Promoting a Patient-Centered Understanding of Safety in Acute Mental Health Wards: A User-Centered Design Approach to Develop a Real-Time Digital Monitoring Tool.

BACKGROUND: Acute mental health services report high levels of safety incidents that involve both patients and staff. The potential for patients to be involved in interventions to improve safety within a mental health setting is acknowledged, and there is a need for interventions that proactively seek the patient perspective of safety. Digital technologies may offer opportunities to address this need. OBJECTIVE: This research sought to design and develop a digital real-time monitoring tool (WardSonar) to collect and collate daily information from patients in acute mental health wards about their perceptions of safety. We present the design and development process and underpinning logic model and programme theory. METHODS: The first stage involved a synthesis of the findings from a systematic review and evidence scan, interviews with patients (n=8) and health professionals (n=17), and stakeholder engagement. Cycles of design activities and discussion followed with patients, staff, and stakeholder groups, to design and develop the prototype tool. RESULTS: We drew on patient safety theory and the concepts of contagion and milieu. The data synthesis, design, and development process resulted in three prototype components of the digital monitoring tool (WardSonar): (1) a patient recording interface that asks patients to input their perceptions into a tablet computer, to assess how the ward feels and whether the direction is changing, that is, "getting worse" or "getting better"; (2) a staff dashboard and functionality to interrogate the data at different levels; and (3) a public-facing ward interface. The technology is available as open-source code. CONCLUSIONS: Recent patient safety policy and research priorities encourage innovative approaches to measuring and monitoring safety. We developed a digital real-time monitoring tool to collect information from patients in acute mental health wards about perceived safety, to support staff to respond and intervene to changes in the clinical environment more proactively.

Implementing and evaluating patient-focused safety technology on adult acute mental health wards.

WHAT IS KNOWN ON THE SUBJECT: Mental health wards can feel unsafe. We know that patients and staff have different ideas about what makes a hospital ward safe or unsafe. Patients are often the first to know when the atmosphere on a ward becomes tense, but often, no one asks them for their views. Patients and staff are experts and should be included in discussions about how to make wards safer. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE: We got together with some service users and staff, and made an app that helps patients to tell staff when they are not feeling safe on a mental health ward. We tried it out on six wards and we asked patients and staff what they thought. The app was easy to use and most people liked the look of it. Patients said staff did not talk with them enough and so they liked using the app. However, some staff said they could tell how patients were feeling without an app and so they did not need it. Ward managers told us that staff were often very busy and did not always have time to use the app. WHAT ARE THE IMPLICATIONS FOR PRACTICE: This app could help staff know straightaway when patients do not feel safe on the ward, so that they can act quickly to calm things down. To make the most of the app, staff need to get used to it and bring it into ward routines. ABSTRACT: INTRODUCTION: Safety improvement on mental health wards is of international concern. It should incorporate patient perspectives. AIM: Implementation and evaluation of 'WardSonar', a digital safety-monitoring tool for adult acute mental health wards, developed with stakeholders to communicate patients' real-time safety perceptions to staff. METHOD: Six acute adult mental health wards in England implemented the tool in 2022. Evaluation over 10 weeks involved qualitative interviews (34 patients, 33 staff), 39 focused ethnographic observations, and analysis of pen portraits. RESULTS: Implementation and evaluation of the WardSonar tool was feasible despite challenging conditions. Most patients valued the opportunity to communicate their immediate safety concerns, stating that staff had a poor understanding of them. Some staff said the WardSonar tool could help enhanced ward safety but recognised a need to incorporate its use into daily routines. Others said they did not need the tool to understand patients' safety concerns. DISCUSSION: Foreseeable challenges, including staff ambivalence and practical issues, appeared intensified by the post-COVID-19 context. IMPLICATIONS FOR PRACTICE: The WardSonar tool could improve ward safety, especially from patients' perspectives. Future implementation could support staff to use the real-time data to inform proactive safety interventions.

All-cause, premature, and cardiovascular death attributable to socioeconomic and ethnic disparities among New Zealanders with type 1 diabetes 1994-2019: a multi-linked population-based cohort study.

BACKGROUND: New Zealand (NZ) research into type 1 diabetes mellitus (T1DM) mortality can inform policy and future research. In this study we aimed to quantify the magnitude to which ethnicity and socioeconomic disparities influenced mortality at the population level among people with Type 1 diabetes (T1DM) in Auckland, New Zealand (NZ). METHODS: The cohort data were derived from the primary care diabetes audit program the Diabetes Care Support Service (DCSS), and linked with national primary care, pharmaceutical claims, hospitalisation, and death registration databases. People with T1DM enrolled in DCSS between 1994-2018 were included. All-cause, premature, and cardiovascular mortalities were estimated by Poisson regression models with adjustment for population-level confounders. The mortality rates ratio (MRR) was standardized against the DCSS type 2 diabetes population. Mortality rates were compared by ethnic group (NZ European (NZE) and non-NZE) and socioeconomic deprivation quintile. The population attributable fraction (PAF) was estimated for ethnic and socioeconomic disparities by Cox regression adjusting for demographic, lifestyle, and clinical covariates. The adjusted slope index inequality (SII) and relative index of inequality (RII) were used to measure the socioeconomic disparity in mortalities. RESULTS: Overall, 2395 people with T1DM (median age 34.6 years; 45% female; 69% NZE) were enrolled, among whom the all-cause, premature and CVD mortalities were 6.69 (95% confidence interval: 5.93-7.53), 3.30 (2.77-3.90) and 1.77 (1.39-2.23) per 1,000 person-years over 25 years. The overall MRR was 0.39 (0.34-0.45), 0.65 (0.52-0.80), and 0.31 (0.24-0.41) for all-cause, premature and CVD mortality, respectively. PAF attributable to ethnicity disparity was not significantly different for mortality. The adjusted PAF indicated that 25.74 (0.84-44.39)% of all-cause mortality, 25.88 (0.69-44.69)% of premature mortality, 55.89 (1.20-80.31)% of CVD mortality could be attributed to socioeconomic inequality. The SII was 8.04 (6.30-9.78), 4.81 (3.60-6.02), 2.70 (1.82-3.59) per 1,000 person-years and RII was 2.20 (1.94-2.46), 2.46 (2.09-2.82), and 2.53 (2.03-3.03) for all-cause, premature and CVD mortality, respectively. CONCLUSIONS: Our results suggest that socioeconomic disparities were responsible for a substantial proportion of all-cause, premature and CVD mortality in people with T1DM in Auckland, NZ. Reducing socioeconomic barriers to management and self-management would likely improve clinical outcomes.

Health Inequality in Eight Adverse Outcomes Over a 25-Year Period in a Multi-Ethnic Population in New Zealand Population with Impaired Glucose Tolerance and/or Impaired Fasting Glucose: An Age-Period-Cohort Analysis.

Purpose: We aimed to examine socioeconomic inequality (SI) in cause-specific outcomes among adults with impaired glucose tolerance (IGT) and/or Impaired fasting glucose (IFG) in New Zealand (NZ) over 25 years. Patients and Methods: A population-based open cohort was derived from Diabetes Care Support Service in NZ with national databases linkage. Patients aged ≥18 years with IGT and/or IFG were enrolled between 01/01/1994 and 31/07/2018 and followed up until death or 31/12/2018. Incident outcomes (all-cause, premature, cardiovascular, and cancer death; cardiovascular, myocardial infarction, stroke, heart failure, and end-stage kidney disease hospitalization) by demographic, anthropometric, socioeconomic status, clinical measurements, enrol-time-periods, and IGT/IFG were evaluated. Adjusted incidence rate ratios, absolute risk difference, and SI measurements (slope and relative index of inequality) were estimated using Age-Period-Cohort models. Results: 29,894 patients (58.5 (SD 14.3) years mean age; 52.2% female) were enrolled with 5.6 (IQR: 4.4-7.4) years of median follow-up. Mortality rates decreased, whereas hospitalization (except myocardial infarction) rates increased. SI was significant for each outcome. Higher mortality and hospitalization rates and worsened SI were common in men, older, the most deprived, and Maori patients, as well as patients with obesity, current smoking, with both IFG and IGT, and greater metabolic derangement (higher systolic blood pressure, lipids, and HbA1c, and lower level of mean arterial pressure). Conclusion: Enhanced management strategies are necessary for people with IGT and/or IFG to address persisting SI, especially for men, older people, current smokers, NZ European and Maori patients, patients with obesity, or with any abnormal metabolic measurements.

A systematic review of interventions to reduce mechanical restraint in adult mental health inpatient settings.

Mechanical restraint is a commonly used restrictive practice worldwide, although reducing its use is an international priority. Interventions to reduce mechanical restraint are needed if reducing mechanical restraint is to succeed. Therefore, this systematic review aimed to examine evaluated evidence-based interventions that seek to reduce the incidence of and/or time in mechanical restraint in adult mental health inpatient settings. The JBI framework was used to guide this systematic review. The search strategy included peer-reviewed primary research literature published between 1999 and 2023. Two authors independently conducted the systematic search, selection process and data extraction process. Forty-one studies were included in this review. Using content analysis, we grouped interventions into four categories: (I) calm-down methods, (II) staff resources, (III) legal and policy changes and (IV) changing staff culture. Interventions to reduce mechanical restraint in adult mental health inpatient settings have shown some promise. Evidence suggests that a range of interventions can reduce the incidence of and/or time in mechanical restraint. However, controlled trials were lacking and consensus was lacking across studies. Furthermore, specific findings varied widely, and reporting was inconsistent, hampering the development of interventions for this issue. Further research is needed to strengthen the evidence base for reducing mechanical restraint in mental health inpatient settings.

Tobacco retailer density and smoking behaviour: how are exposure and outcome measures classified? A systematic review.

INTRODUCTION: To date only a limited number of reviews have focused on how exposure and outcome measures are defined in the existing literature on associations between tobacco retailer density ('density') and smoking behaviour ('smoking'). Therefore this systematic review classified and summarised how both density and smoking variables are operationalised in the existing literature, and provides several methodological recommendations for future density and smoking research. METHODS: Two literature searches between March and April 2018 and April 2022 were conducted across 10 databases. Inclusion and exclusion criteria were developed and keyword database searches were undertaken. Studies were imported into Covidence. Cross-sectional studies that met the inclusion criteria were extracted and a quality assessment was undertaken. Studies were categorised according to the density measure used, and smoking was re-categorised using a modified classification tool. RESULTS: Large heterogeneity was found in the operationalisation of both measures in the 47 studies included for analysis. Density was most commonly measured directly from geocoded locations using circular buffers at various distances (n = 14). After smoking was reclassified using a smoking classification tool, past-month smoking was the most common smoking type reported (n = 26). CONCLUSIONS: It is recommended that density is measured through length-distance and travel time using the street network and weighted (e.g. by the size of an area), or by using Kernel Density Estimates as these methods provide a more accurate measure of geographical to tobacco and e-cigarette retailer density. The consistent application of a smoking measures classification tool, such as the one developed for this systematic review, would enable better comparisons between studies. Future research should measure exposure and outcome measures in a way that makes them comparable with other studies. IMPLICATIONS: This systematic review provides a strong case for improving data collection and analysis methodologies in studies assessing tobacco retailer density and smoking behaviour to ensure that both exposure and outcome measures are clearly defined and captured. As large heterogeneity was found in the operationalisation of both density and smoking behaviour measures in the studies included for analysis, there is a need for future studies to capture, measure and classify exposure measures accurately, and to define outcome measures in a manner that makes them comparable with other studies.

Explanation of context, mechanisms and outcomes in adult community mental health crisis care: the MH-CREST realist evidence synthesis.

Background: Mental health crises cause significant disruption to individuals and families and can be life-threatening. The large number of community crisis services operating in an inter-agency landscape complicates access to help. It is unclear which underpinning mechanisms of crisis care work, for whom and in which circumstances. Aim: The aim was to identify mechanisms to explain how, for whom and in what circumstances adult community crisis services work. Objectives: The objectives were to develop, test and synthesise programme theories via (1) stakeholder expertise and current evidence; (2) a context, intervention, mechanism and outcome framework; (3) consultation with experts; (4) development of pen portraits; (5) synthesis and refinement of programme theories, including mid-range theory; and (6) identification and dissemination of mechanisms needed to trigger desired context-specific crisis outcomes. Design: This study is a realist evidence synthesis, comprising (1) identification of initial programme theories; (2) prioritisation, testing and refinement of programme theories; (3) focused realist reviews of prioritised initial programme theories; and (4) synthesis to mid-range theory. Main outcome: The main outcome was to explain context, mechanisms and outcomes in adult community mental health crisis care. Data sources: Data were sourced via academic and grey literature searches, expert stakeholder group consultations and 20 individual realist interviews with experts. Review methods: A realist evidence synthesis with primary data was conducted to test and refine three initial programme theories: (1) urgent and accessible crisis care, (2) compassionate and therapeutic crisis care and (3) inter-agency working. Results: Community crisis services operate best within an inter-agency system. This requires compassionate leadership and shared values that enable staff to be supported; retain their compassion; and, in turn, facilitate compassionate interventions for people in crisis. The complex interface between agencies is best managed through greater clarity at the boundaries of services, making referral and transition seamless and timely. This would facilitate ease of access and guaranteed responses that are trusted by the communities they serve. Strengths and limitations: Strengths include the identification of mechanisms for effective inter-agency community crisis care and meaningful stakeholder consultation that grounded the theories in real-life experience. Limitations include the evidence being heavily weighted towards England and the review scope excluding full analysis of ethnic and cultural diversity. Conclusions: Multiple interpretations of crises and diverse population needs present challenges for improving the complex pathways to help in a crisis. Inter-agency working requires clear policy guidance with local commissioning. Seamless transitions between services generate trust through guaranteed responses and ease of navigation. This is best achieved where there is inter-agency affiliation that supports co-production. Compassionate leaders engender staff trust, and outcomes for people in crisis improve when staff are supported to retain their compassion. Future work: Further work might explore inter-agency models of crisis delivery, particularly in rural communities. Future work could focus on evaluating outcomes across crisis care provider agencies and include evaluation of individual, as well as service-level, outcomes. The implementation and effect of mental health triage could be explored further, including via telehealth. Barriers to access for marginalised populations warrant a specific focus in future research. Study registration: The study is registered as PROSPERO CRD42019141680. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. 15. See the NIHR Journals Library website for further project information.

A mental health crisis can be traumatic for individuals and families. There are a lot of different agencies delivering crisis care. This can make getting the right help from services difficult, confusing and slow. It is not clear which services work best or who they work best for. This research explored community mental health crisis services for adults. We focused on what is working, who it is working for and in what situations it is working. Service users, carers, mental health professionals and service managers formed an 'expert stakeholder group' to guide the project by helping the researchers make sense of what we learned. We gathered information from research reports, other documents and interviews with experts (i.e. service users, carers, professionals, managers). We focused on three questions: How can services make sure that people in crisis can get the right help, quickly? What makes crisis care compassionate? Does it help if different crisis services work together? Community crisis services are most compassionate and effective when staff from different organisations share information. When leaders of crisis care help staff to work together across services, they find better ways to help people. Close working across teams gives professionals a better understanding of what other services do and makes it easier for them to give people the right help at the right time. When leaders are kind and supportive to staff, they feel better at work and provide better crisis care. It would be useful to explore if the most effective crisis services are the same ones that service users like best. We need to know more about mental health triage, inter-agency working and telehealth. Our project did not explore diversity, but this is an important topic to investigate.

Association Between Onset of Type 2 Diabetes and Risk of Atrial Fibrillation in New Zealanders With Impaired Glucose Tolerance Over 25 Years.

Background The association between the onset of type 2 diabetes (T2D) and atrial fibrillation (AF) risk in individuals with impaired glucose tolerance (IGT) remains unclear. This study aimed to investigate the relationship between the incident onset of T2D and 5- and 10-year (after the landmark period) risks of AF in people with IGT identified in South and West Auckland primary care settings between 1994 and 2019. Methods and Results We compared AF risk in patients with IGT with and without newly diagnosed T2D within a 1- to 5-year exposure window. Tapered matching and landmark analysis (to address immortal bias) were used to control for confounding variables. The cohorts incorporated 785 patients who had T2D newly diagnosed within 5 years from enrollment (landmark date) and 15 079 patients without a T2D diagnosis. Patients progressing to T2D exhibited significantly higher 5-year (after the landmark period) AF risk (hazard ratio [HR], 1.34 [95% CI, 1.10-1.63]) and 10-year (after the landmark period) AF risk (HR, 1.28 [95% CI, 1.02-1.62]) compared with those without incident T2D. The association was more pronounced among men, older patients, socioeconomically deprived individuals, current smokers, those with higher metabolic measures, and lower renal function. New Zealand European ethnicity was associated with a lower 5- and 10-year risk of AF. Conclusions This study found a mediating effect of T2D on the risk of AF in a population with IGT in New Zealand. The development of risk scores and future replication studies can help identify and guide management of individuals with IGT at the highest risk of AF following incident T2D.

GERD-screening before bariatric surgery: the predictive value of the GERD-HRQL questionnaire score compared with preoperative EGD findings.

BACKGROUND: There is an ongoing debate on how to best identify patients with gastroesophageal reflux disease (GERD) before bariatric surgery. The value of routine preoperative esophagogastroduodenoscopy (EGD) is questioned, and patient reported symptoms are commonly used for screening. The goal of this study is to determine if patient reported symptoms using a validated questionnaire correlate with preoperative EGD findings. METHODOLOGY: A prospective cohort study at a single institution was performed. Patients undergoing bariatric surgery between December 2020 and March 2023 were required to report symptoms of reflux by completing a preoperative GERD. Health-Related Quality of Life (GERD-HRQL) questionnaire and undergo a mandatory preoperative screening EGD. Patients were stratified into two cohorts: (group A) asymptomatic (score = 0) and (group B) symptomatic (score > 0). Statistical analysis was conducted using Pearson's chi-squared test and Wilcoxon rank-sum test in RStudio version 4.2.2. The predictive value of the GERD-HRQL score was analyzed using Areas Under the Curve (AUC; AUC = 0.5 not predictive, 0.5 < AUC ≥ 6 poor prediction & AUC > 0.9 excellent prediction) calculated from Receiver Operating Characteristic (ROC) curves. RESULTS: 200 patients were included; median age was 42.0 years (IQR 36.0 to 49.2). There were 79 patients (39.5%) in Group A and 121 patients (60.5%) in Group B. There was no difference in the frequency esophagitis (27.8% vs 32.2%, p = 0.61) or hiatal hernias (49.4% vs 47.1%, p = 0. 867) between group A and group B, respectively. ROC analysis revealed that the total GERD HRQL scores, heartburn only scores and regurgitation only scores, were poor predictors of esophagitis found on EGD (AUC 0.52, 0.53, 0.52), respectively. In asymptomatic patients, higher BMI was significantly associated with esophagitis (OR 1.15, 95% CI 1.06-1.27, p = 0.002). CONCLUSION: Symptoms, identified through the GERD-HRQL questionnaire, are a poor indicator of esophagitis or its severity in patients undergoing workup for bariatric surgery. Therefore, liberal screening upper endoscopy is recommended for pre-bariatric surgery patients to guide appropriate procedure selection.

Explaining context, mechanism and outcome in adult community mental health crisis care: A realist evidence synthesis.

Mental health crises cause significant distress and disruption to the lives of individuals and their families. Community crisis care systems are complex, often hard to navigate and poorly understood. This realist evidence synthesis aimed to explain how, for whom and in what circumstances community mental health crisis services for adults work to resolve crises and is reported according to RAMESES guidelines. Using realist methodology, initial programme theories were identified and then tested through iterative evidence searching across 10 electronic databases, four expert stakeholder consultations and n = 20 individual interviews. 45 relevant records informed the three initial programme theories, and 77 documents, were included in programme theory testing. 39 context, mechanism, outcome configurations were meta-synthesized into three themes: (1) The gateway to urgent support; (2) Values based crisis interventions and (3) Leadership and organizational values. Fragmented cross-agency responses exacerbated staff stress and created barriers to access. Services should focus on evaluating interagency working to improve staff role clarity and ensure boundaries between services are planned for. Organizations experienced as compassionate contributed positively to perceived accessibility but relied on compassionate leadership. Attending to the support needs of staff and the proximity of leaders to the front line of crisis care are key. Designing interventions that are easy to navigate, prioritize shared decision-making and reduce the risk of re-traumatizing people is a priority.

RNA interference targeting ANGPTL3 for triglyceride and cholesterol lowering: phase 1 basket trial cohorts.

Elevated triglycerides and non-high-density lipoprotein cholesterol (HDL-C) are risk factors for atherosclerotic cardiovascular disease (ASCVD). ARO-ANG3 is an RNA interference therapy that targets angiopoietin-like protein 3 (ANGPTL3), a regulator of lipoprotein metabolism. This first-in-human, phase 1, randomized, placebo-controlled, open-label trial investigated single and repeat ARO-ANG3 doses in four cohorts of fifty-two healthy participants and one cohort of nine participants with hepatic steatosis, part of a basket trial. Safety (primary objective) and pharmacokinetics (in healthy participants) and pharmacodynamics (secondary objectives) of ARO-ANG3 were evaluated. ARO-ANG3 was generally well tolerated, with similar frequencies of treatment-emergent adverse events in active and placebo groups. Systemic absorption of ARO-ANG3 in healthy participants was rapid and sustained, with a mean Tmax of 6.0-10.5 h and clearance from plasma within 24-48 h after dosing with a mean t½ of 3.9-6.6 h. In healthy participants, ARO-ANG3 treatment reduced ANGPTL3 (mean -45% to -78%) 85 days after dose. Reductions in triglyceride (median -34% to -54%) and non-HDL-C (mean -18% to -29%) (exploratory endpoints) concentrations occurred with the three highest doses. These early-phase data support ANGPTL3 as a potential therapeutic target for ASCVD treatment. ClinicalTrials.gov identifier: NCT03747224.

SARS-CoV-2 spike protein reduces burst activities in neurons measured by micro-electrode arrays.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) caused a large-scale global pandemic between 2020 and 2022. Despite efforts to understand its biological and pathogenic mechanisms, the viral impact on the neurological systems remains unclear. The main goal of this study was to quantify the neurological phenotypes induced by the SARS-CoV-2 spike protein in neurons, as measured by in-vitro multiwell micro-electrode arrays (MEAs). Materials and methods: The authors extracted the whole-brain neurons from the newborn P1 mice and plated them on multiwell MEAs and administered purified recombinant spike proteins (both S1 and S2 subunits) from the SARS-CoV-2 virus. The signals from the MEAs were transmitted from an amplifier to a high-performance computer for recording and analysis using an in-house developed algorithm to quantify neuronal phenotypes. Results: Primary among the phenotypic features analyzed, we discovered that neuronal treatment with spike 1 protein (S1) protein from SARS-CoV-2 decreased the mean burst numbers observed on each electrode, an effect that could be rescued with an anti-S1 antibody. Conversely, this mean burst number decrease was not observed with spike 2 protein (S2) treatment. Finally, our data strongly suggest that the receptor binding domain of S1 is responsible for the reduction in neuronal burst activity. Conclusion: Overall, our results strongly indicate that spike proteins may play an important role in altering neuronal phenotypes, specifically the burst patterns, when neurons are exposed during early development.

Effect of onset of type 2 diabetes on risks of cardiovascular disease and heart failure among new Zealanders with impaired glucose tolerance over 25 years: tapered-matched landmark analysis.

BACKGROUND: This study aimed to examine the association between the incident onset of T2DM and 5- and 10-year risks of CVD and HF in people with IGT identified in primary care in South and West Auckland, New Zealand (NZ) between 1994 and 2019. METHODS: We compared CVD and HF risks in patients with IGT and with/without T2D newly diagnosed within the exposure window (1-5 years). Tapered matching and landmark analysis (to account for immortal bias) were used to control for potential effects of known confounders. RESULTS: Among 26,794 patients enrolled with IGT, 845 had T2D newly diagnosed within 5 years from enrolment (landmark date) and 15,452 did not have T2D diagnosed. Patients progressing to T2D (vs. those not progressing) had a similar 5-year risk for CVD (hazard ratio 1.19; 95% CI 0.61-2.32) but significantly higher 10-year risk of CVD (2.45(1.40-4.29)), 5-year risk of HF (1.94(1.20-3.12)) and 10-year risk of HF (2.84(1.83-4.39). The association between the onset of T2D and risk of 10-year risk of CVD, 5-year and 10-year risk of HF was more likely among men, the socioeconomically deprived, those currently smoking, patients with higher metabolic measures and/or those with lower renal function. Patients of NZ European ethnicity had a lower 10-year risk of CVD. CONCLUSIONS: The study suggests that the diagnosis of T2D mediates the risk of CVD and HF in people with IGT. The development of risk scores to identify and better manage individuals with IGT at high risk of T2D is warranted.

Adverse Clinical Outcomes Attributable to Socioeconomic and Ethnic Disparities Among People with Type 2 Diabetes in New Zealand Between 1994-2018: A Multiple Linked Cohort Study.

Purpose: The study aimed to examine the separate population-level contributions of the ethnic and socioeconomic disparities among people with type 2 diabetes mellitus (T2DM) and residence in New Zealand (NZ). Patients and Methods: A prospective cohort enrolled T2DM patients from 01/01/1994 into the Diabetes Care Support Service, a primary care audit program in Auckland, NZ. The cohort was linked to national registry databases (socioeconomic status, pharmaceutical claim, hospitalization, and death registration). Each cohort member was followed up till death or the study end time (31/12/2019), whichever came first. Incident clinical events (stroke, myocardial infarction (MI), heart failure (HF), end-stage renal disease (ESRD), and premature mortality (PM)) were used as outcomes. The attributable fractions (AFs) were estimated for the whole population and for specific population with NZ Europeans (NZE) and/or least deprived population as reference, both unadjusted and with adjustment for covariables by Cox Regression models. Results: Among 36,267 patients, adjusted population AFs indicated 6.6(-30.8-33.3)% of PM, 17.1(5.8-27.0)% of MI, 35.3(22.6-46.0)% of stroke, 14.3(3.2-24.2)% of HF, and 15.9(6.7-24.2)% of ESRD could be attributed to deprivation; while 14.3(3.3-25.4)% of PM, -3.3(-8.3-1.5)% of MI, -0.5(-6.7-5.3)% of stroke, 4.7(0.3-8.8)% of HF, 13.3(9.9-16.6)% of ESRD could be attributed to ethnicity. Deprivation contributed a significant AF to stroke, while ethnicity was important for ESRD. Gradient of AF for deprivation indicated NZE and Asians were most affected by deprivation across outcomes. Conversely, Maori, with the highest AFs for ethnicity of PM and ESRD, were unaffected by deprivation. At same deprivations, the AFs of MI and stroke were greatest among NZE compared with other ethnic groups; the AF of ESRD was greatest among Maori and Pasifika. Conclusion: Both socioeconomic deprivation and ethnicity are strongly associated with outcomes in patients with T2DM in NZ, although the extent of the deprivation gradient is greatest among NZE and Asians, and least among Maori.

Worldwide epidemiologic factors in pemphigus vulgaris and bullous pemphigoid.

Autoimmune blistering diseases such as bullous pemphigoid (BP) and pemphigus vulgaris (PV) are complex, multifactorial, and polygenic diseases, whose exact pathogenesis is difficult to pinpoint. Research aimed at elucidating the associated epidemiologic risk factors of these two diseases has been hampered by their rare disease status. Further, a lack of centralization and standardization of available data makes the practical application of this information challenging. In order to collate and clarify the available literature we comprehensively reviewed 61 PV articles from 37 different countries and 35 BP articles from 16 different countries addressing a range of disease relevant clinical parameters including age of onset, sex, incidence, prevalence, and HLA allele association. The reported incidence of PV ranged from 0.098 to 5 patients per 100,000 people, while BP ranged from 0.21 to 7.63 patients per 100,000. Prevalence of PV ranged from 0.38 to 30 per 100,000 people and BP ranged from 1.46 to 47.99 per 100,000. The mean age of onset in patients ranged from 36.5 to 71 years for PV and 64 to 82.6 years for BP. Female-to-male ratios ranged from 0.46 to 4.4 in PV and 1.01 to 5.1 in BP. Our analysis provides support for the reported linkage disequilibrium of HLA DRB1*0402 (an allele previously shown to be associated with PV) and DQB1*0302 alleles in Europe, North America, and South America. Our data also highlight that HLA DQB1*0503 (also known to be associated with PV) appears in linkage disequilibrium with DRB1*1404 and DRB1*1401, mainly in Europe, the Middle East, and Asian countries. The HLA DRB1*0804 allele was only associated with PV in patients of Brazilian and Egyptian descent. Only two HLA alleles were reported as associated with BP more than twice in our review, DQB1*0301 and DQA1*0505. Collectively, our findings provide detailed insights into the variation of disease parameters relevant to PV and BP that can be expected to inform future work aimed at unraveling the complex pathogenesis of these conditions across the globe.

Exposure to multiple ion beams, broadly representative of galactic cosmic rays, causes perivascular cardiac fibrosis in mature male rats.

Long-duration space exploratory missions to the Earth's moon and the planet Mars are actively being planned. Such missions will require humans to live for prolonged periods beyond low earth orbit where astronauts will be continuously exposed to high energy galactic cosmic rays (GCRs). A major unknown is the potential impact of GCRs on the risks of developing degenerative cardiovascular disease, which is a concern to NASA. A ground-based rat model has been used to provide a detailed characterization of the risk of long-term cardiovascular disease from components of GCRs at radiation doses relevant to future human missions beyond low earth orbit. Six month old male WAG/RijCmcr rats were irradiated at a ground-based charged particle accelerator facility with high energy ion beams broadly representative of GCRs: protons, silicon and iron. Irradiation was given either as a single ion beam or as a combination of three ion beams. For the doses used, the single ion beam studies did not show any significant changes in the known cardiac risk factors and no evidence of cardiovascular disease could be demonstrated. In the three ion beam study, the total cholesterol levels in the circulation increased modestly over the 270 day follow up period, and inflammatory cytokines were also increased, transiently, 30 days after irradiation. Perivascular cardiac collagen content, systolic blood pressure and the number of macrophages found in the kidney and in the heart were each increased 270 days after irradiation with 1.5 Gy of the three ion beam grouping. These findings provide evidence for a cardiac vascular pathology and indicate a possible threshold dose for perivascular cardiac fibrosis and increased systemic systolic blood pressure for complex radiation fields during the 9 month follow up period. The development of perivascular cardiac fibrosis and increased systemic systolic blood pressure occurred at a physical dose of the three ion beam grouping (1.5 Gy) that was much lower than that required to show similar outcomes in earlier studies with the same rat strain exposed to photons. Further studies with longer follow up periods may help determine whether humans exposed to lower, mission-relevant doses of GCRs will develop radiation-induced heart disease.

Do more stringent policies reduce daily COVID-19 case counts? Evidence from Canadian provinces.

The enactment of COVID-19 policies in Canada falls under provincial jurisdiction. This study exploits time-series variation across four Canadian provinces to evaluate the effects of stricter COVID-19 policies on daily case counts. Employing data from this time-period allows an evaluation of the efficacy of policies independent of vaccine impacts. While both OLS and IV results offer evidence that more stringent Non-Pharmaceutical Interventions (NPIs) can reduce daily case counts within a short time-period, IV estimates are larger in magnitude. Hence, studies that fail to control for simultaneity bias might produce confounded estimates of the efficacy of NPIs. However, IV estimates should be treated as correlations given the possibility of other unobserved determinants of COVID-19 spread and mismeasurement of daily cases. With respect to specific policies, mandatory mask usage in indoor spaces and restrictions on business operations are significantly associated with lower daily cases. We also test the efficacy of different forecasting models. Our results suggest that Gradient Boosted Regression Trees (GBRT) and Seasonal Autoregressive-Integrated Moving Average (SARIMA) models produce more accurate short-run forecasts relative to Vector Auto Regressive (VAR), and Susceptible-Infected-Removed (SIR) epidemiology models. Forecasts from SIR models are also inferior to results from basic OLS regressions. However, predictions from models that are unable to correct for endogeneity bias should be treated with caution.