Hydrologic Connectivity Regulates Riverine N2O Sources and Dynamics.

Indirect nitrous oxide (N2O) emissions from streams and rivers are a poorly constrained term in the global N2O budget. Current models of riverine N2O emissions place a strong focus on denitrification in groundwater and riverine environments as a dominant source of riverine N2O, but do not explicitly consider direct N2O input from terrestrial ecosystems. Here, we combine N2O isotope measurements and spatial stream network modeling to show that terrestrial-aquatic interactions, driven by changing hydrologic connectivity, control the sources and dynamics of riverine N2O in a mesoscale river network within the U.S. Corn Belt. We find that N2O produced from nitrification constituted a substantial fraction (i.e., >30%) of riverine N2O across the entire river network. The delivery of soil-produced N2O to streams was identified as a key mechanism for the high nitrification contribution and potentially accounted for more than 40% of the total riverine emission. This revealed large terrestrial N2O input implies an important climate-N2O feedback mechanism that may enhance riverine N2O emissions under a wetter and warmer climate. Inadequate representation of hydrologic connectivity in observations and modeling of riverine N2O emissions may result in significant underestimations.

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.

Long-term impact of type 2 diabetes onset on dementia incidence rate among New Zealanders with impaired glucose tolerance: A tapered-matched landmark analysis over 25 years.

INTRODUCTION: We aimed to investigate the association between the onset of type 2 diabetes (T2D) and dementia incidence rates (IR) in the population with impaired glucose tolerance (IGT) identified in primary care in New Zealand (NZ) over 25 years. METHODS: Tapered matching and landmark analysis (accounting for immortal bias) were used to control for potential effects of known confounders. The association between T2D onset and 5- and 10-year IR of dementia was estimated by weighted Cox models. RESULTS: The onset of T2D was significantly associated with the 10-year IR of dementia, especially in the socioeconomically deprived, those of non-NZ European ethnicity, those currently smoking, and patients with higher metabolic measures. DISCUSSION: Our findings suggest that the onset of T2D is a significant risk factor for dementia in individuals with IGT. Dementia screening and structured diabetes prevention are vital in the population with IGT, particularly those from deprived or ethnic minority backgrounds. HIGHLIGHTS: Increased dementia incidence rate links with T2D onset in people with IGT. Significant incidence varied by ethnicity, socioeconomic status, and health factors. Results emphasize the diabetes manage and socioeconomic factors on dementia risk. Secondary analysis highlights the key role of vascular health in dementia prevention.

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.

A 5-year propensity-matched analysis of perioperative outcomes in patients with chronic kidney disease undergoing bariatric surgery.

BACKGROUND: Bariatric surgery can improve renal function in patients with comorbid chronic kidney disease (CKD) and obesity. Additionally, bariatric surgery can enhance outcomes following renal transplantation. The safety of bariatric surgery in patients with CKD has been debated in the literature. This study evaluates the frequency of perioperative complications associated with CKD. METHODS: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was queried from 2015-2019. Patients were included if they had a vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB) and were stratified based on CKD status. An unmatched and propensity-matched analysis was performed comparing 30-day perioperative outcomes between the groups. RESULTS: A total of 717,809 patients included in this study, 5817(0.8%) had CKD, of whom 2266(0.3%) were on dialysis. 74.3% of patients with CKD underwent VSG with 25.7% underwent RYGB. Comparing RYGB to VSG, patients who underwent RYGB had a higher rate of deep organ space infection (0.7%vs.0.1%,p = 0.021) and re-intervention (5.0% vs. 2.2%,p < 0.001). Within the VSG cohort, a matched analysis was performed for those with CKD and without CKD. The CKD cohort had higher risk of complications such as bleeding (2.1%vs. 0.9%,p < 0.001), readmission (9.3%vs.4.9%,p < 0.001), reoperation (2.7%vs.1.3%,p < 0.001), and need for reintervention (2.2%vs.1.3%,p < 0.001). Notably, patients with CKD also had a higher mortality (0.6%vs.0.2%,p = 0.003). No difference was seen between patients with renal insufficiency and patients on dialysis. CONCLUSION: VSG has been the operation of choice in patients with CKD. Our results showed it is the safer option for patients with CKD compared to RYGB. Although this patient population does have an increased risk of adverse perioperative events, dialysis didn't affect the outcome. Bariatric surgeons who operate on patients with CKD should be well informed and remain vigilant given the increased perioperative risk. The risk is still considerably low, and the potential benefit on renal function and improvement in candidacy for renal transplant outweigh the risk. They should be considered as surgical candidates.

Battle of the buttress: 5-year propensity-matched analysis of staple-line reinforcement techniques from the MBSAQIP database.

BACKGROUND: Vertical sleeve gastrectomy (VSG) has demonstrated to be safe; however, controversy remains on how to decrease major complications, particularly bleeding and leaks. There are variations in staple-line reinforcement techniques, including no reinforcement, oversewing, and buttressing. We sought to evaluate the effect of those methods on post-operative complications using the Metabolic and Bariatric Surgery Accreditation Quality Initiative Program (MBSAQIP) database. METHODS: The MBSAQIP was queried for patients who underwent VSG during 2015-2019. A propensity-matched analysis was performed between different staple-line reinforcement (SLR) methods, specifically No reinforcement (NR), Oversewing (OS), and Buttressing (BR). The primary outcome of interest was complications within 30 days. RESULTS: A total of 513,354 VSG cases were analyzed. The cohort was majority female (79.0%), with mean (SD) age of 44.2 ± 11.9 years and mean BMI of 45 ± 7.8 kg/m2. Frequency of SLR methods used was 54%BR, 25.6%NR, 10.8% BR + OS, and 9.8%OS. There were no differences in rate of leaks among SLR methods. Compared to NR, BR was associated with decreased rate of reoperations, overall bleeding, and major bleeding (p < 0.05) but prolonged operative time and length of stay (LOS) (p < 0.05). OS was associated with decreased overall bleeding (p < 0.05) but prolonged operative times and length of stay (p < 0.05) compared to NR. Compared to BR, OS was associated with increased operative times, LOS, and rates of post-operative ventilator use, pneumonia, and venous thrombosis (p < 0.05). Patients with bleeding were associated with lower rate of BR (56% vs 61%) and higher rate of NR (34% vs 28%) compared to patients with no bleeding. Bleeding was associated with a greater frequency of leaks (4.4% vs 0.3%), along with higher morbidity and mortality (p < 0.05). CONCLUSIONS: Of the reinforcement methods evaluated, BR and OS were both associated with decreased bleeding despite longer operative times. No method was found to significantly reduce incidence of leaks; however, bleeding was associated with increased incidence of leaks, morbidity, and mortality. The liberal use of SLR techniques is recommended for further optimization of patient outcomes after VSG.

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.

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.

Ethnic disparities in the use of restrictive practices in adult mental health inpatient settings: a scoping review.

PURPOSE: To identify and summarise extant knowledge about patient ethnicity and the use of various types of restrictive practices in adult mental health inpatient settings. METHODS: A scoping review methodological framework recommended by the JBI was used. A systematic search was conducted in APA PsycINFO, CINAHL with Full Text, Embase, PubMed and Scopus. Additionally, grey literature searches were conducted in Google, OpenGrey and selected websites, and the reference lists of included studies were explored. RESULTS: Altogether, 38 studies were included: 34 were primary studies; 4, reviews. The geographical settings were as follows: Europe (n = 26), Western Pacific (n = 8), Americas (n = 3) and South-East Asia (n = 1). In primary studies, ethnicity was reported according to migrant/national status (n = 16), mixed categories (n = 12), indigenous vs. non-indigenous (n = 5), region of origin (n = 1), sub-categories of indigenous people (n = 1) and religion (n = 1). In reviews, ethnicity was not comparable. The categories of restrictive practices included seclusion, which was widely reported across the studies (n = 20), multiple restrictive practices studied concurrently (n = 17), mechanical restraint (n = 8), rapid tranquillisation (n = 7) and manual restraint (n = 1). CONCLUSIONS: Ethnic disparities in restrictive practice use in adult mental health inpatient settings has received some scholarly attention. Evidence suggests that certain ethnic minorities were more likely to experience restrictive practices than other groups. However, extant research was characterised by a lack of consensus and continuity. Furthermore, widely different definitions of ethnicity and restrictive practices were used, which hampers researchers' and clinicians' understanding of the issue. Further research in this field may improve mental health practice.

Mealtime difficulties in adults with mental health conditions: an integrative review.

BACKGROUND: Dysphagia and choking are highly prevalent in adults with mental health conditions. However, there is scant research considering the personal experience of dysphagia for this population. AIMS: To understand the evidence-base for strategies to involve the patient in recognition, assessment and treatment of mealtime difficulties. METHODS: This integrative review synthesised the literature on the experience of dysphagia in patients with mental health conditions. Patient consultation led to co-designed search terms and eligibility criteria for a systematic search of five scientific databases following Prisma guidance. Quality assessment of the eligible studies and reflexive thematic analysis were completed. RESULTS: 31 studies were included for review. These included case reports, literature reviews and cross-sectional studies. Quality of evidence was weak and no intervention studies were identified. There was scant detail regarding the personal experience of dysphagia or choking. Themes identified related to biomedical perspectives, influencing factors presented without context, and decision-making led by clinicians. CONCLUSIONS: Guidance on mental healthcare calls attention to under-diagnosis of physical co-morbidities and advocates patient inclusion. However, the patient voice in this population is rarely described regarding dysphagia. Further inclusive research is indicated to explore the impact of dysphagia and choking, and implications for interventions and outcome measures.

Clinical outcomes in transient epileptic amnesia: A 10-year follow-up cohort study of 47 cases.

OBJECTIVE: Transient epileptic amnesia (TEA) is a form of adult-onset epilepsy where presenting features are well described, but little is known regarding prognosis. This study aimed to elucidate the long-term prognosis of TEA regarding seizure control, memory, medical comorbidities, and life expectancy. METHODS: Up-to-date clinical information was collected for 47 people diagnosed with TEA who had joined the The Impairment of Memory in Epilepsy (TIME) study 10 years earlier. At entry to the study, information about comorbid conditions was systematically collected. Details regarding subsequent diagnoses, seizure activity, changes to treatment, or reports of cognitive impairment were obtained through the family doctor. The variables of interest were compared with UK population data. RESULTS: Mortality in the cohort was 21 of 47 (45%), with an average age at death of 82.5 years. Seizures remained well controlled for the majority but medications required adjustments in dose and type for some (28%). A small number (three cases) remained seizure-free without medication. History of cardiovascular disorders was frequent (78.7%), typically involving hypertension (55.3%). Autoimmune disorders (25.5%), cancer (23.4%), and depression (21.3%) were also commonly reported. Although persisting memory problems were often noted, dementia was diagnosed in seven cases (14.9%). Life expectancy and comorbidities in TEA did not differ from available population norms. SIGNIFICANCE: Results suggest that life expectancy is not reduced in TEA. Although TEA does not appear to be a self-limiting form of epilepsy, seizures are typically well controlled via medication. Because adjustments to medication may be required, even after long periods of stability, ongoing medical monitoring is recommended. Comorbid vascular disorders are frequent but appear similar to general population estimates. Monitoring mood may be important, given that people with chronic conditions are often vulnerable to depression. Because of persisting memory difficulties, the development of effective memory interventions for people with TEA is warranted.

A large-scale brain network mechanism for increased seizure propensity in Alzheimer's disease.

People with Alzheimer's disease (AD) are 6-10 times more likely to develop seizures than the healthy aging population. Leading hypotheses largely consider hyperexcitability of local cortical tissue as primarily responsible for increased seizure prevalence in AD. However, in the general population of people with epilepsy, large-scale brain network organization additionally plays a role in determining seizure likelihood and phenotype. Here, we propose that alterations to large-scale brain network organization seen in AD may contribute to increased seizure likelihood. To test this hypothesis, we combine computational modelling with electrophysiological data using an approach that has proved informative in clinical epilepsy cohorts without AD. EEG was recorded from 21 people with probable AD and 26 healthy controls. At the time of EEG acquisition, all participants were free from seizures. Whole brain functional connectivity derived from source-reconstructed EEG recordings was used to build subject-specific brain network models of seizure transitions. As cortical tissue excitability was increased in the simulations, AD simulations were more likely to transition into seizures than simulations from healthy controls, suggesting an increased group-level probability of developing seizures at a future time for AD participants. We subsequently used the model to assess seizure propensity of different regions across the cortex. We found the most important regions for seizure generation were those typically burdened by amyloid-beta at the early stages of AD, as previously reported by in-vivo and post-mortem staging of amyloid plaques. Analysis of these spatial distributions also give potential insight into mechanisms of increased susceptibility to generalized (as opposed to focal) seizures in AD vs controls. This research suggests avenues for future studies testing patients with seizures, e.g. co-morbid AD/epilepsy patients, and comparisons with PET and MRI scans to relate regional seizure propensity with AD pathologies.

Systemic safety inequities for people with learning disabilities: a qualitative integrative analysis of the experiences of English health and social care for people with learning disabilities, their families and carers.

BACKGROUND: Failures in care for people with learning disabilities have been repeatedly highlighted and remain an international issue, exemplified by a disparity in premature death due to poor quality and unsafe care. This needs urgent attention. Therefore, the aim of the study was to understand the care experiences of people with learning disabilities, and explore the potential patient safety issues they, their carers and families raised. METHODS: Two data sources exploring the lived experience of care for people with learning disabilities were synthesised using an integrative approach, and explored using reflexive thematic analysis. This comprised two focus groups with a total of 13 people with learning disabilities and supportive staff, and 377 narratives posted publicly via the feedback platform Care Opinion. RESULTS: The qualitative exploration highlighted three key themes. Firstly, health and social care systems operated with varying levels of rigidity. This contributed to an inability to effectively cater to; complex and individualised care needs, written and verbal communication needs and needs for adequate time and space. Secondly, there were various gaps and traps within systems for this population. This highlighted the importance of care continuity, interoperability and attending to the variation in support provision from professionals. Finally, essential 'dependency work' was reliant upon social capital and fulfilled by paid and unpaid caring roles to divergent extents, however, advocacy provided an additional supportive safety net. CONCLUSIONS: A series of safety inequities have been identified for people with learning disabilities, alongside potential protective buffers. These include; access to social support and advocacy, a malleable system able to accommodate for individualised care and communication needs, adequate staffing levels, sufficient learning disabilities expertise within and between care settings, and the interoperability of safety initiatives. In order to attend to the safety inequities for this population, these factors need to be considered at a policy and organisational level, spanning across health and social care systems. Findings have wide ranging implications for those with learning disabilities, their carers and families and health and social care providers, with the potential for international learning more widely.

The timing and development of infections in a fish-cestode host-parasite system.

The cestode Schistocephalus solidus is a common parasite in freshwater threespine stickleback populations, imposing strong fitness costs on their hosts. Given this, it is surprising how little is known about the timing and development of infections in natural stickleback populations. Previous work showed that young-of-year stickleback can get infected shortly after hatching. We extended this observation by comparing infection prevalence of young-of-year stickleback from 3 Alaskan populations (Walby, Cornelius and Wolf lakes) over 2 successive cohorts (2018/19 and 2019/20). We observed strong variation between sampling years (2018 vs 2019 vs 2020), stickleback age groups (young-of-year vs 1-year-old) and sampling populations.

Identifying tobacco retailers in the absence of a licensing system: lessons from Australia.

OBJECTIVES: To estimate the proportion of retailers that sell tobacco in the absence of appropriate local government oversight, and to describe the characteristics by which they differ from those that can expect to receive such oversight. METHODS: A database of listed tobacco retailers was obtained from a regional Victorian local government. Potential unlisted tobacco retailers were added using online searches, and attempts to visit all retailers were undertaken. GPS coordinates and sales type information of retailers that sold tobacco were recorded and attached to neighbourhood-level data on socioeconomic disadvantage and smoking prevalence using ArcMap. Logistic regression analyses, χ2 tests and t-tests were undertaken to explore differences in numbers of listed and unlisted retailers by business and neighbourhood-level characteristics. RESULTS: Of 125 confirmed tobacco retailers, 43.2% were trading potentially without government oversight. Significant differences were found between listed and unlisted retailers by primary business type (p<0.001), and sales type (p<0.001) but not by the other characteristics. CONCLUSIONS: The database of tobacco retailers was inaccurate in two ways: (1) a number of listed retailers no longer operated or sold tobacco, and (2) 43.2% of businesses confirmed as selling tobacco were missing. As no form of licensing system exists in Victoria, it is difficult to identify the number of retailers operating, or to determine how many receive formal regulatory oversight. A positive licensing system is recommended to regulate the sale of tobacco and to generate a comprehensive database of retailers, similar to that which exists for food registration, gaming and liquor-licensed premises.

Understanding the decision-making of critical care nurses when restraining a patient with psychomotor agitation secondary to hyperactive delirium: A 'Think Aloud' study.

AIMS & OBJECTIVES: This study aimed to explore the decision-making processes undertaken by critical care nurses when considering restraint to manage a patient with psychomotor agitation secondary to hyperactive delirium. BACKGROUND: Psychomotor agitation is frequently cited as clinical rationale for initiating chemical or physical restraint. Despite the presence of clinical guidance for restraint in critical care, wide variations in nursing and prescribing practice are evident. Nurses are the primary decision makers when initiating restraint, but little is known about this process and influencing factors. DESIGN: A pragmatic qualitative approach was used to explore critical care nurses' decision-making processes. METHODS: A 'think aloud' approach was undertaken. Audio-visual vignettes featuring simulated patients were used as stimulus to elicit decision-making processes from thirty critical care nurses and practitioners. The COREQ checklist was followed. RESULTS: Five themes relating to restraint were identified: Intrinsic beliefs and aptitudes; Handover and labelling; Failure to maintain a consistent approach; Restraint might be used to replace vigilance; The tyranny of the now. CONCLUSIONS: Restraint was more frequent when staffing ratios were reduced below 1:1 and opportunities for vigilance reduced. Participants described physical and psychological exhaustion when caring for a patient with delirium and how this might lead to restraint to create 'space' for respite. Variations in practice were evident and restraint use appears rooted in custom and culture rather than objective assessment. RELEVANCE TO CLINICAL PRACTICE: The lack of pre-emptive management for hyperactive delirium and reduced staffing ratios lead to the decision to restrain to preserve safety in acute agitation. The struggle to manage agitated behaviour is associated with nurse burnout and reduced engagement with therapeutic management methods, suggesting the need for psychological and educational support for clinical staff. Delirium is an important and debilitating form of organ dysfunction which should be collaboratively managed by the multi-disciplinary team.

A Trend-Based Early Warning Score Can Be Implemented in a Hospital Electronic Medical Record to Effectively Predict Inpatient Deterioration.

OBJECTIVES: To determine whether a statistically derived, trend-based, deterioration index is superior to other early warning scores at predicting adverse events and whether it can be integrated into an electronic medical record to enable real-time alerts. DESIGN: Forty-three variables and their trends from cases and controls were used to develop a logistic model and deterioration index to predict patient deterioration greater than or equal to 1 hour prior to an adverse event. SETTING: Two large Australian teaching hospitals. PATIENTS: Cases were considered as patients who suffered adverse events (unexpected death, unplanned ICU transfer, urgent surgery, and rapid-response alert) between August 1, 2016, and April 1, 2019. INTERVENTIONS: The logistic model and deterioration index were tested on historical data and then integrated into an electronic medical record for a 6-month prospective "silent" validation. MEASUREMENTS AND MAIN RESULTS: Data were acquired from 258,732 admissions. There were 8,002 adverse events. The addition of vital sign and laboratory trend values to the logistic model increased the area under the curve from 0.84 to 0.89 and the sensitivity to predict an adverse event 1-48 hours prior from 0.35 to 0.41. A 48-hour simulation showed that the logistic model had a higher area under the curve than the Modified Early Warning Score and National Early Warning Score (0.87 vs 0.74 vs 0.71). During the silently run prospective trial, the sensitivity of the deterioration index to detect adverse event any time prior to the adverse event was 0.474, 0.369 1 hour prior, and 0.327 4 hours prior, with a specificity of 0.972. CONCLUSIONS: A deterioration prediction model was developed using patient demographics, ward-based observations, laboratory values, and their trends. The model's outputs were converted to a deterioration index that was successfully integrated into a live hospital electronic medical record. The sensitivity and specificity of the tool to detect inpatient deterioration were superior to traditional early warning scores.

Influence of titration of antiseizure medications on treatment selection: Results of an online survey with clinicians in the United States.

INTRODUCTION: Most antiseizure medications (ASM) need to be titrated before the optimal dose is achieved. Titration can last several weeks to months. We assessed the impact titration schedules have on ASM treatment-related decisions in the United States (US). METHODS: An online survey was conducted with different healthcare providers (HCPs) in the US involved in the treatment and management of patients with epilepsy. The survey contained three sections: the first section with screening questions; the second on key factors that influence a HCP's decision-making when selecting treatments for different types of seizures and different treatment lines; and the third on the HCP's knowledge and perceptions regarding ASM titration for the treatment of patients with epilepsy. RESULTS: One-hundred and fifty HCPs (63% neurologists) completed the survey. Most HCPs considered titration schedule to be important, with only 1-3% of HCPs, depending on type of seizure, considering the titration schedule to be "not important at all" when prescribing therapy. Healthcare providers' acceptance of titration increased with shorter durations (≥50% accepted titration periods of ≤2 weeks), and lower number of tablets/capsules per dose (≥50% accepted ≤3 tablets/capsules per dose), doses (≥50% accepted ≤2 doses/day), and steps (≥50% accepted ≤3 steps/dose change). Most HCPs (68-91% depending on type of seizure) considered a titration duration of 6 or more weeks only somewhat acceptable or somewhat or highly unacceptable. Almost all HCPs selected "somewhat familiar", "familiar", or "very familiar" as the attribute that best defines their knowledge level of titration, with only 4% selecting "a little familiar". While 87% of HCPs agreed or strongly agreed that they could easily understand titration schedules, only 27% of them agreed or strongly agreed that patients could easily understand titration schedules and 58% of HCPs considered that adhering to the titration schedule was difficult for patients. Most HCPs agreed or strongly agreed that a complex or long titration schedule renders it difficult to achieve their treatment objectives. CONCLUSIONS: Healthcare providers take into account the duration and complexity of the titration period in their ASM prescribing decision-making and prefer shorter and simpler titration schedules, particularly for patients who are experiencing convulsive seizures and starting monotherapy. There was a clear difference between the HCP's belief in their own ability to understand a titration schedule, and their belief that the patient would be able to follow the titration schedule appropriately.

Biochemometric Analysis of Fatty Acid Amide Hydrolase Inhibition by Echinacea Root Extracts.

Recent research demonstrates that Echinacea possesses cannabimimetic activity with potential applications beyond common contemporary uses for relief of cold and flu symptoms. In this study, we investigated the in vitro inhibitory effect of root extracts of Echinacea purpurea and Echinacea angustifolia on fatty acid amide hydrolase, the main enzyme that degrades the endocannabinoid anandamide. The objective was to relate variation in bioactivity between commercial Echinacea genotypes to their phytochemical profiles and to identify determinants of activity using biochemometric analysis. Forty root extracts of each of species were tested for inhibition of fatty acid amide hydrolase and analyzed by HPLC-DAD/MS to identify and quantitate alkylamides and caffeic acid derivatives. Fatty acid amide hydrolase inhibition ranged from 34 - 80% among E. angustifolia genotypes and from 33 - 87% among E. purpurea genotypes. Simple linear regression revealed the caffeic acid derivatives caftaric acid and cichoric acid, and the alkylamide dodeca-2E,4Z-diene-8,10-diynioc acid 2-methylbutylamide, as the strongest determinants of inhibition in E. purpurea (r* = 0.53, 0.45, and 0.20, respectively) while in E. angustifolia, only CADs were significantly associated with activity, most notably echinacoside (r* = 0.26). Regression analysis using compound groups generated by hierarchical clustering similarly indicated that caffeic acid derivatives contributed more than alkylamides to in vitro activity. Testing pure compounds identified as determinants of activity revealed cichoric acid (IC50 = 45 ± 4 µM) and dodeca-2E,4E,8Z,10E-tetraenoic acid isobutylamide (IC50 = 54 ± 2 µM) as the most active. The results suggest that several phytochemicals may contribute to Echinacea's cannabimimetic activity and that ample variation in genotypes exists for selection of high-activity germplasm in breeding programs.

Biases in open-path carbon dioxide flux measurements: Roles of instrument surface heat exchange and analyzer temperature sensitivity.

Eddy covariance (EC) measurements of ecosystem-atmosphere carbon dioxide (CO2) exchange provide the most direct assessment of the terrestrial carbon cycle. Measurement biases for open-path (OP) CO2 concentration and flux measurements have been reported for over 30 years, but their origin and appropriate correction approach remain unresolved. Here, we quantify the impacts of OP biases on carbon and radiative forcing budgets for a sub-boreal wetland. Comparison with a reference closed-path (CP) system indicates that a systematic OP flux bias (0.54 µmol m-2 s-1) persists for all seasons leading to a 110% overestimate of the ecosystem CO2 sink (cumulative error of 78 gC m-2). Two potential OP bias sources are considered: Sensor-path heat exchange (SPHE) and analyzer temperature sensitivity. We examined potential OP correction approaches including: i) Fast temperature measurements within the measurement path and sensor surfaces; ii) Previously published parameterizations; and iii) Optimization algorithms. The measurements revealed year-round average temperature and heat flux gradients of 2.9 °C and 16 W m-2 between the bottom sensor surfaces and atmosphere, indicating SPHE-induced OP bias. However, measured SPHE correlated poorly with the observed differences between OP and CP CO2 fluxes. While previously proposed nominally universal corrections for SPHE reduced the cumulative OP bias, they led to either systematic under-correction (by 38.1 gC m-2) or to systematic over-correction (by 17-37 gC m-2). The resulting budget errors exceeded CP random uncertainty and change the sign of the overall carbon and radiative forcing budgets. Analysis of OP calibration residuals as a function of temperature revealed a sensitivity of 5 µmol m-3 K-1. This temperature sensitivity causes CO2 calibration errors proportional to sample air fluctuations that can offset the observed growing season flux bias by 50%. Consequently, we call for a new OP correction framework that characterizes SPHE- and temperature-induced CO2 measurement errors.