Artificial fluorescent sensor reveals pre-synaptic NMDA receptors switch cholecystokinin release and LTP in the hippocampus.

Cholecystokinin (CCK) has been confirmed to be essential in NMDA-dependent long-term potentiation (LTP) at mouse cortical synapses. This paper has proven that CCK is necessary for LTP induced by high-frequency stimulation of mouse hippocampal synapses projected from the entorhinal cortex. We show that the subunit of the axonal NMDA receptor dominant modulates the activity-induced LTP by triggering pre-synaptic CCK release. A functional pre-synaptic NMDA receptor is required to induce LTP mediated by the axonal Ca2+ elevation and CCK exocytosis at CCK-specific neurons. Genetic depletion of the GluN1 subunit of NMDA receptors on CCK neurons, which projected from the entorhinal cortex largely abolished the axonal Ca2+ elevation and disturbed the secretion of CCK in hippocampus. These results demonstrate that activity-induced LTP at the hippocampal synapse is CCK-dependent, and CCK secretion from the axonal terminal is modulated by pre-synaptic NMDA receptors.

Clinical outcomes for chest pain patients discharged home from emergency departments using high-sensitivity versus conventional cardiac troponin assays.

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays enhance detection of lower circulating troponin concentrations, but the impact on outcomes in clinical practice is unclear. Our objective was to compare outcomes of chest pain patients discharged from emergency departments (EDs) using hs-cTn and conventional troponin (cTn) assays. METHODS: We conducted an observational study of chest pain patients aged 40-105 years who presented to an ED from April 1, 2013, to March 31, 2017, and were discharged home. We compared 30-day and 1-year outcomes of EDs that used hs-cTn versus cTn assays. The primary outcome was a composite of all-cause death, myocardial infarction or unstable angina. Comparisons were conducted with (1) no adjustment; (2) adjustment for demographic, socioeconomic, and hospital characteristics; and (3) full clinical adjustment. RESULTS: Among the 394,910 patients, 62,138 (15.7%) were evaluated at hs-cTn EDs and 332,772 (84.3%) were evaluated at cTn EDs. Patients discharged from hs-cTn EDs were less likely to have diabetes, hypertension, or prior heart disease. At 30 days, the unadjusted primary outcome rate was lower in hs-cTn EDs (0.9% vs 1.0%, P < .001). The 30-day hazard ratios for the primary outcome were 0.84 (95% CI 0.77-0.92) for no adjustment and 0.98 (95% CI 0.88-1.08) for full adjustment. Over 1 year, patients discharged from hs-cTn EDs had significantly fewer primary outcomes (3.7% vs 4.1%, P < .001) and lower hazard ratio (0.93; 95% CI 0.89-0.98) even after full adjustment. CONCLUSIONS: Hs-cTn testing was associated with a significantly lower adjusted hazard of myocardial infarction, angina, and all-cause hospitalization at 1 year but not 30 days.

Characteristics of quality improvement interventions to improve physical healthcare in mental health settings: a scoping review protocol.

INTRODUCTION: Mental health concerns globally impact millions of people, resulting in significant financial impact and adverse health outcomes. People living with mental health concerns are at higher risk of developing physical health issues, which can lead to a shortened life expectancy. Barriers to physical healthcare, such as limited service capacity, low help seeking and stigma, contribute to health disadvantage. Quality improvement (QI) interventions can address these challenges by addressing staff-level and service-level factors to improve the focus on physical healthcare in mental health settings. The aim of this scoping review is to describe studies of QI interventions to improve physical healthcare in mental health settings. METHODS AND ANALYSIS: The proposed scoping review will be conducted in accordance with guidance for scoping reviews from the Joanna Briggs Institute Manual and in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. A systematic review search for peer-reviewed and published articles will be conducted across eight databases: PubMed, MEDLINE (Ovid), Web of Science, CINAHL (EBSCOhost), ProQuest Central, PsycINFO (Ovid), Scopus and Embase (Elsevier). Two independent reviewers will screen the titles, abstracts and full text using Covidence. Any disagreement will be resolved through discussion or with a third reviewer. Data collection will be facilitated using Microsoft Excel. The details of included studies will be extracted by two authors independently. ETHICS AND DISSEMINATION: No ethical approval is required for the scoping review. The results of this review will be presented at conferences and published in a peer-reviewed scientific journal. This review will also inform the development of a QI strategy to influence mental health staff practices in the provision of physical healthcare in Australian mental health settings.

Planning with care complexity: Factors related to discharge delays of hospitalised people with disability.

Planning for discharge and supports beyond hospital for people with disability in Australia involves negotiation of complex care systems. The aims of this study were to examine how the individualised support pathway of the National Disability Insurance Scheme (NDIS) functioned for admitted people with disability who required funded support to leave hospital; and to explore the factors indicative of increased care complexity associated with delays. Retrospective chart reviews of people with disability were conducted. Data on 198 eligible patients were extracted, including NDIS plan approval and plan implementation timeframes and discharge delay. Participants' median age was 52 years (interquartile range = 41-59). The most common disability type was spinal cord injury (41%). The median NDIS plan approval and implementation timeframes were 89 days (63-123) and 39 days (8-131), respectively, and most participants (72%) experienced a delayed discharge. A longer plan implementation timeframe was associated with higher odds of a delay in discharge (OR = 3.41, 95% credible interval = 1.56, 7.11). We did not find any evidence that plan approval timeframe, or any other variable indicative of increased care complexity, was associated with discharge delays. Our findings suggest that a delayed discharge will likely be the reality for people with disability who require funded supports to leave hospital. They also suggest that NDIS plan implementation is a major challenge and a focus for policy and practice improvements. To target solutions, further research should focus on the interactions and negotiations of the multiple intermediaries involved and resource and structural impediments to plan implementation.

A partnership evaluation: public mental health and dental services.

OBJECTIVE: This study evaluates the partnership between a mental health service and a public dental hospital in providing timely and efficient access to dentistry to patients with a mental illness. In addition, the factors that contributed to the sustainability of the partnership were examined. METHOD: The partnership was appraised using a survey-based evaluation with 20 patients, 43 community mental health staff and 14 dental staff, and focus groups with mental health and dental staff. RESULTS: The partnership between the services is the key element to the success of improving access to dental services for patients. Overall feedback received from mental health staff highlighted the importance of the partnership and its role in meeting the oral health needs of patients. Generally, patients were satisfied with the treatment they received and valued the dental service. Results highlighted an ongoing problem of poor dietary and lifestyle choices. Dental staff felt that mental health patients were less likely to take care of their teeth and were more likely to cancel appointments. Dental staff also acknowledged frustration with patients with a mental illness not attending appointments or following through with a recommended course of treatment. CONCLUSIONS: The partnership with the local dental hospital has created a sustainable way to ensure improved dental health outcomes for patients of mental health services. This partnership has led to increased access to dental services and improved follow-up.

Readmission and Mortality After Hospitalization for Myocardial Infarction and Heart Failure.

BACKGROUND: Readmission rates after acute myocardial infarction (AMI) and heart failure (HF) hospitalizations have decreased in the United States since the implementation of the Hospital Readmissions Reduction Program. OBJECTIVES: This study was designed to examine the temporal trends of readmission and mortality after AMI and HF in Ontario, Canada, where reducing hospital readmissions has not had a policy incentive. METHODS: The cohort was comprised of AMI or HF patients 65 years of age or older who had been hospitalized from 2006 to 2017. Primary outcomes were 30-day readmission and post-discharge mortality. Secondary outcomes included in-hospital mortality, 30-day mortality from admission, and in-hospital mortality or 30-day mortality post-discharge. Adjusted monthly trends for each outcome were examined over the study period. RESULTS: Our cohorts included 152,808 AMI and 223,283 HF patients. Age- and sex-standardized AMI hospitalization rates in Ontario declined 32% from 2006 to 2017 while HF hospitalization rates declined slightly (9.1%). For AMI, risk-adjusted 30-day readmission rates declined from 17.4% in 2006 to 14.7% in 2017. All AMI risk-adjusted mortality rates also declined from 2006 to 2017 with 30-day post-discharge mortality from 5.1% to 4.4%. For HF, overall risk-adjusted 30-day readmission was largely unchanged from 2006 to 2014 at 21.9%, followed by a decline to 20.8% in 2017. Risk-adjusted 30-day post-discharge mortality declined from 7.1% in 2006 to 6.6% in 2017. CONCLUSIONS: The patterns of outcomes in Ontario are consistent with the United States for AMI, but diverge for HF. For AMI and HF, admissions, readmissions, and mortality rates declined over this period. The reasons for the country-specific patterns for HF need further exploration.

Temporal trends in sudden cardiac death in Ontario, Canada.

AIMS: Although the prevention and treatment of cardiovascular conditions have significantly improved over the past decade, whether they have reduced the incidence of sudden cardiac death (SCD) is not known. We sought to evaluate the temporal trends of SCD in a large unselected population. METHODS: We conducted a population-based cohort study using multiple linked longitudinal data in Ontario Canada. We included patients aged 35-74 years who had SCD from April 1st 2003 to March 31st 2014. SCD was defined as those who died of cardiac causes outside of the hospital or the emergency department, and had no recent hospitalization, no serious illness, and who were not residing in long-term care facilities. RESULTS: We identified 36,334 patients who fulfilled criteria for SCD. The overall age and sex-standardized rate of SCD declined from 57.9/100,000 in fiscal year 2003 to 42.4/100,000 in 2013. Men and women had similar declining trends in SCD incidence. Larger reductions were seen among the older age groups. Patients who had prior heart failure experienced the largest decline in SCD incidence from 829/100,000 to 533/100,000 from 2003 to 2013. Patients who had prior myocardial infarction also had significant reduction from 484/100,000 to 381/100,000. In contrast, individuals with cardiac risk factors without disease had much smaller declines in SCD incidence. CONCLUSIONS: Although significant progress to reduce SCD among patients with cardiac conditions was made in the past decade, additional effort should focus on the prevention of SCD in individuals without heart disease.

High-Density Lipoprotein Cholesterol and Cause-Specific Mortality in Individuals Without Previous Cardiovascular Conditions: The CANHEART Study.

BACKGROUND: The prognostic importance of high-density lipoprotein cholesterol (HDL-C) as a specific risk factor for cardiovascular (CV) disease has been challenged by recent clinical trials and genetic studies. OBJECTIVES: This study sought to reappraise the association of HDL-C level with CV and non-CV mortality using a "big data" approach. METHODS: An observational cohort study was conducted using the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) dataset, which was created by linking together 17 different individual-level data sources. People were included if they were between 40 and 105 years old on January 1, 2008, living in Ontario, Canada, without previous CV conditions or severe comorbidities, and had an outpatient fasting cholesterol measurement in the year prior to the inception date. The primary outcome was cause-specific mortality. RESULTS: A total of 631,762 individuals were included. The mean age of our cohort was 57.2 years, 55.4% were women, and mean HDL-C level was 55.2 mg/dl. There were 17,952 deaths during a mean follow-up of 4.9 ± 0.4 years. The overall all-cause mortality rate was 8.1 per 1,000 person-years for men and 6.6 per 1,000 person-years for women. Individuals with lower HDL-C levels were more likely to have low incomes, unhealthy lifestyle, higher triglycerides levels, other cardiac risk factors, and medical comorbidities. Individuals with lower HDL-C levels were independently associated with higher risk of CV, cancer, and other mortality compared with individuals in the reference ranges of HDL-C levels. In addition, individuals with higher HDL levels (>70 mg/dl in men, >90 mg/dl in women) had increased hazard of non-CV mortality. CONCLUSIONS: Complex associations exist between HDL-C levels and sociodemographic, lifestyle, comorbidity factors, and mortality. HDL-C level is unlikely to represent a CV-specific risk factor given similarities in its associations with non-CV outcomes.