Association of Hydroxyethyl Starch Administration With Mortality and Acute Kidney Injury in Critically Ill Patients Requiring Volume ResuscitationA Systematic Review and Meta-analysis

Ryan Zarychanski, MD, MSc; Ahmed M. Abou-Setta, MD, PhD; Alexis F. Turgeon, MD, MSc; Brett L. Houston, BSc; Lauralyn McIntyre, MD, MSc; John C. Marshall, MD; Dean A. Fergusson, PhD, MHA

JAMA. 2013;309(7):678-688. doi:10.1001/jama.2013.430.

ABSTRACT

Importance Hydroxyethyl starch is commonly used for volume resuscitation yet has been associated with serious adverse events, including acute kidney injury and death. Clinical trials of hydroxyethyl starch are conflicting. Moreover, multiple trials from one investigator have been retracted because of scientific misconduct.

Objectives To evaluate the association of hydroxyethyl starch use with mortality and acute kidney injury.

Data Sources Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, Global Health, HealthStar, Scopus, Web of Science, the International Clinical Trials Registry Platform (inception to October 2012), reference lists of relevant articles, and gray literature.

Study Selection Two reviewers independently identified randomized controlled trials comparing hydroxyethyl starch with other resuscitation fluids in critically ill patients receiving acute volume resuscitation.

Data Extraction Two reviewers independently extracted trial-level data including population characteristics, interventions, outcomes, and funding sources. Risk of bias was assessed using the risk of bias tool; the strength of evidence was adjudicated using the GRADE methodology.

Results We included 38 eligible trials comparing hydroxyethyl starch to crystalloids, albumin, or gelatin. The majority of trials were categorized as having an unclear risk or high risk of bias. For the 10 880 patients in studies contributing mortality data, the risk ratio (RR) for death among patients randomized to receive hydroxyethyl starch was 1.07 (95% CI, 1.00 to 1.14; I2, 0%; absolute risk [AR], 1.20%; 95% CI, −0.26% to 2.66%). This summary effect measure included results from 7 trials performed by an investigator whose subsequent research had been retracted because of scientific misconduct. When we excluded these 7 trials that involved 590 patients, hydroxyethyl starch was found to be associated with increased mortality among 10 290 patients (RR, 1.09; 95% CI, 1.02 to 1.17; I2, 0%; AR, 1.51%; 95% CI, 0.02% to 3.00%), increased renal failure among 8725 patients (RR, 1.27; 95% CI, 1.09 to 1.47; I2, 26%; AR, 5.45%; 95% CI, 0.44% to 10.47%), and increased use of renal replacement therapy among 9258 patients (RR, 1.32; 95% CI, 1.15 to 1.50; I2, 0%; AR, 3.12%; 95% CI, 0.47% to 5.78%).

Conclusion and Relevance In critically ill patients requiring acute volume resuscitation, use of hydroxyethyl starch compared with other resuscitation solutions was not associated with a decrease in mortality. Moreover, after

exclusion of 7 trials performed by an investigator whose research has been retracted because of scientific misconduct, hydroxyethyl starch was associated with a significant increased risk of mortality and acute kidney injury. Clinical use of hydroxyethyl starch for acute volume resuscitation is not warranted due to serious safety concerns.

Novel Oral Anticoagulants in Atrial Fibrillation: A Meta-analysis of Large, Randomized, Controlled Trials vs Warfarin

1. Ariel Dogliotti MD1,3, Ernesto Paolasso MD2,3, Robert P. Giugliano MD, SM4,*

Clinical Cardiology Volume 36, Issue 2, pages 61–67, February 2013

Background:

Warfarin reduces ischemic stroke in atrial fibrillation, but has numerous limitations. Novel oral anticoagulants provide more predictable anticoagulation with fewer shortcomings.

Hypothesis:

Novel oral anticoagulants are superior to warfarin to prevent stroke or systemic embolism.

Methods:

Phase III randomized warfarin-controlled trials enrolling >3000 patients that reported clinical efficacy and safety of novel oral anticoagulants in patients with atrial fibrillation were identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through October 2012. Two reviewers extracted data; differences were resolved by consensus. The end points analyzed were stroke or systemic embolism (primary efficacy composite); all-cause mortality, ischemic stroke, systemic embolism (individually, secondary efficacy); and hemorrhagic stroke, major bleeding (individually, safety). The Mantel-Haenszel method was used to calculate pooled relative risk (RR) and 95% confidence intervals (CI) from fixed-effects (if homogenous) or random-effects models (if heterogeneous).

Results:

In 5 studies of 51895 patients, the composite of stroke or systemic embolism (RR: 0.82; 95% CI: 0.69–0.98; P = 0.03) and all-cause mortality (RR: 0.91; 95% CI: 0.85-0.96; P = 0.0026, respectively) were reduced with the novel agents. Factor Xa inhibitors significantly reduced the primary composite (RR: 0.84; 95% CI: 0.74-0.94; P = 0.004) and all-cause mortality (RR: 0.91; 95% CI: 0.84 - 0.98; P = 0.01). Direct thrombin inhibitor achieved results similar to the overall meta-analysis (drug class–outcome interactions P = 0.47 for primary outcome, P = 1.00 for mortality). Compared with warfarin, novel anticoagulants markedly reduced hemorrhagic stroke (RR: 0.51; 95% CI: 0.41-0.64; P < 0.0001).

Conclusions:

Novel oral anticoagulants may be superior to warfarin in patients with atrial fibrillation, reducing the composite of stroke or systemic embolism and lowering all-cause mortality. The benefit is largely due to fewer hemorrhagic strokes.

Ernesto Paolasso, MD, is a national lead investigator for a clinical trial sponsored by Daiichi-Sankyo investigating a novel oral anticoagulant. Robert Giugliano, MD, SM, is a member of the TIMI Study Group, which has received research grant support from Johnson & Johnson and from Daiichi-Sankyo related to clinical trials of anticoagulants. Dr. Giugliano has received honoraria for consultation/lectures from Bristol-Myers Squibb, Daiichi-Sankyo, Johnson & Johnson, and Sanofi-Aventis.

Bike-riding boosts PSA levels

Catherine Hanrahan all articles by this author

This one’s for the bike riders in the department – obviously male!

MEN should abstain from having their PSA levels tested up to two days after a long bike ride, Australian researchers recommend, as new data shows cycling raises PSA levels.

Melbourne researchers found that total PSA (tPSA) levels increased by 9.5% on average, corresponding to a 0.23ng/ml increase, in 129 men when measured within five minutes of them finishing recreational one-day cycling events of between 55km and 160km.

All of the participants were aged over 50, with an average age of 55, and using age-based normal PSA ranges, eight participants had an elevated tPSA after their ride, compared with five before their ride.

The authors, from the department of sports medicine at the Victorian Institute of Sport and the department of Medicine at Monash University, said they considered the increase clinically significant.

“Recording a PSA concentration in the abnormal range may obscure the accuracy of PSA screening, tipping some individuals into a range where further investigations would be considered appropriate,” they said.

“Combining the results of the current study and other studies demonstrating an increase in PSA with cycling, the findings support a period of abstinence of up to 48 hours from cycling and possibly more, before a PSA test is taken.”

Though the study showed both age and distance cycled were individually correlated with tPSA change, only age was significantly related to tPSA change in a multivariate analysis.

The authors said the study showed non-surgical manipulation of the prostate caused by cycling affected tPSA to a similar magnitude as ejaculation, digital rectal examination and cystoscopy.

BMJ. 2013 Jan 7;346:e8539. doi: 10.1136/bmj.e8539.

Egg consumption and risk of coronary heart disease and stroke: dose-response meta-analysis of prospective cohort studies.

Rong Y, Chen L, Zhu T, Song Y, Yu M, Shan Z, Sands A, Hu FB, Liu L.

Source

Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, PR China.

Abstract

OBJECTIVE:

To investigate and quantify the potential dose-response association between egg consumption and risk of coronary heart disease and stroke.

DESIGN:

Dose-response meta-analysis of prospective cohort studies.

DATA SOURCES:

PubMed and Embase prior to June 2012 and references of relevant original papers and review articles. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective cohort studies with relative risks and 95% confidence intervals of coronary heart disease or stroke for three or more categories of egg consumption.

RESULTS:

Eight articles with 17 reports (nine for coronary heart disease, eight for stroke) were eligible for inclusion in the meta-analysis (3,081,269 person years and 5847 incident cases for coronary heart disease, and 4,148,095 person years and 7579 incident cases for stroke). No evidence of a curve linear association was seen between egg consumption and risk of coronary heart disease or stroke (P=0.67 and P=0.27 for non-linearity, respectively). The summary relative risk of coronary heart disease for an increase of one egg consumed per day was 0.99 (95% confidence interval 0.85 to 1.15; P=0.88 for linear trend) without heterogeneity among studies (P=0.97, I(2)=0%). For stroke, the combined relative risk for an increase of one egg consumed per day was 0.91 (0.81 to 1.02; P=0.10 for linear trend) without heterogeneity among studies (P=0.46, I(2)=0%). In a subgroup analysis of diabetic populations, the relative risk of coronary heart disease comparing the highest with the lowest egg consumption was 1.54 (1.14 to 2.09; P=0.01). In addition, people with higher egg consumption had a 25% (0.57 to 0.99; P=0.04) lower risk of developing hemorrhagic stroke.

CONCLUSIONS:

Higher consumption of eggs (up to one egg per day) is not associated with increased risk of coronary heart disease or stroke. The increased risk of coronary heart disease among diabetic patients and reduced risk of hemorrhagic stroke associated with higher egg consumption in subgroup analyses warrant further studies.

JAMA. 2013 Feb 6;309(5):461-9. doi: 10.1001/jama.2013.129.

Effect of corticosteroid injection, physiotherapy, or both on clinical outcomes in patients with unilateral lateral epicondylalgia: a randomized controlled trial.Coombes BK, Bisset L, Brooks P, Khan A, Vicenzino B.

Source

Division of Physiotherapy, School of Health and Rehabilitation Sciences, University of Queensland, St Lucia, Australia.

AbstractIMPORTANCE:Corticosteroid injection and physiotherapy, common treatments for lateral epicondylalgia, are frequently combined in clinical practice. However, evidence on their combined efficacy is lacking.

OBJECTIVE:To investigate the effectiveness of corticosteroid injection, multimodal physiotherapy, or both in patients with unilateral lateral epicondylalgia.

DESIGN, SETTING, AND PATIENTS:A 2 × 2 factorial, randomized, injection-blinded, placebo-controlled trial was conducted at a single university research center and 16 primary care settings in Brisbane, Australia. A total of 165 patients aged 18 years or older with unilateral lateral epicondylalgia of longer than 6 weeks' duration were enrolled between July 2008 and May 2010; 1-year follow-up was completed in May 2011.

INTERVENTIONS:Corticosteroid injection (n = 43), placebo injection (n = 41), corticosteroid injection plus physiotherapy (n = 40), or placebo injection plus physiotherapy (n = 41).

MAIN OUTCOME MEASURES:The 2 primary outcomes were 1-year global rating of change scores for complete recovery or much improvement and 1-year recurrence (defined as complete recovery or much improvement at 4 or 8 weeks, but not later) analyzed on an intention-to-treat basis (P < .01). Secondary outcomes included complete recovery or much improvement at 4 and 26 weeks.

RESULTS:

Corticosteroid injection resulted in lower complete recovery or much improvement at 1 year vs placebo injection (83% vs 96%, respectively; relative risk [RR], 0.86 [99% CI, 0.75-0.99]; P = .01) and greater 1-year recurrence (54% vs 12%; RR, 0.23 [99% CI, 0.10-0.51]; P < .001). The physiotherapy and no physiotherapy groups did not differ on 1-year ratings of complete recovery or much improvement (91% vs 88%, respectively; RR, 1.04 [99% CI, 0.90-1.19]; P = .56) or recurrence (29% vs 38%; RR, 1.31 [99% CI, 0.73-2.35]; P = .25). Similar patterns were found at 26 weeks, with lower complete recovery or much improvement after corticosteroid injection vs placebo injection (55% vs 85%, respectively; RR, 0.79 [99% CI, 0.62-0.99]; P < .001) and no difference between the physiotherapy and no physiotherapy groups (71% vs 69%, respectively; RR, 1.22 [99% CI, 0.97-1.53]; P = .84). At 4 weeks, there was a significant interaction between corticosteroid injection and physiotherapy (P = .01), whereby patients receiving the placebo injection plus physiotherapy had greater complete recovery or much improvement vs no physiotherapy (39% vs 10%, respectively; RR, 4.00 [99% CI, 1.07-15.00]; P = .004). However, there was no difference between patients receiving the corticosteroid injection plus physiotherapy vs corticosteroid alone (68% vs 71%, respectively; RR, 0.95 [99% CI, 0.65-1.38]; P = .57).

CONCLUSION AND RELEVANCE: Among patients with chronic unilateral lateral epicondylalgia, the use of corticosteroid injection vs placebo injection resulted in worse clinical outcomes after 1 year, and physiotherapy did not result in any significant differences.

N Engl J Med. 2013 Jan 3;368(1):11-21. doi: 10.1056/NEJMoa1211801.

Transfusion strategies for acute upper gastrointestinal bleeding.

Villanueva C, Colomo A, Bosch A, Concepción M, Hernandez-Gea V, Aracil C, Graupera I, Poca M, Alvarez-Urturi C, Gordillo J, Guarner-Argente C, Santaló M,Muñiz E, Guarner C.

Source

Gastrointestinal Bleeding Unit, Department of Gastroenterology, Hospital de Sant Pau, Autonomous University, Barcelona, Spain. cvillanueva@santpau.cat

Abstract

BACKGROUND:

The hemoglobin threshold for transfusion of red cells in patients with acute gastrointestinal bleeding is controversial. We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy.

METHODS:

We enrolled 921 patients with severe acute upper gastrointestinal bleeding and randomly assigned 461 of them to a restrictive strategy (transfusion when the hemoglobin level fell below 7 g per deciliter) and 460 to a liberal strategy (transfusion when the hemoglobin fell below 9 g per deciliter). Randomization was stratified according to the presence or absence of liver cirrhosis.

RESULTS:

A total of 225 patients assigned to the restrictive strategy (51%), as compared with 65 assigned to the liberal strategy (15%), did not receive transfusions (P<0.001). The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% vs. 91%; hazard ratio for death with restrictive strategy, 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group as compared with 16% of the patients in the liberal-strategy group (P=0.01), and adverse events occurred in 40% as compared with 48% (P=0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (hazard ratio, 0.70; 95% CI, 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (hazard ratio, 0.30; 95% CI, 0.11 to 0.85), but not in those with cirrhosis and Child-Pugh class C disease (hazard ratio, 1.04; 95% CI, 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P=0.03) but not in those assigned to the restrictive strategy.

CONCLUSIONS:

As compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding.

A Multicentre Randomised Trial of Atorvastatin Therapy in Intensive Care Patients with Severe Sepsis

Peter Kruger 1 ⇓ , Michael Bailey 2 ,Rinaldo Bellomo 3 ,David James Cooper 4 , Meg Harward 5 , Alisa Higgins 6 , Belinda Howe 7 ,Darryl Jones 8 , Chris Joyce 9 , Karam Kostner 10 , John McNeil 11 , Alistair Nichol 12 , Michael S Roberts 13 , Gillian Syres 14 , Bala Venkatesh 15 ,

The ANZ- STATInS Investigators - ANZICS Clinical Trials Group

1. Correspondence: Peter Kruger, Email: peter_kruger@health.qld.gov.au

Abstract

Rationale: Observational studies link statin therapy with improved outcomes in patients with severe sepsis.

Objectives: To test whether atorvastatin therapy affects biological and clinical outcomes in critically ill patients with severe sepsis.

Methods: Phase II, multicenter, prospective, randomized, double-blind, placebo controlled trial stratified by site and prior statin use. A cohort of 250 critically ill patients (123 statins, 127 placebo) with severe sepsis were administrated either atorvastatin (20 mg daily) or matched placebo.

Measurements and Main Results: There was no difference in IL-6 concentrations (primary end point) between the atorvastatin and placebo groups (p=0.76) and no interaction between treatment group and time to suggest that the groups behaved differently over time (p= 0.26). Baseline plasma IL-6, was lower among previous statin users [129(87-191) vs. 244 (187-317) pg/ml, p=0.01]. There was no difference in length of stay, change in SOFA scores or mortality at ICU discharge, hospital discharge, 28 days or 90 days (15 vs. 19%) or adverse effects between the two groups. Cholesterol was lower in atorvastatin treated patients [2.4(0.07) vs. 2.6(0.06) mmol/L, p=0.006]. In the pre -defined group of 77 prior statin users, those randomised to placebo had a greater 28 day mortality (28% vs.5%, P=0.01) compared to those who received atorvastatin. The difference was not statistically significant at 90 days (28 vs. 11%, p=0.06)

Conclusions: Atorvastatin therapy in severe sepsis did not affect IL-6 levels. Prior statin use was associated with a lower baseline IL-6 concentration and continuation of atorvastatin in this cohort was associated with improved survival.

Effect of Daily Chlorhexidine Bathing on Hospital-Acquired Infection

Michael W. Climo, M.D., Deborah S. Yokoe, M.D., M.P.H., David K. Warren, M.D., Trish M. Perl, M.D., Maureen Bolon, M.D., Loreen A. Herwaldt, M.D., Robert A. Weinstein, M.D., Kent A. Sepkowitz, M.D., John A. Jernigan, M.D., Kakotan Sanogo, M.S., and Edward S. Wong, M.D.

N Engl J Med 2013; 368:533-542February 7, 2013DOI: 10.1056/NEJMoa1113849

BACKGROUND

Results of previous single-center, observational studies suggest that daily bathing of patients with chlorhexidine may prevent hospital-acquired bloodstream infections and the acquisition of multidrug-resistant organisms (MDROs).

METHODS

We conducted a multicenter, cluster-randomized, nonblinded crossover trial to evaluate the effect of daily bathing with chlorhexidine-impregnated washcloths on the acquisition of MDROs and the incidence of hospital-acquired bloodstream infections. Nine intensive care and bone marrow transplantation units in six hospitals were randomly assigned to bathe patients either with no-rinse 2% chlorhexidine–impregnated washcloths or with nonantimicrobial washcloths for a 6-month period, exchanged for the alternate product during the subsequent 6 months. The incidence rates of acquisition of MDROs and the rates of hospital-acquired bloodstream infections were compared between the two periods by means of Poisson regression analysis.

RESULTS

A total of 7727 patients were enrolled during the study. The overall rate of MDRO acquisition was 5.10 cases per 1000 patient-days with chlorhexidine bathing versus 6.60 cases per 1000 patient-days

with nonantimicrobial washcloths (P=0.03), the equivalent of a 23% lower rate with chlorhexidine bathing. The overall rate of hospital-acquired bloodstream infections was 4.78 cases per 1000 patient-days with chlorhexidine bathing versus 6.60 cases per 1000 patient-days with nonantimicrobial washcloths (P=0.007), a 28% lower rate with chlorhexidine-impregnated washcloths. No serious skin reactions were noted during either study period.

CONCLUSIONS

Daily bathing with chlorhexidine-impregnated washcloths significantly reduced the risks of acquisition of MDROs and development of hospital-acquired bloodstream infections. (Funded by the Centers for Disease Control and Prevention and Sage Products; ClinicalTrials.gov number, NCT00502476.)

A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke

Chelsea S. Kidwell, M.D., Reza Jahan, M.D., Jeffrey Gornbein, Dr.P.H., Jeffry R. Alger, Ph.D., Val Nenov, Ph.D., Zahra Ajani, M.D., Lei Feng, M.D., Ph.D., Brett C. Meyer, M.D., Scott Olson, M.D., Lee H. Schwamm, M.D., Albert J. Yoo, M.D., Randolph S. Marshall, M.D., Philip M. Meyers, M.D., Dileep R. Yavagal, M.D., Max Wintermark, M.D., Judy Guzy, R.N., Sidney Starkman, M.D., and Jeffrey L. Saver, M.D. for the MR RESCUE Investigators

February 8, 2013DOI: 10.1056/NEJMoa1212793

BACKGROUND

Whether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear.

METHODS

In this study, we randomly assigned patients within 8 hours after the onset of large-vessel, anterior-circulation strokes to undergo mechanical embolectomy (Merci Retriever or Penumbra System) or receive standard care. All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain. Randomization was stratified according to whether the patient had a favorable penumbral pattern (substantial salvageable tissue and small infarct core) or a nonpenumbral pattern (large core or small or absent penumbra). We assessed outcomes using the 90-day modified Rankin scale, ranging from 0 (no symptoms) to 6 (dead).

RESULTS

Among 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment was 5.5 hours, and 58% had a favorable penumbral pattern. Revascularization in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate differed across groups. Among all patients, mean

scores on the modified Rankin scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P=0.99). Embolectomy was not superior to standard care in patients with either a favorable penumbral pattern (mean score, 3.9 vs. 3.4; P=0.23) or a nonpenumbral pattern (mean score, 4.0 vs. 4.4; P=0.32). In the primary analysis of scores on the 90-day modified Rankin scale, there was no interaction between the pretreatment imaging pattern and treatment assignment (P=0.14).

CONCLUSIONS

A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care. (Funded by the National Institute of Neurological Disorders and Stroke; MR RESCUE ClinicalTrials.gov number,NCT00389467.)

Routine versus clinically indicated replacement of peripheral intravenous catheters: a randomised controlled equivalence trial.

Lancet. 2012; 380(9847):1066-74 (ISSN: 1474-547X)

Rickard CM; Webster J; Wallis MC; Marsh N; McGrail MR; French V; Foster L; Gallagher P; Gowardman JR; Zhang L; McClymont A; Whitby MResearch Centre for Clinical and Community Practice Innovation, Griffith Health Institute, Griffith University, Nathan, QLD, Australia. c.rickard@griffith.edu.au

BACKGROUND: The millions of peripheral intravenous catheters used each year are recommended for 72-96 h replacement in adults. This routine replacement increases health-care costs and staff workload and requires patients to undergo repeated invasive procedures. The effectiveness of the practice is not well established. Our hypothesis was that clinically indicated catheter replacement is of equal benefit to routine replacement.

METHODS: This multicentre, randomised, non-blinded equivalence trial recruited adults (≥18 years) with an intravenous catheter of expected use longer than 4 days from three hospitals in Queensland, Australia, between May 20, 2008, and Sept 9, 2009. Computer-generated random assignment (1:1 ratio, no blocking, stratified by hospital, concealed before allocation) was to clinically indicated replacement, or third daily routine replacement. Patients, clinical staff, and research nurses could not be masked after treatment allocation because of the nature of the intervention. The primary outcome was phlebitis during catheterisation or within 48 h after removal. The equivalence margin was set at 3%. Primary analysis was by intention to treat. Secondary endpoints were catheter-related bloodstream and local infections, all bloodstream infections, catheter tip colonisation, infusion failure, catheter numbers used, therapy duration, mortality, and costs. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12608000445370.

FINDINGS: All 3283 patients randomised (5907 catheters) were included in our analysis (1593 clinically indicated; 1690 routine replacement). Mean dwell time for catheters in situ on day 3 was

99 h (SD 54) when replaced as clinically indicated and 70 h (13) when routinely replaced. Phlebitis occurred in 114 of 1593 (7%) patients in the clinically indicated group and in 114 of 1690 (7%) patients in the routine replacement group, an absolute risk difference of 0·41% (95% CI -1·33 to 2·15%), which was within the prespecified 3% equivalence margin. No serious adverse events related to study interventions occurred.

INTERPRETATION: Peripheral intravenous catheters can be removed as clinically indicated; this policy will avoid millions of catheter insertions, associated discomfort, and substantial costs in both equipment and staff workload. Ongoing close monitoring should continue with timely treatment cessation and prompt removal for complications.

FUNDING: Australian National Health and Medical Research Council.

Nontraumatic Subarachnoid Hemorrhage in the Setting of Negative Cranial Computed Tomography Results: External Validation of a Clinical and Imaging Prediction Rule

Presented at the Society for Academic Emergency Medicine meeting, May 2012, Chicago, IL

Dustin G. Mark , MD Yun-Yi Hung , PhD Steven R. Offerman , MD Adina S. Rauchwerger , MA Mary E. Reed , DrPH Uli Chettipally , MD, MPH David R. Vinson , MD Dustin W. Ballard , MD, MBE for the Kaiser Permanente CREST Network Investigators

Study objective

Clinical variables can reliably exclude a diagnosis of nontraumatic subarachnoid hemorrhage in patients with negative cranial computed tomography (CT) results. We externally validated 2 decision rules with 100% reported sensitivity for a diagnosis of subarachnoid hemorrhage, among patients undergoing lumbar puncture after a negative cranial CT result: (1) clinical rule: presence of any combination of age 40 years and older, neck pain or stiffness, loss of consciousness, or headache onset during exertion; and (2) imaging rule: cranial CT performed within 6 hours of headache onset.

Methods

This was a matched case-control study of patients presenting to 21 emergency departments between 2000 and 2011. Patients with a diagnosis of subarachnoid hemorrhage as determined by lumbar puncture after a negative cranial CT result were screened for inclusion. A matched control cohort was selected among patients with a diagnosis of headache after negative cranial CT and lumbar puncture results.

Results

Fifty-five cases of subarachnoid hemorrhage meeting inclusion criteria were identified, 34 (62%) of which were attributed to cerebral aneurysms. External validation of the clinical rule demonstrated a sensitivity of 97.1% (95% confidence interval [CI] 88.6% to 99.7%), a specificity

of 22.7% (95% CI 16.6% to 29.8%), and a negative likelihood ratio of 0.13 (95% CI 0.03 to 0.61) for a diagnosis of subarachnoid hemorrhage. External validation of the imaging rule revealed that 11 of 55 subarachnoid hemorrhage cases (20%) had negative cranial CT results for tests performed within 6 hours of headache onset.

Conclusion

The clinical rule demonstrated useful Bayesian test characteristics when retrospectively validated against this patient cohort. The imaging rule, however, failed to identify 20% of subarachnoid hemorrhage patients with a negative cranial CT result.

Physician Attire in the Intensive Care Unit and Patient Family Perceptions of Physician Professional Characteristics

Selena Au, MD, FRCPC; Farah Khandwala, MSc; Henry T. Stelfox, MD, PhD, FRCPC

JAMA Intern Med. 2013;():1-2. doi:10.1001/jamainternmed.2013.2732.

Patients still love a doctor in a white coat, despite their protestations to the contrary, a study finds. The survey of patients in Canadian ICUs found just 32% explicitly stated that it was important for doctors to wear white coats— instead placing emphasis on neat grooming and easy-to-read name tags. However, a second part of the study told a different story: faced with

photographs of different doctors and asked who they thought was the best, a strong bias shone through for those in white coats. Asked why they preferred these doctors, patients believed them to be more knowledgeable and honest, and likely to provide the best overall care.

Doctors in scrubs were ranked second, followed by those in suits and casual attire. "These results suggest that while families may not express preferences for how physicians dress, there may be subconscious associations with well-recognised physician uniforms including white coats and scrubs," researchers wrote Tuesday in JAMA Internal Medicine (online).

The study involved 337 family members of patients admitted to three Canadian ICUs from 2010-2011. They were typically surveyed three days after arrival.

In the survey of explicit preferences, 77% thought an easy-to-read name tag was important when first meeting a doctor, 65% thought they should be neatly groomed and 59% thought they should wear "professional dress".bDoctors' piercings were important for 39%, white coats for 32%, tattoos for 30% and age for 10%.

"Although currently controversial, if the white coat is shown to be less safe for patients, we should find other ways to honour patient preferences for the recognizability of physicians."

Recent Australian has found that wearing a stethoscope, or having other medical equipment handy, also boosts patients' perceived trust in doctors.

J Hosp Med. 2012 Nov-Dec;7(9):702-5. doi: 10.1002/jhm.1978. Epub 2012 Sep 28.

Predicting bacteremia based on nurse-assessed food consumption at the time of blood culture.

Komatsu T, Onda T, Murayama G, Yamanouchi M, Inukai M, Sakai A, Kikuta M, Branch J, Aoki M, Tierney LM Jr, Inoue K.

Source

Department of Emergency and Critical Care Medicine, Juntendo University Nerima Hospital, Tokyo, Japan.

Abstract

BACKGROUND:

Bacteremia and its complications are important causes of morbidity and mortality in hospitalized patients. However, the yield of blood cultures is relatively low, with many false-positive results from bacterial contamination.

METHODS:

We investigated the relationship between patient food consumption and the presence of bacteremia. This was an observational analysis of a cohort of 1179 patients who underwent blood culture analysis between January 2005 and December 2009. Patients with anorexia-inducing conditions, such as gastrointestinal illness and malignant disease treated with chemotherapy, were excluded. Food consumption was rated by nurses as the percentage of food consumed during the meal preceding the blood culture. Groupings were as follows: low consumption (<50%), moderate (>50% to <80%), and high (>80%).

RESULTS:

Low consumption was observed in 39.8% of patients, moderate in 17.8%, and high in 41.6%. The average body temperature was 38.1 ± 1.1°C. Bacteremia was present in 18.5%, 3.9%, and 1.4% of patients in the low, moderate, and high food consumption groups, respectively. The negative predictive value was 98.3%, suggesting that bacteremia is very unlikely in the setting of good food intake.

CONCLUSION:

Bacteremia is an unlikely occurrence in hospitalized patients who maintain adequate food consumption at the time of blood culture.

Ann Intern Med. 2013 Jan 15;158(2):93-100. doi: 10.7326/0003-4819-158-2-201301150-00003.

Selective d-Dimer Testing for Diagnosis of a First Suspected Episode of Deep Venous Thrombosis: A Randomized Trial.

Linkins LA, Bates SM, Lang E, Kahn SR, Douketis JD, Julian J, Parpia S, Gross P, Weitz JI, Spencer FA, Lee AY, O'Donnell MJ, Crowther MA, Chan HH, Lim W,Schulman S, Ginsberg JS, Kearon C.

BACKGROUND:

d-Dimer testing is sensitive but not specific for diagnosing deep venous thrombosis (DVT). Changing the use of testing and the threshold level for a positive test result on the basis of risk for DVT might improve the tradeoff between sensitivity and specificity and reduce the need for testing.

OBJECTIVE:

To determine whether using a selective d-dimer testing strategy based on clinical pretest probability (C-PTP) for DVT is safe and reduces diagnostic testing compared with using a single d-dimer threshold for all patients.

DESIGN:

Randomized, multicenter, controlled trial. Patients were allocated using a central automated system. Ultrasonographers and study adjudicators but not other study personnel were blinded to trial allocation. (ClinicalTrials.gov: NCT00157677)

SETTING:

5 Canadian hospitals.

PATIENTS:

Consecutive symptomatic patients with a first episode of suspected DVT.

INTERVENTION:

Selective testing (n = 860), defined as d-dimer testing for outpatients with low or moderate C-PTP (DVT excluded at d-dimer levels &lt;1.0 µg/mL [low C-PTP] or &lt;0.5 µg/mL [moderate C-PTP]) and venous ultrasonography without d-dimer testing for outpatients with high C-PTP and inpatients, or uniform testing (n = 863), defined as d-dimer testing for all participants (DVT excluded at d-dimer levels &lt;0.5 µg/mL).

MEASUREMENTS:

The proportion of patients not diagnosed with DVT during initial testing who had symptomatic venous thromboembolism during 3-month follow-up and the proportion of patients undergoing d-dimer testing and ultrasonography.

RESULTS:

The incidence of symptomatic venous thromboembolism at 3 months was 0.5% in both study groups (difference, 0.0 percentage point [95% CI, -0.8 to 0.8 percentage points]). Selective testing reduced the proportion of patients who required d-dimer testing by 21.8 percentage points (CI, 19.1 to 24.8 percentage points). It reduced the proportion who required ultrasonography by 7.6 percentage points (CI, 2.9 to 12.2 percentage points) overall and by 21.0 percentage points (CI, 14.2 to 27.6 percentage points) in outpatients with low C-PTP.

LIMITATION:

Results may not be generalizable to all d-dimer assays or patients with previous DVT, study personnel were not blinded, and the trial was stopped prematurely.

CONCLUSION:

A selective d-dimer testing strategy seems as safe as and more efficient than having everyone undergo d-dimer testing when diagnosing a first episode of suspected DVT.

BMJ. 2013 Jan 18;346:f10. doi: 10.1136/bmj.f10.

Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials.

Myung SK, Ju W, Cho B, Oh SW, Park SM, Koo BK, Park BJ; Korean Meta-Analysis (KORMA) Study Group.

Source

Department of Family Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

Abstract

OBJECTIVE:

To assess the efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular diseases.

DESIGN:

Meta-analysis of randomised controlled trials.

DATA SOURCES AND STUDY SELECTION:

PubMed, EMBASE, the Cochrane Library, Scopus, CINAHL, and ClinicalTrials.gov searched in June and November 2012. Two authors independently reviewed and selected eligible randomised controlled trials, based on predetermined selection criteria.

RESULTS:

Out of 2240 articles retrieved from databases and relevant bibliographies, 50 randomised controlled trials with 294 478 participants (156 663 in intervention groups and 137 815 in control groups) were included in the final analyses. In a fixed effect meta-analysis of the 50 trials, supplementation with vitamins and antioxidants was not associated with reductions in the risk of major cardiovascular events (relative risk 1.00, 95% confidence interval 0.98 to 1.02; I(2)=42%). Overall, there was no beneficial effect of these supplements in the subgroup meta-analyses by type of prevention, type of vitamins and antioxidants, type of cardiovascular outcomes, study design, methodological quality, duration of treatment, funding source, provider of supplements, type of control, number of participants in each trial, and supplements given singly or in combination with other supplements. Among the subgroup meta-analyses by type of cardiovascular outcomes, vitamin and antioxidant supplementation was associated with a marginally increased risk of angina pectoris, while low dose vitamin B(6) supplementation was associated with a slightly decreased risk of major cardiovascular events. Those beneficial or harmful effects disappeared in subgroup meta-analysis of high quality randomised controlled trials within each category. Also, even though supplementation with vitamin B(6) was associated with a decreased risk of cardiovascular death in high quality trials, and vitamin E supplementation with a decreased risk of myocardial infarction, those beneficial effects were seen only in randomised controlled trials in which the supplements were supplied by the pharmaceutical industry.

CONCLUSION:

There is no evidence to support the use of vitamin and antioxidant supplements for prevention of cardiovascular diseases.

High-Frequency Oscillation for Acute Respiratory Distress Syndrome

Duncan Young, D.M., Sarah E. Lamb, D.Phil., Sanjoy Shah, M.D., Iain MacKenzie, M.D., William Tunnicliffe, M.Sc., Ranjit Lall, Ph.D., Kathy Rowan, D.Phil., and Brian H. Cuthbertson, M.D. for the OSCAR Study Group

January 22, 2013DOI: 10.1056/NEJMoa1215716

BACKGROUND

Patients with the acute respiratory distress syndrome (ARDS) require mechanical ventilation to maintain arterial oxygenation, but this treatment may produce secondary lung injury. High-frequency oscillatory ventilation (HFOV) may reduce this secondary damage.

METHODS

In a multicenter study, we randomly assigned adults requiring mechanical ventilation for ARDS to undergo either HFOV with a Novalung R100 ventilator (Metran) or usual ventilatory care. All the patients had a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of 200 mm Hg (26.7 kPa) or less and an expected duration of ventilation of at least 2 days. The primary outcome was all-cause mortality 30 days after randomization.

RESULTS

There was no significant between-group difference in the primary outcome, which occurred in 166 of 398 patients (41.7%) in the HFOV group and 163 of 397 patients (41.1%) in the conventional-ventilation group (P=0.85 by the chi-square test). After adjustment for study center, sex, score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, and the initial PaO2:FiO2 ratio, the odds ratio for survival in the conventional-ventilation group was 1.03 (95% confidence interval, 0.75 to 1.40; P=0.87 by logistic regression).

CONCLUSIONS

The use of HFOV had no significant effect on 30-day mortality in patients undergoing mechanical ventilation for ARDS. (Funded by the National Institute for Health Research Health Technology Assessment Programme; OSCAR Current Controlled Trials number,ISRCTN10416500.)

Ann Intern Med. 2013 Jan 1;158(1):1-9. doi: 10.7326/0003-4819-158-1-201301010-00003.

Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal.

Coffin PO, Sullivan SD.

Source

San Francisco Department of Public Health, San Francisco, CA 94102, USA.

Abstract

BACKGROUND:

Opioid overdose is a leading cause of accidental death in the United States.

OBJECTIVE:

To estimate the cost-effectiveness of distributing naloxone, an opioid antagonist, to heroin users for use at witnessed overdoses.

DESIGN:

Integrated Markov and decision analytic model using deterministic and probabilistic analyses and incorporating recurrent overdoses and a secondary analysis assuming heroin users are a net cost to society.

DATA SOURCES:

Published literature calibrated to epidemiologic data.

TARGET POPULATION:

Hypothetical 21-year-old novice U.S. heroin user and more experienced users with scenario analyses.

TIME HORIZON:

Lifetime.

PERSPECTIVE:

Societal.

INTERVENTION:

Naloxone distribution for lay administration.

OUTCOME MEASURES:

Overdose deaths prevented and incremental cost-effectiveness ratio (ICER).

RESULTS OF BASE-CASE ANALYSIS:

In the probabilistic analysis, 6% of overdose deaths were prevented with naloxone distribution; 1 death was prevented for every 227 naloxone kits distributed (95% CI, 71 to 716). Naloxone distribution increased costs by $53 (CI, $3 to $156) and quality-adjusted life-years by 0.119 (CI, 0.017 to 0.378) for an ICER of $438 (CI, $48 to $1706).

RESULTS OF SENSITIVITY ANALYSIS:

Naloxone distribution was cost-effective in all deterministic and probabilistic sensitivity and scenario analyses, and it was cost-saving if it resulted in fewer overdoses or emergency medical service activations. In a "worst-case scenario" where overdose was rarely witnessed and naloxone was rarely used, minimally effective, and expensive, the ICER was $14 000. If national drug-related expenditures were applied to heroin users, the ICER was $2429.

LIMITATION:

Limited sources of controlled data resulted in wide CIs.

CONCLUSION:

Naloxone distribution to heroin users is likely to reduce overdose deaths and is cost-effective, even under markedly conservative assumptions.