Current Table of Contents

• Failure to Disclose in: Adherence to a Mediterranean Diet, Cognitive Decline, and Risk of Dementia [Correction]
  
• Failure to Report Financial Disclosure Information [Letters]
  
• A 37-Year-Old Man Trying to Choose a High-Quality Hospital [Clinical Crossroads]
  
• Uniform Format for Disclosure of Competing Interests in ICMJE Journals [Editorial]
  
• This Week in JAMA [This Week in JAMA]
  
• Telephone-Delivered Collaborative Care for Treating Post-CABG Depression: A Randomized Controlled Trial [Original Contribution]
  

  Context  Depressive symptoms commonly follow coronary artery bypass graft (CABG) surgery and are associated with less positive clinical outcomes.

  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).

• Trends in High Levels of Low-Density Lipoprotein Cholesterol in the United States, 1999-2006 [Original Contribution]
  

  Context  Studies show that a large proportion of adults with high levels of low-density lipoprotein cholesterol (LDL-C) remain untreated or undertreated despite growing use of lipid-lowering medications.

  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%.

• Clinical and Mutational Spectrum of Neurofibromatosis Type 1-like Syndrome [Original Contribution]
  

  Context  Autosomal dominant inactivating sprouty-related EVH1 domain–containing protein 1 (SPRED1) mutations have recently been described in individuals presenting mainly with café au lait macules (CALMs), axillary freckling, and macrocephaly. The extent of the clinical spectrum of this new disorder needs further delineation.

  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.

• Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12 [Original Contribution]
  

  Context  Recently, concern has been raised about the safety of folic acid, particularly in relation to cancer risk.

  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

• Propagation of Human Spermatogonial Stem Cells In Vitro [Preliminary Communication]
  

  Context  Young boys treated with high-dose chemotherapy are often confronted with infertility once they reach adulthood. Cryopreserving testicular tissue before chemotherapy and autotransplantation of spermatogonial stem cells at a later stage could theoretically allow for restoration of fertility.

  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.

• Does This Patient With Palpitations Have a Cardiac Arrhythmia? [The Rational Clinical Examination]
  

  Context  Many patients have palpitations and seek advice from general practitioners. Differentiating benign causes from those resulting from clinically significant cardiac arrhythmia can be challenging and the clinical examination may aid in this process.

  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.

• Primary Prevention of Cardiovascular Disease: Time to Get More or Less Personal? [Commentary]
  
• Reconsidering the Role for Digoxin in the Management of Acute Heart Failure Syndromes [Commentary]
  
• Simplifying the Approach to the Management of Dyslipidemia [Editorial]
  
• Pigmentary Findings in Neurofibromatosis Type 1-like Syndrome (Legius Syndrome): Potential Diagnostic Dilemmas [Editorial]
  
• Assessing Cancer Prevention Studies--A Matter of Time [Editorial]
  
• Biomarkers for Prediction of Cardiovascular Events [Letters]
  
• Biomarkers for Prediction of Cardiovascular Events [Letters]
  
• Biomarkers for Prediction of Cardiovascular Events--Reply [Letters]
  
• Complications Associated With Use of Bone-Morphogenetic Proteins in Spinal Fusion Procedures [Letters]
  
• Complications Associated With Use of Bone-Morphogenetic Proteins in Spinal Fusion Procedures--Reply [Letters]
  
• Computed Tomographic Assessment of Atherosclerosis in Ancient Egyptian Mummies [Research Letters]
  
• Doctoral-Level Programs Prepare Nurses for Expanded Roles in Care and Research [Medical News & Perspectives]
  
• FDA Exercises New Authority to Regulate Tobacco Products, But Some Limits Remain [Medical News & Perspectives]
  
• Afghan Military Medical School Reopens, Enrolls Women in First Class of Cadets [Medical News & Perspectives]
  
• FDA: Flush Certain Unused Medications [Medical News & Perspectives]
  
• Diarrhea Deaths in Children [The World in Medicine]
  
• Preventing Falls in the Elderly [The World in Medicine]
  
• MicroRNA and Liver Cancer [The World in Medicine]
  
• IBD Drugs and Cancer Risk [The World in Medicine]
  
• Update on Influenza A (H1N1) 2009 Monovalent Vaccines [From the Centers for Disease Control and Prevention]
  
• Influenza Vaccination Coverage Among Children and Adults--United States, 2008-09 Influenza Season [From the Centers for Disease Control and Prevention]
  
• The Comtesse d'Egmont Pignatelli in Spanish Costume [The Cover]
  
• Going Home [A Piece of My Mind]
  
• Babushka [Poetry and Medicine]
  
• THE SCHOOL CHILD'S BREAKFAST [JAMA 100 Years Ago]
  
• Caring for the World: A Guidebook to Global Health Opportunities [Book and Media Reviews]
  
• Globalization and Health: Pathways, Evidence and Policy [Book and Media Reviews]
  
• Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice [Book and Media Reviews]
  
• Clinical Manual of Fever in Children [Book and Media Reviews]
  
• Practicing Medicine in Difficult Times: Protecting Physicians From Malpractice Litigation [Book and Media Reviews]
  
• Neurofibromatosis [JAMA Patient Page]
  
• About This Journal [About This Journal]