Nationwide Actions Against Heart Failure Pandemic in Japan　- What Should We Do From Academia?

Heart failure pandemic is rapidly approaching in Japan, requiring nationwide actions. In particular, the Japanese Circulation Society and related societies launched the Stroke and Cardiovascular Disease Control Act, which was passed by the National Diet, as the first ever legislative policy measure against stroke and cardiovascular disease. In association with this, actions against heart failure pandemic from the scientific field are also important. Because heart failure pandemic is a critical problem not only in Japan but also in many developed countries, we believe the nationwide approach, as summarized here, will greatly contribute to the development of cardiovascular medicine, particularly the management and treatment of heart failure worldwide.

The BMA's guidance on conscientious objection may be contrary to human rights law.

It is argued that the current policy of the British Medical Association (BMA) on conscientious objection is not aligned with recent human rights developments. These grant a right to conscientious objection to doctors in many more circumstances than the very few recognised by the BMA. However, this wide-ranging right may be overridden if the refusal to accommodate the conscientious objection is proportionate. It is shown that it is very likely that it is lawful to refuse to accommodate conscientious objections that would result in discrimination of protected groups. It is still uncertain, however, in what particular circumstances the objection may be lawfully refused, if it poses risks to the health and safety of patients. The BMA's policy has not caught up with these human rights developments and ought to be changed.

Three PAs talk about success in Mississippi.

This article gives the first-hand perspectives of three physician assistants (PAs) involved in the profession's years of struggle to gain practice authority in Mississippi. Through a series of questions and answers, each PA describes his or her part in the historical events that made Mississippi the final US state to regulate PAs.

International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis.

Systemic mastocytosis (SM) is characterized by accumulation of neoplastic mast cells and is classified into indolent and aggressive forms. The latter include aggressive SM (ASM), mast cell leukemia (MCL), and SM associated with a myeloid neoplasm wherein 1 or both disease compartments exhibit advanced features. These variants, henceforth collectively referred to as advanced SM for the purposes of this report, are typically characterized by organ damage and shortened survival duration. In contrast to indolent SM, in which symptoms are usually managed by noncytotoxic antimediator therapy, cytoreduction is usually necessary for disease control in advanced SM. Unfortunately, current drug treatment of these patients rarely results in complete clinical and histopathologic remissions or improved survival time. Previously defined response criteria were adapted to the heterogeneous presentations of advanced SM and the limited effects of available drugs. However, recent advances in understanding the molecular pathogenesis of SM and the corresponding prospect in targeted therapy make it a priority to modify these criteria. Our current study is the product of an international group of experts and summarizes the challenges in accomplishing this task and forwards a new proposal for response criteria, which builds on prior proposals and should facilitate response evaluation in clinical trials.

IMWG consensus on maintenance therapy in multiple myeloma.

Maintaining results of successful induction therapy is an important goal in multiple myeloma. Here, members of the International Myeloma Working Group review the relevant data. Thalidomide maintenance therapy after autologous stem cell transplantation improved the quality of response and increased progression-free survival (PFS) significantly in all 6 studies and overall survival (OS) in 3 of them. In elderly patients, 2 trials showed a significant prolongation of PFS, but no improvement in OS. A meta-analysis revealed a significant risk reduction for PFS/event-free survival and death. The role of thalidomide maintenance after melphalan, prednisone, and thalidomide is not well established. Two trials with lenalidomide maintenance treatment after autologous stem cell transplantation and one study after conventional melphalan, prednisone, and lenalidomide induction therapy showed a significant risk reduction for PFS and an increase in OS in one of the transplant trials. Maintenance therapy with single-agent bortezomib or in combination with thalidomide or prednisone has been studied. One trial revealed a significantly increased OS with a bortezomib-based induction and bortezomib maintenance therapy compared with conventional induction and thalidomide maintenance treatment. Maintenance treatment can be associated with significant side effects, and none of the drugs evaluated is approved for maintenance therapy. Treatment decisions for individual patients must balance potential benefits and risks carefully, as a widely agreed-on standard is not established.

Forecasting the future of stroke in the United States: a policy statement from the American Heart Association and American Stroke Association.

BACKGROUND AND PURPOSE: Stroke is a leading cause of disability, cognitive impairment, and death in the United States and accounts for 1.7% of national health expenditures. Because the population is aging and the risk of stroke more than doubles for each successive decade after the age of 55 years, these costs are anticipated to rise dramatically. The objective of this report was to project future annual costs of care for stroke from 2012 to 2030 and discuss potential cost reduction strategies. METHODS AND RESULTS: The American Heart Association/American Stroke Association developed methodology to project the future costs of stroke-related care. Estimates excluded costs associated with other cardiovascular diseases (hypertension, coronary heart disease, and congestive heart failure). By 2030, 3.88% of the US population>18 years of age is projected to have had a stroke. Between 2012 and 2030, real (2010$) total direct annual stroke-related medical costs are expected to increase from $71.55 billion to $183.13 billion. Real indirect annual costs (attributable to lost productivity) are projected to rise from $33.65 billion to $56.54 billion over the same period. Overall, total annual costs of stroke are projected to increase to $240.67 billion by 2030, an increase of 129%. CONCLUSIONS: These projections suggest that the annual costs of stroke will increase substantially over the next 2 decades. Greater emphasis on implementing effective preventive, acute care, and rehabilitative services will have both medical and societal benefits.

BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet.

Mutations in the Bcr-Abl kinase domain may cause, or contribute to, resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia patients. Recommendations aimed to rationalize the use of BCR-ABL mutation testing in chronic myeloid leukemia have been compiled by a panel of experts appointed by the European LeukemiaNet (ELN) and European Treatment and Outcome Study and are here reported. Based on a critical review of the literature and, whenever necessary, on panelists' experience, key issues were identified and discussed concerning: (1) when to perform mutation analysis, (2) how to perform it, and (3) how to translate results into clinical practice. In chronic phase patients receiving imatinib first-line, mutation analysis is recommended only in case of failure or suboptimal response according to the ELN criteria. In imatinib-resistant patients receiving an alternative TKI, mutation analysis is recommended in case of hematologic or cytogenetic failure as provisionally defined by the ELN. The recommended methodology is direct sequencing, although it may be preceded by screening with other techniques, such as denaturing-high performance liquid chromatography. In all the cases outlined within this abstract, a positive result is an indication for therapeutic change. Some specific mutations weigh on TKI selection.

Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematological malignancies and solid tumors : guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

Bacterial infections are the most common cause for treatment-related mortality in patients with neutropenia after chemotherapy. Here, we discuss the use of antibacterial prophylaxis against bacteria and Pneumocystis pneumonia (PCP) in neutropenic cancer patients and offer guidance towards the choice of drug. A literature search was performed to screen all articles published between September 2000 and January 2012 on antibiotic prophylaxis in neutropenic cancer patients. The authors assembled original reports and meta-analysis from the literature and drew conclusions, which were discussed and approved in a consensus conference of the Infectious Disease Working Party of the German Society of Hematology and Oncology (AGIHO). Antibacterial prophylaxis has led to a reduction of febrile events and infections. A significant reduction of overall mortality could only be shown in a meta-analysis. Fluoroquinolones are preferred for antibacterial and trimethoprim-sulfamethoxazole for PCP prophylaxis. Due to serious concerns about an increase of resistant pathogens, only patients at high risk of severe infections should be considered for antibiotic prophylaxis. Risk factors of individual patients and local resistance patterns must be taken into account. Risk factors, choice of drug for antibacterial and PCP prophylaxis and concerns regarding the use of prophylactic antibiotics are discussed in the review.

Melanoma, version 2.2013: featured updates to the NCCN guidelines.

The NCCN Guidelines for Melanoma provide multidisciplinary recommendations on the clinical management of patients with melanoma. This NCCN Guidelines Insights report highlights notable recent updates. Foremost of these is the exciting addition of the novel agents ipilimumab and vemurafenib for treatment of advanced melanoma. The NCCN panel also included imatinib as a treatment for KIT-mutated tumors and pegylated interferon alfa-2b as an option for adjuvant therapy. Also important are revisions to the initial stratification of early-stage lesions based on the risk of sentinel lymph node metastases, and revised recommendations on the use of sentinel lymph node biopsy for low-risk groups. Finally, the NCCN panel reached clinical consensus on clarifying the role of imaging in the workup of patients with melanoma.

Duties of the Psychiatric Committee for Preventive Measures. Present situation and proposed normative changes / Zadania Komisji Psychiatrycznej do Spraw Srodków Zabezpieczajacych. Stan obecny i postulaty zmian normatywnych.

The aim of this paper is to analyze the present legal model of the Psychiatric Committee for Preventive Measures and formulate proposed changes in regulations based on research findings. In 2003 the legislator delegated the qualifying procedures to the Committee, which resulted in lengthening the time until the moment of detaining the convict in a closed facility, which may cause harm to both the convict and the society. It is proposed that the classification be performed by experts, who must be heard by the court anyway before preventive measures are decreed, with the possibility of consulting the Committee in difficult or doubtful cases, if needed. Most tasks of the Committee, however, should be related to exercising control and to do this, it is necessary for the Committee to liaise with the court's penitentiary supervisors.

Third CECOG consensus on the systemic treatment of non-small-cell lung cancer.

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

SIE, SIES, GITMO evidence-based guidelines on novel agents (thalidomide, bortezomib, and lenalidomide) in the treatment of multiple myeloma.

In this project, we produced drug-specific recommendations targeting the use of new agents for multiple myeloma (MM). We used the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system which separates the judgments on quality of evidence from the judgment about strength of recommendations. We recommended thalidomide and bortezomib in MM patients candidates to autologous stem cell transplantation (ASCT) (weak positive). We did not recommend novel agents as maintenance therapy after ASCT (weak negative). In patients not candidate to ASCT, thalidomide or bortezomib (strong positive) associated with melphalan and prednisone were recommended. In these patients, no specific course of action could be recommended as for maintenance therapy. In patients who are refractory or relapsing after first-line therapy, we recommended bortezomib and pegylated liposomal doxorubicin, or lenalidomide and dexamethasone combinations (weak positive).

Equity in cancer care: pathways, protocols, and guidelines.

The quality of patient care varies based on numerous factors, such as health care setting, geographic location, access to medications, insurance coverage, and treatment protocols. Recently, the issue of whether use of clinical pathways can reduce costs and inappropriate variability in care has been the subject of much debate. As clinical treatment guidelines and pathways are increasingly deployed in oncology practice, they have a growing impact on the quality of treatment and how it is delivered. To fulfill the current need to discuss the use of pathways and clinical treatment guidelines in oncology and to address how patient care is impacted by their use, the National Comprehensive Cancer Network convened the NCCN Oncology Policy Summit: Equity in Cancer Care-Pathways, Protocols, and Guidelines. The summit was a forum to discuss the use and implementation of pathways, including how much flexibility pathways should allow in care, pathways' impact on public and private health insurance benefit design, what data is used to select pathway regimens and protocols, and ultimately what impact pathways may have on variation in care. The use and implementation of clinical treatment guidelines in practice was also explored from a variety of perspectives.

Survival rates for international federation of gynecology and obstetrics stage III ovarian carcinoma by cell type: a study of 262 unselected patients with uniform pathologic review.

OBJECTIVE: Published data are conflicting on the influence of cell type on prognosis in ovarian cancer. The recent separation of low-grade serous carcinoma as a distinctive cell type of ovarian cancer with an indolent behavior, in retrospect, suggests that survival in studies that have not separated this group may be inaccurate. METHODS: An unselected series of 262 International Federation of Gynecology and Obstetrics stage III ovarian carcinomas was studied. Diagnostic classification of each tumor was made with particular attention to recent refinements in cell-type classification. Survival curves were constructed according to Kaplan-Meier and compared with the log-rank test. RESULTS: The 5-year survival for 207 high-grade serous carcinomas was 40%, as compared with 71% for 18 patients with low-grade serous carcinoma (P = 0.0113). Low-grade serous carcinoma was significantly more likely to be optimally debulked (P = 0.0039) and significantly less likely to be substage IIIC (P < 0.0001). The survival for carcinosarcoma was significantly inferior to all serous carcinomas (P = 0.0322). The significance of this latter comparison was lost when carcinosarcomas were compared with only high-grade serous carcinoma (P > 0.05). CONCLUSIONS: Low-grade serous carcinoma has a significantly better prognosis than high-grade serous carcinoma and also differs with regard to substage distribution and proportion of patients optimally debulked. Because of its excellent prognosis, failure to separate low-grade serous carcinomas, notwithstanding its infrequent occurrence, can change the results of survival analyses that do not make this separation.

Validation of the FIGO 2009 staging system for carcinoma of the vulva.

BACKGROUND: The previous (1988) International Federation of Gynecology and Obstetrics (FIGO) vulval cancer staging system failed in 3 important areas: (1) stage 1 and 2 disease showed similar survival; (2) stage 3 represented a most heterogeneous group of patients with a wide survival range; and (3) the number and morphology of positive nodes were not taken into account. OBJECTIVE: To compare the 1988 FIGO vulval carcinoma staging system with that of 2009 with regard to stage migration and prognostication. METHODS: Information on all patients treated for vulval cancer at the Queensland Centre for Gynecological Cancers, Australia, between 1988 to the present was obtained. Data included patients' characteristics as well as details on histopathology, treatments, and follow-up. We recorded the original 1988 FIGO stage, reviewed all patients' histopathology information, and restaged all patients to the 2009 FIGO staging system. Data were analyzed using the Kaplan-Meier method to compare relapse-free survival and overall survival. RESULTS: Data from 394 patients with primary vulval carcinoma were eligible for analysis. Patients with stage IA disease remained unchanged. Tumors formerly classified as stage II are now classified as stage IB. Therefore, FIGO 2009 stage II has become rare, with only 6 of 394 patients allocated to stage II. Stage III has been broken down into 3 substages, thus creating distinct differences in relapse-free survival and overall survival. Prognosis of patients with stage IIIC disease is remarkably poor. CONCLUSION: The FIGO 2009 staging system for vulval carcinoma successfully addresses some concerns of the 1988 system. Especially, it identifies high-risk patients within the heterogeneous group of lymph node-positive patients.

Guidelines for ethical and professional use of social media in a hand surgery practice.

In growing numbers, patients are using social media platforms as resources to obtain health information and report their experiences in the health care setting. More physicians are making use of these platforms as a means to reach prospective and existing patients, to share information with each other, and to educate the public. In this ever-expanding online dialogue, questions have arisen regarding appropriate conduct of the physician during these interactions. The purpose of this article is to review the laws that govern online communication as they pertain to physician presence in this forum and to discuss appropriate ethical and professional behavior in this setting.