Monday, October 31, 2011

Archives of Pathology and Laboratory Medicine--Special Section on Quality

Arch Pathol Lab Med. 2011 Nov;135(11):1384-6.
Quality: walk the walk.
Allen TC.

The College of American Pathologists (CAP) is dedicated to pathology and laboratory medicine quality. The CAP's Laboratory Accreditation Program, Proficiency Testing Program, Q-Probes and Q-Tracks, site-specific cancer checklists, webinars, annual meetings, and Advanced Practical Pathology series are all focused on providing superior patient quality. The CAP is synonymous with quality in pathology and laboratory medicine. As pathology practice becomes more sophisticated, the CAP's many programs will increasingly help pathologists provide appropriate, personalized care.

Arch Pathol Lab Med. 2011 Nov;135(11):1387-90.
Quality improvement in cytology: where do we go from here?
Renshaw AA.

Context.-Cytology is a success because of the many quality controls used to ensure the accuracy of its results. Nevertheless, additional information is becoming available to the cytologist, often from untraditional sources, and the best way to use that information to improve the quality of cytology is not yet known. Objective.-To review ways to use new information to improve the quality of cytology. Data Sources.-Review of relevant literature. Results.-Information contained in many sources can be used in new ways to improve the quality of cytology. These include the timing of cytologic and histologic correlation, electronic medical records, workload information, prior aspirations, and molecular tests. Conclusions.-To maintain their high standard of excellence, cytologists should seek to define the most appropriate way to incorporate this new information into their interpretation of individual cases.

Arch Pathol Lab Med. 2011 Nov;135(11):1391-3.
Unexpected expectations in critical values in anatomic pathology: improving agreement between pathologists and nonpathologists with the treatable immediately, life-threatening terminology.
Renshaw SA, Gould EW, Renshaw AA.

Context.-The degree to which critical values in anatomic pathology are understood in the nonpathology community is not know. Objective.-To measure the degree of agreement between pathologists and nonpathologists regarding critical values in anatomic pathology. Design.-A survey containing 15 anatomic pathologic diagnoses was given to a group of pathologists and nonpathologists who were then asked to state whether they should be regarded as critical values. Results.-Nonpathologists thought that a significantly greater percentage of diagnoses were critical than did pathologists, (49% versus 12%, P < .001). If the term critical value was changed to treatable immediately, life threatening, there was no significant difference between the responses of nonpathologists and pathologists (20% versus 12%, P  =  .06). Conclusions.-There is considerable disagreement between pathologists and nonpathologists concerning which diagnoses are critical values in anatomic pathology. Use of the term treatable immediately, life threatening significantly improves agreement.

Arch Pathol Lab Med. 2011 Nov;135(11):1394-7.
Quality in surgical pathology communication and reporting.
Nakhleh RE.

Context.-Communication in surgical pathology is complex and includes multiple facets. Objective.-To discuss different aspects of pathology practice that represent quality communication in surgical pathology. Data Sources.-Literature review. Conclusions.-Achieving quality communication in surgical pathology is dependent on pathologists addressing multiple situations including managing physicians' expectations for turnaround time and ancillary testing, understanding what information is needed to manage the patient at intraoperative consultation and in the final report, assuring adequate report content with the use of synoptic checklist reports, and using report formatting suggestions that aid report comprehension. Finally, the pathologists' availability to answer questions and discuss cases is an important factor in effective communication, including their willingness to verbally report urgent and significant unexpected diagnoses to ensure that important diagnoses are not overlooked.

Arch Pathol Lab Med. 2011 Nov;135(11):1398-404.
Evidence-based principles in pathology: existing problem areas and the development of "quality" practice patterns.
Wick MR, Marchevsky AM.

Context.-Contrary to the intuitive impressions of many pathologists, several areas exist in laboratory medicine where evidence-based medicine (EBM) principles are not applied. These include aspects of both anatomic and clinical pathology. Some non-EBM practices are perpetuated by clinical "consumers" of laboratory services because of inadequate education, habit, or overreliance on empirical factors. Other faulty procedures are driven by pathologists themselves. Objectives.-To consider (1) several selected problem areas representing non-EBM practices in laboratory medicine; such examples include ideas and techniques that concern metastatic malignancies, "targeted" oncologic therapy, general laboratory testing and data utilization, evaluation of selected coagulation defects, administration of blood products, and analysis of hepatic iron-overload syndromes; and (2) EBM principles as methods for remediation of deficiencies in hospital pathology, and implements for the construction of "quality" practices in our specialty. Data Sources.-Current English literature relating to evidence-based principles in pathology and laboratory medicine, as well as the authors' experience. Conclusions.-Evidence-based medicine holds the promise of optimizing laboratory services to produce "quality" practices in pathology. It will also be a key to restraining the overall cost of health care.

Arch Pathol Lab Med. 2011 Nov;135(11):1405-14.
Assuring Quality in Point-of-Care Testing: Evolution of Technologies, Informatics, and Program Management.
Lewandrowski K, Gregory K, Macmillan D.

Context.-Managing the quality of point-of-care testing (POCT) is a continuing challenge. Advances in testing technologies and the development of specialized informatics for POCT have greatly improved the ability of hospitals to manage their POCT program. Objectives.-To present the evolving role of technology improvement, informatics, and program management as the key developments to ensure the quality of POCT. Data Sources.-This presentation is based on a review of the literature and on our experiences with POCT at the Massachusetts General Hospital (Boston). Conclusions.-Federal and state regulations, along with accreditation standards developed by the College of American Pathologists and The Joint Commission, have established guidelines for the performance of POCT and have provided a strong incentive to improve the quality of testing. Many instruments for POCT have incorporated advanced design features to prevent analytic and operator errors. This, along with the development of connectivity standards and specialized data management software, has enabled remote review of test data and electronic flow of information to hospital information systems. However, documentation of manually performed, visually read tests remains problematic and some POCT devices do not have adequate safeguards to prevent significant errors. In the past 2 decades the structure of a successful POCT management program has been defined, emphasizing the role of POCT managers working in conjunction with a pathology-based medical director. The critical skill set of POCT managers has also been identified. The POCT manager is now recognized as a true specialist in laboratory medicine.

Arch Pathol Lab Med. 2011 Nov;135(11):1415-24.
Managing transfusion service quality.
Blaylock RC, Lehman CM.

Context.-Providing blood products for transfusions is a complex process subject to errors both within and outside the transfusion service. Transfusion-related errors can have grave consequences for the patient undergoing transfusion. As with many processes performed within health care systems, there is an expectation of error-free practice. Although this is an unobtainable goal, a focused quality-management plan, employing a medical event reporting system in a just working environment, can effect measurable system-quality improvement. Objective.-To illustrate the intrinsic value of quality-improvement activities through discussion of examples of quality misadventures from our transfusion service during the past 20 years. Data Sources.-Examples of quality-improvement activities were extracted from our quality-system archives. The published literature on transfusion quality was reviewed. Conclusions.-Active reporting, structured investigation, and systematic resolution of transfusion-related errors are effective methods for improving and maintaining transfusion quality.

Arch Pathol Lab Med. 2011 Nov;135(11):1425-31.
Quality and safety in medical care: what does the future hold?
Liang BA, Mackey T.

Context.-The rapid changes in health care policy, embracing quality and safety mandates, have culminated in programs and initiatives under the Patient Protection and Affordable Care Act. Objective.-To review the context of, and anticipated quality and patient safety mandates for, delivery systems, incentives under health care reform, and models for future accountability for outcomes of care. Design.-Assessment of the provisions of Patient Protection and Affordable Care Act, other reform efforts, and reform initiatives focusing on future quality and safety provisions for health care providers. Results.-Health care reform and other efforts focus on consumerism in the context of price. Quality and safety efforts will be structured using financial incentives, best-practices research, and new delivery models that focus on reaching benchmarks while reducing costs. In addition, patient experience will be a key component of reimbursement, and a move toward "retail" approaches directed at the individual patient may supplant traditional "wholesale" efforts at attracting employers. Conclusions.-Quality and safety have always been of prime importance in medicine. However, in the future, under health care reform and associated initiatives, a shift in the paradigm of medicine will integrate quality and safety measurement with financial incentives and a new emphasis on consumerism.

Arch Pathol Lab Med. 2011 Nov;135(11):1432-5.
College of american pathologists proposal for the oversight of laboratory-developed tests.
Vance GH.

Context.-The US Food and Drug Administration (FDA) announced it will exercise authority over laboratory-developed tests (LDTs). Laboratory-developed tests have traditionally been developed and offered in laboratories as a service to patients and regulated under the Clinical Laboratory Improvement Amendments of 1988 (Clinical Laboratory Improvements Act). Laboratories now face potential dual regulatory oversight from both the Centers for Medicare and Medicaid Services (CMS) and the FDA. The College of American Pathologists (CAP) constructed a proposal to minimize redundancy of agency oversight and burden to laboratories. Modifications to the proposal continue while the laboratory community awaits release of the guidance documents that will stipulate FDA requirements. Objective.-To describe the historical context framing the entry of FDA into the oversight of LDTs and outline the CAP LDT Proposal in its current form. Data Sources.-PubMed review of published literature; United States Constitution; and online information resources from the National Institutes of Health, FDA, and US Government. Conclusion.-The College of American Pathologists is a leader in laboratory quality and has unique insights into the benefits and risks to patients presented by LDTs. Continued dialog with officials from the FDA and CMS will promote public and private collaborative efforts to assure innovation of diagnostic testing, public information, and patient safety for clinical diagnostic testing.

Arch Pathol Lab Med. 2011 Nov;135(11):1436-40.
Assessment of latent factors contributing to error: addressing surgical pathology error wisely.
Smith ML, Raab SS.

Context.-Methods to improve surgical pathology patient safety include measuring the frequency of error in specific steps of the surgical pathology testing process, root cause analysis of active and latent components, and implementation of quality improvement initiatives. Objective.-To determine the frequency and cause of near-miss events in the specimen accessioning, setup, and biopsy-only gross examination testing steps of anatomic pathology. Design.-We used an observational checklist method to identify near-miss events. We performed root cause analysis to determine latent factors contributing to near-miss events. We conducted observations for 45 hours during 5 days, involving the accessioning and processing of 335 specimens. Results.-We detected a total of 2310 process-dependent and 266 operator-dependent near-miss events, resulting in a near-miss-event frequency of 5.5 per specimen. Root cause analysis showed that all process and operator near-miss events were associated with multiple system latent factors, including lack of standardized protocols, appropriate knowledge transfer, and focus on safety culture. Conclusion.-We conclude that the increased focus on surgical pathology near-miss events will reveal latent factors that may be targeted for improvement.

Arch Pathol Lab Med. 2011 Nov;135(11):1441.
Quality and the college of american pathologists.
Allen TC, Hammond ME, Robboy SJ.

The College of American Pathologists (CAP) is dedicated to pathology and laboratory medicine quality. The CAP's Laboratory Accreditation Program, Proficiency Testing Program, Q-Probes and Q-Tracks, site-specific cancer checklists, webinars, annual meetings, and Advanced Practical Pathology series are all focused on providing superior patent quality. The CAP is synonymous with quality in pathology and laboratory medicine. As pathology practice becomes more sophisticated, the CAP's many programs will increasingly help pathologists provide appropriate, personalized patient care.

Thursday, October 27, 2011

From UNC: Genetics and obesity

Br J Nutr. 2011 Oct;106 Suppl 1:S1-S10.
Advances in comparative genetics: influence of genetics on obesity.
Mathes WF, Kelly SA, Pomp D.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Obesity has reached epidemic proportions and is recognised as a significant global health problem. Increased food intake and decreased physical activity are traditionally to blame for the development of obesity; however, many variables such as behaviour, diet, environment, social structures and genetics also contribute to this multifactorial disease. Complex interactions among these variables (for example, gene-environment, gene-diet and gene-gene) contribute not only to individual differences in the development of obesity, but also in treatment response. Mouse models have historically played valuable roles in understanding the genetics of traits related to energy balance and obesity. In the present review, we survey past use and examine new advances in mouse models designed to uncover the genetic architecture of obesity and its component traits. We discuss traditional models such as inbred strains and selectively bred lines and their contributions and shortcomings. We consider the evolution of mouse models into more informative resources such as outbred crosses and the Hybrid Mouse Diversity Panel, as well as novel next-generation approaches such as the Collaborative Cross. Moreover, the genetic architecture of voluntary exercise and the interactive relationship between host genetics and the gut microbiome are presented as novel phenotypes that augment studies using body weight and body fat percentage as endpoints. Understanding the intricate network of phenotypic, genotypic and environmental variables that predispose individuals to obesity will elucidate biological networks involved in the development of obesity. Knowledge obtained from advances in mouse models will inform human health and provide insight into inter-individual variability in the aetiology of obesity-related diseases.

Fructose and blood pressure

Int J Nephrol. 2011;2011:315879. Epub 2011 Jul 17.
The impact of fructose on renal function and blood pressure.
Kretowicz M, Johnson RJ, Ishimoto T, Nakagawa T, Manitius J.
Department of Nephrology, Hypertension and Internal Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, ul. Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland.

Fructose is a sugar present in sucrose, high-fructose corn syrup, honey, and fruits. Fructose intake has increased markedly in the last two centuries, primarily due to increased intake of added sugars. Increasing evidence suggests that the excessive intake of fructose may induce fatty liver, insulin resistance, dyslipidemia, hypertension, and kidney disease. These studies suggest that excessive intake of fructose might have an etiologic role in the epidemic of obesity, diabetes, and cardiorenal disease.

Cystic fibrosis and pain

Physiother Res Int. 2011 Oct 25. doi: 10.1002/pri.524. [Epub ahead of print]
Pain Impacts on Quality of Life and Interferes with Treatment in Adults with Cystic Fibrosis.
Kelemen L, Lee AL, Button BM, Presnell S, Wilson JW, Holland AE.
Physiotherapy, La Trobe University, Bundoora, Victoria, Australia.

Pain has been reported in cystic fibrosis (CF), but its clinical significance and the physical and psychosocial impact in adults who are clinically stable and acutely unwell have not been well described. The aim of this study was to describe the intensity and location of pain and its relationship with health-related quality of life (HRQOL) and pain catastrophizing in adults with CF.

This study was an observational study of adults with CF. Participants completed three questionnaires, the Brief Pain Inventory, Pain Catastrophizing Scale and the CF-Quality of Life questionnaire, when clinically stable and during an acute exacerbation.

A total of 73 participants were included during a period of clinical stability, with 33 repeating the measurements during an acute illness, with a mean (SD) age of 29 (9) years and forced expiratory volume (FEV(1) ) of 60.5 (24.9)% predicted. Mild pain was reported by 89% of stable participants and 79% of those with exacerbations. Severity of lung disease did not affect prevalence or intensity of pain. Pain interfered with airway clearance therapy during exacerbations (p < 0.012) and exercise regimens when participants were clinically stable (p < 0.002) and was related to a poorer physical function, regardless of clinical status (p < 0.05). Although pain intensity was associated with reduced HRQOL (p < 0.001), only FEV(1) and the degree of pain catastrophizing were independent predictors of poorer HRQOL.

Pain is common in adults with CF, irrespective of clinical status, and may interfere with important physiotherapy treatments. Although pain intensity is generally mild, those with a negative emotional response to pain have significantly impaired HRQOL.

Copyright © 2011 John Wiley & Sons, Ltd.


J Am Coll Radiol. 2011 Oct;8(10):687-91.
Unintended consequences of health care legislation.
Thrall JH.
Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.

Unintended consequences of health care legislation threaten the financial and social well-being of the United States. Examples of major legislation resulting in unintended and unforeseen consequences include the Social Security Amendments Acts of 1989 and 1993 (the Stark laws), the Balanced Budget Act of 1997, and the Social Security Amendments Act of 1965 (Medicare and Medicaid). Each of these has had unintended financial and social outcomes. Spending for Medicare and Medicaid now equals an unsustainable 23% of the federal budget. Major reasons for unintended consequences include failure to appreciate the complexity of the issues, the open-ended nature of medical advances with attendant increases in costs, the inducement of change in behaviors in response to legislation, and the moral hazard of people spending other people's money. Actions that should be considered to avoid unintended consequences include more involvement of health professionals in the design of legislation, the inclusion of triggers to target review of legislatively defined programs, and the setting of time limits for sun-setting legislation. The ACR has played an important advocacy role and should continue to offer input to legislators, federal policymakers, and other stakeholders. Many opportunities exist to address the current financial situation by reducing the amount of unnecessary care delivered. Both major US political parties need to find the political will to compromise to chart the way forward. Some level of sacrifice is likely to be necessary from patients and providers and other stakeholders.

From Boston U: Waiting for health care at the VA

J Gen Intern Med. 2011 Nov;26 Suppl 2:676-82.
What are the consequences of waiting for health care in the veteran population?
Pizer SD, Prentice JC.
Department of Health Policy and Management, Boston University School of Public Health, VA Boston Health Care System, 150 South Huntington Avenue; Mail Stop 152H, Boston, MA, 02130, USA,

National health reform is expected to increase how long individuals have to wait between requests for appointments and when their appointment is scheduled. The increase in demand for care due to more widespread insurance will result in longer waits if there is not also a concomitant increase in supply of healthcare services. Long waits for healthcare are hypothesized to compromise health because less frequent outpatient visits result in delays in diagnosis and treatment. Research testing this hypothesis is scarce due to a paucity of data on how long individuals wait for healthcare in the United States. The main exception is the Veterans Health Administration (VA) that has been routinely collecting data on how long veterans wait for outpatient care for over a decade. This narrative review summarizes the results of studies using VA wait time data to answer two main questions: 1) How much do longer wait times decrease healthcare utilization and 2) Do longer wait times cause poorer health outcomes? Longer VA wait times lead to small, yet statistically significant decreases in utilization and are related to poorer health in elderly and vulnerable veteran populations. Both long-term outcomes (e.g. mortality, preventable hospitalizations) and intermediate outcomes such as hemoglobin A1C levels are worse for veterans who seek care at facilities with longer waits compared to veterans who visit facilities with shorter waits. Further research is needed on the mechanisms connecting longer wait times and poorer outcomes including identifying patient sub-populations whose risks are most sensitive to delayed access to care. If wait times increase for the general patient population with the implementation of national reform as expected, U.S. healthcare policymakers and clinicians will need to consider policies and interventions that minimize potential harms for all patients.

From University College London: Smoking and death certificates

J Clin Pathol. 2011 Oct 24. [Epub ahead of print]
Does smoking kill? A study of death certification and smoking.
Proctor I, Sharma V, Khoshzaban M, Winstanley A.
Department of Pathology, University College London, London, UK.

AimTo assess how frequently smoking is cited as a cause of death (COD) on death certificates.MethodsA retrospective study of 2128 death certificates and 236 postmortem reports issued at a large teaching hospital between 2003 and 2009.ResultsSmoking was identified as the underlying COD on only 2 (0.1%) death certificates and included in part II of the death certificate on 10 (0.5%). The two death certificates citing smoking as the underlying COD were in cases of lung cancer and chronic obstructive pulmonary disease. The study included 279 deaths in which these diagnoses were cited on the death certificate and in the majority of these cases the deceased was a smoker or ex-smoker. A review of postmortem reports from the same period failed to identify a single case in which the pathologist cited smoking as causing or contributing to death. In marked contrast to smoking, 57.4% (vs 0.5%) of death certificates, which included diagnoses linked to alcohol use, cited alcohol in part I of the death certificate.ConclusionThis study demonstrates that smoking is rarely cited on death certificates, even in cases where the causal link with smoking is very strong. There are many reasons why smoking is not cited on death certificates. One frequently cited reason is the reluctance of doctors to stigmatise the deceased. Interestingly, such reluctance did not extend to citing alcohol as a COD. By not recording smoking on death certificates doctors are failing to gather important epidemiological and pathological data.

Prognostic significance of lymphovascular invasion in Stage I lung cancer

Eur Surg Res. 2011 Oct 21;47(4):211-217. [Epub ahead of print]
Prognostic Significance of Lymphovascular Invasion for Patients with Stage I Non-Small Cell Lung Cancer.
Hanagiri T, Takenaka M, Oka S, Shigematsu Y, Nagata Y, Shimokawa H, Uramoto H, Yamada S, Tanaka F.
Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

Aims: This study retrospectively investigated the clinical significance of lymphovascular invasion (LVI) following a complete resection for stage I non-small cell lung cancer (NSCLC). Methods: A total of 226 patients who underwent a complete resection for pathological stage I NSCLC were examined. Results: Lymphatic invasion was pathologically diagnosed as ly0 in 156 patients, ly1 in 65, and ly2 in 5 patients. The pathological vascular invasion was diagnosed as v0 in 178 patients, v1 in 35, v2 in 10, and v3 in 3 patients. The 5-year survival rate after surgery of the patients with and without lymphatic invasion was 76.8 and 90.6%, respectively. There was a significantly more unfavorable prognosis in patients with lymphatic invasion (p = 0.042). The 5-year survival rate of the patients with vascular invasion was also significantly more unfavorable (67.8%) than that of patients without vascular invasion (90.4%; p = 0.004). LVI was found to significantly correlate with tumor size and the presence of pleural invasion. Conclusion: The LVI of NSCLC is a significant prognostic factor in patients with stage I tumors. In future clinical trials, it is necessary to evaluate the efficacy of adjuvant therapy for the selection of patients according to this criterion.

Richard Epstein holds court on economic fundamentals

As one comment on the website reads: "I do wish our friend from PBS had called me up prior to his appointment with Professor Epstein. I would have been happy to have told him that interviewing Richard -- particularly with such a facile line of questioning -- is like drinking from a fire hose."

Thursday, October 20, 2011

From MoneyTalks: Health Care Reform's "Free" Preventative Care

Health Care Reform = Free Preventive Care? Not Exactly
Under President Obama's new health care law, "preventive care" is supposed to be free with no deductible or co-pay. So I went for a physical last month – and got billed $730.

"I got my “free” physical last month. But a few days ago, the bills started coming in: $600 worth of “laboratory services,” $70 for “radiology services,” and $60 for “diagnostic services.” Since this was obviously an error, I called my insurance company. What did they say? That much of what constituted my preventive care wasn’t covered by the new law."

Zombie nation: Antidepressant use up 400% since 1988!

"Use of antidepressant drugs has soared nearly 400% since 1988, making the medication the most frequently used by people ages 18-44, a report from the Centers for Disease Control and Prevention shows. Eleven percent of Americans ages 12 years and older took antidepressants during the 2005-08 study period, the authors write."

Plus this: "The survey also found that nearly one in four women ages 40 to 59 are taking antidepressants."

Also worrisome: "In fact, less than one-third of Americans taking one antidepressant and less than one-half of those taking multiple antidepressants have seen a mental-health professional in the past year, the report shows."

From Lucien Chirieac and colleagues: Immunoprofile of sarcomatous mesothelioma

Am J Cancer Res. 2011;1(1):14-24. Epub 2010 Sep 30.
The immunohistochemical characterization of sarcomatoid malignant mesothelioma of the pleura.
Chirieac LR, Pinkus GS, Pinkus JL, Godleski J, Sugarbaker DJ, Corson JM.

The immunohistochemical characteristics of epithelioid malignant mesothelioma are well described. However, immunohistochemical analyses of sarcomatoid mesothelioma, the less common type, are limited and its distinction from other tumors of the chest wall, lung and pleura is often problematic. We evaluated 24 patients with pleural sarcomatoid mesothelioma who had surgery (12 extrapleural pneumonectomies, 9 pleurectomies and 3 large biopsies) between 1989 and 2005. Clinicopathologic features and demographic data were recorded. We describe immunohistochemical results for 10 antibodies: AE1/AE3, CAM5.2 and MNF-116 keratins, calretinin, WT-1 protein, bcl-2, CD34, desmin, D2-40 and podoplanin. The patients were 23 men and one woman with a median age at diagnosis of 64.7 years (range 47 to 76). Tumor cells were positive for the keratin proteins AE1/AE3 in 18/24 cases, CAM 5.2 in 23/24 cases and MNF-116 in 21/21 cases. Calretinin was positive in 6/24 cases, WT-1 (nuclear) in 8/24 cases, bcl-2 in 0/24 cases, CD34 in 0/24 cases, desmin in 0/24 cases, D2-40 in 24/24 cases and podoplanin in 24/24 cases. This panel of antibodies may be helpful in establishing a pathologic diagnosis of sarcomatoid mesothelioma. In our study, D2-40 and podoplanin are highly sensitive immunohistochemical markers for sarcomatoid mesothelioma. Additional studies are required to define their role in the differential diagnosis of other spindle cell tumors.

From Bryan Liang and colleague: The global counterfeit drug trade

J Pharm Sci. 2011 Nov;100(11):4571-9. doi: 10.1002/jps.22679. Epub 2011 Jun 22.
The global counterfeit drug trade: Patient safety and public health risks.
Mackey TK, Liang BA.
Institute of Health Law Studies, California Western School of Law, San Diego, California; Joint Doctoral Program on Global Health, University of California, San Diego State University, San Diego, California.

Counterfeit drugs are a global problem with significant and well-documented consequences for global health and patient safety, including drug resistance and patient deaths. This multibillion-dollar industry does not respect geopolitical borders, and threatens public health in both rich and resource-poor nations alike. The epidemiology of counterfeits is also wide in breadth and scope, including thousands of counterfeit incidents per year, encompassing all types of therapeutic classes, and employing a complex global supply chain network enabling this illegal activity. In addition, information technologies available through the Internet and sales via online pharmacies have allowed the criminal element to thrive in an unregulated environment of anonymity, deception, and lack of adequate enforcement. Though recent global enforcement efforts have led to arrests of online counterfeit sellers, such actions have not stemmed supplies from illegal online sellers or kept up with their creativity in illegally selling their products. To address this issue, we propose a global policy framework utilizing public-private partnership models with centralized surveillance reporting that would enable cooperation and coordination to combat this global health crisis.
© 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4571-4579, 2011.

Copyright © 2011 Wiley-Liss, Inc.

Parkinson's disease and visual creativity

J Neurol. 2011 Oct 19. [Epub ahead of print]
Art and Parkinson's disease: a dramatic change in an artist's style as an initial symptom.
Shimura H, Tanaka R, Urabe T, Tanaka S, Hattori N.
Department of Neurology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba, 113-8421, Japan,

In Parkinson's disease (PD), nonmotor symptoms manifest before motor symptoms. In this report, we present a remarkable case of a semiprofessional painter with PD whose painting style dramatically changed from abstract painting to realism before he developed motor, psychiatric, and autonomic nerve disorders. This case suggests that certain types of visual creativity may be impaired in the very early, presymptomatic stages of PD.

From Japan: Death inquests

Leg Med (Tokyo). 2011 Oct 12. [Epub ahead of print]
Medicolegal death diagnosis in Tokyo Metropolis, Japan (2010): Comparison of the results of death inquests by medical examiners and medical practitioners.
Suzuki H, Fukunaga T, Tanifuji T, Abe N, Sadakane A, Nakamura Y, Sakamoto A.
Division of Forensic Medicine, Department of Anatomy, Jichi Medical University, Japan; Tokyo Medical Examiner's Office, Tokyo Metropolitan Government, Japan.

Japanese methods of death inquests are still in developmental stages and many problems have been uncovered since an inspection error was reported in 2007. In this study, we investigated the latest results of medicolegal deaths in the Tokyo Metropolis, which is composed of areas with and without the medical examiner system, and compared the results of inquests performed by official medical examiners with those by medical practitioners to re-evaluate the effectiveness of the medical examiner system for the Japanese death inquiry system.

By using death certificates as inquest records in the Tokyo Metropolis, 2010, we made a comparison of the autopsy rates, causes of death and the numbers of death certificates containing defects between the inquests performed by official medical examiners and those by medical practitioners.

Age distributions and male to female ratios were not different between the two groups. The autopsy rate of the medical practitioners' cases was only 5.5%, whereas that of official medical examiners' cases was 21%. The proportion of deaths due to circulatory system disease was higher in medical practitioners' cases than in official medical examiners' cases (P<0.01), and the proportion of deaths from cerebrovascular disease in medical practitioners cases was twice as high as that in official medical examiners' cases. The number of ambiguous causes of death, such as unspecific heart failure and arrhythmia, certified without autopsies was much higher in medical practitioners' cases than in official medical examiners' cases. For accidental deaths, the proportion of deaths by poisoning and heatstroke was lower in medical practitioners' cases than in medical examiners' cases (P<0.01). The proportion of death certificates containing defects was much higher in medical practitioners' cases (24.1%), especially in the rural areas (45.4%), as compared to official medical examiners' cases (1.3%).

The lower autopsy rate and the higher frequency of defects in death certificates in medical practitioner's cases likely led to the differences in the mortality statistics between the two groups. On the other hand, the medical examiner system leaves room for further improvement, such as in the autopsy rate. This study supports the necessity for implementation and improvement of the medical examiner system, and for reinforcement of under/postgraduate medicolegal education in Japan.

Florida and vaginal birth after cesarean section

BMC Pregnancy Childbirth. 2011 Oct 12;11(1):72. [Epub ahead of print]
Providers' perspectives on the vaginal birth after cesarean guidelines in Florida, United States: a qualitative study.
Cox KJ.


Women's access to vaginal birth after cesarean (VBAC) in the United States has declined steadily since the mid-1990s, with a current rate of 8.2%. In the State of Florida, less than 1% of women with a previous cesarean deliver vaginally. This downturn is thought to be largely related to the American College of Obstetricians and Gynecologists (ACOG) VBAC guidelines, which mandate that a physician and anesthesiologist be "immediately available" during a trial of labor. The aim of this exploratory qualitative study was to explore the barriers associated with the ACOG VBAC guidelines, as well as the strategies that obstetricians and midwives use to minimize their legal risks when offering a trial of labor after cesarean.

Semi-structured interviews were conducted with 11 obstetricians, 12 midwives, and a hospital administrator (n = 24). Interviews were recorded and transcribed verbatim, and thematic analysis informed the findings.

Fear of liability was a central reason for obstetricians and midwives to avoid attending VBACs. Providers who continued to offer a trial of labor attempted to minimize their legal risks by being highly selective in choosing potential candidates. Definitions of "immediately available" varied widely among hospitals, and providers in solo or small practices often favored the convenience of a repeat cesarean delivery rather than having to remain in-house during a trial of labor. Midwives were often marginalized due to restrictive hospital policies and by their consulting physicians, even though women with previous cesareans were actively seeking their care.

The current ACOG VBAC guidelines limit US obstetricians' and midwives' ability to provide care for women with a previous cesarean, particularly in community and rural hospitals. Although ACOG has proposed that women be allowed to accept "higher levels of risk" in order to be able to attempt a trial of labor in some settings, access to VBAC is unlikely to increase in Florida as long as systemic barriers and liability risks remain high.

Worldwide increase in incidence of melanoma

J Skin Cancer. 2011;2011:858425. Epub 2011 Oct 10.
Worldwide increasing incidences of cutaneous malignant melanoma.
Godar DE.
Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Avenue, WO64-4024, Silver Spring, MD 20993, USA.

The incidence of cutaneous malignant melanoma (CMM) has been increasing at a steady rate in fair-skinned populations around the world for decades. Scientists are not certain why CMM has been steadily increasing, but strong, intermittent UVB (290-320 nm) exposures, especially sunburn episodes, probably initiate, CMM, while UVA (321-400 nm) passing through glass windows in offices and cars probably promotes it. The CMM incidence may be increasing at an exponential rate around the world, but it definitely decreases with increasing latitude up to ~50°N where it reverses and increases with the increasing latitude. The inversion in the incidence of CMM may occur because there is more UVA relative to UVB for most of the year at higher latitudes. If windows, allowing UVA to enter our indoor-working environment and cars, are at least partly responsible for the increasing incidence of CMM, then UV filters can be applied to reduce the rate of increase worldwide.

From Alain Borczuk & colleagues: World Trade Center exposure and lung pathology

J Occup Environ Med. 2011 Sep;53(9):981-91. doi: 10.1097/JOM.0b013e31822fff60.
Lung pathologic findings in a local residential and working community exposed to World Trade Center dust, gas, and fumes.
Caplan-Shaw CE, Yee H, Rogers L, Abraham JL, Parsia SS, Naidich DP, Borczuk A, Moreira A, Shiau MC, Ko JP, Brusca-Augello G, Berger KI, Goldring RM, Reibman J.
NYU School of Medicine, New York, NY 10016, USA.

To describe pathologic findings in symptomatic World Trade Center-exposed local workers, residents, and cleanup workers enrolled in a treatment program.

Twelve patients underwent surgical lung biopsy for suspected interstitial lung disease (group 1, n = 6) or abnormal pulmonary function tests (group 2, n = 6). High-resolution computed axial tomography and pathologic findings were coded. Scanning electron microscopy with energy-dispersive x-ray spectroscopy was performed.

High-resolution computed axial tomography showed reticular findings (group 1) or normal or airway-related findings (group 2). Pulmonary function tests were predominantly restrictive. Interstitial fibrosis, emphysematous change, and small airway abnormalities were seen. All cases had opaque and birefringent particles within macrophages, and examined particles contained silica, aluminum silicates, titanium dioxide, talc, and metals.

In symptomatic World Trade Center-exposed individuals, pathologic findings suggest a common exposure resulting in alveolar loss and a diverse response to injury.

The Massachusetts health plan: Is it sustainable?

J Med Philos. 2011 Oct 13. [Epub ahead of print]
The Massachusetts Health Plan, Individual Mandates, and the Neutrality of the Liberal State.
Murray D.
University of Wisconsin-Baraboo/Sauk County, USA.

In 2007, Massachusetts instituted a universal coverage health plan that requires all citizens to purchase insurance. I argue that there is nothing wrong in principle with the use of an individual mandate to force citizens to secure health insurance. I argue that state neutrality is not tenable on this issue. Then I proceed to show that even if state neutrality were viable, it is not a violation of state neutrality (thought of as neutrality of intent) to force citizens to insure themselves with the primary purpose of securing the normative good of health. I adapt recent work on universal medical coverage to demonstrate that such a mandate is in keeping with several principles of fairness shared in liberal democratic societies. This argument not only applies to the Massachusetts plan but likely to any other health care coverage schemes using individual mandates in the US political context, including recently passed federal health care reform measures. However, even though the Massachusetts plan may provide increased access to health care for many, there are still legitimate worries that it currently places disproportionate financial burdens on the working poor and thus will need refinement.

Health care access for women veterans

J Gen Intern Med. 2011 Nov;26 Suppl 2:655-61.
Access to care for women veterans: delayed healthcare and unmet need.
Washington DL, Bean-Mayberry B, Riopelle D, Yano EM.
VA Greater Los Angeles Health Services Research and Development (HSR&D) Center of Excellence, Sepulveda, CA, USA,

Timely access to healthcare is essential to ensuring optimal health outcomes, and not surprisingly, is at the heart of healthcare reform efforts. While the Veterans Health Administration (VA) has made improved access a priority, women veterans still underutilize VA healthcare relative to men. Eliminating access disparities requires a better understanding of the barriers to care that women veterans' experience.

We examined the association of general and veteran-specific barriers on access to healthcare among women veterans.

Cross-sectional, population-based national telephone survey of 3,611 women veterans.

Delayed healthcare or unmet healthcare need in the prior 12 months.

Of women veterans, 19% had delayed healthcare or unmet need, with higher rates in younger age groups (36%, 29%, 16%, 7%, respectively, in 18-34, 35-49, 50-64, and 65-plus age groups; p < 0.001). Among those delaying or going without care, barriers that varied by age group were: unaffordable healthcare (63% of 18-34 versus 12% of 65-plus age groups); inability to take off from work (39% of those <50); and transportation difficulties (36% of 65-plus). Controlling for age, race/ethnicity, regular source of care, and health status, being uninsured (OR = 6.5; confidence interval [CI] 3.0-14.0), knowledge gaps about VA care (OR = 2.1; 95% CI 1.1-4.0), perception that VA providers are not gender-sensitive (OR = 2.4; CI 1.2-4.7), and military sexual assault history (OR = 2.1; CI 1.1-4.0) predicted delaying or foregoing care, whereas VA use and enrollment priority did not.

Both general and veteran-specific factors impact women veterans' access to needed services. Many of the identified access barriers are potentially modifiable through expanded VA healthcare and social services. Health reform efforts should address these barriers for VA nonusers. Efforts are also warranted to improve women veterans' knowledge of availability and affordability of VA healthcare, and to enhance the gender-sensitivity of this care.

Classical Hodgkin Lymphoma: Lymphocyte/monocyte ratio and survival

Haematologica. 2011 Oct 11. [Epub ahead of print]
Peripheral blood lymphocyte/monocyte ratio at diagnosis and survival in classical Hodgkin lymphoma.
Porrata LF, Ristow K, Colgan J, Habermann T, Witzig T, Thompson C, Inwards D, Ansell S, Micallef I, Johnston P, Nowakowski G, Thompson C, Markovic S.

Background. Lymphopenia and tumor-associated macrophages are negative prognostic factors for survival in classical Hodgkin's lymphoma. Thus, we studied if the peripheral blood absolute lymphocyte count/absolute monocyte count ratio at diagnosis affects survival in classical Hodgkin's lymphoma.Design and Methods. We studied 476 consecutive classical Hodgkin's lymphoma patients followed at Mayo Clinic from 1974 to 2010. Receiver operating characteristic and area under the curve were used for absolute lymphocyte count/absolute monocyte count ratio at diagnosis cut-off value analysis and proportional-hazards models were used to compare survival based on the absolute lymphocyte count/absolute monocyte count ratio at diagnosis ratio.Results. The median follow-up period was 5.6 years (range: 0.1-33.7 years). An absolute lymphocyte count/absolute monocyte count ratio at diagnosis ≥1.1 was the best cut-off value for survival with an area under the curve of 0.91 (95% confidence interval, 0.86 to 0.96), a sensitivity of 90% (95% confidence interval, 85% to 96%) and specificity of 79% (95% confidence interval, 73% to 88%). Absolute lymphocyte count/absolute monocyte count ratio at diagnosis was an independent prognostic factor for overall survival {hazard ratio , 0.18, 95% confidence interval, 0.08 to 0.38, p< 0.0001]; lymphoma-specific survival [hazard ratio, 0.10; 95% confidence interval, 0.04 to 0.25, p <0.0001]; progression-free survival [hazard ratio, 0.35; 95% confidence interval, 0.18 to 0.66, p < 0.002], and time to progression [hazard ratio, 0.27, 95% confidence interval, 0.17 to 0.57, p <0.0006]. Conclusions. Absolute lymphocyte count/absolute monocyte count ratio at diagnosis is an independent prognostic factor for survival and provides a single biomarker to predict clinical outcomes in classical Hodgkin's lymphoma.

Heroin, HIV, and young Nuosu Chinese men

Med Anthropol Q. 2011 Sep;25(3):395-411.
A precarious rite of passage in postreform China: heroin use among Nuosu youths on the move.
Liu SH.
Institute of Ethnology, Academia Sinica, Taiwan.

This article employs the rite of passage concept to analyze why and how heroin use and a subsequent HIV/AIDS epidemic have taken hold among minority Nuosu (Yi) young men in Southwest China. It juxtaposes structural inequalities and sociocultural particularities in social suffering among Nuosu youths as they attempt to create meaningful lives in China's market reform era. Since the 1980s, young Nuosu have ventured out to Han-dominant cities in search of fun and opportunities. This movement has become a new foray into manhood and inadvertently set up their encounter with heroin and the subsequent introduction of HIV into their hometowns. The article is based on my 20-month ethnographic fieldwork in Limu, a mountainous Nuosu community in Liangshan Yi Autonomous Prefecture, Sichuan Province, between 2002 and 2009.

Past time to get a handle on this: Radiation exposure from diagnostic radiologic procedures

Health Phys. 2011 Nov;101(5):583-8.
Communicating the harmful effects of radiation exposure from medical imaging: malpractice considerations.
Berlin L.
* NorthShore University HealthSystem-Skokie Hospital, 9600 Gross Point, Road Skokie, IL 60076.

Concerns about possible harmful effects of exposure to radiation arising from diagnostic radiologic procedures have existed in both the scientific and lay communities for many decades. There is, however, no question that the degree of concern over the past years has escalated to the "anxiety" if not the "fear" level. Potential exposure to radiation is not a new issue, but it is certainly a "hot" issue. Americans were exposed to more than six times as much ionizing radiation from diagnostic medical procedures in 2006 than they were in early 1980s. To what extent this increased exposure elevates the risk of genetic mutations and/or development of cancer is not known with any degree of certainty. The available data are subject to varying interpretations, often debatable and thus controversial. What should be communicated to the public? The medical and scientific communities must encourage public attention and discussion regarding radiologic imaging and associated radiation exposure. They must talk to the public sensibly about the uncertainty regarding the hazards of radiation exposure. Exposure to imaging involving radiation and the hazards related to such exposure has myriad medical/legal ramifications. There has never been a successful medical malpractice lawsuit that alleged development of cancer or genetic defects resulting from diagnostic x-ray examinations. However, there have been and continue to be lawsuits filed alleging soft tissue injury resulting from overexposure to diagnostic radiologic equipment and cancer caused by overexposure to radiation oncology equipment. It is quite likely that lawsuits alleging development of cancer arising from diagnostic imaging using standard levels of ionizing radiation will be forthcoming. How the courts will deal with these remains to be determined.

Medical malpractice risk: New news, same as the old news

Oral Maxillofac Surg Clin North Am. 2011 Nov;23(4):601-7.
What are the Lessons We Can Glean from a Review of Recent Closed Malpractice Cases Involving Oral and Maxillofacial Infections?
Holmes SM, Udey DK.
Risk Management, OMS National Insurance Company, 6133 North River Road, Suite 650, Rosemont, IL 60018-5173, USA.

OMS National Insurance Company insures over 4700 oral and maxillofacial surgeons, 83% of the fellows and members of the American Association of Oral and Maxillofacial Surgeons. The company has over 10,000 closed malpractice claims involving oral and maxillofacial surgeons. Data and trends involving infections that developed following elective surgical procedures and trends involving patients with preexisting odontogenic infections with adverse outcomes are well known to the company. Seven percent of the 10,000+ closed claims involve infections. Recognition and diagnosis of the infection leads to appropriate and timely treatment of infections. Delayed recognition, consultation, and referral leads to delay in the institution of appropriate treatment and can lead to adverse outcomes.

Legal issues of stroke treatment in Taiwan

Acta Neurol Taiwan. 2011 Sep;20(3):163-71.
The medicolegal issue of tissue plasminogen activator in ischemic stroke: a review of judiciary decrees in taiwan.
Chen WH, Lin HS, Chen CI, Chou MS, Liou CW, Chen SS; Stroke Center-CGMH/Kaohsiung.
Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, and College of Medicine, Chang Gung University, Kaohsiung, Taiwan.

Purpose: Tissue plasminogen activator (tPA) was approved by the Food and Drug Administration for ischemic stroke treatment since 1996 at the United States of America and also 2002 at Taiwan. Since after it is strongly advertised for a promising benefit to early thrombolysis that is further echoed by a recommendation in clinical guidelines from multiple medical associations in worldwide. Because of an overwhelming data of positive benefit collected in the evidence-based medicine database, legal dispute subsequently occurs when tPA is failed to be administrated in appropriate time. Methods: In order to elucidate the legal viewpoint for tPA used in ischemic stroke, a review of the domestic judiciary decrees regarding this issue was conducted. Cases in Taiwan were executed from the open access database of the Judicial Yuan, Taiwan. The background, legal dispute and judgment of each case were analyzed. Results: Till August, 2010, there were 6 cases in Taiwan. All cases occurred after 2003. The causes of disputes were a loss of chance for thrombolysis due to a delay of diagnosis (4 cases, 67%) and a failure of thrombolytic treatment after a diagnosis of ischemic stroke (2 cases, 23%). All cases were presented to non-neurologists at initial. Five cases expired or terminated into vegetation before litigation. Conclusion: A failure of early diagnosis or treatment after a diagnosis of ischemic stroke are important for medicolegal dispute in tPA usage, which is expected to become prevalent in Taiwan in future. A fatal or poor outcome may be a triggering factor for litigation. Therefore, an improvement of the knowledge and practice to increase early diagnosis of ischemic stroke is the key factor for reducing medicolegal issue regarding tPA use in ischemic stroke. This is particularly true for non-neurologist physicians.

From Wash U: Depression after a heart attack

Circ Cardiovasc Qual Outcomes. 2011 Oct 18. [Epub ahead of print]
Depression and Rehospitalization Following Acute Myocardial Infarction.
Reese RL, Freedland KE, Steinmeyer BC, Rich MW, Rackley JW, Carney RM.
Department of Psychology, Department of Psychiatry, and Department of Medicine, Washington University School of Medicine, St Louis, MO.

BACKGROUND: Whether depressive disorders predict rehospitalization after AMI is unknown. METHODS AND RESULTS: <0.001; major depression adjusted hazard ratio, 2.54; 95% CI, 1.84-3.53; P<0.001), had more hospitalizations (minor, P<0.001; major, P<0.001) and emergency department visits (minor, P=0.003; major, P<0.001), and spent more days in the hospital (minor, P<0.001; major, P<0.001). The interview and questionnaire methods of assessing depression did not significantly differ in their overall accuracy of predicting rehospitalization.ConclusionsDepressive disorders increase the risk of rehospitalization after AMI. Future work should focus on developing multivariable models to predict risk of rehospitalization after AMI, and depression should be included in these.

Sarcopenia in older men and women

Gait Posture. 2011 Oct 6. [Epub ahead of print]
Sarcopenia and predictors of the fat free mass index in community-dwelling and assisted-living older men and women.
Krause KE, McIntosh EI, Vallis LA.
Department of Human Health and Nutritional Sciences, University of Guelph, 50 Stone Road West, Guelph, ON, Canada N1G 2W1; Research Associate, Schlegel-UW Research Institute for Aging, 325 Max Becker Dr., Suite 202 Kitchener, ON, Canada N2E 4H5.

The purpose of this study was to assess the relationship of the fat free mass index (FFMI), an indicator of sarcopenia in older adults, to anthropometric, gait, balance, and strength measures. We hypothesized that strength, balance, and mobility measures will correlate, and could be used to predict FFMI in older adults. Thirty-three older adults (81.5±7.9 years) participated. Fat free mass (FFM) was measured using Air-Displacement Plethysmography (ADP). Anthropometric measures, maximum handgrip (MG) and quadriceps strength were quantified. Clinical tests included the Berg Balance Scale (BBS), Dynamic Gait Index (DGI), and the Timed-up and Go (TUG) test. Finally, variability measures in gait and balance were calculated. Means, standard deviations (SD), correlations and multiple linear regression statistical analyses were then performed using functional predictor variables for FFMI. In total, 54.5% males and 36.3% females in our population were classified sarcopenic. FFMI correlated only to waist circumference (Total population (Pop), R(2)=0.649 p<0.01; Sarcopenics (Sarc), R(2)=0.636, p<0.05) and maximum grip strength (Pop, R(2)=0.633, p<0.01; Sarc, R(2)=0.771, p<0.01), nullifying our hypothesis. Multiple linear regression analyses revealed waist circumference, maximum handgrip strength, greater variability of time spent in double support, and anterior-posterior balance variability predicted 70.7% of the variance within the population. Results demonstrate a successful predictor model for FFMI based on a combination of strength, circumference and gait/balance variance measures. The ability to predict FFMI based on these variables will facilitate the diagnosis of sarcopenia in older adults.

Copyright © 2011 Elsevier B.V. All rights reserved.

From Wash U: Exercise for obesity. What a concept!

Pediatr Blood Cancer. 2011 Oct 18. doi: 10.1002/pbc.23368. [Epub ahead of print]
Exercise intervention for management of obesity.
Deusinger SS.
Washington University School of Medicine, St. Louis, Missouri.

Obesity touches the lives of most Americans regardless of age. In adults, accrual of co-morbidities, including frank disability, impacts health in ways that mandate aggressive public health action. In children, the rising prevalence of overweight and obesity raises serious prospective concerns for life as these children enter adulthood. Action is imperative to provide medical interventions and preventive strategies to reduce the threat this condition poses to future generations. Obesity primarily results from an energy regulation imbalance within the body; understanding its origin and effects requires considering both the intake (via eating) and output (via moving) of energy. This article focuses on how exercise and physical activity (i.e., energy output) can influence the primary condition of obesity and its health sequelae. Components, strategies, and expected outcomes of exercise and lifestyle activity are addressed. Successful long-term participation in daily movement requires matching exercise regimens and physical activity outlets to individual preferences and environmental conditions. Activity habits of Americans must change at home and in the workplace, schools and the community to positively influence health. Although the goals of Healthy People 2010 to reduce sedentary behavior have not been met, success of other public health interventions (e.g., immunizations, use of bicycle helmets) suggests that social change to alter activity habits can be achieved. Failure to reach our public health goals should serve as a catalyst for broad-based action to help children, adolescents, and adults attain and maintain behaviors that reduce the risk of obesity and its health insults. Pediatr Blood Cancer © 2011 Wiley Periodicals, Inc.

Copyright © 2011 Wiley Periodicals, Inc.

From Johns Hopkins: Cystic Fibrosis and venous thromboembolism

Pediatr Pulmonol. 2011 Oct 17. doi: 10.1002/ppul.21566. [Epub ahead of print]
Venous thromboembolism in cystic fibrosis.
Takemoto CM.
Division of Pediatric Hematology, The Johns Hopkins University, Baltimore, Maryland.
The incidence of venous thromboembolism (VTE) is increasing in the pediatric population. Individuals with cystic fibrosis (CF) have an increased risk of thrombosis due to central venous catheters (CVCs), as well as acquired thrombophilia secondary to inflammation, or deficiencies of anticoagulant proteins due to vitamin K deficiency and/or liver dysfunction. CVC-associated thrombosis commonly results in line occlusion, but may develop into serious life-threatening conditions such as deep venous thrombosis (DVT), superior vena cava syndrome or pulmonary embolism (PE). Post-thrombotic syndrome (PTS) may be a long complication. Local occlusion of the catheter tip may be managed with instillation of thrombolytics (such as tPA) within the lumen of the catheter; however, CVC-associated thrombosis involving the proximal veins is most often is treated with systemic anticoagulation. Initial treatment with heparin is a standard approach, but thrombolytic therapy, which may carry higher bleeding risks, should be considered for life and limb threatening episodes of VTE. Recommended duration of anticoagulation with low molecular weight heparin (LMWH) or warfarin ranges from 3 to 6 months for major removable thrombotic risks; longer anticoagulation is considered for recurrent thrombosis, major persistent thrombophilia, or the continued presence of a major risk factor such as a CVC. While CVCs are the most common risk for development of VTE in children, studies have not demonstrated a clear benefit with routine use of systemic thromboprophylaxis. The incidence and risk factors of VTE in CF patients will be reviewed and principles of diagnosis and management will be summarized. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

Sunitinib therapy for Mesothelioma

J Thorac Oncol. 2011 Nov;6(11):1950-4.
Brief Report: A Phase II Study of Sunitinib in Malignant Pleural Mesothelioma. The NCIC Clinical Trials Group.
Laurie SA, Gupta A, Chu Q, Lee CW, Morzycki W, Feld R, Foo AH, Seely J, Goffin JR, Laberge F, Murray N, Rao S, Nicholas G, Laskin J, Reiman T, Sauciuc D, Seymour L.
The NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada.

: Malignant pleural mesothelioma (MPM) is an aggressive malignancy that most often presents at an advanced, incurable stage. After the failure of standard first-line cisplatin/antifolate chemotherapy, there is no accepted treatment. The vascular endothelial growth factor pathway may be a relevant therapeutic target in MPM.

: This open-labeled phase II trial evaluated single-agent sunitinib, an inhibitor of multiple receptor tyrosine kinases including the vascular endothelial growth factor receptors, given at 50 mg daily orally for 4 weeks followed by a 2-week rest, in patients with advanced MPM. Two cohorts were studied: cohort 1, in which patients had previously received cisplatin-based chemotherapy, and cohort 2, consisting of previously untreated patients. A two-stage design was used for both cohorts; the primary outcome was objective response rate as determined by the RECIST criteria modified for MPM. Secondary outcomes included rates and duration of disease control, progression-free survival and overall survival, and safety and tolerability.

: A total of 35 eligible patients were enrolled (17 to cohort 1 and 18 to cohort 2). Neither cohort met the criteria for continuing to the second stage of accrual; only one objective response, confirmed by independent review, was observed in a previously untreated patient. Median progression-free and overall survivals were 2.8 and 8.3 months in cohort 1, and 2.7 and 6.7 months in cohort 2, respectively. Observed toxicity was within that expected for sunitinib.

: Sunitinib, similar to other angiogenesis inhibitors, has limited activity in MPM. Future trials of angiogenesis inhibitors given as single agents in unselected patients with MPM are not warranted.

Asbestos and tumor immunity

Clin Dev Immunol. 2011;2011:481439. Epub 2011 Oct 4.
Asbestos induces reduction of tumor immunity.
Kumagai-Takei N, Maeda M, Chen Y, Matsuzaki H, Lee S, Nishimura Y, Hiratsuka J, Otsuki T.
Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan.

Asbestos-related cancers such as malignant mesothelioma and lung cancer are an important issue in the world. There are many conflicts concerning economical considerations and medical evidence for these cancers and much confusion regarding details of the pathological mechanisms of asbestos-induced cancers. For example, there is uncertainty concerning the degree of danger of the iron-absent chrysotile compared with iron-containing crocidolite and amosite. However, regarding bad prognosis of mesothelioma, medical approaches to ensure the recognition of the biological effects of asbestos and the pathological mechanisms of asbestos-induced carcinogenesis, as well as clinical trials to detect the early stage of mesothelioma, should result in better preventions and the cure of these malignancies. We have been investigating the immunological effects of asbestos in relation to the reduction of tumor immunity. In this paper, cellular and molecular approaches to clarify the immunological effects of asbestos are described, and all the findings indicate that the reduction of tumor immunity is caused by asbestos exposure and involvement in asbestos-induced cancers. These investigations may not only allow the clear recognition of the biological effects of asbestos, but also present a novel procedure for early detection of previous asbestos exposure and the presence of mesothelioma as well as the chemoprevention of asbestos-related cancers.

CAP/ADASP consensus statement on effective communication of surgical and cytologic diagnoses

Arch Pathol Lab Med. 2011 Oct 13. [Epub ahead of print]
Consensus Statement on Effective Communication of Urgent Diagnoses and Significant, Unexpected Diagnoses in Surgical Pathology and Cytopathology From the College of American Pathologists and Association of Directors of Anatomic and Surgical Pathology.
Nakhleh RE, Myer JL, Allen TC, Deyoung BR, Fitzgibbons PL, Funkhouser WK, Mody DR, Lynn A, Fatheree LA, Smith AT, Lal A, Silverman JF.

Context.-Recognizing the difficulty in applying the concept of critical values to anatomic pathology diagnoses, the College of American Pathologists and the Association of Directors of Anatomic and Surgical Pathology have chosen to reevaluate the concept of critical diagnoses. Objective.-To promote effective communication of urgent and significant, unexpected diagnoses in surgical pathology and cytology. Design.-A comprehensive literature search was conducted and reviewed by an expert panel. Results.-A policy of effective communication of important results in surgical pathology and cytology is desirable to enhance patient safety and to address multiple regulatory requirements. Conclusions.-Each institution should create its own policy regarding urgent diagnoses and significant, unexpected diagnoses in anatomic pathology. This policy should be separate from critical results or panic-value policies in clinical pathology, with the expectation of a different time frame for communication. Urgent diagnosis is defined as a medical condition that, in most cases, should be addressed as soon as possible. Significant, unexpected diagnosis is defined as a medical condition that is clinically unusual or unforeseen and should be addressed at some point in the patient's course. Further details of this statement are provided.

Friday, October 14, 2011

CAP/ADASP consensus statement on effective communication of surgical and cytologic diagnoses

Arch Pathol Lab Med. 2011 Oct 13. [Epub ahead of print]
Consensus Statement on Effective Communication of Urgent Diagnoses and Significant, Unexpected Diagnoses in Surgical Pathology and Cytopathology From the College of American Pathologists and Association of Directors of Anatomic and Surgical Pathology.
Nakhleh RE, Myer JL, Allen TC, Deyoung BR, Fitzgibbons PL, Funkhouser WK, Mody DR, Lynn A, Fatheree LA, Smith AT, Lal A, Silverman JF.
Context.-Recognizing the difficulty in applying the concept of critical values to anatomic pathology diagnoses, the College of American Pathologists and the Association of Directors of Anatomic and Surgical Pathology have chosen to reevaluate the concept of critical diagnoses. Objective.-To promote effective communication of urgent and significant, unexpected diagnoses in surgical pathology and cytology. Design.-A comprehensive literature search was conducted and reviewed by an expert panel. Results.-A policy of effective communication of important results in surgical pathology and cytology is desirable to enhance patient safety and to address multiple regulatory requirements. Conclusions.-Each institution should create its own policy regarding urgent diagnoses and significant, unexpected diagnoses in anatomic pathology. This policy should be separate from critical results or panic-value policies in clinical pathology, with the expectation of a different time frame for communication. Urgent diagnosis is defined as a medical condition that, in most cases, should be addressed as soon as possible. Significant, unexpected diagnosis is defined as a medical condition that is clinically unusual or unforeseen and should be addressed at some point in the patient's course. Further details of this statement are provided.

Wednesday, October 12, 2011

From National Review: The End of the Future

The state can successfully push science; there is no sense denying it. The Manhattan Project and the Apollo program remind us of this possibility. Free markets may not fund as much basic research as needed. On the day after Hiroshima, the New York Times could with some reason pontificate about the superiority of centralized planning in matters scientific: “End result: An invention [the nuclear bomb] was given to the world in three years which it would have taken perhaps half a century to develop if we had to rely on prima donna research scientists who work alone.”

But in practice, we all sense that such gloating belongs to a very different time. Most of our political leaders are not engineers or scientists and do not listen to engineers or scientists. Today a letter from Einstein would get lost in the White House mail room, and the Manhattan Project would not even get started; it certainly could never be completed in three years. I am not aware of a single political leader in the U.S., either Democrat or Republican, who would cut health-care spending in order to free up money for biotechnology research — or, more generally, who would make serious cuts to the welfare state in order to free up serious money for major engineering projects.

Nanoparticle interaction with bronchial epithelium: Important issue for optimal drug delivery

Biomacromolecules. 2011 Oct 7. [Epub ahead of print]
Biodegradable nanoparticles meet the bronchial airway barrier: how surface properties affect their interaction with mucus and epithelial cells.
Mura S, Hillaireau H, Nicolas J, Kerdine-Römer S, Le Droumaguet B, Delomenie C, Nicolas V, Pallardy M, Tsapis N, Fattal E.

Despite the wide interest raised by lung administration of nanoparticles (NPs) for the treatment of various diseases, little information is available on their effect towards the airway epithelial barrier function. In this study, the potential damage of the pulmonary epithelium upon exposure to poly(lactide-co-glycolide) (PLGA) NPs has been assessed in vitro using a Calu-3-based model of the bronchial epithelial barrier. Positively and negatively charged as well as neutral PLGA NPs were obtained by coating their surface with chitosan (CS), poloxamer (PF68) or poly(vinyl alcohol) (PVA), respectively. The role of NP surface chemistry and charge on the epithelial resistance and mucus turnover, using MUC5AC as a marker, was investigated. The interaction with mucin reduced the penetration of CS- and PVA-coated NPs while the hydrophilic PF68-coated NPs diffused across the mucus barrier leading to a higher intracellular accumulation. Only CS-coated NPs caused a transient but reversible decrease of the trans-epithelial electrical resistance (TEER). None of the NPs formulations increased MUC5AC mRNA expression or the protein levels. These in vitro results highlight the safety PLGA NPs towards the integrity and function of the bronchial airway barrier and demonstrate the crucial role of NPs surface properties to achieve a controlled and sustained delivery of drugs via the pulmonary route.

From Modern Pathology: Snails, slugs, and mesothelioma

Mod Pathol. 2011 Oct 7. doi: 10.1038/modpathol.2011.144. [Epub ahead of print]
Epithelial-mesenchymal transition in malignant mesothelioma.
Fassina A, Cappellesso R, Guzzardo V, Dalla Via L, Piccolo S, Ventura L, Fassan M.
Department of Diagnostic Medical Sciences and Special Therapies, Surgical Pathology and Cytopathology Unit, University of Padova, Padova, Italy.

Epithelial-mesenchymal transition is a physiopathological process by which epithelial cells acquire mesenchymal shape and properties. Malignant mesothelioma is histologically characterized by the concomitant presence of epithelioid and sarcomatoid features, the latter being associated to worse prognosis, thus suggesting a role of epithelial-mesenchymal transition in this dual phenotype. We studied 109 malignant mesotheliomas (58 epithelioid, 26 sarcomatoid, and 25 biphasic) by immunohistochemistry and qRT-PCR analysis, and demonstrated a substantial switch from epithelial markers (E-cadherin, β-catenin, and cytokeratins 5/6) to mesenchymal markers (N-cadherin, vimentin, α-smooth muscle actin, Snail, Slug, Twist, ZEB1, ZEB2, S100A4, MMP2, and MMP9) through epithelioid to biphasic and sarcomatoid histotypes. In agreement with these findings, the ectopic expression of miR-205 (a repressor of ZEB1 and ZEB2 expression) in MeT-5A (mesothelial cell line), H2452 (an epithelioid malignant mesothelioma cell line) and MSTO-211H (a biphasic malignant mesothelioma cell line) not only induced a significant reduction of ZEB1 and ZEB2 and a consequent up-regulation of E-cadherin gene expression, but also inhibited migration and invasion. Moreover, miR-205 was significantly down-regulated in biphasic and sarcomatoid histotypes (qRT-PCR and in situ hybridization analyses). Collectively, our findings indicate that epithelial-mesenchymal transition has a significant part in the morphological features of malignant mesothelioma. In particular, miR-205 down-regulation correlated significantly with both a mesenchymal phenotype and a more aggressive behavior.

From Seoul: Health care financing in Asia

Asia Pac J Public Health. 2011 Sep;23(5):651-61.
Health care financing in Asia: key issues and challenges.
Kwon S.
Seoul National University, Seoul, South Korea.

This article examines the major elements of health care financing such as financial risk protection, resource generation, resource pooling, and purchasing and payment; provides key lessons; and discusses the challenges for health care financing systems of Asian countries. With the exception of Japan, Korea, Taiwan, and Thailand, most health care systems of Asia provide very limited financial risk protection. The role of public prepaid schemes such as tax and social health insurance is minimal, and out-of-pocket payment is a major source of financing. The large informal sector is a major challenge to the extension of population coverage in many low-income countries of Asia, which must seek the optimal mix of tax subsidy and health insurance for universal coverage. Implementation of effective payment systems to control the behavior of health care providers is also a key factor in the success of health care financing reform in Asia.

From JAMA: Tension between evidence-based medicine and health advocacy groups

JAMA. 2011 Oct 5;306(13):1443-4; author reply 1444-5.
Evidence-based practice and health advocacy organizations.
Johnson LB, Warren BE.

Comment on: JAMA. 2011 Jun 22;305(24):2569-70.

"Both population-based recommendations and individualized decision making can play a role in evidence-based health care, depending on whether the science is uncertain or involves trade-offs contingent on patient values and preferences. Preserving patient choice within the context of evidence-based decision aids improves patient adherence and health outcomes and reduces rates of invasive elective surgery and the use of menopausal hormones and prostate-specific antigen screenings. Whereas many medical professionals are wary of consumers, many consumers distrust EBM and believe it is vulnerable to corruption by stakeholders seeking to control costs and take away personal choice and individualized care."

From U Colorado: Ethnic differences in nonalcoholic liver disease

Hepatology. 2011 Oct 10. doi: 10.1002/hep.24726. [Epub ahead of print]
Ethnicity and nonalcoholic fatty liver disease.
Bambha K, Belt P, Abraham M, Wilson LA, Pabst M, Ferrell L, Unalp-Arida A, Bass N; For the NASH CRN Research Group.
University of Colorado Denver, Aurora, CO.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in the U.S.; however, few data are available about racial and ethnic variation. We investigated relationships between ethnicity, NAFLD severity, metabolic derangements and socio-demographic characteristics in a well-characterized cohort of adults with biopsy-proven NAFLD. Data were analyzed from 1026 adults (≥18 years) in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) from 2004-2008 for whom liver histology data were available within 6-months of enrollment. Associations between ethnicity (Latino versus Non-Latino White) and NAFLD severity (NASH versus Non-NASH histology; and mild versus advanced fibrosis) were explored with multiple logistic regression analysis. We also investigated effect modification of ethnicity on metabolic derangements for NAFLD severity. Within the NASH CRN, 77% (N=785) were Non-Latino White and 12% (N=118) Latino. Sixty-one percent (N=668) had NASH histology and 29% (N=291) had advanced fibrosis. Latinos with NASH were younger, performed less physical activity and had higher carbohydrate intake compared to Non-Latino Whites with NASH. Gender, diabetes, hypertension, hypertriglyceridemia, aspartate aminotransferase (AST), platelets, and the homeostasis model assessment of insulin resistance (HOMA-IR) were significantly associated with NASH. Age, gender, AST, alanine aminotransferase, alkaline phosphatase, platelets, total cholesterol, hypertension and HOMA-IR, but not ethnicity, were significantly associated with advanced fibrosis. The effect of HOMA-IR on risk of NASH was modified by ethnicity: HOMA-IR was not a significant risk factor for NASH among Latinos (Odds Ratio, OR=0.93 [95% Confidence Interval, CI, 0.85-1.02]), but was significant among Non-Latino Whites (OR 1.06, [95%CI 1.01-1.11]).

CONCLUSION: Metabolic risk factors and socio-demographic characteristics associated with NASH differ by ethnicity. Additional insights into NASH pathogenesis may come from further studies focused on understanding ethnic differences in this disease. (HEPATOLOGY 2011.).

From Penn State: School-based obesity prevention programs

Health Educ Res. 2011 Oct 10. [Epub ahead of print]
Translating evidence based violence and drug use prevention to obesity prevention: development and construction of the Pathways program.
Sakuma KL, Riggs NR, Pentz MA.
1Prevention Research Center, College of Health.uman Development, The Pennsylvania State University, 402 Marion Place, University Park, PA 16802, USA.

Effective school-based obesity prevention programs are needed to prevent and reduce the growing obesity risk among youth. Utilizing the evidence-rich areas of violence and substance use prevention, translation science may provide an efficient means for developing curricula across multiple health behaviors. This paper introduces Pathways to Health, a school-based obesity prevention program that was developed by translating from evidence-based violence and drug use prevention programs, Promoting Alternative THinking Strategies and the Midwestern Prevention Project STAR (STAR). We illustrate how a hypothesized underlying behavior change mechanism in two domains of risk behavior, violence and substance use, can be applied to obesity prevention. A 4-step translational process is provided and may be relevant for use in developing other curricula to address multiple health risk behaviors. Practical application and decision points are also provided.

From J Clinical Pathology: Using the right test to get accurate EGFR and KRAS test results

J Clin Pathol. 2011 Oct;64(10):884-92.
EGFR and KRAS quality assurance schemes in pathology: generating normative data for molecular predictive marker analysis in targeted therapy.
Thunnissen E, Bovée JV, Bruinsma H, van den Brule AJ, Dinjens W, Heideman DA, Meulemans E, Nederlof P, van Noesel C, Prinsen CF, Scheidel K, van de Ven PM, de Weger R, Schuuring E, Ligtenberg M.
Department of Pathology, Vrije Universteit Medical Centre, Amsterdam, The Netherlands.

Introduction The aim of this study was to compare the reproducibility of epidermal growth factor receptor (EGFR) immunohistochemistry (IHC), EGFR gene amplification analysis, and EGFR and KRAS mutation analysis among different laboratories performing routine diagnostic analyses in pathology in The Netherlands, and to generate normative data.

Methods In 2008, IHC, in-situ hybridisation (ISH) for EGFR, and mutation analysis for EGFR and KRAS were tested. Tissue microarray sections were distributed for IHC and ISH, and tissue sections and isolated DNA with known mutations were distributed for mutation analysis. In 2009, ISH and mutation analysis were evaluated. False-negative and false-positive results were defined as different from the consensus, and sensitivity and specificity were estimated.

Results In 2008, eight laboratories participated in the IHC ring study. In only 4/17 cases (23%) a consensus score of ≥75% was reached, indicating that this analysis was not sufficiently reliable to be applied in clinical practice. For EGFR ISH, and EGFR and KRAS mutation analysis, an interpretable result (success rate) was obtained in ≥97% of the cases, with mean sensitivity ≥96% and specificity ≥95%. For small sample proficiency testing, a norm was established defining outlier laboratories with unsatisfactory performance.

Conclusions The result of EGFR IHC is not a suitable criterion for reliably selecting patients for anti-EGFR treatment. In contrast, molecular diagnostic methods for EGFR and KRAS mutation detection and EGFR ISH may be reliably performed with high accuracy, allowing treatment decisions for lung cancer.

From MD Anderson: Small cell lung cancer treatments

Nat Rev Clin Oncol. 2011 Jun 21;8(10):611-9. doi: 10.1038/nrclinonc.2011.90.
Novel strategies for the treatment of small-cell lung carcinoma.
William WN Jr, Glisson BS.
Department of Thoracic and Head and Neck Medical Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 432, Houston, TX 77030, USA.

Small-cell lung cancer (SCLC) is a disease with a poor prognosis and limited treatment options. Over the past 30 years, basic and clinical research have translated to little innovation in the treatment of this disease. The Study of Picoplatin Efficacy After Relapse (SPEAR) evaluated best supportive care with or without picoplatin for second-line SCLC treatment and failed to meet its primary end point of overall survival. As the largest second-line, randomized study in patients with SCLC, SPEAR provides an opportunity to critically examine the drug development model in this disease. In this Review, we discuss the current standard approach for the management of SCLC that progresses after first-line therapy, analyze the preliminary data that supported the evaluation of picoplatin in this setting, and critically evaluate the SPEAR trial design and results. Lastly, we present advances in the understanding of the molecular biology of SCLC that could potentially inform future clinical trials and hopefully lead to the successful development of molecular targeted agents for the treatment of this disease.

Counterintuitive study from Norway showing lung cancer patients with diabetes have increased survival. Need more studies on this.

J Thorac Oncol. 2011 Sep 29. [Epub ahead of print]
Prolonged Survival in Patients with Lung Cancer with Diabetes Mellitus.
Hatlen P, Grønberg BH, Langhammer A, Carlsen SM, Amundsen T.
*Department of Thoracic Medicine, St. Olavs Hospital HF, Trondheim University Hospital, Trondheim, Norway; †Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; ‡Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; §Department of Oncology, St. Olavs Hospital HF, Trondheim University Hospital, Trondheim, Norway; ∥Department of Public Health and General Practice, Faculty of Medicine, HUNT Research Center, Norwegian University of Science and Technology, Levanger, Norway; ¶Department of Endocrinology, St. Olavs Hospital HF, Trondheim University Hospital, Trondheim, Norway; and #Department of Cancer Research and Molecular Medicine, Unit for Applied Clinical Research, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

Patients with lung cancer have a high frequency of comorbidity. Data on the impact of diabetes mellitus, the most frequent endocrine disorder, on the prognosis of lung cancer are conflicting. The aim was to investigate the impact of diabetes mellitus on survival in lung cancer.

We analyzed data from a cohort, the Nord-Trøndelag Health Study (HUNT study) linked to the Norwegian Cancer Registry and controlled the results using two lung cancer studies, the Pemetrexed Gemcitabine study and the Norwegian Lung Cancer Biobank. Survival in lung cancer with and without diabetes mellitus was compared using the Kaplan-Meier method and Cox regression model for each study and the studies combined.

One thousand six hundred seventy-seven cases of lung cancer were included, 1031 from HUNT study, 436 from the Pemetrexed Gemcitabine study, and 210 from the Norwegian Lung Cancer Biobank registry, and among these 77 patients had diabetes mellitus. In the combined analysis, patients with lung cancer with diabetes mellitus had increased survival compared with those without (p = 0.005). The 1-, 2-, and 3-year survival in patients with lung cancer with and without diabetes mellitus were 43% versus 28%, 19% versus 11%, and 3% versus 1%, respectively. Adjusting for age, gender, histology, and stage of disease in the Cox regression model, the hazard ratio for survival in patients with lung cancer with diabetes mellitus was 0.55 (95% CI, 0.41-0.75) as compared with without.

Patients with lung cancer with diabetes mellitus have an increased survival compared with those without diabetes mellitus.

Associations between changes in quality of life and survival after lung cancer surgery

J Thorac Oncol. 2011 Sep 29. [Epub ahead of print]
Associations Between Changes in Quality of Life and Survival After Lung Cancer Surgery.
Möller A, Sartipy U.
*Karolinska Institutet; †Department of Cardiothoracic Surgery and Anesthesiology, Karolinska University Hospital; and ‡Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

The aim of this study was to analyze the association between changes in quality of life and survival after lung cancer surgery.

In a prospective population-based cohort study, quality of life was estimated using the Medical Outcomes Study 36-Item Short Form (SF-36) questionnaire before and 6 months after lung cancer surgery. Cox regression models adjusting for potential confounding factors were used to analyze the association between baseline SF-36 scores and changes in SF-36 scores and survival.

A SF-36 questionnaire was distributed to 249 patients at baseline. We excluded 79 patients with histopathology other than primary lung cancer. Six months after surgery, 11 patients died and 18 patients did not return the questionnaire, leaving 141 patients with data from both baseline and follow-up. The baseline SF-36 physical component summary score was significantly associated with survival, but the baseline mental component was not. Declines of 10% in the physical and mental component summary scores from baseline to follow-up were associated with an 18 and 13% higher risk of death, respectively.

Changes in quality of life during 6 months after surgery for lung cancer may provide prognostic information regarding survival.

From Nature: Over-optimism is a brain disease? Wow.

Nat Neurosci. 2011 Oct 9. doi: 10.1038/nn.2949. [Epub ahead of print]
How unrealistic optimism is maintained in the face of reality.
Sharot T, Korn CW, Dolan RJ.
1] Wellcome Trust Centre for Neuroimaging, University College London, London, UK. [2].

Unrealistic optimism is a pervasive human trait that influences domains ranging from personal relationships to politics and finance. How people maintain unrealistic optimism, despite frequently encountering information that challenges those biased beliefs, is unknown. We examined this question and found a marked asymmetry in belief updating. Participants updated their beliefs more in response to information that was better than expected than to information that was worse. This selectivity was mediated by a relative failure to code for errors that should reduce optimism. Distinct regions of the prefrontal cortex tracked estimation errors when those called for positive update, both in individuals who scored high and low on trait optimism. However, highly optimistic individuals exhibited reduced tracking of estimation errors that called for negative update in right inferior prefrontal gyrus. These findings indicate that optimism is tied to a selective update failure and diminished neural coding of undesirable information regarding the future.

Friday, October 7, 2011

From Seoul: EGFR mutations and lung adenocarcinomas

Arch Pathol Lab Med. 2011 Oct;135(10):1329-34.
Histopathologic characteristics of lung adenocarcinomas with epidermal growth factor receptor mutations in the international association for the study of lung cancer/american thoracic society/european respiratory society lung adenocarcinoma classification.
Shim HS, Lee da H, Park EJ, Kim SH.

Context.-The proposed International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinomas has been published. Objective.-To evaluate the correlation between epidermal growth factor receptor mutations and histologic subtypes of lung adenocarcinomas according to the upcoming new classification of lung adenocarcinomas. Design.-Medical records and pathologic slides were reviewed for a total of 107 surgically resected lung adenocarcinomas. All tumors were reclassified according to the predominant histologic subtype, and comprehensive histologic subtyping with semiquantitative assessment of each of the histologic subtypes in increments of 5% was performed. Correlations with epidermal growth factor receptor status were then evaluated. Results.-Epidermal growth factor receptor mutations were found in 54 cases (50.5%). Epidermal growth factor receptor mutations were significantly associated with the micropapillary-predominant subtype (P  =  .02) and with the presence (any amount) of the lepidic component (P  =  .02). Conclusion.-The upcoming International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma is relevant in that it shows a phenotype-genotype correlation. Comprehensive histologic subtyping should be recommended because of the association of particular subtypes with epidermal growth factor receptor mutations.

Confocal laser endomicroscopy: Brave new world for pathology?

Arch Pathol Lab Med. 2011 Oct;135(10):1343-8.
Confocal laser endomicroscopy: a primer for pathologists.
Paull PE, Hyatt BJ, Wassef W, Fischer AH.

Context.-The advent of new endoscopic optical techniques is likely to change pathologists' role in diagnosis. Objective.-To describe how confocal laser endomicroscopy (CLE) works, show its advantages and limitations compared to cytohistologic biopsy, and explore how it may affect the practice of pathology. Data Sources.-Literature review. Conclusions.-Confocal laser endomicroscopy is proving its ability to provide histology-like images of tissues in vivo to help avoid risks and costs of conventional biopsies. Confocal imaging restricts light to 1 plane, emulating a paraffin section, and topical or systemic optical contrast agents allow subcellular resolution. New contrast agents could theoretically permit molecular characterization. In vivo imaging has begun to demonstrate novel, dynamic types of diagnostic features. Decreased histologic biopsies can be anticipated for a few scenarios. Significant limitations of CLE include the inability to create a tissue archive for broad molecular classification, suboptimal contrast agents, small fields of view and shallow penetration, paucity of clinical validation studies, and problems with reimbursement. Confocal laser endomicroscopy exposes new opportunities for pathologists: CLE technologies can be exploited in pathology, and diagnostic criteria expanded based on endoscopists' discoveries. Potential synergy exists between CLE and cytology, allowing the low-magnification diagnostic architectural changes by CLE and cytomorphology to emulate the full diagnostic information in a histologic biopsy while providing an archive of material for molecular or immunohistochemical studies. Confocal laser endomicroscopy will decrease some types of biopsies, but offers an opportunity for pathologists to find new ways to provide value and improve patient care.

From Sanja Dacic: Lung cancer - Morphology or mutational profile?

Arch Pathol Lab Med. 2011 Oct;135(10):1242-3.
Lung carcinoma morphology or mutational profile: that is the question.
Dacic S.

"...[T]he rapid development of extremely powerful, new sequencing technologies may take us into a new area of a pure molecular classification of lung carcinomas."

From the Atlantic-Doctors, manage your messages well

Why Doctors Protest Too Much
OCT 3 2011, 8:59 AM ET 11
We have the right to be political actors -- doctors are citizens too -- but we risk harming the default credibility that comes with the profession if we don't choose our battles carefully

"Doctors are in the cross-hairs of the nation's politics more than ever. We're all being asked to achieve more with less. We must cope with nightmare scenarios precipitated by cracks in the social and healthcare infrastructure so often these days that medical schools insist students become effective patient advocates as well as healers. Practicing good medicine necessitates navigating a minefield of competing interests. Doctors are increasingly tempted to just walk out, to lay down the pen, or to use their power in ways that subvert the system."

"Doctors have achieved their standing in society through the delivery of highly skilled services to those in dire need. When we engage in hotheaded public protest and civil disobedience, we must have a reason that rises to the level of endangering our ability to practice medicine at all, and a clear explanation for how our actions fit into the medical narrative we all share. If we do not manage our messages well, others will interpret our actions for us, and we cannot expect their version to be favorable."