Objective  To evaluate whether the public release of data on cardiac quality indicators effectively stimulates hospitals to undertake quality improvement activities that improve health care processes and patient outcomes.

Design, Setting, and Patients  Population-based cluster randomized trial (Enhanced Feedback for Effective Cardiac Treatment [EFFECT]) of 86 hospital corporations in Ontario, Canada, with patients admitted for acute myocardial infarction (AMI) or congestive heart failure (CHF).

Intervention  Participating hospital corporations were randomized to early (January 2004) or delayed (September 2005) feedback of a public report card on their baseline performance (between April 1999 and March 2001) on a set of 12 process-of-care indicators for AMI and 6 for CHF. Follow-up performance data (between April 2004 and March 2005) also were collected.

Main Outcome Measures  The coprimary outcomes were composite AMI and CHF indicators based on 12 AMI and 6 CHF process-of-care indicators. Secondary outcomes were the individual process-of-care indicators, a hospital report card impact survey, and all-cause AMI and CHF mortality.

Results  The publication of the early feedback hospital report card did not result in a significant systemwide improvement in the early feedback group in either the composite AMI process-of-care indicator (absolute change, 1.5%; 95% confidence interval [CI], –2.2% to 5.1%; P = .43) or the composite CHF process-of-care indicator (absolute change, 0.6%; 95% CI, –4.5% to 5.7%; P = .81). During the follow-up period, the mean 30-day AMI mortality rates were 2.5% lower (95% CI, 0.1% to 4.9%; P = .045) in the early feedback group compared with the delayed feedback group. The hospital mortality rates for CHF were not significantly different.

Conclusion  Public release of hospital-specific quality indicators did not significantly improve composite process-of-care indicators for AMI or CHF.

Trial Registration  clinicaltrials.gov Identifier: NCT00187460

Published online November 18, 2009 (doi:10.1001/jama.2009.1731).

Objective  To assess the relationship between hospital primary angioplasty volume and outcomes and quality of care measures in patients presenting with STEMI.

Design, Setting, and Patients  An observational analysis of data on 29 513 patients presenting with STEMI and undergoing primary angioplasty in the American Heart Association's Get With the Guidelines registry. Patients were treated between July 5, 2001, and December 31, 2007, at 166 angioplasty-capable hospitals across the United States. Hospitals were divided into tertiles (<36 procedures per year, 36-70 procedures per year, and >70 procedures per year) based on their annual primary angioplasty volume.

Main Outcome Measures  Door-to-balloon (DTB) times, length of hospital stay, adherence with evidence-based quality of care measures, and in-hospital mortality.

Results  Compared with low- and medium-volume centers, high-volume centers had better median DTB times (98 vs 90 vs 88 minutes, respectively; P for trend < .001). High-volume centers were more likely than low-volume centers to follow evidence-based guidelines at discharge. Length of stay was similar between the 3 groups (P for trend = .13). There was no significant difference in the crude mortality between the tertiles of volume (incidence rate, 3.9% vs 3.2% vs 3.0% for low-, medium-, and high-volume centers, respectively; P = .26 and P = .99 for low- and medium- vs high-volume hospitals, respectively). Sequential multivariable modeling using generalized estimating equations revealed no significant association between hospital primary angioplasty volume and in-hospital mortality (adjusted odds ratio [OR], 1.22; 95% confidence interval [CI], 0.78-1.91; P = .38 and adjusted OR, 1.14; 95% CI, 0.78-1.66; P = .49 for low- and medium- vs high-volume hospitals, respectively).

Conclusion  In a contemporary registry of patients with STEMI, higher-volume primary angioplasty centers vs lower-volume centers were associated with shorter DTB times and more use of evidence-based therapies, but not with adjusted in-hospital mortality or length of hospital stay.

Objective  To determine whether chronic musculoskeletal pain is associated with an increased occurrence of falls in a cohort of community-living older adults.

Design, Setting, and Participants  The Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) Boston Study is a population-based longitudinal study of falls involving 749 adults aged 70 years and older. Participants were enrolled from September 2005 through January 2008.

Main Outcome Measure  Participants recorded falls on monthly calendar postcards mailed to the study center during an 18-month period.

Results  There were 1029 falls reported during the follow-up. A report of 2 or more locations of musculoskeletal pain at baseline was associated with greater occurrence of falls. The age-adjusted rates of falls per person-year were 1.18 (95% confidence interval [CI], 1.13-1.23) for the 300 participants with 2 or more sites of joint pain, 0.90 (95% CI, 0.87-0.92) for the 181 participants with single-site pain, and 0.78 (95% CI, 0.74-0.81) for the 267 participants with no joint pain. Similarly, more severe or disabling pain at baseline was associated with higher fall rates (P < .05). The association persisted after adjusting for multiple confounders and fall risk factors. The greatest risk for falls was observed in persons who had 2 or more pain sites (adjusted rate ratio [RR], 1.53; 95% CI, 1.17-1.99), and those in the highest tertiles of pain severity (adjusted RR, 1.53; 95% CI, 1.12-2.08) and pain interference with activities (adjusted RR, 1.53; 95%CI, 1.15-2.05), compared with their peers with no pain or those in the lowest tertiles of pain scores.

Conclusions  Chronic pain measured according to number of locations, severity, or pain interference with daily activities was associated with greater risk of falls in older adults.

Objective  To determine whether removing intravenous drug administration from an ACLS protocol would improve survival to hospital discharge after out-of-hospital cardiac arrest.

Design, Setting, and Patients  Prospective, randomized controlled trial of consecutive adult patients with out-of-hospital nontraumatic cardiac arrest treated within the emergency medical service system in Oslo, Norway, between May 1, 2003, and April 28, 2008.

Interventions  Advanced cardiac life support with intravenous drug administration or ACLS without access to intravenous drug administration.

Main Outcome Measures  The primary outcome was survival to hospital discharge. The secondary outcomes were 1-year survival, survival with favorable neurological outcome, hospital admission with return of spontaneous circulation, and quality of CPR (chest compression rate, pauses, and ventilation rate).

Results  Of 1183 patients for whom resuscitation was attempted, 851 were included; 418 patients were in the ACLS with intravenous drug administration group and 433 were in the ACLS with no access to intravenous drug administration group. The rate of survival to hospital discharge was 10.5% for the intravenous drug administration group and 9.2% for the no intravenous drug administration group (P = .61), 32% vs 21%, respectively, (P<.001) for hospital admission with return of spontaneous circulation, 9.8% vs 8.1% (P = .45) for survival with favorable neurological outcome, and 10% vs 8% (P = .53) for survival at 1 year. The quality of CPR was comparable and within guideline recommendations for both groups. After adjustment for ventricular fibrillation, response interval, witnessed arrest, or arrest in a public location, there was no significant difference in survival to hospital discharge for the intravenous group vs the no intravenous group (adjusted odds ratio, 1.15; 95% confidence interval, 0.69-1.91).

Conclusion  Compared with patients who received ACLS without intravenous drug administration following out-of-hospital cardiac arrest, patients with intravenous access and drug administration had higher rates of short-term survival with no statistically significant improvement in survival to hospital discharge, quality of CPR, or long-term survival.

Trial Registration  clinicaltrials.gov Identifier: NCT00121524

Objective  To determine the prevalence of author COI policies, requirements for signed disclosure statements, and variability in COI definitions among medical journals.

Design  A cross-sectional survey of Instructions for Authors and manuscript submission documents, including authorship responsibility forms, for high-impact medical journals across 35 subject categories available from March through October 2008.

Main Outcome Measure  Presence of language referring to COI disclosure in the Instructions for Authors or manuscript submission documents.

Results  Of 256 journals, 89% had author COI policies. Fifty-four percent required authors to sign a disclosure statement, and 77% provided definitions of COI. Most definitions were limited to direct financial relationships; a minority of journals requested disclosure of other potential conflicts such as personal relationships (42%), paid expert testimony (42%), relationships with other organizations (26%), or travel grants (12%). The prevalence of policies varied by subject category: all internal medicine, respiratory medicine, and toxicology journals studied had comprehensive COI definitions, with 19 of these 24 journals requiring signed disclosure attestations. In contrast, 6 of 19 geriatrics, radiology, and rehabilitation journals requested author COI disclosure. Most journals that officially endorsed International Committee of Medical Journal Editors guidelines had COI policies (68/69), compared with 84% of journals not endorsing the guidelines (158/187).

Conclusions  In 2008, most medical journals with relatively high impact factors had author COI policies available for public review. Among journals, there was substantial variation in policies for solicitation of author COIs and in definitions of COI.

Objective  To investigate the relationship between very preterm birth and VLBW and motor development.

Data Sources  The computerized databases EMBASE, PubMed, and Web of Knowledge were used to search for English-language peer-reviewed articles published between January 1992 and August 2009.

Study Selection  Studies were included if they reported motor scores of very preterm and VLBW children without congenital anomalies using 1 of 3 established and widely used motor tests: the Bayley Scales of Infant Development II (BSID-II), the Movement Assessment Battery for Children (MABC), and the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP). Forty-one articles were identified, encompassing 9653 children.

Results  In comparison with term-born peers, very preterm and VLBW children obtained significantly lower scores on all 3 motor tests: BSID-II: d = –0.88 (95% confidence interval [CI], –0.96 to –0.80; P < .001), MABC: d = –0.65 (95% CI, –0.70 to –0.60; P < .001), and BOTMP: d = –0.57 (95% CI, –0.68 to –0.46; P < .001). Whereas motor outcomes on the BSID-II show a catch-up effect in the first years of development (r = 0.50, P = .01), the results on the MABC demonstrate a nonsignificantly greater deficit with increasing age during elementary school and early adolescence (r = –0.59, P = .07).

Conclusion  Being born preterm or VLBW is associated with significant motor impairment persisting throughout childhood.

Objective  To quantify the association between relevant clinical variables and risk of retinal tear in patients presenting with acute-onset floaters and/or flashes and PVD.

Data Sources  Structured MEDLINE (January 1950–September 2009) and EMBASE (January 1980–September 2009) searches and a hand search of references and citations of retrieved articles yielded 17 relevant studies.

Study Selection  Studies of high-level methods that related elements of the history or physical examination in patients presenting with floaters and/or flashes and PVD to the likelihood of retinal tear.

Results  For patients with acute onset of floaters and/or flashes who are self-referred or referred to an ophthalmologist, the prevalence of retinal tear is 14% (95% confidence interval [CI], 12%-16%). Subjective visual reduction is the most important symptom associated with retinal tear (likelihood ratio [LR], 5.0; 95% CI, 3.1-8.1). Vitreous hemorrhage on slitlamp biomicroscopy is the best-studied finding with the narrowest positive LR for retinal tear (summary LR, 10; 95% CI, 5.1-20). Absence of vitreous pigment during this examination is the best-studied finding with the narrowest negative LR (summary LR, 0.23; 95% CI, 0.12-0.43). Patients initially diagnosed as having uncomplicated PVD have a 3.4% chance of a retinal tear within 6 weeks. The risk increases with new onset of at least 10 floaters (summary LR, 8.1-36) or subjective visual reduction (summary LR, 2.3-17) during this period.

Conclusions  Primary care physicians should evaluate patients with acute-onset floaters and/or flashes due to suspected PVD, or patients with known PVD and a change in symptoms, for high-risk features of retinal tear and detachment. Physicians should always assess these patients' visual acuity. Patients at increased risk should be triaged for urgent ophthalmologic assessment.

Objective  To test the effectiveness of telephone-delivered collaborative care for post-CABG depression vs usual physician care.

Design, Setting, and Participants  Single-blind effectiveness trial at 7 university-based and community hospitals in or near Pittsburgh, Pennsylvania. Participants were 302 post-CABG patients with depression (150, intervention; 152, usual care) and a comparison group of 151 randomly sampled post-CABG patients without depression recruited between March 2004 and September 2007 and observed as outpatients until June 2008.

Intervention  Eight months of telephone-delivered collaborative care provided by nurses working with patients' primary care physicians and supervised by a psychiatrist and primary care physician from this study.

Main Outcome Measures  Mental health–related quality of life (HRQL) measured by the Short Form-36 Mental Component Summary (SF-36 MCS) at 8-month follow-up; secondary outcome measures included assessment of mood symptoms (Hamilton Rating Scale for Depression [HRS-D]), physical HRQL (SF-36 PCS), and functional status (Duke Activity Status Index [DASI]); and hospital readmissions.

Results  The intervention patients reported greater improvements in mental HRQL (all P ≤ .02) (SF-36 MCS: , 3.2 points; 95% confidence interval [CI], 0.5-6.0), physical functioning (DASI: , 4.6 points; 95% CI, 1.9-7.3), and mood symptoms (HRS-D: , 3.1 points; 95% CI, 1.3-4.9); and were more likely to report a 50% or greater decline in HRS-D score from baseline (50.0% vs 29.6%; number needed to treat, 4.9 [95% CI, 3.2-10.4]) than usual care patients (P < .001). Men with depression were particularly likely to benefit from the intervention (SF-36 MCS: , 5.7 points; 95% CI, 2.2-9.2; P = .001). However, the mean HRQL and physical functioning of intervention patients did not reach that of the nondepressed comparison group.

Conclusion  Compared with usual care, telephone-delivered collaborative care for treatment of post-CABG depression resulted in improved HRQL, physical functioning, and mood symptoms at 8-month follow-up.

Trial Registration  clinicaltrials.gov Identifier: NCT00091962

Published online November 16, 2009 (doi:10.1001/jama.2009.1670).

Objective  To investigate trends in screening prevalence, use of cholesterol-lowering medications, and LDL-C levels across 4 study cycles (1999-2000, 2001-2002, 2003-2004, and 2005-2006).

Design, Setting, and Participants  The National Health and Nutrition Examination Survey (NHANES) is a cross-sectional, stratified, multistage probability sample survey of the US civilian, noninstitutionalized population. After we restricted the study sample to fasting participants aged 20 years or older (n = 8018) and excluded pregnant women (n = 464) and participants with missing data (n = 510), our study sample consisted of 7044 participants.

Main Outcome Measure  High LDL-C levels, defined as levels above the specific goal for each risk category outlined in guidelines from the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). All presented results are weighted and age-standardized to 2000 standard population estimates.

Results  Prevalence of high LDL-C levels among persons aged 20 years or older decreased from 31.5% in 1999-2000 to 21.2% in 2005-2006 (P < .001 for linear trend) but varied by risk category. By the 2005-2006 study cycle, prevalence of high LDL-C was 58.9%, 30.2%, and 11.0% for high-, intermediate-, and low-risk categories, respectively. Self-reported use of lipid-lowering medications increased from 8.0% to 13.4% (P < .001 for linear trend), but screening rates did not change significantly, remaining less than 70% (P = .16 for linear trend) during the study periods.

Conclusions  Among the NHANES population aged 20 years or older, the prevalence of high LDL-C levels decreased from 1999-2000 to 2005-2006. In the most recent period, the prevalence was 21.2%.

Objective  To determine the frequency, mutational spectrum, and phenotype of neurofibromatosis type 1–like syndrome (NFLS) in a large cohort of patients.

Design, Setting, and Participants  In a cross-sectional study, 23 unrelated probands carrying a SPRED1 mutation identified through clinical testing participated with their families in a genotype-phenotype study (2007-2008). In a second cross-sectional study, 1318 unrelated anonymous samples collected in 2003-2007 from patients with a broad range of signs typically found in neurofibromatosis type 1 (NF1) but no detectable NF1 germline mutation underwent SPRED1 mutation analysis.

Main Outcome Measures  Comparison of aggregated clinical features in patients with or without a SPRED1 or NF1 mutation. Functional assays were used to evaluate the pathogenicity of missense mutations.

Results  Among 42 SPRED1-positive individuals from the clinical cohort, 20 (48%; 95% confidence interval [CI], 32%-64%) fulfilled National Institutes of Health (NIH) NF1 diagnostic criteria based on the presence of more than 5 CALMs with or without freckling or an NF1-compatible family history. None of the 42 SPRED1-positive individuals (0%; 95% CI, 0%-7%) had discrete cutaneous or plexiform neurofibromas, typical NF1 osseous lesions, or symptomatic optic pathway gliomas. In the anonymous cohort of 1318 individuals, 34 different SPRED1 mutations in 43 probands were identified: 27 pathogenic mutations in 34 probands and 7 probable nonpathogenic missense mutations in 9 probands. Of 94 probands with familial CALMs with or without freckling and no other NF1 features, 69 (73%; 95% CI, 63%-80%) had an NF1 mutation and 18 (19%; 95% CI, 12%-29%) had a pathogenic SPRED1 mutation. In the anonymous cohort, 1.9% (95% CI, 1.2%-2.9%) of individuals with the clinical diagnosis of NF1 according to the NIH criteria had NFLS.

Conclusions  A high SPRED1 mutation detection rate was found in NF1 mutation–negative families with an autosomal dominant phenotype of CALMs with or without freckling and no other NF1 features. Among individuals in this study, NFLS was not associated with the peripheral and central nervous system tumors seen in NF1.

Objective  To evaluate effects of treatment with B vitamins on cancer outcomes and all-cause mortality in 2 randomized controlled trials.

Design, Setting, and Participants  Combined analysis and extended follow-up of participants from 2 randomized, double-blind, placebo-controlled clinical trials (Norwegian Vitamin Trial and Western Norway B Vitamin Intervention Trial). A total of 6837 patients with ischemic heart disease were treated with B vitamins or placebo between 1998 and 2005, and were followed up through December 31, 2007.

Interventions  Oral treatment with folic acid (0.8 mg/d) plus vitamin B₁₂ (0.4 mg/d) and vitamin B₆ (40 mg/d) (n = 1708); folic acid (0.8 mg/d) plus vitamin B₁₂ (0.4 mg/d) (n = 1703); vitamin B₆ alone (40 mg/d) (n = 1705); or placebo (n = 1721).

Main Outcome Measures  Cancer incidence, cancer mortality, and all-cause mortality.

Results  During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B₁₂ vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B₁₂ vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B₁₂ vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B₁₂. Vitamin B₆ treatment was not associated with any significant effects.

Conclusion  Treatment with folic acid plus vitamin B₁₂ was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods.

Trial Registration  clinicaltrials.gov Identifier: NCT00671346

Objective  To establish in vitro propagation of human spermatogonial stem cells from small testicular biopsies to obtain an adequate number of cells for successful transplantation.

Design, Setting, and Participants  Study performed from April 2007 to July 2009 using testis material donated by 6 adult men who underwent orchidectomy as part of prostate cancer treatment. Testicular cells were isolated and cultured in supplemented StemPro medium; germline stem cell clusters that arose were subcultured on human placental laminin–coated dishes in the same medium. Presence of spermatogonia was determined by reverse transcriptase polymerase chain reaction and immunofluorescence for spermatogonial markers. To test for the presence of functional spermatogonial stem cells in culture, xenotransplantation to testes of immunodeficient mice was performed, and migrated human spermatogonial stem cells after transplantation were detected by COT-1 fluorescence in situ hybridization. The number of colonized spermatogonial stem cells transplanted at early and later points during culture were counted to determine propagation.

Main Outcome Measures  Propagation of spermatogonial stem cells over time.

Results  Testicular cells could be cultured and propagated up to 15 weeks. Germline stem cell clusters arose in the testicular cell cultures from all 6 men and could be subcultured and propagated up to 28 weeks. Expression of spermatogonial markers on both the RNA and protein level was maintained throughout the entire culture period. In 4 of 6 men, xenotransplantation to mice demonstrated the presence of functional spermatogonial stem cells, even after prolonged in vitro culture. Spermatogonial stem cell numbers increased 53-fold within 19 days in the testicular cell culture and increased 18 450-fold within 64 days in the germline stem cell subculture.

Conclusion  Long-term culture and propagation of human spermatogonial stem cells in vitro is achievable.

Objective  To systematically review the accuracy of historical features, physical examination, and cardiac testing for the diagnosis of cardiac arrhythmia in patients with palpitations.

Data Source, Study Selection, and Data Extraction  MEDLINE (1950 to August 25, 2009) and EMBASE (1947 to August 2009) searches of English-language articles that compared clinical features and diagnostic tests in patients with palpitations with a reference standard for cardiac arrhythmia. Of the 277 studies identified by the search strategy, 7 studies were used for accuracy analysis and 16 studies for diagnostic yield analysis. Two authors independently reviewed articles for study data and quality and a third author resolved disagreements.

Data Synthesis  Most data were obtained from single studies with small sample sizes. A known history of cardiac disease (likelihood ratio [LR], 2.03; 95% confidence interval [CI], 1.33-3.11), having palpitations affected by sleeping (LR, 2.29; 95% CI, 1.33-3.94), or while the patient is at work (LR, 2.17; 95% CI, 1.19-3.96) slightly increase the likelihood of a cardiac arrhythmia. A known history of panic disorder (LR, 0.26; 95% CI, 0.07-1.01) or having palpitations lasting less than 5 minutes (LR, 0.38; 95% CI, 0.22-0.63) makes the diagnosis of cardiac arrhythmia slightly less likely. The presence of a regular rapid-pounding sensation in the neck (LR, 177; 95% CI, 25-1251) or visible neck pulsations (LR, 2.68; 95% CI, 1.25-5.78) in association with palpitations increases the likelihood of a specific type of arrhythmia (atrioventricular nodal reentry tachycardia). The absence of a regular rapid-pounding sensation in the neck makes detecting the same arrhythmia less likely (LR, 0.07; 95% CI, 0.03-0.19). No other features significantly alter the probability of clinically significant arrhythmia. Diagnostic tests for prolonged periods of electrocardiographic monitoring vary in their yield depending on the modality used, duration of monitoring, and occurrence of typical symptoms during monitoring. Loop monitors have the highest diagnostic yield (34%-84%) for identifying an arrhythmia.

Conclusions  While the presence of a regular rapid-pounding sensation in the neck or visible neck pulsations associated with palpitations makes the diagnosis of atrioventricular nodal reentry tachycardia likely, the reviewed studies suggest that the clinical examination is not sufficiently accurate to exclude clinically significant arrhythmias in most patients. Thus, prolonged electrocardiographic monitoring with demonstration of symptom-rhythm correlation is required to make the diagnosis of a cardiac arrhythmia for most patients with recurrent palpitations.

Objective  To assess possible outcome benefits of prone positioning in patients with moderate and severe hypoxemia who are affected by ARDS.

Design, Setting, and Patients  The Prone-Supine II Study, a multicenter, unblinded, randomized controlled trial conducted in 23 centers in Italy and 2 in Spain. Patients were 342 adults with ARDS receiving mechanical ventilation, enrolled from February 2004 through June 2008 and prospectively stratified into subgroups with moderate (n = 192) and severe (n = 150) hypoxemia.

Interventions  Patients were randomized to undergo supine (n = 174) or prone (20 hours per day; n = 168) positioning during ventilation.

Main Outcome Measures  The primary outcome was 28-day all-cause mortality. Secondary outcomes were 6-month mortality and mortality at intensive care unit discharge, organ dysfunctions, and the complication rate related to prone positioning.

Results  Prone and supine patients from the entire study population had similar 28-day (31.0% vs 32.8%; relative risk [RR], 0.97; 95% confidence interval [CI], 0.84-1.13; P = .72) and 6-month (47.0% vs 52.3%; RR, 0.90; 95% CI, 0.73-1.11; P = .33) mortality rates, despite significantly higher complication rates in the prone group. Outcomes were also similar for patients with moderate hypoxemia in the prone and supine groups at 28 days (25.5% vs 22.5%; RR, 1.04; 95% CI, 0.89-1.22; P = .62) and at 6 months (42.6% vs 43.9%; RR, 0.98; 95% CI, 0.76-1.25; P = .85). The 28-day mortality of patients with severe hypoxemia was 37.8% in the prone and 46.1% in the supine group (RR, 0.87; 95% CI, 0.66-1.14; P = .31), while their 6-month mortality was 52.7% and 63.2%, respectively (RR, 0.78; 95% CI, 0.53-1.14; P = .19).

Conclusion  Data from this study indicate that prone positioning does not provide significant survival benefit in patients with ARDS or in subgroups of patients with moderate and severe hypoxemia.

Trial Registration  clinicaltrials.gov Identifier: NCT00159939

Objective  To examine prevalence of and factors associated with persistent pain after surgical treatment for breast cancer.

Design, Setting, and Patients  A nationwide cross-sectional questionnaire study of 3754 women aged 18 to 70 years who received surgery and adjuvant therapy (if indicated) for primary breast cancer in Denmark between January 1, 2005, and December 31, 2006. A study questionnaire was sent to the women between January and April 2008.

Main Outcome Measures  Prevalence, location, and severity of persistent pain and sensory disturbances in 12 well-defined treatment groups assessed an average of 26 months after surgery, and adjusted odds ratio (OR) of reported pain and sensory disturbances with respect to age, surgical technique, chemotherapy, and radiotherapy.

Results  By June 2008, 3253 of 3754 eligible women (87%) returned the questionnaire. A total of 1543 patients (47%) reported pain, of whom 201 (13%) had severe pain, 595 (39%) had moderate pain, and 733 (48%) had light pain. Factors associated with chronic pain included young age (18-39 years: OR, 3.62; 95% confidence interval [CI], 2.25-5.82; P < .001) and adjuvant radiotherapy (OR, 1.50; 95% CI, 1.08-2.07; P = .03), but not chemotherapy (OR, 1.01; 95% CI, 0.85-1.21; P = .91). Axillary lymph node dissection (ALND) was associated with increased likelihood of pain (OR, 1.77; 95% CI, 1.43-2.19; P < .001) compared with sentinel lymph node dissection. Risk of sensory disturbances was associated with young age (18-39 years: OR, 5.00; 95% CI, 2.87-8.69; P < .001) and ALND (OR, 4.97; 95% CI, 3.92-6.30; P < .001). Pain complaints from other parts of the body were associated with increased risk of pain in the surgical area (P < .001). A total of 306 patients (20%) with pain had contacted a physician within the prior 3 months for pain complaints in the surgical area.

Conclusion  Two to 3 years after breast cancer treatment, persistent pain and sensory disturbances remain clinically significant problems among Danish women who received surgery in 2005 and 2006.

Objective  To assess major lipids and apolipoproteins in vascular risk.

Design, Setting, and Participants  Individual records were supplied on 302 430 people without initial vascular disease from 68 long-term prospective studies, mostly in Europe and North America. During 2.79 million person-years of follow-up, there were 8857 nonfatal myocardial infarctions, 3928 coronary heart disease [CHD] deaths, 2534 ischemic strokes, 513 hemorrhagic strokes, and 2536 unclassified strokes.

Main Outcome Measures  Hazard ratios (HRs), adjusted for several conventional factors, were calculated for 1-SD higher values: 0.52 log_e triglyceride, 15 mg/dL high-density lipoprotein cholesterol (HDL-C), 43 mg/dL non–HDL-C, 29 mg/dL apolipoprotein AI, 29 mg/dL apolipoprotein B, and 33 mg/dL directly measured low-density lipoprotein cholesterol (LDL-C). Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis.

Results  The rates of CHD per 1000 person-years in the bottom and top thirds of baseline lipid distributions, respectively, were 2.6 and 6.2 with triglyceride, 6.4 and 2.4 with HDL-C, and 2.3 and 6.7 with non–HDL-C. Adjusted HRs for CHD were 0.99 (95% CI, 0.94-1.05) with triglyceride, 0.78 (95% CI, 0.74-0.82) with HDL-C, and 1.50 (95% CI, 1.39-1.61) with non–HDL-C. Hazard ratios were at least as strong in participants who did not fast as in those who did. The HR for CHD was 0.35 (95% CI, 0.30-0.42) with a combination of 80 mg/dL lower non–HDL-C and 15 mg/dL higher HDL-C. For the subset with apolipoproteins or directly measured LDL-C, HRs were 1.50 (95% CI, 1.38-1.62) with the ratio non–HDL-C/HDL-C, 1.49 (95% CI, 1.39-1.60) with the ratio apo B/apo AI, 1.42 (95% CI, 1.06-1.91) with non–HDL-C, and 1.38 (95% CI, 1.09-1.73) with directly measured LDL-C. Hazard ratios for ischemic stroke were 1.02 (95% CI, 0.94-1.11) with triglyceride, 0.93 (95% CI, 0.84-1.02) with HDL-C, and 1.12 (95% CI, 1.04-1.20) with non–HDL-C.

Conclusion  Lipid assessment in vascular disease can be simplified by measurement of either total and HDL cholesterol levels or apolipoproteins without the need to fast and without regard to triglyceride.

Objective  To study the association between the use of statins, fibrates, or other lipid-lowering agents and the risk of incident gallstone disease followed by cholecystectomy.

Design, Setting, and Participants  Case-control analysis using the UK-based General Practice Research Database. Incident patients between 1994 and 2008 and 4 controls per each patient were identified and matched on age, sex, general practice, calendar time, and years of history in the database. The study population was 76% women and the mean (SD) age was 53.4 (15.0) years at the index date. Conditional logistic regression was used to estimate the odds ratio (OR) of developing gallstones followed by cholecystectomy in relation to exposure to lipid-lowering agents, stratified by exposure timing and duration. The ORs and 95% confidence intervals (CIs) were adjusted for smoking, body mass index, ischemic heart disease, stroke, and estrogen use.

Main Outcome Measure  The adjusted OR (AOR) for developing gallstone disease followed by cholecystectomy in relation to exposure to lipid-lowering agents.

Results  A total of 27 035 patients with cholecystectomy and 106 531 matched controls were identified, including 2396 patients and 8868 controls who had statin use. Compared with nonuse, current statin use (last prescription recorded within 90 days before the first-time diagnosis of the disease) was 1.0% for patients and 0.8% for controls (AOR, 1.10; 95% CI, 0.95-1.27) for 1 to 4 prescriptions; 2.6% vs 2.4% (AOR, 0.85; 95% CI, 0.77-0.93) for 5 to 19 prescriptions, and 3.2% vs 3.7% (AOR, 0.64; 95% CI, 0.59-0.70) for 20 or more prescriptions. The AORs for current use of statins defined as 20 or more prescriptions were similar (around 0.6) across age, sex, and body mass index categories, and across the statin class.

Conclusion  Long-term use of statins was associated with a decreased risk of gallstones followed by cholecystectomy.

Objective  To compare the surgical mask with the N95 respirator in protecting health care workers against influenza.

Design, Setting, and Participants  Noninferiority randomized controlled trial of 446 nurses in emergency departments, medical units, and pediatric units in 8 tertiary care Ontario hospitals.

Intervention  Assignment to either a fit-tested N95 respirator or a surgical mask when providing care to patients with febrile respiratory illness during the 2008-2009 influenza season.

Main Outcome Measures  The primary outcome was laboratory-confirmed influenza measured by polymerase chain reaction or a 4-fold rise in hemagglutinin titers. Effectiveness of the surgical mask was assessed as noninferiority of the surgical mask compared with the N95 respirator. The criterion for noninferiority was met if the lower limit of the 95% confidence interval (CI) for the reduction in incidence (N95 respirator minus surgical group) was greater than –9%.

Results  Between September 23, 2008, and December 8, 2008, 478 nurses were assessed for eligibility and 446 nurses were enrolled and randomly assigned the intervention; 225 were allocated to receive surgical masks and 221 to N95 respirators. Influenza infection occurred in 50 nurses (23.6%) in the surgical mask group and in 48 (22.9%) in the N95 respirator group (absolute risk difference, –0.73%; 95% CI, –8.8% to 7.3%; P = .86), the lower confidence limit being inside the noninferiority limit of –9%.

Conclusion  Among nurses in Ontario tertiary care hospitals, use of a surgical mask compared with an N95 respirator resulted in noninferior rates of laboratory-confirmed influenza.

Trial Registration  clinicaltrials.gov Identifier: NCT00756574

Published online October 1, 2009 (doi:10.1001/jama.2009.1466).

Objective  To describe the clinical and epidemiologic features of pandemic 2009 influenza A(H1N1) cases that led to hospitalization or death.

Design, Setting, and Participants  Statewide enhanced public health surveillance of California residents who were hospitalized or died with laboratory evidence of pandemic 2009 influenza A(H1N1) infection reported to the California Department of Public Health between April 23 and August 11, 2009.

Main Outcome Measure  Characteristics of hospitalized and fatal cases.

Results  During the study period there were 1088 cases of hospitalization or death due to pandemic 2009 influenza A(H1N1) infection reported in California. The median age was 27 years (range, <1-92 years) and 68% (741/1088) had risk factors for seasonal influenza complications. Sixty-six percent (547/833) of those with chest radiographs performed had infiltrates and 31% (340/1088) required intensive care. Rapid antigen tests were falsely negative in 34% (208/618) of cases evaluated. Secondary bacterial infection was identified in 4% (46/1088). Twenty-one percent (183/884) received no antiviral treatment. Overall fatality was 11% (118/1088) and was highest (18%-20%) in persons aged 50 years or older. The most common causes of death were viral pneumonia and acute respiratory distress syndrome.

Conclusions  In the first 16 weeks of the current pandemic, the median age of hospitalized infected cases was younger than is common with seasonal influenza. Infants had the highest hospitalization rates and persons aged 50 years or older had the highest mortality rates once hospitalized. Most cases had established risk factors for complications of seasonal influenza.

Objective  To describe characteristics, treatment, and outcomes of critically ill patients in Canada with 2009 influenza A(H1N1) infection.

Design, Setting, and Patients  A prospective observational study of 168 critically ill patients with 2009 influenza A(H1N1) infection in 38 adult and pediatric intensive care units (ICUs) in Canada between April 16 and August 12, 2009.

Main Outcome Measures  The primary outcome measures were 28-day and 90-day mortality. Secondary outcomes included frequency and duration of mechanical ventilation and duration of ICU stay.

Results  Critical illness occurred in 215 patients with confirmed (n = 162), probable (n = 6), or suspected (n = 47) community-acquired 2009 influenza A(H1N1) infection. Among the 168 patients with confirmed or probable 2009 influenza A(H1N1), the mean (SD) age was 32.3 (21.4) years; 113 were female (67.3%) and 50 were children (29.8%). Overall mortality among critically ill patients at 28 days was 14.3% (95% confidence interval, 9.5%-20.7%). There were 43 patients who were aboriginal Canadians (25.6%). The median time from symptom onset to hospital admission was 4 days (interquartile range [IQR], 2-7 days) and from hospitalization to ICU admission was 1 day (IQR, 0-2 days). Shock and nonpulmonary acute organ dysfunction was common (Sequential Organ Failure Assessment mean [SD] score of 6.8 [3.6] on day 1). Neuraminidase inhibitors were administered to 152 patients (90.5%). All patients were severely hypoxemic (mean [SD] ratio of Pao₂ to fraction of inspired oxygen [Fio₂] of 147 [128] mm Hg) at ICU admission. Mechanical ventilation was received by 136 patients (81.0%). The median duration of ventilation was 12 days (IQR, 6-20 days) and ICU stay was 12 days (IQR, 5-20 days). Lung rescue therapies included neuromuscular blockade (28% of patients), inhaled nitric oxide (13.7%), high-frequency oscillatory ventilation (11.9%), extracorporeal membrane oxygenation (4.2%), and prone positioning ventilation (3.0%). Overall mortality among critically ill patients at 90 days was 17.3% (95% confidence interval, 12.0%-24.0%; n = 29).

Conclusion  Critical illness due to 2009 influenza A(H1N1) in Canada occurred rapidly after hospital admission, often in young adults, and was associated with severe hypoxemia, multisystem organ failure, a requirement for prolonged mechanical ventilation, and the frequent use of rescue therapies.

Published online October 12, 2009 (doi:10.1001/jama.2009.1496).

Objective  To describe baseline characteristics, treatment, and outcomes of consecutive critically ill patients in Mexico hospitals that treated the majority of such patients with confirmed, probable, or suspected 2009 influenza A(H1N1).

Design, Setting, and Patients  Observational study of 58 critically ill patients with 2009 influenza A(H1N1) at 6 hospitals between March 24 and June 1, 2009. Demographic data, symptoms, comorbid conditions, illness progression, treatments, and clinical outcomes were collected using a piloted case report form.

Main Outcome Measures  The primary outcome measure was mortality. Secondary outcomes included rate of 2009 influenza (A)H1N1–related critical illness and mechanical ventilation as well as intensive care unit (ICU) and hospital length of stay.

Results  Critical illness occurred in 58 of 899 patients (6.5%) admitted to the hospital with confirmed, probable, or suspected 2009 influenza (A)H1N1. Patients were young (median, 44.0 [range, 10-83] years); all presented with fever and all but 1 with respiratory symptoms. Few patients had comorbid respiratory disorders, but 21 (36%) were obese. Time from hospital to ICU admission was short (median, 1 day [interquartile range {IQR}, 0-3 days]), and all patients but 2 received mechanical ventilation for severe acute respiratory distress syndrome and refractory hypoxemia (median day 1 ratio of Pao₂ to fraction of inspired oxygen, 83 [IQR, 59-145] mm Hg). By 60 days, 24 patients had died (41.4%; 95% confidence interval, 28.9%-55.0%). Patients who died had greater initial severity of illness, worse hypoxemia, higher creatine kinase levels, higher creatinine levels, and ongoing organ dysfunction. After adjusting for a reduced opportunity of patients dying early to receive neuraminidase inhibitors, neuraminidase inhibitor treatment (vs no treatment) was associated with improved survival (odds ratio, 8.5; 95% confidence interval, 1.2-62.8).

Conclusion  Critical illness from 2009 influenza A(H1N1) in Mexico occurred in young individuals, was associated with severe acute respiratory distress syndrome and shock, and had a high case-fatality rate.

Published online October 12, 2009 (doi:10.1001/jama.2009.1536).

Objectives  To describe the characteristics of all patients with 2009 influenza A(H1N1)–associated ARDS treated with ECMO and to report incidence, resource utilization, and patient outcomes.

Design, Setting, and Patients  An observational study of all patients (n = 68) with 2009 influenza A(H1N1)–associated ARDS treated with ECMO in 15 intensive care units (ICUs) in Australia and New Zealand between June 1 and August 31, 2009.

Main Outcome Measures  Incidence, clinical features, degree of pulmonary dysfunction, technical characteristics, duration of ECMO, complications, and survival.

Results  Sixty-eight patients with severe influenza-associated ARDS were treated with ECMO, of whom 61 had either confirmed 2009 influenza A(H1N1) (n = 53) or influenza A not subtyped (n = 8), representing an incidence rate of 2.6 ECMO cases per million population. An additional 133 patients with influenza A received mechanical ventilation but no ECMO in the same ICUs. The 68 patients who received ECMO had a median (interquartile range [IQR]) age of 34.4 (26.6-43.1) years and 34 patients (50%) were men. Before ECMO, patients had severe respiratory failure despite advanced mechanical ventilatory support with a median (IQR) Pao₂/fraction of inspired oxygen (Fio₂) ratio of 56 (48-63), positive end-expiratory pressure of 18 (15-20) cm H₂O, and an acute lung injury score of 3.8 (3.5-4.0). The median (IQR) duration of ECMO support was 10 (7-15) days. At the time of reporting, 48 of the 68 patients (71%; 95% confidence interval [CI], 60%-82%) had survived to ICU discharge, of whom 32 had survived to hospital discharge and 16 remained as hospital inpatients. Fourteen patients (21%; 95% CI, 11%-30%) had died and 6 remained in the ICU, 2 of whom were still receiving ECMO.

Conclusions  During June to August 2009 in Australia and New Zealand, the ICUs at regional referral centers provided mechanical ventilation for many patients with 2009 influenza A(H1N1)–associated respiratory failure, one-third of whom received ECMO. These ECMO-treated patients were often young adults with severe hypoxemia and had a 21% mortality rate at the end of the study period.

Published online October 12, 2009 (doi:10.1001/jama.2009.1535).