Bacharier LB, Guilbert TW, Mauger DT et al. Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses (LRTI) in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial. JAMA. 2015 Nov 17;314(19):2034-44. doi: 10.1001/jama.2015.13896.
CONCLUSIONS: Among young children with histories of recurrent severe LRTIs, the use of azithromycin early during an apparent RTI compared with placebo reduced the likelihood of severe LRTI. More information is needed on the development of antibiotic-resistant pathogens with this strategy. PMID: 26575060
Comments: Call me crazy, but is this study saying they gave antibiotics to kids with colds? The devil is in the details of defining severe LRTI. Here are the inclusion criteria: "children aged 12 through 71 months with recurrent severe wheezing in the context of clinically significant LRTIs that required systemic corticosteroids, an unscheduled physician office visit, an urgent or emergency department visit, or hospitalization." I hope every parent doesn't start asking for antibiotics now, because of course, their child has had recurrent severe infections! I am not sure what to do with this information. It seems starting an antibiotic on kids with mild URI symptoms but with prior severe wheezing is overkill and will promote antibiotic resistance.
1. JAMA. 2015 Oct 6;314(13):1376-85. doi: 10.1001/jama.2015.12180.
Rehabilitation After Immobilization for Ankle Fracture: The EXACT Randomized
Moseley AM(1), Beckenkamp PR(1), Haas M(2), Herbert RD(3), Lin CW(1); EXACT Team.
Collaborators: Evans P, Taylor D, Wines A, Hogan J, Penn J, Horsley M, Abbott V,
Elias L, Thomas B, Lee K, Chen J, Cameron J, Appleby M, Russell T.
(1)The George Institute for Global Health and Sydney Medical School, University
of Sydney, Sydney, Australia. (2)Centre for Health Economics Research and
Evaluation (CHERE), University of Technology Sydney, Sydney, Australia.
(3)Neuroscience Research Australia, Sydney, Australia.
IMPORTANCE: The benefits of rehabilitation after immobilization for ankle
fracture are unclear.
OBJECTIVES: To determine the effectiveness of a supervised exercise program and
advice (rehabilitation) compared with advice alone and to determine if effects
are moderated by fracture severity or age and sex.
DESIGN, SETTING, AND PARTICIPANTS: The EXACT trial was a pragmatic, randomized
clinical trial conducted from December 2010 to June 2014. Patients with isolated
ankle fracture presenting to fracture clinics in 7 Australian hospitals were
randomized on the day of removal of immobilization. Of 571 eligible patients, 357
chose not to participate and 214 were allocated to rehabilitation (n = 106) or
advice alone (n = 108), with 194 (91%) followed up at 1 month, 173 (81%) at 3
months, and 170 (79%) at 6 months. There were no withdrawals attributed to
adverse effects. Recruitment terminated early on December 31, 2013 (planned
enrollment, 342; actual, 214), because funding was exhausted.
INTERVENTIONS: Supervised exercise program and advice about self-management
(rehabilitation) (individually tailored, prescribed, monitored, and progressed)
or advice alone, both delivered by a physical therapist.
MAIN OUTCOMES AND MEASURES: Primary outcomes were activity limitation assessed
using the Lower Extremity Functional Scale (score range, 0-80; higher scores
indicate better activity), and quality of life assessed using the Assessment of
Quality of Life (score range, 0-1; higher scores indicate better quality of
life), measured at baseline and at 1, 3 (primary time point), and 6 months.
RESULTS: Mean activity limitation and quality of life at baseline were 30.1 (SD,
12.5) and 0.51 (SD, 0.24), respectively, for advice and 30.2 (SD, 13.2) and 0.54
(SD, 0.24) for rehabilitation, increasing to 64.3 (SD, 13.5) and 0.85 (SD, 0.17)
for advice vs 64.3 (SD, 15.1) and 0.85 (SD, 0.20) for rehabilitation at 3 months.
Rehabilitation was not more effective than advice for activity limitation (mean
effect at 3 months, 0.4 [95% CI, -3.3 to 4.1]) or quality of life (-0.01 [95% CI,
-0.06 to 0.04]). Treatment effects were not moderated by fracture severity or age
CONCLUSIONS AND RELEVANCE: A supervised exercise program and advice did not
confer additional benefits in activity limitation or quality of life compared
with advice alone for patients with isolated and uncomplicated ankle fracture.
These findings do not support the routine use of supervised exercise programs
after removal of immobilization for patients with isolated and uncomplicated
TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12610000979055.
PMID: 26441182 [PubMed - indexed for MEDLINE]
2. JAMA. 2015 Oct 27;314(16):1701-10. doi: 10.1001/jama.2015.12334.
Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among
Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial.
Young P(1), Bailey M(2), Beasley R(3), Henderson S(4), Mackle D(3), McArthur
C(5), McGuinness S(6), Mehrtens J(7), Myburgh J(8), Psirides A(9), Reddy S(3),
Bellomo R(10); SPLIT Investigators; ANZICS CTG.
Collaborators: Young P, Reddy S, Hunt A, Hurford S, Navarra L, Jason-Smith A,
Andrews L, Henderson S, Hitchings L, Closey D, Parker K, Minto E, Morris A,
Mehrtens J, McArthur C, McConnochie R, Chen Y, Newby L, McGuinness S, Parke R,
McCarthy L, Gilder E, Lammert A, Long S, Cowdrey KA.
(1)Medical Research Institute of New Zealand, Wellington, New Zealand2Intensive
Care Unit, Wellington Regional Hospital, Wellington, New Zealand. (2)Australian
and New Zealand Intensive Care Research Center, Monash University, Melbourne,
Victoria, Australia. (3)Medical Research Institute of New Zealand, Wellington,
New Zealand. (4)Medical Research Institute of New Zealand, Wellington, New
Zealand4Department of Intensive Care Medicine, Christchurch Hospital,
Christchurch, New Zealand. (5)Medical Research Institute of New Zealand,
Wellington, New Zealand3Australian and New Zealand Intensive Care Research
Center, Monash University, Melbourne, Victoria, Australia5Department of Critical
Care Medicine, Auckland City Hospital, Auckland, New Zea. (6)Medical Research
Institute of New Zealand, Wellington, New Zealand3Australian and New Zealand
Intensive Care Research Center, Monash University, Melbourne, Victoria,
Australia6Cardiothoracic and Vascular Intensive Care Unit, Auckland City
Hospital, Auckla. (7)Department of Intensive Care Medicine, Christchurch
Hospital, Christchurch, New Zealand. (8)Intensive Care Unit, St George Hospital,
Sydney, New South Wales, Australia8Critical Care Division, George Institute for
Global Health, Sydney, New South Wales, Australia. (9)Intensive Care Unit,
Wellington Regional Hospital, Wellington, New Zealand. (10)Australian and New
Zealand Intensive Care Research Center, Monash University, Melbourne, Victoria,
Australia9Intensive Care Unit, Austin Hospital, Melbourne, Victoria, Australia.
JAMA. 2015 Oct 27;314(16):1695-7.
IMPORTANCE: Saline (0.9% sodium chloride) is the most commonly administered
intravenous fluid; however, its use may be associated with acute kidney injury
(AKI) and increased mortality.
OBJECTIVE: To determine the effect of a buffered crystalloid compared with saline
on renal complications in patients admitted to the intensive care unit (ICU).
DESIGN AND SETTING: Double-blind, cluster randomized, double-crossover trial
conducted in 4 ICUs in New Zealand from April 2014 through October 2014. Three
ICUs were general medical and surgical ICUs; 1 ICU had a predominance of
cardiothoracic and vascular surgical patients.
PARTICIPANTS: All patients admitted to the ICU requiring crystalloid fluid
therapy were eligible for inclusion. Patients with established AKI requiring
renal replacement therapy (RRT) were excluded. All 2278 eligible patients were
enrolled; 1152 of 1162 patients (99.1%) receiving buffered crystalloid and 1110
of 1116 patients (99.5%) receiving saline were analyzed.
INTERVENTIONS: Participating ICUs were assigned a masked study fluid, either
saline or a buffered crystalloid, for alternating 7-week treatment blocks. Two
ICUs commenced using 1 fluid and the other 2 commenced using the alternative
fluid. Two crossovers occurred so that each ICU used each fluid twice over the 28
weeks of the study. The treating clinician determined the rate and frequency of
MAIN OUTCOMES AND MEASURES: The primary outcome was proportion of patients with
AKI (defined as a rise in serum creatinine level of at least 2-fold or a serum
creatinine level of ≥3.96 mg/dL with an increase of ≥0.5 mg/dL); main secondary
outcomes were incidence of RRT use and in-hospital mortality.
RESULTS: In the buffered crystalloid group, 102 of 1067 patients (9.6%) developed
AKI within 90 days after enrollment compared with 94 of 1025 patients (9.2%) in
the saline group (absolute difference, 0.4% [95% CI, -2.1% to 2.9%]; relative
risk [RR], 1.04 [95% CI, 0.80 to 1.36]; P = .77). In the buffered crystalloid
group, RRT was used in 38 of 1152 patients (3.3%) compared with 38 of 1110
patients (3.4%) in the saline group (absolute difference, -0.1% [95% CI, -1.6% to
1.4%]; RR, 0.96 [95% CI, 0.62 to 1.50]; P = .91). Overall, 87 of 1152 patients
(7.6%) in the buffered crystalloid group and 95 of 1110 patients (8.6%) in the
saline group died in the hospital (absolute difference, -1.0% [95% CI, -3.3% to
1.2%]; RR, 0.88 [95% CI, 0.67 to 1.17]; P = .40).
CONCLUSIONS AND RELEVANCE: Among patients receiving crystalloid fluid therapy in
the ICU, use of a buffered crystalloid compared with saline did not reduce the
risk of AKI. Further large randomized clinical trials are needed to assess
efficacy in higher-risk populations and to measure clinical outcomes such as
TRIAL REGISTRATION: clinicaltrials.gov Identifier: ACTRN12613001370796.
PMID: 26444692 [PubMed - indexed for MEDLINE]
3. JAMA. 2015 Oct 20;314(15):1572-80. doi: 10.1001/jama.2015.13043.
Naproxen With Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating
Acute Low Back Pain: A Randomized Clinical Trial.
Friedman BW(1), Dym AA(2), Davitt M(1), Holden L(1), Solorzano C(3), Esses D(1),
Bijur PE(1), Gallagher EJ(1).
(1)Department of Emergency Medicine, Montefiore Medical Center, Albert Einstein
College of Medicine, Bronx, New York. (2)Medical College, Albert Einstein College
of Medicine, Bronx, New York. (3)Pharmacy Department, Montefiore Medical Center,
Bronx, New York.
IMPORTANCE: Low back pain (LBP) is responsible for more than 2.5 million visits
to US emergency departments (EDs) annually. These patients are usually treated
with nonsteroidal anti-inflammatory drugs, acetaminophen, opioids, or skeletal
muscle relaxants, often in combination.
OBJECTIVE: To compare functional outcomes and pain at 1 week and 3 months after
an ED visit for acute LBP among patients randomized to a 10-day course of (1)
naproxen + placebo; (2) naproxen + cyclobenzaprine; or (3)
naproxen + oxycodone/acetaminophen.
DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blind, 3-group study
was conducted at one urban ED in the Bronx, New York City. Patients who presented
with nontraumatic, nonradicular LBP of 2 weeks' duration or less were eligible
for enrollment upon ED discharge if they had a score greater than 5 on the
Roland-Morris Disability Questionnaire (RMDQ). The RMDQ is a 24-item
questionnaire commonly used to measure LBP and related functional impairment on
which 0 indicates no functional impairment and 24 indicates maximum impairment.
Beginning in April 2012, a total of 2588 patients were approached for enrollment.
Of the 323 deemed eligible for participation, 107 were randomized to receive
placebo and 108 each to cyclobenzaprine and to oxycodone/acetaminophen. Follow-up
was completed in December 2014.
INTERVENTIONS: All participants were given 20 tablets of naproxen, 500 mg, to be
taken twice a day. They were randomized to receive either 60 tablets of placebo;
cyclobenzaprine, 5 mg; or oxycodone, 5 mg/acetaminophen, 325 mg. Participants
were instructed to take 1 or 2 of these tablets every 8 hours, as needed for LBP.
They also received a standardized 10-minute LBP educational session prior to
MAIN OUTCOMES AND MEASURES: The primary outcome was improvement in RMDQ between
ED discharge and 1 week later.
RESULTS: Demographic characteristics were comparable among the 3 groups. At
baseline, median RMDQ score in the placebo group was 20 (interquartile range
[IQR],17-21), in the cyclobenzaprine group 19 (IQR,17-21), and in the
oxycodone/acetaminophen group 20 (IQR,17-22). At 1-week follow-up, the mean RMDQ
improvement was 9.8 in the placebo group, 10.1 in the cyclobenzaprine group, and
11.1 in the oxycodone/acetaminophen group. Between-group difference in mean RMDQ
improvement for cyclobenzaprine vs placebo was 0.3 (98.3% CI, -2.6 to 3.2;
P = .77), for oxycodone/acetaminophen vs placebo, 1.3 (98.3% CI, -1.5 to 4.1;
P = .28), and for oxycodone/acetaminophen vs cyclobenzaprine, 0.9 (98.3% CI, -2.1
to 3.9; P = .45).
CONCLUSIONS AND RELEVANCE: Among patients with acute, nontraumatic, nonradicular
LBP presenting to the ED, adding cyclobenzaprine or oxycodone/acetaminophen to
naproxen alone did not improve functional outcomes or pain at 1-week follow-up.
These findings do not support use of these additional medications in this
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01587274.
PMID: 26501533 [PubMed - indexed for MEDLINE]
4. JAMA. 2015 Oct 13;314(14):1498-506. doi: 10.1001/jama.2015.12763.
Evaluation and Treatment of Pericarditis: A Systematic Review.
Imazio M(1), Gaita F(2), LeWinter M(3).
(1)Cardiology Department, Maria Vittoria Hospital and Department of Public Health
and Pediatrics, University of Torino, Torino, Italy. (2)University Division of
Cardiology, Department of Medical Sciences, Città della Salute e Della Scienza,
University of Torino, Torino, Italy. (3)Cardiology Unit, University of Vermont
College of Medicine and University of Vermont Medical Center, Burlington.
JAMA. 2015 Nov 10;314(18):1978.
IMPORTANCE: Pericarditis is the most common form of pericardial disease and a
relatively common cause of chest pain.
OBJECTIVE: To summarize published evidence on the causes, diagnosis, therapy,
prevention, and prognosis of pericarditis.
EVIDENCE REVIEW: A literature search of BioMedCentral, Google Scholar, MEDLINE,
Scopus, and the Cochrane Database of Systematic Reviews was performed for human
studies without language restriction from January 1, 1990, to August 31, 2015.
After literature review and selection of meta-analyses, randomized clinical
trials, and large observational studies, 30 studies (5 meta-analyses, 10
randomized clinical trials, and 16 cohort studies) with 7569 adult patients were
selected for inclusion.
FINDINGS: The etiology of pericarditis may be infectious (eg, viral and
bacterial) or noninfectious (eg, systemic inflammatory diseases, cancer, and
post-cardiac injury syndromes). Tuberculosis is a major cause of pericarditis in
developing countries but accounts for less than 5% of cases in developed
countries, where idiopathic, presumed viral causes are responsible for 80% to 90%
of cases. The diagnosis is based on clinical criteria including chest pain, a
pericardial rub, electrocardiographic changes, and pericardial effusion. Certain
features at presentation (temperature >38°C [>100.4°F], subacute course, large
effusion or tamponade, and failure of nonsteroidal anti-inflammatory drug [NSAID]
treatment) indicate a poorer prognosis and identify patients requiring hospital
admission. The most common treatment for idiopathic and viral pericarditis in
North America and Europe is NSAID therapy. Adjunctive colchicine can ameliorate
the initial episode and is associated with approximately 50% lower recurrence
rates. Corticosteroids are a second-line therapy for those who do not respond,
are intolerant, or have contraindications to NSAIDs and colchicine. Recurrences
may occur in 30% of patients without preventive therapy.
CONCLUSIONS AND RELEVANCE: Pericarditis is the most common form of pericardial
disease worldwide and may recur in as many as one-third of patients who present
with idiopathic or viral pericarditis. Appropriate triage and treatment with
NSAIDs may reduce readmission rates for pericarditis. Treatment with colchicine
can reduce recurrence rates.
PMID: 26461998 [PubMed - indexed for MEDLINE]
5. JAMA. 2015 Oct 13;314(14):1459-67. doi: 10.1001/jama.2015.11648.
Early Physical Therapy vs Usual Care in Patients With Recent-Onset Low Back Pain:
A Randomized Clinical Trial.
Fritz JM(1), Magel JS(2), McFadden M(1), Asche C(3), Thackeray A(2), Meier W(1),
(1)Department of Physical Therapy, University of Utah, Salt Lake City.
(2)Department of Physical Therapy, University of Utah, Salt Lake City2Department
of Physical Therapy, Intermountain Healthcare, Salt Lake City, Utah.
(3)Department of Internal Medicine, University of Illinois College of Medicine at
Peoria, Peoria, Illinois. (4)Department of Physical Therapy, Intermountain
Healthcare, Salt Lake City, Utah.
IMPORTANCE: Low back pain (LBP) is common in primary care. Guidelines recommend
delaying referrals for physical therapy.
OBJECTIVE: To evaluate whether early physical therapy (manipulation and exercise)
is more effective than usual care in improving disability for patients with LBP
fitting a decision rule.
DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial with 220
participants recruited between March 2011 and November 2013. Participants with no
LBP treatment in the past 6 months, aged 18 through 60 years (mean age, 37.4
years [SD, 10.3]), an Oswestry Disability Index (ODI) score of 20 or higher,
symptom duration less than 16 days, and no symptoms distal to the knee in the
past 72 hours were enrolled following a primary care visit.
INTERVENTIONS: All participants received education. Early physical therapy
(n = 108) consisted of 4 physical therapy sessions. Usual care (n = 112) involved
no additional interventions during the first 4 weeks.
MAIN OUTCOMES AND MEASURES: Primary outcome was change in the ODI score (range:
0-100; higher scores indicate greater disability; minimum clinically important
difference, 6 points) at 3 months. Secondary outcomes included changes in the ODI
score at 4-week and 1-year follow-up, and change in pain intensity, Pain
Catastrophizing Scale (PCS) score, fear-avoidance beliefs, quality of life,
patient-reported success, and health care utilization at 4-week, 3-month, and
RESULTS: One-year follow-up was completed by 207 participants (94.1%). Using
analysis of covariance, early physical therapy showed improvement relative to
usual care in disability after 3 months (mean ODI score: early physical therapy
group, 41.3 [95% CI, 38.7 to 44.0] at baseline to 6.6 [95% CI, 4.7 to 8.5] at 3
months; usual care group, 40.9 [95% CI, 38.6 to 43.1] at baseline to 9.8 [95% CI,
7.9 to 11.7] at 3 months; between-group difference, -3.2 [95% CI, -5.9 to -0.47],
P = .02). A significant difference was found between groups for the ODI score
after 4 weeks (between-group difference, -3.5 [95% CI, -6.8 to -0.08],
P = .045]), but not at 1-year follow-up (between-group difference, -2.0 [95% CI,
-5.0 to 1.0], P = .19). There was no improvement in pain intensity at 4-week,
3-month, or 1-year follow-up (between-group difference, -0.42 [95% CI, -0.90 to
0.02] at 4-week follow-up; -0.38 [95% CI, -0.84 to 0.09] at 3-month follow-up;
and -0.17 [95% CI, -0.62 to 0.27] at 1-year follow-up). The PCS scores improved
at 4 weeks and 3 months but not at 1-year follow-up (between-group difference,
-2.7 [95% CI, -4.6 to -0.85] at 4-week follow-up; -2.2 [95% CI, -3.9 to -0.49] at
3-month follow-up; and -0.92 [95% CI, -2.7 to 0.61] at 1-year follow-up). There
were no differences in health care utilization at any point.
CONCLUSIONS AND RELEVANCE: Among adults with recent-onset LBP, early physical
therapy resulted in statistically significant improvement in disability, but the
improvement was modest and did not achieve the minimum clinically important
difference compared with usual care.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01726803.
PMID: 26461996 [PubMed - indexed for MEDLINE]
6. JAMA. 2015 Nov 3;314(17):1832-43. doi: 10.1001/jama.2015.13767.
Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-analysis.
Badhiwala JH(1), Nassiri F(1), Alhazzani W(2), Selim MH(3), Farrokhyar F(2),
Spears J(1), Kulkarni AV(1), Singh S(2), Alqahtani A(4), Rochwerg B(2),
Alshahrani M(5), Murty NK(2), Alhazzani A(6), Yarascavitch B(7), Reddy K(2),
Zaidat OO(8), Almenawer SA(2).
(1)Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada.
(2)Division of Neurosurgery, Department of Clinical Epidemiology and
Biostatistics, McMaster University, Hamilton, Ontario, Canada. (3)Department of
Neurology, Stroke Division, Beth Israel Deaconess Medical Center and Harvard
Medical School, Boston, Massachusetts. (4)Department of Medicine, University of
Ottawa, Ottawa, Ontario, Canada. (5)Department of Medicine, Dammam University,
Dammam, Saudi Arabia. (6)Department of Neurology, King Khalid University, Abha,
Saudi Arabia. (7)Department of Neurological Surgery, University of Texas
Southwestern Medical Center, Dallas. (8)Departments of Neurology, Radiology, and
Neurosurgery, Medical College of Wisconsin, Milwaukee.
JAMA. 2015 Nov 3;314(17):1803-5.
IMPORTANCE: Endovascular intervention for acute ischemic stroke improves
revascularization. But trials examining endovascular therapy yielded variable
functional outcomes, and the effect of endovascular intervention among subgroups
needs better definition.
OBJECTIVE: To examine the association between endovascular mechanical
thrombectomy and clinical outcomes among patients with acute ischemic stroke.
DATA SOURCES: We systematically searched MEDLINE, EMBASE, CINAHL, Google Scholar,
and the Cochrane Library without language restriction through August 2015.
STUDY SELECTION: Eligible studies were randomized clinical trials of endovascular
therapy with mechanical thrombectomy vs standard medical care, which includes the
use of intravenous tissue plasminogen activator (tPA).
DATA EXTRACTION AND SYNTHESIS: Independent reviewers evaluated the quality of
studies and abstracted the data. We calculated odds ratios (ORs) and 95% CIs for
all outcomes using random-effects meta-analyses and performed subgroup and
sensitivity analyses to examine whether certain imaging, patient, treatment, or
study characteristics were associated with improved functional outcome. The
strength of the evidence was examined for all outcomes using the GRADE method.
MAIN OUTCOMES AND MEASURES: Ordinal improvement across modified Rankin scale
(mRS) scores at 90 days, functional independence (mRS score, 0-2), angiographic
revascularization at 24 hours, symptomatic intracranial hemorrhage within 90
days, and all-cause mortality at 90 days.
RESULTS: Data were included from 8 trials involving 2423 patients (mean [SD] age,
67.4 [14.4] years; 1131 [46.7%] women), including 1313 who underwent endovascular
thrombectomy and 1110 who received standard medical care with tPA. In a
meta-analysis of these trials, endovascular therapy was associated with a
significant proportional treatment benefit across mRS scores (OR, 1.56; 95% CI,
1.14-2.13; P = .005). Functional independence at 90 days (mRS score, 0-2)
occurred among 557 of 1293 patients (44.6%; 95% CI, 36.6%-52.8%) in the
endovascular therapy group vs 351 of 1094 patients (31.8%; 95% CI, 24.6%-40.0%)
in the standard medical care group (risk difference, 12%; 95% CI, 3.8%-20.3%; OR,
1.71; 95% CI, 1.18-2.49; P = .005). Compared with standard medical care,
endovascular thrombectomy was associated with significantly higher rates of
angiographic revascularization at 24 hours (75.8% vs 34.1%; OR, 6.49; 95% CI,
4.79-8.79; P < .001) but no significant difference in rates of symptomatic
intracranial hemorrhage within 90 days (70 events [5.7%] vs 53 events [5.1%]; OR,
1.12; 95% CI, 0.77-1.63; P = .56) or all-cause mortality at 90 days (218 deaths
[15.8%] vs 201 deaths [17.8%]; OR, 0.87; 95% CI, 0.68-1.12; P = .27).
CONCLUSIONS AND RELEVANCE: Among patients with acute ischemic stroke,
endovascular therapy with mechanical thrombectomy vs standard medical care with
tPA was associated with improved functional outcomes and higher rates of
angiographic revascularization, but no significant difference in symptomatic
intracranial hemorrhage or all-cause mortality at 90 days.
PMID: 26529161 [PubMed - indexed for MEDLINE]
7. JAMA. 2015 Nov 10;314(18):1955-65. doi: 10.1001/jama.2015.12735.
Does This Patient With Chest Pain Have Acute Coronary Syndrome?: The Rational
Clinical Examination Systematic Review.
Fanaroff AC(1), Rymer JA(1), Goldstein SA(2), Simel DL(3), Newby LK(4).
(1)Division of Cardiology, Duke University, Durham, North Carolina2Department of
Medicine, Duke University, Durham, North Carolina. (2)Department of Medicine,
Duke University, Durham, North Carolina. (3)Durham Veterans Affairs Medical
Center, Durham, North Carolina. (4)Division of Cardiology, Duke University,
Durham, North Carolina2Department of Medicine, Duke University, Durham, North
Carolina4Duke Clinical Research Institute, Duke University, Durham, North
IMPORTANCE: About 10% of patients with acute chest pain are ultimately diagnosed
with acute coronary syndrome (ACS). Early, accurate estimation of the probability
of ACS in these patients using the clinical examination could prevent many
hospital admissions among low-risk patients and ensure that high-risk patients
are promptly treated.
OBJECTIVE: To review systematically the accuracy of the initial history, physical
examination, electrocardiogram, and risk scores incorporating these elements with
the first cardiac-specific troponin.
STUDY SELECTION: MEDLINE and EMBASE were searched (January 1, 1995-July 31,
2015), along with reference lists from retrieved articles, to identify
prospective studies of diagnostic test accuracy among patients admitted to the
emergency department with symptoms suggesting ACS.
DATA EXTRACTION AND SYNTHESIS: We identified 2992 unique articles; 58 met
MAIN OUTCOMES AND MEASURES: Sensitivity, specificity, and likelihood ratio (LR)
of findings for the diagnosis of ACS. The reference standard for ACS was either a
final hospital diagnosis of ACS or occurrence of a cardiovascular event within 6
RESULTS: The clinical findings and risk factors most suggestive of ACS were prior
abnormal stress test (specificity, 96%; LR, 3.1 [95% CI, 2.0-4.7]), peripheral
arterial disease (specificity, 97%; LR, 2.7 [95% CI, 1.5-4.8]), and pain
radiation to both arms (specificity, 96%; LR, 2.6 [95% CI, 1.8-3.7]). The most
useful electrocardiogram findings were ST-segment depression (specificity, 95%;
LR, 5.3 [95% CI, 2.1-8.6]) and any evidence of ischemia (specificity, 91%; LR,
3.6 [95% CI,1.6-5.7]). Both the History, Electrocardiogram, Age, Risk Factors,
Troponin (HEART) and Thrombolysis in Myocardial Infarction (TIMI) risk scores
performed well in diagnosing ACS: LR, 13 (95% CI, 7.0-24) for the high-risk range
of the HEART score (7-10) and LR, 6.8 (95% CI, 5.2-8.9) for the high-risk range
of the TIMI score (5-7). The most useful for identifying patients less likely to
have ACS were the low-risk range HEART score (0-3) (LR, 0.20 [95% CI,
0.13-0.30]), low-risk range TIMI score (0-1) (LR, 0.31 [95% CI, 0.23-0.43]), or
low to intermediate risk designation by the Heart Foundation of Australia and
Cardiac Society of Australia and New Zealand risk algorithm (LR, 0.24 [95% CI,
CONCLUSIONS AND RELEVANCE: Among patients with suspected ACS presenting to
emergency departments, the initial history, physical examination, and
electrocardiogram alone did not confirm or exclude the diagnosis of ACS. Instead,
the HEART or TIMI risk scores, which incorporate the first cardiac troponin,
provided more diagnostic information.
PMID: 26547467 [PubMed - in process]
8. JAMA. 2015 May 19;313(19):1915-23. doi: 10.1001/jama.2015.4468.
Oral steroids for acute radiculopathy due to a herniated lumbar disk: a
randomized clinical trial.
Goldberg H(1), Firtch W(2), Tyburski M(3), Pressman A(4), Ackerson L(5), Hamilton
L(5), Smith W(6), Carver R(3), Maratukulam A(2), Won LA(6), Carragee E(7), Avins
(1)Kaiser Permanente Northern California Spine Care Program, San Jose2Division of
Research, Kaiser Permanente Northern California, Oakland. (2)Kaiser Permanente
Northern California Spine Care Program, Redwood City. (3)Kaiser Permanente
Northern California Spine Care Program, Roseville. (4)Division of Research,
Kaiser Permanente Northern California, Oakland5Sutter Health Research,
Development, and Dissemination, Walnut Creek, California. (5)Division of
Research, Kaiser Permanente Northern California, Oakland. (6)Kaiser Permanente
Northern California Spine Care Program, San Jose. (7)Orthopedic Spine Surgery
Division, Department of Orthopedics, Stanford University, Palo Alto, California.
(8)Division of Research, Kaiser Permanente Northern California,
Oakland7Department of Medicine, University of California, San
Francisco8Department of Epidemiology and Biostatistics, University of California,
Evid Based Med. 2015 Aug;20(4):138.
Rev Med Suisse. 2015 Jun 10;11(478):1317.
IMPORTANCE: Oral steroids are commonly used to treat acute sciatica due to a
herniated disk but have not been evaluated in an appropriately powered clinical
OBJECTIVE: To determine if oral prednisone is more effective than placebo in
improving function and pain among patients with acute sciatica.
DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled
clinical trial conducted from 2008 to 2013 in a large integrated health care
delivery system in Northern California. Adults (n=269) with radicular pain for 3
months or less, an Oswestry Disability Index (ODI) score of 30 or higher (range,
0-100; higher scores indicate greater dysfunction), and a herniated disk
confirmed by magnetic resonance imaging were eligible.
INTERVENTIONS: Participants were randomly assigned in a 2:1 ratio to receive a
tapering 15-day course of oral prednisone (5 days each of 60 mg, 40 mg, and 20
mg; total cumulative dose = 600 mg; n = 181) or matching placebo (n = 88).
MAIN OUTCOMES AND MEASURES: The primary outcome was ODI change at 3 weeks;
secondary outcomes were ODI change at 1 year, change in lower extremity pain
(measured on a 0-10 scale; higher scores indicate more pain), spine surgery, and
Short Form 36 Health Survey (SF-36) Physical Component Summary (PCS) and Mental
Component Summary (MCS) scores (0-100 scale; higher scores better).
RESULTS: Observed baseline and 3-week mean ODI scores were 51.2 and 32.2 for the
prednisone group and 51.1 and 37.5 for the placebo group, respectively. The
prednisone-treated group showed an adjusted mean 6.4-point (95% CI, 1.9-10.9;
P = .006) greater improvement in ODI scores at 3 weeks than the placebo group and
a mean 7.4-point (95% CI, 2.2-12.5; P = .005) greater improvement at 52 weeks.
Compared with the placebo group, the prednisone group showed an adjusted mean
0.3-point (95% CI, -0.4 to 1.0; P = .34) greater reduction in pain at 3 weeks and
a mean 0.6-point (95% CI, -0.2 to 1.3; P = .15) greater reduction at 52 weeks.
The prednisone group showed an adjusted mean 3.3-point (95% CI, 1.3-5.2;
P = .001) greater improvement in the SF-36 PCS score at 3 weeks, no difference in
the SF-36 PCS score at 52 weeks (mean, 2.5; 95% CI, -0.3 to 5.4; P = .08), no
change in the SF-36 MCS score at 3 weeks (mean, 2.2; 95% CI, -0.4 to 4.8;
P = .10), and an adjusted 3.6-point (95% CI, 0.6-6.7; P = .02) greater
improvement in the SF-36 MCS score at 52 weeks. There were no differences in
surgery rates at 52-week follow-up. Having 1 or more adverse events at 3-week
follow-up was more common in the prednisone group than in the placebo group
(49.2% vs 23.9%; P < .001).
CONCLUSIONS AND RELEVANCE: Among patients with acute radiculopathy due to a
herniated lumbar disk, a short course of oral steroids, compared with placebo,
resulted in modestly improved function and no improvement in pain.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00668434.
PMID: 25988461 [PubMed - indexed for MEDLINE]
9. JAMA. 2015 Mar 10;313(10):1037-47. doi: 10.1001/jama.2015.1629.
Surgical vs nonsurgical treatment of adults with displaced fractures of the
proximal humerus: the PROFHER randomized clinical trial.
Rangan A(1), Handoll H(2), Brealey S(3), Jefferson L(3), Keding A(3), Martin
BC(3), Goodchild L(1), Chuang LH(4), Hewitt C(3), Torgerson D(3); PROFHER Trial
Collaborators: Peckham T, Rossiter N, Kalogrianitis S, Charalambous CP, Crowther
M, Costa M, Sinha A, Sharma S, Roberts C, Rangan A, Sinha J, Hackney R, Armstrong
A, Maqsood M, Sandher D, Gray A, Donell S, McClelland D, Middleton A, Pratt R,
Jepson A, Wallace A, Willett K, Srinivasan M, Jacobs L, Seagger R, Smith M,
Johnstone SO, Jeyam M, Shafqat O, Loh W, Nadkarni J, Tourett L, Conboy V, Roy B,
Candal-Couto J, Chambler A, Smibert J.
(1)James Cook University Hospital, Middlesbrough, England. (2)Health and Social
Care Institute, School of Health and Social Care, Teesside University,
Middlesbrough, England. (3)York Trials Unit, Department of Health Sciences,
University of York, York, England. (4)Pharmerit Europe, Rotterdam, the
J Physiother. 2015 Jul;61(3):159.
J Physiother. 2015 Jul;61(3):159.
IMPORTANCE: The need for surgery for the majority of patients with displaced
proximal humeral fractures is unclear, but its use is increasing.
OBJECTIVE: To evaluate the clinical effectiveness of surgical vs nonsurgical
treatment for adults with displaced fractures of the proximal humerus involving
the surgical neck.
DESIGN, SETTING, AND PARTICIPANTS: A pragmatic, multicenter, parallel-group,
randomized clinical trial, the Proximal Fracture of the Humerus Evaluation by
Randomization (PROFHER) trial, recruited 250 patients aged 16 years or older
(mean age, 66 years [range, 24-92 years]; 192 [77%] were female; and 249 [99.6%]
were white) who presented at the orthopedic departments of 32 acute UK National
Health Service hospitals between September 2008 and April 2011 within 3 weeks
after sustaining a displaced fracture of the proximal humerus involving the
surgical neck. Patients were followed up for 2 years (up to April 2013) and 215
had complete follow-up data. The data for 231 patients (114 in surgical group and
117 in nonsurgical group) were included in the primary analysis.
INTERVENTIONS: Fracture fixation or humeral head replacement were performed by
surgeons experienced in these techniques. Nonsurgical treatment was sling
immobilization. Standardized outpatient and community-based rehabilitation was
provided to both groups.
MAIN OUTCOMES AND MEASURES: Primary outcome was the Oxford Shoulder Score (range,
0-48; higher scores indicate better outcomes) assessed during a 2-year period,
with assessment and data collection at 6, 12, and 24 months. Sample size was
based on a minimal clinically important difference of 5 points for the Oxford
Shoulder Score. Secondary outcomes were the Short-Form 12 (SF-12), complications,
subsequent therapy, and mortality.
RESULTS: There was no significant mean treatment group difference in the Oxford
Shoulder Score averaged over 2 years (39.07 points for the surgical group vs
38.32 points for the nonsurgical group; difference of 0.75 points [95% CI, -1.33
to 2.84 points]; P = .48) or at individual time points. There were also no
significant between-group differences over 2 years in the mean SF-12 physical
component score (surgical group: 1.77 points higher [95% CI, -0.84 to 4.39
points]; P = .18); the mean SF-12 mental component score (surgical group: 1.28
points lower [95% CI, -3.80 to 1.23 points]; P = .32); complications related to
surgery or shoulder fracture (30 patients in surgical group vs 23 patients in
nonsurgical group; P = .28), requiring secondary surgery to the shoulder (11
patients in both groups), and increased or new shoulder-related therapy (7
patients vs 4 patients, respectively; P = .58); and mortality (9 patients vs 5
patients; P = .27). Ten medical complications (2 cardiovascular events, 2
respiratory events, 2 gastrointestinal events, and 4 others) occurred in the
surgical group during the postoperative hospital stay.
CONCLUSIONS AND RELEVANCE: Among patients with displaced proximal humeral
fractures involving the surgical neck, there was no significant difference
between surgical treatment compared with nonsurgical treatment in
patient-reported clinical outcomes over 2 years following fracture occurrence.
These results do not support the trend of increased surgery for patients with
displaced fractures of the proximal humerus.
TRIAL REGISTRATION: isrctn.com Identifier: ISRCTN50850043.
PMID: 25756440 [PubMed - indexed for MEDLINE]
10. JAMA. 2015 Jun 16;313(23):2340-8. doi: 10.1001/jama.2015.6154.
Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute
Appendicitis: The APPAC Randomized Clinical Trial.
Salminen P(1), Paajanen H(2), Rautio T(3), Nordström P(4), Aarnio M(5), Rantanen
T(6), Tuominen R(7), Hurme S(8), Virtanen J(9), Mecklin JP(10), Sand J(4), Jartti
A(11), Rinta-Kiikka I(12), Grönroos JM(1).
(1)Division of Digestive Surgery and Urology, Departments of Acute and Digestive
Surgery, Turku University Hospital, Turku, Finland2Department of Surgery, Turku
University, Turku, Finland. (2)Department of Surgery, Mikkeli Central Hospital,
Mikkeli, Finland4Institute of Clinical Medicine, University of Eastern Finland,
Joensuu, Finland. (3)Department of Surgery, Oulu University Hospital, Oulu,
Finland. (4)Division of Surgery, Gastroenterology and Oncology, Tampere
University Hospital, Tampere, Finland. (5)Department of Surgery, Jyväskylä
Central Hospital, Jyväskylä, Finland. (6)Institute of Clinical Medicine,
University of Eastern Finland, Joensuu, Finland8Department of Surgery, Kuopio
University Hospital, Kuopio, Finland9Department of Surgery, Seinäjoki Central
Hospital, Seinäjoki, Finland. (7)Department of Public Health, University of
Turku, Turku, Finland11Primary Health Care Unit, Hospital District of Southwest
Finland, Turku, Finland. (8)Department of Biostatistics, University of Turku,
Turku, Finland. (9)Department of Radiology, Turku University Hospital, Turku,
Finland. (10)Institute of Clinical Medicine, University of Eastern Finland,
Joensuu, Finland7Department of Surgery, Jyväskylä Central Hospital, Jyväskylä,
Finland. (11)Department of Radiology, Oulu University Hospital, Oulu, Finland.
(12)Department of Radiology, Tampere University Hospital, Tampere, Finland.
JAMA. 2015 Oct 6;314(13):1402-3.
JAMA. 2015 Jun 16;313(23):2327-8.
JAMA. 2015 Oct 6;314(13):1402.
JAMA. 2015 Oct 6;314(13):1401-2.
JAMA. 2015 Oct 6;314(13):1403-4.
Summary for patients in
JAMA. 2015 Jun 16;313(23):2394.
IMPORTANCE: An increasing amount of evidence supports the use of antibiotics
instead of surgery for treating patients with uncomplicated acute appendicitis.
OBJECTIVE: To compare antibiotic therapy with appendectomy in the treatment of
uncomplicated acute appendicitis confirmed by computed tomography (CT).
DESIGN, SETTING, AND PARTICIPANTS: The Appendicitis Acuta (APPAC) multicenter,
open-label, noninferiority randomized clinical trial was conducted from November
2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60
years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were
randomly assigned to early appendectomy or antibiotic treatment with a 1-year
INTERVENTIONS: Patients randomized to antibiotic therapy received intravenous
ertapenem (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once
daily) and metronidazole (500 mg 3 times per day). Patients randomized to the
surgical treatment group were assigned to undergo standard open appendectomy.
MAIN OUTCOMES AND MEASURES: The primary end point for the surgical intervention
was the successful completion of an appendectomy. The primary end point for
antibiotic-treated patients was discharge from the hospital without the need for
surgery and no recurrent appendicitis during a 1-year follow-up period.
RESULTS: There were 273 patients in the surgical group and 257 in the antibiotic
group. Of 273 patients in the surgical group, all but 1 underwent successful
appendectomy, resulting in a success rate of 99.6% (95% CI, 98.0% to 100.0%). In
the antibiotic group, 70 patients (27.3%; 95% CI, 22.0% to 33.2%) underwent
appendectomy within 1 year of initial presentation for appendicitis. Of the 256
patients available for follow-up in the antibiotic group, 186 (72.7%; 95% CI,
66.8% to 78.0%) did not require surgery. The intention-to-treat analysis yielded
a difference in treatment efficacy between groups of -27.0% (95% CI, -31.6% to ∞)
(P = .89). Given the prespecified noninferiority margin of 24%, we were unable to
demonstrate noninferiority of antibiotic treatment relative to surgery. Of the 70
patients randomized to antibiotic treatment who subsequently underwent
appendectomy, 58 (82.9%; 95% CI, 72.0% to 90.8%) had uncomplicated appendicitis,
7 (10.0%; 95% CI, 4.1% to 19.5%) had complicated acute appendicitis, and 5 (7.1%;
95% CI, 2.4% to 15.9%) did not have appendicitis but received appendectomy for
suspected recurrence. There were no intra-abdominal abscesses or other major
complications associated with delayed appendectomy in patients randomized to
CONCLUSIONS AND RELEVANCE: Among patients with CT-proven, uncomplicated
appendicitis, antibiotic treatment did not meet the prespecified criterion for
noninferiority compared with appendectomy. Most patients randomized to antibiotic
treatment for uncomplicated appendicitis did not require appendectomy during the
1-year follow-up period, and those who required appendectomy did not experience
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01022567.
PMID: 26080338 [PubMed - indexed for MEDLINE]
11. JAMA. 2015 Jul 14;314(2):151-61. doi: 10.1001/jama.2015.7446.
Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and
Diabetic Kidney Disease: The AMETHYST-DN Randomized Clinical Trial.
Bakris GL(1), Pitt B(2), Weir MR(3), Freeman MW(4), Mayo MR(5), Garza D(5),
Stasiv Y(5), Zawadzki R(5), Berman L(5), Bushinsky DA(6); AMETHYST-DN
Collaborators: Drvodelic-Sunic E, Galesic K, Racki S, Laganovic M, Jakic M,
Baotic I, Chapidze G, Chumburidze V, Shaburishvili T, Kobulia B, Khintibidze I,
Pagava Z, Paposhvili K, Mamatsashvili M, Megreladze I, Kurashavili R, Giorgadze
E, Jermendy G, Juhasz F, Reiber I, Szentpeteri I, Simonyi G, Vandorfi G, Vertes
A, Takacs J, Voros P, Nagy A, Lippai J, Kiss I, Ferenczi S, Mezei L, Kovacevic Z,
Pudar Brankovic G, Mitic I, Pljesa S, Lalic N, Jelacic R, Bevc S, Zuran I,
Vujkovac B, Lainscak M, Klancic D, Rus I.
(1)ASH Comprehensive Hypertension Center, Division of Endocrinology, Diabetes,
and Metabolism, Department of Medicine, University of Chicago Medicine, Chicago,
Illinois. (2)University of Michigan, Ann Arbor. (3)Division of Nephrology,
Department of Medicine, University of Maryland School of Medicine, Baltimore.
(4)Department of Medicine, Massachusetts General Hospital, Boston. (5)Relypsa,
Redwood City, California. (6)Division of Nephrology, Department of Medicine,
University of Rochester, Rochester, New York.
JAMA. 2015 Aug 18;314(7):731. Dosage error in article text.
JAMA. 2015 Jul 14;314(2):129-30.
IMPORTANCE: Hyperkalemia is a potentially life-threatening condition
predominantly seen in patients treated with renin-angiotensin-aldosterone system
(RAAS) inhibitors with stage 3 or greater chronic kidney disease (CKD) who may
also have diabetes, heart failure, or both.
OBJECTIVES: To select starting doses for a phase 3 study and to evaluate the
long-term safety and efficacy of a potassium-binding polymer, patiromer, in
outpatients with hyperkalemia.
DESIGN, SETTING, AND PARTICIPANTS: Phase 2, multicenter, open-label,
dose-ranging, randomized clinical trial (AMETHYST-DN), conducted at 48 sites in
Europe from June 2011 to June 2013 evaluating patiromer in 306 outpatients with
type 2 diabetes (estimated glomerular filtration rate, 15 to <60 mL/min/1.73 m2
and serum potassium level >5.0 mEq/L). All patients received RAAS inhibitors
prior to and during study treatment.
INTERVENTIONS: Patients were stratified by baseline serum potassium level into
mild or moderate hyperkalemia groups and received 1 of 3 randomized starting
doses of patiromer (4.2 g [n = 74], 8.4 g [n = 74], or 12.6 g [n = 74] twice
daily [mild hyperkalemia] or 8.4 g [n = 26], 12.6 g [n = 28], or 16.8 g [n = 30]
twice daily [moderate hyperkalemia]). Patiromer was titrated to achieve and
maintain serum potassium level 5.0 mEq/L or lower.
MAIN OUTCOMES AND MEASURES: The primary efficacy end point was mean change in
serum potassium level from baseline to week 4 or prior to initiation of dose
titration. The primary safety end point was adverse events through 52 weeks.
Secondary efficacy end points included mean change in serum potassium level
through 52 weeks.
RESULTS: A total of 306 patients were randomized. The least squares mean
reduction from baseline in serum potassium level at week 4 or time of first dose
titration in patients with mild hyperkalemia was 0.35 (95% CI, 0.22-0.48) mEq/L
for the 4.2 g twice daily starting-dose group, 0.51 (95% CI, 0.38-0.64) mEq/L for
the 8.4 g twice daily starting-dose group, and 0.55 (95% CI, 0.42-0.68) mEq/L for
the 12.6 g twice daily starting-dose group. In those with moderate hyperkalemia,
the reduction was 0.87 (95% CI, 0.60-1.14) mEq/L for the 8.4 g twice daily
starting-dose group, 0.97 (95% CI, 0.70-1.23) mEq/L for the 12.6 g twice daily
starting-dose group, and 0.92 (95% CI, 0.67-1.17) mEq/L for the 16.8 g twice
daily starting-dose group (P < .001 for all changes vs baseline by hyperkalemia
starting-dose groups within strata). From week 4 through week 52, statistically
significant mean decreases in serum potassium levels were observed at each
monthly point in patients with mild and moderate hyperkalemia. Over the 52 weeks,
hypomagnesemia (7.2%) was the most common treatment-related adverse event, mild
to moderate constipation (6.3%) was the most common gastrointestinal adverse
event, and hypokalemia (<3.5 mEq/L) occurred in 5.6% of patients.
CONCLUSIONS AND RELEVANCE: Among patients with hyperkalemia and diabetic kidney
disease, patiromer starting doses of 4.2 to 16.8 g twice daily resulted in
statistically significant decreases in serum potassium level after 4 weeks of
treatment, lasting through 52 weeks.
TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01371747.
PMID: 26172895 [PubMed - indexed for MEDLINE]
12. JAMA. 2015 Feb 3;313(5):471-82. doi: 10.1001/jama.2015.12.
Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio
and mortality in patients with severe trauma: the PROPPR randomized clinical
Holcomb JB(1), Tilley BC(2), Baraniuk S(2), Fox EE(1), Wade CE(1), Podbielski
JM(1), del Junco DJ(1), Brasel KJ(3), Bulger EM(4), Callcut RA(5), Cohen MJ(5),
Cotton BA(1), Fabian TC(6), Inaba K(7), Kerby JD(8), Muskat P(9), O'Keeffe T(10),
Rizoli S(11), Robinson BR(12), Scalea TM(13), Schreiber MA(14), Stein DM(13),
Weinberg JA(6), Callum JL(15), Hess JR(16), Matijevic N(1), Miller CN(17), Pittet
JF(18), Hoyt DB(19), Pearson GD(20), Leroux B(21), van Belle G(22); PROPPR Study
Collaborators: Holcomb JB, Wade CE, del Junco DJ, Fox EE, Matijevic N, Podbielski
JM, Beeler AM, Tilley BC, Baraniuk S, DeSantis SM, Zhu H, Nixon J, Seay R, Appana
SN, Yang H, Gonzalez MO, Baer L, Wang YW, Hula BS, Espino E, Nguyen A, Pawelczyk
N, Arora-Nutall KD, Sharma R, Cardenas JC, Rahbar E, Burnett T Jr, Clark D, van
Belle G, May S, Leroux B, Hoyt D, Powell J, Sheehan K, Hubbard A, Arkin AP, Hess
JR, Callum JL, Pittet JF, Miller CN, Cotton BA, Vincent L, Welch T, Poole T,
Pivalizza EG, Gumbert SD, Bai Y, McCarthy JJ, Noland A, Hobbs R, Bulger EM, Klotz
P, Cattin L, Warner KJ, Wilson A, Boman D, White N, Grabinsky A, Daniel-Johnson
JA, Cohen MJ, Callcut RA, Nelson M, Redick B, Conroy A, Steurer MP, Maxim PC,
Fiebig E, Moore J, Mallari E, Muskat P, Johannigman JA, Robinson BR, Branson RD,
Gomaa D, Barczak C, Bennett S, Carey PM, Hancock H, Rodriguez C, Inaba K, Zhu JG,
Wong MD, Menchine M, Katzberg K, Henderson SO, McKeever R, Shulman IA, Nelson JM,
Tuma CW, Matsushita CY, Scalea TM, Stein DM, Shaffer CK, Wade C, Herrera AV,
Kallam S, Wade SE, Galvagno SM Jr, Fontaine MJ, Hunt JM, Cooke RK, Fabian TC,
Weinberg JA, Croce MA, Wilson S, Panzer-Baggett S, Waddle-Smith L, Flax S, Brasel
KJ, Walsh P, Milia D, Nelson A, Kaslow O, Aufderheide TP, Gottschall JL,
Carpenter E, O'Keeffe T, Rokowski LL, Denninghoff KR, Redford DT, Novak DJ, Knoll
S, Kerby JD, Bosarge PL, Pierce AT, Williams CR, Stephens SW, Wang HE, Marques
MB, Schreiber MA, Watters JM, Underwood SJ, Groat T, Newgard C, Merkel M, Scanlan
RM, Miller B, Rizoli S, Tien H, Nascimento B, Trpcic S, Sobrian-Couroux S, Reis
M, Pérez A, Belo SE, Merkley L, Colavecchia C.
JAMA. 2015 May 26;313(20):2078.
JAMA. 2015 May 26;313(20):2078-9.
JAMA. 2015 May 26;313(20):2077.
JAMA. 2015 May 26;313(20):2077-8.
IMPORTANCE: Severely injured patients experiencing hemorrhagic shock often
require massive transfusion. Earlier transfusion with higher blood product ratios
(plasma, platelets, and red blood cells), defined as damage control
resuscitation, has been associated with improved outcomes; however, there have
been no large multicenter clinical trials.
OBJECTIVE: To determine the effectiveness and safety of transfusing patients with
severe trauma and major bleeding using plasma, platelets, and red blood cells in
a 1:1:1 ratio compared with a 1:1:2 ratio.
DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, phase 3, multisite, randomized
clinical trial of 680 severely injured patients who arrived at 1 of 12 level I
trauma centers in North America directly from the scene and were predicted to
require massive transfusion between August 2012 and December 2013.
INTERVENTIONS: Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342
patients) during active resuscitation in addition to all local standard-of-care
MAIN OUTCOMES AND MEASURES: Primary outcomes were 24-hour and 30-day all-cause
mortality. Prespecified ancillary outcomes included time to hemostasis, blood
product volumes transfused, complications, incidence of surgical procedures, and
RESULTS: No significant differences were detected in mortality at 24 hours (12.7%
in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% [95% CI, -9.6% to
1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7%
[95% CI, -10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant
cause of death within the first 24 hours, was significantly decreased in the
1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% [95% CI, -10.4% to
-0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in
the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group
receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6
U, P < .001) and similar amounts of red blood cells (9 U) over the first 24
hours, no differences between the 2 groups were found for the 23 prespecified
complications, including acute respiratory distress syndrome, multiple organ
failure, venous thromboembolism, sepsis, and transfusion-related complications.
CONCLUSIONS AND RELEVANCE: Among patients with severe trauma and major bleeding,
early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio
compared with a 1:1:2 ratio did not result in significant differences in
mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group
achieved hemostasis and fewer experienced death due to exsanguination by 24
hours. Even though there was an increased use of plasma and platelets transfused
in the 1:1:1 group, no other safety differences were identified between the 2
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01545232.
PMID: 25647203 [PubMed - indexed for MEDLINE]
13. JAMA. 2014 Dec 3;312(21):2223-33. doi: 10.1001/jama.2014.15688.
Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among
outpatients with hyperkalemia: the HARMONIZE randomized clinical trial.
Kosiborod M(1), Rasmussen HS(2), Lavin P(3), Qunibi WY(4), Spinowitz B(5),
Packham D(6), Roger SD(7), Yang A(8), Lerma E(9), Singh B(2).
(1)Saint Luke's Mid America Heart Institute, Kansas City, Missouri2University of
Missouri-Kansas City. (2)ZS Pharma, Coppell, Texas. (3)Boston Biostatistics
Research Foundation, Framingham, Massachusetts. (4)University of Texas Health
Science Center at San Antonio. (5)Weill Medical College of Cornell University,
New York, New York. (6)Melbourne Renal Research Group and Department of Medicine,
University of Melbourne, Melbourne, Australia. (7)Renal Research, Gosford,
Australia. (8)Xelay Acumen, Belmont, California. (9)University of Illinois at
Chicago College of Medicine, Chicago11Advocate Christ Medical Center, Oak Lawn,
JAMA. 2015 Feb 3;313(5):526. Dosage error in text.
JAMA. 2014 Dec 3;312(21):2217-8.
IMPORTANCE: Hyperkalemia is a common electrolyte abnormality that may be
difficult to manage because of a lack of effective therapies. Sodium zirconium
cyclosilicate is a nonabsorbed cation exchanger that selectively binds potassium
in the intestine.
OBJECTIVE: To evaluate the efficacy and safety of zirconium cyclosilicate for 28
days in patients with hyperkalemia.
DESIGN, SETTING, AND PARTICIPANTS: HARMONIZE was a phase 3, multicenter,
randomized, double-blind, placebo-controlled trial evaluating zirconium
cyclosilicate in outpatients with hyperkalemia (serum potassium ≥5.1 mEq/L)
recruited from 44 sites in the United States, Australia, and South Africa
INTERVENTIONS: Patients (n = 258) received 10 g of zirconium cyclosilicate 3
times daily in the initial 48-hour open-label phase. Patients (n = 237) achieving
normokalemia (3.5-5.0 mEq/L) were then randomized to receive zirconium
cyclosilicate, 5 g (n = 45 patients), 10 g (n = 51), or 15 g (n = 56), or placebo
(n = 85) daily for 28 days.
MAIN OUTCOMES AND MEASURES: The primary end point was mean serum potassium level
in each zirconium cyclosilicate group vs placebo during days 8-29 of the
RESULTS: In the open-label phase, serum potassium levels declined from 5.6 mEq/L
at baseline to 4.5 mEq/L at 48 hours. Median time to normalization was 2.2 hours,
with 84% of patients (95% CI, 79%-88%) achieving normokalemia by 24 hours and 98%
(95% CI, 96%-99%) by 48 hours. In the randomized phase, serum potassium was
significantly lower during days 8-29 with all 3 zirconium cyclosilicate doses vs
placebo (4.8 mEq/L [95% CI, 4.6-4.9], 4.5 mEq/L [95% CI, 4.4-4.6], and 4.4 mEq/L
[95% CI, 4.3-4.5] for 5 g, 10 g, and 15 g; 5.1 mEq/L [95% CI, 5.0-5.2] for
placebo; P < .001 for all comparisons). The proportion of patients with mean
potassium <5.1 mEq/L during days 8-29 was significantly higher in all zirconium
cyclosilicate groups vs placebo (36/45 [80%], 45/50 [90%], and 51/54 [94%] for
the 5-g, 10-g, and 15-g groups, vs 38/82 [46%] with placebo; P < .001 for each
dose vs placebo). Adverse events were comparable between zirconium cyclosilicate
and placebo, although edema was more common in the 15-g group (edema incidence:
2/85 [2%], 1/45 [2%], 3/51 [6%], and 8/56 [14%] patients in the placebo, 5-g,
10-g, and 15-g groups). Hypokalemia developed in 5/51 (10%) and 6/56 patients
(11%) in the 10-g and 15-g zirconium cyclosilicate groups, vs none in the 5-g or
CONCLUSIONS AND RELEVANCE: Among outpatients with hyperkalemia, open-label sodium
zirconium cyclosilicate reduced serum potassium to normal levels within 48 hours;
compared with placebo, all 3 doses of zirconium cyclosilicate resulted in lower
potassium levels and a higher proportion of patients with normal potassium levels
for up to 28 days. Further studies are needed to evaluate the efficacy and safety
of zirconium cyclosilicate beyond 4 weeks and to assess long-term clinical
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02088073.
PMID: 25402495 [PubMed - indexed for MEDLINE]
14. JAMA. 2014 Dec 24-31;312(24):2678-9. doi: 10.1001/jama.2014.12839.
Antibiotics for acute bronchitis.
Smith SM(1), Smucny J(2), Fahey T(1).
(1)HRB Centre for Primary Care Research, Department of General Practice, Royal
College of Surgeons in Ireland Medical School, Dublin. (2)Palo Alto Medical
Foundation, Dublin Center, Dublin, California.
JAMA. 2015 Apr 14;313(14):1476.
Ann Emerg Med. 2015 May;65(5):566-7.
Cochrane Database Syst Rev. 2014;3:CD000245.
CLINICAL QUESTION: Are antibiotics associated with improved outcomes in patients
with acute bronchitis?
BOTTOM LINE: Prescribing antibiotics for acute bronchitis was associated with
reduced overall and nighttime cough and with an approximately half-day reduction
in duration of cough, in days feeling ill, and in days with impaired activities.
However, at follow-up, there were no significant differences in patients
receiving antibiotics compared with those receiving placebo in overall clinical
improvements or limitations in work or other activities. There was a significant
increase in adverse effects in the antibiotic group, particularly
PMID: 25536260 [PubMed - indexed for MEDLINE]
15. JAMA. 2014 Dec 10;312(22):2364-73. doi: 10.1001/jama.2014.15273.
Association of the 2011 ACGME resident duty hour reforms with mortality and
readmissions among hospitalized Medicare patients.
Patel MS(1), Volpp KG(1), Small DS(2), Hill AS(3), Even-Shoshan O(4), Rosenbaum
L(5), Ross RN(3), Bellini L(6), Zhu J(7), Silber JH(8).
(1)Center for Health Equity Research and Promotion, Veterans Administration
Hospital, Philadelphia, Pennsylvania2Department of Medicine, Perelman School of
Medicine, University of Pennsylvania, Philadelphia3Department of Health Care
Management, The Wharton S. (2)The Leonard Davis Institute, Center for Health
Incentives and Behavioral Economics, University of Pennsylvania,
Philadelphia6Department of Statistics, The Wharton School, University of
Pennsylvania, Philadelphia. (3)Center for Outcomes Research, The Children's
Hospital of Philadelphia, Philadelphia, Pennsylvania. (4)Center for Outcomes
Research, The Children's Hospital of Philadelphia, Philadelphia,
Pennsylvania8Leonard Davis Institute of Health Economics, University of
Pennsylvania, Philadelphia. (5)Department of Medicine, Brigham and Womens
Hospital, Boston, Massachusetts. (6)Department of Medicine, Perelman School of
Medicine, University of Pennsylvania, Philadelphia. (7)Department of Medicine,
Perelman School of Medicine, University of Pennsylvania, Philadelphia4The Leonard
Davis Institute, Center for Health Incentives and Behavioral Economics,
University of Pennsylvania, Philadelphia. (8)Department of Health Care
Management, The Wharton School, University of Pennsylvania, Philadelphia7Center
for Outcomes Research, The Children's Hospital of Philadelphia, Philadelphia,
Pennsylvania8Leonard Davis Institute of Health Economics, University of.
JAMA. 2014 Dec 10;312(22):2342-4.
JAMA. 2015 Mar 24-31;313(12):1269.
JAMA. 2015 Mar 24-31;313(12):1268-9.
IMPORTANCE: Patient outcomes associated with the 2011 Accreditation Council for
Graduate Medical Education (ACGME) duty hour reforms have not been evaluated at a
OBJECTIVE: To evaluate the association of the 2011 ACGME duty hour reforms with
mortality and readmissions.
DESIGN, SETTING, AND PARTICIPANTS: Observational study of Medicare patient
admissions (6,384,273 admissions from 2,790,356 patients) to short-term, acute
care, nonfederal hospitals (n = 3104) with principal medical diagnoses of acute
myocardial infarction, stroke, gastrointestinal bleeding, or congestive heart
failure or a Diagnosis Related Group classification of general, orthopedic, or
vascular surgery. Of the hospitals, 96 (3.1%) were very major teaching, 138
(4.4%) major teaching, 442 (14.2%) minor teaching, 443 (14.3%) very minor
teaching, and 1985 (64.0%) nonteaching.
EXPOSURE: Resident-to-bed ratio as a continuous measure of hospital teaching
MAIN OUTCOMES AND MEASURES: Change in 30-day all-location mortality and 30-day
all-cause readmission, comparing patients in more intensive relative to less
intensive teaching hospitals before (July 1, 2009-June 30, 2011) and after (July
1, 2011-June 30, 2012) duty hour reforms, adjusting for patient comorbidities,
time trends, and hospital site.
RESULTS: In the 2 years before duty hour reforms, there were 4,325,854 admissions
with 288,422 deaths and 602,380 readmissions. In the first year after the
reforms, accounting for teaching hospital intensity, there were 2,058,419
admissions with 133,547 deaths and 272,938 readmissions. There were no
significant postreform differences in mortality accounting for teaching hospital
intensity for combined medical conditions (odds ratio [OR], 1.00; 95% CI,
0.96-1.03), combined surgical categories (OR, 0.99; 95% CI, 0.94-1.04), or any of
the individual medical conditions or surgical categories. There were no
significant postreform differences in readmissions for combined medical
conditions (OR, 1.00; 95% CI, 0.97-1.02) or combined surgical categories (OR,
1.00; 95% CI, 0.98-1.03). For the medical condition of stroke, there were higher
odds of readmissions in the postreform period (OR, 1.06; 95% CI, 1.001-1.13).
However, this finding was not supported by sensitivity analyses and there were no
significant postreform differences for readmissions for any other individual
medical condition or surgical category.
CONCLUSIONS AND RELEVANCE: Among Medicare beneficiaries, there were no
significant differences in the change in 30-day mortality rates or 30-day
all-cause readmission rates for those hospitalized in more intensive relative to
less intensive teaching hospitals in the year after implementation of the 2011
ACGME duty hour reforms compared with those hospitalized in the 2 years before
PMID: 25490327 [PubMed - indexed for MEDLINE]
Clinical Prediction Rules