disease, heart failure, and chronic kidney disease significantly contributed to readmission as compared to those without similar comorbidities.

Bottom line: The reason for readmission often is not related to the index hospitalization diagnosis but, rather, to comorbidities present at the index episode of care; thus, attention to management of comorbidities in the post-discharge period is important in circumventing potentially avoidable readmissions.

Citation: Donzé J, Lipsitz S, Bates DW, Schnipper JL. Causes and patterns of readmissions in patients with common comorbidities: retrospective cohort study. BMJ. 2013;347:F7171.

Resident Handoff Bundle Reduces Medical Errors and Adverse Events, Improves Handoff Quality

Clinical question: In a pediatric inpatient setting, is the use of a handoff program associated with improved patient safety measures and handoff quality?

Background: Sentinel events related to errors in communication are a significant patient safety dilemma and an impetus for ongoing efforts to improve handoffs in postgraduate medical education. Various strategies to be incorporated into the handoff process have been suggested in the literature, but research is limited with regard to the relationship between handoffs and patient safety.

Study design: Prospective, pre-post study.

Setting: Academic, pediatric hospital in an urban setting.

Synopsis: Overall, 1,255 patient admissions (642 pre-/613 post-handoff intervention) were evaluated on two inpatient units during the periods of July 2009-September 2009 (pre-intervention) and November 2009-January 2010 (post-intervention). The intervention was a handoff “bundle” consisting of a standardized communication and handoff training session, a verbal mnemonic to standardize handoffs, and a new unified resident-intern handoff structure in a private, quiet setting. A computerized handoff tool was also added in one unit. Primary outcomes were a comparison of the rate of medical errors per 100 admissions and rates of preventable adverse events before and after the intervention.

Implementation of the bundle resulted in a significant decrease in medical errors (18.3 from 33.8 per 100 admissions, P<0.001) and preventable adverse events (1.5 from 3.3 per 100 admissions, P=0.04). Secondary outcomes included reductions in omissions of key data in the written handoff (even greater in the group using the computerized tool) and increased percentage of time spent in direct patient care, with no change in handoff duration. Additionally, handoffs were more likely to occur in a quiet, private location.

Limitations included the potential for confounding in a pre-post intervention design, the difficulty in ascertaining the value of the individual components of the bundle, and the potential lack of generalizability.

Bottom line: In a pediatric hospital setting, a multifaceted handoff bundle is associated with improved handoff quality and reductions in medical errors and preventable adverse events.

Citation: Starmer AJ, Sectish TC, Simon DW, et al. Rates of medical errors and preventable adverse events among hospitalized children following implementation of a resident handoff bundle. JAMA. 2013;310(21):2262-2270.

Uncomplicated Skin Infections in Ambulatory Setting Commonly Involve Avoidable Antibiotic Exposure

Clinical question: What are the current prescribing practices for antibiotics used to treat skin and soft tissue infections in the outpatient setting?

Background: Uncomplicated skin and soft tissue infections are among the most frequent indications for outpatient antibiotic use. Because antibiotic use is associated with bacterial resistance and adverse events, understanding antibiotic prescribing practices is necessary to minimize these types of complications.

Study design: Retrospective cohort.

Setting: Ambulatory care setting in the Denver Health System.

Synopsis: Data from 364 adults and children who presented to an ambulatory setting with a primary diagnosis of skin and soft tissue infection were analyzed using a stepwise multivariate logistic regression in order to determine factors associated with avoidable antibiotic exposure. Among cellulitis cases, 61% of patients were prescribed antibiotics to treat methicillin-resistant Staphylococcus aureus. Avoidable antibiotic exposure occurred in 46% of cases, including use of antibiotics with broad Gram-negative activity (4%), combination therapy (12%), and treatment for ≥10 days (42%). Use of short-course, single-antibiotic treatment approaches consistent with national guidelines would have reduced prescribed antibiotic days by 19%, to 55%.

Bottom line: Avoidable antibiotic exposure frequently occurs in the treatment of uncomplicated skin infections; using short-course, single-antibiotic treatment strategies could significantly reduce total antibiotic use.

Citation: Hurley HJ, Knepper BC, Price CS, Mehler PS, Burman WJ, Jenkins TC. Avoidable antibiotic exposure for uncomplicated skin and soft tissue infections in the ambulatory care setting. Am J Med. 2013;126(12):1099-1106.

Warfarin Initiation in Atrial Fibrillation Associated with Increased Short-Term Risk of Stroke

Clinical question: Is the initiation of warfarin associated with an increased risk of ischemic stroke in patients with atrial fibrillation (Afib)?

Background: Two Afib trials of oral factor Xa inhibitors showed an increased risk of stroke when patients were transitioned to open label warfarin at the end of the study. Warfarin can, theoretically, lead to a transient hypercoagulable state upon treatment initiation, so further study is indicated to determine if the initiation of warfarin is associated with increased stroke risk among Afib patients.

Study design: Population-based, nested case-control.

Setting: UK Clinical Practice Research Datalink.

Synopsis: A cohort of 70,766 patients with newly diagnosed Afib was identified from a large primary care database. Conditional logistic regression was used to estimate adjusted rate ratios (RR) of stroke associated with warfarin monotherapy, classified according to time since initiation of treatment when compared to patients not on antithrombotic therapy.

Warfarin was associated with a 71% increased risk of stroke in the first 30 days of use (RR 1.71, 95% CI 1.39-2.12). Risk was highest in the first week of warfarin treatment, which is consistent with the known transient pro-coagulant effect of warfarin. Decreased risks were observed with warfarin initiation >30 days before the ischemic event (31-90 days: RR 0.50, 95% CI 0.34-0.75; >90 days: RR 0.55, 95% CI 0.50-0.61).

Limitations included the extraction of data from a database, which could lead to misclassification of diagnosis or therapy, and the observational nature of the study.

Bottom line: There may be an increased risk of ischemic stroke during the first 30 days of treatment with warfarin in patients with Afib.

Citation: Azoulay L, Dell-Aniello S, Simon T, Renoux C, Suissa S. Initiation of warfarin in patients with atrial fibrillation: early effects on ischaemic strokes [published online ahead of print December 18, 2013]. Eur Heart J.

Multifaceted Discharge Interventions Reduce Rates of Pediatric Readmission and Post-Hospital ED Utilization

Clinical question: Do interventions at discharge reduce the rate of readmissions and post-hospitalization ED visits among pediatric patients?

Background: Readmissions are a high-priority quality measure in both the adult and pediatric settings. Although a broadening body of literature is evaluating the impact of interventions on readmissions in adult populations, the literature does not contain a similar breadth of assessments of interventions in the pediatric setting.

Study design: Systematic review.

Setting: English-language articles studying pediatric inpatient discharge interventions.

Synopsis: A total of 1,296 unique articles were identified from PubMed and the Cumulative Index to Nursing and Allied Health Literature. Additional articles were identified on review of references, yielding 14 articles that met inclusion criteria. Included studies evaluated the effect of pediatric discharge interventions on the primary outcomes of hospital readmission or post-hospitalization ED visits. Interventions focused on three main patient populations: asthma, cancer, and prematurity.

Six studies demonstrated statistically significant reductions in readmissions and/or ED visits, while two studies actually demonstrated an increase in post-discharge utilization. All successful interventions began in the inpatient setting and were multifaceted, with four of six studies including an educational component and a post-discharge follow-up component.

While all of the studies evaluated sought to enhance the transitional care from the inpatient to outpatient setting, only the interventions that included one responsible party (individual or team) with expertise in the medical condition providing oversight and support were successful in reducing the specified outcomes. A significant limitation was that many of the studies identified were not sufficiently powered to detect either outcome of interest.

Bottom line: A multifaceted intervention involving educational and post-discharge follow-up components with an experienced individual or team supporting the transition is associated with a reduction in hospital readmissions and post-discharge ED utilization.

Citation: Auger KA, Kenyon CC, Feudtner C, Davis MM. Pediatric hospital discharge interventions to reduce subsequent utilization: a systematic review [published online ahead of print December 20, 2013]. J Hosp Med.

Sepsis Diagnoses Are Common in ED, but Many Septic Patients in the ED Do Not Receive Antibiotics

Clinical question: Has the frequency of sepsis rates, along with administration of antibiotics in U.S. emergency departments (EDs), changed over time?

Background: Prior studies reviewing discharge data from hospitals suggest an increase of sepsis over time; however, little epidemiological research has evaluated the diagnosis of sepsis and antibiotic use in ED settings.

Study design: Retrospective, four-stage probability sample.

Setting: National Hospital Ambulatory Medical Care Survey (NHAMCS).

Synopsis: The NHAMCS includes a sample of all U.S. ED visits, except federal, military, and VA hospitals. According to NHAMCS data, an estimated 1.3 billion visits by adults to U.S. EDs occurred from 1994-2009, or approximately 81 million visits per year. Explicit sepsis was defined by the presence of the following, with ICD-9 codes: septicemia (038), sepsis (995.91), severe sepsis (995.92), or septic shock (785.52). Implicit sepsis was defined as a code indicating infection plus a code indicting organ dysfunction.

In U.S. EDs, explicit sepsis did not become more prevalent from 1994-2009; however, implicitly diagnosed sepsis increased by 7% every two years. There were 260,000 explicit sepsis-related ED visits per year, or 1.23 visits per 1,000 U.S. population. In-hospital mortality was 17% and 9% for the explicit and implicit diagnosis groups, respectively. On review of the explicit sepsis group, only 61% of the patients were found to have received antibiotics in the ED. The rate did increase over the time studied, from 52% in 1994-1997 to 69% in 2006-2009.

The study was limited by the retrospective analysis of data not designed to track sepsis or antibiotic use.

Bottom Line: Explicitly recognized sepsis remained stable in the ED setting from 1994-2009, and early antibiotic use has improved during this time, but there is still much opportunity for improvement.

Citation: Filbin MR, Arias SA, Camargo CA Jr, Barche A, Pallin DJ. Sepsis visits and antibiotic utilization in the U.S. emergency departments. Crit Care Med. 2014;42(3):528-535.

New Oral Anticoagulants Safe and Effective for Atrial Fibrillation Treatment

Clinical question: Is there a difference in efficacy and safety among new oral anticoagulants compared to warfarin in subgroups of patients with atrial fibrillation (Afib)?

Background: Studies of new oral anticoagulants have demonstrated that these agents are at least as safe and effective as warfarin for prevention of stroke and systemic embolism in Afib. This study was designed to look at available phase 3 randomized trials, with the goal of subgroup analysis for both efficacy and bleeding risks.

Study design: Meta-analysis.

Setting: Phase 3 randomized controlled trials of patients with Afib.

Synopsis: The analysis included four trials of Afib patients randomized to receive warfarin or a novel oral anticoagulant (NOAC), including dabigatran, rivaroxaban, apixaban, and edoxaban. In total, 42,411 patients received an NOAC and 29,272 patients received warfarin. Separate analyses were performed for high-dose and low-dose NOACs.

The high-dose NOAC demonstrated a 19% reduction in stroke and systemic embolic events as compared to warfarin, largely due to the reduction of hemorrhagic strokes by the NOAC. The low-dose NOAC showed similar efficacy to warfarin for reduction of stroke and systemic embolic events, with an increase noted in the subset of ischemic stroke in low-dose NOAC. Both doses of NOAC demonstrated a significant reduction in all-cause mortality. NOAC showed a non-significant reduction in bleeding compared to warfarin; however, subset analysis demonstrated an increase in gastrointestinal bleeding with high-dose NOAC and a significant reduction in intracranial hemorrhage with low-dose NOAC.

A notable limitation of the study is that it only included clinical trials in the analysis.

Bottom line: In relation to stroke, systemic embolic events, and all-cause mortality, new oral anticoagulants showed a favorable efficacy and safety profile as compared to warfarin in Afib patients.

Citation: Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Healthcare-associated infections financially impact the U.S. system
2. No mortality benefit with treatment of single peripheral pulmonary emboli
3. Modified (shorter) IV acetylcysteine infusion reduces adverse effects
4. Comorbidities contribute to potentially avoidable hospital readmissions
5. Resident handoff bundle reduces medical errors and adverse events, improves handoff quality
6. Uncomplicated skin infections in the ambulatory setting commonly involve avoidable antibiotic exposure
7. Warfarin initiation in atrial fibrillation associated with increased short-term risk of stroke
8. Multifaceted discharge interventions reduce rates of pediatric readmission and post-hospital ED utilization
9. Sepsis diagnoses are common, but many septic patients in ED do not receive antibiotics
10. New oral anticoagulants safe, effective for atrial fibrillation treatment

Healthcare-Associated Infections Continue to Impact the U.S. Healthcare System Financially

Clinical question: What is the estimated cost of healthcare-associated infections (HAI) to the U.S. healthcare system?

Background: In spite of education efforts, HAIs occur frequently and contribute to high healthcare costs in the U.S. This study sought to estimate the costs of HAIs to the U.S. system using statistical analyses of published data.

Study design: Simulations of published data.

Setting: Published studies on five major HAIs.

Synopsis: Monte Carlo simulations based upon published point estimates were used to estimate per-case cost and confidence intervals, with extrapolation to total costs to the U.S. healthcare system. Overall, five major HAIs occur approximately 440,000 times annually and cost the healthcare system an estimated $9.78 billion (range $8.28 to $11.5 billion) in 2009.

Surgical site infections (36.0%) were the most common of the studied HAIs, with increased per-case cost of $20,785, equating to an estimated $3.30 billion annually (33.7% of total HAI costs). Clostridium difficile infection accounted for 30.3% of HAI but only 15.4% of costs ($1.51 billion). Central line-associated bloodstream infections were most costly per case ($45,814), with total costs of $1.85 billion (18.9% of costs). Ventilator-associated pneumonia accounted for $3.09 billion, or 31.7% of total costs. Catheter-associated urinary tract infection only represented 0.3% of total costs, or $27.9 million annually.

The authors suggest that changes in payment reform likely will drive hospitals to further invest in HAI reduction efforts.

Bottom line: HAIs remain frequent and expensive complications of hospitalization, in spite of improvement efforts to date.

Citation: Zimlichman E, Henderson D, Tamir O, et al. Health care-associated infections: a meta-analysis of costs and financial impact on the US health care system. JAMA Intern Med. 2013;173(22):2039-2046.

No Mortality Benefit with Treatment of Single Peripheral Pulmonary Emboli

Clinical question: Does treatment of single peripheral pulmonary emboli impact mortality and rates of post-discharge venous thromboembolism (VTE)?

Background: With the increase in CT pulmonary angiography (CTPA) use the past decade, there has been an increased rate of detection of peripheral filling defects. When confronted with a single peripheral filling defect (SPFD), clinicians face the dilemma of whether treatment is necessary, given the risks associated with anticoagulation.

Study design: Retrospective cohort.

Setting: Community teaching hospital in Norwalk, Conn.

Synopsis: A total of 4,906 CTPAs were screened, revealing 153 scans with an SPFD. Primary analysis included 134 patients 18 years or older. Of these patients, 61 (45.5%) received treatment with anticoagulation (n=51) or IVC filter alone (n=10).

This study revealed no difference in adjusted 90-day mortality between treated and untreated groups. No statistically significant difference was found in the rate of post-discharge VTE within 90 days.

Characteristics associated with treatment for SPFD were patient immobility, previous VTE, and radiology labeling the filling defect as a pulmonary embolus. It is important to note that none of the patients who had a normal second imaging study (e.g. V/Q scan or ultrasound) were treated; therefore, the use of secondary studies could mitigate some of the uncertainty around SPFD management, though this is not recommended in current diagnostic algorithms. Because this is a single-center study with a modest sample size, the comparability of findings to other centers might be limited. Larger studies are needed to help clarify these findings.

Bottom line: Treatment of SPFD was not associated with a difference in mortality or post-discharge VTE within 90 days.

Citation: Green O, Lempel J, Kolodziej A, et al. Treatment of single peripheral pulmonary emboli: patient outcomes and factors associated with decision to treat. J Hosp Med. 2014;9(1):42-47.

Modified IV Acetylcysteine Infusion Reduces Adverse Effects

Clinical question: Does a shorter regimen of IV acetylcysteine reduce adverse effects compared to the standard regimen?

Background: Acetaminophen poisoning is common, and recommended treatment is IV acetylcysteine; however, the standard regimen has many adverse effects, including vomiting and anaphylactoid reactions. Although studies have outlined these side effects, no published trials have compared their frequency to that of a shorter protocol.

Study design: Double-blinded, randomized controlled trial.

Setting: Three acute care hospitals in the United Kingdom.

Synopsis: Of 3,311 patients who presented with acetaminophen overdose, 222 underwent randomization to the standard (duration 20-25 hours) or modified (12 hours) acetylcysteine regimen, with or without pre-treatment with IV ondansetron 4 mg. The primary outcome of vomiting, retching, or need for rescue antiemetic treatment within two hours of acetylcysteine initiation was significantly less frequent in patients who received the shorter regimen, compared to those allocated to the standard regimen.

Specifically, the adjusted odds ratio was 0.26 with the modified regimen (97.5% CI, 0.13-0.52; P<0.0001). The primary outcome was significantly less in patients pre-treated with ondansetron compared to placebo (OR 0.41, 97.5% CI 0.2-0.8; P=0.003). Anaphylactic reactions were significantly reduced with the shorter protocol; no significant difference in hepatotoxicity was noted.

It is reasonable to infer that the shorter acetylcysteine regimen substantially reduces the frequency of vomiting and serious anaphylactoid reactions when compared with the standard schedule; however, hospitalists should note that this study was not powered to assess for non-inferiority of the shorter regimen with regard to prevention of acetaminophen’s hepatotoxic effects. Further studies are needed to confirm the efficacy and safety of the modified regimen before widespread adoption into clinical practice.

Bottom line: A shorter acetylcysteine regimen is associated with decreased occurrence of vomiting and anaphylactoid reactions compared to the standard protocol for treating acetaminophen toxicity. Additional research is needed to assess non-inferiority of this modified regimen for prevention of hepatotoxic effects.

Citation: Bateman DN, Dear JW, Thanacoody HK, et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomized controlled trial. Lancet. 2014;383(9918):697-704.

Comorbidities Contribute to Potentially Avoidable Hospital Readmissions

Clinical question: What is the role of comorbidities in 30-day potentially avoidable readmissions?

Background: Higher comorbidity burden has been associated with 30-day readmissions. This study evaluated the role of comorbidities in the 30-day rate of potentially avoidable readmissions from a tertiary-care medical center.

Study design: Retrospective cohort.

Setting: Tertiary-care teaching hospital and affiliated network.

Synopsis: Investigators tested the hypothesis that comorbidities significantly contribute to 30-day, potentially avoidable readmissions in a cohort of consecutively discharged medical patients at an academic medical center over a 12-month period. Out of a total of 10,731 discharges, there were 2,398 readmissions to hospitals in the same health system. Of those 2,398 readmissions, 858 (35.8%) were judged potentially avoidable using a validated algorithm. Frequently, the reason for readmission was not related to the index discharge diagnosis but to a complication of known comorbidities.

The authors identified the top five diagnoses for readmission as infection, neoplasm, heart failure, gastrointestinal disorder, and liver disorder. Among those patients who had a readmission diagnosis different from the index-case discharge diagnosis, the comorbidities of neoplastic disease, heart failure, and chronic kidney disease significantly contributed to readmission as compared to those without similar comorbidities.

Bottom line: The reason for readmission often is not related to the index hospitalization diagnosis but, rather, to comorbidities present at the index episode of care; thus, attention to management of comorbidities in the post-discharge period is important in circumventing potentially avoidable readmissions.

Citation: Donzé J, Lipsitz S, Bates DW, Schnipper JL. Causes and patterns of readmissions in patients with common comorbidities: retrospective cohort study. BMJ. 2013;347:F7171.

Resident Handoff Bundle Reduces Medical Errors and Adverse Events, Improves Handoff Quality

Clinical question: In a pediatric inpatient setting, is the use of a handoff program associated with improved patient safety measures and handoff quality?

Background: Sentinel events related to errors in communication are a significant patient safety dilemma and an impetus for ongoing efforts to improve handoffs in postgraduate medical education. Various strategies to be incorporated into the handoff process have been suggested in the literature, but research is limited with regard to the relationship between handoffs and patient safety.

Study design: Prospective, pre-post study.

Setting: Academic, pediatric hospital in an urban setting.

Synopsis: Overall, 1,255 patient admissions (642 pre-/613 post-handoff intervention) were evaluated on two inpatient units during the periods of July 2009-September 2009 (pre-intervention) and November 2009-January 2010 (post-intervention). The intervention was a handoff “bundle” consisting of a standardized communication and handoff training session, a verbal mnemonic to standardize handoffs, and a new unified resident-intern handoff structure in a private, quiet setting. A computerized handoff tool was also added in one unit. Primary outcomes were a comparison of the rate of medical errors per 100 admissions and rates of preventable adverse events before and after the intervention.

Implementation of the bundle resulted in a significant decrease in medical errors (18.3 from 33.8 per 100 admissions, P<0.001) and preventable adverse events (1.5 from 3.3 per 100 admissions, P=0.04). Secondary outcomes included reductions in omissions of key data in the written handoff (even greater in the group using the computerized tool) and increased percentage of time spent in direct patient care, with no change in handoff duration. Additionally, handoffs were more likely to occur in a quiet, private location.

Limitations included the potential for confounding in a pre-post intervention design, the difficulty in ascertaining the value of the individual components of the bundle, and the potential lack of generalizability.

Bottom line: In a pediatric hospital setting, a multifaceted handoff bundle is associated with improved handoff quality and reductions in medical errors and preventable adverse events.

Citation: Starmer AJ, Sectish TC, Simon DW, et al. Rates of medical errors and preventable adverse events among hospitalized children following implementation of a resident handoff bundle. JAMA. 2013;310(21):2262-2270.

Uncomplicated Skin Infections in Ambulatory Setting Commonly Involve Avoidable Antibiotic Exposure

Clinical question: What are the current prescribing practices for antibiotics used to treat skin and soft tissue infections in the outpatient setting?

Background: Uncomplicated skin and soft tissue infections are among the most frequent indications for outpatient antibiotic use. Because antibiotic use is associated with bacterial resistance and adverse events, understanding antibiotic prescribing practices is necessary to minimize these types of complications.

Study design: Retrospective cohort.

Setting: Ambulatory care setting in the Denver Health System.

Synopsis: Data from 364 adults and children who presented to an ambulatory setting with a primary diagnosis of skin and soft tissue infection were analyzed using a stepwise multivariate logistic regression in order to determine factors associated with avoidable antibiotic exposure. Among cellulitis cases, 61% of patients were prescribed antibiotics to treat methicillin-resistant Staphylococcus aureus. Avoidable antibiotic exposure occurred in 46% of cases, including use of antibiotics with broad Gram-negative activity (4%), combination therapy (12%), and treatment for ≥10 days (42%). Use of short-course, single-antibiotic treatment approaches consistent with national guidelines would have reduced prescribed antibiotic days by 19%, to 55%.

Bottom line: Avoidable antibiotic exposure frequently occurs in the treatment of uncomplicated skin infections; using short-course, single-antibiotic treatment strategies could significantly reduce total antibiotic use.

Citation: Hurley HJ, Knepper BC, Price CS, Mehler PS, Burman WJ, Jenkins TC. Avoidable antibiotic exposure for uncomplicated skin and soft tissue infections in the ambulatory care setting. Am J Med. 2013;126(12):1099-1106.

Warfarin Initiation in Atrial Fibrillation Associated with Increased Short-Term Risk of Stroke

Clinical question: Is the initiation of warfarin associated with an increased risk of ischemic stroke in patients with atrial fibrillation (Afib)?

Background: Two Afib trials of oral factor Xa inhibitors showed an increased risk of stroke when patients were transitioned to open label warfarin at the end of the study. Warfarin can, theoretically, lead to a transient hypercoagulable state upon treatment initiation, so further study is indicated to determine if the initiation of warfarin is associated with increased stroke risk among Afib patients.

Study design: Population-based, nested case-control.

Setting: UK Clinical Practice Research Datalink.

Synopsis: A cohort of 70,766 patients with newly diagnosed Afib was identified from a large primary care database. Conditional logistic regression was used to estimate adjusted rate ratios (RR) of stroke associated with warfarin monotherapy, classified according to time since initiation of treatment when compared to patients not on antithrombotic therapy.

Warfarin was associated with a 71% increased risk of stroke in the first 30 days of use (RR 1.71, 95% CI 1.39-2.12). Risk was highest in the first week of warfarin treatment, which is consistent with the known transient pro-coagulant effect of warfarin. Decreased risks were observed with warfarin initiation >30 days before the ischemic event (31-90 days: RR 0.50, 95% CI 0.34-0.75; >90 days: RR 0.55, 95% CI 0.50-0.61).

Limitations included the extraction of data from a database, which could lead to misclassification of diagnosis or therapy, and the observational nature of the study.

Bottom line: There may be an increased risk of ischemic stroke during the first 30 days of treatment with warfarin in patients with Afib.

Citation: Azoulay L, Dell-Aniello S, Simon T, Renoux C, Suissa S. Initiation of warfarin in patients with atrial fibrillation: early effects on ischaemic strokes [published online ahead of print December 18, 2013]. Eur Heart J.

Multifaceted Discharge Interventions Reduce Rates of Pediatric Readmission and Post-Hospital ED Utilization

Clinical question: Do interventions at discharge reduce the rate of readmissions and post-hospitalization ED visits among pediatric patients?

Background: Readmissions are a high-priority quality measure in both the adult and pediatric settings. Although a broadening body of literature is evaluating the impact of interventions on readmissions in adult populations, the literature does not contain a similar breadth of assessments of interventions in the pediatric setting.

Study design: Systematic review.

Setting: English-language articles studying pediatric inpatient discharge interventions.

Synopsis: A total of 1,296 unique articles were identified from PubMed and the Cumulative Index to Nursing and Allied Health Literature. Additional articles were identified on review of references, yielding 14 articles that met inclusion criteria. Included studies evaluated the effect of pediatric discharge interventions on the primary outcomes of hospital readmission or post-hospitalization ED visits. Interventions focused on three main patient populations: asthma, cancer, and prematurity.

Six studies demonstrated statistically significant reductions in readmissions and/or ED visits, while two studies actually demonstrated an increase in post-discharge utilization. All successful interventions began in the inpatient setting and were multifaceted, with four of six studies including an educational component and a post-discharge follow-up component.

While all of the studies evaluated sought to enhance the transitional care from the inpatient to outpatient setting, only the interventions that included one responsible party (individual or team) with expertise in the medical condition providing oversight and support were successful in reducing the specified outcomes. A significant limitation was that many of the studies identified were not sufficiently powered to detect either outcome of interest.

Bottom line: A multifaceted intervention involving educational and post-discharge follow-up components with an experienced individual or team supporting the transition is associated with a reduction in hospital readmissions and post-discharge ED utilization.

Citation: Auger KA, Kenyon CC, Feudtner C, Davis MM. Pediatric hospital discharge interventions to reduce subsequent utilization: a systematic review [published online ahead of print December 20, 2013]. J Hosp Med.

Sepsis Diagnoses Are Common in ED, but Many Septic Patients in the ED Do Not Receive Antibiotics

Clinical question: Has the frequency of sepsis rates, along with administration of antibiotics in U.S. emergency departments (EDs), changed over time?

Background: Prior studies reviewing discharge data from hospitals suggest an increase of sepsis over time; however, little epidemiological research has evaluated the diagnosis of sepsis and antibiotic use in ED settings.

Study design: Retrospective, four-stage probability sample.

Setting: National Hospital Ambulatory Medical Care Survey (NHAMCS).

Synopsis: The NHAMCS includes a sample of all U.S. ED visits, except federal, military, and VA hospitals. According to NHAMCS data, an estimated 1.3 billion visits by adults to U.S. EDs occurred from 1994-2009, or approximately 81 million visits per year. Explicit sepsis was defined by the presence of the following, with ICD-9 codes: septicemia (038), sepsis (995.91), severe sepsis (995.92), or septic shock (785.52). Implicit sepsis was defined as a code indicating infection plus a code indicting organ dysfunction.

In U.S. EDs, explicit sepsis did not become more prevalent from 1994-2009; however, implicitly diagnosed sepsis increased by 7% every two years. There were 260,000 explicit sepsis-related ED visits per year, or 1.23 visits per 1,000 U.S. population. In-hospital mortality was 17% and 9% for the explicit and implicit diagnosis groups, respectively. On review of the explicit sepsis group, only 61% of the patients were found to have received antibiotics in the ED. The rate did increase over the time studied, from 52% in 1994-1997 to 69% in 2006-2009.

The study was limited by the retrospective analysis of data not designed to track sepsis or antibiotic use.

Bottom Line: Explicitly recognized sepsis remained stable in the ED setting from 1994-2009, and early antibiotic use has improved during this time, but there is still much opportunity for improvement.

Citation: Filbin MR, Arias SA, Camargo CA Jr, Barche A, Pallin DJ. Sepsis visits and antibiotic utilization in the U.S. emergency departments. Crit Care Med. 2014;42(3):528-535.

New Oral Anticoagulants Safe and Effective for Atrial Fibrillation Treatment

Clinical question: Is there a difference in efficacy and safety among new oral anticoagulants compared to warfarin in subgroups of patients with atrial fibrillation (Afib)?

Background: Studies of new oral anticoagulants have demonstrated that these agents are at least as safe and effective as warfarin for prevention of stroke and systemic embolism in Afib. This study was designed to look at available phase 3 randomized trials, with the goal of subgroup analysis for both efficacy and bleeding risks.

Study design: Meta-analysis.

Setting: Phase 3 randomized controlled trials of patients with Afib.

Synopsis: The analysis included four trials of Afib patients randomized to receive warfarin or a novel oral anticoagulant (NOAC), including dabigatran, rivaroxaban, apixaban, and edoxaban. In total, 42,411 patients received an NOAC and 29,272 patients received warfarin. Separate analyses were performed for high-dose and low-dose NOACs.

The high-dose NOAC demonstrated a 19% reduction in stroke and systemic embolic events as compared to warfarin, largely due to the reduction of hemorrhagic strokes by the NOAC. The low-dose NOAC showed similar efficacy to warfarin for reduction of stroke and systemic embolic events, with an increase noted in the subset of ischemic stroke in low-dose NOAC. Both doses of NOAC demonstrated a significant reduction in all-cause mortality. NOAC showed a non-significant reduction in bleeding compared to warfarin; however, subset analysis demonstrated an increase in gastrointestinal bleeding with high-dose NOAC and a significant reduction in intracranial hemorrhage with low-dose NOAC.

A notable limitation of the study is that it only included clinical trials in the analysis.

Bottom line: In relation to stroke, systemic embolic events, and all-cause mortality, new oral anticoagulants showed a favorable efficacy and safety profile as compared to warfarin in Afib patients.

Citation: Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962.

Clinical question: What are the changes in the updated Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines?

Background: Chronic obstructive pulmonary disease (COPD) remains a leading cause of death in the U.S. and worldwide. The GOLD guidelines are an international consensus report on COPD diagnosis, management, and prevention, first released in 2001. The 2011 revision to the guidelines was recently published and outlines substantial changes based on updated literature and expert opinion.

Study design: Guidelines based on studies with varying designs.

Setting: Expert panel review of multiple studies from different settings.

Synopsis: While the diagnosis of COPD remains based on a post-bronchodilator fixed ratio of FEV1/FVC <0.70, there is more emphasis on global clinical assessment in the new guidelines. The updated approach describes classifying COPD severity based on risk/symptom frequency using established symptom assessment and the frequency of acute exacerbations of COPD. Instead of five “stages” based on FEV1 measures alone, there are now four "grades" of A through D (A: low risk/fewer symptoms; B: low risk/more symptoms; C: high risk/fewer symptoms; D: high risk/more symptoms) to more easily guide treatment options.

Treatment strategies are also updated, focusing not only on reduction of current symptoms, but also risk of future events. Pharmacologic treatment recommendations include using bronchodilator monotherapy in Group A patients, favoring long-acting over short-acting bronchodilators in Group B patients, prescribing inhaled corticosteroids only in combination with long-acting bronchodilators in Groups C and D patients, and considering newer agents such as phosphodiesterase-4 inhibitors in Group D patients.

Non-pharmacologic interventions include ongoing smoking cessation strategies, exercise promotion, treatment of comorbidities, and even public health strategies in pollution control.

Bottom line: The GOLD guidelines have undergone major revisions that provide a more practical approach to classification of COPD based on symptom severity and risk assessment in order to direct providers in evidence-based treatment that addresses both short-term and long-term impact of the disease.

Citation: Global Initiative for Chronic Obstructive Lung Disease. Global strategy for diagnosis, management, and prevention of COPD. Global Initiative for Chronic Obstructive Lung Disease website. Accessed Oct. 29, 2012.

For more physician reviews of recent HM-relevant literature, visit our website.

Clinical question: What are the changes in the updated Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines?

Background: Chronic obstructive pulmonary disease (COPD) remains a leading cause of death in the U.S. and worldwide. The GOLD guidelines are an international consensus report on COPD diagnosis, management, and prevention, first released in 2001. The 2011 revision to the guidelines was recently published and outlines substantial changes based on updated literature and expert opinion.

Study design: Guidelines based on studies with varying designs.

Setting: Expert panel review of multiple studies from different settings.

Synopsis: While the diagnosis of COPD remains based on a post-bronchodilator fixed ratio of FEV1/FVC <0.70, there is more emphasis on global clinical assessment in the new guidelines. The updated approach describes classifying COPD severity based on risk/symptom frequency using established symptom assessment and the frequency of acute exacerbations of COPD. Instead of five “stages” based on FEV1 measures alone, there are now four "grades" of A through D (A: low risk/fewer symptoms; B: low risk/more symptoms; C: high risk/fewer symptoms; D: high risk/more symptoms) to more easily guide treatment options.

Treatment strategies are also updated, focusing not only on reduction of current symptoms, but also risk of future events. Pharmacologic treatment recommendations include using bronchodilator monotherapy in Group A patients, favoring long-acting over short-acting bronchodilators in Group B patients, prescribing inhaled corticosteroids only in combination with long-acting bronchodilators in Groups C and D patients, and considering newer agents such as phosphodiesterase-4 inhibitors in Group D patients.

Non-pharmacologic interventions include ongoing smoking cessation strategies, exercise promotion, treatment of comorbidities, and even public health strategies in pollution control.

Bottom line: The GOLD guidelines have undergone major revisions that provide a more practical approach to classification of COPD based on symptom severity and risk assessment in order to direct providers in evidence-based treatment that addresses both short-term and long-term impact of the disease.

Citation: Global Initiative for Chronic Obstructive Lung Disease. Global strategy for diagnosis, management, and prevention of COPD. Global Initiative for Chronic Obstructive Lung Disease website. Accessed Oct. 29, 2012.

For more physician reviews of recent HM-relevant literature, visit our website.

Clinical question: What are the changes in the updated Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines?

Background: Chronic obstructive pulmonary disease (COPD) remains a leading cause of death in the U.S. and worldwide. The GOLD guidelines are an international consensus report on COPD diagnosis, management, and prevention, first released in 2001. The 2011 revision to the guidelines was recently published and outlines substantial changes based on updated literature and expert opinion.

Study design: Guidelines based on studies with varying designs.

Setting: Expert panel review of multiple studies from different settings.

Synopsis: While the diagnosis of COPD remains based on a post-bronchodilator fixed ratio of FEV1/FVC <0.70, there is more emphasis on global clinical assessment in the new guidelines. The updated approach describes classifying COPD severity based on risk/symptom frequency using established symptom assessment and the frequency of acute exacerbations of COPD. Instead of five “stages” based on FEV1 measures alone, there are now four "grades" of A through D (A: low risk/fewer symptoms; B: low risk/more symptoms; C: high risk/fewer symptoms; D: high risk/more symptoms) to more easily guide treatment options.

Treatment strategies are also updated, focusing not only on reduction of current symptoms, but also risk of future events. Pharmacologic treatment recommendations include using bronchodilator monotherapy in Group A patients, favoring long-acting over short-acting bronchodilators in Group B patients, prescribing inhaled corticosteroids only in combination with long-acting bronchodilators in Groups C and D patients, and considering newer agents such as phosphodiesterase-4 inhibitors in Group D patients.

Non-pharmacologic interventions include ongoing smoking cessation strategies, exercise promotion, treatment of comorbidities, and even public health strategies in pollution control.

Bottom line: The GOLD guidelines have undergone major revisions that provide a more practical approach to classification of COPD based on symptom severity and risk assessment in order to direct providers in evidence-based treatment that addresses both short-term and long-term impact of the disease.

Citation: Global Initiative for Chronic Obstructive Lung Disease. Global strategy for diagnosis, management, and prevention of COPD. Global Initiative for Chronic Obstructive Lung Disease website. Accessed Oct. 29, 2012.

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