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The mechanisms by which brain insults lead to subsequent epilepsy remain unclear. Insults, including trauma, stroke, tumors, infections, and long seizures [status epilepticus (SE)], create a neuronal state of increased metabolic demand or decreased energy supply. Neurons express molecules that monitor their metabolic state, including sirtuins (Sirts). Sirtuins deacetylate cytoplasmic proteins and nuclear histones, and their epigenetic modulation of the chromatin governs the expression of many genes, influencing neuronal properties. Thus, sirtuins are poised to enduringly modulate neuronal properties following SE, potentially contributing to epileptogenesis, a hypothesis supported by the epilepsy-attenuating effects of blocking a downstream target of Sirt1, Neuron-Restrictive Silencer Factor (NRSF) also know as REST (RE1-Silencing Transcription factor). Here we used an adult male rat model of epileptogenesis provoked by kainic acid-induced SE (KA-SE). We assessed KA-SE-provoked Sirt1 activity, infused a Sirt1 inhibitor (EX-527) after KA-SE, and examined for epileptogenesis using continuous digital video-EEG. Sirt1 activity, measured using chromatin immunoprecipitation for Sirt1 binding at a target gene, increased rapidly after SE. Post hoc infusion of the Sirt1 inhibitor prevented Sirt1-mediated repression of a target gene. Blocking Sirt1 activity transiently after KA-SE did not significantly influence the time- course and all of the parameters of epilepsy development. Specifically, latency to first seizure and seizure number, duration, and severity (using the Racine scale and EEG measures) as well as the frequency and duration of interictal spike series, were all unchanged. KA-SE provoked a robust inflammatory response and modest cell loss, yet neither was altered by blocking Sirt1. In conclusion, blocking Sirt1 activity after KA-SE does not abrogate epilepsy development, suggesting that the mechanisms of such acquired epileptogenesis are independent of Sirt1 function.

• The fetus aborted at 9 months was developmentally equivalent to a 5-month fetus. • Parentage testing confirmed that both fetuses were from the same sire and dam. • In this instance initiating treatment for placentitis probably saved the co-twin. Twin pregnancy in mares is one of the leading causes of abortions. Abortion invariably impacts both fetuses. This report describes an unusual case of a twin surviving to term following the abortion of its co-twin at 9 months in a 7-year-old Egyptian Arabian mare. At the time of abortion at 9 months of gestation, the size of the aborted fetus was equivalent to one of approximately 5 months of age while the age of the live co-twin was 9 months. Both fetuses were males. A skin sample was collected from the aborted fetus and hair samples were collected from the dam, sire and live foal for parentage analysis. The parentage analysis confirmed that both fetuses were by the same dam and sire stallion. The authors suggest several scenarios to explain this condition. This report describes a unique case of a twin surviving to term following the abortion of its co-twin at 9 months in a mare. [ABSTRACT FROM AUTHOR]

Abstract Background Low income individuals with diabetes are at particularly high risk for poor health outcomes. While specialized diabetes care may help reduce this risk, it is not currently known whether there are significant clinical differences across income groups at the time of referral. The objective of this study is to determine if the clinical profiles and medication use of patients referred for diabetes care differ across income quintiles. Methods This cross-sectional study was conducted using a Canadian, urban, Diabetes Education Centre (DEC) database. Clinical information on the 4687 patients referred to the DEC from May 2000 – January 2002 was examined. These data were merged with 2001 Canadian census data on income. Potential differences in continuous clinical parameters across income quintiles were examined using regression models. Differences in medication use were examined using Chi square analyses. Results Multivariate regression analysis indicated that income was negatively associated with BMI (p < 0.0005) and age (p = 0.023) at time of referral. The highest income quintiles were found to have lower serum triglycerides (p = 0.011) and higher HDL-c (p = 0.008) at time of referral. No significant differences were found in HBA1C, LDL-c or duration of diabetes. The Chi square analysis of medication use revealed that despite no significant differences in HBA1C, the lowest income quintiles used more metformin (p = 0.001) and sulfonylureas (p < 0.0005) than the wealthy. Use of other therapies were similar across income groups, including lipid lowering medications. High income patients were more likely to be treated with diet alone (p < 0.0005). Conclusion Our findings demonstrate that low income patients present to diabetes clinic older, heavier and with a more atherogenic lipid profile than do high income patients. Overall medication use was higher among the lower income group suggesting that differences in clinical profiles are not the result of under-treatment, thus invoking lifestyle factors as potential contributors to these findings.

Background: There is a large body of evidence evaluating quality improvement (QI) programmes to improve care for adults living with diabetes. These programmes are often comprised of multiple QI strategies, which may be implemented in various combinations. Decision-makers planning to implement or evaluate a new QI programme, or both, need reliable evidence on the relative effectiveness of different QI strategies (individually and in combination) for different patient populations., Objectives: To update existing systematic reviews of diabetes QI programmes and apply novel meta-analytical techniques to estimate the effectiveness of QI strategies (individually and in combination) on diabetes quality of care., Search Methods: We searched databases (CENTRAL, MEDLINE, Embase and CINAHL) and trials registers (ClinicalTrials.gov and WHO ICTRP) to 4 June 2019. We conducted a top-up search to 23 September 2021; we screened these search results and 42 studies meeting our eligibility criteria are available in the awaiting classification section., Selection Criteria: We included randomised trials that assessed a QI programme to improve care in outpatient settings for people living with diabetes. QI programmes needed to evaluate at least one system- or provider-targeted QI strategy alone or in combination with a patient-targeted strategy. - System-targeted: case management (CM); team changes (TC); electronic patient registry (EPR); facilitated relay of clinical information (FR); continuous quality improvement (CQI). - Provider-targeted: audit and feedback (AF); clinician education (CE); clinician reminders (CR); financial incentives (FI). - Patient-targeted: patient education (PE); promotion of self-management (PSM); patient reminders (PR). Patient-targeted QI strategies needed to occur with a minimum of one provider or system-targeted strategy., Data Collection and Analysis: We dual-screened search results and abstracted data on study design, study population and QI strategies. We assessed the impact of the programmes on 13 measures of diabetes care, including: glycaemic control (e.g. mean glycated haemoglobin (HbA1c)); cardiovascular risk factor management (e.g. mean systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), proportion of people living with diabetes that quit smoking or receiving cardiovascular medications); and screening/prevention of microvascular complications (e.g. proportion of patients receiving retinopathy or foot screening); and harms (e.g. proportion of patients experiencing adverse hypoglycaemia or hyperglycaemia). We modelled the association of each QI strategy with outcomes using a series of hierarchical multivariable meta-regression models in a Bayesian framework. The previous version of this review identified that different strategies were more or less effective depending on baseline levels of outcomes. To explore this further, we extended the main additive model for continuous outcomes (HbA1c, SBP and LDL-C) to include an interaction term between each strategy and average baseline risk for each study (baseline thresholds were based on a data-driven approach; we used the median of all baseline values reported in the trials). Based on model diagnostics, the baseline interaction models for HbA1c, SBP and LDL-C performed better than the main model and are therefore presented as the primary analyses for these outcomes. Based on the model results, we qualitatively ordered each QI strategy within three tiers (Top, Middle, Bottom) based on its magnitude of effect relative to the other QI strategies, where 'Top' indicates that the QI strategy was likely one of the most effective strategies for that specific outcome. Secondary analyses explored the sensitivity of results to choices in model specification and priors.  Additional information about the methods and results of the review are available as Appendices in an online repository. This review will be maintained as a living systematic review; we will update our syntheses as more data become available., Main Results: We identified 553 trials (428 patient-randomised and 125 cluster-randomised trials), including a total of 412,161 participants. Of the included studies, 66% involved people living with type 2 diabetes only. Participants were 50% female and the median age of participants was 58.4 years. The mean duration of follow-up was 12.5 months. HbA1c was the commonest reported outcome; screening outcomes and outcomes related to cardiovascular medications, smoking and harms were reported infrequently. The most frequently evaluated QI strategies across all study arms were PE, PSM and CM, while the least frequently evaluated QI strategies included AF, FI and CQI. Our confidence in the evidence is limited due to a lack of information on how studies were conducted.  Four QI strategies (CM, TC, PE, PSM) were consistently identified as 'Top' across the majority of outcomes. All QI strategies were ranked as 'Top' for at least one key outcome. The majority of effects of individual QI strategies were modest, but when used in combination could result in meaningful population-level improvements across the majority of outcomes. The median number of QI strategies in multicomponent QI programmes was three.  Combinations of the three most effective QI strategies were estimated to lead to the below effects:  - PR + PSM + CE: decrease in HbA1c by 0.41% (credibility interval (CrI) -0.61 to -0.22) when baseline HbA1c < 8.3%; - CM + PE + EPR: decrease in HbA1c by 0.62% (CrI -0.84 to -0.39) when baseline HbA1c > 8.3%;  - PE + TC + PSM: reduction in SBP by 2.14 mmHg (CrI -3.80 to -0.52) when baseline SBP < 136 mmHg; - CM + TC + PSM: reduction in SBP by 4.39 mmHg (CrI -6.20 to -2.56) when baseline SBP > 136 mmHg;  - TC + PE + CM: LDL-C lowering of 5.73 mg/dL (CrI -7.93 to -3.61) when baseline LDL < 107 mg/dL; - TC + CM + CR: LDL-C lowering by 5.52 mg/dL (CrI -9.24 to -1.89) when baseline LDL > 107 mg/dL. Assuming a baseline screening rate of 50%, the three most effective QI strategies were estimated to lead to an absolute improvement of 33% in retinopathy screening (PE + PR + TC) and 38% absolute increase in foot screening (PE + TC + Other)., Authors' Conclusions: There is a significant body of evidence about QI programmes to improve the management of diabetes. Multicomponent QI programmes for diabetes care (comprised of effective QI strategies) may achieve meaningful population-level improvements across the majority of outcomes. For health system decision-makers, the evidence summarised in this review can be used to identify strategies to include in QI programmes. For researchers, this synthesis identifies higher-priority QI strategies to examine in further research regarding how to optimise their evaluation and effects. We will maintain this as a living systematic review., (Copyright © 2023 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Introduction: Patient-centred care (PCC) has come to the forefront for many institutions, funding agencies and clinicians, and is integrated into care. Does a disconnect in understanding still exist between patients, healthcare organizations and clinicians in what PCC means and how outstanding issues might be addressed?, Methods: We conducted interviews and focus groups with self-reported chronic care patients and clinicians providing care to these patients exploring PCC experiences, expectations and practices. These data were initially analysed using inductive thematic analysis. This paper reports on the findings of a secondary analysis examining the alignment between patients and clinicians on five key predetermined dimensions of PCC., Results: Eighteen patients participated, representing a range of chronic conditions. Thirty-eight clinicians participated. One thousand and three hundred patient and 1800 clinician codes were identified and grouped into 5 main topics with 140 unique themes (patients) and 9 main topics with 54 unique themes (clinicians). A total of 166 quotes (patient = 93, clinician = 73) were identified for this PCC definition alignment analysis. Partial or complete alignment of patient and clinician perspectives was seen on most dimensions. Key disconnects were observed in patient involvement, patient empowerment and clinician-patient communication. Only 18% of patients reported experiencing patient-centred communication, whereas 57% of clinicians reported using patient-focused communication approaches., Conclusion: Overall, study patients and clinicians endorse that many PCC elements occur. This study highlights key differences between patients and clinicians, suggesting persistent challenges. Clinician participants relayed their PCC approaches of informing and educating patients; however, patients often perceive these approaches as didactic, role-diminishing and noncollaborative. Collaborative approaches, such as shared decision-making, hold promise to bridge persistent PCC gaps and should be integrated into medical education programmes., Patient or Public Contribution: This project was conceived and executed with a co-design approach wherein patients with chronic conditions who are trained in research (i.e., see descriptions of Patient and Community Engagement Research in the text) were involved in all stages of the research project alongside other researchers on the project team. Healthcare providers were involved as participants and as principal investigators in the project., (© 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Objective: To summarize the literature on the impact of video-based educational interventions on patient outcomes in inpatient settings as compared to standard education techniques., Methods: This review followed a scoping review methodology. English language articles were searched in Pubmed, Medline, Cochrane, and CINAHL databases. Inclusion criteria were: use of video-based educational interventions, and inpatient hospital settings. Abstracts were reviewed and selected according to predetermined criteria, followed by full-text scrutiny., Results: Sixty-two empirical studies were identified, with 38 (61%) reporting a significant positive effect of video-based educational interventions on patient outcomes, compared to control groups (i.e., standard education). Three different types of video-based educational intervention formats were identified: animated presentations, professionals in practice, and patient narratives. Outcome types included: knowledge-based, clinical, emotional, and behavioral, with knowledge-based most prevalent., Conclusion: Video-based educational interventions are common in the hospital setting. These interventions are effective at improving short-term health literacy goals, but their impact on behavior or lifestyle modifications is unclear. Their effectiveness also depends on presentation format, timing, and the patient's emotional well-being., Practice Implications: Video-based educational delivery is effective for improving short-term health literacy, however a combination of approaches delivered over an extended period of time may support improving longer-term health outcomes., (Copyright © 2018. Published by Elsevier B.V.)

Background: Little is known about how multimorbidity, dementia and increasing age combine to influence health outcomes or utilization. Our objective was to examine the joint associations between age, dementia and burden of morbidity with mortality and other clinical outcomes., Methods: We did a retrospective population-based cohort study of all adults aged 65 years and older residing in Alberta, Canada, between 2002 and 2013. We used validated algorithms applied to administrative and laboratory data from the provincial health ministry to assess the presence/absence of dementia and 29 other morbidities, and their associations with mortality (our primary outcome), other clinical outcomes (emergency department visits, all-cause hospital admissions) and a proxy for loss of independent living (discharge to long-term care). Cox and Poisson models were adjusted for year-varying covariates. A 3-way interaction was modelled for dementia, the number of comorbidities, and age., Results: There were 610 457 adults aged 65 years and older living in Alberta over the study period. Over median follow-up of 6.8 years, 153 125 (25.1%) participants died and 5569 (0.9%) were discharged to long-term care. The prevalence of people with at least 3 morbidities was 33.7% in 2003 and 50.2% in 2012. The prevalence of dementia rose from 6.2% in fiscal year 2003 to 8.3% in fiscal year 2012, representing a net increase of approximately 13 700 people. The likelihood of all 4 outcomes increased with age and with greater burden of morbidity; the presence of dementia further increased these risks. For example, the risk of mortality increased by 1.54 to 6.38 in the presence of dementia, depending on age and morbidity burden. The risk associated with dementia was attenuated by increasing comorbidity., Interpretation: Older age, multimorbidity and dementia are all strongly correlated with adverse health outcomes as well as a proxy for loss of independent living. The increasing prevalences of dementia and multimorbidity over time suggest the need for coordinated national strategies aimed at mitigating the health challenges associated with the aging of the population., Competing Interests: Competing interests: Dr. James reports receiving an investigator-initiated research grant from Amgen Canada., (Copyright 2017, Joule Inc. or its licensors.)

Chronic kidney disease (CKD) is associated with poor outcomes, perhaps due to a high burden of comorbidity. Most studies of CKD populations focus on concordant comorbidities, which cause CKD (such as hypertension and diabetes) or often accompany CKD (such as heart failure or coronary disease). Less is known about the burden of mental health conditions and discordant conditions (those not concordant but still clinically relevant, like dementia or cancer). Here we did a retrospective population-based cohort study of 530,771 adults with CKD residing in Alberta, Canada between 2003 and 2011. Validated algorithms were applied to data from the provincial health ministry to assess the presence/absence of 29 chronic comorbidities. Linkage between comorbidity burden and adverse clinical outcomes (mortality, hospitalization or myocardial infarction) was examined over median follow-up of 48 months. Comorbidities were classified into three categories: concordant, mental health/chronic pain, and discordant. The median number of comorbidities was 1 (range 0-15) but a substantial proportion of participants had 3 and more, or 5 and more comorbidities (25 and 7%, respectively). Concordant comorbidities were associated with excess risk of hospitalization, but so were discordant comorbidities and mental health conditions. Thus, discordant comorbidities and mental health conditions as well as concordant comorbidities are important independent drivers of the adverse outcomes associated with CKD.

Background: To improve quality of care and patient outcomes, health system decision-makers need to identify and implement effective interventions. An increasing number of systematic reviews document the effects of quality improvement programs to assist decision-makers in developing new initiatives. However, limitations in the reporting of primary studies and current meta-analysis methods (including approaches for exploring heterogeneity) reduce the utility of existing syntheses for health system decision-makers. This study will explore the role of innovative meta-analysis approaches and the added value of enriched and updated data for increasing the utility of systematic reviews of complex interventions., Methods/design: We will use the dataset from our recent systematic review of 142 randomized trials of diabetes quality improvement programs to evaluate novel approaches for exploring heterogeneity. These will include exploratory methods, such as multivariate meta-regression analyses and all-subsets combinatorial meta-analysis. We will then update our systematic review to include new trials and enrich the dataset by surveying authors of all included trials. In doing so, we will explore the impact of variables not, reported in previous publications, such as details of study context, on the effectiveness of the intervention. We will use innovative analytical methods on the enriched and updated dataset to identify key success factors in the implementation of quality improvement interventions for diabetes. Decision-makers will be involved throughout to help identify and prioritize variables to be explored and to aid in the interpretation and dissemination of results., Discussion: This study will inform future systematic reviews of complex interventions and describe the value of enriching and updating data for exploring heterogeneity in meta-analysis. It will also result in an updated comprehensive systematic review of diabetes quality improvement interventions that will be useful to health system decision-makers in developing interventions to improve outcomes for people with diabetes., Systematic Review Registration: PROSPERO registration no. CRD42013005165.

Background: Strategic clinical networks, a recent development in the health system in Alberta, have been charged with bringing together front-line clinicians, researchers and policy-makers to identify variation in clinical care, and to propose standards, pathways and innovative solutions to improve access and quality of care. Here, we describe a collaborative workshop held between researchers and the Obesity, Diabetes and Nutrition Strategic Clinical Network to describe barriers to and facilitators of care for people with diabetes and to identify quality improvement interventions that should be prioritized., Methods: Through collaboration between health researchers and the strategic clinical network, and using principles of the knowledge-to-action cycle, we identified barriers to and facilitators of diabetes care using data from a patient survey and a provider focus group (5 primary care physicians and 1 diabetes educator). In addition, we identified best evidence from a systematic review of quality improvement initiatives in diabetes. This information was reviewed at a multistakeholder workshop where potential quality improvement initiatives were considered at various service levels., Results: A pilot survey involving 59 patients with diabetes and a focus group of primary care and allied health care providers identified several important barriers to optimal outcomes in diabetes care, including patient-level financial barriers to care and difficulty navigating the health system. Our collaborative discussion using the knowledge-to-action cycle prioritized feasible, evidence-based interventions to improve outcomes for patients with diabetes, including enabling care by allied health care providers and creating clear care maps and processes for system navigation., Interpretation: We identified important barriers to achieving optimal outcomes in diabetes that may be overcome through the use of evidence-based quality improvement interventions. As recommended within the knowledge-to-action cycle, future research is required to determine whether program implementation improves outcomes and is cost-effective.

Objective: To determine the types of chronic disease management (CDM) programs offered for patients with diabetes in Alberta's primary care networks (PCNs)., Design: A survey was administered to PCNs to determine the types of CDM programs offered for patients with diabetes; CDM programs were organized into categories by their resource intensity and effectiveness. Results of the survey were reported using frequencies and percentages., Setting: Alberta has recently created PCNs-groups of family physicians who receive additional funds to enable them to support activities that fall outside the typical physician-based fee-for-service model, but which address specified objectives including CDM. It is currently unknown what additional programs are being provided through the PCN supplemental funding., Participants: A survey was administered to the individual responsible for CDM in each PCN. This included executive directors, chronic disease managers, and CDM nurses., Main Outcome Measures: We determined the CDM strategies used in each PCN to care for patients with diabetes, whether they were available to all patients, and whether the services were provided exclusively by the PCN or in conjunction with other agencies., Results: There was considerable variation across PCNs with respect to the CDM programs offered for people with diabetes. Nearly all PCNs used multidisciplinary teams (which could include nurses, dietitians, and pharmacists) and patient education. Fewer than half of the PCNs permitted personnel other than the primary physician to write or alter prescriptions for medications., Conclusion: Alberta's PCNs have successfully established many different types of CDM programs. Multidisciplinary care teams, which are among the most effective CDM strategies, are currently being used by most of Alberta's PCNs.

Background: Primary care networks are a newer model of primary care that focuses on improved access to care and the use of multidisciplinary teams for patients with chronic disease. We sought to determine the association between enrolment in primary care networks and the care and outcomes of patients with diabetes., Methods: We used administrative health care data to study the care and outcomes of patients with incident and prevalent diabetes separately. For patients with prevalent diabetes, we compared those whose care was managed by physicians who were or were not in a primary care network using propensity score matching. For patients with incident diabetes, we studied a cohort before and after primary care networks were established. Each cohort was further divided based on whether or not patients were cared for by physicians enrolled in a network. Our primary outcome was admissions to hospital or visits to emergency departments for ambulatory care sensitive conditions specific to diabetes., Results: Compared with patients whose prevalent diabetes is managed outside of primary care networks, patients in primary care networks had a lower rate of diabetes-specific ambulatory care sensitive conditions (adjusted incidence rate ratio 0.81, 95% confidence interval [CI] 0.75 to 0.87), were more likely to see an ophthalmologist or optometrist (risk ratio 1.19, 95% CI 1.17 to 1.21) and had better glycemic control (adjusted mean difference -0.067, 95% CI -0.081 to -0.052)., Interpretation: Patients whose diabetes was managed in primary care networks received better care and had better clinical outcomes than patients whose condition was not managed in a network, although the differences were very small.

Improving the health of individuals and populations while assuring the sustainability of modern healthcare systems requires a greater commitment to chronic disease prevention and management. In Canada, national challenges in the management of health care systems, such as prolonged wait times, have benefited from targeted federal investment, with provincial and territorial collaboration in the development and implementation of local strategies. The lead paper "An Inconvenient Truth: A Sustainable Healthcare System Requires Chronic Disease Prevention and Management Transformation," makes a sound argument for a similar investment toward the epidemic of chronic disease. Any strategy that might emerge from such a federal commitment ought to recognize two fundamentally important issues. First, as chronic disease prevention and management activities are largely community-based (rather than hospital or facility-based), Canada has an opportunity to move beyond a potentially disparate collection of provincial and territorial approaches to a truly national strategy. Second, and more important, effective chronic disease prevention and management will only be achievable if we reframe the challenge as a societal issue, not simply a health system concern. This reframing exercise might benefit from a greater understanding of how societal responses to other crises, such as global warming, have been triggered or accelerated.

Controversy has surrounded the 'paradigm' of evidence-based medicine since its introduction in 1992 as a new approach to the teaching and practice of medicine. Here, we address two questions: (1) is evidence-based medicine a good thing?; and (2) why has so much controversy arisen? In addressing these questions, we propose that the discussion surrounding evidence-based medicine should no longer be about whether the application of evidence in clinical practice is a good thing, because it obviously is. Instead, the debate ought to focus on the more difficult question of how to enhance its acceptability among busy clinicians practising in the 'real world'. For the future, we optimistically anticipate an enhanced adoption of evidence-based medicine, as clinicians will become increasingly capable of efficiently accessing existing and forthcoming evidence resources.

Charcoal hemoperfusion is effective in the treatment of theophylline overdose. Estimation of the time required for charcoal hemoperfusion has been based on personal experience and judgment. We used pharmacokinetic data from a patient and from case reports to generate a formula for predicting treatment time. Pharmacokinetic parameters were calculated using model-independent analysis of concentration-time curves from two treatments of charcoal hemoperfusion. These values were compared with published data and incorporated into a formula that was derived from the elimination rate constant to estimate treatment time of charcoal hemoperfusion: Time (min) = (ln conci-ln concd)/0.0057, where the concentration of theophylline is in mumol/L. The formula may be valid in patients in whom the serum theophylline concentration is less than or equal to 516 mumol/L or 92 mg/L. It may be used as a guide to estimate the length of charcoal hemoperfusion in the treatment of theophylline toxicity. Its validation requires implementation and evaluation in future cases.