Wednesday, September 28, 2011

From NY Review of Books: Hemingway

"Hemingway’s declining health and psychological problems were more serious at the end of the 1950s. He had shock treatments at the Mayo Clinic and believed the FBI was following him. (In fact FBI agents had compiled a large file on him.) He was delusional and slurring his speech. It was kept from the public. He was unable to write as much as a single sentence. In chilling detail Hendrickson gives the almost step-by-step account of his final hour when he rose early one morning in Ketchum, Idaho, put on his slippers, and went quietly past the master bedroom where his wife was sleeping. The suicide could be seen as an act of weakness, even moral weakness, a sudden revelation of it in a man whose image was of boldness and courage, but Hendrickson’s book is testimony that it was not a failure of courage but a last display of it.

Hemingway’s Boat is a book written with the virtuosity of a novelist, hagiographic in the right way, sympathetic, assiduous, and imaginative. It does not rival the biographies but rather stands brilliantly beside them—the sea, Key West, Cuba, all the places, the life he had and gloried in. His commanding personality comes to life again in these pages, his great charm and warmth as well as his egotism and aggression.

'Forgive him anything,' as George Seldes’s wife said in the early days, 'he writes like an angel.'”

From Kevin Leslie and colleagues: Bird Fancier's Lung!

Clin Rev Allergy Immunol. 2011 Aug 26. [Epub ahead of print]
Bird Fancier's Lung: A State-of-the-Art Review.
Chan AL, Juarez MM, Leslie KO, Ismail HA, Albertson TE.
Division of Pulmonary, Critical Care and Sleep Medicine, University of California at Davis, School of Medicine and VA Northern California Health Care System, 4150 V Street, Suite 3400, Sacramento, CA, 95817, USA,

Bird fancier's lung (BFL) resulting from avian antigen exposure is a very common form of hypersensitivity pneumonitis. Its pathogenesis is modified by genetic polymorphisms located within the major histocompatibility complex, and also by smoking, which may decrease serum antibody response to inhaled antigen. Acute, subacute, and chronic presentations of BFL are recognized, but often overlap clinically. Continued antigen exposure in the chronic phase portends a worse prognosis. Chronic bronchitis symptoms may be part of the BFL clinical spectrum, and rhinitis may suggest an allergic component. The diagnosis of BFL is enhanced by a high index of suspicion of exposure to avian antigen, recurrent symptomatic episodes occurring 4-8 h after exposure, inspiratory "velcro" crackles on auscultation, weight loss, and positive IgG precipitins to the antigen. Characteristic findings on high-resolution computed tomography of the chest include centrilobular nodules, ground-glass opacification, and mosaicism due to air trapping. Bronchoalveolar lavage will classically show >25% lymphocytosis, a CD4/CD8 ratio of <1.0 and >1% mast cells in the acute phase. Lung biopsies, if obtained in the subacute phase of the disease, typically show loosely formed granulomas, giant cells, a lymphoplasmacytic interstitial infiltrate, and possibly some degree of fibrosis. In some patients, usual interstitial pneumonia or fibrotic non-specific interstitial pneumonia patterns may be seen on surgical biopsy. Skin testing, serological testing, and bronchial provocation tests for BFL frequently suffer from a lack of standardization. Effective treatment for BFL consists mainly of antigen avoidance, as corticosteroids likely do not alter long-term prognosis. Lung transplantation can be considered for progressive chronic disease refractory to medical measures.

Lung cancer: "major breakthrough", "paradigm shift", "fantastic development"

"Paul Bunn, MD, professor of medicine and James Dudley Chair in Cancer Research at the University of Colorado School of Medicine, in Aurora, who was on the panel, noted that the approval of crizotinib is part of a paradigm shift in the care and management of lung cancer."

"Mark G. Kris, MD, chief of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center in New York City, noted that this is a 'fantastic development.' 'I see this as a delivery on the promise of personalized medicine and genomic medicine,' he said during the panel discussion. 'Clinical trials have shown that virtually every patient with an ALK fusion who received crizotinib has had some benefit. It is very effective.'"

From Investor's Business Daily: Health care costs continue to rise

"Until now, many of the fears about ObamaCare have been theoretical. But this year's 9% spike in premiums is concrete evidence of the substantial harm it's already doing to our health care system.

As soon as the Kaiser Family Foundation's annual report on insurance premiums was released, ObamaCare defenders dismissed its most troubling finding: Insurance premiums for family coverage shot up an average $1,482 this year."

From Florida State U: Background music and stereotypes

J Music Ther. 2011 Summer;48(2):208-25.
The effect of background music on the perception of personality and demographics.
Lastinger DL 5th.
The Florida State University, FL, USA.

This study seeks to discover stereotypes people may have about different music genres and if these stereotypes are projected onto an individual. Also, the study investigates if music therapy students are more or less biased than non-music majors in this regard. Subjects (N=388) were comprised of student members of the American Music Therapy Association (N=182) and students from a college in the southeastern United States who were not music majors (N=206). Subjects were asked to listen to a recording and complete a short survey. Subjects assigned to the control condition heard only a person reading a script. Subjects assigned to one of the four experimental conditions heard the same recording mixed with background music and ambient crowd noise, intended to simulate a live performance. Subjects were asked to rate the person in the recording on personality descriptors and predict demographic information in the survey. Many of the survey responses were significantly affected by the genre of music. For example, it was shown that when in the presence of rap or country music, all subjects rated the personality of the person in the recording significantly more negative than when in the presence of classical, jazz, or no music. There were no significant differences between the groups for any variable or condition when comparing survey responses between college students and AMTA student members.

From LERES-France: Don't drink the water?

J Environ Monit. 2011 Sep 12. [Epub ahead of print]
Contamination levels of human pharmaceutical compounds in French surface and drinking water.
Mompelat S, Thomas O, Le Bot B.
School of Advanced Studies in Public Health (EHESP), Laboratoire d'Etude et de Recherche en Environnement et Sante (LERES), Avenue Professeur Leon Bernard, 35043, Rennes Cedex, France.

The occurrence of 20 human pharmaceutical compounds and metabolites from 10 representative therapeutic classes was analysed from resource and drinking water in two catchment basins located in north-west France. 98 samples were analysed from 63 stations (surface water and drinking water produced from surface water). Of the 20 human pharmaceutical compounds selected, 16 were quantified in both the surface water and drinking water, with 22% of the values above the limit of quantification for surface water and 14% for drinking water). Psychostimulants, non-steroidal anti-inflammatory drugs, iodinated contrast media and anxiolytic drugs were the main therapeutic classes of human pharmaceutical compounds detected in the surface water and drinking water. The results for surface water were close to results from previous studies in spite of differences in prescription rates of human pharmaceutical compounds in different countries. The removal rate of human pharmaceutical compounds at 11 water treatment units was also determined. Only caffeine proved to be resistant to drinking water treatment processes (with a minimum rate of 5%). Other human pharmaceutical compounds seemed to be removed more efficiently (average elimination rate of over 50%) by adsorption onto activated carbon and oxidation/disinfection with ozone or chlorine (not taking account of the disinfection by-products). These results add to the increasing evidence of the occurrence of human pharmaceutical compounds in drinking water that may represent a threat to human beings exposed to a cocktail of human pharmaceutical compounds and related metabolites and by-products in drinking water.

From the FDA: Feeding botanical supplements and teas to infants

Pediatrics. 2011 Jun;127(6):1060-6. Epub 2011 May 2.
Feeding of dietary botanical supplements and teas to infants in the United States.
Zhang Y, Fein EB, Fein SB.
Office of Regulations, Policy and Social Sciences, Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, Maryland, USA.

To describe the use of dietary botanical supplements and teas among infants, the characteristics of mothers who give them the specific botanical supplements and teas used, reasons for use, and sources of information.

We used data from the Infant Feeding Practices Study II, a longitudinal survey of women studied from late pregnancy through their infant's first year of life conducted by the US Food and Drug Administration and the Centers for Disease Control and Prevention between 2005 and 2007. The sample was drawn from a nationally distributed consumer opinion panel and was limited to healthy mothers with healthy term or near-term singleton infants. The final analytical sample included 2653 mothers. Statistical techniques include frequencies, χ² tests, and ordered logit models.

Nine percent of infants were given dietary botanical supplements or teas in their first year of life, including infants as young as 1 month. Maternal herbal use (P < .0001), longer breastfeeding (P < .0001), and being Hispanic (P = .016) were significantly associated with giving infants dietary botanical supplements or teas in the multivariate model. Many supplements and teas used were marketed and sold specifically for infants. Commonly mentioned information sources included friends or family, health professionals, and the media.

A substantial proportion of infants in this sample was given a wide variety of supplements and teas. Because some supplements given to infants may pose health risks, health care providers need to recognize that infants under their care may be receiving supplements or teas.

From U Utah: Increased ER admits for pneumonia showed no reduced mortality

Ann Emerg Med. 2011 Sep 8. [Epub ahead of print]
Hospital Admission Decision for Patients With Community-Acquired Pneumonia: Variability Among Physicians in an Emergency Department.
Dean NC, Jones JP, Aronsky D, Brown S, Vines CG, Jones BE, Allen T.
Pulmonary and Critical Care Medicine Division at Intermountain Medical Center and the University of Utah, Salt Lake City, UT.

We examine variability among emergency physicians in rate of hospitalization for patients with pneumonia and the effect of variability on clinical outcomes.

We studied 2,069 LDS Hospital emergency department (ED) patients with community-acquired pneumonia who were aged 18 years or older during 1996 to 2006, identified by International Classification of Diseases, Ninth Revision coding and compatible chest radiographs. We extracted vital signs, laboratory and radiographic results, hospitalization, and outcomes from the electronic medical record. We defined "low severity" as PaO(2)/FiO(2) ratio greater than or equal to 280 mm Hg, predicted mortality less than 5% by an electronic version of CURB-65 that uses continuous and weighted elements (eCURB), and less than 3 Infectious Disease Society of America-American Thoracic Society 2007 severe pneumonia minor criteria. We adjusted hospitalization decisions and outcomes for illness severity and patient demographics.

Initial hospitalization rate was 58%; 10.7% of patients initially treated as outpatients were secondarily hospitalized within 7 days. Median age of admitted patients was 63 years; median eCURB predicted mortality was 2.65% (mean 6.8%) versus 46 years and 0.93% for outpatients. The 18 emergency physicians (average age 44.9 [standard deviation 7.6] years; years in practice 8.4 [standard deviation 6.9]) objectively calculated and documented illness severity in 2.7% of patients. Observed 30-day mortality for inpatients was 6.8% (outpatient mortality 0.34%) and decreased over time. Individual physician admission rates ranged from 38% to 79%, with variability not explained by illness severity, time of day, day of week, resident care in conjunction with an attending physician, or patient or physician demographics. Higher hospitalization rates were not associated with reduced mortality or fewer secondary hospital admissions.

We observed a 2-fold difference in pneumonia hospitalization rates among emergency physicians, unexplained by objective data.

From Weill Cornell: Current status of Pseudomonas vaccines for Cystic Fibrosis patients

Hum Vaccin. 2011 Oct 1;7(10). [Epub ahead of print]
Recent developments for Pseudomonas vaccines.
Sharma A, Worgall S.
Department of Genetic Medicine and Department of Pediatrics, Weill Medical College of Cornell University, New York, NY USA.

Infections with Pseudomonas aeruginosa are a major health problem for immune-compromised patients and individuals with cystic fibrosis. A vaccine against: P. aeruginosa has long been sought after, but is so far not available. Several vaccine candidates have been assessed in experimental animals and humans, which include sub-cellular fractions, capsule components, purified and recombinant proteins. Unique characteristics of the host and the pathogen have complicated the vaccine development. This review summarizes the current state of vaccine development for this ubiquitous pathogen, in particular to provide mucosal immunity against infections of the respiratory tract in susceptible individuals with cystic fibrosis.

Sarcopenia and postmenopausal osteoporosis

J Osteoporos. 2011;2011:536735. Epub 2011 Aug 28.
Similarities in acquired factors related to postmenopausal osteoporosis and sarcopenia.
Sirola J, Kröger H.
Department of Orthopedics, Traumatology and Hand Surgery, Kuopio University Hospital, 70211 Kuopio, Finland.
Postmenopausal population is at increased risk of musculoskeletal impairments. Sarcopenia and osteoporosis are associated with significant morbidity and social and health-care costs. These two conditions are uniquely linked with similarities in pathophysiology and diagnostic methods. Uniform diagnostic criteria for sarcopenia are still evolving. Postmenopausal sarcopenia and osteoporosis share many environmental risk- and preventive factors. Moreover, geriatric frailty syndrome may result from interaction of osteoporosis and sarcopenia and may lead to increased mortality. The present paper reviews the factors in evolution of postmenopausal sarcopenia and osteoporosis.

Physicians, get ready to "adapt"

Health Care Manage Rev. 2011 Sep 19. [Epub ahead of print]
The cultural complexity of medical groups.
Nembhard IM, Singer SJ, Shortell SM, Rittenhouse D, Casalino LP.
Ingrid M. Nembhard, PhD, MS*, is Assistant Professor, Yale School of Public Health and Yale School of Management, Yale University, New Haven, Connecticut. E-mail: Sara J. Singer, PhD, MBA*, is Assistant Professor, Harvard School of Public Health and Harvard Medical School, Boston, Massachusetts. E-mail: Stephen M. Shortell, PhD, MPH, MBA, is Blue Cross of California Distinguished Professor of Health Policy and Management, School of Public Health, Haas School of Business, and is Dean, School of Public Health, University of California, Berkeley. E-mail: Diane Rittenhouse, MD, MPH, is Associate Professor, Department of Family and Community Medicine, Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco. E-mail: Lawrence P. Casalino, MD, PhD, is Chief of the Division of Outcomes and Effectiveness Research and The Livingston Farrand Associate Professor of Public Health, Department of Public Health, Weill Cornell Medical College, New York, New York. E-mail:

Organizational culture is an important driver of organizational performance. However, little is known about the cultures of medical groups, which play an important role in health care.

We sought to characterize the cultures of medical groups and identify factors that influence these cultures.

We conducted a qualitative study of the organizational cultures of 8 U.S. multispecialty medical groups, using data collected during site visits and in-depth interviews with clinical and administrative staff (N = 69). Groups were randomly selected from those that participated in the second National Study of Physician Organizations using stratified sampling along three dimensions (i.e., ownership type, use of care management practices, and outcome performance). We analyzed the data to assess the presence of seven culture types-group, hierarchical, rational, developmental, quality oriented, patient centered, and physician centered-using the constant comparative method.

We found that a multiplicity and diversity of cultures exist within and across multispecialty medical groups, with a dominance of patient-centered, physician-centered, rational, or quality-oriented cultures and less emphasis on group, developmental, and hierarchical cultures. Culture types that may seem antithetical, for example, patient-centered and physician-centered cultures, often coexisted within the same group. Across culture types, we found that six factors influenced medical group culture: financial, people, leadership, structural, processes, and environmental.

As medical groups adapt to changes under health care reform, their success likely depends on their having cultures that facilitate collaboration with other organizations (e.g., hospitals) that possess different cultures and adaptation to changes in payment and regulation. Our study suggests that some groups may not have the developmental and group cultures needed to adapt. Our study identifies six categories of levers they can use to alter their culture as desired.

Med mal in the UK

Head Neck Oncol. 2011 Sep 17;3(1):41. [Epub ahead of print]
English Law for the Surgeon I: Consent, Capacity and Competence.
Jerjes W, Mahil J, Upile T.

ABSTRACT: Traditionally, in the United Kingdom and Europe the surgeon was generally not troubled by litigation from patients presenting as elective as well as emergency cases, but this aspect of custom has changed. Litigation by patients now significantly affects surgical practice and vicarious liability often affects hospitals. We discuss some fundamental legal definitions, a must to know for a surgeon, and highlight some interesting cases.

Lung cancer treatment: Third CECOG concensus

Ann Oncol. 2011 Sep 22. [Epub ahead of print]
Third CECOG consensus on the systemic treatment of non-small-cell lung cancer.
Brodowicz T, Ciuleanu T, Crawford J, Filipits M, Fischer JR, Georgoulias V, Gridelli C, Hirsch FR, Jassem J, Kosmidis P, Krzakowski M, Manegold C, Pujol JL, Stahel R, Thatcher N, Vansteenkiste J, Minichsdorfer C, Zöchbauer-Müller S, Pirker R, Zielinski CC; for the Central European Cooperative Oncology Group (CECOG).
Clinical Division of Oncology, Comprehensive Cancer Center, Medical University Vienna-General Hospital, Vienna, Austria.

The current third consensus on the systemic treatment of non-small-cell lung cancer (NSCLC) builds upon and updates similar publications on the subject by the Central European Cooperative Oncology Group (CECOG), which has published such consensus statements in the years 2002 and 2005 (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer-update 2004. Lung Cancer 2005; 50: 129-137). The principle of all CECOG consensus is such that evidence-based recommendations for state-of-the-art treatment are given upon which all participants and authors of the manuscript have to agree (Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771-1785). This is of particular importance in diseases in which treatment options depend on very particular clinical and biologic variables (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer-update 2004. Lung Cancer 2005; 50: 129-137; Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771-1785). Since the publication of the last CECOG consensus on the medical treatment of NSCLC, a series of diagnostic tools for the characterization of biomarkers for personalized therapy for NSCLC as well as therapeutic options including adjuvant treatment, targeted therapy, and maintenance treatment have emerged and strongly influenced the field. Thus, the present third consensus was generated that not only readdresses previous disease-related issues but also expands toward recent developments in the management of NSCLC. It is the aim of the present consensus to summarize minimal quality-oriented requirements for individual patients with NSCLC in its various stages based upon levels of evidence in the light of a rapidly expanding array of individual therapeutic options.

Thursday, September 22, 2011

From Cancer: Radiotherapy for lung cancer

Predicting the need for palliative thoracic radiation after first-line chemotherapy for advanced nonsmall cell lung carcinoma.

AuthorsHigginson DS, et al.
Cancer. 2011 Sep 20. doi: 10.1002/cncr.26495. [Epub ahead of print]

Department of Radiation Oncology, Division of Hematology and Oncology, University of North Carolina, Chapel Hill, North Carolina.,

BACKGROUND: The objective of this secondary analysis was to identify patients with selected stage IIIB/IV nonsmall cell lung carcinoma and good performance status who were at high risk for requiring subsequent palliative thoracic radiotherapy after initial treatment with first-line chemotherapy.

METHODS: The authors conducted a pooled analysis of patients at a single institution who enrolled onto 10 prospective phase 2 and 3 clinical trials that involved first-line, platinum-based chemotherapy. Baseline lung-related characteristics before trial enrollment were analyzed as possible prognostic factors for freedom from pulmonary events (defined either as subsequent thoracic radiation or as a new collapsed lung, which is an indication for thoracic radiation).

RESULTS: Of 244 consecutive patients who were reviewed, 42 patients received a palliative course of thoracic radiation, 40 exhibited evidence of new lobar collapse on follow-up chest imaging, and 14 received thoracic radiation for lobar collapse. On univariable analysis, pulmonary symptoms (P = .043) or pneumonia at presentation (P = .0001), increasing size of hilar disease (P < .0001), and evidence of obstruction of major bronchi or vessels (P = .0003) were associated with subsequent pulmonary events. On multivariable analysis, hilar disease measuring >3 cm (hazard ratio, 1.8; P = .003) and prechemotherapy pneumonia (hazard ratio, 2.1; P = .009) were associated with pulmonary events; patients who had both risk factors or hilar disease >5 cm in greatest dimension exhibited a >50% risk of subsequent events.

CONCLUSIONS: Patients with bulky hilar disease and a history of pneumonia at presentation were at high risk for requiring palliative thoracic radiation. The authors propose studying these patients to determine whether early thoracic radiation may be beneficial by preserving quality of life and performance status. Cancer 2011. © 2011 American Cancer Society.

Copyright © 2011 American Cancer Society.

Wednesday, September 21, 2011

Miliary mesothelioma?

J Thorac Oncol. 2011 Oct;6(10):1753-6.
Miliary mesothelioma: a new clinical and radiological presentation in mesothelioma patients with prolonged survival after trimodality therapy.
Purek L, Laroumagne S, Dutau H, Maldonado F, Astoul P.
*Department of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, Hôpital Nord, University of the Mediterranean, Marseille, France; and †Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota.

Malignant pleural mesothelioma is usually a fatal disease and is considered a locally aggressive tumor. Consequently, distant metastases are very rare and a diffuse involvement of the lung is seldom reported. However, due to more efficient chemotherapy protocols and aggressive management strategies including induction chemotherapy followed by extrapleural pneumonectomy and adjuvant high-dose hemithoracic radiation therapy, so called trimodality therapy, survival is prolonged in selected patients. Therefore, new presentations of the disease are appearing with new diagnostic and therapeutic challenges. Herein, we report two cases of treated mesothelioma patients who developed a miliary mesothelioma in the remaining lung 36 and 41 months after undergoing multimodal therapy. Diagnostic assessment and therapeutic strategy are discussed taking into account the different evolutions of each patient.

From Nature: The evolution of overconfidence

Nature. 2011 Sep 14;477(7364):317-20. doi: 10.1038/nature10384.
The evolution of overconfidence.
Johnson DD, Fowler JH.
Politics and International Relations, University of Edinburgh, Edinburgh EH8 9LD, UK.

Confidence is an essential ingredient of success in a wide range of domains ranging from job performance and mental health to sports, business and combat. Some authors have suggested that not just confidence but overconfidence--believing you are better than you are in reality--is advantageous because it serves to increase ambition, morale, resolve, persistence or the credibility of bluffing, generating a self-fulfilling prophecy in which exaggerated confidence actually increases the probability of success. However, overconfidence also leads to faulty assessments, unrealistic expectations and hazardous decisions, so it remains a puzzle how such a false belief could evolve or remain stable in a population of competing strategies that include accurate, unbiased beliefs. Here we present an evolutionary model showing that, counterintuitively, overconfidence maximizes individual fitness and populations tend to become overconfident, as long as benefits from contested resources are sufficiently large compared with the cost of competition. In contrast, unbiased strategies are only stable under limited conditions. The fact that overconfident populations are evolutionarily stable in a wide range of environments may help to explain why overconfidence remains prevalent today, even if it contributes to hubris, market bubbles, financial collapses, policy failures, disasters and costly wars.

Chronic diseases and anxiety

Gen Hosp Psychiatry. 2011 Sep 9. [Epub ahead of print]
Comorbid physical health conditions and anxiety disorders: a population-based exploration of prevalence and health outcomes among older adults.
El-Gabalawy R, Mackenzie CS, Shooshtari S, Sareen J.
Department of Psychology, University of Manitoba, Winnipeg, MB Canada R3E 3N4.

The primary objectives of this study were to examine the likelihood of anxiety disorders among respondents with common physical health conditions and to explore the associations between this comorbidity and older adults' perceived mental and physical health.

The sample consisted of older adults from the Canadian Community Health Survey 1.2 (n=12,792). Trained lay interviewers assessed psychiatric disorders based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Physical health conditions were based on self-reported diagnoses by health professionals. Multiple logistic regressions examined whether suffering from a physical health condition increased the odds of any assessed anxiety disorder (panic, agoraphobia, social phobia and posttraumatic stress disorder). Multiple linear regressions examined associations between self-rated health and comorbid physical health conditions and anxiety.

After adjusting for confounding variables, the presence of chronically painful conditions (i.e., arthritis, back pain and migraine) and of other commonly occurring diseases (i.e., allergies, cataracts and gastrointestinal, lung and heart disease) were positively associated with anxiety. The comorbidity of anxiety with allergies, cataracts, arthritis and lung disease resulted in poorer self-rated physical and/or mental health after adjusting for confounding variables.

Health problems in older adults are associated with increased odds of anxiety, and this comorbidity is associated with poorer self-reported health than medical problems or anxiety alone. These findings have important clinical implications for health professionals.

Copyright © 2011 Elsevier Inc. All rights reserved.

The Framingham Heart Study and chronic kidney disease

Hypertension. 2011 Sep 19. [Epub ahead of print]
Fatty Kidney, Hypertension, and Chronic Kidney Disease: The Framingham Heart Study.
Foster MC, Hwang SJ, Porter SA, Massaro JM, Hoffmann U, Fox CS.
Framingham Heart Study, Framingham, MA; Division of Intramural Research and the Center for Population Studies, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; Department of Epidemiology, Harvard School of Public Health, Boston, MA; Division of Endocrinology and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Biostatistics, Boston University School of Public Health, Boston, MA; Department of Radiology, Massachusetts General Hospital, Boston, MA.

Ectopic fat depots may mediate local and systemic disease. Animal models of diet-induced obesity demonstrate increased fat accumulation in the renal sinus. The association of renal sinus fat with hypertension, chronic kidney disease, and other metabolic disorders has not been studied in a large, community-based sample. Participants from the Framingham Heart Study (n=2923; mean age: 54 years; 51% women) underwent quantification of renal sinus fat area using computed tomography. High renal sinus fat ("fatty kidney") was defined using sex-specific 90th percentiles in a healthy referent subsample. Multivariable linear and logistic regression was used to model metabolic risk factors as a function of fatty kidney and log-transformed renal sinus fat. Multivariable models were adjusted for age, sex, and outcome-specific covariates and then additionally adjusted for body mass index or abdominal visceral adipose tissue. The prevalence of fatty kidney was 30.1% (n=879). Individuals with fatty kidney had a higher odds ratio (OR) of hypertension (OR: 2.12; P<0.0001), which persisted after adjustment for body mass index (OR: 1.49; P<0.0001) or visceral adipose tissue (OR: 1.24; P=0.049). Fatty kidney was also associated with an increased OR for chronic kidney disease (OR: 2.30; P=0.005), even after additionally adjusting for body mass index (OR: 1.86; P=0.04) or visceral adipose tissue (OR: 1.86; P=0.05). We observed no association between fatty kidney and diabetes mellitus after adjusting for visceral adipose tissue. In conclusion, fatty kidney is a common condition that is associated with an increased risk of hypertension and chronic kidney disease. Renal sinus fat may play a role in blood pressure regulation and chronic kidney disease.

Off label drug use, the FDA, and law

Am J Law Med. 2011;37(2-3):258-77.
Commercial speech and off-label drug uses: what role for wide acceptance, general recognition and research incentives?
Gilhooley M.
Seton Hall Law School, USA.

This article provides an overview of how the constitutional protections for commercial speech affect the Food and Drug Administration's (FDA) regulation of drugs, and the emerging issues about the scope of these protections. A federal district court has already found that commercial speech allows manufacturers to distribute reprints of medical articles about a new off-label use of a drug as long as it contains disclosures to prevent deception and to inform readers about the lack of FDA review. This paper summarizes the current agency guidance that accepts the manufacturer's distribution of reprints with disclosures. Allergan, the maker of Botox, recently maintained in a lawsuit that the First Amendment permits drug companies to provide "truthful information" to doctors about "widely accepted" off-label uses of a drug. While the case was settled as part of a fraud and abuse case on other grounds, extending constitutional protections generally to "widely accepted" uses is not warranted, especially if it covers the use of a drug for a new purpose that needs more proof of efficacy, and that can involve substantial risks. A health law academic pointed out in an article examining a fraud and abuse case that off-label use of drugs is common, and that practitioners may lack adequate dosage information about the off-label uses. Drug companies may obtain approval of a drug for a narrow use, such as for a specific type of pain, but practitioners use the drug for similar uses based on their experience. The writer maintained that a controlled study may not be necessary to establish efficacy for an expanded use of a drug for pain. Even if this is the case, as discussed below in this paper, added safety risks may exist if the expansion covers a longer period of time and use by a wider number of patients. The protections for commercial speech should not be extended to allow manufacturers to distribute information about practitioner use with a disclosure about the lack of FDA approval. Distributions of information about unapproved uses should not be acceptable unless experts consider the expanded use to be generally recognized as safe and effective based on adequate studies. The last part of this paper considers the need to develop better research incentives to encourage more testing and post-market risk surveillance by drug makers on off-label uses of their drugs. Violations of the Federal Food Drug and Cosmetic Act (FFDCA) can be considered violations of the False Claims Act, which opens the way to fraud and abuse suits. The scale of penalties involved in these suits may lead to more examination of the scope of FDA regulation and commercial speech protections. Thus this symposium's consideration of these issues is timely and important.

More on Cystic Fibrosis and Pseudomonas infection

Infect Immun. 2011 Sep 19. [Epub ahead of print]
Genotypic and phenotypic variation in P. aeruginosa reveals signatures of secondary infection and mutator activity in certain CF patients with chronic lung infections.
Warren AE, Boulianne-Larsen CM, Chandler CB, Chiotti K, Kroll E, Miller SR, Taddei F, Sermet-Gaudelus I, Ferroni A, McInnerney K, Franklin MJ, Rosenzweig F.
Division of Biological Sciences, The University of Montana, Missoula, Montana.

Evolutionary adaptation of Pseudomonas aeruginosa to the cystic fibrosis lung is limited by genetic variation, which depends on rates of horizontal gene transfer and mutation supply. Because each may increase following secondary infection or mutator emergence we sought to ascertain incidence of secondary infection and genetic variability in populations containing or lacking mutators. Forty-nine strains collected over three years from sixteen patients were phenotyped for antibiotic resistance and mutator status, and genotyped by rep-PCR, PFGE, and MLST. Though phenotypic and genetic polymorphisms were widespread and clustered more strongly within rather than between longitudinal series, their distribution revealed instances of secondary infection. Sequence data, however, indicated that inter-lineage recombination predated initial strain isolation. Mutator series were more likely to be multiply antibiotic-resistant, but not necessarily more variable in their nucleotide sequences than non-mutators. One mutator and one non-mutator series were sequenced at mismatch repair loci and analyzed for gene content using DNA microarrays. Both were wild-type with respect to mutL, but mutators encoded an 8-bp mutS deletion causing a frameshift mutation. Both series lacked 126 genes encoding pilins, siderophores and virulence factors whose inactivation has been linked to adaptation during chronic infection. Mutators exhibited loss of several-fold more genes having functions related to mobile elements, motility and attachment. A 105kb, 86-gene deletion was observed in one non-mutator that resulted in loss of virulence factors related to pyoverdine synthesis and elements of the multi-drug efflux regulon. Diminished DNA repair activity may facilitate but not be absolutely required for rapid evolutionary change.

From Archer Daniels Midland Co.: No association between fructose and metabolic syndrome.

Food Chem Toxicol. 2011 Aug 25. [Epub ahead of print]
Fructose and non-fructose sugar intakes in the US population and their associations with indicators of metabolic syndrome.
Sun SZ, Anderson GH, Flickinger BD, Williamson-Hughes PS, Empie MW.
Office of Compliance and Ethics, Archer Daniels Midland Company, 1001 North Brush College Road, Decatur, IL 62521, USA.

Relationships of sugar intakes with indicators of metabolic syndrome are important concerns for public health and safety. For individuals, dietary intake data for fructose and other sugars are limited.

Descriptive statistics. The data from 25,506 subjects, aged 12-80yr, contained in the NHANES 1999-2006 databases were analyzed for sugar intakes and health parameters.

Dietary fructose was almost always consumed with other sugars. On average, fructose provided 37% of total simple sugar intake and 9% of energy intake. In more than 97% of individuals studied, fructose caloric contribution was lower than that of non-fructose sugars. Fructose and non-fructose sugar intakes had no positive association with blood concentrations of TG, HDL cholesterol, glycohemoglobin, uric acid, blood pressure, waist circumference, and BMI in the adults studied (aged 19 to 80yr, n=17,749).

Daily fructose intakes with the American diet averaged approximately 37% of total sugars and 9% of daily energy. Fructose was rarely consumed solely or in excess over non-fructose sugars. Fructose and non-fructose sugar ordinary consumption was not positively associated with indicators of metabolic syndrome, uric acid and BMI.

Copyright © 2011 Elsevier Ltd. All rights reserved.

From Mayo Clinic: Vitamin D and sarcopenia--any link?

J Bone Miner Res. 2011 Sep 13. doi: 10.1002/jbmr.510. [Epub ahead of print]
Is vitamin D a determinant of muscle mass and strength?
Marantes I, Achenbach SJ, Atkinson EJ, Khosla S, Melton LJ 3rd, Amin S.
Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA; Department of Hygiene and Epidemiology, OPorto Medical School, Portugal.

There remains little consensus on the link between vitamin D levels and muscle mass or strength. We therefore investigated the association of serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)(2) D), and parathyroid hormone (PTH) levels with skeletal muscle mass and strength.

We studied 311 men (mean age, 56 yrs; range, 23-91 yrs) and 356 women (mean age, 57 yrs; range, 21-97 yrs) representing an age-stratified, random sample of community adults. Multivariate linear regression models were used to examine the association of skeletal muscle mass (by total body dual-energy x-ray absorptiometry) and strength (handgrip force and isometric knee extension moment) with each of 25(OH)D, 1,25(OH)(2) D and PTH quartiles, adjusted for age, physical activity, fat mass and season.

We found no consistent association between 25(OH)D or PTH and any of our measurements of muscle mass or strength, in either men or women. However, in subjects younger than 65 years, there was a statistically significant association between low 1,25(OH)(2) D levels and low skeletal mass in both men and women and low isometric knee extension moment and force in women, after adjustment for potential confounders.

Modestly low 25(OH)D or high PTH levels may not contribute significantly to sarcopenia or muscle weakness in community adults. The link between low 25(OH)D and increased fall risk reported by others may be due to factors that affect neuromuscular function rather than muscle strength. The association between low 1,25(OH)(2) D and low skeletal mass and low knee extension moment, particularly in younger people, needs further exploration. © 2011 American Society for Bone and Mineral Research.

Quality and efficiency in US health care

Int J Health Care Qual Assur. 2011;24(5):366-88.
Examining quality and efficiency of the U.S. healthcare system.
Kumar S, Ghildayal NS, Shah RN.
Opus College of Business, University of St. Thomas, Minneapolis, Minnesota, USA.

The fundamental concern of this research study is to learn the quality and efficiency of U.S. healthcare services. It seeks to examine the impact of quality and efficiency on various stakeholders to achieve the best value for each dollar spent for healthcare. The study aims to offer insights on quality reformation efforts, contemporary healthcare policy and a forthcoming change shaped by the Federal healthcare fiscal policy and to recommend the improvement objective by comparing the U.S. healthcare system with those of other developed nations.

The US healthcare system is examined utilizing various data on recent trends in: spending, budgetary implications, economic indicators, i.e., GDP, inflation, wage and population growth. Process maps, cause and effect diagrams and descriptive data statistics are utilized to understand the various drivers that influence the rising healthcare cost. A proposed cause and effect diagram is presented to offer potential solutions, for significant improvement in U.S. healthcare.

At present, the US healthcare system is of vital interest to the nation's economy and government policy (spending). The U.S. healthcare system is characterized as the world's most expensive yet least effective compared with other nations. Growing healthcare costs have made millions of citizens vulnerable. Major drivers of the healthcare costs are institutionalized medical practices and reimbursement policies, technology-induced costs and consumer behavior.

Reviewing many articles, congressional reports, internet websites and related material, a simplified process map of the US healthcare system is presented. The financial process map is also created to further understand the overall process that connects the stakeholders in the healthcare system. Factors impacting healthcare are presented by a cause and effect diagram to further simplify the complexities of healthcare. This tool can also be used as a guide to improve efficiency by removing the "waste" from the system. Trend analyses are presented that display the crucial relationship between economic growth and healthcare spending.

There are many articles and reports published on the US healthcare system. However, very few articles have explored, in a comprehensive manner, the links between the economic indicators and measures of the healthcare system and how to reform this system. As a result of the US healthcare system's complex structure, process map and cause-effect diagrams are utilized to simplify, address and understand. This study linked top-level factors, i.e., the societal, government policies, healthcare system comparison, potential reformation solutions and the enormity of the recent trends by presenting serious issues associated with U.S. healthcare.

From Lung Cancer: A smell test for mesothelioma?

Lung Cancer. 2011 Sep 14. [Epub ahead of print]
An electronic nose distinguishes exhaled breath of patients with Malignant Pleural Mesothelioma from controls.
Dragonieri S, van der Schee MP, Massaro T, Schiavulli N, Brinkman P, Pinca A, Carratú P, Spanevello A, Resta O, Musti M, Sterk PJ.
Department of Respiratory Diseases, University of Bari, Bari, Italy; Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

Malignant Pleural Mesothelioma (MPM) is a tumour of the surface cells of the pleura that is highly aggressive and mainly caused by asbestos exposure. Electronic noses capture the spectrum of exhaled volatile organic compounds (VOCs) providing a composite biomarker profile (breathprint).

We tested the hypothesis that an electronic nose can discriminate exhaled air of patients with MPM from subjects with a similar long-term professional exposure to asbestos without MPM and from healthy controls.

13 patients with a histology confirmed diagnosis of MPM (age 60.9±12.2 year), 13 subjects with certified, long-term professional asbestos exposure (age 67.2±9.8), and 13 healthy subjects without asbestos exposure (age 52.2±16.2) participated in a cross-sectional study. Exhaled breath was collected by a previously described method and sampled by an electronic nose (Cyranose 320). Breathprints were analyzed by canonical discriminant analysis on principal component reduction. Cross-validated accuracy (CVA) was calculated.

Breathprints from patients with MPM were separated from subjects with asbestos exposure (CVA: 80.8%, sensitivity 92.3%, specificity 85.7%). MPM was also distinguished from healthy controls (CVA: 84.6%). Repeated measurements confirmed these results.

Molecular pattern recognition of exhaled breath can correctly distinguish patients with MPM from subjects with similar occupational asbestos exposure without MPM and from healthy controls. This suggests that breathprints obtained by electronic nose have diagnostic potential for MPM.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Lung and head & neck cancer and social stigma

Psychooncology. 2011 Sep 19. doi: 10.1002/pon.2063. [Epub ahead of print]
The psychosocial impact of stigma in people with head and neck or lung cancer.
Lebel S, Castonguay M, Mackness G, Irish J, Bezjak A, Devins GM.
University of Ottawa, Ottawa, Ontario, Canada.

Lung and head and neck cancers are widely believed to produce psychologically destructive stigma because they are linked to avoidable risk-producing behaviors and are highly visible, but little research has tested these ideas. We examined cancer-related stigma, its determinants, and its psychosocial impact in lung (n = 107) and head and neck cancer survivors (n = 99) ≤3 years post-diagnosis. We investigated cancer site, self-blame, disfigurement, and sex as determinants, benefit finding as a moderator, and illness intrusiveness as a mediator of the relation between stigma and its psychosocial impact.

Prospective participants received questionnaire packages 2 weeks before scheduled follow-up appointments. They self-administered widely used measures of subjective well-being, distress, stigma, self-blame, disfigurement, illness intrusiveness, and post-traumatic growth.

As hypothesized, stigma correlated significantly and uniquely with negative psychosocial impact, but contrary to common beliefs, reported stigma was comparatively low. Reported stigma was higher in (i) men than women, (ii) lung as compared with head and neck cancer, and (iii) people who were highly disfigured by cancer and/or its treatment. Benefit finding buffered stigma's deleterious effects, and illness intrusiveness was a partial mediator of its psychosocial impact.

Stigma exerts a powerful, deleterious psychosocial impact in lung and head and neck cancers, but is less common than believed. Patients should be encouraged to remain involved in valued activities and roles and to use benefit finding to limit its negative effects. Copyright © 2011 John Wiley & Sons, Ltd.

Friday, September 16, 2011

Tumor necrosis factor, airway damage, and Cystic Fibrosis

Am J Physiol Lung Cell Mol Physiol. 2011 Sep 9. [Epub ahead of print]
Regulation of normal and cystic fibrosis airway epithelial repair processes by TNF{alpha} after injury.
Maille E, Trinh NT, Prive A, Bilodeau C, Bissonnette E, Grandvaux N, Brochiero E.
1Centre de Recherche, CHUM-Hotel-Dieu.

Chronic infection and inflammation have been associated with progressive airway epithelial damage in cystic fibrosis (CF) patients. However, the effect of inflammatory products on the repair capacity of respiratory epithelia is unclear. Our objective was to study the regulation of repair mechanisms by tumor necrosis factor-alpha (TNFα), a major component of inflammation in CF, in a model of mechanical wounding, in 2 bronchial cell lines, non-CF NuLi and CF CuFi. We observed that TNFα enhanced the NuLi and CuFi repair rates. Chronic exposure (24-48 h) to TNFα augmented this stimulation as well as the migration rate during repair. The cellular mechanisms involved in this stimulation were then evaluated. First, we discerned that TNFα induced metalloproteinase-9 release, EGF shedding and subsequent EGFR trans-activation. Second, TNFα-induced stimulation of the NuLi and CuFi wound closure rates was prevented by GM6001 (metalloproteinase inhibitor), EGF-Ab (to titrate secreted EGF) and EGFR tyrosine kinase inhibitors. Furthermore, we recently reported a relationship between the EGF response and K(+) channel function, both controlling bronchial repair. We now show that TNFα enhances KvLQT1 and K(ATP) currents, while their inhibition abolishes TNFα-induced repair stimulation. These results indicate that TNFα's effect is mediated, at least in part, through EGFR trans-activation and K(+) channel stimulation. In contrast, cell proliferation during repair was slowed by TNFα, suggesting that TNFα could exert contrasting actions on repair mechanisms of CF airway epithelia. Finally, the stimulatory effect of TNFα on airway wound repair was confirmed on primary airway epithelial cells, from non-CF and CF patients.

Serving individual health care needs: Soon to be extinct?

Theor Med Bioeth. 2011 Sep 6. [Epub ahead of print]
Health care reform: Can a communitarian perspective be salvaged?
Callahan D.
The Hastings Center, 21 Malcolm Gordon Road, Garrison, NY, 10524, USA,

The United States is culturally oriented more toward individual rights and values than to communitarian values. That proclivity has made it hard to develop a common good, or solidarity-based, perspective on health care. Too many people believe they have no obligation to support the health care of others and resist a strong role for government, higher taxation, or reduced health benefits. I argue that we need to build a communitarian perspective on the concept of solidarity, which has been the concept underlying European health care systems, by focusing not on individual needs, but rather, on those of different age groups-that is, what people need at different stages of life.

More on medical research integrity

J Vasc Surg. 2011 Sep;54(3 Suppl):22S-5S.
Shining the light on physician-pharmaceutical and medical device industry financial relationships.
Conn L, Vernaglia L.
Foley & Lardner LLP, Boston, Mass.

Long subject to legal scrutiny under the federal Anti-Kickback Statute, financial ties between physicians and drug manufacturers have recently come under additional pressure as a result of recently enacted state and federal disclosure laws and state gift restrictions, the latest coming in connection with the Federal Health Reform Law. These "sunshine" laws have been motivated by the concern that gifts and payments by manufacturers to physicians may lead to conflicts of interest and improperly influence physicians in their drug- or device-prescribing decisions. As a backdrop to these new laws, it is helpful to review prior guidance regarding manufacturer-physician financial relationships, both from the federal government and the industry itself. These laws do not prohibit physician involvement with industry in research and education, but they impose various new compliance requirements on these relationships, and also in many cases, require public disclosure of arrangements that previously were treated as confidential. It is still too early to tell if these laws will stifle innovation, but they do require a heightened degree of diligence to avoid, at a minimum, adverse publicity and embarrassment and, at worst, criminal and civil liability.

Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Standard of medical care during disasters

Confusing. Standard of care already takes into account circumstances surrounding an event.

Ann Emerg Med. 2011 Sep 8. [Epub ahead of print]
Altering the Standard of Care in Disasters-Unnecessary and Dangerous.
Schultz CH, Annas GJ.
Center for Disaster Medical Sciences, Department of Emergency Medicine, UC Irvine School of Medicine, Orange, CA.

After September 11, 2001, the United States began examining approaches to the delivery of medical care during disasters when demand exceeds available resources. One seemingly popular option is the creation of "crisis" or "altered" care standards meant to reduce the legal standard or duty of care for medical responders. However, evidence supporting the need for reduced care standards is lacking. Concern for liability exists but it is not evidence based. The actual risk for litigation is minimal, according to experience with multiple disasters during the last 15 years. Even if a lower legal standard or duty of care were to be adopted, it is unlikely this would reduce the risk of liability because violation of this lower standard could still result in an allegation of malpractice. Creating algorithms to equitably and rationally allocate scarce resources is necessary and appropriate, but altering the legal standard of care will not contribute to this process. Rather than inhibiting the creation of these protocols, the current legal standard of care helps guarantee that disaster policies are created in an ethical and transparent manner. Adoption of a lower legal care standard would encourage implementation of less effective approaches and could undermine the impetus to constantly improve the care of disaster victims. Once lowering the legal standard of care becomes accepted practice, it becomes unclear what will prevent this process from moving downward indefinitely. The most rational approach buttressed by evidence to date supports maintaining the current legal standard of care defined by the actions of reasonably prudent physicians under the same or similar circumstances.

Health Care Act, ACOs, PAs, and tort reform. Schizophrenia?

Ann Health Law. 2011 Summer;20(2):205-51, 5-6p preceding i.
The schizophrenia of physician extender utilization.
McLean TR.
Third Millennium Consultants, LLC, Shawnee, KS, USA.

The Patient Protection and Affordable Care Act of 2010 provides incentives for healthcare to be delivered by Affordable Care Organizations (ACOs). The public face of many, if not most, ACOs is likely to be the Patient Centered Medical Home (PCMHs), a business structure that evolved from Retail Medical Clinics, which made greater use of physician extenders (PAs). Accordingly, this paper examines the evolution and structure of PCMHs as well as how the PCMH is regulated. As neither legal or market regulatory mechanisms are ideal for policing business structures that employ PAs, this paper concludes that the tort reform most appropriate for PCMHs is the introduction of either no-fault or enterprise liability coverage.

Lobectomies: Thorascopic vs. Open

Surg Endosc. 2011 Sep 5. [Epub ahead of print]
Lobectomy for early-stage lung carcinoma: a cost analysis of full thoracoscopy versus posterolateral thoracotomy.
Ramos R, Masuet C, Gossot D.
Thoracic Department, Institut Mutualiste Montsouris, 42 Bd Jourdan, 75014, Paris, France.

Major pulmonary resections for early-stage non-small-cell lung cancer (NSCLC) are increasingly being performed by thoracoscopy, but there are economic concerns related to the use of many disposable items and increased operative time. We evaluated and compared the costs of thoracoscopic lobectomy versus open lobectomy.

Data from all patients who underwent lobectomy for clinical stage I NSCLC from January 1, 2007, to December 31, 2009 were reviewed. Two hundred eighty-seven major pulmonary resections (269 lobectomies and 18 anatomic segmentectomies) for NSCLC were performed: 98 cases via a totally endoscopic approach (TS) and 189 via a classical posterolateral thoracotomy (PLT). Direct medical costs [hospital stay, intensive care unit (ICU) stay, disposables, theatre time, laboratory, and radiology costs] were evaluated.

Patient demographics were similar in both groups. The two groups did not differ in histology, pathologic stage, or type of lobectomy. There were no differences in postoperative complications or readmissions during the 30-day postoperative period; however, patients in the TS group had significantly fewer chest tube days and shorter hospital length of stay (p < 0.001). Theatre costs were significantly higher in the TS group [2,861 ± 458 vs. 2,260 ± 399 (p < 0.001)]. Mean cost for disposables for TS was 1,800 ± 560.46 vs. 901 ± 328 for PLT (p < 0.001). Thoracoscopic upper-right lobectomy and anatomic segmentectomy were more expensive than other thoracoscopic lobectomies. Mean costs for hospital stay, laboratory, and radiological services for TS were less than for PLT (p < 0.001), although mean ICU stay was similar in both groups. Finally, overall costs were significantly greater for the PLT group (14,145.57 ± 7,117.84) than for the TS group (11,934.13 ± 6,690.25) (p < 0.001).

Thoracoscopic lobectomy was less expensive than open lobectomy for patients with early-stage NSCLC. Although thoracoscopic lobectomy has a higher initial cost, overall cost is less expensive due to a shorter hospital stay.

Octogenerians and the safety of lung surgery

Eur J Cardiothorac Surg. 2011 Sep 5. [Epub ahead of print]
Is it safe to include octogenarians at the start of a video-assisted thoracic surgery lobectomy programme?
Amer K, Khan AZ, Vohra H, Saad R.
The Cardiovascular & Thoracic Unit, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK.

Objective: The study aimed to investigate the safety of including patients ≥80 years of age at the start of a video-assisted thoracic surgery major pulmonary resection (VMPR) programme. Methods: Patients were considered for VMPR if the computed tomography/positron emission tomography (CT/PET) was suggestive of T1-3, N0-1 and M0 lesion. Age was not a criterion for exclusion at the very start of the programme. Data were collected prospectively and comparison made between two groups, (A) <80 years of age and (B) ≥80 years, in terms of preoperative risk factors, oncological and functional data, operative results, postoperative complications and survival. Results: Between April 2005 and January 2011, 200 consecutive patients were considered for VMPR. A total of 160 had non-small-cell lung cancer, of whom 136 were in group A, with a median age of 66.5 (range: 42.8-79.4 years) and 24 in group B with a median age of 82 (range: 80-85.5 years). In group B, 13 were men and 11 were women. Rate of conversion to thoracotomy was similar (3 (12.5%) in group B vs 17 (12.5%) in group A, p=0.65), and so was the mean hospital stay (5.8±3.3 days in group B vs 5.9±4.6 days in group A, p=0.899). Admission to intensive care unit and atrial fibrillation were significantly higher in octogenarians (six (25%) and six (25%) in group B vs eight (5.9%) and nine (6.6%) in group A, p=0.008 and p=0.012, respectively). There was significantly less mean days of air leak in octogenarians (0.06±0.3 days in group B vs 2.8±5.6 days in group A, p=0.000). Otherwise, there were no age-related differences in relation to morbidity, mortality and the 3-year survival rate. Conclusion: Octogenarians undergoing VMPR have a higher incidence of atrial fibrillation and admission to the intensive care unit for cardiopulmonary support but otherwise are no different from younger age groups when it comes to rate of conversion to thoracotomy, hospital stay, morbidity and mortality. Age should not be an excuse to deny the elderly curative VATS resection. In our experience, accepting octogenarians early in the VMPR programme did not compromise the outcome results.

From Keith Kerr: Lung cancer, personalized medicine, and new challenges

Histopathology. 2011 Sep 14. doi: 10.1111/j.1365-2559.2011.03854.x. [Epub ahead of print]
Personalized medicine for lung cancer: new challenges for pathology.
Kerr KM.
Aberdeen University Medical School, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, UK.

Recent advances in non-small-cell lung cancer (NSCLC) therapy mean the relatively simple discrimination between small-cell and 'non-small-cell' carcinoma is insufficient to determine the best treatment for individual patients. Safety, efficacy and prescribing requirements mandate more specific subtyping of NSCLC for several new drugs: practice made difficult by the tumour heterogeneity combined with the paucity of tissue in most diagnostic samples. Immunohistochemical approaches have emerged as accurate predictors of probable tumour histotype. P63 and/or cytokeratins 5 and 6 and thyroid transcription factor 1 (TTF1) are among the best predictors, respectively, of squamous and adenocarcinoma histology. Molecular characteristics may predict response to both newer molecular targeted agents and traditional cytotoxic agents. Specific mutations in the epidermal growth factor receptor (EGFR) gene as predictors of response to EGFR tyrosine kinase inhibitors (erlotinib, gefitinib) is the first example of markers which predict response to targeted agents. Actual drug targets [e.g. thymidilate synthase (TS) - pemetrexed] or markers of the tumour's ability to repair cytotoxic drug-induced damage [e.g. excision repair cross-complementation group 1 (ERCC1) - cisplatin] may well also complement NSCLC diagnosis. This extended diagnostic requirement from increasingly limited material provided by minimally invasive biopsy techniques poses major challenges for pathology.

From CDC: Lung cancer disparities. Need to study why. Just smoking rates?

Cancer. 2011 Sep 14. doi: 10.1002/cncr.26479. [Epub ahead of print]
Racial and regional disparities in lung cancer incidence.
Underwood JM, Townsend JS, Tai E, Davis SP, Stewart SL, White A, Momin B, Fairley TL.
Centers for Disease Control and Prevention, Atlanta, Georgia; Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia; Epidemic Intelligence Service Officer assigned to the National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.

Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer-related death in the United States (US). We examined data from 2004 to 2006 for lung cancer incidence rates by demographics, including race and geographic region, to identify potential health disparities.

Data from cancer registries affiliated with the Centers for Disease Control and Prevention's (CDC) National Program of Cancer Registries (NPCR), and the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results Program (SEER) were used for this study; representing 100% of the US population. Age-adjusted incidence rates and 95% confidence intervals for demographic (age, sex, race, ethnicity, and US Census region), and tumor (stage, grade, and histology) characteristics were calculated.

During 2004 to 2006, 623,388 people (overall rate of 68.9 per 100,000) were diagnosed with lung cancer in the US. Lung cancer incidence rates were highest among men (86.2), Blacks (73.0), persons aged 70 to 79 years (431.1), and those living in the South (74.7). Among Whites, the highest lung cancer incidence rate was in the South (75.6); the highest rates among Blacks (88.9) and American Indians/Alaska Natives (65.4) in the Midwest, Asians/Pacific Islanders in the West (40.0), and Hispanics in the Northeast (40.3).

Our findings of racial, ethnic, and regional disparities in lung cancer incidence suggest a need for the development and implementation of more effective culturally specific preventive and treatment strategies that will ultimately reduce the disproportionate burden of lung cancer in the US. Cancer 2011. © 2011 American Cancer Society.

Sunday, September 11, 2011

LRP-1 and human pleural mesothelial cells

Am J Respir Cell Mol Biol. 2011 Sep 1. [Epub ahead of print]
LRP-1 Regulates Collagen 1 Expression, Proteolysis, and Migration in Human Pleural Mesothelial Cells.
Tucker TA, Williams L, Koenig K, Kothari H, Komissarov AA, Florova G, Mazar AP, Allen TC, Bdeir K, Rao LV, Idell S.
Texas Lung Injury Institute, University of Texas Health Science Center at Tyler, 11937 US Higway 271, Tyler, Texas, 75708, United States.

The low-density lipoprotein receptor-related protein 1 (LRP-1) binds and can internalize a diverse group of ligands including members of the fibrinolytic pathway; urokinase plasminogen activator (uPA) and its receptor, uPAR. In this study, we characterized the role of LRP-1 in uPAR processing, collagen synthesis, proteolysis and migration in pleural mesothelial cells (PMCs). When PMCs were treated with the pro-inflammatory cytokines TNF-α and IL-1β, LRP-1 significantly decreased at both the mRNA and protein levels (70% and 90% respectively, p<0.05). Consequently, uPA-mediated uPAR internalization was reduced by 80% in the presence of TNF-α or IL-1β (p<0.05). In parallel studies, LRP-1 neutralization with receptor associated protein; RAP, significantly reduced uPA-dependent uPAR internalization and increased uPAR stability in PMCs. LRP-1 deficient cells demonstrated increased uPAR t1/2 versus LRP-1 expressing PMCs. uPA enzymatic activity was also increased in LRP-1 deficient and neutralized cells and RAP potentiated uPA-dependent migration in PMCs. Collagen expression in PMCs was also induced by uPA and the effect was potentiated in RAP-treated cells. These studies indicate that TNF-α and IL-1β regulate LRP-1 in PMCs and that LRP-1 thereby contributes to a range of pathophysiologically relevant responses of these cells.

Thursday, September 8, 2011

From Lung Cancer: Pemetrexed therapy for pleural mesothelioma

Lung Cancer. 2011 Sep 2. [Epub ahead of print]
Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study.
Kuribayashi K, Voss S, Nishiuma S, Arakawa K, Nogi Y, Mikami K, Kudoh S.
Department of Respiratory Medicine, Murakami Memorial Hospital, Asahi University, Gifu, Japan.

Background Pemetrexed in combination with cisplatin (Pem/Cis) is the only approved chemotherapeutic regimen for malignant pleural mesothelioma (MPM). At the time of launch, limited safety information was available. The purpose of this postmarketing all-case registry study was to investigate the safety and effectiveness of pemetrexed in patients with MPM. Methods From January 2007 to May 2008, MPM patients to be treated with pemetrexed in Japan were registered to this study to monitor its safety and effectiveness. Supply of pemetrexed was restricted to institutions with experienced medical oncologists based on predetermined criteria. Results Of 953 patients registered, data from 903 patients were eligible for analysis. Most patients were male, with median age of 65 years and 68.5% had a history of asbestos exposure. More than 90% of patients received the first cycle of Pem/Cis treatment; median number of treatment cycles was 4.0. Treatment-associated death was reported in 0.8% of patients. The incidence of Interstitial lung disease (ILD) associated with Pem/Cis during the observation period was 0.9%. The frequency of ILD in patients with pre-existing asbestosis was higher than that in patients without it. For tumor response, the overall response rate was 25.0% (95% confidence interval (CI): 22.2-28.0%). The six-month survival rate estimated by the Kaplan-Meier method was 75.9%. Conclusions This large scale all case registry study appeared to have enrolled a major portion of Japanese MPM patients. Treatment with pemetrexed was generally well tolerated and showed safety and effectiveness comparable to prior clinical trials.

From NCI: Frailty in the elderly

Consult Pharm. 2011 Sep;26(9):634-45.
Understanding frailty in the geriatric population.
Wick JY.
National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Clinicians who work with the frail elderly know what frailty looks like, but until recently, they have had no science-based definition of this condition. Frailty is classified as a medical syndrome, and Fried et al. were among the first to standardize the definition of frailty as a distinct syndrome with biologic underpinnings. Their definition describes a clinical phenotype of decreased reserve and resistance to stressors, with clinical manifestations of a mutually exacerbating cycle of negative energy balance, sarcopenia, diminished strength, and exertion intolerance. Age is no longer considered a defining characteristic, although frailty is still considered primarily a geriatric problem. Approximately two-thirds of affected individuals enter frailty in a slow, progressive way, while one-third become frail cataclysmically. Weakness is a common early sign, and exhaustion and weight loss are often late manifestations. Observing early behavioral changes before frailty develops could provide insight into its development and suggest early interventions. Since frailty is clearly associated with adverse outcomes, a healthy, active lifestyle is the cornerstone of prevention, and many researchers suggest that resistance training can reverse some muscle loss and improve functioning. When the health care team proposes any change in care, including a new medication, it should be prepared to describe how the intervention may affect cognition, memory, energy, or function.

From Vanderbilt: Fructose and obesity in rhesus monkeys

Clin Transl Sci. 2011 Aug;4(4):243-52. doi: 10.1111/j.1752-8062.2011.00298.x.
Fructose-fed rhesus monkeys: a nonhuman primate model of insulin resistance, metabolic syndrome, and type 2 diabetes.
Bremer AA, Stanhope KL, Graham JL, Cummings BP, Wang W, Saville BR, Havel PJ.
Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA Department of Molecular Biosciences, School of Veterinary Medicine and Department of Nutrition, University of California, Davis, California, USA Department of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA.

The incidence of insulin resistance has increased dramatically over the past several years, and we and others have proposed that this increase may at least in part be attributable to increased dietary fructose consumption. However, a major limitation to the study of diet-induced insulin resistance is the lack of relevant animal models. Numerous studies, mostly in rodents, have demonstrated that diets high in fructose induce insulin resistance; however, important metabolic differences exist between rodents and primates. Thus, the results of metabolic studies performed in primates are substantively more translatable to human physiology, underscoring the importance of establishing nonhuman primate models of common metabolic conditions. In this report, we demonstrate that a high-fructose diet in rhesus monkeys produces insulin resistance and many features of the metabolic syndrome, including central obesity, dyslipidemia, and inflammation within a short period of time; moreover, a subset of monkeys developed type 2 diabetes. Given the rapidity with which the metabolic changes occur, and the ability to control for many factors that cannot be controlled for in humans, fructose feeding in rhesus monkeys represents a practical and efficient model system in which to investigate the pathogenesis, prevention, and treatment of diet-induced insulin resistance and its related comorbidities. Clin Trans Sci 2011; Volume 4: 243-252.

Smoking and telephone quitlines. Hmm...there ought to be an app for that...

CA Cancer J Clin. 2011 Sep 6. doi: 10.3322/caac.20130. [Epub ahead of print]
Smoking cessation telephone quitlines effective regardless of recruitment method.
Barton MK.

Hodgkin lymphoma: balancing toxicity and cure

Nat Rev Clin Oncol. 2011 Sep 6. doi: 10.1038/nrclinonc.2011.137. [Epub ahead of print]
Chemotherapy: Advanced Hodgkin lymphoma-balancing toxicity and cure.
Lim SH, Johnson PW.
Cancer Research UK Centre, Faculty of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK.
PMID: 21894205 [PubMed - as supplied by publisher]

The combination of doxorubicin, bleomycin, vincristine and dacarbazine (ABVD) has emerged as a standard of care in advanced-stage Hodgkin lymphoma over the past four decades. Clinicians treating patients with cancer frequently walk a tightrope where the requirements of efficacy have to be balanced against the morbidity caused by the treatment.

From Oncogene: The molecular basis for platinum-based chemotherapy resistance

Oncogene. 2011 Sep 5. doi: 10.1038/onc.2011.384. [Epub ahead of print]
Molecular mechanisms of cisplatin resistance.
Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, Castedo M, Kroemer G.
1] INSERM, U848 'Apoptosis, Cancer and Immunity', Villejuif, France [2] Institut Gustave Roussy, Villejuif, France [3] Université Paris Sud-XI, Villejuif, France.

Platinum-based drugs, and in particular cis-diamminedichloroplatinum(II) (best known as cisplatin), are employed for the treatment of a wide array of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. Cisplatin exerts anticancer effects via multiple mechanisms, yet its most prominent (and best understood) mode of action involves the generation of DNA lesions followed by the activation of the DNA damage response and the induction of mitochondrial apoptosis. Despite a consistent rate of initial responses, cisplatin treatment often results in the development of chemoresistance, leading to therapeutic failure. An intense research has been conducted during the past 30 years and several mechanisms that account for the cisplatin-resistant phenotype of tumor cells have been described. Here, we provide a systematic discussion of these mechanism by classifying them in alterations (1) that involve steps preceding the binding of cisplatin to DNA (pre-target resistance), (2) that directly relate to DNA-cisplatin adducts (on-target resistance), (3) concerning the lethal signaling pathway(s) elicited by cisplatin-mediated DNA damage (post-target resistance) and (4) affecting molecular circuitries that do not present obvious links with cisplatin-elicited signals (off-target resistance). As in some clinical settings cisplatin constitutes the major therapeutic option, the development of chemosensitization strategies constitute a goal with important clinical implications.Oncogene advance online publication, 5 September 2011; doi:10.1038/onc.2011.384.

From Oxford American: College-who are you and what are you doing here?

Who Are You and What Are You Doing Here?
Published on August 22 2011
by Mark Edmundson

A message in a bottle to the incoming class.

"The students and the professors have made a deal: Neither of them has to throw himself heart and soul into what happens in the classroom. The students write their abstract, over-intellectualized essays; the professors grade the students for their capacity to be abstract and over-intellectual—and often genuinely smart. For their essays can be brilliant, in a chilly way; they can also be clipped off the Internet, and often are. Whatever the case, no one wants to invest too much in them—for life is elsewhere. The professor saves his energies for the profession, while the student saves his for friends, social life, volunteer work, making connections, and getting in position to clasp hands on the true grail, the first job.

No one in this picture is evil; no one is criminally irresponsible. It’s just that smart people are prone to look into matters to see how they might go about buttering their toast. Then they butter their toast.

As for the administrators, their relation to the students often seems based not on love but fear. Administrators fear bad publicity, scandal, and dissatisfaction on the part of their customers. More than anything else, though, they fear lawsuits. Throwing a student out of college, for this or that piece of bad behavior, is very difficult, almost impossible. The student will sue your eyes out."

From LiveScience: Dophins "talk" like human beings

Dolphins 'Talk' Like Humans, New Study Suggests
Jeanna Bryner, LiveScience Managing EditorDate: 07 September 2011 Time: 09:32 AM ET

"The dolphins aren't actually talking, though.

'It does not mean that they talk like humans, only that they communicate with sound made in the same way,' Madsen told LiveScience.

'Cetean ancestors lived on land some 40 million years ago and made sounds with vocal folds in their larynx," Madsen said, referring to the group of mammals to which dolphins belong. "They lost that during the adaptations to a fully aquatic lifestyle, but evolved sound production in the nose that functions like that of vocal folds.'

This vocal ability also likely gives dolphins a broader range of sounds."

Wednesday, September 7, 2011

From the Lancet: Cancer in NYC firefighters after 9/11

Lancet. 2011 Sep 3;378(9794):898-905.
Early assessment of cancer outcomes in New York City firefighters after the 9/11 attacks: an observational cohort study.
Zeig-Owens R, Webber MP, Hall CB, Schwartz T, Jaber N, Weakley J, Rohan TE, Cohen HW, Derman O, Aldrich TK, Kelly K, Prezant DJ.
Department of Medicine, Albert Einstein College of Medicine Montefiore Medical Center, Bronx, NY, USA.

The attacks on the World Trade Center (WTC) on Sept 11, 2001 (9/11) created the potential for occupational exposure to known and suspected carcinogens. We examined cancer incidence and its potential association with exposure in the first 7 years after 9/11 in firefighters with health information before 9/11 and minimal loss to follow-up.

We assessed 9853 men who were employed as firefighters on Jan 1, 1996. On and after 9/11, person-time for 8927 firefighters was classified as WTC-exposed; all person-time before 9/11, and person-time after 9/11 for 926 non-WTC-exposed firefighters, was classified as non-WTC exposed. Cancer cases were confirmed by matches with state tumour registries or through appropriate documentation. We estimated the ratio of incidence rates in WTC-exposed firefighters to non-exposed firefighters, adjusted for age, race and ethnic origin, and secular trends, with the US National Cancer Institute Surveillance Epidemiology and End Results (SEER) reference population. CIs were estimated with overdispersed Poisson models. Additional analyses included corrections for potential surveillance bias and modified cohort inclusion criteria.

Compared with the general male population in the USA with a similar demographic mix, the standardised incidence ratios (SIRs) of the cancer incidence in WTC-exposed firefighters was 1·10 (95% CI 0·98-1·25). When compared with non-exposed firefighters, the SIR of cancer incidence in WTC-exposed firefighters was 1·19 (95% CI 0·96-1·47) corrected for possible surveillance bias and 1·32 (1·07-1·62) without correction for surveillance bias. Secondary analyses showed similar effect sizes.

We reported a modest excess of cancer cases in the WTC-exposed cohort. We remain cautious in our interpretation of this finding because the time since 9/11 is short for cancer outcomes, and the reported excess of cancers is not limited to specific organ types. As in any observational study, we cannot rule out the possibility that effects in the exposed group might be due to unidentified confounders. Continued follow-up will be important and should include cancer screening and prevention strategies.

National Institute for Occupational Safety and Health.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Khmer Rouge terrorism: 30 years later and still healing

Torture. 2011;21(2):71-83.
Reconciliation in Cambodia: thirty years after the terror of the Khmer Rouge regime.
Bockers E, Stammel N, Knaevelsrud C.
Treatment Center for Torture Victims, and Department of Clinical Psychology and Psychotherapy, Freie Universität Berlin, Germany.

During the Khmer Rouge regime one quarter of the Cambodian population was killed as a result of malnutrition, overwork and mass killings. Although the regime ended 30 years ago, its legacy continues to affect Cambodians. Mental health problems as well as feelings of anger and revenge resulting from traumatic events experienced during the Khmer Rouge regime are still common in Cambodia. These conditions continue to impede social coexistence and the peace-building process in society. Thirty years after the Khmer Rouge regime this article gives an overview on the status of the country's current reconciliation process and recommends potential future steps.

From American Psychologist: Expulsion from Disneyland-the social psychological impact of 9/11

Am Psychol. 2011 Sep;66(6):447-54.
The expulsion from Disneyland: The social psychological impact of 9/11.
Morgan GS, Wisneski DC, Skitka LJ.
Department of Psychology.

People expressed many different reactions to the events of September 11th, 2001. Some of these reactions were clearly negative, such as political intolerance, discrimination, and hate crimes directed toward targets that some, if not many, people associated with the attackers. Other reactions were more positive. For example, people responded by donating blood, increasing contributions of time and money to charity, and flying the American flag. The goal of this article is to review some of Americans' negative and positive reactions to 9/11. We also describe two frameworks, value protection and terror management theory, that provide insights into Americans' various reactions to the tragedy of 9/11. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

From Carnegie Mellon: Communicating about terrorism risk

Am Psychol. 2011 Sep;66(6):520-31.
Communicating about the risks of terrorism (or anything else).
Fischhoff B.
Carnegie Mellon University.

Communication is essential to preventing terrorists from achieving their objectives. Effective communication can reduce terrorists' chances of mounting successful operations, creating threats that disrupt everyday life, and undermining the legitimacy of the societies that they attack. Psychological research has essential roles to play in that communication, identifying the public's information needs, designing responsive communications, and evaluating their success. Fulfilling those roles requires policies that treat two-way communication with the public as central to ensuring that a society is strengthened, rather than weakened, by its struggle with terror. There are scientific, organizational, and political barriers to achieving those goals. Psychological research can help to overcome them-and advance its science in the process. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

From the Lancet: Taking the terror out of terrorism: mortality data after 9/11

Lancet. 2011 Sep 3;378(9794):851-2.
Taking the terror out of terrorism: mortality data after 9/11.
Feeney JM, Wallack MK.

"Outside of psychiatric research, few data on the long-term sequelae of any terrorist event exist, but researchers caring for the WTC victims and responders are systematically rectifying that lack of reliable information."

IgG4-related disease: Associated malignancies

Mod Rheumatol. 2011 Sep 6. [Epub ahead of print]
Risk of malignancies in IgG4-related disease.
Yamamoto M, Takahashi H, Tabeya T, Suzuki C, Naishiro Y, Ishigami K, Yajima H, Shimizu Y, Obara M, Yamamoto H, Himi T, Imai K, Shinomura Y.
First Department of Internal Medicine, Sapporo Medical University School of Medicine, South 1-West 16, Chuo-ku, Sapporo, Hokkaido, 0608543, Japan,

IgG4-related disease (IgG4-RD) is considered a systemic, chronic, and inflammatory disorder that is characterized by the enlargement of involved organs, elevated levels of IgG4, and abundant infiltration of plasmacytes with IgG4 and fibrosis in involved organs. It is necessary to differentiate IgG4-RD from malignant tumors. Recently we have looked at case reports of IgG4-RD with malignancy that was discovered at systemic screening. In this study, we analyzed the relationship between IgG4-RD and malignancies. The study subjects were 106 patients with IgG4-RD who had been referred to our hospital since April 1997. We analyzed the clinical characteristics of IgG4-RD patients who had cancer that was observed upon the initial diagnosis of IgG4-RD or that occurred during an average follow-up period of 3.1 years. Using data from national cancer registries that monitor cancer incidence in Japan, we evaluated the standardized incidence ratio (SIR) for malignancies in IgG4-RD. Malignancies were observed in 11 of the IgG4-RD patients (10.4%). The malignancies were all different and included lung cancer, colon cancer, and lymphoma. With the exception of the age at which the IgG4-RD diagnosis was made, there were no common features in patients with cancer and those without. The SIR for these malignancies in IgG4-RD was 383.0, which was higher than that for the general population. We should be cognizant of the possible existence of malignancies in patients with IgG4-RD at the time of diagnosis and during follow-up care.

Developing a rapid sideline test for concussion

J Neurol Sci. 2011 Oct 15;309(1-2):34-9. Epub 2011 Aug 16.
The King-Devick test and sports-related concussion: Study of a rapid visual screening tool in a collegiate cohort.
Galetta KM, Brandes LE, Maki K, Dziemianowicz MS, Laudano E, Allen M, Lawler K, Sennett B, Wiebe D, Devick S, Messner LV, Galetta SL, Balcer LJ.
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Concussion, defined as an impulse blow to the head or body resulting in transient neurologic signs or symptoms, has received increasing attention in sports at all levels. The King-Devick (K-D) test is based on the time to perform rapid number naming and captures eye movements and other correlates of suboptimal brain function. In a study of boxers and mixed martial arts (MMA) fighters, the K-D test was shown to have high degrees of test-retest and inter-rater reliability and to be an accurate method for rapidly identifying boxers and mixed martial arts fighters with concussion. We performed a study of the K-D test as a rapid sideline screening tool in collegiate athletes to determine the effect of concussion on K-D scores compared to a pre-season baseline.

In this longitudinal study, athletes from the University of Pennsylvania varsity football, sprint football, and women's and men's soccer and basketball teams underwent baseline K-D testing prior to the start of the 2010-11 playing season. Post-season testing was also performed. For athletes who had concussions during the season, K-D testing was administered immediately on the sidelines and changes in score from baseline were determined.

Among 219 athletes tested at baseline, post-season K-D scores were lower (better) than the best pre-season scores (35.1 vs. 37.9s, P=0.03, Wilcoxon signed-rank test), reflecting mild learning effects in the absence of concussion. For the 10 athletes who had concussions, K-D testing on the sidelines showed significant worsening from baseline (46.9 vs. 37.0s, P=0.009), with all except one athlete demonstrating worsening from baseline (median 5.9s).

This study of collegiate athletes provides initial evidence in support of the K-D test as a strong candidate rapid sideline visual screening tool for concussion. Data show worsening of scores following concussion, and ongoing follow-up in this study with additional concussion events and different athlete populations will further examine the effectiveness of the K-D test.

From U of Muenster: Infantilized behavior in wild cavies

Dev Psychobiol. 2011 Sep;53(6):575-84. doi: 10.1002/dev.20585. Epub 2011 Jul 14.
The social environment during pregnancy and lactation shapes the behavioral and hormonal profile of male offspring in wild cavies.
Siegeler K, Sachser N, Kaiser S.
Department of Behavioural Biology, University of Muenster, Badestraße 13, D-48149 Muenster, Germany.

In mammals, the development of individual behavioral profiles can be influenced considerably by social factors during early phases of life. In guinea pigs, for instance, sons whose mothers experienced social instability during pregnancy and lactation show an infantilized behavioral profile. Here, we examined whether the same phenomenon exists also in wild cavies, the ancestor of the domestic guinea pig. Using a comparable experimental approach, our results revealed a similar behavioral infantilization as well as a delayed gonadal development of sons when their mothers had lived under unstable social conditions. These data show clearly that the behavioral and hormonal profile of male wild cavies can be shaped significantly by the social environment in which their mothers lived during pregnancy and lactation. Hence the underlying mechanisms cannot have been brought about by artificial selection during domestication. Rather, they represent maternal effects evolved through natural selection adjusting the offspring to the current environmental conditions. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 53:575-584, 2011.

Psychiatric presentation of Fragile X Syndrome

Dev Neurosci. 2011 Sep 2. [Epub ahead of print]
The Psychiatric Presentation of Fragile X: Evolution of the Diagnosis and Treatment of the Psychiatric Comorbidities of Fragile X Syndrome.
Tranfaglia MR.
FRAXA Research Foundation, Newburyport, Mass., USA.

Fragile X syndrome (FXS) is the leading inherited cause of mental retardation and autism spectrum disorders worldwide. It presents with a distinct behavioral phenotype which overlaps significantly with that of autism. Unlike autism and most common psychiatric disorders, the neurobiology of fragile X is relatively well understood. Lack of the fragile X mental retardation protein causes dysregulation of synaptically driven protein synthesis, which in turn causes global disruption of synaptic plasticity. Thus, FXS can be considered a disorder of synaptic plasticity, and a developmental disorder in the purest sense: mutation of the FMR1 (fragile X mental retardation 1) gene results in abnormal synaptic development in response to experience. Accumulation of this abnormal synaptic development, over time, leads to a characteristic and surprisingly consistent behavioral phenotype of attention deficit, hyperactivity, impulsivity, multiple anxiety symptoms, repetitive/perseverative/stereotypic behaviors, unstable affect, aggression, and self-injurious behavior. Many features of the behavioral and psychiatric phenotype of FXS follow a developmental course, waxing and waning over the life span. In most cases, symptoms present as a mixed clinical picture, not fitting established diagnostic categories. There have been many clinical trials in fragile X subjects, but no placebo-controlled trials of adequate size or methodology utilizing the most commonly prescribed psychiatric medications. However, large and well-designed trials of investigational agents which target the underlying pathology of FXS have recently been completed or are under way. While the literature offers little guidance to the clinician treating patients with FXS today, potentially disease-modifying treatments may be available in the near future.

Personal consequences of med mal lawsuits for surgeons

J Am Coll Surg. 2011 Sep 2. [Epub ahead of print]
Personal Consequences of Malpractice Lawsuits on American Surgeons.
Balch CM, Oreskovich MR, Dyrbye LN, Colaiano JM, Satele DV, Sloan JA, Shanafelt TD.
Johns Hopkins Medical Institutions, Baltimore, MD.

Our objective was to identify the prevalence of recent malpractice litigation against American surgeons and evaluate associations with personal well-being. Although malpractice lawsuits are often filed against American surgeons, the personal consequences with respect to burnout, depression, and career satisfaction are poorly understood.

Members of the American College of Surgeons were sent an anonymous, cross-sectional survey in October 2010. Surgeons were asked if they had been involved in a malpractice suit during 2 previous years. The survey also evaluated demographic variables, practice characteristics, career satisfaction, burnout, and quality of life.

Of the approximately 25,073 surgeons sampled, 7,164 (29%) returned surveys. Involvement in a recent malpractice suit was reported by 1,764 of 7,164 (24.6%) responding surgeons. Surgeons involved in a recent malpractice suit were younger, worked longer hours, had more night call, and were more likely to be in private practice (all p <0.0001). Recent malpractice suits were strongly related to burnout (p < 0.0001), depression (p < 0.0001), and recent thoughts of suicide (p < 0.0001) among surgeons. In multivariable modeling, both depression (odds ratio = 1.273; p = 0.0003) and burnout (odds ratio = 1.168; p = 0.0306) were independently associated with a recent malpractice suit after controlling for all other personal and professional characteristics. Hours worked, nights on call, subspecialty, and practice setting were also independently associated with recent malpractice suits. Surgeons who had experienced a recent malpractice suit reported less career satisfaction and were less likely to recommend a surgical or medical career to their children (p < 0.0001).

Malpractice lawsuits are common and have potentially profound personal consequences for US surgeons. Additional research is needed to identify individual, organizational, and societal interventions to support surgeons subjected to malpractice litigation.

Diabetics and bladder dysfunction

Curr Urol Rep. 2011 Sep 6. [Epub ahead of print]
Bladder Dysfunction in Patients with Diabetes.
Gomez CS, Kanagarajah P, Gousse AE.
Bladder Health and Reconstructive Urology Institute, Memorial Hospital Miramar, 1951 Southwest 172nd Avenue, Suite #408, Miramar, FL, 33029, USA.

With diabetes mellitus (DM) reaching epidemic proportions, the identification of voiding dysfunction as a common and burdensome complication of this disease is critical. Research into diabetic voiding dysfunction significantly lags behind other complications of DM, such as retinopathy and nephropathy. Recent studies have revealed that DM predisposes patients to a wide range of lower urinary tract dysfunction, from the classic diabetic cystopathy of incomplete emptying to urgency incontinence. In this review, we discuss the current concepts of diabetic voiding dysfunction with a critical analysis of the available evidence.