In This Edition
Literature At A Glance
A guide to this month’s studies
- Early treatment with intravenous tPA for acute stroke
- Perioperative morbidity, mortality for current smokers
- Statins associated with musculoskeletal conditions
- Antithrombotic medications in patients with history of stroke
- Extended prophylaxis with aspirin for patients after total hip arthroplasty
- Prognosis for symptomatic subsegmental pulmonary embolism
- Video-based educational workshops for academic hospitalists
- Increased mortality for elective surgeries on Fridays, weekends
- Basal plus correction insulin regimen and Type 2 diabetes
- Capnography to diagnose diabetic ketoacidosis in the ED
- How publicly reported mortality rates correlate with hospitals’ overall mortality
- Cost savings and preventable acute-care visits for Medicare patients
Early tPA in Acute Stroke Is Associated with Better Short-Term Outcomes in Routine Clinical Practice
Clinical question: Does early treatment with intravenous (IV) tissue plasminogen activator (tPA) result in better outcomes among patients with acute ischemic stroke in routine clinical practice?
Background: IV tPA for acute ischemic stroke is beneficial if given in the first 4.5 hours after symptom onset. However, pooled data from clinical trials have been limited in characterizing the extent to which onset-to-treatment (OTT) with IV tPA influences outcomes and how effective tPA is in routine clinical practice.
Study design: Data analysis from a stroke registry.
Setting: One thousand three hundred ninety-five U.S. hospitals participating in the Get with the Guidelines—Stroke Program.
Synopsis: Data were analyzed from 58,353 tPA-treated patients within 4.5 hours of symptom onset. Clinical outcomes were compared among patients treated in the 0-90-, 91-180-, and 181-270-minute OTT windows. Patient factors strongly associated with shorter OTT were greater stroke severity (odds ratio [OR] 2.8; 95% confidence interval [CI], 2.5-3.1 per five-point increase), arrival by ambulance (OR 5.9; 95% CI, 4.5-7.3), and arrival during regular hours (OR 4.6; 95% CI, 3.8-5.4). Faster OTT, in 15-minute increments, was associated with reduced in-hospital mortality (OR 0.96; 95% CI, 0.95-0.98; P<.001), reduced symptomatic intracranial hemorrhage (OR 0.96; 95% CI, 0.95-0.98; P<.001), increased achievement of independent ambulation at discharge (OR 1.04; 95% CI, 1.03-1.05; P<.001), and increased discharge to home (OR 1.03; 95% CI, 1.02-1.04; P<.001).
Data collected were dependent on the accuracy and completeness of the chart abstraction, and only short-term outcomes were reported. Although no post-discharge outcomes were reported, previous studies have shown that functional status at discharge strongly correlates with three-month disability outcomes.
Bottom line: In routine clinical practice, earlier tPA for acute ischemic strokes results in better short-term clinical outcomes.
Citation: Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA. 2013;309:2480-2488.
Current Smokers Have Higher Perioperative Morbidity and Mortality Compared to Past Smokers
Clinical question: Is there an association between current and past smoking on outcomes among patients having major surgery?
Background: Smoking is associated with adverse postoperative outcomes, but it is not known whether the associations are dose-dependent or limited to patients with smoking-related diseases. Smoking-related effects on postoperative events among patients having major surgery are also not well established.
Study design: Retrospective cohort study.
Setting: Four hundred forty-eight non-VA hospitals across the U.S., Canada, Lebanon, and the United Arab Emirates.
Synopsis: Data from 607,558 adult patients undergoing major surgery were obtained from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. After adjusting for confounders (cardiopulmonary diseases and cancer), the effects of current and past smoking (quit >1 year prior) on 30-day post-operative outcomes were measured.
There were 125,192 (21%) current smokers and 78,763 (13%) past smokers. Increased odds of post-op mortality were noted in current smokers only (odds ratio [OR] 1.17; 95% CI, 1.10-1.24). The adjusted odds ratios were higher for arterial and respiratory events among current smokers compared with past smokers (OR 1.65; 95% CI, 1.51-1.81 vs. OR 1.20; CI, 1.09-1.31 for arterial events, respectively) and (OR, 1.45; CI, 1.40-1.51 vs. OR, 1.13; CI, 1.08-1.18, for respiratory events, respectively). No significant effects on venous events were observed.
There was an increased adjusted odds of mortality for current smokers with <10 pack-years, while the effects on arterial and respiratory events increased incrementally with increased pack-years. Smoking was associated with adverse post-op outcomes regardless of smoking-related diseases. Variability in hospital quality or surgical strategies may have confounded the results.
Bottom line: Among patients undergoing major surgery, current but not past smoking was associated with higher mortality; smoking cessation for at least a year prior to surgery may decrease post-operative adverse events.
Citation: Musallam KM, Rosendaal FR, Zaatari G, et al. Smoking and the risk of mortality and vascular and respiratory events in patients undergoing major surgery. JAMA Surg. 2013 Jun 19:1-8. doi: 10.1001/jamasurg.2013.2360 [Epub ahead of print].
Statins Associated with Several Musculoskeletal Conditions
Clinical question: Is statin use associated with musculoskeletal adverse events, including arthropathy and injury, in physically active individuals?
Background: Statin-induced musculoskeletal adverse events (AEs) include myalgias, muscle weakness, cramps, rhabdomyolysis, and tendinous disease. The full spectrum of AEs is unknown because randomized clinical trials have not been powered to detect uncommon AEs.
Study design: Retrospective cohort study with propensity score matching.
Setting: San Antonio military area.
Synopsis: A total of 46,249 patients aged 30 to 85 years who met study criteria were propensity-matched into 6,967 statin users and 6,967 nonusers. The occurrence of musculoskeletal conditions were categorized using ICD-9 codes: Msk1, all musculoskeletal diseases; Msk1a, arthropathies and related diseases; Msk1b, injury-related diseases; and Msk2, drug-associated musculoskeletal pain. Of these, statin users had a higher odds ratio (OR) for Msk1 (OR 1.19; 95% CI, 1.08-1.30), Msk1b (1.13; 1.05-1.21), and Msk2 (1.09; 1.02-1.18). Msk1b (arthropathies) had an OR of 1.07 (0.9-1.16, P=0.07). Simvastatin was used by 73.5% of patients, and years of simvastatin use was not a significant predictor of any of the outcome measures. Secondary and sensitivity analyses showed higher adjusted ORs for statin users in all groups. This study was limited by the use of ICD-9-CM codes for identification of baseline characteristics, and the musculoskeletal diagnosis groups used were not validated.
Bottom line: Statin use is associated with an increased likelihood of musculoskeletal conditions, arthropathies, injuries, and pain.
Citation: Mansi I, Frei CR, Pugh M, Makris U, Mortensen EM. Statins and musculoskeletal conditions, arthropathies, and injuries. JAMA Intern Med. 2013;173:1318-1326.
Evidence-Based Guidelines on Periprocedural Management of Antithrombotic Medications in Patients with History of Stroke
Clinical question: What is the evidence for the periprocedural management of antithrombotics in patients with ischemic cerebrovascular accidents (CVAs)?
Background: Evidence-based guidelines are needed to help clinicians determine the thromboembolic risk of temporary discontinuation of antithrombotic medications, the perioperative bleeding risks of continuing antithrombotic agents, whether bridging therapy should be used, and the appropriate timing of antithrombotic agent discontinuation.
Study design: Systematic literature review with practice recommendations.
Setting: American Academy of Neurology Guideline Development Subcommittee convened an expert panel to review and provide recommendations.
Synopsis: Researchers analyzed 133 literature reviews via MEDLINE and EMBASE. Aspirin in stroke patients:
- Should routinely be continued for dental procedures (Level A);
- Should probably be continued for invasive ocular anesthesia, cataract surgery, dermatologic procedures, transrectal ultrasound-guided prostate biopsy, spinal/epidural procedures, and carpal tunnel surgery (Level B); and
- Should possibly be continued for vitreoretinal surgery, electromyogram (EMG), transbronchial lung biopsy, colonoscopic polypectomy, upper endoscopy and biopsy/sphincterotomy, and abdominal ultrasound-guided biopsies (Level C).
Warfarin in stroke patients:
- Should routinely be continued for dental procedures (Level A); and
- Should possibly continued for dermatologic procedures (Level B) and EMG, prostate procedures, inguinal hemiorrhaphy, and endothermal ablation of great saphenous vein (Level C).
- There is a lack of evidence on warfarin for ophthalmologic procedures, with the exception of ocular anesthesia, where it probably does not increase clinically significant bleeding (Level B).
There was not enough evidence to support or refute a recommendation regarding heparin bridge therapy in reducing thromboembolism in chronically anticoagulated patients (Level B).
Bottom line: These are the most up-to-date guidelines for anticoagulant and antiplatelet agents in patients with transient ischemic attacks and strokes undergoing procedures, but further research is needed in many areas.
Citation: Armstrong MJ, Gronseth G Anderson DC, et al. Summary of evidence-based guideline: periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013;80:2065-2069.
Extended Prophylaxis with Aspirin Was Noninferior to Extended Prophylaxis with Low-Molecular-Weight Heparin
Clinical question: Is aspirin as effective as low-molecular-weight heparin (LMWH) for the extended prophylaxis of venous thromboembolism (VTE) after total hip arthroplasty (THA)?
Background: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common complications after THA. After initial prophylaxis, LMWH given for up to 30 days has been shown to reduce VTE compared with placebo. However, LMWH is costly and may increase the risk of minor bleeding. Aspirin is a potentially simple, low-cost alternative.
Study design: Randomized, placebo-controlled trial.
Setting: Twelve university-affiliated orthopedic hospitals in Canada.
Synopsis: Patients undergoing elective THA without hip fracture, metastatic cancer, or bleeding precluding anticoagulants were eligible. All patients received dalteparin for 10 days and were then randomized to aspirin 81 mg daily or to continue dalteparin. The primary outcome was symptomatic proximal DVT or PE during 90 days’ follow-up. The study was terminated early due to slow enrollment. At that time, 2,364 patients had been enrolled, and an analysis by an independent data safety and monitoring board determined that continuing the study was unlikely to alter the main findings. Extended prophylaxis with aspirin was noninferior to LMWH for the primary outcome, which occurred in 0.3% vs. 1.3%, respectively (95% CI, -0.5% to 2.5%, P<.001 for noninferiority). There were no significant differences in major or minor bleeding.
Though the early termination is a concern, the sample size was large and the results do not suggest inadequate power as a reason for lack of superiority for LMWH. Also, all patients received 10 days of LMWH, which indicates a period of LMWH after discharge will still be needed for most patients prior to initiating aspirin.
Bottom line: After initial LMWH prophylaxis for 10 days, extended prophylaxis with aspirin can be considered, particularly for patients for whom LMWH may not be feasible.
Citation: Anderson DR, Dunbar MJ, Bohm ER, et al. Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty: a randomized trial. Ann Intern Med. 2013;158:800-806.
Symptomatic Subsegmental Pulmonary Embolism (PE) Has a Prognosis Similar to Proximal PE
Clinical question: Is the prognosis of a symptomatic subsegmental pulmonary embolism (PE) similar to that of a more proximal PE?
Background: The use of multidetector computed tomography angiography (CTA) has allowed for better assessment of the pulmonary vasculature and increased detection of distal emboli. Prior studies have raised questions on the clinical importance of subsegmental PE but have been limited by small size or retrospective design.
Study design: Combined data from two prospective trials of management of suspected PE.
Setting: Twelve hospitals in the Netherlands and four tertiary-care emergency departments in Canada.
Synopsis: The study cohort consisted of 3,769 patients with suspected PE, of which 2,688 underwent CTA. Of patients diagnosed with PE, 15.5% had isolated subsegmental emboli. All patients were treated with anticoagulation. During three months of follow-up, the incidence of symptomatic recurrence for subsegmental PE was similar to patients with proximal PE (3.6% vs. 2.5%, respectively). The mortality rates for patients with subsegmental and proximal PE were also similar (10.3% vs. 6.3%, respectively).
The study may have been underpowered to detect small differences in event rates; however, there was no trend suggesting that subsegmental PE had better outcomes than more proximal PE. Also, the study did not specifically investigate whether any management strategy is preferred based on thrombus location on CTA.
Bottom line: Clinicians should continue to anticoagulate patients with subsegmental PE as the prognosis is similar to those with proximal PE.
Citation: Den Exter PL, van Es J, Klok FA, et al. Risk profile and clinical outcome of symptomatic subsegmental pulmonary embolism. Blood. 2013;122:1144-1149.
Video-Based Educational Workshop for Academic Hospitalists and House Staff May Improve Professionalism
Clinical question: Can video-based education promote professionalism among academic hospitalists and house staff?
Background: Unprofessional behavior by academic hospitalists and residents can negatively impact the learning environment and patient safety. This behavior increases throughout training, and faculty behavior can be influential. There is a paucity of educational materials to train hospitalists and house staff to recognize and ameliorate unprofessional behaviors.
Study design: Educational survey study.
Setting: University of Chicago, Northwestern University, and NorthShore University Health System teaching hospitals.
Synopsis: Three videos were developed displaying three types of unprofessional behavior: disparaging other physicians, “blocking” admissions, and misrepresenting tests to expedite their completion. There were 44 hospitalists and 244 house staff who received a 60-minute workshop in which they watched the videos using a viewing tool and discussed the videos in small groups.
For all three videos, more than three-quarters of both hospitalists and house staff felt the behavior was unprofessional or somewhat unprofessional. Hospitalists and house staff found the workshop useful and effective (65.9% and 77.1%, respectively) and would change their behavior as a result of the workshop (65.9% and 67.2%, respectively). Those who perceived the videos as “very realistic” were more likely to report intent to change behavior (93% vs. 53%, P=0.01).
This study is limited by its small sample size and possible selection bias. Those interested or concerned about unprofessional behavior may have been more likely to attend the workshop.
Bottom line: Video-based professionalism education is a feasible and well-received way to educate hospitalists and residents about unprofessional behavior and may even affect their future behavior.
Citation: Farnan JM, O’Leary KJ, Didwania A, et al. Promoting professionalism via a video-based educational workshop for academic hospitalists and housestaff. J Hosp Med. 2013;8:386-389.
Friday and Weekend Elective Surgeries Have Increased Mortality
Clinical question: How can the association between mortality and the day of elective surgical procedures be assessed?
Background: Several studies have described the “weekend effect” for both surgical and medical patients, with higher mortality and length of stay in patients admitted on the weekend compared to weekdays. Two potential explanations are poorer quality of care being delivered on the weekend or more severely ill patients being operated on or admitted on the weekend.
Study design: Retrospective analysis of national hospital administrative data.
Setting: All acute-care and specialist hospitals in England from 2008 to 2011.
Synopsis: There were 4,133,346 elective, inpatient surgical procedures studied. Friday surgeries had an adjusted odds ratio of death within 30 days and within two days of 1.44 [95% CI, 1.39-1.50] and 1.42 [95% CI, 1.26-1.60], respectively, when compared with Monday. Weekend surgeries had an adjusted odds ratio of death within 30 days and within two days of 1.82 [95% CI, 1.71-1.94] and 2.67 [95% CI, 2.30-3.09], respectively, when compared with Monday. There were significant trends toward higher mortality at the end of the workweek and weekends for four high-risk procedures: esophagus and/or stomach excision, colon and/or rectum excisions, coronary artery bypass graft, and lung excision. For lower-risk procedures, there was a significant increase in mortality for Friday surgeries but not weekend surgeries. As with all studies using administrative data, inherent selection biases could not be adjusted for Friday or weekend procedures.
Bottom line: Elective surgeries that occur on the weekend and later in the week have an increased risk of mortality, implying that the weekend effect is due to poorer quality of care during weekends, rather than higher-acuity patients presenting on weekends.
Citation: Aylin P, Alexandrescu R, Jen MH, Mayer EK, Bottle A. Day of week of procedure and 30 day mortality for elective surgery: retrospective analysis of hospital episode statistics. BMJ. 2013;346:f2424.
Basal Plus Correction Insulin Regimen Is Effective in Hospitalized Patients with Type 2 Diabetes
Clinical question: Does a basal plus correction insulin regimen (as needed with meals) result in similar glycemic control and lower rates of hypoglycemia compared to a basal-bolus regimen?
Background: Basal bolus is the preferred insulin regimen for non-critically-ill hospitalized patients as per clinical guidelines. But use is limited due to the complexity of the regimen and the fear of inducing hypoglycemia. A less complex, easier-to-implement basal plus correction insulin regimen may be an effective alternative.
Study design: Multicenter, prospective, open-label, randomized study.
Setting: Six hospitals in the U.S.
Synopsis: A group of 375 medical and surgical patients with Type 2 diabetes treated with diet, oral anti-diabetic agents, or low-dose insulin (≤ 0.4 units/kg/day) were randomized to:
- Basal-bolus insulin regimen with glargine once daily and fixed doses of glusiline before meals;
- Basal plus correction insulin (“basal plus”) regimen with glargine once daily and glusiline sliding scale insulin (SSI) before meals; or
- Regular SSI alone.
After the first day of therapy, treatment with basal-bolus and basal-plus regimens resulted in similar improvements in daily blood glucose (BG) (P=0.16), and both were superior to SSI alone (P=0.04). Both regimens also resulted in less treatment failure (defined as mean daily BG of >240 mg/dl or >2 consecutive BG >240 mg/dl) than did treatment with SSI. Hypoglycemia (BG <70 mg/dl) occurred in 16%, 13%, and 3% of patients in the basal-bolus, basal-plus, and SSI groups, respectively (P=0.02). There were no between-group differences in the frequency of severe hypoglycemia (<40 mg/dl; P=0.76).
The study was not powered to evaluate hospital complications (infection, mortality, hospital stay, and readmissions) across groups.
Bottom line: The basal-plus regimen resulted in glycemic control similar to standard basal-bolus regimen and is an effective alternative for the initial management of hyperglycemia in general medical and surgical patients with Type 2 diabetes.
Citation: Umpierrez GE, Smiley D, Hermayer K, et al. Randomized study comparing a basal-bolus with a basal plus correction insulin regimen for the hospital management of medical and surgical patients with type 2 diabetes: Basal plus trial. Diabetes Care. 2013;36:2169-2174.
Capnography Can Help Diagnose Diabetic Ketoacidosis in the ED
Clinical question: Can capnography be used as a screening tool to identify patients with diabetic ketoacidosis (DKA)?
Background: Metabolic acidosis is a major criterion for diagnosing DKA. Previous studies have shown that end-tidal carbon dioxide (ETCO2) measurement by capnography can provide an accurate estimation of arterial carbon dioxide tension (PaCO2) and may be a noninvasive, fast, inexpensive measurement of acidosis in DKA. However, those studies were in pediatric patients and had small sample sizes.
Study design: Cross-sectional, prospective descriptive-analytic study.
Setting: The ED of Imam Reza Medical Research and Training Hospital, Tabriz, East Azarbaijan, Iran.
Synopsis: A total of 181 adult patients older than 18 with suspected DKA and blood sugar >250 mg/dl were included in the study. Simultaneous capnography and arterial blood gas (ABG) were obtained on all patients. Urine ketones, complete blood count, serum levels of potassium, urea, and creatinine were collected. Sixty-two patients were found to have DKA, while 119 had other conditions associated with metabolic acidosis. There was a significant linear relationship between pH and ETCO2 (P>0.0001, relative risk (R)=0.253), PaCO2 and ETCO2 (P>0.0001, R=0.572), and bicarbonate (HCO3) and ETCO2 (P>0.0001, R=0.730). ETCO2 values >24.5 mmHg had a sensitivity and specificity of 0.90 for ruling out DKA. No cutoff point could be determined for ruling in DKA.
The study was open to selection bias as patient collection was only done during the day, so eligible subjects may have been missed. Moreover, though the study suggests that capnography has a role in ruling out DKA, the exact cutoff value is unclear. Other studies found that higher values were needed to exclude diagnosis.
Bottom line: Using ETCO2 values >24.5 mmHg, capnography can help exclude the diagnosis of DKA in adult patients with elevated BG.
Citation: Soleimanour H, Taghizadieh A, Niafar M, Rahmani F, Golzari S, Esfanjani RM. Predictive value of capnography for diagnosis in patients with suspected diabetic ketoacidosis in the emergency department. West J Emerg Med. 2013. doi: 10.5811/westjem.2013.4.14296.
Publicly Reported Mortality Correlates with Overall Mortality
Clinical question: Are publicly reported mortality rates associated with a hospital’s overall medical and surgical mortality rate?
Background: Public reporting of mortality has become an important strategy in Medicare’s quality-improvement initiative. However, the mortality rate for only three conditions, acute myocardial infarction, congestive heart failure, and pneumonia are reported. It is unclear if these rates correlate to a hospital’s overall mortality rate.
Study design: Retrospective cohort.
Setting: National Medicare fee-for-service population.
Synopsis: Using 2008-2009 data from 2,322 acute-care hospitals with 6.7 million admissions, an aggregate mortality rate for the three publicly reported conditions, a standardized 30-day mortality rate for selected medical and surgical conditions, and an overall average composite mortality score was calculated for each hospital. Based on their mortality for the three publicly reported conditions, hospitals were grouped into quartiles from highest (top-performing hospitals) to lowest mortality (poor-performing hospitals).
Top-performing hospitals had a 3.6% (9.4%vs 13.0%; P<.001) lower mortality rate than poor-performing hospitals and an odds ratio >5 of being a top performer in overall mortality (OR 5.3; 95% CI, 4.3-6.5). They also had an 81% lower chance of being in the worst-performing quartile in overall mortality (OR 0.19; 95% CI, 0.14-0.27). Conversely, poor-performing hospitals had a 4.5 times higher risk of being in the lowest quartile in overall mortality. The study is limited by the use of administrative data, which limits the ability to adjust for severity of illness, overall health, and socioeconomic status of each hospital’s population.
Bottom line: A hospital’s mortality performance on the three publicly reported conditions may predict mortality rates across a wide range of medical and surgical conditions.
Citation: McCrum ML, Joynt KE, Orav EJ, Gawande AA, Jha AK. Mortality for publicly reported conditions and overall hospital mortality rates. JAMA Intern Med. 2013;173:1351-1357.
Cost Savings in Decreasing Preventable Acute-Care Visits Are Limited among High-Cost Medicare Utilizers
Clinical question: What role do preventable acute-care visits play in the overall costs of care for the highest Medicare utilizers?
Background: Some 10% of Medicare patients account for more than half the costs. Interventions targeted at decreasing acute-care costs (ED visits and inpatient hospitalizations) for this high-cost population are widespread, but it is unknown what impact they can have.
Study design: Retrospective cohort.
Setting: National Medicare fee-for-service population.
Synopsis: Standardized total costs were created for fee-for-service Medicare patients for 2009 and 2010 in order to identify high-cost and persistently high-cost patients. Algorithms were used to identify preventable ED visits and hospitalizations in both the high-cost and non-high-cost cohorts.
Of the more than 1 million patients in the sample Medicare population, as many as 113,341 were high-cost. As much as 73% of acute-care spending was attributable to this cohort. Overall, 10% of acute-care costs were felt to be preventable in the high-cost group, 13.5% in the persistently high-cost group, and 19% in the non-high-cost group for 2010. The most common reasons for preventable acute care in the high-cost cohort were heart failure, bacterial pneumonia, and chronic obstructive pulmonary disease. Catastrophic events (myocardial infarction, stroke, sepsis), cancer, and orthopedic procedures drove overall inpatient costs in the high-cost group.
Preventable costs were higher per capita in areas with higher numbers of primary-care and specialist physicians, but it’s unclear if this was a supply or demand issue. The study also used algorithms that possibly overestimate the amount of preventable acute care.
Bottom line: In the highest Medicare utilizers, cost savings aimed at preventable acute care may be limited and might be better targeted at efficiency during acute-care episodes.
Citation: Joynt KE, Gawande AA, Orav EJ, Jha AK. Contribution of preventable acute care spending to total spending for high-cost Medicare patients. JAMA. 2013;309:2572-2578.