Blood- and tissue-based biomarkers for prediction of outcomes in urothelial carcinoma of the bladder

ObjectivesUrothelial carcinoma of the bladder (UCB) is a highly heterogeneous malignancy that causes significant morbidity and mortality. Standard pathologic features (stage, grade, and nodal status) are insufficient to predict accurately a patient's outcome. Biomarkers could help clinicians provide individualized prognostications and allow risk-stratified clinical decision making regarding surgical and medical treatment. This review summarizes the existing tissue- and blood-based biomarkers in UCB.Material and methodsA PubMed/Medline search was conducted to identify original articles regarding molecular biomarkers and UCB. Searches were limited to papers published in English. Keywords included urothelial carcinoma, bladder cancer, transitional cell, biomarker, marker, staining, cystectomy, recurrence or progression, survival, prediction, and prognosis.ResultsThe articles with the highest level of evidence were selected and reviewed, with the consensus of all the authors of this paper.ConclusionsThere is no doubt that a panel of biomarkers would eventually improve our clinical decision making regarding treatment and follow-up. However, to date, no biomarker panel is yet validated for daily clinical practice.     

From the Cover: Near-linear cost increase to reduce climate-change risk

One approach in climate-change policy is to set normative long-term targets first and then infer the implied emissions pathways. An important example of a normative target is to limit the global-mean temperature change to a certain maximum. In general, reported cost estimates for limiting global warming often rise rapidly, even exponentially, as the scale of emission reductions from a reference level increases. This rapid rise may suggest that more ambitious policies may be prohibitively expensive. Here, we propose a probabilistic perspective, focused on the relationship between mitigation costs and the likelihood of achieving a climate target. We investigate the qualitative, functional relationship between the likelihood of achieving a normative target and the costs of climate-change mitigation. In contrast to the example of exponentially rising costs for lowering concentration levels, we show that the mitigation costs rise proportionally to the likelihood of meeting a temperature target, across a range of concentration levels. In economic terms investing in climate mitigation to increase the probability of achieving climate targets yields “constant returns to scale,” because of a counterbalancing rapid rise in the probabilities of meeting a temperature target as concentration is lowered.     

Use of a Learning Collaborative to Support Implementation of Integrated Care for Smoking Cessation for Veterans With Posttraumatic Stress Disorder

Objectives. We evaluated the feasibility of incorporating integrated care (IC) for smoking cessation into routine treatment for posttraumatic stress disorder (PTSD) at Department of Veterans Affairs (VA) Medical Centers and the utility of the Learning Collaborative (LC) model in facilitating implementation.Methods. We conducted 2 LCs aimed at implementing IC for smoking cessation using multidisciplinary teams comprising 70 staff members from 12 VA PTSD clinics. Using questionnaires, we evaluated providers’ perceptions of the LC methodology and the effectiveness and feasibility of routine IC delivery. We assessed number of providers delivering and patients receiving IC using medical record data.Results. More than 85% of participating VA staff considered the LC to be an effective training and implementation platform. The majority thought IC effectively addressed an important need and could be delivered in routine PTSD care. All LC participants who planned to deliver IC did so (n = 52). Within 12 months of initial training, an additional 46 locally trained providers delivered IC and 395 veterans received IC.Conclusions. The LC model effectively facilitated rapid and broad implementation of IC. Facilitators and barriers to sustained use of IC are unknown and should be identified to understand how best to promote ongoing access to evidence-based treatment for smoking cessation in mental health populations.Despite gains in reducing tobacco use among the general public, nicotine dependence continues to disproportionately affect individuals with mental illness, including those with posttraumatic stress disorder (PTSD), a prevalent mental health disorder1 associated with heavy cigarette consumption and low cessation rates.2 One in 10 current US smokers have had PTSD at some point in their lives.2 Tobacco dependence likely contributes to the high mortality,3 morbidity,4 and health care costs5 of persons with PTSD. Recent epidemiological studies, although unable to elucidate causal pathways unequivocally, strongly suggest that smoking cessation reduces risk for suicidal ideation,6 depression,7,8 and anxiety,9 emphasizing the critical importance for cessation among those with PTSD and other mental health conditions. Thus, effective cessation treatment interventions and delivery systems are needed to reach this population.To address this need within the Veterans Health Administration, McFall et al.10 developed integrated care (IC) for smoking cessation, which incorporates guideline-based cessation treatment into mental health care for veterans with PTSD. IC is delivered by veterans’ PTSD providers, capitalizing on the existing therapeutic relationship between provider and patient. A randomized trial at 10 Department of Veterans Affairs (VA) Medical Centers, VA Cooperative Study No. 519 (CSP 519), found that, compared with referral to specialized smoking cessation clinics, IC improved cessation outcomes among veterans with PTSD without detracting from mental health treatment.10Although providers who participated in CSP 519 held positive views of IC and supported delivering cessation treatment in mental health care,11 most did not continue delivering IC at the study’s conclusion (C. Wallace, PhD, unpublished data, August 2011). Such a finding is unsurprising given that the use of evidence-based treatments in mental health remains sparse and inconsistent outside of academic settings.12,13 The challenge of making best practice usual practice has been identified as a major public health priority.12,14 Information dissemination and training remain 2 of the most widely used strategies for attempting to spread new practices13,15 but are insufficient for ensuring broad and sustained use of evidence-based treatments; longer-term multilevel implementation strategies are necessary to overcome numerous and complex barriers to adoption.15–17Quality collaboratives are one methodology used to support health care system change and improve quality of care.18–21 The Breakthrough Series is a quality collaborative model that brings together multidisciplinary teams from different organizations with recognized experts to work in a structured way to accelerate spread of best practices.22 The National Center for Child Traumatic Stress’s Learning Collaborative (LC) Model, an adaptation of the Breakthrough Series, supports rapid delivery and sustained use of effective treatments in community settings23 by melding best practices in training and consultation with quality improvement methods.In 2010, the VA partnered with the Duke Evidence-Based Practice Implementation Center to conduct an LC to implement IC in 6 Veterans Affairs PTSD clinics, followed by a second LC with 6 additional Veterans Affairs PTSD clinics in 2012. The objective of this project evaluation was to assess the feasibility of delivering IC as part of routine PTSD care and the utility of the LC model in facilitating IC implementation. Specifically, we examined whether (1) VA staff actively participated in the collaborative and considered LC methodology useful in supporting IC implementation; (2) collaborative participation resulted in rapid delivery of IC (i.e., delivery within 3 months of training) and continued use of the intervention after LC completion; and (3) VA providers viewed IC as compatible with current clinical practices and feasible to deliver as part of routine mental health care for veterans with PTSD. Because troops newly returning from deployment have higher rates of smoking than the general population24,25 and high rates of PTSD,26 it is imperative than an evidence-based treatment such as IC be widely implemented to preserve the physical and mental health of our returning service members.     

Fatty acid ethanolamide levels are altered in borderline personality and complex posttraumatic stress disorders

Borderline personality (BPD) and complex posttraumatic stress disorders (PTSD) are both powerfully associated with the experience of interpersonal violence during childhood and adolescence. The disorders frequently co-occur and often result in pervasive problems in, e.g., emotion regulation and altered pain perception, where the endocannabinoid system is deeply involved. We hypothesize an endocannabinoid role in both disorders. We investigated serum levels of the endocannabinoids anandamide and 2-arachidonoylglycerol and related fatty acid ethanolamides (FAEs) in BPD, PTSD, and controls. Significant alterations were found for both endocannabinoids in BPD and for the FAE oleoylethanolamide in PTSD suggesting a respective link to both disorders.     

From embouchure problems to embouchure dystonia? A survey of self-reported embouchure disorders in 585 professional orchestra brass players

Objectives

Data concerning embouchure problems in professional brass players are scarce. Embouchure problems can potentially lead to focal dystonia. The aim of this study was to investigate the frequency of distinct embouchure problems in professional brass players. Furthermore, the frequency of “cramping”, a distinct symptom of embouchure dystonia, was evaluated in the context of established embouchure dystonia risk factors.

Methods

Five hundred and eighty-five professional brass players participated in a cross-sectional study concerning embouchure problems. A self-administered questionnaire was developed to evaluate embouchure fatigue, embouchure disorders and their consequences. To study the association between risk factors and cramping (a symptom of embouchure dystonia), a log-binomial regression analysis was conducted, enabling estimation of prevalence ratios (PR) and 95 % confidence intervals (95 % CI).

Results

Thirty percent (95 % CI 25.9–33.3) reported embouchure fatigue. The relative frequency of embouchure disorders was 59 % (95 % CI 54.6–63.6), with 26 % (95 % CI 22.4–29.5) reporting embouchure cramping. Embouchure disorders resulted in sick leave in 16 % (95 % CI 12.7–20.6). Female brass players (PR 2.0, 95 % CI 0.98–3.98) and musicians with a prior change in their embouchure (PR 2.4, 95 % CI 1.38–4.05) or breathing technique (PR 2.2, 95 % CI 1.25–3.72) and musicians with embouchure fatigue (PR 1.9, 95 % CI 1.18–2.93) presented more frequently with embouchure cramping than musicians with other or without risk factors.

Conclusion

This study shows a high relative frequency of embouchure problems in professional brass players. Given that embouchure dystonia is often preceded by embouchure problems, these findings may assist in gaining further insight into the characteristics of embouchure dystonia and the development of preventive strategies.