RNA editing study under intense scrutiny : Nature News & Comment

RNA editing study under intense scrutiny 

The idea that RNA is often edited after being transcribed from DNA is a controversial one.

PASIEKA/SCIENCE PHOTO LIBRARY

Medscape: New Medical Admissions Test for New Generation of Physicians

New Medical Admissions Test for New Generation of Physicians

"People who have taken the MCAT see it as an exam that emphasizes physics, chemistry, and math, first and foremost, Darrell Kirch, MD, president and chief executive officer of the Association of American Medical Colleges, said in a video on the association's Web site."

OncoLink launches redesigned website based on search habits and feedback from patients, caregivers

OncoLink launches redesigned website based on search habits and feedback from patients, caregivers:

OncoLink, a free cancer information website developed by experts at the University of Pennsylvania's Abramson Cancer Center has launched a redesigned website based on the search habits and feedback from patients, caregivers and health care providers who use the site.

abstract: Shared Genetic Basis for Breast Cancer and Breast Density

Shared Genetic Basis for Breast Cancer and Breast Density:

" Together, our results show that PMD and breast cancer have a shared genetic basis that is mediated through a large number of common variants."

Percent mammographic breast density (PMD) is a strong heritable risk factor for breast cancer. However, the pathways through which this risk is mediated are still unclear. To explore whether PMD and breast cancer have a shared genetic basis, we identified genetic variants most strongly associated with PMD in a published meta-analysis of five genome-wide association studies (GWAS) and used these to construct risk scores for 3,628 breast cancer cases and 5,190 controls from the UK2 GWAS of breast cancer.

abstract: Phase 1 Dose-Escalation Study of Aflibercept Plus Docetaxel

Phase 1 Dose-Escalation Study of Aflibercept Plus Docetaxel:

Purpose: This phase I study cohort investigated aflibercept in combination with docetaxel in patients with advanced solid tumors.

Materials and Methods: Eligible patients had metastatic or nonresectable cancer for which docetaxel was considered appropriate. Patients received intravenous aflibercept (either 2, 4, 5, 6, 7, or 9 mg/kg) with docetaxel (75 mg/m²) on day 1 every 3 weeks until disease progression or unacceptable toxicity. Primary objectives were to evaluate dose-limiting toxicities (DLT) during cycle 1 and to determine the aflibercept recommended phase II trial dose (RP2D) for combination with docetaxel. Pharmacokinetics, tolerability, and antitumor activity were also investigated.

Results: Fifty-four patients (mean age, 56 y) were enrolled. Most had prior chemotherapy (96%) and most (24.1%) had breast cancer. In the dose-escalation phase (n = 34), there were three DLTs: grade 4 neutropenic infection (2 mg/kg), grade 3 dysphonia (7 mg/kg), and grade 2 hypertension (9 mg/kg). An excess of free-over-bound aflibercept was observed at doses of 5 mg/kg or more. The pharmacokinetics of aflibercept and docetaxel were not modified by coadministration. Aflibercept (6 mg/kg) was defined as the RP2D based on DLT and pharmacokinetic data.
Overall, the most frequent grade 3/4 adverse events (AE) were neutropenia (85.2%), leukopenia (74.1%), hypertension (18.5%), and stomatitis (16.7%). AEs associated with vascular endothelial growth factor blockade included epistaxis (all grades, 83.3%), proteinuria (68.5%), dysphonia (68.5%), and hypertension (53.7%). Seven patients had partial responses, and 32 patients had stable disease (>3 months in 18 patients).

Conclusion: On the basis of findings from this study, aflibercept (6 mg/kg) was the dose recommended for further clinical development. Clin Cancer Res; 18(6); 1743–50. ©2012 AACR.

abstract: Evaluation of Iniparib as a PARP Inhibitor (BRCA2....)

Evaluation of Iniparib as a PARP Inhibitor:

Purpose:

Poly(ADP-ribose) polymerase (PARP) inhibitors are undergoing extensive clinical testing for their single-agent activity in homologous recombination (HR)-deficient tumors and ability to enhance the action of certain DNA-damaging agents. Compared with other PARP inhibitors in development, iniparib (4-iodo-3-nitrobenzamide) is notable for its simple structure and the reported ability of its intracellular metabolite 4-iodo-3-nitrosobenzamide to covalently inhibit PARP1 under cell-free conditions. The present preclinical studies were conducted to compare the actions iniparib with the more extensively characterized PARP inhibitors olaparib and veliparib.

Results:

Consistent with earlier reports, olaparib and veliparib selectively induced apoptosis and inhibited colony formation in cells lacking BRCA2 or ATM. Moreover, like earlier generation PARP inhibitors, olaparib and veliparib sensitized cells to the topoisomerase I poisons camptothecin and topotecan. Finally, olaparib and veliparib inhibited formation of pADPr in intact cells. In contrast, iniparib exhibited little or no ability to selectively kill HR-deficient cells, sensitize cells to topoisomerase I poisons, or inhibit pADPr formation in situ. In further experiments, iniparib also failed to sensitize cells to cisplatin, gemcitabine, or paclitaxel.


Conclusions:

While iniparib kills normal and neoplastic cells at high (>40 μmol/L) concentrations, its effects are unlikely to reflect PARP inhibition and should not be used to guide decisions about other PARP inhibitors.  

Clin Cancer Res; 18(6); 1655–62. ©2012 AACR.

abstract: Impact of Preanalytic Factors on the Design and Application of Integral Biomarkers

Impact of Preanalytic Factors on the Design and Application of Integral Biomarkers:

Molecular assays have been routinely applied to improve diagnosis for the last 25 years. Assays that guide therapy have a similar history; however, their evolution has lacked the focus on analytic integrity that is required for the molecularly targeted therapies of today. New molecularly targeted agents require assays of greater precision/quantitation to predict the likelihood of response, i.e., to identify patients whose tumors will respond, while at the same time excluding and protecting those patients whose tumors will not respond or in whom treatment will cause unacceptable toxicity. The handling of tissue has followed a fit-for-purpose approach focused on appropriateness for diagnostic needs, which is less rigorous than the demands of new molecular assays that interrogate DNA, RNA, and proteins in a quantitative, multiplex manner. There is a new appreciation of the importance and fragility of tissue specimens as the source of analytes to direct therapy. By applying a total test paradigm and defining and measuring sources of variability in specimens, we can develop a set of specifications that can be incorporated into the clinical-care environment to ensure that a specimen is appropriate for analysis and will return a true result. 

abstract: Leveling the Playing Field: Bringing Development of Biomarkers and Molecular Diagnostics up to the Standards for Drug Development

Leveling the Playing Field: Bringing Development of Biomarkers and Molecular Diagnostics up to the Standards for Drug Development

 "....One way to accomplish this is to emphasize phase IV postmarketing, hypothesis-driven clinical trials with biological characterization that would permit an accurate definition of the association of low-prevalence gene alterations with toxicity or response in large cohorts."

Drug data reveal sneaky side effects : Nature News & Comment

Drug data reveal sneaky side effects : Nature 

 Mining of surveillance data highlights thousands of previously unknown consequences when drugs are taken together.

14 March 2012

An algorithm designed by US scientists to trawl through a plethora of drug interactions has yielded thousands of previously unknown side effects caused by taking drugs in combination.
The work, published today in Science Translational Medicine¹, provides a way to sort through the hundreds of thousands of 'adverse events' reported to the US Food and Drug Administration (FDA) each year. “It’s a step in the direction of a complete catalogue of drug–drug interactions,” says the study's lead author, Russ Altman, a bioengineer at Stanford University in California.........“Even if you show a drug is safe in a clinical trial, that doesn’t mean it’s going to be safe in the real world,” says Paul Watkins, director of the Hamner–University of North Carolina Institute for Drug Safety Sciences in Research Triangle Park, North Carolina, who was not involved in the work. “This approach is addressing a better way to rapidly assess a drug’s safety in the real world once it is approved.”.....

abstract: Cancer stem cells and metastasis

Cancer stem cells and metastasis
Publication year: 2012

Seminars in Cancer Biology


Cancer stem cells (CSCs) represent a subpopulation of tumour cells endowed with self-renewal and multi-lineage differentiation capacity but also with an innate resistance to cytotoxic agents, a feature likely to pose major clinical challenges towards the complete eradication of minimal residual disease in cancer patients. Operationally, CSCs are defined by their tumour-propagating ability when serially transplanted into immune-compromised mice and by their capacity to fully recapitulate the original heterogeneity of cell types observed in the primary lesions they are derived from. CSCs were first identified in hematopoietic malignancies and later in a broad spectrum of solid tumours including those of the breast, colon and brain. Notably, several CSC characteristics are relevant to metastasis, such as motility, invasiveness and, as mentioned above, resistance to DNA damage-induced apoptosis. Here, we have reviewed the current literature on the relation between CSCs and metastasis formation. Preliminary studies on cancer cell lines and patient-derived material suggest a rate-limiting role for stem-like cells in the processes of tumour cell dissemination and metastasis formation. However, additional studies are needed to deliver formal proof of their identity as the cell of origin of recurrences at distant organ sites. Nevertheless, several studies have already provided pre-clinical evidence of the efficacy of novel therapies directed against disseminated CSCs.

abstract: Cancer during pregnancy: perinatal outcome after in utero exposure to chemotherapy.

Cancer during pregnancy: perinatal outcome after in utero exposure to chemotherapy

Cancer during pregnancy: perinatal outcome after in utero exposure to chemotherapy.

Abstract

OBJECTIVES:

To study the outcome of pregnancies complicated by malignant disease, in particular neonatal morbidity and mortality after in utero exposure to chemotherapy.

METHODS:

This prospective study included 118 patients diagnosed with malignant disease for the first time during pregnancy over an 8-year period (March 2003-March 2011). Outcome of neonates born to mothers who received chemotherapy during pregnancy was studied and compared with a control group.

RESULTS:

The commonest cancer type diagnosed during pregnancy (56/118 = 47.45 %) was breast carcinoma followed by lymphoma/leukemia (32 = 27.12 %). Gynecological tumors (all ovarian) represented 10.16 %, soft tissue tumors 5.08 %, colorectal 4.23 %, thyroid 2.54 % and others 3.38 %. Sixty-one (51.64 %) women received chemotherapy (average 3 ± 2 cycles) during the second and third trimesters. The incidence of neonatal survival, preterm birth, small for gestational age and congenital malformations was not significantly different between women who received chemotherapy during pregnancy and the control group. Five (4.23 %) women with advanced disease died during or shortly after termination of pregnancy.

CONCLUSION:

In utero exposure to chemotherapy during the second and third trimesters of pregnancy carries minimal morbidity to the unborn fetus.

discussion (U.S.) : Clinical Pathways for Oncology: More Rigor Needed When Evaluating Models

Clinical Pathways for Oncology: More Rigor Needed When Evaluating Models

Wiley: Cochrane Review - Specialist cancer care may improve patient outcomes (ovarian/gyn cancers)

Wiley: Specialist cancer care may improve patient outcomes

The Cochrane Library

 More Press Releases related to this journal

Vol 2012 (4 Issues in 2012)

Specialist cancer care may improve patient outcomes

Survival rates for cancer patients may be improved by treatment in specialised cancer centres, according to Cochrane researchers. In a review of recent studies, they found that women diagnosed with gynaecological cancer lived longer when treated in specialist compared to non-specialist units.
In the past, cancer patients were often treated by non-specialist surgeons and hospitals. This is changing and in developed countries, most cancer care is now organised into networks of specialised centres, with on-site experts and specialised nursing staff. This centralised approach, although costly, may help improve outcomes for patients.
The review focused on data from five studies, altogether involving more than 62,000 women who were treated from the late 1990s onwards. Over 48,000 of the participants were involved in one study carried out in 2009, whilst the smallest study involved just 250. Due to clinical differences between the studies, the researchers combined the data in different ways. Incorporating three studies and over 50,000 women with gynaecological cancer, one analysis showed that women treated at teaching centres or regional cancer centres lived longer compared to those treated at community or general hospitals. An alternative combination of three of the studies, involving over 9,000 women with ovarian cancer, showed that those treated at institutions with on-site gynaecologists lived longer compared to those treated at community or general hospitals.
“We found consistent evidence for specialist treatment prolonging survival rates in women with gynaecological cancer,” said lead researcher, Professor Yin Ling Woo of the University of Malaya Cancer Research Institute, University of Malaya, in Kuala Lumpur, Malaysia. “The effect seemed to be strongest for ovarian cancer, although most evidence came from developed countries.”
The researchers estimate that survival rates could be improved by around 10%, although uncertainties in the data mean the actual figure could range between 1% and 18%. Better designed studies are needed to confirm the results. All five studies included in the review used electronic records to identify patients after they had received treatment, meaning it was difficult to be sure that the centralised and de-centralised treatment groups were similar.
“Ideally, women should be allocated to specialist and non-specialist treatment groups in advance to ensure that there is no bias in the data,” said Professor Woo. “These higher quality trials are needed to assess whether the extra cost is worthwhile, especially as many countries have limited resources for specialist care.”

interactive: First Ever Local Area Health System Scorecard Finds Significant Differences in Access, Costs, Quality, and Outcomes Within States and Among Nation's Biggest Cities

First Ever Local Area Health System Scorecard Finds Significant Differences in Access, Costs, Quality, and Outcomes Within States and Among Nation's Biggest Cities:

In the first scorecard measuring how 306 local U.S. areas are doing on key health care indicators such as insurance coverage, preventive care, and mortality rates, researchers at The Commonwealth Fund found significant differences between the best- and worst-performing localities.

Bloomberg News: Canadian Hospitals That Spend More on Patients Get More - Businessweek

Canadian Hospitals That Spend More on Patients Get More - Businessweek

Bloomberg News

Canadian Hospitals That Spend More on Patients Get More

By Drew Armstrong on March 13, 2012

Canadian hospitals that spent the most on patient care may be getting a bigger bang for their buck than their U.S. counterparts, researchers suggested.

A study reported today in the Journal of the American Medical Association compared patient results between Canadian hospitals that spent more on care, and those that spent less. It found patients in the first category had lower death rates and were less likely to be admitted to intensive care.
Research on the U.S. health-care system, however, has shown that higher spending at hospital systems doesn’t guarantee better results, according to the study’s author, Therese Stukel.
“When we spend more, and when we place these specialized resources, we’re doing it in an efficient way,” said Stukel, a senior scientist at the Institute for Clinical Evaluative Sciences in Toronto, in a telephone interview. “That’s in contrast to the U.S.”
Under Canada’s system of universal health care, patients at high-spend hospitals had longer lengths of stay and more specialist visits, the study found. That’s because the health plan in Canada, where per capita health expenditures are 57 percent of those in the U.S., better allocates expensive specialists and technology, Stukel said.
While the U.S. has a 3- to 4-times higher per capita supply of expensive, specialized technology, such as MRIs, it has a similar supply of hospital beds and nurses as Canadian hospitals, according to the study.

Dartmouth Atlas

The Canadian findings may help to better understand studies such as the Dartmouth Atlas of Healthcare, a 20-year research project that has documented variations in how medical resources are distributed in the U.S. The data has shown that the parts of the country that spent the most per patient have worse patient outcomes than low-spending areas.
Today’s study “breaks through the generalization,” that all spending is bad, said David Goodwin, co-principal investigator at the Dartmouth Atlas, in a telephone interview. “It’s important that we look at spending in the aggregate and where more is better, and where more is worse.”
The U.S. health-care law signed in 2010 has several components designed to slow spending and have U.S. hospitals emulate the coordinated care of their Canadian brethren. Those measures haven’t been without controversy. Republicans are seeking to repeal the law’s Independent Payment Advisory Board, which will cut Medicare rates with limited oversight from lawmakers.
The law’s Accountable Care Organizations have Medicare pay hospitals bonuses when they coordinate to provide better care and save money. Health systems are penalized if they overspend or produce worse outcomes.

Misinterpreting Dartmouth

In an editorial accompanying the research, Karen Joynt and Ashish Jha, researchers at the Harvard School of Public Health, said some policymakers have drawn wrong conclusions from the Dartmouth data.
“What Dartmouth investigators have documented through careful work is that dysfunctional systems produce expensive, poor-quality care,” Joynt and Jha wrote.
Stukel’s Canadian study examined nearly 400,000 cases of heart attack, heart failure, hip fracture and colon cancer in Ontario hospitals over 10 years, looking at whether the patients died or were readmitted.
The most expensive Canadian hospitals in the study spent about twice as much per patient than their lower-spending counterparts. For every condition the study looked at, patients died less often and were readmitted less often at the more expensive hospitals.

Expensive Hospitals

Those more expensive hospitals had something else in common -- they were often academic hospitals, or community hospitals that saw more patients than others, they had cancer centers attached, lots of specialists on staff, performed more advanced procedures, had more technology and nurses that spent more time with patients. Patients were also more likely to get a follow-up visit within a year and get more intensive discharge care.
That’s not to say that putting more money into lower- spending Canadian hospitals would produce better care there.
“It would be facile to interpret this study as demonstrating that higher spending is causally related to better outcomes and providing more money to lower spending hospitals would necessarily improve their outcomes,” Stukel and her co- authors said in the study.
Instead, it’s better care coordination and spending on the right types of care that improve outcomes, as well as limited budgets on overall spending, Stukel said.

Coordinated Systems

Stukel said she doesn’t advocate a Canadian-style system of universal coverage in the U.S. She said that coordinated U.S. managed care systems, like Kaiser Permanente in California, Intermountain Healthcare in Salt Lake City, and Geisinger Health System in Pennsylvania are models the rest of the country emulate.
She predicts that Canadian hospitals will likely use her study to ask the government there for more money, even though that’s not the point of her research.

“If we put more dollars into the acute care system, it might still improve, it might peak,” she said. “It’s not just putting money into the system, it’s where we spend it.”

Comments needed - exp March 15th - Patients: Your Researcher Will See You Now!--Kathleen O'Malley

 CLICK HERE TO SUBMIT COMMENTS to PCORI.

Patients: Your Researcher Will See You Now!--Kathleen O'Malley:

Guest blogger Susan Woods, a physician and SPM board member, urges patients to help shape PCORI’s draft National Priorities for Research and initial Research Agenda, and offers her own comments here. The public comment period ends at 11:59 pm EST on March 15.

Patient voices are needed now!

The Patient Centered Outcomes Research Institute (PCORI) is soliciting input about patient-centered outcomes research. We blogged about this when they were seeking people to apply to be participants.

           Now the deadline to submit your comments is almost here.

PCORI is an independent, non-profit organization established by Congress through the 2010 Patient Protection and Affordable Care Act. Its mission is to help people make informed health care decisions by producing and promoting high integrity, evidence-based information that comes from research guided by patients, caregivers, and the broader health care community.
The legislation creating this group, governed by a 21-member board, is fascinating. Patient advocates must be part of the process: “For identifying research priorities, they take into account…a number of factors including variations and health disparities, the potential for new evidence to improve patient health, well-being, and the quality of care…as well as patient needs, outcomes, and preferences, the relevance to patients and clinicians in making informed health decisions….”
This is enlightenment in medical research. The law also states:
“All funded studies will have a strong orientation to the patient perspective and all will have patients involved in the development of the research, its governance and oversight, and its dissemination strategy.”

Editorial: The Relationship Between Cost and Quality, No Free Lunch - March 14, 2012 — JAMA + link to original article

The Relationship Between Cost and Quality, March 14, 2012, Joynt and Jha 307 (10): 1082 — JAMA
 Editorial: The Relationship Between Cost and Quality 

No Free Lunch

Since this article does not have an abstract, we have provided the first 150 words of the full text. (Blogger's Note: subscription required to view $$$)

"For the past 30 years, research from investigators at Dartmouth has demonstrated large and persistent variations in costs and quality across the US health care system. Beyond simply showing that cost and quality vary by geography, the Dartmouth Atlas has demonstrated that in many communities, care is so fragmented and ineffective that greater spending on Medicare beneficiaries often leads to worse outcomes^1,2 because some patients receive services that are redundant and low value and that may even have substantial risks. 

However, some US policy makers have misinterpreted the Dartmouth research and in the troves of data have found what they believe to be a free lunch: given the inverse relationship between costs and quality, it follows that it should be possible to simultaneously reduce spending and improve care. Although this notion is attractive, much of the subtlety of the Dartmouth work has been lost in translation. What ....."

[Full Text of this Article] (subscription required to view)

Related article

• Association of Hospital Spending Intensity With Mortality and Readmission Rates in Ontario Hospitals  
   JAMA. 2012;307(10):1037-1045.doi:10.1001/jama.2012.265
  • Abstract
  • Full Text
  • Full Text (PDF)
  • eSupplement
  • Author Video/Audio Interview
  • JAMA Report Video

YouTube: Interview with Dr Stukel, Author of Hospital Spending Intensity and Patient Outcomes

Also, planning a comparison study with London School of Economics and Havard

open access: Association of Hospital Spending Intensity With Mortality and Readmission Rates in Ontario (Canada) Hospitals, March 14, 2012 — JAMA

 Blogger's Note: universal healthcare system, this study included colorectal cancer patients, comparisons between Canadian/U.S. systems, note authors' affiliations

Association of Hospital Spending Intensity With Mortality and Readmission Rates in Ontario Hospitals, March 14, 2012

"Our objective was to assess whether acute care patients admitted to Canadian hospitals that treat patients more intensively (and at higher cost) have lower mortality and readmissions and higher quality of care.......We studied 4 common conditions that have moderate to high incidence and mortality, that can be validly ascertained using health administrative data, and for which treatment follows relatively standard protocols. "

Design Overview

We undertook a longitudinal cohort study of patients hospitalized with selected acute clinical conditions in Ontario, Canada, and assessed the content, quality, and outcomes with respect to “exposure” to the index hospital's medical spending intensity. Medical intensity is defined as the quantity of medical care provided overall to similarly ill patients and is a marker of a hospital's propensity to treat similarly ill patients more (or less) intensively. It reflects the component of spending variation attributable to practice style rather than to differences in illness or price.

Because sicker patients use more services, higher-spending hospitals may appear to have worse outcomes, in part because patients are more severely ill. We used several techniques to remove this potential “reverse causality,” as in previous work.1,2​,3,4

 COMMENT

We found that higher hospital spending intensity was associated with better survival, lower readmission rates, and better quality of care for seriously ill, hospitalized patients in Ontario in a universal health care system with more selective access to medical technology. Higher-spending hospitals were higher-volume teaching or community hospitals with high-volume or specialist attending physicians and having specialized programs, such as regional cancer centers, and specialized services, such as on-site cardiac catheterization, cardiac surgery, and diagnostic imaging facilities. The study also points to plausible mechanisms through which higher spending may be associated with better outcomes. 

Benefits appeared early, suggesting an acute-phase hospital effect. For acute conditions, timely access to preoperative and in-hospital specialist care, skilled nursing staff, rapid response teams, cardiac high-technology services, and regional cancer centers, all found in the higher-spending systems, are related to better outcomes.^{21​,27,34​,35,36​,37,38​,39} These systems also provided consistently, but not strikingly, higher levels of evidence-based care and collaborative ambulatory care, both shown to improve care.^{22​,23,40​} Higher spending on evidence-based services delivered in the acute phase of care for severely ill hospitalized patients—by far the largest component of spending for our cohorts—is indeed likely to be beneficial. 

It would be facile to interpret this study as demonstrating that higher spending is causally related to better outcomes and that providing more money to lower-spending hospitals would necessarily improve their outcomes. Higher-spending hospitals differed in many ways, such as greater use of evidence-based care, skilled nursing and critical care staff, more intensive inpatient specialist services, and high technology, all of which are more expensive. 

To place the study in context, the United States has a 3- to 4-times higher per capita supply of specialized technology, such as computed tomography and magnetic resonance imaging scanners, but a similar supply of acute care beds and nurses.⁴¹ Ontario 2001 population rates of cardiac testing and revascularization lagged behind corresponding 1992 US rates and paralleled the supply of cardiologists and catheterization facilities.^{42​,43,44​} It is therefore possible that Canadian hospitals, with fewer specialized resources, selective access to medical technology, and global budgets, are using these resources more efficiently, especially during the inpatient episode for care-sensitive conditions.^45,46​ Canada's health care expenditures per capita are about 57% of those in the United States.⁴⁷ At this spending level, there might still be a positive association between spending and outcomes. For example, the same-day PCI rate for patients with AMI in low-intensity hospitals in 2008 was 3.5%, leaving room for improvement. This pattern is consistent with studies in the United States showing a positive association between spending and outcomes among low-intensity hospitals or regions but no association at average or higher intensity levels.^5​,6

Strengths of the study include the population-based, longitudinal cohort design; the consistency of findings across cardiac, cancer, medical, and surgical patients; the examination of plausible clinical mechanisms whereby higher intensity may be associated with better outcomes; and the examination of readmissions. The “look-back” (EOL-EI) and “look-forward” (AC-EI) measures of spending intensity were highly correlated and produced similar findings, as in US studies.²

 ^​

Several limitations should be considered. Because the design precludes strong inferences about causation, we cannot know which components of care may have led to better outcomes. In observational studies, comparisons of exposure groups may be biased because of unobserved selection bias.¹³ It is unlikely that the findings are the result of unmeasured case mix, because patients in higher-spending hospitals had similar or higher illness severity at admission, which would, if anything, bias toward finding worse outcomes. We cannot rule out the possibility that higher-intensity hospitals coded more aggressively, but there is less incentive to do so in a system with global hospital budgets. Although admission severity would be determined more accurately using clinical detail from medical charts, previous work has shown high concordance between risk-adjusted hospital outcomes using chart and administrative data.^48​,49 Canadian data distinguish between comorbidities present at admission and complications, leading to improved admission severity coding. The EOL-EI has been critiqued for the purpose of estimating hospital efficiency^50​,51 but is used here simply to distinguish high- and low-intensity hospitals, as in other US studies.^{1​,2,3​,4} The findings may not generalize to chronic conditions, for which avoiding exacerbations of disease that lead to hospitalization through coordinated ambulatory care is key. The findings also may not generalize to jurisdictions in which hospital resources are more abundant and are used in cost-effective as well as cost-ineffective ways, leading to inefficiency.^45​,46

This study shows that in Ontario, a province with global hospital budgets and fewer specialized health care resources than the United States, outcomes following an acute hospitalization are positively associated with higher hospital spending intensity. Higher spending intensity, in turn, is associated with greater use of specialists, better patient care, and more use of advanced procedures. These results suggest that it is critical to understand not simply how much money is spent but whether it is spent on effective procedures and services. 

pdf file: 

http://jama.ama-assn.org/content/307/10/1037.full.pdf

open access: PLoS Medicine: A Comparison of DSM-IV and DSM-5 Panel Members' Financial Associations with Industry: A Pernicious Problem Persists

PLoS Medicine: A Comparison of DSM-IV and DSM-5 Panel Members' Financial Associations with Industry: A Pernicious Problem Persists

 Introduction

All medical subspecialties have been subject to increased scrutiny about the ways by which their financial associations with industry, such as pharmaceutical companies, may influence, or give the appearance of influencing, recommendations in review articles [1] and clinical practice guidelines [2]. Psychiatry has been at the epicenter of these concerns, in part because of high-profile cases involving ghostwriting [3],[4] and failure to report industry-related income [5], and studies highlighting conflicts of interest in promoting psychotropic drugs [6],[7]. The revised Diagnostic and Statistical Manual of Mental Disorders (DSM), scheduled for publication in May 2013 by the American Psychiatric Association (APA), has created a firestorm of controversy because of questions about undue industry influence. Some have questioned whether the inclusion of new disorders (e.g., Attenuated Psychotic Risk Syndrome) and widening of the boundaries of current disorders (e.g., Adjustment Disorder Related to Bereavement) reflects corporate interests [8],[9]. These concerns have been raised because the nomenclature, criteria, and standardization of psychiatric disorders codified in the DSM have a large public impact in a diverse set of areas ranging from insurance claims to jurisprudence. Moreover, through its relationship to the International Classification of Diseases [10], the system used for classification by many countries around the world, the DSM has a global reach.........

Summary Points

• The American Psychiatric Association (APA) instituted a financial conflict of interest disclosure policy for the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM).
• The new disclosure policy has not been accompanied by a reduction in the financial conflicts of interest of DSM panel members.
• Transparency alone cannot mitigate the potential for bias and is an insufficient solution for protecting the integrity of the revision process.
• Gaps in APA's disclosure policy are identified and recommendations for more stringent safeguards are offered.

Stop the Multivitamin Madness - Cancerwise | Cancer blog from MD Anderson Cancer Center

Stop the Multivitamin Madness - Cancerwise | Cancer blog from MD Anderson Cancer Center

Drug Shortages > Current Drug Shortages - Ondansetron Injection 2 mg/mL

Drug Shortages > Current Drug Shortages

Disruptive Women in Health Care » Blog Archive » What Does It Matter to You: Patient Activation and Good Health Outcomes (on attitudes, knowledge, communication and abuse??)

Disruptive Women in Health Care » Blog Archive » What Does It Matter to You: Patient Activation and Good Health Outcomes

Social Networking Sites and Politics - Pew Research Center

Social Networking Sites and Politics - Pew Research Center
 
Postings on social networking sites reveal surprises for many users when it comes to the political views of their friends. Nearly four-in-ten users discovered through postings by friends that their political beliefs were different than they thought. A small percentage of users blocked, unfriended or hidden someone on the site because their postings were too frequent or they disagreed with them.
Three-quarters of social networking site users say their friends post at least some content related to politics on the sites from time to time. They amount to 40% of the entire adult population.
For some users politics is an off-limits subject. Some 22% of SNS users say they have decided not to post political comments or links to political material because they were worried it might upset or offend someone.
Read the full report which includes:

• Users' responses by partisan affiliation and ideology
• How users have responded to political content they do not like
• Frequency of agreement and disagreement among "friends"

open access: Children and young adults with parents with cancer: a population-based study

Children and young adults with parents with cancer: a population-based study

Background: 
Today many people are choosing to have children later in life. Additionally, the use of sophisticated diagnostic tools and screening modalities has increased over recent years. Because of these factors, cancer is being diagnosed more frequently during the child-rearing years. Sociodemographic and cancer-related information on families and minor (0–18 years) and young adult (YA) (19–25 years) children experiencing parental cancer is scarce, but this information is vital for healthcare initiatives aimed toward those potentially adversely affected. Therefore, the aim of this study was to describe features of families and minor and YA children affected by parental cancer in a nationwide population.
  
Conclusion: 
Adequate assistance for minor and YA children affected by parental cancer requires knowledge of their number and characteristics. Parental cancer is more common than previously suggested: the annual incidence of parental cancer for children under 18 years of age is 0.3%, whereas approximately 4% of children aged 0–25 years have or have had parents diagnosed with cancer, corresponding to a population prevalence of 1.4%. Around 20% of these children experience parental death, and surveys of live respondents should account for this.

abstract: Management and prognosis of endometrioid borderline tumors of the ovary

Management and prognosis of endometrioid borderline tumors of the ovary
Source: Surgical Oncology

Background 
The Endometrioid Borderline ovarian tumor (EBOT) is the third most common histological subtype of borderline ovarian tumors. Very little is known about the prognosis and management of this entity. This paper consists of a review of the literature and an analysis of clinical series.

Study design 
A review of the literature on this topic was conducted identifying series reporting consecutive cases of EBOT using 2 search engines (MEDLINE and Pubmed). Personal data on this topic have been included and concern a series of patients treated between 1985 and 2009 for EBOT. These cases included in this series had complete data concerning patient management and follow-up >12 months.

Results 
16 patients were studied: 7 had been treated conservatively and 9 radically. All 16/16 patients had stage I disease at the initial diagnosis but one patient had also developed synchronous endometrioid adenocarcinoma of the uterine corpus. After a median time of 24 months (range, 12–132) post treatment, one (1/16) patient had developed two recurrences. She remains disease-free 42 months after the end of treatment of the last recurrence. These data were compared to the results of 4 series previously reported in the literature. In fact, the present series reports on the first recurrence in EBOT (which was an invasive lesion).

Conclusion 
Endometrioid borderline ovarian tumors carry a good prognosis. Most EBOT tumors are stage I, therefore surgical staging is not necessary in most of the cases. However, uterine curettage is required in cases of uterine preservation.

open access: JCO Editorial: Palliative Sedation: When and How?

 Palliative Sedation: When and How?

".....As with many other medical interventions, the controversy that
surrounds palliative sedation is not linked to the question of “yes or
no?” but rather, “when and how?”"

abstract and podcast: Palliative Sedation in End-of-Life Care and Survival: A Systematic Review [Palliative and Supportive Care] (unbearable suffering)

 Blogger's Note: search blog for other articles regarding palliative sedation

 
Palliative Sedation in End-of-Life Care and Survival: A Systematic Review [Palliative and Supportive Care]:

Purpose
Palliative sedation is a clinical procedure aimed at relieving refractory symptoms in patients with advanced cancer. It has been suggested that sedative drugs may shorten life, but few studies exist comparing the survival of sedated and nonsedated patients. We present a systematic review of literature on the clinical practice of palliative sedation to assess the effect, if any, on survival.

 Conclusion
Even if there is no direct evidence from randomized clinical trials, palliative sedation, when appropriately indicated and correctly used to relieve unbearable suffering, does not seem to have any detrimental effect on survival of patients with terminal cancer. In this setting, palliative sedation is a medical intervention that must be considered as part of a continuum of palliative care.
  
                            ~~~~~~~~~~~~~~~~~~~~~~~~

Users can play the podcast directly in the audio player embedded below. If Flash is disabled on your browser, you can save the file directly to your computer or open on your mobile device by clicking on "download file."

Sedation for the Management of Refractory Suffering
by Nathan Cherny


(Download file - duration 0:10:41, file size 9.80 MB)
This podcast presenter indicated no conflicts of interest.

abstract: Web-Based Tailored Education Program for Disease-Free Cancer Survivors With Cancer-Related Fatigue: A Randomized Controlled Trial

Web-Based Tailored Education Program for Disease-Free Cancer Survivors With Cancer-Related Fatigue: A Randomized Controlled Trial
  
Abstract

Purpose 

To determine whether an Internet-based tailored education program is effective for disease-free cancer survivors with cancer-related fatigue (CRF). 

Conclusion 

An Internet-based education program based on NCCN guidelines and TTM may help patients manage CRF.

JCO Letter: Is It Possible to Identify Clinically Useful Prognostic Groups for Patients With Desmoid Tumors

Is It Possible to Identify Clinically Useful Prognostic Groups for Patients
With Desmoid Tumors

 TO THE EDITOR: 

In their recent article, Salas et al1 report the results of a retrospective study of 426 patients with extra-abdominal desmoid tumors from 24 participating centers.Toour knowledge, this is the largest such cohort ever reported. Three hundred seventy patients (86.9%) had surgical treatment initially; a wait-and-see policy was adopted for only 27 patients (6.3%). Patients who had non–lifethreatening tumors or who were at risk for mutilation were selected for the wait-and-see approach. Detailed characteristics of the patients in the wait-and-see group were not provided. Factors that had a significant impact on progression-free survival were age, tumor size, and tumor site in multivariate analysis. It can be understood that there are different prognostic subgroups of patients with desmoid tumors who could benefit from different therapeutic strategies...."

Salas S, Dufresne A, Bui B, et al: Prognostic factors influencing progressionfree survival determined from a series of sporadic desmoid tumors: A wait-andsee policy according to tumor presentation. J Clin Oncol 29:3553-3558, 2011

JCO Letter: Is It Possible to Identify Clinically Useful Prognostic Groups for Patients With Desmoid Tumors

JCO.2011.39.8636.full.pdf (application/pdf Object)

"TO THE EDITOR:
In their recent article, Salas et al1 report the results of a retrospective study of 426 patients with extra-abdominal desmoid tumors from 24 participating centers.Toour knowledge, this is the largest such cohort ever reported. Three hundred seventy patients (86.9%) had surgical treatment initially; a wait-and-see policy was adopted for only 27 patients (6.3%). Patients who had non–lifethreatening tumors or who were at risk for mutilation were selected for the wait-and-see approach. Detailed characteristics of the patients in the wait-and-see group were not provided........."

abstract: Psychosocial Care for Family Caregivers of Patients With Cancer [Review Articles]

Psychosocial Care for Family Caregivers of Patients With Cancer [Review Articles]:

Purpose
To understand family caregivers' needs for better preparation and care, this state-of-the-science review examines the effect of caregiving on the health and well-being of caregivers, the efficacy of research-tested interventions on patient and caregiver outcomes, implications of the research on policy and practice, and recommendations for practice and future research.

Methods
We reviewed research that described the multiple effects of cancer on caregivers' well-being. Five meta-analyses were analyzed to determine the effect of interventions with caregivers on patient and caregiver outcomes. In addition, we reviewed legislation such as the Affordable Care Act and the Family Leave Act along with current primary care practice to determine whether family caregivers' needs have been addressed.

abstract: Oncologist Burnout: Causes, Consequences, and Responses

Oncologist Burnout: Causes, Consequences, and Responses

 Abstract

"Although the practice of oncology can be extremely rewarding, it is also one of the most demanding and stressful areas of medicine. Oncologists are faced with life and death decisions on a daily basis, administer incredibly toxic therapies with narrow therapeutic windows, must keep up with the rapid pace of scientific and treatment advances, and continually walk a fine line between providing palliation and administering treatments that lead to excess toxicity. Personal distress precipitated by such work-related stress may manifest in a variety of ways including depression, anxiety, fatigue, and low mental quality of life. Burnout also seems to be one of the most common manifestations of distress among physicians, with studies suggesting a prevalence of 35% among medical oncologists, 38% among radiation oncologists, and 28% to 36% among surgical oncologists. Substantial evidence suggests that burnout can impact quality of care in a variety of ways and has potentially profound personal implications for physicians including suicidal ideation. In this review, we examine the causes, consequences, and personal ramifications of oncologist burnout and explore the steps oncologists can take to promote personal well-being and professional satisfaction."

abstract: Communication Skills Training for Oncology Professionals

Communication Skills Training for Oncology Professionals

 Conclusion

"Future communication challenges include genetic risk communication, concepts like watchful waiting, cumulative radiation risk, late effects of treatment, discussing Internet information and unproven therapies, phase I trial enrollment, and working as a multidisciplinary team. Patient benefits, such as increased treatment adherence and enhanced adaptation, need to be demonstrated from CST."

abstract: (review of the literature) Screening for Distress and Unmet Needs in Patients With Cancer: Review and Recommendations

Screening for Distress and Unmet Needs in Patients With Cancer: Review and Recommendations

"....Many distress screening and unmet need tools have been subject to preliminary validation, but few have been compared head to head in independent centers and in different stages of cancer...."

abstract: Psychosocial Care of Adolescent and Young Adult Patients With Cancer and Survivors

Psychosocial Care of Adolescent and Young Adult Patients With Cancer and Survivors

JCO - Editorial: Caring for the Whole Patient: The Science of Psychosocial Care

open access: Editorial (special series) Caring for the Whole Patient: The Science of Psychosocial Care

"This Journal of Clinical Oncology Special Series relates to the
science of psychosocial care. This series is designed to provide oncology
professionals with the most recent information about the psychological,
psychiatric, and social aspects of cancer care. The emergence of
the field of psychosocial care reflects growing public and professional
awareness of the potential for cancer and its treatment to have profound
effects on many aspects of life. A principal goal of psychosocial
care is to recognizeandaddress the effects that cancerandits treatment
have on the mental status and emotional well-being of patients, their
family members, and their professional caregivers....."