Drug burden index of people ageing with intellectual disability and cognitive complaints attending a specialist memory service.

BACKGROUND: Medications with sedative or anticholinergic properties should be prescribed with caution in those with cognitive complaints. This is particularly relevant in people ageing with an intellectual disability (ID). Higher drug burden index (DBI) scores are associated with increased frailty and falls and reduced quality of life in older people and increased risk of adverse effects (daytime somnolence, constipation) in those with ID. While previous studies have shown that the ID population has higher rates of drug burden and a higher propensity to be prescribed an antipsychotic than the general population, the degree of burden has not been assessed specifically in those with ID and cognitive complaints. METHODS: We assessed drug burden in a cohort of sequential referrals to a national memory service for people with ID. All patients were referred for assessment of cognitive complaints (self-reported or caregiver-reported problems with memory or cognition). DBI was calculated individually for each participant, and the impact of aetiology of ID, level of ID, age, psychiatric/neurological comorbidities and diagnostic outcome on DBI scores was assessed. RESULTS: The study population was 58.6% female with a median age of 55 years and aetiology of ID was Down syndrome (DS) in 71.3%. Consensus diagnosis was Alzheimer's dementia in 40.2%, mild cognitive impairment in 29.9% and cognitively unimpaired from baseline in 25.3%. Medication use was high with 95.4% taking medications, with a median number of medications of 4 (interquartile range 4) and a rate of polypharmacy (≥5 medications) of 51.7%. Overall, 65.5% were exposed to sedative or anticholinergic medications with 39.1% exposed to a clinically significant DBI score >1. Those with psychiatric comorbidities, non-DS aetiology or epilepsy were significantly more likely to have a DBI score >1. CONCLUSIONS: People with ID and incipient cognitive complaints have a high level of drug burden, which concerningly exceeds that of the general population.

Ambient air pollutant concentrations and asthma-related hospital admissions during COVID-19 transport restrictions.

OBJECTIVES: Exposure to air pollution is a known risk factor for asthma exacerbations and hospitalisations. This study aimed to identify if COVID-19 transport restrictions led to improvements in air quality in Dublin and if this had an impact on asthma-related hospital admissions. STUDY DESIGN: This was a population-based retrospective cohort study. METHODS: Daily concentration levels of particulate matter (PM2.5 and PM10) and nitrogen dioxide (NO2) were obtained from the Environmental Protection Agency (EPA). The Hospital In-Patient Enquiry (HIPE) system provided the daily number of asthma-related hospital admissions in Dublin. The figures for 2018-2019 were compared with the period of transport restrictions (from March 2020). RESULTS: During the period of transport restrictions, there was a significant decrease in mean daily concentrations in both PM2.5 (8.9 vs 7.8 µg/m3, P = 0.002) and NO2 (24.0 vs 16.7 µg/m3, P < 0.001). There was also a significant reduction in the mean number of daily asthma admissions (4.5 vs 2.8 admissions, P < 0.001). Only NO2 showed a statistically significant correlation with asthma admissions (r = 0.132, P < 0.001). CONCLUSION: Transport restrictions introduced to mitigate against COVID-19 led to lower pollutant levels and improved air quality. Previously described associations between pollutants and asthma would indicate that these improvements in air quality contributed to the reduction in asthma-related admissions. The complex nature of PM is the likely explanation for the lack of correlation between its concentration and asthma admissions, unlike NO2 whose primary source is vehicular emissions. Public Health needs to advocate for transport policies, which can improve air quality and hence improve human health.

COVID-19 transport restrictions in Ireland: impact on air quality and respiratory hospital admissions.

AIM: Exposure to poor air quality is a well-established factor for exacerbation of respiratory system diseases (RSDs); whether air pollutants are a cause of the development of RSD, however, remains unclear. This study aimed to examine the relationship between COVID-19 transport restrictions and hospital admissions because of RSD in Dublin city and county for 2020. STUDY DESIGN: This was a retrospective population-based cohort. METHODS: Admission data were collected from the Health Service Executive Hospital In-patient Enquiry. Daily count of hospital admissions with Dublin city and county address with primary diagnosis of RSD was performed. The daily air nitrogen dioxide (NO2) data were obtained from the Environmental Protection Agency (EPA). RESULTS: During the period of transport restrictions, there was a reduction in the annual mean NO2 from 25 µg/m3 to 17 µg/m3 (P < 0.001), and decreases in hospital admissions for RSD were observed. Among the 9934 patient episodes included in this study, the mean age at admission was 61.5 years, 57.8% were female (n = 5744), and mean (standard deviation) length of stay was 7.5 (13.52) days. CONCLUSION: This study, using routinely gathered data, suggests that decreases in ambient NO2 as related to COVID-19 transport restrictions were significantly associated with lower asthma and chronic obstructive pulmonary disease admissions.

Impact of COVID-19 Lockdown Restrictions: Ambient NO2 and Asthma Hospital Admissions.

Aim The World Health Organization (WHO) declared the COVID-19 pandemic a global health emergency. Many countries of the world, including Ireland, closed their borders and imposed nationwide lockdown. During this period, all major anthropogenic transport activities, which contribute to atmospheric pollution, were restricted. The current study examines the impact of the transport restrictions on ambient nitrogen dioxide (NO2) concentrations and hospital admissions for asthma across Ireland. Methods This is a retrospective population-based cohort study. National ambient air quality monitoring network data were analysed to investigation variations in NO2 concentrations. Asthma hospital admissions data were collected from the HSE Hospital In-patient Enquiry (HIPE) for Cork, Dublin, and Meath. Results During the period of transport restrictions, there were reductions in the annual mean NO2 for Cork, Dublin and Meath (i.e. 12µg/m3 to 11µg/m3 (p = 1); 25µg/m3 to 17µg/m3 (p < 0.001); and 23µg/m3 to 21µg/m3 (p = 1)). Reductions in asthma hospital admissions were also observed. Among the 8,471 patient episodes included in this study, the mean [SD] age at admission was 47.2[22.9] years; 61% were female (n=5,134); mean [SD] length of stay was 4.9[10.9] days. Conclusion The findings of this study provide an opportunity to explore the impact of NO2 emissions for Cork, Dublin and Meath on asthma hospital admissions, in order to improve air quality modelling and policy development of management of asthma.

Biopsychosocial factors associated with depression and anxiety in older adults with intellectual disability: results of the wave 3 Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing.

BACKGROUND: Depression and anxiety are amongst the most prevalent mental health disorders in the older population with intellectual disability (ID). There is a paucity of research that pertains to associative biopsychosocial factors for depression and anxiety in this population. The aim of this study is to determine the biopsychosocial factors associated with depression and anxiety in a population of older adults with ID in Ireland. METHODS: The study was part of 'The Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing'. Depressive symptoms were assessed using the Glasgow Depression Scale for people with a Learning Disability. Anxiety symptoms were measured using the Glasgow Anxiety Scale for people with a Learning Disability. The cross-sectional associations of depression and anxiety with biopsychosocial parameters were measured using a variety of self-report and proxy-completed questionnaires. RESULTS: For the study population, 9.97% met the criteria for depression, and 15.12% met the criteria for an anxiety disorder. Participants meeting criteria for depression were more likely to be taking regular mood stabiliser medications and to exhibit aggressive challenging behaviour. Participants meeting criteria for anxiety were more likely to have sleep difficulties and report loneliness. Participants meeting criteria for either/both depression and anxiety were more likely to report loneliness. CONCLUSIONS: This study identified both treatable and modifiable, as well as unmodifiable, biopsychosocial factors associated with depression and/or anxiety in older adults with ID. A longitudinal study follow-up will further develop our knowledge on the causality and direction of associated biopsychosocial factors with depression and anxiety in older adults with ID and better inform management strategies, prevention policies and funding of services.

Air Quality and Its Association with Cardiovascular and Respiratory Hospital Admissions in Ireland.

Aim Cardiovascular (CVD) and respiratory (RSD) diseases are leading causes of morbidity and mortality in Ireland. Clear links have been demonstrated in the literature between poor air quality and these diseases. This study aimed to use routinely available data to examine the relationship between air quality index for health (AQIH) (Available URL: http://www.epa.ie/air/quality/index/) and hospital admissions due to CVD and RSD in Dublin City and County between 2014 and 2018. Methods Admission data were collected from the HSE Hospital In-Patient Enquiry (HIPE). Daily count of hospital admissions with Dublin city and county address with a primary diagnosis of CVS and RSD was performed. The daily AQIH were obtained from the EPA for Dublin. Results Overall, AQIH distribution was: Good: 96% (1,575/1,642); Fair: 3% (52/1,642); and Poor: 1% (11/1,642). There were significant rises in admissions with change in AQIH (i.e. from good to very poor) for asthma, chronic obstructive airways disease and heart failure. There were also varying significant changes in short-term admission rates (i.e. up to 72 hours) following change in AQIH. Conclusions This study, using routinely gathered data, suggests that in Dublin city, where the AQ is predominantly good, that change in ambient AQ appears to impact admissions with CVD and RSD.

The association of life events and mental ill health in older adults with intellectual disability: results of the wave 3 Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing.

BACKGROUND: Exposures to life events are associated with emotional, psychological and behavioural problems in those with intellectual disability (ID). Older adults with ID may experience different life events given differences in living circumstances, cognitive decline, greater dependency on others and less autonomy. This study examines the relationship of life events and mental ill health in an older ID population in Ireland. METHODS: The study was part of 'The Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing'. The frequency of life events was assessed using a 20-item checklist, and the level of stress experienced was assessed using a three-point Likert scale measuring the burden of the life event. The associations of life events with factors associated with mental ill health were measured using a variety of self-report and proxy completed questionnaires. RESULTS: For the study population, 88.1% had been exposed to at least one life event in the preceding 12 months and 64.5% to two or more life events. Frequency and burden of life events were significantly higher in individuals living in institutional settings and in individuals with any current psychiatric condition, increased depressive and anxiety symptoms, challenging behaviour and reported poorer self-rated mental and physical health. More life events were significantly associated with new psychiatric diagnoses as well as initiation and increased dosage of mood stabilising, hypnotic and sedative medications. CONCLUSIONS: Life events are significantly associated with mental ill health in the older ID population. Service providers must focus on limiting the exposure to these events and, in situations where they cannot be avoided, should support and manage individuals compassionately and effectively, prioritising their mental and physical well-being.

An Under-Recognised Cause of Iatrogenic, Severe Metabolic Acidosis

Case Pyroglutamic acidosis is an uncommonly diagnosed but important cause of a high anion gap metabolic acidosis. Our case report concerns an elderly male admitted to the Intensive Care Unit (ICU) following the acute onset of coma which developed during treatment of a prosthetic joint infection. A diagnosis of pyroglutamic acidosis was ultimately made and later confirmed with laboratory testing. Blood gas analysis revealed a profound high anion gap metabolic acidosis. Treatment Treatment included withdrawal of the precipitating medications, N-acetylcysteine and sodium bicarbonate. Discussion This case highlights an unusual cause of severe metabolic acidosis caused by commonly used medications and readily reversible if recognised. This is of particular relevance in elderly, frail patients as incorrect alternate diagnoses may result in decisions which incorrectly limit critical care therapies.

Prevalence and patterns of anti-epileptic medication prescribing in the treatment of epilepsy in older adults with intellectual disabilities.

BACKGROUND: The prevalence of epilepsy is higher in people with intellectual disability (ID) and increases with the degree of ID. Although life expectancy for people with ID is increasing, people with ID coexisting with epilepsy have a higher mortality rate, particularly those who had recent seizures. There have been few observational studies of the prevalence and patterns of anti-epileptic prescribing among older people with ID and epilepsy. The aim of this study was to investigate prevalence and patterns of anti-epileptic prescribing in the treatment of epilepsy in a representative population of older people with ID and epilepsy. METHODS: This was an observational cross-sectional study from wave 1 (2009/2010) of Intellectual Disability Supplement to the Irish Longitudinal Study on Aging, a nationally representative sample of 753 persons with ID aged between 41 and 90 years. Participants and/or proxies recorded medicines used on a regular basis and reported doctor's diagnosis of epilepsy; medication data were available for 736 (98%). Prescribing of anti-epileptic drugs (AEDs) for epilepsy in those with a doctor's diagnosis of epilepsy (N = 205) was the primary exposure of interest for this study. Participant exposure to these AEDs was then categorised into AED monotherapy and polytherapy. Participants/carers reported seizure frequency, when epilepsy was last reviewed and which practitioner reviewed epilepsy. In addition, medications that may lower the seizure threshold that were listed in the Maudsley prescribing guidelines in psychiatry were examined. RESULTS: Of the 736 participants with reported medicines use, 38.9% (n = 287) were exposed to AEDs, and 30.6% (225) had a doctor's diagnosis of epilepsy. Of those with epilepsy (n = 225), 90.9% (n = 205) reported concurrent use of AEDs and epilepsy. Of these 205 participants, 50.3% (n = 103) were exposed to AED polytherapy, and 63 different polytherapy regimes were reported. The most frequently reported AEDs were valproic acid (n = 100, 48.7%), carbamazepine (n = 89, 46.3%) and lamotrigine (n = 57, 27.8%). In total, 13.7% had a concurrent psychotropic, which should be avoided in epilepsy, and 32.6% had a psychotropic where caution is required. Antipsychotics with potential epileptogenic potential accounted for 80% of these medications. Of those with AED polytherapy (n = 103), 29.5% (28) reported being seizure free for the previous 2 years. CONCLUSIONS: Prevalence of epilepsy was high among older people with ID, and half were exposed to two or more AEDs. Despite the use of AED therapy, over half had seizures in the previous 2 years. As the primary goals of optimal AED treatment are to achieve seizure freedom without unacceptable adverse effects, this was not achievable for many older patients with ID and epilepsy. Our findings indicated that people with ID and epilepsy were often exposed to psychotropic medications that may lower the seizure threshold. Regular review of epilepsy and medicines (including medicines that may interact with AEDs or lower the seizure threshold) by multidisciplinary teams working to agreed standards may improve quality of prescribing. Improved exchange of information and coordination of care between specialists and primary care practitioners in line with expert consensus recommendations could bring substantial benefit.

Prevalence, patterns and factors associated with psychotropic use in older adults with intellectual disabilities in Ireland.

BACKGROUND: People with intellectual disability (ID) are at increased risk of exposure to psychotropic drugs and psychotropic polypharmacy because of the higher prevalence of mental health conditions present and more controversially, the use of these agents to treat challenging behaviours. Despite the fact that many adults with ID are exposed to psychotropic polypharmacy, few studies to date have focused on the patterns of use of multiple psychotropics, or factors associated with psychotropic polypharmacy, particularly in the older population. This study aims to examine the prevalence, patterns and factors associated with psychotropic use in general and psychotropic polypharmacy in particular in a representative sample of ageing people with ID. METHODS: This was an observational cross-sectional study from Wave 1 of Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing; a nationally representative sample of 753 persons with ID aged between 41 and 90 years. Participants/proxy reported medicines (prescription and over the counter) taken on a regular basis; medication data were available for 736 participants (98%). Participants were divided into those with no psychotropic exposure, exposure to 1 psychotropic and psychotropic polypharmacy (2+ psychotropics). Patterns of psychotropic use were analysed. A multinomial logistic regression model identified factors associated with use of 1 psychotropic and psychotropic polypharmacy. RESULTS: Overall, 59.1% (436) of the sample was exposed to any psychotropic; of these, 66.2% reported psychotropic polypharmacy. Antipsychotics were the most frequently reported psychotropic class by 43% of the sample. Living in a residential institution and having a history of reporting a mental health condition or sleep problems were associated with psychotropic polypharmacy after adjusting for confounders, while those with epilepsy were less likely to experience exposure to polypharmacy, but age, gender had no significant effect. CONCLUSIONS: Psychotropic use and polypharmacy were commonplace for older adults with ID. Psychotropic use, particularly the use of psychotropic combinations, needs to be regularly reviewed for safety, efficacy and adverse effects, and rationale for use of multiple agents needs to be clear and documented.

Prospective Assessment of Radiation in Pediatric Urology: The Pediatric Urology Radiation Safety Evaluation Study.

PURPOSE: Pediatric tissues are exquisitely sensitive to ionizing radiation from diagnostic studies and therapies involving fluoroscopy. We prospectively monitored radiation exposure in our pediatric urology patients during fluoroscopy guided operative procedures with single point dosimeters to quantify radiation dose. MATERIALS AND METHODS: Children undergoing fluoroscopy guided urological procedures were prospectively enrolled in the study from 2013 to 2015. Single point dosimeters were affixed to skin overlying the procedural site for the durations of the procedures to record dosimetry data. Patient demographics, procedural variables and fluoroscopic settings were recorded. RESULTS: A total of 78 patients underwent 96 procedures, including retrograde pyelography, ureteral stent insertion, ureteroscopy and percutaneous nephrolithotomy. Median patient age was 12 years (range 0.3 to 17) and median body mass index percentile for age was 70.7 (1.0 to 99.1). Median skin entrance radiation dose for all procedures performed was 0.56 mGy. Median dosages associated with the 29 diagnostic procedures and 49 definitive interventions were 0.6 mGy (mean 0.8, range 0.1 to 2.2) and 0.7 mGy (1.1, 0.0 to 5.5), respectively. The dose associated with the 18 procedures of temporization was significantly higher by comparison (median 1.0 mGy, mean 2.6, range 0.1 to 10.7, p = 0.02). CONCLUSIONS: Pediatric radiation exposure is not insignificant during urological procedures. Further multi-institutional work would provide context for our findings. Protocols to optimize fluoroscopic settings and minimize patient exposure, and guidelines for radiation based imaging should have a key role in all pediatric radiation safety initiatives.

Effect of natalizumab on brain atrophy and disability progression in multiple sclerosis patients over 5 years.

BACKGROUND AND PURPOSE: The long-term benefit of natalizumab on brain atrophy progression in multiple sclerosis (MS) patients is unknown. Our aim was to investigate its effect over 5 years. METHODS: This prospective study included 60 relapsing MS patients who started natalizumab treatment in years 2006-2007. RESULTS: At the 5-year follow-up, 20 patients discontinued natalizumab after an average of 29.5 cycles, 27 continued natalizumab treatment with some periods of honeymoon (average of 38.4 infusions) and 13 never stopped natalizumab (average of 60.6 infusions). In multiple linear regression analysis, adjusted for age, sex and baseline magnetic resonance imaging (MRI) status, the number of natalizumab infusions was associated with decrease of relapse rate (adjusted P = 0.037), but no association was found with the progression of disability, accumulation of lesion burden or brain volume loss. However, only one (8%) patient in the continuous monthly group experienced disability progression compared to 10 (37%) in the non-continuous and seven (35%) in the discontinuation natalizumab groups. At the follow-up, two patients had died [one from a fatal case of progressive multifocal leukoencephalopathy (PML) and one from a car accident] and 15 patients were lost to follow-up. There was another case of non-fatal PML over the follow-up. CONCLUSIONS: In line with previous reports, MS patients with longer and continuous use of natalizumab had fewer relapses and remained stable in their disability status. No difference in lesion burden accumulation or brain atrophy development was found in relation to the duration of natalizumab use. PML occurred in 2.5% of patients in this small sample cohort. Given the increased risk of PML and uncertain benefit of prolonged natalizumab use on clinical and MRI outcomes of disease progression found in this study, a careful risk-benefit therapeutic assessment is mandatory.

FUNDAMENTAL MOVEMENT SKILLS OF PRESCHOOL CHILDREN IN NORTHWEST ENGLAND.

This cross-sectional study examined fundamental movement skill competency among deprived preschool children in Northwest England and explored sex differences. A total of 168 preschool children (ages 3-5 yr.) were included in the study. Twelve skills were assessed using the Children's Activity and Movement in Preschool Motor Skills Protocol and video analysis. Sex differences were explored at the subtest, skill, and component levels. Overall competence was found to be low among both sexes, although it was higher for locomotor skills than for object-control skills. Similar patterns were observed at the component level. Boys had significantly better object-control skills than girls, with greater competence observed for the kick and overarm throw, while girls were more competent at the run, hop, and gallop. The findings of low competency suggest that developmentally appropriate interventions should be implemented in preschool settings to promote movement skills, with targeted activities for boys and girls.

Retinal nerve fiber layer thickness and thalamus pathology in multiple sclerosis patients.

BACKGROUND AND PURPOSE: Visual impairments are frequent in multiple sclerosis (MS). Optic neuritis can directly reduce retinal nerve fiber layer (RNFL) thickness. Our objectives were to evaluate associations of the RNFL thickness (RNFLT) of MS patients with magnetic resonance imaging (MRI) measures of regional brain atrophy and tissue injury in the post-chiasmatic deep gray matter (GM) section of the visual pathway. METHODS: Retinal nerve fiber layer thickness was measured using optical coherence tomography (OCT) in 96 relapsing-remitting MS (RR-MS) patients and 46 controls. MRI was obtained within ±3 months of OCT. RNFLT associations with MRI measures from diffusion tensor imaging and regional and tissue specific atrophy were assessed. RESULTS: In RR-MS, lower RNFLT was associated with lower white matter volume and lower whole brain volume. Lower RNFLT was associated with lower total deep gray matter volume and lower thalamus volume. Lower RNFLT was associated with greater mean diffusivity (MD) in normal appearing (NA) brain tissue and NA gray matter. Trends were found for lower RNFLT with greater MD in NA white matter and thalamus. RNFLT in controls was not associated with MD. CONCLUSIONS: Lower RNFLT is associated with microscopic tissue injury in NA regions of the brain and with neurodegeneration of the deep gray matter and thalamus in RR-MS.

NK cell line modified to express a potent, DR5 specific variant of TRAIL, show enhanced cytotoxicity in ovarian cancer models.

Objective: Ovarian cancer is a lethal gynaecological malignancy with unsatisfactory 5 year survival rates of 30-50 %. Cell immunotherapy is a promising new cancer treatment where immune cells, such as Natural Killer (NK) cells, are administered to enable the patient to fight cancer through direct cytotoxicity. NK cells orchestrate an adaptive immune response by enabling the release of tumour antigens. NK cell cytotoxicity and effector responses are largely driven by TRAIL engagement. In this study we investigated the cytotoxic potential of a human NK cell line that were modified to express a potent DR5 specific TRAIL variant. We hypothesised that this modification would enhance NK cell cytotoxicity against TRAIL sensitive and resistant ovarian cancer cell lines in vitro. Methods: KHYG-1 human NK cells were modified with a TRAIL variant targeting DR5 (TRAILv-KHYG-1). Human ovarian cancer cell lines, OVCAR-3 and SKOV-3, were cultured with modified or non-modified NK cells at different effector:target (E:T) ratios for 4 or 16 h. Apoptosis was assessed by Annexin-APC and 7-AAD and measured using flow cytometry. Apoptotic cells were defined as annexin V 7-AAD double positive. Cytokine expression was measured by multiplex ELISA, and analysed by flow cytometry. Results: Modified and non-modified NK cells significantly reduced OVCAR-3 cell viability as compared to OVCAR-3 cells that were cultured alone after 4 and 16 h treatment. OVCAR-3 cell viability was reduced after treatment with 1:1 E:T ratio with TRAILv-KHYG-1 cells after 16 h. On the contrary, neither NK cell line had any effect of SKOV-3 cell viability despite SKOV-3 cells having more DR5 surface expression compared to OVCAR-3 cells. Conclusions: TRAILv-KHYG-1 cells significantly reduced OVCAR-3 cell viability as compared to non-modified NK cells. However, no significant reduction in viability was observed when SKOV-3 cell were cultured with either NK cells, despite having more DR5 surface expression compared to OVCAR-3 cells. These data indicate that mechanisms other than DR5 expression drive TRAIL resistance in ovarian cancer.

Multimodal imaging in systemic lupus erythematosus patients with diffuse neuropsychiatric involvement.

OBJECTIVES: The objective of this paper is to investigate conventional and nonconventional brain magnetic resonance imaging (MRI) findings in systemic lupus erythematosus (SLE) patients with diffuse neuropsychiatric involvement (dNPSLE) compared to healthy controls (HCs). METHODS: Twenty-six (26) SLE patients with one or more diffuse NP syndromes related to the central nervous system (CNS) (dNPSLE) and 36 age- and sex-matched HCs were scanned on a 3T MRI using a multimodal imaging approach. Univariate and multivariate analyses were used to determine MRI-specific measure differences between dNPSLE and HCs for lesion burden, tissue-specific atrophy, magnetization transfer ratio (MTR) and diffusion-tensor imaging (DTI) outcomes. RESULTS: In univariate analyses, dNPSLE patients showed significantly increased T1 lesion number (p = .001) and T1-lesion volume (LV, p = .008) compared to HCs. dNPSLE patients showed decreased whole brain volume (p < .0001), gray matter volume (p < .0001), cortical volume (p < .0001) and increased lateral ventricle volume (p = .004) compared to HCs. dNPSLE patients had increased axial diffusivity (AD) of NAWM (p = .008) and NA brain tissue (p = .017) compared to HCs. In the multivariate regression analysis, decreased cortical volume was associated with SLE (R (2) = 0.59, p < .0001). CONCLUSIONS: This study shows that cortical and central atrophy are associated with SLE patients with diffuse CNS syndromes. Microscopic tissue injury in the NAWM on AD DTI measures in SLE patients indicates a predominant reduction of axonal density.

Impact of opening a new emergency department on healthcare service and patient outcomes: analyses based on linking ambulance, emergency and hospital databases.

BACKGROUND: Emergency department (ED) crowding caused by access block is an increasing public health issue and has been associated with impaired healthcare delivery, negative patient outcomes and increased staff workload. AIM: To investigate the impact of opening a new ED on patient and healthcare service outcomes. METHODS: A 24-month time series analysis was employed using deterministically linked data from the ambulance service and three ED and hospital admission databases in Queensland, Australia. RESULTS: Total volume of ED presentations increased 18%, while local population growth increased by 3%. Healthcare service and patient outcomes at the two pre-existing hospitals did not improve. These outcomes included ambulance offload time: (Hospital A PRE: 10 min, POST: 10 min, P < 0.001; Hospital B PRE: 10 min, POST: 15 min, P < 0.001); ED length of stay: (Hospital A PRE: 242 min, POST: 246 min, P < 0.001; Hospital B PRE: 182 min, POST: 210 min, P < 0.001); and access block: (Hospital A PRE: 41%, POST: 46%, P < 0.001; Hospital B PRE: 23%, POST: 40%, P < 0.001). Time series modelling indicated that the effect was worst at the hospital furthest away from the new ED. CONCLUSIONS: An additional ED within the region saw an increase in the total volume of presentations at a rate far greater than local population growth, suggesting it either provided an unmet need or a shifting of activity from one sector to another. Future studies should examine patient decision making regarding reasons for presenting to a new or pre-existing ED. There is an inherent need to take a 'whole of health service area' approach to solve crowding issues.

Effect of a school-based active play intervention on sedentary time and physical activity in preschool children.

Early childhood is a critical time for promoting physical activity. Few studies have investigated the effect of interventions in this population. The aim of this study was to investigate the effect of a school-based active play intervention on preschool children's sedentary time and physical activity. Preschool children were recruited from randomly selected preschools. Schools were randomly assigned to an intervention or comparison group. One teacher per intervention school received training from active play professionals in the delivery of a 6-week active play programme. Comparison schools continued their usual practice. Children wore a uni-axial accelerometer for 7 days at baseline, immediately after and at 6-month post-intervention. No significant intervention effects were observed for sedentary time or physical activity. However, sex and hours spent at school were significant predictors of physical activity. Children who spent fewer hours (half-day children) at school were significantly more active than their full-day counterparts. Physical activity during the intervention classes was high even though neither daily physical activity nor sedentary time changed. Notably children who spent more time at preschool were less active suggesting that preschool was not as conducive to physical activity engagement as other environments.

Using Reddit as a recruitment strategy for addiction science research.

Reddit is a forum-based social media and message board platform that has been used in the social sciences as a recruitment source of human subject data. In addiction science, Reddit remains a viable but underutilized tool, compared to other websites (e.g., Amazon's Mechanical Turk, Prolific). The purpose of this commentary is to provide a rationale and recommendations for the successful use of Reddit for addiction science researchers interested in adding it as a recruitment tool. We provide an example of how Reddit can be used to target specific populations of interest, such as individuals struggling with depression or alcohol use disorder. Last, we discuss the limitations of Reddit as a research tool and some considerations for future research to help promote effective use of the platform.

Voxel-wise magnetization transfer imaging study of effects of natalizumab and IFNß-1a in multiple sclerosis.

OBJECTIVE: To determine the effects of intravenous natalizumab and intramuscular interferon beta-1a (IFNß-1a) on the volume of white-matter (WM) lesions and normal appearing brain tissue (NABT) undergoing voxel-wise (VW) increases in magnetization transfer ratio (MTR) suggestive of remyelination in patients with relapsing multiple sclerosis. METHODS: This prospective, open-label, single-blinded study enrolled patients with relapsing-remitting multiple sclerosis (RRMS) and relapsing secondary progressive multiple sclerosis (RSPMS) as well as a group of age/sex-matched healthy controls (n=22). Patients with multiple sclerosis were assigned to receive natalizumab monotherapy (n=77; RRMS/RSPMS) or intramuscular IFNß-1a (n=26) as either monotherapy (RRMS) or combined with pulsed i.v. methylprednisolone, as needed (RSPMS). The primary endpoint was the two-year change in volume of NABT VWMTR, by quantifying the number of voxels that increased (suggesting remyelination) or decreased (suggesting demyelination) in their MTR value. RESULTS: The volume of tissue undergoing increases in VWMTR was significantly larger in natalizumab compared with IFNß-1a-treated patients (year 1: p=0.001 in NABT and p<0.006 in WM lesions; year 2: p=0.008 in NABT) and compared with healthy control subjects (year 1: p=0.05 and year 2: p=0.007 in NABT). The larger volume within NABT undergoing decreases in VWMTR was detected in multiple sclerosis patients compared with healthy controls (p<0.001), and in the IFNß-1a group compared with the natalizumab group (year 1: p=0.05; year 2: p=0.002). One patient on natalizumab died from progressive multifocal leukoencephalopathy eight months after completing the study. CONCLUSION: Natalizumab may promote remyelination and stabilize demyelination in lesions and NABT in relapsing multiple sclerosis, compared with intramuscular IFNß-1a.