Christopher J. Longo

A prospective, observational registry of patients with severe sepsis: The Canadian Sepsis Treatment and Response Registry*

Objective:To determine the location of acquisition, timing, and outcomes associated with severe sepsis in community and teaching hospital critical care units. Design:Prospective, observational study. Setting:Twelve Canadian community and teaching hospital critical care units. Patients:All patients admitted between March 17, 2003, and November 30, 2004 to the study critical care units with at least a 24-hr length of stay or severe sepsis identified during the first 24 hrs. Interventions:Daily monitoring for severe sepsis. Measurements and Main Results:We recorded data describing characteristics of patients, infections, systemic responses, and organ dysfunction. Severe sepsis occurred in 1238 patients (overall rate, 19.0%; range, 8.2%–35.3%). Hospital mortality was 38.1% (95% confidence interval [CI]: 35.4–40.8). Median intensive care unit length of stay was 10.3 days (interquartile range: 5.5, 17.9). Variables associated with mortality in multivariable analysis included age (odds ratio [OR] by decade 1.50; 95% CI: 1.36–1.65), acquisition location of severe sepsis (with community as the reference—hospital [OR: 1.69; CI: 1.16–2.46], early intensive care unit [OR: 2.15; CI: 1.42–3.25], late intensive care unit [OR: 2.65; CI: 1.82–3.87]), late intensive care unit (OR: 2.65; CI: 1.82–3.87), any comorbidity (OR: 1.42; CI: 1.04–1.93), chronic renal failure (OR: 2.03; CI: 1.10–3.76), oliguria (OR: 1.34; CI: 1.02–1.76), thrombocytopenia (OR: 2.12; CI: 1.43–3.13), metabolic acidosis (OR: 1.54; CI: 1.13–2.10), Multiple Organ Dysfunction Score (OR: 1.15; CI: 1.09–1.21) and Acute Physiology and Chronic Health Evaluation II predicted risk (OR: 3.75; CI: 2.08–6.76). Conclusion:These data confirm that sepsis is common and has high mortality in general intensive care unit populations. Our results can inform healthcare system planning and clinical study designs. Modifiable variables associated with worse outcomes, such as nosocomial infection (hospital acquisition), and metabolic acidosis indicate potential targets for quality improvement initiatives that could decrease mortality and morbidity.

Comparative Effectiveness of Phosphate Binders in Patients with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis.

Background Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been linked to poor health outcomes, including diminished quality and length of life. This condition is characterized by high phosphate levels and requires phosphate-lowering agents—phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on patient-important outcomes in patients with CKD-MBD. Methods Data sources included MEDLINE and EMBASE Trials from 1996 to February 2016. We also searched the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD, randomized them to receive calcium (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet, placebo or no treatment, and reported effects on all-cause mortality, cardiovascular mortality or hospitalization at ≥4 weeks follow-up. We performed network meta-analyses (NMA) for all cause-mortality for individual agents (seven-node analysis) and conventional meta-analysis of calcium vs. NCBPBs for all-cause mortality, cardiovascular mortality and hospitalization. In the NMAs, we calculated the effect estimates for direct, indirect and network meta-analysis estimates; for both NMA and conventional meta-analysis, we pooled treatment effects as risk ratios (RR) and calculated 95% confidence intervals (CIs) using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each paired comparison. Results Our search yielded 1190 citations, of which 71 RCTs were retrieved for full review and 15 proved eligible. With 13 eligible studies from a prior review, we included 28 studies with 8335 participants; 25 trials provided data for our quantitative synthesis. Results suggest higher mortality with calcium than either sevelamer (NMA RR, 1.89 [95% CI, 1.02 to 3.50], moderate quality evidence) or NCBPBs (conventional meta-analysis RR, 1.76 [95% CI, 1.21 to 2.56, moderate quality evidence). Conventional meta-analysis suggested no difference in cardiovascular mortality between calcium and NCBPBs (RR, 2.54 [95% CI, 0.67 to 9.62 low quality evidence). Our results suggest higher hospitalization, although non-significant, with calcium than NCBPBs (RR, 1.293 [95% CI, 0.94 to 1.74, moderate quality evidence). Discussion/Conclusions Use of calcium results in higher mortality than either sevelamer in particular and NCBPBs in general (moderate quality evidence). Our results raise questions about whether administration of calcium as an intervention for CKD- MBD remains ethical. Further research is needed to explore the effects of different types of phosphate binders, including novel agents such as iron, on quality and quantity of life. Systematic Review Registration PROSPERO CRD-42016032945

Effectiveness of Health System Services and Programs for Youth to Adult Transitions in Mental Health Care: A Systematic Review of Academic Literature

Abstract Youth shifting to adult mental health services often report experiencing frustrations with accessing care that adequately replaces the youth services they had received. This systematic review assesses the peer reviewed evidence on services/programs aimed at addressing youth to adult transitions in mental health services. Findings suggest little data exists on the effectiveness of transition services/programs. While the available evidence supports meetings between youth and youth caseworkers prior to transitions occurring, it also verifies that this is not common practice. Other identified barriers to effective transitions were categorized as logistical (ineffective system communication), organizational (negative incentives), and related to clinical governance.

Do Canadian Researchers and the Lay Public Prioritize Biomedical Research Outcomes Equally? A Choice Experiment

Purpose To quantify and compare the preferences of researchers and laypeople in Canada regarding the outcomes of basic biomedical research. Method In autumn 2010, the authors conducted a cross-sectional, national survey of basic biomedical researchers funded by Canada’s national health research agency and a representative sample of Canadian citizens to assess preferences for research outcomes across five attributes using a discrete choice experiment. Attributes included advancing scientific knowledge (assessed by published papers); building research capacity (assessed by trainees); informing decisions in the health products industry (assessed by patents); targeting economic, health, or scientific priorities; and cost. The authors reduced a fractional factorial design (18 pairwise choices plus an opt-out option) to three blocks of six. They also computed part worth utilities, differences in predicted probabilities, and willingness-to-pay values using nested logit models. Results Of 3,260 potential researchers, 1,749 (53.65% response rate) completed the questionnaire, along with 1,002 citizens. Researchers and citizens prioritized high-quality scientific outcomes (papers, trainees) over other attributes. Both groups disvalued research targeted at economic priorities relative to health priorities. Researchers granted a premium to proposals targeting scientific priorities. Conclusions Citizens and researchers fundamentally prioritized the same outcomes for basic biomedical research. Notably, they prioritized traditional scientific outcomes and disvalued the pursuit of economic returns. These findings have implications for how academic medicine assigns incentives and value to basic health research and how biomedical researchers and the public may jointly contribute to setting the future research agenda.

A scoping review of evaluated interventions addressing developmental transitions for youth with mental health disorders.

BACKGROUND Youth with mental health disorders often experience challenges when transitioning into adult roles (e.g. independent living, work and community engagement). Health interventions that address the needs of youth with mental health disorders during these challenges in their development (i.e. developmental transitions) have not been reviewed in the literature. This scoping review examines the peer-reviewed research that describes evaluated interventions addressing developmental transitions for youth with mental health disorders. METHODS A search of four prominent health literature databases (CINAHL, Embase, MEDLINE and PsycINFO) was conducted to identify evaluated developmental transition interventions for adolescents and youth (12-25 years) with mental health disorders. Study selection and analysis were guided by a methodological framework for conducting scoping reviews. Selected studies were described, assessed for quality and collated based on ten dimensions from two notable conceptual frameworks in developmental transitions and disability. RESULTS Nine studies met the inclusion criteria. The interventions within these studies demonstrated five specialized and four multi-faceted programmes (i.e. multiple domains). All domains from the two conceptual frameworks were represented differently across studies. The sub-domains from these studies were most frequently related to vocational-focused interventions, least frequently related to social activities and living situation and did not explicitly map onto the sexuality sub-domain. Three multi-faceted interventions incorporated all domains and utilized each intervention approach. Study quality was rated for seven of the nine studies. Quantitative methodology for five of the seven studies was rated as higher quality. CONCLUSIONS Evaluated interventions described in the transitions literature for youth with mental health disorders predominantly focus on vocational needs. The least studied areas were the personal and interpersonal domains. These domains were only incorporated within interventions addressing multiple domains of developmental transitions. These insights can be helpful in guiding evidence-based practice and policy development, as well as informing gaps for future research programmes.

Guidelines for Health Technologies: Specific Guidance for Oncology Products in Canada

OBJECTIVE Specific methodological challenges are often encountered during cancer-related economic evaluations. The objective of this study was to provide specific guidance to analysts on the methods for the conduct of high-quality economic evaluations in oncology by building on the Canadian Agency for Drugs and Technologies in Health Guidelines for the Economic Evaluation of Health Technologies (third edition). METHODS Fifteen oncologists, health economists, health services researchers, and decision makers from across Canada identified sections in Canadian Agency for Drugs and Technologies in Health guidelines that would benefit from oncology-specific guidance. Fifteen sections of the guidelines were reviewed to determine whether 1) Canadian Agency for Drugs and Technologies in Health guidelines were sufficient for the conduct of oncology economic evaluations without further guidance specific for oncology products or 2) additional guidance was necessary. A scoping review was conducted by using a comprehensive and replicable search to identify relevant literature to inform recommendations. Recommendations were reviewed by representatives of academia, government, and the pharmaceutical industry in an iterative and formal review of the recommendations. RESULTS Major adaptations for guidance related to time horizon, effectiveness, modeling, costs, and resources were required. Recommendations around the use of final outcomes over intermediate outcomes to calculate quality-adjusted life-years and life-years gained, the type of evidence, the source of evidence, and the use of time horizon and modeling were made. CONCLUSIONS This article summarizes key recommendations for the conduct of economic evaluations in oncology and describes methods required to ensure that economic assessments in oncology are conducted in a standardized manner.

The transition from youth to adult mental health services and the economic impact on youth and their families

The transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) can be challenging for youth, their families, and healthcare providers. The purpose of this study was to identify, summarize, and assess evidence found in scholarly literature regarding the economic impact on youth and their families during the transition from CAMHS to AMHS. Relevant studies were identified through a search of 7 electronic platforms. The search identified 829 articles; 5 of which met all inclusion criteria. Evidence from the included studies suggests that, when continuity of care is lacking, transitions from CAMHS to AMHS have substantial impacts on the financial demands of youth and their families. These demands are due to increases in the cost of care, loss of employment income and productivity, and changes in insurance coverage. However, there remains limited information in this area, which highlights the need for further research.

Encouraging pharmaceutical innovation to meet the needs of both developed and developing countries

Purpose - Current pharmaceutical global pricing strategies functionally exclude developing countries from the market for drugs to treat many diseases. The purpose of this paper is to evaluate some of the proposed patent reward models to determine their feasibility in the current environment. Design/methodology/approach - A review of a variety of proposals including special financing or tax arrangements, public-private partnerships, and government-funded patent purchases are briefly reviewed. A more in-depth examination of the recently proposed health impact fund (HIF) is undertaken. Findings - In brief, the HIF requires developed countries to donate to a fund that finances the release of pharmaceutical patents. The pharmaceutical companies would be reimbursed over a ten-year period from the government donation pool based on the medicines health impact. The expected consequence of this policy would be affordable medicines for developed and developing countries. This examination highlights deficiencies in the current HIF strategy and offers a number of suggestions mostly focused on a more balanced sharing of the inherent risks in pharmaceutical product development to improve the strategies viability. Practical implications - Although among the proposed strategies, the HIF offers the most promise, the suggested changes would result in a program viewed more favourably by the pharmaceutical industry and participating countries. Originality/value - Although it is recognized that pricing challenges are limiting the availability to essential medications in developing countries, current strategies often ignore many of the market dynamics for pharmaceuticals. This critique, focused on the HIF strategy, is presented in an effort to improve the likely success of the most promising of these strategies.

A Tale of Two Health-Care Systems: Cost-Utility Analysis of Open Carpal Tunnel Release in Canada and the United States:

Purpose: Canadian health care is often criticized for extended wait times, whereas the United States suffers from increased costs. The purpose of this pilot study was to determine the cost-utility of open carpal tunnel release in Canada versus the United States. Methods: A prospective cohort study evaluated patients undergoing open carpal tunnel release at an institution in Canada and the United States. All costs from a societal perspective were captured. Utility was measured using validated health-related quality of life (HRQOL) scales—the EuroQol-5D and the Michigan Hand Outcome Questionnaire. Results: Twenty-one patients at the Canadian site and 8 patients at the US site participated. Mean total costs were US

Design of effective interventions for smoking cessation through financial and non-financial incentives

1581 ±