Wednesday, June 22, 2011

The 2nd edition of Leslie and Wick's Practical Pulmonary Pathology is now available

Pulmonary fibrosis in patients with sarcoidosis

Curr Opin Pulm Med. 2011 Jun 15. [Epub ahead of print]
Sarcoidosis and interstitial pulmonary fibrosis; two distinct disorders or two ends of the same spectrum.
Shigemitsu H, Azuma A.
aDivision of Pulmonary & Critical Care Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, USA bDivision of Respiratory Medicine, Department of Infection and Oncology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo, Japan.

Pulmonary fibrosis is a reparative response characterized by accumulation of extracellular matrix in the lung parenchyma that may be observed in end-stage sarcoidosis. This article will discuss the recent advancements in the understanding of the pathogenesis of pulmonary fibrosis in sarcoidosis in comparison with idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP).

A recent study examined clinical, radiographic, and histopathologic findings of end-stage sarcoidosis patients with lung fibrosis who underwent lung transplantation. The authors found many of the patients to have moderate-to-severe interstitial pneumonitis in some cases with UIP considered to be atypical of end-stage sarcoidosis. Furthermore, these patients had diagnosis of sarcoidosis for a shorter time prior to transplant compared with individuals without interstitial pneumonitis (mean 4.8 years vs. 23.3 years). Another study found a promoter polymorphism in prostaglandin-endoperoxide synthase 2 (PTGS2), -765G>C, to be associated with susceptibility and increased risk for pulmonary fibrosis in sarcoidosis in the white population compared with healthy controls. An altered Sp1/Sp3 binding to the -765 region has been proposed as a possible mechanism for reduced PTGS2 expression.

A subset of patients with sarcoidosis that progresses to pulmonary fibrosis may share some similar mechanistic and morphologic aberrations with IPF/UIP. Future studies are needed to examine the significance of chronic interstitial pneumonitits and UIP pattern in fibrotic sarcoidosis as a potential marker for progressive disease, and the roles of PTGS2 polymorphism in various ethnic groups and Sp1/Sp3 binding in other fibrotic lung diseases.

PMID: 21681100 [PubMed - as supplied by publisher]

Part-time surgeons

J Am Coll Surg. 2011 Jun 18. [Epub ahead of print]
The Impact of Employment of Part-Time Surgeons on the Expected Surgeon Shortage.
Satiani B, Williams TE, Ellison EC.
Department of Surgery, The Ohio State University College of Medicine, Columbus, OH.

The trend for choosing to work part-time (PT) in medicine is increasing. We hypothesize that strategies to employ PT surgeons and prolong the duration of practice might reduce the surgeon shortage considerably. We calculated the effects of PT employment on the surgical workforce.

We estimated the surgical workforce in obstetrics and gynecology, general surgery, thoracic surgery, ENT, orthopaedic surgery, urology, and neurosurgery to be 99,000 in 2005. We assumed 3,635 Board Certificates would be granted each year and surgeons will practice for 30 years, with 3,300 retiring each year. Scenarios were constructed with one-quarter (scenario 1), one-half (scenario 2), or three-quarters (scenario 3) of potential retirees working half-time for an additional 10 years.

By 2030, with other variables unchanged, the United States would have 4,125; 8,250; and 12,375 additional PT surgeons under scenario 1 (4% increase), scenario 2 (8% increase), and scenario 3 (12% increase), respectively, with a corresponding reduction in the shortage of surgeons.

An opportunity exists to reduce the shortage of surgeons by offering models for PT employment particularly to mid-career women and retiring surgeons. Employment models should address flexible work schedules, malpractice premium adjustments, academic promotion, maintenance of certification and licensure, and employment benefits.

Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

The role of palliative radiotherapy in patients with pleural diffuse malignant mesothelioma

Eur J Cancer. 2011 Jun 7. [Epub ahead of print]
Re-evaluating the role of palliative radiotherapy in malignant pleural mesothelioma.
Jenkins P, Milliner R, Salmon C.
Gloucestershire Oncology Centre, Cheltenham General Hospital, Cheltenham GL53 7AN, UK.

To determine the objective response rate of malignant pleural mesothelioma (MPM) to short course radiation therapy.

We reviewed the cases of 54 patients with advanced MPM who were treated with palliative radiotherapy according to a standardised institutional policy. Pre- and post-treatment computed tomography scans were used to assess response.

Fifty-seven percent of patients reported some improvement in their symptoms following radiotherapy. The radiology response rate was 43% (22 patients had a partial response and 1 patient a complete response). Response to treatment was correlated with the European Organisation for Research and Treatment of Cancer (EORTC) prognostic index (p=0.001), performance status (p=0.02) and histological subtype (p=0.04). In the EORTC good prognosis group 56% of patients responded, compared with only 7% in the poor prognosis group (p=0.001). The median survivals from diagnosis and from the start of radiotherapy were 11.3months and 5.2months, respectively. Survival following treatment was correlated with the EORTC prognostic index (p<0.001), histological subtype (p<0.001), performance status (p=0.001), treatment response (p=0.002) and haemoglobin level (0.02). The EORTC good and poor prognostic groups had survivals of 7.1 and 2.1months, respectively (p<0.001). Neither tumour volume nor stage were associated with prognosis.

Palliative radiotherapy produces a response rate in MPM that is equivalent to chemotherapy. The EORTC prognostic index can be used to select patients who are most likely to benefit from this treatment.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Maladjustment to blindness in Nigeria

Ann Afr Med. 2011 Apr-Jun;10(2):155-64.
Psychological and social adjustment to blindness: Understanding from two groups of blind people in Ilorin, Nigeria.
Tunde-Ayinmode MF, Akande TM, Ademola-Popoola DS.

Department of Behavioral Sciences, University of Ilorin Teaching Hospital, Ilorin, Nigeria.
Background: Blindness can cause psychosocial distress leading to maladjustment if not mitigated. Maladjustment is a secondary burden that further reduces quality of life of the blind. Adjustment is often personalized and depends on nature and quality of prevailing psychosocial support and rehabilitation opportunities. This study was aimed at identifying the pattern of psychosocial adjustment in a group of relatively secluded and under-reached totally blind people in Ilorin, thus sensitizing eye doctors to psychosocial morbidity and care in the blind. Materials and Methods: A cross-sectional descriptive study using 20-item Self-Reporting Questionnaire (SRQ) and a pro forma designed by the authors to assess the psychosocial problems and risk factors in some blind people in Ilorin metropolis. Result: The study revealed that most of the blind people were reasonably adjusted in key areas of social interaction, marriage, and family. Majority were considered to be poorly adjusted in the areas of education, vocational training, employment, and mobility. Many were also considered to be psychologically maladjusted based on the high rate of probable psychological disorder of 51%, as determined by SRQ. Factors identified as risk factors of probable psychological disorder were poor educational background and the presence of another medical disorder. Conclusion: Most of the blind had no access to formal education or rehabilitation system, which may have contributed to their maladjustment in the domains identified. Although their prevailing psychosocial situation would have been better prevented yet, real opportunity still exists to help this group of people in the area of social and physical rehabilitation, meeting medical needs, preventive psychiatry, preventive ophthalmology, and community health. This will require the joint efforts of medical community, government and nongovernment organizations to provide the framework for delivery of these services directly to the communities.

Nicotine addiction: Questioning the Surgeon General's data

Harm Reduct J. 2011 May 19;8:12.
If the data contradict the theory, throw out the data: Nicotine addiction in the 2010 report of the Surgeon General.
Frenk H, Dar R.
Department of Psychology, Tel Aviv University, Ramat Aviv 69978, Israel.

ABSTRACT: The reports of US Surgeon General on smoking are considered the authoritative statement on the scientific state of the art in this field. The previous report on nicotine addiction published in 1988 is one of the most cited references in scientific articles on smoking and often the only citation provided for specific statements of facts regarding nicotine addiction. In this commentary we review the chapter on nicotine addiction presented in the recent report of the Surgeon General. We show that the nicotine addiction model presented in this chapter, which closely resembles its 22 years old predecessor, could only be sustained by systematically ignoring all contradictory evidence. As a result, the present SG's chapter on nicotine addiction, which purportedly "documents how nicotine compares with heroin and cocaine in its hold on users and its effects on the brain," is remarkably biased and misleading.

Wrong-level spine surgery

Surg Neurol Int. 2011;2:47. Epub 2011 Apr 19.
Wrong-level surgery: A unique problem in spine surgery.
Hsiang J.

Department of Spine Center, Swedish Neuroscience Institute, 550 17 Ave., Suite 500, Seattle, WA 98122, USA.
Even though a lot of effort has gone into preventing operating at the wrong site and wrong patient, wrong-level surgery is a unique problem in spine surgery.

The current method to prevent wrong level spine surgery performed is mainly relied on intra-operative X-ray. Unfortunately, because of the unique features and anatomy of the spinal column, wrong level spine surgery still happens. There are situations that even with intraoperative X-ray, correct level still cannot be reliably identified.

Examples of patient whose surgery can easily be performed on the wrong level are illustrated. A protocol to prevent wrong-level spine surgery preformed is developed.

The consequence of wrong-level spine surgery not only generates another surgery of the intended level; it is usually also associated with lawsuit. Strictly following this protocol can prevent wrong-level spine surgery.

Binge drinking in Australia

BMC Public Health. 2011 Jun 20;11(1):482. [Epub ahead of print]
The Australian National Binge Drinking Campaign: Campaign recognition among young people at a music festival who report risky drinking.
van Gemert C, Dietze P, Gold J, Sacks-Davis R, Stoove M, Vally H, Hellard M.


The Australian Government launched a mass media campaign in 2009 to raise awareness of the harms and costs associated risky drinking among young Australians. The aim of this study was to assess if young people attending a music festival who report frequent risky single occasions of drinking (RSOD) recognise the key message of the campaign, "Binge drinking can lead to injuries and regrets", compared to young people who report less frequent RSOD.

A cross-sectional behavioural survey of young people (aged 16-29) years attending a music festival in Melbourne, Australia, was conducted in January 2009. We collected basic demographics, information on alcohol and other drug use and sexual health and behaviour during the previous 12 months, and measured recognition of the Australian National Binge Drinking Campaign key message. We calculated the odds of recognition of the key slogan of the Australian National Binge Drinking Campaign among participants who reported frequent RSOD (defined as reported weekly or more frequent RSOD during the previous 12 months) compared to participants who reported less frequent RSOD.

Overall, three-quarters (74.7%) of 1072 participants included in this analysis recognised the campaign message. In the adjusted analysis, those reporting frequent RSOD had significantly lower odds of recognising the campaign message compared to those not reporting frequent RSOD (OR 0.7, 95% CI 0.5-0.9), whilst females had significantly greater odds of recognising the campaign message compared to males (OR 1.8, 95% CI 1.4-2.1).

Whilst a high proportion of the target group recognised the campaign, our analysis suggests that participants that reported frequent RSOD - and thus the most important group to target - had statistically significantly lower odds of recognising the campaign message.

Asthma and Russian trawlers

Am J Ind Med. 2011 Jun 20. doi: 10.1002/ajim.20978. [Epub ahead of print]
An analysis of the respiratory health status among seafarers in the Russian trawler and merchant fleets.
Shiryaeva O, Aasmoe L, Straume B, Bang BE.
Institute of Community Medicine, Faculty of Health Sciences, University of Tromsoe, Tromsoe, Norway; Department of Occupational and Environmental Medicine, University Hospital North Norway, Tromsoe, Norway.

Trawler fishermen and merchant seafarers have tough working conditions. While workers in both occupations are exposed to a challenging environment, trawler fishermen are also engaged in onboard fish processing, which is considered to be additional exposure. The aim of the present study was to characterize respiratory health status in both groups of seamen.

In total 127 trawler fishermen and 118 merchant seafarers were enrolled during their regular medical health examinations. The study protocol comprised a standardized questionnaire, lung function test and measurements of fractional nitric oxide concentrations (FE(NO) ) in exhaled air.

Doctor-diagnosed asthma was reported only by trawler fishermen (3.9%, P < 0.05, Pearson Chi-square test). Adjusted odds ratios (OR) of respiratory symptoms were more often elevated in trawler fishermen compared to merchant seafarers. Trawler fishermen had reduced spirometric parameters: FEV(1) % of predicted values (adjusted β: -5.28, 95%CI: -9.28 to -1.27), FVC % of predicted values (adjusted β: -5.21, 95%CI: -9.25 to -1.17). Increased OR of the work-related cough with phlegm (OR: 6.6, 95% CI: 1.8-21.9), running nose (OR: 3.0, 95%CI: 1.2-7.7), and frequent sneezing (OR: 3.4, 95%CI: 1.0-12.7) were found among those trawler workers whose work tasks included filleting of fish. FE(NO) levels were not significantly different between trawler and merchant seamen.

The present study indicated that trawler fishermen exhibited impaired lung function and were more likely to have asthma. The environment of the onboard factories where fishermen fillet fish is suggested as a risk factor for work-related respiratory symptoms. Am. J. Ind. Med. © 2011 Wiley-Liss, Inc.

Copyright © 2011 Wiley-Liss, Inc.

From Harvard: New directions in medical liability reform

N Engl J Med. 2011 Apr 21;364(16):1564-72.
New directions in medical liability reform.
Kachalia A, Mello MM.

Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
PMID: 21506746 [PubMed - indexed for MEDLINE]

Patient autonomy

Chest. 2011 Jun;139(6):1491-7.
A Brief Historical and Theoretical Perspective on Patient Autonomy and Medical Decision Making: Part II: The Autonomy Model.
Will JF.

JD, Bioethics and Health Law Center, Mississippi College School of Law, 151 East Griffith St, Jackson, MS 39201.
As part of a larger series addressing the intersection of law and medicine, this essay is the second of two introductory pieces. Beginning with the Hippocratic tradition and lasting for the next 2,400 years, the physician-patient relationship remained relatively unchanged under the beneficence model, a paternalistic framework characterized by the authoritative physician being afforded maximum discretion by the trusting, obedient patient. Over the last 100 years or so, in response to certain changes taking place in both research and clinical practice, the bioethics movement ushered in the autonomy model, and with it, a profoundly different way of approaching decision making in medicine. The shift from the beneficence model to the autonomy model is governed legally by the informed consent doctrine, which emphasizes disclosure to patients of information sufficient to permit them to make intelligent choices regarding treatment alternatives. As this legal doctrine became established, philosophers identified an inherent value in respecting patients as autonomous agents, even where patient choice seems to conflict with the physician's duty to act in the patient's best interests. Whereas the beneficence model presumed that the physician knew what was in the patient's best interests, the autonomy model starts from the premise that the patient knows what treatment decision is in line with his or her true sense of well-being, even where that decision is the refusal of treatment and the result is the patient's death.

From Norway: Physicians' professional subculture and health care reform

Soc Sci Med. 2011 May 23. [Epub ahead of print]
Resisting market-inspired reform in healthcare: The role of professional subcultures in medicine.
Martinussen PE, Magnussen J.

SINTEF Technology and Society, Department of Health Research, Trondheim, Norway.
The reorganisation efforts of the hospital sector in many Western countries in recent decades have challenged the role, identity and autonomy of medical professionals. This has led to increased focus on the role and impact of physicians who are also managers and on the unique discourse being formed through the integration of medical and managerial knowledge. Following the line of studies addressing the professional subcultures in medicine, we investigated whether assessments of health reform differ between medical doctors with managerial responsibilities and their colleagues at the clinical level as well as between those involved in direct patient care and those who are not. The analysis was performed within the context of the Norwegian hospital sector, where a major reform was implemented in 2002, and it was based on a survey of a representative sample of hospital physicians in 2006. The analysis focused on how the respondents viewed the overall effect of the reform and on the reform's effect on three central health policy goals: equity, quality and productivity. Combining data from the survey with organisational and financial data from the hospitals, we employed multilevel techniques to control for a number of individual and hospital-specific factors that could explain the physicians' views. As expected, respondents with managerial responsibilities were more positive in their evaluations of the reform, whereas respondents who spent time on direct patient-related work showed the opposite pattern. Of the hospital-specific factors of interest, the share of department managers with medical backgrounds and the economic situation positively affected the evaluations. Our findings support the view that, rather than managerialist values colonising the medical profession through a process of hybridisation, there is heterogeneity within the profession: some physician managers are adopting management values and tools, whereas others remain alienated from them.

Lung cancer in survivors of Hodgkin disease

Cancer. 2011 Jun 20. doi: 10.1002/cncr.26257. [Epub ahead of print]
Survival after second primary lung cancer: A population-based study of 187 hodgkin lymphoma patients.
Milano MT, Li H, Constine LS, Travis LB.

Department of Radiation Oncology and Rubin Center for Cancer Survivorship, University of Rochester School of Medicine, Rochester, New York.
Lung cancer accounts for the largest absolute risk of second malignancies among Hodgkin lymphoma (HL) survivors. However, no population-based studies have compared overall survival (OS) between HL survivors who developed nonsmall cell lung cancer (HL-NSCLC) versus patients with first primary NSCLC (NSCLC-1).

The authors compared the OS of 178,431 patients who had NSCLC-1 and 187 patients who had HL-NSCLC (among 22,648 HL survivors), accounting for sex, race, sociodemographic status, calendar year, and age at NSCLC diagnosis, and NSCLC histology and stage. All patients were reported to the population-based Surveillance, Epidemiology, and End Results Program. Hazard ratios (HRs) were derived from a Cox proportional hazards model.

Although the NSCLC stage distribution was similar in both groups (20% localized, 30% regional, and 50% distant), HL survivors experienced significantly inferior stage-specific OS. For patients with localized, regional, and distant stage NSCLC, the HRs (95% confidence interval [CI]) for death among HL survivors were 1.60 (95% CI, 1.08-2.37; P < .0001), 1.67 (95% CI, 1.26-2.22; P = .0004), and 1.31 (95% CI, 1.06-1.61; P = .013), respectively. Among HL-NSCLC patients, significant associations were observed between more advanced NSCLC stage and the following variables: younger age at HL diagnosis (P = .003), younger age at NSCLC diagnosis (P = .048), and longer latency between HL and NSCLC diagnoses (P = .015).

Compared with patients who had de novo NSCLC, HL survivors experienced a significant 30% to 60% decrease in OS after an NSCLC diagnosis. Further research is needed to not only elucidate the clinical-biologic underpinnings of NSCLC after HL, including the influence of previous HL treatment, but also to define the role of lung cancer screening in selected patients. Cancer 2011;. © 2011 American Cancer Society.

Monday, June 20, 2011

From Yale: DSM and the criminal justice system

J Am Acad Psychiatry Law. 2011;39(2):245-9.
Sexual Disorders: New and Expanded Proposals for the DSM-5--Do We Need Them?
Zonana H.

Yale Department of Psychiatry, Connecticut Mental Health, Center, 34 Park Street, New Haven, CT 06519.

The sexual disorders in the current and proposed DSM contain a potpourri of categories that increasingly intersect with the criminal justice system. Caveats saying the DSM is designed for clinical and not legal purposes notwithstanding, our classification system has difficulty distinguishing what we consider criminal behavior from culturally unacceptable behavior and mental disorder. Several current proposals continue this trend and seem more responsive to criminal justice concerns than mental illness considerations. They also lack sufficient specificity to warrant being called a disorder.

More on direct to consumer advertising from Bryan Liang and colleague

Nat Biotechnol. 2011 May;29(5):397-400.
Reforming direct-to-consumer advertising.
Liang BA, Mackey T.

1] Department of Anesthesiology, San Diego Center for Patient Safety, University of California, San Diego School of Medicine, San Diego, California, USA. [2] Institute of Health Law Studies, California Western School of Law, San Diego, California, USA.
PMID: 21552236 [PubMed - in process]

From NCI: Over-recommendation of mammography in the terminally ill

Cancer. 2011 Jun 16. doi: 10.1002/cncr.26233. [Epub ahead of print]
Physician over-recommendation of mammography for terminally ill women.
Leach CR, Klabunde CN, Alfano CM, Smith JL, Rowland JH.

Office of Cancer Survivorship, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda Maryland; Behavioral Research Center, American Cancer Society, Atlanta, Georgia.
There has been recent, sometimes intense, debate about when to begin screening and how often to screen women for breast cancer with mammography. However, there should be no controversy regarding screening women who are unlikely to benefit from the procedure, such as those with a serious, life-limiting illness who would not live long enough to benefit from the potential detection and treatment of breast cancer. Identifying characteristics of physicians who recommend mammography for terminally ill women can help guide efforts to minimize patient risks and make better use of health care resources.

The authors used data from a nationally representative survey of primary care physicians (PCPs) (N = 1196; response rate, 67.5%) conducted in 2006 and 2007 to examine PCPs' breast cancer screening recommendations for hypothetical patients ages 50 years, 65 years, and 80 years who were healthy, had a moderate comorbidity, or had a terminal comorbidity.

Many PCPs (47.7%) reported that they would recommend mammography to a woman aged 50 years, 65 years, or 80 years with terminal lung cancer, indicating over-recommendation. Physician characteristics associated with over-recommending mammography included obstetrician/gynecologist (odds ratio [OR], 1.69) or internal medicine (OR, 0.45) specialty, being a woman (OR, 1.40), being a racial/ethnic minority (OR, 1.72), and working in a smaller practice (OR, 1.41).

The current results indicated that physician over-recommendation of screening mammography among terminally ill women is common. Certain physician and practice characteristics, including specialty, were associated with over-recommending mammography. The authors concluded that an informed and shared mammography decision-making process for terminally ill women may eliminate unnecessary patient risks and health care expenditures. Cancer 2011;. © 2011 American Cancer Society.

Copyright © 2011 American Cancer Society.

Colon cancer after a negative colonoscopy

Dig Dis Sci. 2011 Jun 17. [Epub ahead of print]
Predictors of Colorectal Cancer Following a Negative Colonoscopy in the Medicare Population.
Singh A, Kuo YF, Riall TS, Raju GS, Goodwin JS.

Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch (UTMB), 301 University Blvd., Galveston, TX, 77555-0764, USA,

The incidence of colorectal cancer following a normal colonoscopy in the Medicare population is not known.

A 5% national sample of Medicare enrollees from 1996 to 2005 was used to identify patients undergoing complete colonoscopy. A colonoscopy not associated with any procedure (e.g., biopsy, polypectomy or fulguration) was defined as a negative colonoscopy. Patients with history of inflammatory bowel disease, colorectal cancer or death within 12 months of colonoscopy were excluded. A multivariable model was constructed to evaluate the factors associated with a new diagnosis of colorectal cancer in the period from 12 to 120 months following the negative colonoscopy.

Among 200,857 patients (mean age 74 years, 61% female, 92% White) with a negative colonoscopy, the incidence of colorectal cancer was 1.8 per 1,000 person-years. The incidence rate for matched follow-up periods decreased from 2.0/1,000 person-years for patients undergoing colonoscopy during 1996-2000 to 1.2/1,000 person years during 2001-2005. Multivariate analysis revealed a significant regional variation in the incidence of colorectal cancer following a negative colonoscopy. The incidence was higher in patients >85 years, males and patients who underwent a negative colonoscopy by a non-gastroenterologist or endoscopist in the lowest volume quartile. On stratified analyses, endoscopist volume was a significant predictor for non-gastroenterologists only.

The specialty and experience of the endoscopist are significant predictors of the incidence rate of colorectal cancer in Medicare patients with a negative colonoscopy.

Increased mortality risk in obese-but not overweight-people

Eur J Epidemiol. 2011 Jun 17. [Epub ahead of print]
Obesity but not overweight is associated with increased mortality risk.

Faeh D, Braun J, Tarnutzer S, Bopp M.
Institute of Social and Preventive Medicine (ISPM), University of Zurich, Hirschengraben 84, 8001, Zurich, Switzerland,

The association between body mass index (BMI) and survival has been described in various populations. However, the results remain controversial and information from low-prevalence Western countries is sparse. Our aim was to examine this association and its public health impact in Switzerland, a country with internationally low mortality rate and obesity prevalence. We included 9,853 men and women aged 25-74 years who participated in the Swiss MONICA (MONItoring of trends and determinants in CArdiovscular disease) study (1983-1992) and could be followed up for survival until 2008 by using anonymous record linkage. Cox regression models were used to calculate mortality hazard ratios (HRs) and to estimate excess deaths. Independent variables were age, sex, survey wave, diet, physical activity, smoking, educational class. After adjustment for age and sex the association between BMI and all-cause mortality was J shaped (non-smokers) or U shaped (smokers). Compared to BMI 18.5-24.9, among those with BMI ≥ 30 (obesity) HR for all-cause mortality was 1.41 (95% confidence interval: 1.23-1.62), for cardiovascular disease (CVD) 2.05 (1.60-2.62), for cancer 1.29 (1.04-1.60). Further adjustment attenuated the obesity-mortality relationship but the associations remained statistically significant. No significant increase was found for overweight (BMI 25-29.9). Between 4 and 6.5% of all deaths, 8.8-13.7% of CVD deaths and 2.4-3.9% of cancer deaths could be attributed to obesity. Obesity, but not overweight was associated with excess mortality, mainly because of an increased risk of death from CVD and cancer. Public health interventions should focus on preventing normal- and overweight persons from becoming obese.

Disease exacerbation in adults with Cystic Fibrosis

Thorax. 2011 Jun 15. [Epub ahead of print]
Exacerbation frequency and clinical outcomes in adult patients with cystic fibrosis.
de Boer K, Vandemheen KL, Tullis E, Doucette S, Fergusson D, Freitag A, Paterson N, Jackson M, Lougheed MD, Kumar V, Aaron SD.
The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Background Despite advances in treatment of cystic fibrosis (CF), pulmonary exacerbations remain common. The aim of this study was to determine if frequent pulmonary exacerbations are associated with greater declines in lung function, or an accelerated time to death or lung transplantation in adults with CF. Methods A 3-year prospective cohort study was conducted on 446 adult patients with CF from Ontario, Canada who could spontaneously produce sputum. Patients enrolled from 2005 to 2008 and were stratified into groups based upon their exacerbation rates over the 3 year study: <1 exacerbation/year (n=140), 1-2 exacerbations/year (n=160) and >2 exacerbations/year (n=146). Exacerbations were defined as acute/subacute worsening of respiratory symptoms severe enough to warrant oral or intravenous antibiotics. Patient-related factors associated with frequent exacerbations were determined, and clinical outcomes were compared among the three exacerbation groups. Results Patients with frequent exacerbations were more likely to be female, diabetic and have poorer baseline lung function. Patients with >2 exacerbations/year had an increased risk of experiencing a 5% decline from baseline forced expiratory volume in 1 s (FEV(1)); unadjusted HR 1.47 (95% CI 1.07 to 2.01, p=0.02), adjusted HR 1.55 (95% CI 1.10 to 2.18, p=0.01) compared with patients with <1 exacerbation/year. Patients with >2 exacerbations/year also had an increased risk of lung transplant or death over the 3 year study; unadjusted HR 12.74 (95% CI 3.92 to 41.36, p<0.0001), adjusted HR 4.05 (95% CI 1.15 to 14.28, p=0.03). Conclusions Patients with CF with frequent exacerbations appear to experience an accelerated decline in lung function, and they have an increased 3 year risk of death or lung transplant.

From NEJM: Health care reform and the Netherlands

N Engl J Med. 2011 Jun 15. [Epub ahead of print]
Managed Competition for Medicare? Sobering Lessons from the Netherlands.
Okma KG, Marmor TR, Oberlander J.
From New York University, New York (K.G.H.O.); Yale University, New Haven, CT (T.R.M.); and the University of North Carolina, Chapel Hill (J.O.).
Discussions about U.S. health care reform are often parochial, with scant attention paid to other countries' experiences. It is thus surprising that in the ongoing debate over Medicare, some U.S. commentators have turned to the Netherlands as a model of regulated competition among private insurance companies.(1) The Dutch experience is particularly relevant given the proposal by Congressman Paul Ryan (R-WI) to eliminate traditional Medicare and instead provide beneficiaries with vouchers to purchase private insurance. (The Republican majority in the House passed the Ryan plan as part of the 2012 budget resolution, but it was defeated in the Senate.) It is . . .

Take a lap! The health coach is back.

Hosp Top. 2011 Apr-Jun;89(2):37-42.
Introducing the health coach at a primary care practice: a pilot study (part 2).
Lanese BS, Dey A, Srivastava P, Figler R.
College of Business Administration, University of Akron, Akron, Ohio.
It is well known that the cost of healthcare in the United States is a poor value proposition. One of the primary goals of the healthcare reform act is to reduce cost while improving healthcare quality. The authors believe that adding a health coach helps to achieve this goal. In part I, the authors discuss the role of a health coach in the healthcare field. They present the findings from a pilot study at a primary care practice managing diabetes of patients using a health coach. The findings from the study suggest that adding a health coach helps in cost savings as well as improved health for the patients.

Medical liability reform in Mississippi

Obstet Gynecol. 2011 Jun 10. [Epub ahead of print]
Medical Liability Reform: A Case Study of Mississippi.
Behrens MA.
From Shook, Hardy & Bacon, L.L.P., Washington, DC.
Mississippi enacted medical negligence and other tort reform legislation that generally became effective for causes of action filed on or after January 1, 2003, and September 1, 2004. Data regarding lawsuits against physicians insured by the Medical Assurance Company of Mississippi (MACM), the largest medical liability insurer in the state, and MACM-insured Obstetrician-gynecologists (ob-gyns) in particular, were compared by year from 1986 to 2010. The data encompassed the periods before and after the implementation of Mississippi's tort reform legislation. In addition, MACM medical liability premiums were compared by year from 2000 to 2010. Mississippi's tort reform laws were associated with a steep drop in lawsuits against MACM-insured physicians, particularly MACM-insured ob-gyns, as well as medical liability premium reductions and refunds.

Cancer-associated cachexia

Science. 2011 Jun 16. [Epub ahead of print]
Adipose Triglyceride Lipase Contributes to Cancer-Associated Cachexia.
Das SK, Eder S, Schauer S, Diwoky C, Temmel H, Guertl B, Gorkiewicz G, Tamilarasan KP, Kumari P, Trauner M, Zimmermann R, Vesely P, Haemmerle G, Zechner R, Hoefler G.
Institute of Pathology, Medical University of Graz, Austria.
Cachexia is a multifactorial wasting syndrome most common in patients with cancer that is characterized by the uncontrolled loss of adipose and muscle mass. Here, we show that the inhibition of lipolysis through genetic ablation of adipose triglyceride lipase (Atgl) or hormone-sensitive lipase (Hsl) ameliorates certain features of cancer-associated cachexia (CAC). In wildtype C57BL/6 mice, the injection of Lewis lung carcinoma or B16 melanoma cells causes tumor growth, loss of white adipose tissue (WAT), and a marked reduction of gastrocnemius muscle. In contrast, Atgl-deficient mice with tumors resisted the increased WAT lipolysis, myocyte apoptosis, and proteasomal muscle degradation, and maintained normal adipose and gastrocnemius muscle mass. Hsl-deficient mice with tumors were also protected although to a lesser degree. Thus, functional lipolysis is essential in the pathogenesis of CAC. Pharmacological inhibition of metabolic lipases may help prevent cachexia.

Tuesday, June 14, 2011

Molecular mechanisms involved in sepsis

Contrib Microbiol. 2011;17:48-85. Epub 2011 Jun 9.
Molecular mechanisms of sepsis.
Russell JA, Boyd J, Nakada T, Thair S, Walley KR.
Heart and Lung Institute, St. Paul's Hospital, Vancouver, BC, Canada.
In cancer, therapies are targeted at 6 important pathways. In sepsis, there is ongoing controversy regarding the number and relative roles of pathways that are activated or repressed and which are important in the progression from health to death. Adding to complexity, there is interaction of pathways, there are differences in temporal pattern of up and down-regulation of pathways and there are different responses of pathways to therapies of sepsis. In this review, we define four key pathways of sepsis: (1) inflammation and immunity, (2) coagulation and fibrinolysis, (3) apoptosis, and (4) endocrine. Each of these pathways can impair endothelial function, a unifying aspect of the pathophysiology of sepsis. There are few studies of interactions of pathways except for the interacttion of inflammation/immunity with coagulation/fibrinolysis. Successful treatment of cancer requires that cancer therapies interrupt several key pathways of cancer. Accordingly, we suggest that successful treatment of sepsis will require therapies that interrupt several key pathways of sepsis. Perhaps the paucity of approved therapies for sepsis is related in part to the underevaluation of novel pathways, to lack of understanding of interactions of pathways and to lack of interruption of key pathways of sepsis.

Reducing the risk of lung cancer overdiagnosis

J Cell Physiol. 2011 Sep;226(9):2213-4. doi: 10.1002/jcp.22558.
Reducing the risk of overdiagnosis in lung cancer: A support from molecular biology.
Barba M, Felsani A, Rinaldi M, Giunta S, Malorni W, Paggi MG.
Epidemiology, National Cancer Institute "Regina Elena", Rome, Italy.
Early detection and swift treatment, when achievable, may significantly affect prognosis in lung cancer patients. Therefore, individuals with a high risk for lung cancer are invited to participate into international screening programs, such as the International Early Lung Cancer Action Program (I-ELCAP). An undesirable consequence of such massive enterprises is the detection of pulmonary nodules also in subjects who are unlikely to ultimately die from lung cancer. Nevertheless, the individuals with pulmonary nodule undergo stringent diagnostic procedures to assess the nature of the lesion. This implies a noticeable (physical and emotional) stress for our patients and the likelihood of overdiagnosis and, potentially, consequent overtreatment. Molecular markers, more specifically, microRNAs, might significantly add value to the workup process aiming at the distinction between benign and malignant lesions and, among the malignant ones, those concretely threatening for the patients' survival. We are confident that such a multidisciplinary approach would better suit our patients' diagnostic and/or therapeutic, actual needs. J. Cell. Physiol. 226: 2213-2214, 2011. © 2010 Wiley-Liss, Inc.

Physician trainees' attitudes toward physicians striking

Acad Med. 2011 May;86(5):580-585.
Developing Personal Values: Trainees' Attitudes Toward Strikes by Health Care Providers.
Li ST, Srinivasan M, Der-Martirosian C, Kravitz RL, Wilkes MS.
Dr. Li is assistant professor, vice chair of education, and pediatric program director, Department of Pediatrics, University of California, Davis, School of Medicine, Sacramento, California. Dr. Srinivasan is associate professor, Department of Internal Medicine, University of California, Davis, School of Medicine, Sacramento, California. Dr. Der-Martirosian is senior statistician, University of California, Davis, School of Medicine, Sacramento, California. Dr. Kravitz is professor and co-vice chair, Department of Internal Medicine, University of California, Davis, School of Medicine, Sacramento, California. Dr. Wilkes is professor, Office of the Dean and Department of Internal Medicine, University of California, Davis, School of Medicine, Sacramento, California.

Worldwide, health care providers use strikes and job actions to influence policy. For health care providers, especially physicians, strikes create an ethical tension between an obligation to care for current patients (e.g., to provide care and avoid abandonment) and an obligation to better care for future patients by seeking system improvements (e.g., improvements in safety, to access, and in the composition and strength of the health care workforce). This tension is further intensified when the potential benefit of a strike involves professional self-interest and the potential risk involves patient harm or death. By definition, trainees are still forming their professional identities and values, including their opinions on fair wages, health policy, employee benefits, professionalism, and strikes. In this article, the authors explore these ethical tensions, beginning with a discussion of reactions to a potential 2005 nursing strike at the University of California, Davis, Medical Center. The authors then propose a conceptual model describing factors that may influence health care providers' decisions to strike (including personal ethics, personal agency, and strike-related context). In particular, the authors explore the relationship between training level and attitudes toward taking a job action, such as going on strike. Because trainees' attitudes toward strikes continue to evolve during training, the authors maintain that open discussion around the ethics of health care professionals' strikes and other methods of conflict resolution should be included in medical education to enhance professionalism and systems-based practice training. The authors include sample case vignettes to help initiate these important discussions.

Friday, June 10, 2011

Medicaid final rule on health care-acquired infections

Fed Regist. 2011 Jun 6;76(108):32816-38.
Medicaid program; payment adjustment for provider-preventable conditions including health care-acquired conditions. Final rule.
Centers for Medicare and Medicaid Services (CMS), HHS.
This final rule will implement section 2702 of the Patient Protection and Affordable Care Act which directs the Secretary of Health and Human Services to issue Medicaid regulations effective as of July 1, 2011 prohibiting Federal payments to States under section 1903 of the Social Security Act for any amounts expended for providing medical assistance for health care-acquired conditions specified in the regulation. It will also authorize States to identify other provider-preventable conditions for which Medicaid payment will be prohibited.

Doctors on Strike! America's future?

Acad Med. 2011 May;86(5):548-51.
Commentary: professionalism, unionization, and physicians' strikes.
Cruess RL, Cruess SR.
Dr. R. Cruess is professor of surgery and member, Centre for Medical Education, McGill University, Montreal, Quebec, Canada. Dr. S. Cruess is professor of medicine and member, Centre for Medical Education, McGill University, Montreal, Quebec, Canada.
Professionalism is the basis of medicine's social contract with society. The details of that contract are influenced by the presence or absence of a national health plan. In countries with such a plan, unlike in the United States, negotiations are dictated by the nature of medicine's contract with society and take place between the medical profession and society directly. This system has required that medicine be represented at the negotiating table, and, in most instances, it has resulted in the unionization of physicians. To influence these negotiations, the medical profession has used various forms of collective action, including strikes. As the United States continues on the path toward health care reform, it seems likely that the American medical profession will also require an organization to represent it at the negotiating table and will be under the same pressures to strike as are physicians in other countries. Because both unionization and strikes pose potential threats to the professionalism of students, residents and practicing physicians, such issues should be a part of the medical education curriculum at both the undergraduate and postgraduate levels. The authors briefly review the literature on strikes and job actions and share personal experiences to support this discussion. Students and residents should have an opportunity to consider these issues in a safe environment, both to understand the potential impact of a strike on patients and the profession and to determine their own personal course of action should such a situation arise.

Health care reform in Massachusetts: increased short term disability durations

J Occup Environ Med. 2011 Jun;53(6):605-9.
The impact of health care reform on employer costs: an analysis of the massachusetts experience.
Poplaski JJ, Poe JA, Menn ER.
From the Liberty Mutual Group, Boston, Massachusetts.
: The objective of this study was to learn if health care reform in Massachusetts lead to significant increases in diagnosis-specific short-term disability (STD) durations associated with specialist physician populations in short supply.

: We examined group STD claim durations for Massachusetts-resident claimants, from Liberty Mutual's book of business, whose conditions generally required consultation or treatment by specialist physicians.

: Two specialties in short supply in Massachusetts, neurology and oncology, showed a significant increase in duration during 2008 and 2009.

: Short-term disability durations for certain diagnoses associated with specialists in short supply have increased since the introduction of health care reform in Massachusetts. These increased durations will directly affect employer costs because short-term disability payments are generally borne by employers.

Lung cancer and personalized medicine

Cancer. 2011 Jun 15;117(12):2583-5. doi: 10.1002/cncr.26258.
Lung cancer a hot topic at AACR meeting: Studies offer promise in detection, prevention, and personalized medicine.
Printz C.

CT screening for lung cancer: How effective is it in reducing mortality?

Cancer. 2011 Jun 15;117(12):2703-8. doi: 10.1002/cncr.25847. Epub 2011 Jan 10.
Modeling the mortality reduction due to computed tomography screening for lung cancer.
Foy M, Yip R, Chen X, Kimmel M, Gorlova OY, Henschke CI.
Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas.
The efficacy of computed tomography (CT) screening for lung cancer remains controversial because results from the National Lung Screening Trial are not yet available. In this study, the authors used data from a single-arm CT screening trial to estimate the mortality reduction using a modeling-based approach to construct a control comparison arm.

To estimate the potential lung cancer mortality reduction because of CT screening, a previously developed and validated model was applied to the screening trial to predict the number of lung cancer deaths in the absence of screening. By using age, gender, and smoking characteristics matching those of the trial participants, the model was used to simulate 5000 trials in the absence of CT screening to produce the expected number of lung cancer deaths along with 95% confidence intervals (95% CIs), while adjusting for healthy volunteer bias.

There were 64 observed lung cancer deaths in the screening cohort (n = 7995), whereas the model predicted 117.7 deaths (95% CI, 98 deaths-139 deaths), indicating a mortality reduction of 45.6% (P < .001). When a more conservative healthy volunteer adjustment was applied, 111.3 lung cancer deaths were predicted (95% CI, 91 deaths-132 deaths), for a lung cancer-specific mortality reduction of 42.5% (P < .001).

The results of the current study indicate that CT screening along with early stage treatment can reduce lung cancer-specific mortality. This mortality reduction is greatly influenced by the protocol of nodule follow-up and treatment, and the length of follow-up. Cancer 2011. © 2011 American Cancer Society.

Wednesday, June 1, 2011

From Stanford Law: Options for medical malpractice reform

J Econ Perspect. 2011 Spring;25(2):93-110.
Evaluating the medical malpractice system and options for reform.
Kessler DP.
Stanford Law School, Graduate School of Business, and Hoover Institution, Stanford University, Stanford, California, and National Bureau of Economic Research, Cambridge, Massachusetts, USA.
The U.S. medical malpractice liability system has two principal objectives: to compensate patients who are injured through the negligence of healthcare providers and to deter providers from practicing negligently. In practice, however, the system is slow and costly to administer. It both fails to compensate patients who have suffered from bad medical care and compensates those who haven't. According to opinion surveys of physicians, the system creates incentives to undertake cost-ineffective treatments based on fear of legal liability--to practice "defensive medicine." The failures of the liability system and the high cost of health care in the United States have led to an important debate over tort policy. How well does malpractice law achieve its intended goals? How large of a problem is defensive medicine and can reforms to malpractice law reduce its impact on healthcare spending? The flaws of the existing system have led a number of states to change their laws in a way that would reduce malpractice liability--to adopt "tort reforms." Evidence from several studies suggests that wisely chosen reforms have the potential to reduce healthcare spending significantly with no adverse impact on patient health outcomes.

From Bill Travis and colleagues: Immunostain algorithm to differentiate lung adenocarcinoma and squamous cell carcinoma

Mod Pathol. 2011 May 27. [Epub ahead of print]
Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens.
Rekhtman N, Ang DC, Sima CS, Travis WD, Moreira AL.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Immunohistochemistry is increasingly utilized to differentiate lung adenocarcinoma and squamous cell carcinoma. However, detailed analysis of coexpression profiles of commonly used markers in large series of whole-tissue sections is lacking. Furthermore, the optimal diagnostic algorithm, particularly the minimal-marker combination, is not firmly established. We therefore studied whole-tissue sections of resected adenocarcinoma and squamous cell carcinoma (n=315) with markers commonly used to identify adenocarcinoma (TTF-1) and squamous cell carcinoma (p63, CK5/6, 34βE12), and prospectively validated the devised algorithm in morphologically unclassifiable small biopsy/cytology specimens (n=38). Analysis of whole-tissue sections showed that squamous cell carcinoma had a highly consistent immunoprofile (TTF-1-negative and p63/CK5/6/34βE12-diffuse) with only rare variation. In contrast, adenocarcinoma showed significant immunoheterogenetity for all 'squamous markers' (p63 (32%), CK5/6 (18%), 34βE12 (82%)) and TTF-1 (89%). As a single marker, only diffuse TTF-1 was specific for adenocarcinoma whereas none of the 'squamous markers,' even if diffuse, were entirely specific for squamous cell carcinoma. In contrast, coexpression profiles of TTF-1/p63 had only minimal overlap between adenocarcinoma and squamous cell carcinoma, and there was no overlap if CK5/6 was added as a third marker. An algorithm was devised in which TTF-1/p63 were used as the first-line panel, and CK5/6 was added for rare indeterminate cases. Prospective validation of this algorithm in small specimens showed 100% accuracy of adenocarcinoma vs squamous cell carcinoma prediction as determined by subsequent resection. In conclusion, although reactivity for 'squamous markers' is common in lung adenocarcinoma, a two-marker panel of TTF-1/p63 is sufficient for subtyping of the majority of tumors as adenocarcinomas vs squamous cell carcinoma, and addition of CK5/6 is needed in only a small subset of cases. This simple algorithm achieves excellent accuracy in small specimens while conserving the tissue for potential predictive marker testing, which is now an essential consideration in advanced lung cancer specimens.Modern Pathology advance online publication, 27 May 2011; doi:10.1038/modpathol.2011.92.

Urokinase plasminogen activator regulates pulmonary arterial contractility and vascular permeability in mice

Am J Respir Cell Mol Biol. 2011 May 26. [Epub ahead of print]
Urokinase Plasminogen Activator Regulates Pulmonary Arterial Contractility and Vascular Permeability in Mice.
Nassar T, Yarovoi S, Abu Fanne R, Waked O, Allen TC, Idell S, Cines DB, Higazi AA.
Clinical Biochemistry, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Urokinase plasminogen activator (uPA) is elevated in pathological settings such as acute lung injury where pulmonary arterial contractility and permeability are disrupted. uPA limits fibrin accretion post-injury. Here we asked whether uPA also regulates pulmonary arterial contractility and permeability. Contractility was measured using isolated pulmonary arterial rings. Pulmonary blood flow was measured in vivo by Doppler and pulmonary vascular permeability by extravasation of Evans Blue. Our data show that uPA regulates both in vitro pulmonary arterial contractility induced by phenylephrine in a dose-dependent manner through two receptor-dependent pathways and regulates vascular contractility and permeability in vivo. Physiological concentrations of uPA (≤1 nM) stimulate contractility of pulmonary arterial rings induced by phenylephrine through the LDL receptor related protein receptor (LRP). The procontractile effect of uPA is independent of its catalytic activity. At pathophysiological concentrations, uPA (20 nM) inhibits contractility and increases vascular permeability. Inhibition of vascular contractility and increase of vascular permeability is mediated through a two-step process that involves docking to N-methyl-D-aspartate (NMDA) receptor-1 (NMDA-R1) on pulmonary vascular smooth muscle cells and requires catalytic activity. Peptides that specifically inhibit uPA docking to NMDA-R or a uPA variant with a mutated receptor docking site abolished both its effects on vascular contractility and permeability without affecting its catalytic activity. These data show that uPA, at concentrations found in pathological conditions, reduces pulmonary arterial contractility and increases permeability though activation of NMDA-R1. Selective inhibition of NMDAR-1 activation by uPA can be accomplished without loss of fibrinolytic activity.