Evidence-Based PracticeA Peer-Reviewed Journal of the Family Physicians Inquiries Network VOLUME 19 NUMBER 8 AUGUST 2016

Evidence-Based Practice / Vol. 19, No. 8 1

IN DEPTH

Evidence-based answerYes. Participation in an exercise program can slow decline in cognitive function in patients with Alzheimer’s disease (AD) (SOR: B, systematic review of randomized and nonrandomized studies and single RCT). Furthermore, walking less than 2 miles per day is associated with excess risk of AD (SOR: B, single prospective cohort study).

Evidence summaryA 2014 systematic review of 14 randomized and nonrandomized studies (N=618) evaluated the effect of exercise on AD.1 The authors included all longitudinal, randomized and nonrandomized studies addressing exercise in the treatment of AD published from 2003 to 2013; correlational or cross-sectional studies that did not involve the practice of regular physical exercise and studies without a homogenous dementia type were excluded. The authors identified 2,787 studies, but only 14 met inclusion criteria. Cognitive outcomes were assessed in 5 of the studies (n=125) including nursing home and community dwellers. The exercise interventions occurred 1 to 4 times per week for 16 to 24 weeks and included walking, aerobics, stretching, low-intensity weight training, balance, and agility training. Control groups used nonexercise protocols including social events, memory exercises, and social support. Four of the 5 studies showed a benefit of exercise on slowing cognitive decline compared with control, as measured by various scales such as the Mini-Mental State Examination (MMSE), Clock Drawing Test, and Brief Cognitive Battery. The standardized mean difference calculated in 3 of these studies ranged from 0.64 to 3.85, which was consistent with a moderate to very large positive effect on the aforementioned outcomes.1

A 2012 RCT (N=40) not included in the above systematic review assessed the effectiveness of an exercise program in improving

Does a daily exercise program lead to prolonged retention of cognitive function in patients with Alzheimer’s disease?

3 Gloves, lots of gloves EDITORIAL

15 What is the role of prolonged-release oxycodone/naloxone for chronic nonmalignant pain?

SPOTLIGHT ON PHARMACY

6 CT urography imaging for gross hematuria

7 Routine deworming programs for children

8 Morphine sleep in latent labor

Cryotherapy for cutaneous warts

9 Annual preventive examinations for better mortality outcomes

10 Transcutaneous electrical nerve stimulation for chronic low back pain

11 Ultrasound-guided steroid injections for trochanteric bursitis

12 Most effective corticosteroid regimen for COPD

13 Safety of polyethylene glycol for constipation

14 Increased risk of melanoma in patients using tanning beds

E1 Lead screening for adolescents

Pediatric obesity and effectiveness of group visits

E2 Preventing recurrent kidney stones

E3 Risk for developing Guillain-Barré syndrome from influenza vaccination

E4 Impact of vertical birthing position on the duration of the second stage of labor

E5 Effect of delivery position on perineal lacerations

Steroids for chronic plantar fasciitis pain

E6 Trusting a negative cardiac stress test

HELPDESK ANSWERS

5 Limiting screen time for children PEDIATRICS

4 Management of PROM

Sitagliptin does not appear to cause cardiovascular problems

DIVING FOR PURLs

Evidence-Based Practice / August 20162

cognition of patients with AD.2 All participants were community dwelling and living with a caretaker or had a caretaker who could visit daily. Patients were excluded if they had any physical condition that could limit full participation in the exercise program, had evidence of other neurodegenerative disorders, had started dementia medications in the last 3 months, or were already participating in exercise more than once a week. Patients were randomized to an intervention group that included an exercise program in addition to standard AD treatment versus standard AD treatment alone. The exercise program consisted of a daily strengthening and balancing exercise program with 30 minutes of walking supervised by the patient’s caregiver. The primary cognitive outcomes included the MMSE (scored 0–30, with higher scores indicating less impairment) and ADAS-Cog (Alzheimer’s Disease Assessment Scale-cognitive subscale), a 70-point scale that assesses memory, language, praxis, attention, and other cognitive abilities (with higher scores indicating greater the impairment). The outcomes assessor was blinded to group assignment. At the end of the 4-month follow-up, participants assigned to the exercise group scored 2.6 points higher on the MMSE (P=.001) and 7.1 points lower on the ADAS-Cog (P=.001) compared with the control group.2

A 2004 prospective cohort study not included in the above systematic review included 2,257 physically capable men without AD aged 71 to 93 years living in Honolulu, Hawaii, and evaluated the association of walking with the risk of dementia.3 Distance walked per

In Depth

GLOSSARY

ARR=absolute risk reduction

CDC= Centers for Disease Control and Prevention

CI=confidence interval

CT=computed tomography

FDA= US Food and Drug Administration

HR=hazard ratio

LOE=level of evidence

MRI=magnetic resonance imaging

NNH=number needed to harm

NNT=number needed to treat

NSAID= nonsteroidal anti-inflammatory drug

OR=odds ratio

RCT=randomized controlled trial

RR=relative risk

SOR=strength of recommendation

SSRI= selective serotonin reuptake inhibitor

WHO=World Health Organization

day was assessed via patient self-report. The average length of follow-up was 7 years. Over the course of follow-up, 158 cases of dementia were diagnosed. Diagnosis of dementia was made using the Cognitive Abilities Screening Instrument (CASI), which was administered at baseline and twice during follow-up.3

After adjusting for age, men who walked the least (<0.25 mile/day) had a 1.8-fold excess risk of dementia compared with men who walked more than 2 miles/day (17.8 vs 10.3/1,000 person-years; relative hazard [RH] 1.8; 95% CI, 1.0–3.0). Compared with men who walked the most (>2 miles/day), an excess dementia risk was also observed for men who walked 0.25 to 1 mile/day (17.6 vs 10.3/1,000 years; RH 1.7; 95% CI, 1.0–2.9). The associations persisted after accounting for factors such as the possibility that limited amounts of walking related to decline in physical function or preclinical dementia.3

Albert Chmielewski, MDRavneet Kaur, MD, MPH, MBBS

Jennifer Holmes, DO, CPECedar Rapids Medical Education Foundation

Cedar Rapids, IA

REFERENCES

1. Hernández SS, Sandreschi PF, da Silva FC, et al. What are the benefits of exercise for Alzheimer's disease? A systematic review of the past 10 years. J Aging Phys Act. 2014; 23(4):659–668. [STEP 1]

2. Vreugdenhil A, Cannell J, Davies A, et al. A community-based exercise programme to improve functional ability in people with Alzheimer's disease: a randomized controlled trial. Scand J Caring Sci. 2012; 26(1):12–19. [STEP 2]

3. Abbott RD, White LR, Ross GW, et al. Walking and dementia in physically capable elderly men. JAMA. 2004; 292(12):1447–1453. [STEP 3]

We invite your questions and feedback. Email us at EBP@fpin.org.

EBP

Evidence-Based Practice / Vol. 19, No. 8 3

Statement of Purpose Evidence-Based Practice (EBP) addresses important patient care questions asked by practicing family physicians, using the best sources of evidence in a brief, clinically useful format. Our goal is to instruct our authors on how to write peer-reviewed scholarly research for the medical and scientific community.

Editorial PolicyStatements and opinions expressed in articles and communications in this journal are those of the author(s) and not necessarily those of the editor, publisher, or any organizations endorsing this journal. Unless noted, authors have reported no competing interests and have nothing to disclose.

Disclosure

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

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Statements and opinions expressed in abstracts and communications herein are those of the author(s) and not necessarily those of the Publisher. The Publisher and editors of EBP do not endorse any methods, product, or ideas mentioned in the journal, and disclaim any liability, which may arise from any material herein.

Copyright © 2016 by Family Physicians Inquiries Network, Inc.

HelpDesk Answers Tom Satre, MDUniversity of Minnesota

eMedRefRobert Marshall, MD, MPHValley Medical Center

Diving for PURLs Kate Rowland, MDRush–Copley Medical Center

Brian Bacak, MD, FAAFPUniversity of Colorado

Philip Dooley, MDKUSM-W FMR at Via Christi

John Epling, MD, MSEdSUNY Upstate Medical University

Corey Lyon, DO, FAAFPUniversity of Colorado Family Medicine Residency

Douglas Maurer, DO, MPH, FAAFPMadigan Army Medical Center Family Medicine Residency, Seattle, WA

Andrew McDermott, MDUnited States Navy

Anne Mounsey, MD University of North Carolina Department of Family Medicine

Karlynn Sievers, MDUniversity of Wyoming Casper Family Medicine Residency

EDITOR-IN-CHIEFJon O. Neher, MD, FAAFP University of Washington

EXECUTIVE EDITORTimothy Mott, MD, FAAFP Naval Hospital Pensacola FMR

Behavioral Health MattersVanessa Rollins, PhDUniversity of Colorado

EBM on the WardsCorey Lyon, DOUniversity of Colorado

EBPediatricsJonas A. Lee, MDA. Ildiko Martonffy, MDUniversity of Wisconsin

GeriatricsIrene Hamrick, MD University of Wisconsin

Integrative MedicineAdam Rindfleisch, MDUniversity of Wisconsin

Maternity CareLee Dresang, MDUniversity of Wisconsin

Musculoskeletal HealthAndrew W. Gottschalk, MDCleveland Clinic

Pharmacy HDAsConnie Kraus, PharmD, BCACPUniversity of Wisconsin

EDITORS

ASSOCIATE EDITORS

SECTION EDITORS

Evidence-Based Practice

Medical Copy EditorMelissa L. Bogen, ELSChester, NY

PRODUCTIONLayout and DesignRobert ThatcherHaworth, New Jersey

Senior Editorial AssistantAdelina Colbert, BScColumbia, MO

Personal subscriPtions:FPIN Member $59Non-member $119International (outside of the US or Canada) $179

institutional subscriPtions: US and Canadian Institutions $209International Institutions $259

EBP Electronic Archives $500

EditorialGloves, lots of glovesThere is a terrifying scene early in the nonfiction book, The Hot Zone, where a triple-gloved microbiologist working with the Ebola virus gets a hole in her outer glove.1 In a near panic, she strips off layer after layer of decontamination gear with mounting fear that the breech has gone all the way through. When she discovers that her last glove layer was not compromised after all, she faints. Fortunately, most of us do not have to work with Ebola, but there are plenty of other nasty blood-borne viruses out there, the 2 most common heavies being hepatitis C and HIV. Many of us have had our own minor versions of the “Hot Zone” experience. My most recent went something like this: I was lancing an abscess on a patient of mine known to be hepatitis C antibody positive. After using a number 11 blade on the patient, I accidently nicked myself with the blade. Fortunately for everyone, he turned out to be one of the 20% of antibody-positive patients with a negative viral load. But the day it took to sort this out was a long one for me. So it was with great interest that I read a recent Cochrane review that evaluated 34 RCTs involving 6,890 operations for 46 different interventions that various researchers thought might decrease the risk of virus-laden accidents: double gloves, triple gloves, thicker gloves, and special feature gloves.2 The authors determined that there was moderate quality evidence that double gloves reduced the risk of completed perforations compared with single gloves (rate ratio 0.29; 95% CI, 0.23–0.37) without increasing the overall number of perforations (rate ratio 1.1; 95% CI, 0.93–1.3). There was lower quality evidence that triple gloves lowered the risk even more. I don’t know about you, but I don’t like relying on my luck or even on my own skills. So with apologies to my business manager, I am going to be double-gloving from here on out. If I’m having a particularly nervous kind of day, I might even go for triple-gloving.

Jon O. Neher, MD

REFERENCES

1. Preston R. The Hot Zone: A Terrifying True Story. New York, NY: Random House; 1994.

2. Mischke C, Verbeek JH, Saarto A, et al. Gloves, extra gloves or special types of gloves for preventing percutaneous exposure injuries in healthcare personnel. Cochrane Database Syst Rev. 2014; (3):CD009573.

Evidence-Based Practice / August 20164

Diving for PURLs

Management of PROMMorris JM, Roberts CL, Bowen JR, et al. Immediate delivery compared with expectant management after preterm pre-labour rupture of the membranes close to term (PPROMT trial): a randomised controlled trial. Lancet. 2016; 387(10017):444–452.

This multicenter RCT compared immediate delivery of 1,839 women with premature rupture of membranes (PROM) near term with expectant management, assessing neonatal and maternal outcomes. Immediate delivery was defined as delivery as soon as possible, generally within 24 hours, and expectant management as birth after spontaneous labor, at term, or whenever the clinician thought necessary by clinical indications. The primary outcome was incidence of neonatal sepsis. Secondary outcomes for neonates included mechanical ventilation, stillbirth, or death, and for women were peripartum complications, mode of delivery, and length of hospitalization. Neonatal sepsis occurred in 2% (23/923) in the immediate delivery group and 3% (29/912) in the expectant management group (relative risk [RR] 0.8; 95% CI, 0.5–1.3). For neonatal secondary outcomes, the immediate birth group had an increased incidence of respiratory distress syndrome (RR 1.6; 95% CI, 1.1–2.3), increased mechanical ventilation (RR 1.4; 95% CI, 1.0–1.8), and longer hospital stay (median 6 vs 4 days; P<.0001). Among secondary maternal outcomes, the immediate delivery women had less ante- or intrapartum hemorrhage (RR 0.6; 95% CI, 0.4–0.9), less intrapartum fever (RR 0.4; 95% CI, 0.2–0.9), and decreased length of stay (5 vs 6 days, P<.0001), but a higher risk of cesarean section (26% vs 20%; RR 1.4; 95% CI, 1.2–1.7).

Bottom line: When pregnant women present with PROM near term, expectant management is a good option that may not increase neonatal sepsis. However, decision-making must include a discussion that balances the risks of prematurity and mode of delivery with the risk of hemorrhage and fever for the mother. Local hospital policy and the protocols of obstetric backup teams for family physicians may be barriers to implementation.

Review and Summary Author: Janice L. Benson, MD, University of Chicago/NorthShore UHS, Chicago, IL

Sitagliptin does not appear to cause cardiovascular problems

Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015; 373(3):232–242.

This randomized, double-blind, noninferiority trial compared sitagliptin (n=7,332) with placebo (n=7,339) in patients older than 50 years. All patients had type 2 diabetes mellitus (with an average HbA1C between 6.5% and 8% at the time of enrollment) and had a history of cardiovascular disease. Patients received sitagliptin 100 mg tablets or matched placebo daily for 3 years with the use of other antihyperglycemic agents. The primary outcome was a composite of cardiovascular events including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Secondary outcomes included individual components of the primary composite outcome, all-cause mortality, or hospitalization for heart failure. In the per-protocol noninferiority analysis, 839 (11.4%) patients in the sitagliptin group and 851 (11.4%) patients in the placebo group experienced one of the composite events (hazard ratio 0.98; 95% CI, 0.88–1.09). No significant difference was noted in secondary outcomes such as hospitalization for heart failure or death, or safety outcomes (such as infections, cancer, kidney failure, or severe hypoglycemia) between the sitagliptin and placebo groups.

Bottom line: Sitagliptin does not increase the risk of major cardiovascular events or other safety outcomes.

Review and Summary Authors: Alexandra Terry, PharmD, University of Illinois at Chicago College of Pharmacy at Rockford,

Rockford, IL, and Kate Rowland, MD, Rush-Copley FMR, Aurora, IL

Relevant Yes

Valid Yes

Change in practice No

Medical care setting Yes

Implementable Yes

Clinically meaningful NoRelevant Yes

Valid Yes

Change in practice Yes

Medical care setting Yes

Implementable Yes

Clinically meaningful Yes

Additional information regarding the PURLs and Diving for PURLs series can be found at:

http://www.fpin.org/purls-faqs/

EBP

Evidence-Based Practice / Vol. 19, No. 8 5

EBPediatrics

What evidence supports the recommendation to limit screen time to fewer than 2 hours for children 2 to 18 years old?

Evidence-based answerNumerous cohort and survey studies have found an association between the risk of obesity, poor cardiovascular health, increased cigarette smoking, and attention problems later in life in children and adolescents exposed to more than 2 hours of screen time per day. Study limitations include recall bias and confounding factors such as socioeconomic status, parental body mass index (BMI), and parental education level (SOR: A, based on consistent findings from multiple good-quality cohort studies with patient-oriented evidence).

Evidence summaryAn analytic sample from the 2003 National Survey of Children’s Health (with 33,117 children 0–17 years old) found that children and adolescents watching 2 to 3 hours of TV or engaging in nonschool computer time per day were more likely to be overweight than children who watched none (odds ratio [OR] 1.48; 95% CI, 1.24–1.76).1 In the California Teen Longitudinal Survey (conducted 1993–1996) among 2,223 adolescents 12 to 17 years old, those who watched more than 2 hours of TV daily were more likely to be overweight at the 3-year follow-up than adolescents who watched less (OR 2.2; 95% CI, 1.4–3.6), independent of baseline BMI.2

Researchers followed a 1970 British birth cohort of 16,567 children for 30 years and assessed television viewing times and BMI based on surveys at 10 years (parental responses) and 30 years of age (subject self-report).3 Each additional hour of weekend TV viewing at 5 years of age was associated with higher BMI at 10 years of age (OR 1.10; 95% CI, 1.03–1.18) and at 30 years of age (OR 1.07; 95% CI, 1.01–1.13), independent of maternal attitudes toward TV, family socioeconomic status, exercise habits, parental BMI, and birth weight. In a prospective longitudinal cohort study of 1,037 New Zealand children born between 1972 and 1973, parents were surveyed regarding their children’s television habits every 2 years from ages

5 to 11.4 Children themselves were surveyed at ages 13 and 15. Follow-up testing at 26 years of age (n=980) indicated increased cigarette smoking (OR 1.36; 95% CI, 1.17–1.54), poorer cardiorespiratory fitness (linear regression beta coefficient [β] –0.11; standard error [SE] 0.03; P=.0003), and higher serum cholesterol (β 0.11; SE 0.04; P=.0037) in participants with longer weeknight television viewing at ages 5 to 15. Associations remained when adjusted for socioeconomic status, parental smoking, parental BMI, and physical activity level. Data from the same New Zealand birth cohort also indicated a positive association between adolescent attention problems and daily childhood television viewing (OR 1.44; 95% CI, 1.08–1.91; adjusted for early attention problems, early cognitive ability, and socioeconomic status).5 The cutpoint for statistically significant increases in risk of attention problems was at more than 2 hours of daily childhood television time.

RecommendationPhysicians should advise parents to limit screen time to fewer than 2 hours per day for children 2 to 18 years old, as higher amounts of daily screen time are associated with a variety of adverse physical, emotional, and social outcomes.

Patrick Huffer, MDJonas Lee, MD

The University of Wisconsin Department of Family Medicine and Community Health

Madison, WI

REFERENCES

1. Sisson S, Broyles S, Baker B, et al. Television, reading, and computer time: correlates of school-day leisure-time sedentary behavior and relationship with overweight in children in the U.S. J Phys Act Health. 2011; 8(suppl 2):S188–S197. [STEP 3]

2. Kaur H, Choi W, Mayo M, et al. Duration of television watching is associated with increased body mass index. J Pediatr. 2003; 143(4):506–511. [STEP 3]

3. Viner R, Cole T. Television viewing in early childhood predicts adult body mass index. J Pediatr. 2005; 147(4):429–435. [STEP 3]

4. Hancox R, Milne B, Poulton R. Association between child and adolescent television viewing and adult health: a longitudinal birth cohort study. Lancet. 2004; 364(9430):257–262. [STEP 3]

5. Landhuis C, Poulton R, Welch D, et al. Does childhood television viewing lead to attention problems in adolescence? Results from a prospective longitudinal study. Pediatrics. 2007; 120(3):532–537. [STEP 3]

EBP

Evidence-Based Practice / August 20166

When should CT urography be used as the initial imaging test in adults with gross hematuria?

Evidence-Based AnswerComputed tomography urography (CTU) is appropriate as an initial imaging test to evaluate gross hematuria in adults older than 40 years or adults younger than 40 years with predisposing medical conditions for urologic disease. Unenhanced CT is appropriate for adults 40 years or younger without predisposing medical conditions for urologic disease. In patients with gross hematuria, CTU has a positive likelihood ratio (LR+) of 108 and a negative likelihood ratio (LR–) of 0.07 for detecting bladder cancer. Patients with gross hematuria are twice as likely as those with microscopic hematuria to have an abnormal CTU (SOR: C, cohort studies of disease-oriented evidence and consensus guidelines).

A 2012 retrospective cohort study (N=359) compared unenhanced CT with CTU for detecting disease in adults 40 years of age or younger (mean age 32.7 years) presenting with microscopic and gross hematuria.1 Findings were correlated with follow-up examinations and medical record data to determine true- or false-positive results. A clinically significant source—including tumor, laceration, calculi, cystitis, obstruction, fistula, atrophic kidney, and neurogenic bladder—was found in 30% (42/142) of CTUs for patients with gross hematuria. Overall, 95% (92/97) of significant findings for gross and microscopic hematuria were evident on unenhanced images. All important missed lesions occurred in patients with predisposing conditions for urologic disease such as prior malignancy, history of recurrent UTIs, spinal cord injury, multiple sclerosis, and pyuria.1

A 2006 prospective cohort study (N=200) evaluated CTU for diagnosing bladder cancer in patients older than 40 years (mean 67 years) with gross hematuria and no infection.2 Patients received same-day CTU, urine cytology, and flexible cystoscopy. CTUs and flexible cystoscopies were scored on a 3-point scale quantifying the probability of bladder cancer: (1) normal, (2) equivocal or abnormal, and (3) bladder tumor. CTU, cystoscopy, and pathological findings were subsequently compared. Two lesions out of 45 (prostate cancer and squamous metaplasia) were missed on CTU. Conversely, 1 tumor originally classified as negative on

cystoscopy was identified on CTU. CTU compared with histopathological findings obtained through cystoscopy had a sensitivity of 93% and a specificity of 99% with a LR+ of 108 (95% CI, 15–763) and LR– of 0.07 (95% CI, 0.02–0.20) for detecting bladder cancer. A 2011 prospective cohort study evaluated CTU for upper urinary tract (UUT) imaging in 841 consecutive patients 18 to 99 years old (mean 56.7 years) with microscopic or gross hematuria.3 Patients underwent initial evaluation with history and examination, urine dipstick confirmed by microscopic urinalysis, ultrasonography, cystoscopy, and cytology. Additional UUT imaging (n=525) using 4-phase CTU (or magnetic resonance urography [MRU] when CTU was contraindicated) was determined according to a risk-based algorithm and abnormal findings on cystoscopy or ultrasonography. Predictors for positive CTU/MRU findings were patients with gross hematuria compared to microscopic hematuria (odds ratio [OR] 2.6; 95% CI, 1.3–5.1) and positive initial ultrasonography results of renal mass, UUT tumor, or stones (OR 7.7; 95% CI, 4.0–14.9).3

A 2014 review article described consensus guidelines from various professional organizations on the initial diagnostic workup for hematuria.4 The 2008 American College of Radiology Appropriateness Criteria gave its highest rating to CTU for the initial evaluation of hematuria in all patients except for those with generalized renal parenchymal disease or young females with hemorrhagic cystitis. The 2012 revised American Urological Association guidelines endorse multiphasic CTU as the first-line imaging modality for gross hematuria, and MRU when CTU is contraindicated.

Thomas Kern, MDFariz Remtulla, MD

Jasminder Singh, MDFrances Wen, PhD

Karen Sanders, MS, MS, RNUniversity of Oklahoma School of Community Medicine

Tulsa, OK

1. Lokken RP, Sadow CA, Silverman SG. Diagnostic yield of CT urography in the evaluation of young adults with hematuria. AJR Am J Roentgenol. 2012; 198(3):609–615. [STEP 2]

2. Turney BW, Willatt JM, Nixon D, et al. Computed tomography urography for diagnosing bladder cancer. BJU Int. 2006; 98(2):345–348. [STEP 2]

3. Cauberg EC, Nio CY, de la Rosette JM, et al. Computed tomography-urography for upper urinary tract imaging: is it required for all patients who present with hematuria? J Endourol. 2011; 25(11):1733–1740. [STEP 3]

4. Heller MT, Tublin ME. In search of a consensus: evaluation of the patient with hematuria in an era of cost containment. AJR Am J Roentgenol. 2014; 202(6):1179–1186. [STEP 5]

Evidence-Based Practice / Vol. 19, No. 8 7

attendance (2 trials, n=30,243; MD 4% higher attendance; 95% CI, –6 to 14).1

In a 2013 cluster-randomized trial, 1 million children <5 years old in STH endemic areas of Northern India were randomized to 4 treatment groups and followed for 5 years.2 The primary endpoint of the study was mortality. Effects on weight were evaluated as a secondary endpoint. Participants received oral administration of vitamin A (retinol capsule of 200,000 IU every 6 months), deworming with albendazole 400 mg, both, or neither (control group). After at least 2 years of treatment, helminth infection decreased in the albendazole treatment groups (the study data incorporated both the albendazole alone and albendazole plus vitamin A groups) with nematode egg presence decreasing from 36% to 16%, but no significant difference was noted in weight gain between the control and the combined 3 treatment groups (MD 0.04 kg; 95% CI, –0.14 to 0.21). Deworming also had little effect on mortality (2.5% albendazole vs 2.6% control; risk ratio [RR] 0.95; 95% CI, 0.89–1.0). The study’s authors noted the study was underpowered to detect a small weight change but was adequate to detect an important effect on mortality.2

Listing both “S” (formal systematic reviews, including more than 1 RCT) and “E” (expert opinion/consensus) evidence, the World Health Organization (WHO) 2006 manual for health professionals reaffirmed the recommendations of the 2002 WHO Expert Committee on Prevention and Control of STH disease by continuing to recommend routine community deworming of children (albendazole 400 mg or mebendazole 500 mg orally every 6 or 12 months) in areas with a high prevalence (>50%) of STH infection, in order to decrease the morbidity associated with the disease.3

Ricardo Sequeira, MDLyrad Riley, MD

Eglin FMREglin Air Force Base, FL

The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views

of the US Air Force Medical Service or the US Air Force at large.

1. Taylor-Robinson DC, Maayan N, Soares-Weiser K, et al. Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin and school performance. Cochrane Database Syst Rev. 2012; (7):CD000371. [STEP 1]

2. Awashti S, Peto R, Read S, et al. Population deworming every 6 months with albendazole in 1 million pre-school children in North India: DEVTA, a cluster-randomised trial. Lancet. 2013; 381(9876):1478–1486. [STEP 2]

3. World Health Organization. Preventive chemotherapy in human helminthiasis. Coordinated use of antihelminthic drugs in control interventions: a manual for health professionals and programme managers. Geneva, Switzerland: WHO; 2006. http://apps.who.int/iris/bitstream/10665/43545/1/9241547103_eng.pdf. Accessed July 14, 2016. [STEP 5]

Do routine community deworming programs in populations with high disease burdens decrease morbidity or improve child growth, cognition, and school performance?

Evidence-Based AnswerTargeted deworming programs that include a “test and treat” strategy for soil-transmitted helminth (STH) infections improve child growth and decrease morbidity (increase in weight, 0.58 kg and hemoglobin, 0.37 g/dL). Targeted deworming programs do not improve cognitive function (SOR: B, few small RCTs). There is no evidence to support routine treatment of all at-risk children in populations with a high disease burden (SOR: B, systematic reviews of low-quality RCTs).

A 2012 Cochrane review of 41 RCTs (N=65,168 children ≤16 years old from 23 low income countries with a high endemic burden of STH infection) compared the effects of deworming on weight, hemoglobin (considered a marker of disease burden and morbidity), and formal intellectual development tests with placebo or no treatment.1 Children who tested positive during screening for intestinal helminthes and were treated with albendazole (400 mg × 3 doses, on 3 consecutive days), pyrantel (11 mg/kg once), or piperazine (3 g once) gained more weight over 4 to 16 weeks compared with children given placebo (3 trials, n=139; mean difference [MD] 0.58 kg; 95% CI, 0.4–0.6). Children who tested positive and were treated as above also showed an increase in hemoglobin over 2 to 8 months (2 trials, n=108; MD 0.37 g/dL; 95% CI, 0.1–0.64). In 2 other low-quality trials no statistically significant effect was noted on cognitive function after treatment.1

In trials comparing treatment with multiple doses of deworming medication (albendazole, mebendazole, levamisole, or pyrantel) versus placebo over 1 year in children living in areas with high endemic burden of STH infection who were not screened for disease, there was no improvement in growth as measured by either an increase in weight (7 trials, n=2,460; MD 0.06 kg; 95% CI, –0.17 to 0.30) or an increase in height (7 trials, n=1,779; MD –0.02 cm; 95% CI; –0.17 to 0.12). Additionally, the trials did not show an increase in hemoglobin (4 trials, n=807; MD 0.01 g/dL lower; 95% CI, –0.14 to 0.13); change in cognition (3 trials, n=30,243; psychometric testing data not provided in review); or an improvement in school

Evidence-Based Practice / August 20168

Does morphine sleep prolong latent labor?

Evidence-Based AnswerThe answer is unknown. However, approximately 62% of patients with latent labor treated with morphine sleep will then be admitted for labor. Patients who are at term, primigravid, and have cervical effacement >50% are more likely to be admitted for active labor after morphine sleep (SOR: B, retrospective cohort study).

A retrospective cohort study examined the incidence of admission for labor after morphine sleep and evaluated which maternal factors led to progression of labor.1 Charts were reviewed of pregnant patients over 37 weeks who had painful contractions without cervical change treated with morphine sulfate (>10 mg IM or IV) and observed on labor and delivery. A total of 58 patients were treated with morphine and 36 patients (62%) were admitted for active labor. An additional 5 patients (9%) were admitted for category 2 fetal tracing. Characteristics associated with subsequent admission for labor versus being discharged pregnant were term gestation (32 patients admitted vs 7 patients discharged; P<.01), primigravid status (21 patients admitted vs 4 patients discharged; P<.02), and effacement >50% (23 patients admitted vs 3 patients discharged; P=.03). Patients with a previous cesarean were more likely to be discharged pregnant (1 vs 4 patients; P<.01). Bishop score and >6 contractions an hour were not helpful in predicting admission for labor.1

A systematic review, which included 2 systematic reviews and 48 RCTS (N≥9,800), examined the effectiveness of various modes of administration and formulations of opioids for labor pain relief.2 Data could not be pooled due to a lack of consistency in outcome measures. IV morphine compared with IV pethidine did not show a difference in mother’s satisfaction with pain relief after labor (1 trial, n=141; 14% vs 4%; P>.05). This review was unable to determine the rates of cesarean section with morphine and did not examine the effects of opioids on latent labor. A Cochrane review included 57 RCTs involving more than 7,000 women studying the effectiveness and side effects of parenteral opioids in labor.3 Two trials (n=163) were included in a comparison of IV morphine and IV pethidine. Patients receiving morphine were

less likely to be satisfied with analgesia than patients receiving pethidine (1 trial, n=143; RR 0.87; 95% CI, 0.78–0.98) and were more likely to request a second dose (1 trial, n=143; RR 3.4; 95% CI, 1.9–6.1).

Alison Shmerling, MD, MPHMelissa Beagle, MD, MPH

University of Colorado FMRDenver, CO

1. Mackeen AD, Fehnel E, Berghella V, et al. Morphine sleep in pregnancy. Am J Perinatol. 2014; 1(1):85–89. [STEP 3]

2. Bricker L, Lavender T. Parenteral opioids for labor pain relief: a systematic review. Am J Obstet Gynecol. 2002; 186(5 suppl Nature):S94–S109. [STEP 2]

3. Ullman R, Smith LA, Burns E, et al. Parenteral opioids for maternal pain management in labour. Cochrane Database Syst Rev. 2010; (9):CD007396. [STEP 2]

Is cryotherapy the best treatment for cutaneous warts?

Evidence-Based AnswerProbably not. Standard cryotherapy (liquid nitrogen for ≤15 seconds) is no better than placebo or no therapy. Although aggressive cryotherapy (15–30 seconds) is better than standard cryotherapy, it appears to have an increased risk of harm and has not been compared with other therapies. Salicylic acid treatment may be preferable because it is more effective than placebo and appears to have a better safety profile than aggressive cryotherapy. Other therapies are more effective than placebo, but have not been compared with salicylic acid or cryotherapy (SOR: A, systematic review of RCTs).

In a 2012 Cochrane review of pooled data from 85 RCTs (N=8,815) conducted in primary and secondary care settings in Europe and the United States, various treatments for cutaneous warts on otherwise healthy children and adults were compared with placebo, no treatment, and, to a lesser extent, each other.1 When standard cryotherapy (liquid nitrogen for ≤15 seconds usually applied every 2 weeks) was compared with placebo for all body sites, no difference was noted in cure rate (disappearance of warty growth) assessed at 2 to 4 months (see TABLE). Aggressive cryotherapy was differentiated from gentle cryotherapy by duration of application (usually 20–30 seconds vs 10–20 seconds, but 1 study used 2 minutes vs 15 seconds) or number of freezes per session (double vs single). Aggressive cryotherapy (usually applied every 1–3 weeks) led to an increased cure rate

Evidence-Based Practice / Vol. 19, No. 8 9

(vs gentle cryotherapy assessed at 1–3 months; 4 trials, n=304; RR 1.9; 95% CI 1.15–3.15), but more pain (1 trial, n=124; RR 1.5; 95% CI, 0.96–2.2) and more blistering (RR 1.3; 95% CI, 0.84–1.9).1

When standard cryotherapy, applied every 1 to 3 weeks, was directly compared with daily topical salicylic acid, usually 17% to 40% concentration with or without lactic acid in 4% to 17% concentration, no significant difference was noted in cure rates assessed at 3 to 6 months. There was no comparison of aggressive cryotherapy and salicylic acid.1

Salicylic acid was significantly more effective than placebo in clearance of warts from all sites. Only a single case of cellulitis and some minor skin irritation was reported with salicylic acid.1

A previous 2011 meta-analysis of data from 77 RCTs also evaluated topical treatments of cutaneous warts and included many of the same studies as the previously referenced 2012 study.2 However, this meta-analysis estimated the cure rate of each treatment from pooled data of all studies in each treatment arm. Although not representing a head-to-head comparison, this analysis did provide some information on relative effectiveness of the treatments (see TABLE). Both salicylic acid and aggressive cryotherapy were similarly effective in treating warts, but salicylic acid treatment may have had fewer adverse effects. This finding led the authors to recommend topical application of salicylic acid as first-line treatment of warts and aggressive cryotherapy as second line.

Other therapies that performed better than placebo (bleomycin, dinitrochlorobenzene, and 5-fluorouacil) were recommended as third line.2

Jennifer E. Salguero, DORobert K. Persons, DO, FAAFP

Eglin FMREglin Air Force Base, FL

The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views

of the US Air Force Medical Service or the US Air Force at large.

1. Kwok CS, Gibbs S, Bennett C, et al. Topical treatments for cutaneous warts. Cochrane Database Syst Rev. 2012; (9):CD001781. [STEP 1]

2. Kwok CS, Holland R, Gibbs S. Efficacy of topical treatments for cutaneous warts: a meta-analysis and pooled analysis of randomized controlled trials. Br J Dermatol. 2011; 165(2):233–246. [STEP 1]

Do annual preventive examinations lead to better mortality outcomes?

Evidence-Based AnswerNo. Routine periodic physical health examinations do not lead to improved cardiovascular, cancer, or total mortality outcomes (SOR: A, meta-analyses of RCTs).

A 2012 systematic review and meta-analysis of 14 RCTs (N=182,880) evaluated the effect of adult health checks on mortality outcomes.1 Patients were 18 to 74 years old (trials enrolling only patients >65 were excluded) and were not recruited with any specific disease or risk factor for disease.

Risk ratios of cure and summary cure rates of various wart treatments1,2

Treatment Comparison No. of trials No. of patients Risk ratio of cure 95% CI Summary cure rate

Cryotherapy1 Placebo 3 227 1.5 0.65–3.2 NA

Cryotherapy1 Salicylic acid 4 707 1.2 0.88–1.7 NA

Aggressive cryotherapy1 Gentle cryotherapy 4 592 1.9 1.2–3.2a NA

Salicylic acid1 Placebo/no treatment 6 486 1.6 1.2–2.0a NA

Salicylic acid2 NA 16 813 NA NA 52%

Cryotherapy² NA 17 692 NA NA 49%

Aggressive cryotherapy² NA 4 184 NA NA 54%

Bleomycin² NA 3 72 NA NA 90%

Topical NA 2 40 NA NA 80% dinitrochlorobenzene (DNCB)2

Topical 5-fluorouracil NA 3 129 NA NA 52% (5-FU)² aStatistically significant.NA=not applicable.

TABLE

continued

Evidence-Based Practice / August 201610

Health checks were defined as screening for more than 1 disease or risk factor in more than 1 organ system, whether performed only once or repeatedly and thus excluded trials screening for a single disease or multiple diseases in only 1 organ system. Health checks were performed by any type of healthcare provider in general practice settings (5 RCTs), community screening clinics (8 RCTs), or the workplace (1 RCT). The control group was not offered health checks.1

All-cause mortality was not reduced after a median follow-up of 9 years (range 4–22 years) in patients undergoing health checks (9 trials, n=155,899 with 11,940 deaths; risk ratio [RR] 0.99; 95% CI, 0.95–1.0). Cardiovascular death was not reduced in the health check group at a median follow-up of 10 years (8 trials, n=152,435 with 4,567 deaths; RR 1.0; 95% CI, 0.91–1.2); however, there was statistically significant heterogeneity in this outcome. Health checks did not reduce cancer-related deaths after a median follow-up of 10 years (8 trials, n=139,290 with 3,663 deaths; RR 1.0; 95% CI, 0.92–1.1). There was no statistically significant heterogeneity in the all-cause mortality or cancer-related death outcomes. Six trials began before 1970 when some current risk reduction interventions were not available. The most recent study started in 1999. Six RCTs had less than 10 years of follow-up, which may have not been long enough to observe a mortality benefit. There was a risk of performance bias because 3 of 9 studies evaluating total mortality were not blinded.1

A 2014 systematic review and meta-analysis of 6 RCTs (N=42,787) evaluated the mortality benefits of health checks conducted within general medical practices.2 Four of the RCTs were included in the 2012 systematic review and 2 had been excluded because they screened for specific diseases (cardiovascular disease and diabetes mellitus). The trials enrolled patients with mean ages from 35 to 65 years old. Trials offering health checks in community settings or the workplace were excluded. Health checks were defined as a comprehensive assessment to detect and manage risk factors and/or chronic diseases in a single visit (1 RCT) or multiple visits (5 RCTs). Health checks were performed by a clinician or trained practice staff.2

All-cause mortality was not reduced with health checks compared with usual care (4 trials, n=23,957; odds ratio [OR] 1.0; 95% CI, 0.90–1.2). Cardiovascular

disease (CVD) mortality was increased in the health check group (3 trials, n=22,450; OR 1.3; 95% CI, 1.0–1.7). Despite differences in CVD definitions, there was no statistically significant heterogeneity. All of the trials were limited by relatively short follow-up (≤10 years), lack of blinding, and possible contamination bias (patients in the usual care group may have received the same interventions as health check groups). The increased CVD mortality in the health check group may have been caused by an increased recognition of asymptomatic CVD diagnosed through screening.2

Russell Mayo, MDMichael Downs, MD

Cherry Fu, MDDavid Horner, MD

UAMS Southwest FMRTexarkana, AR

1. Krogsbøll LT, Jørgensen KJ, Grønhøj Larsen C, et al. General health checks in adults for reducing morbidity and mortality from disease: Cochrane systematic review and meta-analysis. BMJ. 2012; 345:e7191. [STEP 1]

2. Si S, Moss JR, Sullivan TR, et al. Effectiveness of general practice-based health checks: a systematic review and meta-analysis. Br J Gen Pract. 2014; 64(618):e47–e53. [STEP 1]

Is transcutaneous electrical nerve stimulation (TENS) more effective than placebo for management of chronic low back pain?

Evidence-Based AnswerTENS offers no significant benefit for chronic low back pain (LBP) in multiple disability and quality-of-life measures (SOR: A, meta-analysis of RCTs), but does offer small benefit in pain reduction compared with sham treatment (SOR: B, 2 RCTs). TENS may be useful as an adjunct in select patients for pain control to reduce the need for medications (SOR: C, based on consensus guideline).

A 2008 meta-analysis of 4 RCTS (N=585) compared the use of TENS with placebo in the management of chronic LBP.1 Patients older than 18 years with pain localized between the gluteal fold and the costal margin and lasting longer than 12 weeks were treated with TENS for 20 minutes to 3 hours per day over 2 to 4 weeks. No differences were noted between TENS and placebo in back-specific functional status (as assessed by the Roland Morris Disability Questionnaire [RDQ] and Oswestry Disability Index), generic health status

Evidence-Based Practice / Vol. 19, No. 8 11

(as assessed by the Sickness Impact Profile or SF-36 Health Survey [SF-36]), or work disability (loss of work, sick days). Improvement was limited in pain intensity in a small single trial (n=27) at the end of 2 weeks, as measured on a 0–100 mm visual analog scale (VAS) (mean difference [MD] –17; 95% CI, –27 to –7).1

A 2012 multicenter RCT (N=236) compared TENS for the treatment of chronic LBP with or without unilateral radicular pain to sham therapy (placebo).2 Patients 28 to 86 years old (mean age 53 years) with pain lasting ≥3 months at an average intensity of >40 on a 0–100 mm VAS were treated with TENS or sham therapy for four 1-hour daily treatment sessions over the course of 3 months. No difference was noted in the primary outcome of improvement in functional status at 6 weeks as assessed by the RDQ. Secondary outcomes, measured at 12 weeks, noted no change in functional status determined by RDQ, no change in functional repercussions of pain on quality of life (4 dimensions of Dallas questionnaire), no change in quality of life (SF-36 scale), no decrease in the use of analgesic and anti-inflammatory medications, and no difference in patient compliance with assigned treatment. TENS did result in 25% of patients achieving a 50% decrease in lumbar pain from the initial VAS to the 12th week VAS, as measured by a 0–100 mm VAS, compared with 6.7% of patients in the sham therapy group (P=.0003; NNT=5).2

The 2011 Agency for Healthcare Research and Quality guideline for the management of LBP stated that TENS may be useful for some patients for pain control and to reduce the need for medications after a short trial (2–3 treatments) using different stimulation parameters to determine if the patient will respond to this modality.3

Matthew W. Greene, MDRoselyn Jan W. Clemente-Fuentes, MD

Eglin FMREglin Air Force Base, FL

The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views

of the US Air Force Medical Service or the US Air Force at large.

1. Khaddilkar A, Odebiyi DO, Brosseau L, et al. Transcutaneous electrical nerve stimulation (TENS) versus placebo for chronic low-back pain. Cochrane Database Syst Rev. 2008; (4):CD003008. [STEP 1]

2. Buchmuller A, Navez M, Milletre-Bernardin, et al. Value of TENS for relief of chronic low back pain with or without radicular pain. Eur J Pain. 2012; 16(5):656–665. [STEP 2]

3. Agency for Healthcare Research and Quality. Guideline for the evidence-informed primary care management of low back pain. 3rd ed. Edmonton (AB): Toward Optimized Practice; 2011. http://www.guideline.gov/content.aspx?id=37954. Accessed July 14, 2016. [STEP 5]

Do ultrasound-guided steroid injections have better results than blind injections in patients with trochanteric bursitis (greater trochanteric pain syndrome)?

Evidence-Based AnswerThe answer is unclear. The greater trochanteric bursa appears to be the right target, because ultrasound-guided injections of the greater trochanteric bursa improve greater trochanteric pain syndrome (GTPS) more than ultrasound-guided injection of the subgluteus medius bursa (SOR: C, case series). Blind corticosteroid injections of the greater trochanter result in improvement at 3 months but not at 12 months (SOR: B, single RCT). However, fluoroscopy-guided and blind injections of the trochanteric bursa have equivalent outcomes at 1 and 3 months (SOR: B, single RCT).

A 2013 single-site retrospective analysis of 65 ultrasound-guided injections of either the greater trochanteric bursa or the subgluteus medius bursa in adults with GTPS evaluated improvement of pain scores via a 10-cm visual analog scale (VAS) between preprocedure and 14 days postprocedure.1 Injections of 1 mL triamcinolone (40 mg/mL) with 2 mL 0.5% preservative-free ropivacaine of the greater trochanteric bursa showed an average 3-point improvement on VAS scoring compared with a 0-point change in scoring after injection of the subgluteus medius bursa (P<.01). There was no association between pain reduction and the variables of age, sex, and number of previous injections and no association of pain reduction and ultrasound findings, including tendinopathy, bursitis, and enthesopathy.1

A 2011 RCT (N=120) evaluated the effectiveness of corticosteroid injections versus routine care for GTPS.2

A 5 mL solution containing 40 mg triamcinolone acetate combined with 1%–2% lidocaine was used to inject around the greater trochanter, whereas routine care consisted of administration of analgesics. The primary outcomes were recovery, defined as totally or strongly recovered on a 7-point Likert scale (1=fully recovered to 7=worse than ever) and severity of pain, at rest and with activity (numeric rating scale, 0=no pain, 10=worst conceivable pain), at 3 and 12 months. Recovery at 3 months was noted more often in the steroid group than the routine care group (odds ratio [OR] 2.4; 95% CI, 1.1–5.0, NNT=5). This benefit was

Evidence-Based Practice / August 201612

no longer observed at 12 months (OR 1.1; 95% CI, 0.5–2.3). At 3 months there was greater improvement in pain at rest (adjusted mean difference [aMD] 1.2; 95% CI, 0.31–2.1) and with activity (aMD 1.3; 95% CI, 0.32–2.3) in the injection group. At 12 months, pain at rest and pain with activity did not differ between groups (aMD 0.14; 95% CI, –0.75 to 1.0; and aMD 0.45; 95% CI, –0.55 to1.5, respectively).2

In 2008, a multicenter double-blind RCT (N=65 adults) compared intra-trochanteric bursa fluoroscopy-guided versus blind landmark trochanteric bursa corticosteroid injections of a 4 mL solution containing 60 mg depo-methylprednisolone and 0.5% bupivacaine for GTPS.3 A greater than 50% improvement in the 0–10 pain scale scores at 1 and 3 months was used to quantify pain relief postinjection. Compared with baseline in both groups, fluoroscopy-guided and landmark-guided injection yielded statistically significant pain improvement scores at 1 month (fluoroscopy-guided: 5.1 to 2.7, P=.0001 at rest and 7.8 to 5.0, P<.0001 with activity; landmark-guided: 4.6 to 2.2, P=.0001 at rest and 7.2 to 4.0, P<.0001 with activity). However, no significant difference in pain was noted between fluoroscopy-guided and blind injections at the 1- and 3-month follow-ups.3

Kevin Ericson, MDTravis Dams, MD

Kelly Marszalek, MDMegan LaBuz, MD

St. Joseph Regional Medical Center FMRMishawaka, IN

1. Mcevoy JR, Lee KS, Blankenbaker DG, et al. Ultrasound-guided corticosteroid injections for treatment of greater trochanteric pain syndrome: greater trochanter bursa versus subgluteus medius bursa. AJR Am J Roentgenol. 2013; 201(2):W313–W317. [STEP 4]

2. Brinks A, van Rijn RM, Willemsen SP, et al. Corticosteroid injections for greater trochanteric pain syndrome: a randomized controlled trial in primary care. Ann Fam Med. 2011; 9(3):226–234. [STEP 2]

3. Cohen SP, Strassels SA, Foster L, et al. Comparison of fluoroscopically guided and blind corticosteroid injections for greater trochanteric pain syndrome: multicentre randomised controlled trial. BMJ. 2009; 338:b1088. [STEP 2]

What is the most effective corticosteroid regimen for treating COPD exacerbations?

Evidence-Based AnswerThree- to 7-day courses of systemic corticosteroids appear to be as effective as 10- to 15-day courses for the treatment of acute chronic obstructive pulmonary disease (COPD) exacerbations, although optimum dosage and route are unclear (SOR B; meta-analysis of heterogeneous RCTs). Currently recommended doses include 30 to 40 mg orally a day with durations between 5 and 14 days (SOR C; expert opinions).

A 2014 meta-analysis compared short-duration (3–7 days) with long-duration (10–15 days) corticosteroids in adults with COPD exacerbations who did not require mechanical ventilation (5 RCTs, N=519, mean ages 54–73 years, male predominance).1 All patients had COPD classified as severe or very severe. Three trials used oral prednisolone (most commonly 30 mg daily), 1 trial used intravenous (IV) methylprednisolone 40 mg IV on day 1 followed by oral prednisolone 40 mg daily, and 1 trial used IV methylprednisolone 0.5 mg/kg every 6 hours for 3 days in the short course arm and tapering IV doses for 10 days in the long course arm. Reported outcomes included mortality, treatment failure (defined as the need for additional treatment, hospital admission/readmission, or urgent/unscheduled physician encounter), relapse (defined as treatment for new acute exacerbation of COPD, or hospital admission/readmission for COPD), and adverse events (hyperglycemia, symptomatic gastroesophageal reflux, or hypertension). No differences were noted between short and long courses of systemic steroids for treatment failure (4 RCTs, n=457; odds ratio [OR] 0.72; 95% CI, 0.36–1.5), relapse (4 RCTs, n=478; OR 1.0; 95% CI, 0.70–1.6), mortality (2 RCTs, n=336; OR 0.91; 95% CI, 0.40–2.1), or adverse events. Studies had incomplete reporting of data and unclear definitions of exacerbation. The authors of this review concluded that 5 days of oral corticosteroid treatment are likely sufficient for acute COPD exacerbations.1

Evidence-informed guidelines by the National Institute for Health and Care Excellence (NICE) recommended that oral corticosteroids be considered for COPD exacerbations in the outpatient setting (grade B, based on at least 1 controlled study or quasi-

ERRATUM

In the July 2016 issue, the second title in the Table of Contents for page 6 was misprinted. The title should have been, "Detrimental effects of delayed antibioticsin bacterial meningitis."

We sincerely regret the error and apologize for any confusion.

Evidence-Based Practice / Vol. 19, No. 8 13

experimental design) and be given to all patients in the hospital setting.2 The recommended dose was prednisolone 30 mg daily for 7 to 14 days. Evidence-informed 2015 guidelines by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommended treating COPD exacerbations preferably with oral prednisone 40 mg daily for 5 days, although data were insufficient to provide a firm conclusion on optimal duration.3

Natalia Mendoza, MDAnne Cooper, MD

Tacoma Family MedicineTacoma, WA

1. Walters JAE, Tan DJ, White CJ, et al. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014; (12):CD006897. [STEP 2]

2. National Institute for Health and Care Excellence. Chronic obstructive pulmonary disease. CG101. https://www.nice.org.uk/guidance/cg101. Published June 2010. Accessed July 17, 2016. [STEP 5]

3. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease: Updated 2015. http://www.goldcopd.it/materiale/2015/GOLD_Report_2015.pdf. Accessed July 17, 2016. [STEP 5]

In otherwise healthy patients with chronic inorganic constipation, are there adverse effects from long-term daily use of polyethylene glycol?

Evidence-Based AnswerChronic daily use (≥3 months) of polyethylene glycol (PEG) does not appear to cause major adverse effects or laboratory abnormalities in children (SOR: A, systematic review of RCTs) or adults (SOR: B, single RCT). Minor gastrointestinal side effects such as transient diarrhea, flatus, and abdominal distention were reported, but were not consistently different from comparators (SOR: B, RCTs with inconsistent results).

A 2012 systematic review studied various osmotic and stimulant laxatives for the outpatient management of functional (defined as no underlying organic cause identified) constipation in patients 0 to 18 years old.1 This meta-analysis identified 3 RCTs evaluating PEG compared with lactulose and Milk of Magnesia (MOM) for periods of 12 weeks or longer. One study (n=58) compared PEG 3350 plus electrolytes 1 packet daily (13.8 g powder) with lactulose 10 g daily. Another study (n=96) compared

PEG 4000 4 g daily with lactulose 3.33 g daily, with doses doubled if ineffective. Laboratory tests of total protein, albumin, iron, electrolytes, and vitamins B9, A, and D were performed.1

No serious treatment-related adverse effects or laboratory test changes were reported in either trial over 12 weeks. Common adverse effects were diarrhea, abdominal pain, nausea, vomiting, and pruritus ani. However, no statistically significant difference was noted between the 2 groups—24% of PEG patients compared with 37% of lactulose patients experienced at least 1 adverse event (odds ratio [OR] 0.37; 95% CI, 0.14–1.0).1

The third RCT examined PEG compared with MOM over 12 months of treatment. Seventy-nine children older than 4 years were included. The PEG group received an initial dose of 0.7 g/kg daily, and the MOM group received 2 mL/kg daily. Both groups were given instructions to titrate medication doses to achieve 1 or 2 soft stools daily without diarrhea. Parents kept a diary of bowel movements, fecal incontinence, and abdominal pain. In some children, electrolytes, BUN, creatinine, alkaline phosphatase, AST, ALT, and CBC were performed at baseline and at the 3-, 6-, and 12-month follow-up visits.1

No clinically significant changes in these laboratory tests were noted in either group. The only adverse effect was an allergy to PEG reported in 1 patient. There were no complaints of increased flatus, abdominal distention, or new onset of abdominal pain, and no abnormal physical examination findings in either the PEG or MOM group.1

In adults, 1 RCT published in 2007 examined the safety and efficacy of PEG over 6 months among 304 otherwise healthy patients 20 to 92 years old without irritable bowel syndrome who had chronic constipation based on modified ROME criteria.2 Patients received PEG 17 g or placebo once daily. Laboratory tests including hematology, electrolytes, amylase, GGT, TSH, uric acid, lipids, and urinalysis collected at baseline and repeated at 6 months. Gastrointestinal (GI) symptoms and any other self-reported adverse effects were recorded. At 6 months, GI complaints of distention, diarrhea, flatulence, and nausea as a group were more frequent in the PEG group compared with placebo (PEG 39.7% vs placebo 25%; P=.015). However, these side effects were not individually statistically significant. No clinically

Evidence-Based Practice / August 201614

significant changes in laboratory results were reported but no numbers or comparisons are available.2

Tina Y. Chang, MDGrant Scull, MD

Group Health Cooperative FMRSeattle, WA

1. Gordon M, Naidoo K, Akobeng AK, et al. Osmotic and stimulant laxatives for the management of childhood constipation. Cochrane Database Syst Rev. 2012; (7):CD009118. [STEP 1]

2. Dipalma J, Cleveland MV, McGowan J, et al. A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation. Am J Gastroenterol. 2007; 102(7):1436–1441. [STEP 2]

Is there increased risk of melanoma in patients that use tanning beds?

Evidence-Based AnswerYes. The risk of melanoma is increased by about 20% in patients who have ever used a tanning bed compared to nonusers and the rate increases with frequent use (SOR: B, meta-analysis of cohort and case-control studies). There appears to be an increased risk of melanoma with use of newer tanning devices compared with older versions (SOR: B, case-control study).

A 2014 meta-analysis of 31 studies (N=248,062) evaluated the incidence of melanoma and the use of indoor tanning, adjusting for geographic location.1 This meta-analysis included cohort, case-control, and cross-sectional studies that evaluated melanoma development, use or nonuse of indoor tanning, and gave outcomes as odds ratios (ORs). Melanoma was more likely to develop in patients who had ever used versus never used indoor tanning (OR 1.2; 95% CI, 1.1–1.3). There was also an increased risk of melanoma in patients who had used tanning beds more than 10 times compared with patients who had never used a tanning bed (OR 1.3; 95% CI, 1.1–1.7).1

A 2010 case-control study included in the 2014 meta-analysis involved 1,167 cases of melanoma and 1,101 controls (matched 1:1 to cases based on age and sex). This study evaluated the association of melanoma with various types of tanning equipment.2 Investigators enrolled anyone with a valid driver’s license or government identification card and a new diagnosis of cutaneous melanoma in the state of Minnesota between July 2004 and December 2007. The device types included conventional, high-speed/high intensity, and high-pressure based tanning equipment.

The risk of subsequent melanoma development was elevated in patients who used high-speed/intensity beds (OR 2.9; 95% CI, 2.0–4.0), high-pressure beds (OR 4.4; 95% CI, 2.5–8.0), and conventional beds (OR 1.8; 95% CI, 1.4–2.2) compared with controls. The differences in these risks suggested a higher risk of melanoma in newer styles of tanning beds.2

In 2009, the International Agency for Research on Cancer (IARC) first declared tanning devices to be carcinogenic.3 The IARC based this claim on the findings of a 2006 systematic review and meta-analysis of 19 case-control studies (N=7,355 cases of melanoma) evaluating the risk of melanoma with use of tanning beds.4 Studies were included if they were case-control, cohort, or cross-sectional studies published as original articles that at a minimum evaluated the risk of melanoma in patients exposed to a tanning device. Studies were excluded if they did not contain a relative risk for melanoma associated with tanning bed exposure. Any use of a tanning bed was associated with an increased risk of melanoma compared with nonuse (relative risk 1.2; 95% CI, 1.0–1.3). In August 2015, the American Academy of Dermatology/Association (AAD/A) amended their 1998 position statement on the use of indoor tanning.5 The AAD/A strongly recommended against the use of indoor tanning devices, given the rising incidence of melanoma and nonmelanoma skin cancer in the United States. They recommended that minors not be allowed to use tanning beds, and encouraged the implementation of educational resources to better inform the general public of the harms associated with indoor tanning.

Alex Houser, DOSean Wise, MD

Womack FMRFt. Bragg, NC

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views

of the Medical Department of the US Army or the US Army Service at large.

1. Colantonio S, Bracken MB, Beecker J. The association of indoor tanning and melanoma in adults: systematic review and meta-analysis. J Am Acad Dermatol. 2014; 70(5):847–57.e1–18. [STEP 2]

2. Lazovich DA, Vogel RI, Berwick M, et al. Indoor tanning and risk of melanoma: a case-control study in a highly exposed population. Cancer Epidemiol Biomarkers Prev. 2010; 19(6):1557–1568. [STEP 4]

3. WHO International Agency for Research on Cancer Monograph Working Group. A review of human carcinogens—part D: radiation. Lancet Oncol. 2009; 10(8):751–752. [STEP 5]

4. International Agency for Research on Cancer Working Group on artificial ultraviolet (UV) light and skin cancer. The association of use of sunbeds with cutaneous malignant melanoma and other skin cancers: a systematic review. Int J Cancer. 2007; 120(5):1116–1122. [STEP 3]

5. American Academy of Dermatology (AAD) and AAD Association. Position statement on indoor tanning. https://www.aad.org/forms/policies/uploads/ps/ps-indoor%20tanning.pdf. Amended August 22, 2015. Accessed July 15, 2016.

EBP

Evidence-Based Practice / Vol. 19, No. 8 15

Spotlight on Pharmacy

Is prolonged-release oxycodone/naloxone as safe, tolerable, and effective as prolonged-release oxycodone monotherapy for chronic nonmalignant pain?

Bottom lineProlonged-release oxycodone/naloxone (OXN) is no different from prolonged-release oxycodone alone (OXY) for pain control (SOR: A, pooled analysis of 2 RCTs and single RCT); however, OXN use is associated with less euphoria and a lower incidence of constipation (SOR: B, RCTs).

Evidence summaryIn a prospective, pooled analysis of 2 double-blinded RCTs (N=587), patients previously receiving OXY were randomized blindly to continue OXY or switch to OXN for chronic, nonmalignant, moderate to severe pain (doses 20–80 mg/d titrated for efficacy).1 Patients’ pain scores on an 11–point visual analog scale (0=no pain, 10=worst pain) at each study visit reflected their pain over the previous 24 hours. Mean pain intensity scores were similar at weeks 1, 4, and 12: OXY 3.5, 3.5, and 3.5 versus OXN 3.6, 3.5, and 3.6, respectively (95% CI for difference at 12 weeks, –0.07 to 0.23). The incidence of constipation was 0.7% for OXN versus 3.4% for OXY (no statistical test reported). Laxative intake was reported less commonly in the OXN group than in the OXY group (36.5% vs 59%; P<.0001).1

A 2012 RCT compared OXN with OXY for postoperative pain control after knee arthroplasty (N=137) for patients aged 18 to 75 years with osteoarthritis who had not received opioids during the past 3 months.2 Pain was assessed using an 11-point numerical rating scale before the first dose of study medication and 1 hour after each dose (administered twice daily). Doses were based on age: 20/10 mg OXN or 20 mg OXY for patients younger than 65 years, 10/5 OXN or 10 OXY for patients aged 65 years or older. The 24-hour average change in pain intensity score from baseline to postoperative day 3 was –1.2 (95% CI, –1.5 to –0.9) for the OXN group and –1.1 (95% CI, –1.4 to –0.9) for the OXY group, with a mean difference between groups of –0.1 (95% CI, –0.5 to 0.3).2

A randomized, double-blind, crossover study tested the abuse potential of OXN versus OXY in nondependent recreational drug users (N=24).3 Visual analog scale scores for “drug liking” (0=strong disliking, 50=neutral, and 100=strong liking) were reported at specific time points from 5 minutes to 8 hours after IV administration of each of the 3 study drugs at each visit. Each visit lasted 2 days and included an overnight stay. Study drugs included placebo (normal saline), oxycodone 0.07 mg/kg + naloxone placebo, and oxycodone 0.07 mg/kg + naloxone 0.035 mg/kg. The mean scores for “drug liking” were higher after OXY than after OXN (95 vs 57, P<.001).

Nicole Payette, PharmD, BCPSAmy J. DiPlacido, MD

Ashley Higbea, PharmD, BCPSUPMC St. Margaret Hospital

Pittsburgh, PA

REFERENCES

1. Löwenstein O, Leyendecker P, Lux EA, et al. Efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of moderate/severe chronic non-malignant pain: results of a prospectively designed pooled analysis of two randomised, double-blind clinical trials. BMC Clin Pharmacol. 2010; 10:10–12. [STEP 2]

2. Kuusniemi K, Zöllner J, Sjövall S, et al. Prolonged-release oxycodone/naloxone in postoperative pain management: from a randomized clinical trial to usual clinical practice. J Int Med Res. 2012; 40(5):1775–1793. [STEP 2]

3. Colucci SV, Perrino PJ, Shram M, et al. Abuse potential of intravenous oxycodone/naloxone solution in nondependent recreational drug users. Clin Drug Investig. 2014; 34(6):421–429. [STEP 2]

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E-1Evidence-Based Practice / Vol. 19, No. 8

Evidence-Based PracticeELECTRONIC VERSION • VOLUME 19 NUMBER 8 AUGUST 2016

When is lead screening appropriate in adolescents?

Evidence-Based AnswerScreen adolescents for lead poisoning only if they are an immigrant or foreign adoptee between the ages of 6 months and 16 years. Routine screening of adolescents is not indicated (SOR: C, based on expert opinion).

No studies specifically address lead screening in adolescents. However, a single study that included adolescents in its population was the basis for a recommendation from the Centers for Disease Control and Prevention (CDC).1 A case series of 242 newly arrived refugees (aged 6 months to 16 years) in New Hampshire conducted in 2003 to 2004 evaluated screening for elevated blood lead levels (BLLs). Ninety-two children were tested on 2 separate occasions. Lead poisoning was defined by at least 1 positive BLL test. Overall, 10.9% had an elevated BLL only on initial testing and 29.3% had an elevated level only on the follow-up test. Of the 92 children, 14.1% had elevated BLLs on both tests. Based largely on this study, the CDC recommends universal lead screening for recent immigrants or foreign adoptees between the ages of 6 months and 16 years.1

In 2006, an evidence summary prepared for the US Preventive Services Task Force (USPSTF) discussed the benefits and harms of screening and intervention for elevated BLLs in asymptomatic children ages 1 to 5 years and pregnant women.2 This review found that likely because of the decreased prevalence of lead poisoning in the United States with the discontinuation of lead-based paints and improved housing environments for children, there was no direct evidence from controlled studies that screening children for elevated BLLs result in improved health outcomes.

Ben Proctor, MDDavid Palombo, MD

Alan LeBato, MDMemorial/LSUHSC-NO FMR

Lake Charles, LA

1. Centers for Disease Control and Prevention (CDC). Elevated blood lead levels in refugee children—New Hampshire 2003–2004. MMWR Morb Mortal Wkly Rep. 2005; 54(2):42–46. [STEP 4]

2. Rischitelli G, Nygren P, Bougatsos C, et al. Screening for elevated lead levels in childhood and pregnancy: an updated summary of evidence for the US Preventive Services Task Force. Pediatrics. 2006; 118(6):e1867–e1895. [STEP 1]

Are pediatric group visits effective for the treatment of obesity?

Evidence-Based AnswerNo. Ambulatory group visit settings have not been shown to have any significant effects on decreasing body mass index (BMI) in obese pediatric patients. Inpatient group visits are effective while continued, but all effects are gone by 18 months after discharge (SOR: B, RCTs).

A 2013 recreation center-based RCT of 541 families in San Diego County, California, examined the effectiveness of family group visits over 2 years on BMI.1 The intervention group participated in six 60-minute group workshops at the recreation center, which were focused on nutritional goals and exercise classes. They also received weekly telephone counseling sessions during the first 6 months. The control group attended science and crafts workshops and were given handouts on nonobesity-related topics. There was no statistically significant change observed in BMI between intervention and control groups over the course of the study. Small decreases were seen in the intervention group’s number of sugary beverages per day (mean of 0.38 vs 0.50 servings; P=.008) and total fat consumption per day (assessed using the Patient-Centered Assessment and Counseling for Exercise plus Nutrition Health and Environment Survey, range of 0–105 points) (mean of 18 vs 19 points; P=.038).1

A 6-month RCT of 165 adolescents with BMI above the 85th percentile examined whether a school-based group visit approach would be effective in decreasing BMI over an academic year.2 All students in the study received preventive services including physical examinations and laboratory screening. The intervention group met with a health educator weekly who helped the students set and reach lifestyle goals. Patients in the control group were more likely to maintain or decrease their BMI z-scores (number of standard deviations above the mean) than patient in the intervention group (72% vs 55%; P<.05). A confounding factor could be sports participation, which was noted to be higher in the control group than in the intervention group (47% vs 28%; P=.02).2

patients were men 40 to 60 years old. Two RCTs investigated increasing fluid intake in patients with 1 past symptomatic calcium stone. One poor-quality study (n=220) supported increasing fluid intake to achieve a urine output of more than 2 L compared with no intervention for the prevention of radiographic or symptomatic recurrence (relative risk [RR] 0.45; 95% CI, 0.24–0.84; NNT=7). The second study (n=21) was of fair quality and showed no effect of high urine output compared with no intervention on radiographic stone recurrence (RR 0.15; 95% CI, 0.02–1.1).1

Hydrochlorothiazide (50 mg daily) and chlorthalidone (25 mg daily) reduced the radiographic or symptomatic recurrence of stones in 5 heterogeneous RCTs (n=300) that compared the intervention with placebo or control in patients with more than 1 previous stone who were already taking increased fluids (RR 0.52; 95% CI, 0.39–0.69; NNT=3). Data from a separate trial (n=51) evaluated symptomatic recurrence separately and did not find a significant effect for hydrochlorothiazide (RR 1.0; 95% CI, 0.39–2.8).1

Citrates were found to be effective in 4 RCTs (n=197) compared with placebo or control in reducing the radiographic or symptomatic recurrence of stones (RR 0.25; 95% CI, 0.14–0.44; NNT=3). Potassium citrate (30–60 mEq daily), potassium-magnesium citrate (63 mEq daily), and potassium–sodium citrate (27 mEq, 3 times daily) were all effective. No results were reported for symptomatic stones alone.1

Allopurinol (100 mg, 3 times daily) was shown to be effective in 2 RCTs (n=152) compared with placebo or control in reducing the radiographic or symptomatic recurrence of stones in patients with a previous calcium stone and hyperuricemia or hyperuricosuria (RR 0.59; 95% CI, 0.42–0.84; NNT=5). The reduction in symptomatic stones was not statistically significant, possibly due to the small sample size (1 trial, n=60; RR 0.34; 95% CI 0.11–1.2).1

Data quality was frequently limited by unclear allocation concealment, limited blinding, and lack of intention-to-treat analysis. Adverse events did occur with medication use, but the rates were low and the effects mild. Other than in the trials of allopurinol, patients were not selected by urine or blood chemistry criteria.1

A 2014 American College of Physicians consensus guideline recommended increased fluids to achieve a

E-2 Evidence-Based Practice / August 2016

A 2014 RCT of a 6-month treatment with a 2-year follow-up examined 90 children with severe obesity (BMI above the 99th percentile) to determine whether an inpatient treatment program was more effective than an ambulatory treatment program for sustainable weight loss.3 The intervention or inpatient group was hospitalized for 26 weeks. During this time, they followed a regimented nutrition and exercise program during weekdays and were allowed home on the weekends. The control or ambulatory group, attended 12 group visits at increasing time intervals over the 6-month time period. Immediately after treatment, a statistically significant decrease was noted in BMI z-score in the inpatient group versus the ambulatory group (18% vs 11%; P=.04). However, these effects could not be sustained after 2 years in follow-up review.3

Meghan Ward, MDHelena Russell, MD

Sarah Maples, MDCatherine McCarthy, MD

University of Nevada Reno FPRPReno, NV

1. Elder JP, Crespo NC, Corder K, et al. Childhood obesity prevention and control in city recreation centres and family homes: the MOVE/me Muevo Project. Pediatr Obes. 2013; 9(3):218–231. [STEP 2]

2. Love-Osbourne K, Fortune R, Sheeder J, et al. School-based health center-based treat-ment for obese adolescents: feasibility and body mass index effects. Child Obes. 2014; 10(5): 424–431. [STEP 2]

3. Van der Baan-Slootweg O, Benninga MA, Beelen A, et al. Inpatient treatment of children and adolescents with severe obesity in the Netherlands: a randomized clinical trial. JAMA Pediatr. 2014; 168(9):807–814. [STEP 2]

What is the best way to prevent recurrent kidney stones?

Evidence-Based AnswerThiazide-type diuretics and citrates decrease the risk of radiographic and symptomatic recurrence of calcium stones. In patients with hyperuricemia or hyperuricosuria, allopurinol reduces the risk of radiographic and symptomatic recurrence of calcium stones. It is unclear if these interventions reduce the recurrence of symptomatic stones only (SOR: B, systematic review of RCTs with disease-oriented outcomes and consensus guideline).

A 2014 systematic review of 28 RCTs evaluated interventions to prevent recurrent calcium nephrolithiasis as measured by a composite of symptoms and radiographic evidence.1 Most of the

Evidence-Based Practice / Vol. 19, No. 8 E-3

urinary output of at least 2 L daily to prevent recurrent nephrolithiasis and pharmacologic monotherapy with a thiazide, citrate, or allopurinol for prevention in patients with active disease when fluid alone fails.2

Ariel Leifer, MDThomas Gavagan, MD

U of Illinois at ChicagoChicago, IL

1. Fink HA, Wilt TJ, Eidman KE, et al. Medical management to prevent recurrent neph-rolithiasis in adults: a systematic review for an American College of Physicians clinical guideline. Ann Inter Med. 2013; 158 (7):535–543. [STEP 1]

2. Qaseem A, Dallas P, Forciea M, et al. Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014; 161(9):659–667. [STEP 5]

What is the risk for developing Guillain-Barré syndrome as a consequence of influenza vaccination?

Evidence-Based AnswerThere is about a 40% increase in the background rate of Guillain-Barré syndrome (GBS) after influenza vaccination (SOR: B, meta-analysis of observational studies). However, the risk of GBS within 6 weeks of an influenza illness may be more than 10 times greater than the risk after influenza vaccination (SOR: C, risk-interval cohort study).

A 2015 meta-analysis evaluated the risk of developing GBS within 6 weeks of the seasonal influenza vaccination (22 studies including 6 matched-cohort trials, 4 case-control trials, 8 risk-interval [vaccinated only] studies, and 4 self-controlled case series) and the pandemic influenza vaccination (16 studies including 4 matched-cohort trials, 2 case-control trials, 5 risk-interval [vaccinated only] studies, and 5 self-controlled case series; N=10,358 total patients overall).1 In the matched-cohort studies, individuals exposed to the vaccine were matched one-to-one to unexposed cohort members. For case-control studies, a group of GBS cases was compared with a control group of event-free individuals from the same time period. Controls were matched to cases on 1 or more variables (age, sex, vaccination site, etc) at the date of the event. For the risk-interval cohort studies, incidence rates for the risk and nonrisk time periods for developing GBS were compared, but only vaccinated individuals were included to minimize biases by introduced by comparing vaccinated and unvaccinated populations.

For the self-controlled case series, cases acted as their own control; each cases’ observation time was divided into control and risk periods and then the incidence rates for the relative risk for GBS to the control periods were determined.1 For seasonal influenza vaccination, 6 of 22 studies identified a statistically significant increased risk of GBS with vaccination. When all 22 studies were pooled, the combined risk ratio for developing GBS after vaccination was 1.22 (95% CI, 1.0–1.5). For the pandemic influenza vaccine, 7 of 16 studies identified a statistically significant increased risk of GBS with vaccination. When all 16 studies were pooled, the combined risk ratio for developing GBS after vaccination was 1.8 (95% CI, 1.4–2.5). For any influenza vaccination (seasonal or pandemic; all 39 studies), the overall relative risk for developing GBS was 1.4 (95% CI, 1.2–1.7). The difference in relative risk for GBS between seasonal and pandemic influenza vaccinations was not statistically significant.1

A 2013 self-controlled interval design study (included in the meta-analysis above) evaluated other outcomes including comparing GBS risk from vaccination with GBS risk from influenza illness as well as time of greatest risk.2 These authors reviewed 2,831 incident hospital admissions for GBS and identified 330 patients who received the unadjuvanted seasonal influenza vaccine and 109 patients who had influenza illness within the 42 weeks before hospitalization. The self-controlled, interval design anchors observation periods to exposure date and time after exposure to construct control intervals. This study required only identification of cases with a history of exposure (vaccination or influenza illness) and an outcome of GBS. Each patient served as his or her own control in order to eliminate confounding from comparing groups of vaccinated and unvaccinated individuals. The risk interval was identified as the first 6 weeks after vaccination or influenza illness and the control interval as 9 to 42 weeks. The relative incidence of GBS within 6 weeks of seasonal influenza vaccination was higher during the control interval (relative incidence [RI] 1.5; 95% CI, 1.2–2.0). The greatest risk of GBS postvaccination was during the second week (RI 1.8; 95% CI, 1.0–3.1) and the third week (RI 2.0; 95% CI, 1.4–3.0). The relative incidence of GBS within 6 weeks of an influenza illness–related healthcare encounter was also higher than

Evidence-Based Practice / August 2016E-4

during the control interval and greater than that after influenza vaccination (RI 15.8; 95% CI, 10.3–24.3), with the highest risk being within the first week after the healthcare encounter (RI 61.6; 95% CI, 39.3–96.8) and decreasing over the 6-week interval. The estimated GBS risk attributable to vaccination was 1.0 GBS admissions per million vaccinations versus 17.2 GBS admissions per million influenza-coded healthcare encounters.2

Darrell R. Over, MD, MScGregory Henson, MD

UAMS (South Central) FMRPine Bluff, AR

1. Martin-Aria LH, Sanz R, Sáinz M, et al. Guillain-Barré syndrome and influenza vaccines: a meta-analysis. Vaccine. 2015; 33(31):3773–3778. [STEP 2]

2. Kwong JC, Vasa PP, Campitelli MA, et al. Risk of Guillain-Barré syndrome after seasonal influenza vaccination and influenza health-care encounters: a self-controlled study. Lan-cet Infect Dis. 2013; 13(9):769–776. [STEP 3]

Do women experience a shorter second stage of labor when birthing in the vertical position as compared to the horizontal position?

Evidence-Based AnswerWomen birthing in the vertical position aided by a cushion or a seat appear to have a 6- to 11-minute shorter second stage compared to women birthing in a horizontal position. Use of a birthing table to achieve a vertical birthing position compared to a horizontal position does not change the duration of the second stage of labor. The use of the vertical/supported squatting position has no effect on neonatal outcomes or maternal hemorrhage, but reduces second degree perineal lacerations while increasing labial tears (most requiring no repair) (SOR: B, based on moderate quality heterogeneous RCTs).

A 2013 Swedish RCT included 1,002 mothers using a birthing seat to measure the average duration of the second stage of labor in the vertical position as compared to 5 alternative positions: supine, supine with stirrups, lateral, lateral with one stirrup and kneeling/standing positions.1 Women were primiparous with a singleton gestation in the cephalic position, no antenatal risk factors, a BMI <30, and spontaneous onset of labor between 37 and 41 6/7 weeks’ gestation. There was a significant decrease in the mean duration of the second stage in women allocated to the birthing seat compared to the mean of all other positions (38 vs 44 minutes; mean difference [MD]

6 minutes; 95% CI, 1.3–10.7). Despite an intention to treat analysis, the study was limited by a high non-compliance rate in the experimental group. Of 500 patients allocated to the experimental (vertical) group, 264 did not receive the allocated intervention for various reasons including medical, and maternal or midwife preference. There were no significant differences in neonatal Apgar scores <7, use of oxytocin or placental delivery time.1

A 1998 Brazilian RCT including 248 primiparous or multiparous mothers with uncomplicated singleton term pregnancies in the cephalic position used a modified birthing table to study the effect of the upright position (inclination of back support to 60° with legs bent at 90°) on the duration of the second stage of labor compared to the horizontal position.2 The average duration of the second stage was no different between the vertical position compared with the horizontal position (22 vs 25 minutes; P=.06). There were no significant differences between the 2 methods for Apgar score at 1 minute, placental delivery or blood loss. A 1989 British RCT including 427 primiparous women with uncomplicated term singleton pregnancies and cephalic presentation compared the duration of the second stage of labor in a supported squatting position using a ‘Birth Cushion’ versus the traditional semi-recumbent position.3 The mean duration of the second stage of labor in the vertical (supported squatting) position was 11 minutes less than the horizontal position (39 vs 50 minutes; MD 11 minutes; 95% CI, 7.1–14.9). Fewer women in the vertical position experienced a second stage longer than 60 minutes compared to the horizontal position (31 vs 65; P<.001). There was an increase in labial tears in the vertical group (82 vs 51; P<.05), but also an increase in intact perineum (92 vs 55; P<.01). No difference was seen in neonatal outcomes or estimated blood loss.

Michaela McCuddy, MD candidateAnne Mounsey, MD

University of North Carolina School of MedicineChapel Hill, NC

1. Thies-Lagergren L, Kvist LJ, Sandin-Bojö AK, et al. Labour augmentation and fetal out-comes in relation to birth positions: a secondary analysis of an RCT evaluating birth seat births. Midwifery. 2013; 29(4):344–350. [STEP 2]

2. Bomfim-Hyppolito, S. Influence of the position of the mother at delivery over some mater-nal and neonatal outcomes. Int J Gynecol Obstet. 1998; 63(1):67–73. [STEP 2]

3. Gardosi J, Hutson N, B-Lynch C. Randomised, controlled trial of squatting in the second stage of labour. Lancet. 1989; 2(8654):74–77. [STEP 2]

Evidence-Based Practice / Vol. 19, No. 8 E-5

Does delivery position affect the frequency or severity of perineal lacerations?

Evidence-Based AnswerThere is no significant difference between upright and recumbent position during the second stage of labor on the incidence of third and fourth degree perineal lacerations, but the incidence of second-degree lacerations is increased in women delivering in upright positions (SOR: A, meta-analysis). Among women with an epidural, there is no difference between upright or recumbent position in the incidence of any perineal laceration requiring suturing (SOR: A, meta-analysis). Delivering with or without stirrups does not affect the incidence or severity of perineal lacerations (SOR: B, single RCT).

A 2012 systematic review of 22 RCTs including 7,280 women examined the effect of maternal position during the second stage of labor on birth outcomes including the incidence of perineal lacerations.1 Maternal position was defined as upright (obstetric chair/stool, kneeling, and squatting) or recumbent/supine (lateral, semirecumbent up to 30 degrees, lithotomy, and Trendelenburg positions). Epidural status and parity were not differentiated. No significant difference was noted in the incidence of third and fourth degree lacerations between upright and recumbent positions (5 trials, n=1,685; relative risk [RR] 0.58; 95% CI, 0.22–1.5). An increase was found in second-degree lacerations in the upright position group (14 studies, n=5,369; RR 1.4; 95% CI, 1.2–1.5).1

A 2013 systematic review of 5 RCTs not evaluated in the previous review and including 879 primigravida and multigravida women with epidural analgesia evaluated upright versus recumbent/supine positions in the second stage of labor.2 Outcome measures in the 2 small studies specific to the issue of perineal lacerations did not differentiate among second, third, and fourth degree, but combined any trauma to the birth canal that required suturing. These studies found no significant difference in second stage position and trauma to the birth canal (2 trials, n=173; RR 0.95; 95% CI, 0.66–1.4). An additional 2012 RCT including 214 nulliparous women evaluated the effect of delivery with or without stirrups on perineal lacerations.3 In a young, largely Hispanic population with uncomplicated pregnancies,

no significant difference was noted in the incidence of any degree perineal laceration between groups. This was a small study that may have been underpowered to detect differences. Given the Hispanic predominance, results may not generalize to other race/ethnic groups, although there is no inherent reason to expect differences.

Talia Firestein, MDJennifer Hoock, MD, MPH

Group Health FMRSeattle, WA

1. Gupta JK, Hofmeyr GJ, Shehmar M. Position in the second stage of labour for wom-en without epidural anaesthesia. Cochrane Database Syst Rev. 2012; (5):CD002006. [STEP 1]

2. Kemp E, Kingswood CJ, Kibuka M, et al. Position in the second stage of labour for women with epidural anaesthesia. Cochrane Database Syst Rev. 2013; (1):CD008070. [STEP 1]

3. Corton MM, Lankford JC, Ames R, et al. A randomized trial of birthing with and without stirrups. Am J Obstet Gynecol. 2012; 207(2):133.e1–e5. [STEP 2]

Do steroid injections improve pain symptoms in adults with chronic plantar fasciitis?

Evidence-Based AnswerSteroid injections provide initial symptom relief compared with placebo; however, this difference does not persist beyond 4 weeks. Ultrasound-guided injection is associated with a lower recurrence of pain at 1 year. Steroid injections are no better than physiotherapy and not as effective as botulinum toxin A (BTX-A) or platelet-rich plasma injections (SOR: B, RCTs).

A 2012 placebo-controlled, double-blinded RCT of 82 patients with plantar fasciitis compared the effects of ultrasound-guided dexamethasone injection (1 mL of 4 mg/mL) of the plantar fascia with placebo injection.1 Treatment with steroid injection reduced pain at 4 weeks as measured by the foot health status questionnaire (0–100) more than the placebo injection (mean difference [MD] 11; 95% CI, 1.4–20). Between-group differences for pain scores at 8 and 12 weeks were not statistically significant. The pain data were dichotomized to consider a clinically significant reduction in pain to be a reduction of more than 19.5 points. Using this criterion, the number needed to treat with dexamethasone for clinically significant reduction in pain at 4 weeks was 2.93 (95% CI, 2.76–3.12). A 2006 RCT of 25 previously healthy patients with unilateral plantar fasciitis compared pain after either ultrasound-guided (n=12) or palpation-guided (n=13)

Evidence-Based Practice / August 2016E-6

injection of 7 mg (1 mL) betamethasone as evaluated by a visual analog scale (VAS).2 No statistical differences were noted in demographic factors including body mass index or initial pre-injection symptoms. Pain improvement at 2 weeks was not statistically different between the 2 groups; however, recurrence at 1 year was significantly lower in the ultrasound-guided group (8% vs 46%; P<.05). A 2014 parallel-group nonblinded RCT compared a 12-week physiotherapy program (n=28) versus a single palpation-guided injection of 4 mg (1 mL) dexamethasone with 0.5 mL 1% lidocaine (n=28) in adults with chronic plantar fasciitis.3 Follow-up was performed at 6 and 12 weeks with the Foot and Ankle Disability Index (FADI; 0–100, with 100 equaling no pain). Compared with baseline FADI scores (injection group 66; physiotherapy group 65), FADI scores in both groups significantly improved at 6 weeks (injection group 79, P≤.001; physiotherapy group 73, P<.01) and 12 weeks (injection group 84, P≤.001; physiotherapy group 79, P<.01). However, no statistically significant difference was noted when comparing groups (6 weeks, MD 6.8; 95% CI, –3.3 to 15; 12 weeks, MD 5.3; 95% CI, –5.2 to 14).3

A 2013 double-blinded RCT of 36 patients with plantar fasciitis compared botulinum toxin A (BTX-A) injection with a blind injection of a combination of 2 mL lidocaine 2% and 8 mg (2 mL) dexamethasone.4

All patients were instructed to perform plantar fascia stretching exercises. Patients were evaluated by a 1–10 VAS. The pretreatment BTX-A VAS score was 7.1 and the steroid group score was 7.7, which was not significantly different. At 6 months, the BTX-A group VAS was significantly lower than that of the steroid group (1.1 vs 3.8; P=.0005).4

A 2014 RCT of 40 adult patients with unilateral chronic plantar fasciitis compared a single ultrasound-guided injection of 3 mL autologous platelet-rich plasma with a single ultrasound-guided injection of 40 mg Depo Medrol cortisone.5 Patients had at least 4 months of foot pain and failed conservative treatment. American Orthopedic Foot and Ankle Society (AOFAS; 1–100 with higher score equaling less pain) hindfoot scoring was completed on all patients immediately prior to the injection and at 3, 6, 12, and 24 months after the injection of PRP or cortisone.

The cortisone group had an improved AOFAS score over the 24 months (baseline: 52; 3 months: 81; 6 months: 74; 12 months: 58; 24 months: 56). The PRP group also improved in AOFAS score over 24 months (baseline: 37; 3 months: 95; 6 months: 94; 12 months: 94; 24 months: 92), which was significantly better than the corticosteroid group (P=.001 ANOVA).5

Jennifer Ludwig, MDTheodore Neumann, MD

Anthony Aspesi, MDAndrew Cureton, MD

Bryan Norkus, MDSt. Joseph Regional Medical Center FMRP

Mishawaka, IN

1. McMillan AM, Landorf KB, Gilheany MF, et al. Ultrasound guided corticosteroid injection for plantar fasciitis: randomised controlled trial. BMJ. 2012; 344:e3260. [STEP 2]

2. Tsai WC, Hsu CC, Chen CP, et al. Plantar fasciitis treated with local steroid injection: comparison between sonographic and palpation guidance. J Clin Ultrasound. 2006; 34(1):12–16. [STEP 2]

3. Ryan M, Hartwell J, Fraser S, et al. Comparison of a physiotherapy program versus dexa-methasone injections for plantar fasciopathy in prolonged standing workers: a randomized clinical trial. Clin J Sport Med. 2014; 24(3):211–217. [STEP 2]

4. Elizondo-Rodriguez J, Araujo-Lopez Y, Moreno-Gonzalez JA, et al. A comparison of botuli-num toxin a and intralesional steroids for the treatment of plantar fasciitis: a randomized, double-blinded study. Foot Ankle Int. 2013; 34(1):8–14. [STEP 2]

How long is an exercise stress test reliable in a patient with chest pain and a recent negative exercise stress test?

Evidence-Based AnswerThere is a high negative predictive value (NPV) for myocardial infarction (MI) or cardiac death in patients with known coronary artery disease (CAD) and a negative exercise stress echocardiogram (98%) or exercise stress myocardial perfusion imaging (MPI) (99%) for approximately 3 years (SOR: B, meta-analysis of cohort trials). In patients with no known CAD evaluated in an office setting, an exercise stress test (EST) has a sensitivity of 71% and NPV of 99% for diagnosis of new CAD at 6 years (SOR: B, case series).

A meta-analysis of 20 prospective cohort studies examined the accuracy of a negative exercise stress echocardiogram or exercise stress MPI studies of 11,029 adults with known or suspected CAD.1 The review excluded studies in which stress testing was done exclusively after MI, percutaneous coronary intervention, coronary artery bypass grafting (CABG), and hospitalization for acute coronary syndrome, or CAD documented with coronary angiography.

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After a negative exercise stress echocardiogram (defined as no wall motion abnormalities at rest or stress), there was a low rate of MI or cardiac death over 33 months (4 trials, n=3,021; event rate 1.6%; 95% CI, 1.1–2.0; NPV 98%). After negative MPI, there was also a low rate of MI or cardiac death over 36 months (17 trials, n=8,008; event rate 1.2%; 95% CI, 0.98–1.5; NPV 99%). The overall annualized event rate after a negative stress test was 1.03% and 0.58% for echocardiographic and MPI testing, respectively. The authors noted good homogeneity of studies. The authors stated that a major limitation to the review was that annualized event rate estimates were not adjusted for risk factors and several large cohort studies were not included in the meta-analysis due to inability to combine the primary data from these studies with others.1

A retrospective case series examined the predictive value of EST in 339 patients who had undergone office exercise treadmill stress testing.2 Patients with known CAD were excluded. The most common indication for EST was a history of chest pain (59% of patients). Other indications included shortness of breath (4%), evaluation due to multiple cardiac risk factors (3.8%), pre-exercise evaluation (8%), and generic screening (2.3%). There was no indication listed in 23% of patients. Almost all patients had low or intermediate

pretest probability for CAD. All patients underwent treadmill EST using the Bruce protocol. Out of 302 patients with a negative test, 2 had a cardiac outcome, defined as MI, coronary artery angiography with angioplasty and stenting, CABG, a new diagnosis of CAD, or cardiac death. Equivocal results were considered positive for analyses. Out of 37 patients with a positive (n=5) or equivocal (n=32) test, 5 had a coronary outcome. The mean follow-up period was 47 months. The overall sensitivity and specificity were 71% and 90%, respectively (positive likelihood ratio [LR+] 7.4; negative likelihood ratio [LR–] 0.32). The positive predictive value was 14% and the NPV was 99%. Two patients had false-negative results: One had an MI that was successfully stented within 2 months of the negative EST. The second had an abnormal echo for new symptoms and a subsequent CABG 29 months after the negative EST.2

Alex Sable-Smith, MD, MPHCorey Lyon, DO

University of Colorado FMRDenver, CO

1. Metz LD, Beattie M, Hom R, et al. The prognostic value of normal exercise myocardial per-fusion imaging and exercise echocardiography. J Am Coll Cardiol. 2007; 49(2):227–237. [STEP 3]

2. Newman RJ, Darrow M, Cummings D, et al. Predictive value of exercise stress testing in a family medicine population. J Am Board Fam Med. 2008; 21(6):531–538. [STEP 4]