Clinical Criteria for Physician Aid in Dying

More than 20 years ago, even before voters in Oregon had enacted the first aid in dying (AID) statute in the United States, Timothy Quill and colleagues proposed clinical criteria AID. Their proposal was carefully considered and temperate, but there were little data on the practice of AID at the time. (With AID, a physician writes a prescription for life-ending medication for a terminally ill, mentally capacitated adult.) With the passage of time, a substantial body of data on AID has developed from the states of Oregon and Washington. For more than 17 years, physicians in Oregon have been authorized to provide a prescription for AID. Accordingly, we have updated the clinical criteria of Quill, et al., based on the many years of experience with AID. With more jurisdictions authorizing AID, it is critical that physicians can turn to reliable clinical criteria. As with any medical practice, AID must be provided in a safe and effective manner. Physicians need to know (1) how to respond to a patient's inquiry about AID, (2) how to assess patient decision making capacity, and (3) how to address a range of other issues that may arise. To ensure that physicians have the guidance they need, Compassion & Choices convened the Physician Aid-in-Dying Clinical Criteria Committee, in July 2012, to create clinical criteria for physicians who are willing to provide AID to patients who request it. The committee includes experts in medicine, law, bioethics, hospice, nursing, social work, and pharmacy. Using an iterative consensus process, the Committee drafted the criteria over a one-year period

Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti-Mi-2 autoantibodies in women.

OBJECTIVE: Because studies suggest that ultraviolet (UV) radiation modulates the myositis phenotype and Mi-2 autoantigen expression, we conducted a retrospective investigation to determine whether UV radiation may influence the relative prevalence of dermatomyositis and anti-Mi-2 autoantibodies in the US. METHODS: We assessed the relationship between surface UV radiation intensity in the state of residence at the time of onset with the relative prevalence of dermatomyositis and myositis autoantibodies in 380 patients with myositis from referral centers in the US. Myositis autoantibodies were detected by validated immunoprecipitation assays. Surface UV radiation intensity was estimated from UV Index data collected by the US National Weather Service. RESULTS: UV radiation intensity was associated with the relative proportion of patients with dermatomyositis (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 0.9-5.8) and with the proportion of patients expressing anti-Mi-2 autoantibodies (OR 6.0, 95% CI 1.1-34.1). Modeling of these data showed that these associations were confined to women (OR 3.8, 95% CI 1.3-11.0 and OR 17.3, 95% CI 1.8-162.4, respectively) and suggests that sex influences the effects of UV radiation on autoimmune disorders. Significant associations were not observed in men, nor were UV radiation levels related to the presence of antisynthetase or anti-signal recognition particle autoantibodies. CONCLUSION: This first study of the distribution of myositis phenotypes and UV radiation exposure in the US showed that UV radiation may modulate the clinical and immunologic expression of autoimmune disease in women. Further investigation of the mechanisms by which these effects are produced may provide insights into pathogenesis and suggest therapeutic or preventative strategies

Validation of potential classification criteria for systemic sclerosis

Objective Classification criteria for systemic sclerosis (SSc; scleroderma) are being updated jointly by the American College of Rheumatology and European League Against Rheumatism. Potential items for classification were reduced to 23 using Delphi and nominal group techniques. We evaluated the face, discriminant, and construct validity of the items to be further studied as potential criteria. Methods Face validity was evaluated using the frequency of items in patients sampled from the Canadian Scleroderma Research Group, 1000 Faces of Lupus, and the Pittsburgh, Toronto, Madrid, and Berlin connective tissue disease (CTD) databases. Patients with SSc (n = 783) were compared to 1,071 patients with diseases similar to SSc (mimickers): systemic lupus erythematosus (n = 499), myositis (n = 171), Sjögren's syndrome (n = 95), Raynaud's phenomenon (RP; n = 228), mixed CTD (n = 29), and idiopathic pulmonary arterial hypertension (PAH; n = 49). Discriminant validity was evaluated using odds ratios (ORs). For construct validity, empirical ranking was compared to expert ranking. Results Compared to mimickers, patients with SSc were more likely to have skin thickening (OR 427); telangiectasias (OR 91); anti–RNA polymerase III antibody (OR 75); puffy fingers (OR 35); finger flexion contractures (OR 29); tendon/bursal friction rubs (OR 27); anti–topoisomerase I antibody (OR 25); RP (OR 24); fingertip ulcers/pitting scars (OR 19); anticentromere antibody (OR 14); abnormal nailfold capillaries (OR 10); gastroesophageal reflux disease symptoms (OR 8); antinuclear antibody, calcinosis, dysphagia, and esophageal dilation (all OR 6); interstitial lung disease/pulmonary fibrosis (OR 5); and anti–PM‐Scl antibody (OR 2). Reduced carbon monoxide diffusing capacity, PAH, and reduced forced vital capacity had ORs of <2. Renal crisis and digital pulp loss/acroosteolysis did not occur in SSc mimickers (OR not estimated). Empirical and expert ranking were correlated (Spearman's ρ = 0.53, P = 0.01). Conclusion The candidate items have good face, discriminant, and construct validity. Further item reduction will be evaluated in prospective SSc and mimicker cases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90121/1/20684_ftp.pd

Correlates and Responsiveness to Change of Measures of Skin and Musculoskeletal Disease in Early Diffuse Systemic Sclerosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109290/1/acr22339.pd

Brief Report: Effect of ambrisentan treatment on exercise‐induced pulmonary hypertension in systemic sclerosis: A prospective single‐center, open‐label pilot study

Objective Exercise‐induced pulmonary hypertension (ePH) may represent an early, clinically relevant phase in the spectrum of pulmonary vascular disease. The purpose of this pilot study was to describe the changes in hemodynamics and exercise capacity in patients with systemic sclerosis (SSc) spectrum–associated ePH treated with open‐label daily ambrisentan. Methods Patients were treated with ambrisentan, 5 mg or 10 mg once daily, for 24 weeks. At baseline and 24 weeks, patients with SSc spectrum disorders exercised in a supine position, on a lower extremity cycle ergometer. All patients had normal hemodynamics at rest. We defined baseline ePH as a mean pulmonary artery pressure of >30 mm Hg with maximum exercise and a transpulmonary gradient (TPG) of >15 mm Hg. The primary end point was change in pulmonary vascular resistance (PVR) with exercise. Secondary end points included an improvement from baseline in 6‐minute walking distance, health‐related quality of life assessments, and cardiopulmonary hemodynamics. Results Of the 12 enrolled patients, 11 completed the study. At 24 weeks there were improvements in mean exercise PVR (85.8 dynes × second/cm 5 ; P = 0.003) and mean distance covered during 6‐minute walk (44.5 meters; P = 0.0007). Improvements were also observed in mean exercise cardiac output (1.4 liters/minute; P = 0.006), mean pulmonary artery pressure (−4.1 mm Hg; P = 0.02), and total pulmonary resistance (−93.0 dynes × seconds/cm 5 ; P = 0.0008). Three patients developed resting pulmonary arterial hypertension during the 24 weeks. Conclusion Exercise hemodynamics and exercise capacity in patients with SSc spectrum–associated ePH improved over 24 weeks with exposure to ambrisentan. Placebo‐controlled studies are needed to confirm whether this is a drug‐related effect and to determine optimal therapeutic regimens for patients with ePH.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94508/1/34614_ftp.pd

Ontario's water quality objective development process

As part of its program to ensure that the surface waters of Ontario are satisfactory for aquatic life and recreation, the Ontario Ministry of the Environment develops Provincial Water Quality Objectives (PWQOs) and Guidelines (PWQGs). This report details the procedures used to develop PWQOs and PWQGs. PWQOs are developed from the best available knowledge on the effects of substances on aquatic life. Data are required for acute and chronic toxicity, bioaccumulation and mutagenicity. Also considered is available information on environmental fate, physical-chemical properties, taste and odour in water and tainting of fish tissues. If adequate information is unavailable for setting a PWQO, a PWQG is developed using uncertainty factors which depend on the quantity and quality of the toxicological data

Aortic stiffness as a marker of cardiac function and myocardial strain in patients undergoing aortic valve replacement

Background: Cardiac function and myocardial strain are affected by cardiac afterload, which is in part due to the stiffness of the aortic wall. In this study, we hypothesize that aortic pulse wave velocity (PWV) as a marker of aortic stiffness correlates with conventional clinical and biochemical markers of cardiac function and perioperative myocardial strain in aortic valve replacement (AVR). Methods: Patients undergoing AVR for aortic stenosis between June 2010 and August 2012 were recruited for inclusion in this study. PWV, NYHA class and left ventricular (LV) function were assessed pre-operatively. PWV was analysed both as a continuous and dichotomous variable according to age-standardized reference values. B-type natriuretic peptide (BNP) was measured pre-operatively, and at 3 h and 18-24 h after cardiopulmonary bypass (CPB). NYHA class, leg edema, and LV function were recorded at follow-up (409 ± 159 days). Results: Fifty-six patients (16 females) with a mean age of 71 ± 8.4 years were included, with 50 (89%) patients completing follow-up. The NYHA class of PWV-norm patients was significantly lower than PWV-high patients both pre- and post-operatively. Multiple logistic regression also highlighted PWV-cut off as an independent predictor of NYHA class pre- and post-operatively (OR 8.3, 95%CI [2.27,33.33] and OR 14.44, 95%CI [1.49,139.31] respectively). No significant relationship was observed between PWV and either LV function or plasma BNP. Conclusion: In patients undergoing AVR for aortic stenosis, PWV is independently related to pre- and post-operative NYHA class but not to LV function or BNP. These findings provisionally support the use of perioperative PWV as a non-invasive marker of clinical functional status, which when used in conjunction with biomarkers of myocardial strain such as BNP, may provide a holistic functional assessment of patients undergoing aortic valve surgery. However, in order for PWV assessment to be translated into clinical practice and utilised as more than simply a research tool, further validation is required in the form of larger prospective studies specifically designed to assess the relationship between PWV and these functional clinical outcomes

EFSA Panel on Biological Hazards (BIOHAZ) Panel; Scientific Opinion on the risk posed by pathogens in food of non-animal origin. Part 1 (outbreak data analysis and risk ranking of food/pathogen combinations)

Food of non-animal origin (FoNAO) is consumed in a variety of forms, and a major component of almost all meals. These food types have the potential to be associated with large outbreaks as seen in 2011 associated with VTEC O104. A comparison of the incidence of human cases linked to consumption of FoNAO and of food of animal origin (FoAO) was carried out to provide an indication of the proportionality between these two groups of foods. It was concluded that outbreak data reported as part of EU Zoonoses Monitoring is currently the only option for EU-wide comparative estimates. Using this data from 2007 to 2011, FoNAO were associated with 10% of the outbreaks, 26% of the cases, 35% of the hospitalisations and 46% of the deaths. If the data from the 2011VTEC O104 outbreak is excluded, FoNAO was associated with 10% of the outbreaks, 18% of cases, but only 8% of the hospitalisations and 5% of the deaths. From 2008 to 2011 there was an increase in the numbers of reported outbreaks, cases, hospitalisations and deaths associated with food of non-animal origin. In order to identify and rank specific food/pathogen combinations most often linked to human cases originating from FoNAO in the EU, a model was developed using seven criteria: strength of associations between food and pathogen based on the foodborne outbreak data from EU Zoonoses Monitoring (2007-11), incidence of illness, burden of disease, dose-response relationship, consumption, prevalence of contamination and pathogen growth potential during shelf life. Shortcomings in the approach using outbreak data were discussed. The top ranking food/pathogen combination was Salmonellaspp. and leafy greens eaten raw followed by (in equal rank) Salmonellaspp. and bulb and stem vegetables, Salmonellaspp. and tomatoes, Salmonellaspp. and melons, and pathogenic Escherichia coli and fresh pods, legumes or grain

Patients' preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study

BACKGROUND: Patients with HER2-positive early breast cancer (EBC) preferred subcutaneous (SC) trastuzumab, delivered via single-use injection device (SID), over the intravenous (IV) formulation (Cohort 1 of the PrefHer study: NCT01401166). Here we report patient preference, healthcare professional satisfaction, and safety data pooled from Cohort 1 and also Cohort 2, where SC trastuzumab was delivered via hand-held syringe. PATIENTS AND METHODS: Patients were randomized to receive 4 adjuvant cycles of 600 mg fixed-dose SC trastuzumab followed by 4 cycles of standard IV trastuzumab, or vice versa. The primary endpoint was overall preference proportions for SC or IV, assessed by patient interviews in the evaluable ITT population. RESULTS: A total of 245 patients were randomized to receive SC followed by IV and 243 received IV followed by SC (evaluable ITT populations: 235 and 232 patients, respectively). SC was preferred by 415/467 (88.9%; 95% CI, 85.7-91.6; P<.0001; two-sided test against null hypothesis of 65% SC preference); 45/467 preferred IV (9.6%; 7-13); 7/467 indicated no preference (1.5%; 1-3). Clinician-reported adverse events occurred in 292/479 (61.0%) and 245/478 (51.3%) patients during the pooled SC and IV periods, respectively (P<.05; 2x2 chi2); 16 patients (3.3%) in each period experienced grade 3 events; none were grade 4/5. CONCLUSION: PrefHer revealed compelling and consistent patient preferences for SC over IV trastuzumab, regardless of SID or hand-held syringe delivery. SC was well tolerated and safety was consistent with previous reports, including the HannaH study (NCT00950300). No new safety signals were identified compared to the known IV profile in EBC. PrefHer and HannaH confirm that SC trastuzumab is a validated and preferred option over IV for improving patients' care in HER2-positive breast cancer

Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility: a case-only study.

INTRODUCTION: We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA). METHODS: The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria. RESULTS: An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication. CONCLUSIONS: Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA