Overcoming Common Anxieties in Knowledge Translation: Advice for Scholarly Issue Advocates.

Policy Points Faced with urgent threats to human health and well-being such as climate change, calls among the academic community are getting louder to contribute more effectively to the implementation of the evidence generated by our research into public policy. As interest in knowledge translation (KT) surges, so have a number of anxieties about the field's shortcomings. Our paper is motivated by a call in the literature to render useful advice for those beginning in KT on how to advance impact at a policy level. By integrating knowledge from fields such as political science, moral psychology, and marketing, we suggest that thinking and acting like marketers, lobbyists, movements, and political scientists would help us advance on the quest to bridge the chasm between evidence and policy.

Framing climate change as a human health issue: enough to tip the scale in climate policy?

Almost four decades of climate science have not yet led to transformative policy change at the pace and scale required to confront the climate crisis. Colleagues in the planetary health community attribute much potential to framing climate change as human health issue in order to create greater impact on policy makers. In this Personal View, we discuss the promise and limitations of this approach by drawing on insights from political science and public policy with regards to the complexity of these contentious policy issues. We argue that we, as academics, have a moral obligation to embrace an active role in the knowledge-to-action (KTA) sphere and that we would be well advised to expand our KTA approach to include evidence-based strategies, such as lobbying or civil resistance. As scientists, we can no longer wait to embrace the realpolitik insights of political science to move our evidence into policy action.

A "health in all policies" review of Canadian public finance.

RéSUMé: OBJECTIF: Il est démontré que la santé est principalement le fruit de ses déterminants sociaux, et comme de fait, la recherche sur les systèmes de santé montre que les dépenses publiques relatives aux programmes sociaux sont souvent plus fortement corrélées à la santé des populations que les investissements dans les soins médicaux. Notre étude vise à aider les Cabinets provinciaux et fédéraux du Canada à en prendre acte en introduisant le concept de « la santé dans toutes les politiques ¼ (Health in All Policies, ou HiAP) dans les débats budgétaires. MéTHODE: L'étude est descriptive; elle analyse des données secondaires accessibles au public sur les budgets fédéraux et provinciaux pour déterminer comment le financement public des investissements dans les déterminants sociaux de la santé (DSS) aux stades précoces (< 45 ans) et ultérieurs (65 ans et plus) du parcours de vie a évolué depuis 1976 par rapport aux investissements dans les soins médicaux. RéSULTATS: Les dépenses en soins médicaux ont augmenté de 3 983 $ par personne de 65 ans et plus depuis 1976. Cette augmentation dépasse de 45 % l'augmentation combinée des dépenses en services de garde, en congés parentaux, en aide au revenu familial, en éducation et en soins médicaux par personne pour les moins de 45 ans. De toutes les nouvelles dépenses pour les Canadiens plus jeunes, les soins médicaux ont reçu les investissements les plus importants. Alors que les dépenses médicales pour les retraités ont dépassé d'un peu plus de la moitié le rythme des dépenses en revenus de retraite, les dépenses médicales pour les Canadiens plus jeunes ont augmenté presque autant que les dépenses pour l'ensemble des politiques de DSS à leur endroit. CONCLUSION: Depuis 1976, il y a une plus grande concordance entre l'approche HiAP et le financement public du Canada pour les aînés que pour les Canadiens plus jeunes. Ces résultats offrent aux décideurs d'importantes informations rétrospectives pour évaluer les futurs investissements publics dans les soins médicaux et les déterminants sociaux de la santé pour tout le parcours de vie, ainsi que les plans de financement de ces investissements.

A surgical intervention for the body politic: Generation Squeeze applies the Advocacy Coalition Framework to social determinants of health knowledge translation.

SETTING: The World Health Organization Commission on the Social Determinants of Health (SDoH) observes that building political will is central to all its recommendations, because governments respond to those who organize and show up. Since younger Canadians are less likely to vote or to organize in between elections, they are less effective at building political will than their older counterparts. This results in an age gap between SDoH research and government budget priorities. Whereas Global AgeWatch ranks Canada among the top countries for aging, UNICEF ranks Canada among the least generous OECD (Organisation for Economic Co-operation and Development) countries for the generations raising young children. INTERVENTION: A surgical intervention into the body politic. Guided by the "health political science" literature, the intervention builds a non-profit coalition to perform science-based, non-partisan democratic engagement to increase incentives for policy-makers to translate SDoH research about younger generations into government budget investments. OUTCOMES: All four national parties integrated policy recommendations from the intervention into their 2015 election platforms. Three referred to, or consulted with, the intervention during the election. The intervention coincided with all parties committing to the single largest annual increase in spending on families with children in over a decade. IMPLICATIONS: Since many population-level decisions are made in political venues, the concept of population health interventions should be broadened to include activities designed to mobilize SDoH science in the world of politics. Such interventions must engage with the power dynamics, values, interests and institutional factors that mediate the path by which science shapes government budgets.

The reallocation challenge: Containing Canadian medical care spending to invest in the social determinants of health.

We argue that Canadian provincial governments should contain medical care spending in order to invest more in the social determinants of health (SDH). Others have said this, many times. Doing it has not proven easy. We therefore emphasize the potential contribution of the priority-setting and resource allocation literature. This literature identifies formal tools and approaches that have built cultures of support for resource shifts, while providing pragmatic means for advancing efficiency and equity. Although reallocation towards SDH from other areas of the health care system is financially viable and supported by existing research, it will require new emphasis on the design of population health interventions that make reallocation politically expedient.

The politics and power in caregiving for identity: insights for Indian residential school truth and reconciliation.

The authors examine the politics of caregiving for identity to enrich scholarship about power. They report on a qualitative study with Aboriginal mothers who parent in the wake of the Canadian Indian residential schools (IRS). Just as this system disrupted familial caregiving to assimilate Aboriginal Peoples, data show some mothers now strive to organize their caregiving in ways that serve decolonization and community empowerment. Building on their expertise, the authors argue that counter-colonial family policy investments to support such caregiving should factor in any just compensation for the IRS system if its population, and not just individual, costs are to be redressed.

Selection of area-level variables from administrative data: an intersectional approach to the study of place and child development.

Given data limitations, neighborhood effects scholarship relies heavily on administrative data to measure area-level constructs. We provide new evidence to guide the selection of indicators from routinely collected sources, focusing on effects on early child development. Informed by an analytic paradigm attuned to the intersection of race, class, and sex, along with population-level data in British Columbia, Canada, our findings signal the need for greater precision when choosing variables in place of the now dominant approaches for measuring constructs like income/wealth, employment, family structure and race/ethnicity. We also provide new evidence about which area-level variables associate with the different domains of child development, as well as how area-level associations vary across urban and rural contexts.

The economic costs of early vulnerability in Canada.

OBJECTIVE: The study estimates the economic costs of early vulnerability in the light of population-level data showing that between 25% and 30% of Canadian children do not arrive at kindergarten meeting all of the developmental benchmarks they need to thrive both now and into the future. METHODS: The study examines Early Development Instrument (EDI) data across Canada as of 2008/09, and across time within British Columbia since 2001. We then link the BC EDI data with school achievement results on standardized tests in grades four and seven, along with graduation records and criminal justice information. RESULTS: The result is a synthetic cohort with which we can simulate the impact on economic growth of reducing early vulnerability in BC from its current rate of 29% to 10%, a threshold above which child vulnerability is biologically unnecessary. DISCUSSION: Nearly three times what it should be, a rate of early vulnerability that approaches 30% signals that the country now tolerates an unnecessary brain drain that will dramatically deplete our future stock of human capital. Economic analyses reveal that this depletion will cause Canada to forgo 20% in GDP (gross domestic product) growth over the next 60 years. The economic value of this loss is equivalent to investing $2.2 trillion to $3.4 trillion today at a rate of 3.5% interest, even after paying for the social investment required to reduce vulnerability.

Is a pan-Canadian early child development system possible? Yes, when we redress what ails Canadian culture.

Canada lags behind other countries when it comes to investing in families with children. Canada, therefore, fails to promote health by not optimizing early development. The authors diagnose the Canadian failure. The problem is not research or fiscal capacity, but rather a sickness in Canadian culture. Four ailments are identified: Canadians are convinced they cannot afford new social investments, tend to treat illness rather than promote health, ignore that good family policy requires gender equality, and discount intergenerational justice. In response, the authors propose four policy solutions. Their pan-Canadian framework would cost $22 billion annually, not even one-half of current elderly and pension benefits. The new investment would reduce child vulnerability from approximately 30% to just 10% of children within 10 years. This reduction in early vulnerability would increase gross domestic product 20% more over 60 years than if Canadians tolerate the status quo.

The safety and efficacy of fentanyl iontophoretic transdermal system compared with morphine intravenous patient-controlled analgesia for postoperative pain management: an analysis of pooled data from three randomized, active-controlled clinical studies.

BACKGROUND: Postoperative pain is often managed using IV patient-controlled analgesia (PCA). In this analysis of pooled data, we compared the safety and efficacy of the fentanyl iontophoretic transdermal system (ITS) with morphine IV PCA. METHODS: Data were obtained from three multicenter, randomized, active-controlled trials (N = 1941). The primary efficacy measure was success ("good"/"excellent" ratings) on the 24-h patient global assessment of the method of pain control. Pain intensity, relative dosing ratios, discontinuation rates, and adverse events were assessed. Efficacy was evaluated across age, surgery type, and body mass index (BMI). RESULTS: Comparable percentages of patients reported success on the 24-h patient global assessment of the method of pain control (fentanyl ITS, 80.5%; morphine IV PCA, 81.0%; difference = -0.5%; 95% confidence interval, -4.0% to 3.0%). Mean last pain intensity scores in the first 24 h were comparable (fentanyl ITS, 3.1; morphine IV PCA, 3.0; difference = 0.07; 95% confidence interval, -0.14 to 0.29). Relative dosing ratios of fentanyl to morphine overall and in subpopulations (age, BMI) were comparable over 6, 12, and 24 h. Fentanyl ITS was equally effective when compared with morphine IV PCA for patient subpopulations (age, surgery type, and BMI). Discontinuation rates and the incidence of adverse events were similar between groups. CONCLUSIONS: These pooled data represent one of the largest head-to-head comparisons of fentanyl versus morphine in a postoperative acute pain setting. Results suggest that fentanyl ITS is effective across subpopulations defined by age and BMI, and support a consistent safety and efficacy profile of fentanyl delivered by fentanyl ITS for postoperative pain management.

Effects of statins on cognitive function in patients with Alzheimer's disease in galantamine clinical trials.

BACKGROUND AND OBJECTIVE: A number of reports have been published on the possible involvement of changes in brain cholesterol metabolism in the origin of Alzheimer's disease (AD) and the potential for influencing these changes by administration of HMG-CoA reductase inhibitors ('statins'). The aim of this study was to evaluate a potential association between use of statins and maintenance of cognitive function in patients with AD in galantamine clinical trials. METHOD: A post hoc analysis was conducted on data pooled from three double-blind, placebo-controlled, clinical trials of galantamine in patients with AD. Patients were divided into four treatment groups: statin plus galantamine (n = 42), statin alone (n = 50), galantamine alone (n = 614) or neither galantamine nor statin (n = 619). RESULTS: Galantamine was associated with a significant beneficial effect on cognitive status (p < 0.001). The association of use of statins with changes in cognitive status was not significant (p = 0.083). There was no significant interaction between the effects on cognition of statins and galantamine (p = 0.183) and no statistically significant changes in adverse effect rates were observed. CONCLUSION: These findings suggest the need for larger long-term trials to confirm or refute possible effects of statins on cognitive function and the potential interaction of statins with acetylcholinesterase inhibitors in the treatment of AD.

Long-term outcomes of galantamine treatment in patients with Alzheimer disease.

OBJECTIVE: The authors evaluated the long-term safety, efficacy, and tolerability of galantamine 24 mg/day in the treatment of Alzheimer disease by means of a 12-month, open-label extension of an earlier 5-month, double-blind, placebo-controlled trial with a 6-week withdrawal phase. METHODS: Patients completing two double-blind, placebo-controlled trials (N=699) were escalated to a 24-mg dose (12 mg bid) of galantamine during a period of 2 weeks and treated for 12 months beyond the initial 6.5-month, double-blind period (total treatment duration: 18.5 months). The primary efficacy measure was the change from baseline in the Alzheimer's Disease Assessment Scale (ADAS-Cog/11) score at 18.5 months; secondary endpoints included total scores on the Alzheimer's Disease Cooperative Study of Activities of Daily Living and the Neuropsychiatric Inventory. Standard safety evaluations, including adverse-event monitoring, were performed. RESULTS: Patients taking galantamine continuously throughout the double-blind and open-label studies (N=288) showed sustained cognitive benefits on ADAS-Cog/11 scores at 18.5 months. Patients were maintained close to baseline cognitive ability for 12 months, and safety was as expected and documented in other large studies of galantamine. Analysis of the subgroup of patients (N=113) who completed the entire 18.5 months of galantamine treatment showed that cognitive function was maintained up to 14 months. CONCLUSIONS: Results of this open-label extension support the findings from previous galantamine studies and demonstrate the safety and tolerability of galantamine for up to 18.5 months.

Galantamine maintains ability to perform activities of daily living in patients with Alzheimer's disease.

OBJECTIVES: To examine the effect of galantamine on activities of daily living (ADLs) with respect to baseline dementia severity, correlation with cognitive and global function, specific ADLs affected, and maintenance of ADL independence. DESIGN: Secondary analysis of a 5-month randomized, placebo-controlled trial. SETTING: Multiple U.S. clinical centers. PARTICIPANTS: Six hundred fifty-nine patients with mild to moderate Alzheimer's disease (AD) who completed 5 months of treatment. INTERVENTION: Galantamine at a maintenance dose of 16 or 24 mg/d. MEASUREMENTS: The AD Cooperative Study ADL Inventory (ADCS/ADL). RESULTS: Galantamine resulted in more improvement in ADCS/ADL scores than placebo regardless of baseline dementia severity, with the greatest differences occurring in patients with more severe disease. Changes in ADCS/ADL scores correlated significantly with change scores on the cognitive subscale of the AD Assessment Scale (r=-0.24). Galantamine treatment resulted in maintenance or improvement of basic and instrumental ADLs, and change from baseline to Month 5 in scores for each individual ADL item favored galantamine over placebo in three of six basic ADLs and six of 17 instrumental ADLs. CONCLUSION: Galantamine has a favorable effect on ADL performance in patients with AD, detectable after 5 months of treatment, regardless of dementia severity. The ADCS/ADL appears to better measure distinct abilities that may be relevant not only in clinical trials but also in individual patients than do cognitive assessments.

The clinical efficacy and safety of galantamine in the treatment of Alzheimer's disease.

Alzheimer's disease is a progressive, neurodegenerative condition characterized by deficits in cognition, inability to perform activities of daily living, and alterations in behavior. Galantamine hydrobromide is the newest acetylcholinesterase inhibitor (AChEI) approved in the United States for the treatment of mild-to-moderate AD. The safety and efficacy of galantamine has been demonstrated in multiple randomized, Phase III trials of >2,600 patients with mild-to-moderate AD. Studies have found that galantamine improved or maintained performance in all domains of AD (cognition, function, behavior, and caregiver burden) in the short term and slowed the decline in performance or maintained baseline performance through 12 months. The dual mechanism of action may make galantamine a reasonable treatment option for both newly diagnosed patients and patients who have not benefitted from or have poorly tolerated current therapy.

Reduction of behavioral disturbances and caregiver distress by galantamine in patients with Alzheimer's disease.

OBJECTIVE: Alzheimer's disease pathology includes both histologic changes and neurotransmitter deficits. The cholinergic deficit contributes to both cognitive and behavioral disturbances, and cholinesterase inhibitors may improve behavior in Alzheimer's disease patients. This analysis was conducted to assess the impact of galantamine, a cholinesterase inhibitor with nicotinic-receptor-modulating properties, on the pattern and evolution of behavioral disturbances in patients with Alzheimer's disease and on caregiver distress related to patients' behavior. METHOD: Data from 978 patients with mild to moderate Alzheimer's disease who were randomly assigned to placebo or galantamine (8, 16, or 24 mg/day) were analyzed. Behavioral changes were assessed with the Neuropsychiatric Inventory, and alterations in caregiver distress were measured by the Neuropsychiatric Inventory distress scale. Data collected at baseline and 12 and 21 weeks postbaseline were analyzed. RESULTS: Neuropsychiatric Inventory scores worsened with placebo, whereas patients treated with 16 or 24 mg/day of galantamine had no change in total Neuropsychiatric Inventory scores. Treated patients, asymptomatic or symptomatic at baseline, had better Neuropsychiatric Inventory subscale scores than did patients receiving placebo. Behavioral improvement in patients symptomatic at baseline ranged from 29% to 48%. Changes were evident in patients receiving 16 or 24 mg/day of galantamine. High-dose galantamine was associated with a significant reduction in caregiver distress. CONCLUSIONS: Galantamine therapy was associated with reduced emergence of behavioral disturbances and improvement in existing behavioral problems in patients with mild to moderate Alzheimer's disease, with a concomitant reduction in reported caregiver distress.

The cognitive benefits of galantamine are sustained for at least 36 months: a long-term extension trial.

BACKGROUND: Alzheimer disease (AD) causes progressive cognitive and functional decline over years. Although cholinesterase inhibitors have demonstrated efficacy in studies lasting 3 to 6 months, little is known about long-term therapy. OBJECTIVE: To report the long-term cognitive effects of galantamine hydrobromide given continuously for 36 months in AD patients. PARTICIPANTS: Subjects were 194 US patients with mild to moderate AD who had been randomized to continuous galantamine therapy in either of 2 double-blind placebo-controlled trials. Subjects subsequently received open-label continuous galantamine therapy for up to 36 months. MAIN OUTCOME MEASURES: Effects on cognition were analyzed as change from study enrollment baseline in scores on the Alzheimer's Disease Assessment Scale-11-item cognitive subscale. Cognitive decline in galantamine-treated subjects was compared with that in a clinically similar historical control sample of AD patients who had received placebo for 12 months and with the mathematically predicted decline of untreated patients over 36 months. The rate of cognitive decline of patients who completed the entire 36-month trial (n = 119) was compared with that of patients who withdrew for any reason during the long-term open-label extension (n = 75). An inverted responder analysis was also performed in 36-month completers. RESULTS: Patients treated continuously with galantamine for 36 months increased a mean +/- SE of 10.2 +/- 0.9 points on the Alzheimer's Disease Assessment Scale-11-item cognitive subscale-a substantially smaller cognitive decline (approximately 50%) than that predicted for untreated patients. Patients discontinuing galantamine therapy before 36 months had declined at a similar rate before discontinuation as those completing 36 months of treatment. Almost 80% of patients who received galantamine continuously for up to 36 months seemed to demonstrate cognitive benefits compared with those predicted for untreated patients. CONCLUSIONS: Cognitive decline over 36 months of continuous galantamine treatment was substantially less than the predicted cognitive decline of untreated patients with mild to moderate dementia. Thus, the cognitive benefits of galantamine seemed to be sustained for at least 36 months. These findings suggest that galantamine slows the clinical progression of AD.

A long-term comparison of galantamine and donepezil in the treatment of Alzheimer's disease.

OBJECTIVE: To compare the long-term efficacy and safety of galantamine 24 mg/day and donepezil 10 mg/day in patients with Alzheimer's disease. PATIENTS AND STUDY DESIGN: This was a rater-blinded, randomised, parallel-group multicentre study (18 outpatient clinics) in the UK. 182 patients (69 male, 113 female) with Alzheimer's disease were randomised to galantamine (n = 94) or donepezil (n = 88) for 52 weeks. MAIN OUTCOME MEASURES: The effects of galantamine and donepezil on function using the Bristol Activities of Daily Living Scale (BrADL); cognition using the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog/11); behaviour using the Neuropsychiatric Inventory (NPI); caregiver burden using the Screen for Caregiver Burden; and safety were assessed. RESULTS: BrADL total scores showed no significant difference between treatment groups in mean change from baseline to week 52. In the total population, in terms of cognition, galantamine patients' scores on the MMSE at week 52 did not differ significantly from baseline (-0.52 +/- 0.39, p < 0.5 vs baseline), whereas donepezil patients' scores deteriorated significantly from baseline (-1.58 +/- 0.42, p < 0.0005 vs baseline). The between-group difference in MMSE change, which showed a trend for superiority of galantamine, did not reach statistical significance (p < or = 0.1). In the ADAS-cog/11 analysis, between-group differences for the total population were not significant, whereas galantamine-treated patients with MMSE scores of 12-18 demonstrated an increase (worsening) in the ADAS-cog/11 score of 1.61 +/- 0.80 versus baseline, compared with an increase of 4.08 +/- 0.84 for patients treated with donepezil, with a significant between-group difference in favour of galantamine (p < or = 0.05). More caregivers of patients receiving galantamine reported reductions in burden compared with donepezil. Changes from baseline in NPI were similar for both treatments. Both treatments were well tolerated; most adverse events were transient and of mild-to-moderate intensity, and were consistent with the findings of previous clinical trials. CONCLUSIONS: Significant advantages were found in the treatment response to galantamine (versus donepezil) on cognition as measured by response rates on the MMSE and ADAS-cog/11.