Comorbidities,Treatment and Ensuing Survival in Men with Prostate Cancer

Background  

Comorbidity is poorly integrated into prostate cancer decision making.     

A framework for discussion on how to improve prevention, management, and control of hypertension in Canada

Increased blood pressure is a leading risk for premature death and disability. The causes of increased blood pressure are intuitive and well known. However, the fundamental basis and means for improving blood pressure control are highly integrated into our complex societal structure both inside and outside our health system and hence require a comprehensive discussion of the pathway forward. A group of Canadian experts was appointed by Hypertension Canada with funding from Public Health Agency of Canada and the Heart and Stroke Foundation of Canada, Canadian Institute for Health Research (HSFC-CIHR) Chair in Hypertension Prevention and Control to draft a discussion Framework for prevention and control of hypertension. The report includes an environmental scan of past and current activities, proposals for key indicators, and targets to be achieved by 2020, and what changes are likely to be required in Canada to achieve the proposed targets. The key targets are to reduce the prevalence of hypertension to 13% of adults and improve control to 78% of those with hypertension. Broad changes in government policy, research, and health services delivery are required for these changes to occur. The Hypertension Framework process is designed to have 3 phases. The first includes the experts' report which is summarized in this report. The second phase is to gather input and priorities for action from individuals and organizations for revision of the Framework. It is hoped the Framework will stimulate discussion and input for its full intended lifespan 2011-2020. The third phase is to work with individuals and organizations on the priorities set in phase 2.     

Cause-specific mortality adjudication in the UPLIFT® COPD trial: findings and recommendations

Mortality is an important endpoint in chronic obstructive pulmonary disease (COPD) trials, although accurately determining cause of death is difficult. In the Understanding the Potential Long-term Impacts on Function with Tiotropium (UPLIFT?) trial, a mortality adjudication committee (MAC) provided systematic, independent and blinded assessment of cause-specific mortality of all 981 reported deaths. Here we describe this process of mortality adjudication and methodological revisions introduced to help standardise the adjudication of two areas recognised to pose particular difficulty; firstly, the classification of fatal COPD exacerbations that occur in the setting of pneumonia and secondly, the categorisation of sudden death. In addition MAC determined cause of death was compared with that reported by site investigators (SIs). MAC-assigned causes of death were: respiratory, 35%; cancer, 25%; cardiovascular, 11%; sudden cardiac death, 4.4%; sudden death, 3.4%; other, 8.8%; unknown, 12.4%. Cancer/cardiac deaths were more common in Global Initiative for Chronic Obstructive Lung Disease stage II, respiratory deaths in stages III and IV. Agreement between MAC and SI regarding cause of death was complete (50.2%), incomplete (18.5%) or none (31.3%). The SI classified deaths as cardiac three-fold more frequently than MAC (incidence rate [IR]/100 patient-years 0.797 vs. 0.257), although IR ratios for cardiac deaths for tiotropium vs. control were similar between SI and MAC. Discrepancies between MAC- and SI-adjudicated causes of death are common, especially increased reporting of cardiac deaths by the SI. Future multicentre COPD trials should plan appropriate infrastructure before study initiation to ensure collection and interpretation of fatal events data.     

Exercise-induced bronchoconstriction update: therapeutic management

Management of exercise-induced bronchoconstriction (EIB) should include both prevention and treatment directed toward the underlying asthma and bronchial hyperresponsiveness. Both nonpharmacologic and pharmacologic approaches should be followed. Preexercise warm-up, to take advantage of the refractory period that follows EIB, is an important preventive technique. Dietary interventions such as fish oil, vitamin D, and ascorbic acid have shown promising results. Beta 2-agonists are considered the most effective agents for EIB at this time but intermittent use is recommended to avoid tolerance or decreased effectiveness with daily regular use. Leukotriene inhibitors and mast cell stabilizing agents can be useful in EIB but are less effective than beta 2-agonists. Tolerance to beta 2-agonists is not prevented by concomitant use of inhaled corticosteroid but it is not known whether use of leukotriene inhibitors can affect tolerance. EIB in elite athletes with no underlying asthma may have a different pathogenesis.     

Embolic Protection Devices in Saphenous Vein Graft and Native Vessel Percutaneous Intervention: A Review

The clinical benefit of percutaneous intervention (PCI) depends on both angiographic success at the site of intervention as well as the restoration of adequate microvascular perfusion. Saphenous vein graft intervention is commonly associated with evidence of distal plaque embolization, which is correlated with worse clinical outcomes. Despite successful epicardial intervention in the acute MI patient treated with primary PCI, distal tissue perfusion may still be absent in up to 25% of cases [1-3]. Multiple devices and pharmacologic regimens have been developed and refined in an attempt to protect the microvascular circulation during both saphenous vein graft intervention and primary PCI in the acute MI setting. We will review the evidence for various techniques for embolic protection of the distal myocardium during saphenous vein graft PCI and primary PCI in the native vessel.     

Local insulin therapy affects fracture healing in a rat model

A significant number of lower extremity fractures result in mal‐union necessitating effective treatments to restore ambulation. Prior research in diabetic animal fracture models demonstrated improved healing following local insulin application to the fracture site and indicated that local insulin therapy can aid bone regeneration, at least within an insulin‐dependent diabetic animal model. This study tested whether local insulin therapy could accelerate femur fracture repair in normal, non‐diabetic rats. High (20 units) and low (10 units) doses of insulin were delivered in a calcium sulfate carrier which provided sustained release of the exogenous insulin for 7 days after fracture. Histomorphometry, radiographic scoring, and torsional mechanical testing were used to measure fracture healing. The fracture calluses from rats treated with high‐dose insulin had significantly more cartilage than untreated rats after 7 and 14 days of healing. After 4 weeks of healing, femurs from rats treated with low‐dose insulin had significantly higher radiographic scores and mechanical strength (p < 0.05), compared to the no treatment control groups. The results of this study suggest that locally delivered insulin is a potential therapeutic agent for treating bone fractures. Further studies are necessary, such as large animal proof of concepts, prior to the clinical use of insulin for bone fracture treatment. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 776–782, 2013