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Background: Healthcare facilities have experienced many challenges during the COVID-19 pandemic, including limited personal protective equipment (PPE) supplies. Healthcare personnel (HCP) rely on PPE, vaccines, and other infection control measures to prevent SARS-CoV-2 infections. We describe PPE concerns reported by HCP who had close contact with COVID-19 patients in the workplace and tested positive for SARS-CoV-2. Method: The CDC collaborated with Emerging Infections Program (EIP) sites in 10 states to conduct surveillance for SARS-CoV-2 infections in HCP. EIP staff interviewed HCP with positive SARS-CoV-2 viral tests (ie, cases) to collect data on demographics, healthcare roles, exposures, PPE use, and concerns about their PPE use during COVID-19 patient care in the 14 days before the HCP’s SARS-CoV-2 positive test. PPE concerns were qualitatively coded as being related to supply (eg, low quality, shortages); use (eg, extended use, reuse, lack of fit test); or facility policy (eg, lack of guidance). We calculated and compared the percentages of cases reporting each concern type during the initial phase of the pandemic (April–May 2020), during the first US peak of daily COVID-19 cases (June–August 2020), and during the second US peak (September 2020–January 2021). We compared percentages using mid-P or Fisher exact tests (α = 0.05). Results: Among 1,998 HCP cases occurring during April 2020–January 2021 who had close contact with COVID-19 patients, 613 (30.7%) reported ≥1 PPE concern (Table 1). The percentage of cases reporting supply or use concerns was higher during the first peak period than the second peak period (supply concerns: 12.5% vs 7.5%; use concerns: 25.5% vs 18.2%; p Conclusions: Although lower percentages of HCP cases overall reported PPE concerns after the first US peak, our results highlight the importance of developing capacity to produce and distribute PPE during times of increased demand. The difference we observed among selected groups of cases may indicate that PPE access and use were more challenging for some, such as nonphysicians and nursing home HCP. These findings underscore the need to ensure that PPE is accessible and used correctly by HCP for whom use is recommended.
Clozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear.
The aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine.
This was a naturalistic study of community patients recommended for clozapine treatment.
Of 158 patients recommended for clozapine treatment, 88 (56%) patients agreed to clozapine initiation and, of these, 58 (66%) were successfully established on clozapine. The success rate for community initiation was 65.4%; which was not significantly different from that for in-patient initiation (58.82%, χ2(1,88) = 0.47, P = 0.49). Following clozapine initiation, there was a significant reduction in median out-patient visits over 1 year (from 24.00 (interquartile range (IQR) = 14.00–41.00) to 13.00 visits (IQR = 5.00–24.00), P < 0.001), and 2 years (from 47.50 visits (IQR = 24.75–71.00) to 22.00 (IQR = 11.00–42.00), P < 0.001), and a 74.71% decrease in psychiatric hospital bed days (z = −2.50, P = 0.01). Service-use costs decreased (1 year: –£963/patient (P < 0.001); 2 years: –£1598.10/patient (P < 0.001). Subanalyses for community-only initiation also showed significant cost reductions (1 year: –£827.40/patient (P < 0.001); 2 year: –£1668.50/patient (P < 0.001) relative to costs prior to starting clozapine. Relative to before initiation, symptom severity was improved in patients taking clozapine at discharge (median Positive and Negative Syndrome Scale total score: initial visit: 80 (IQR = 71.00–104.00); discharge visit 50.5 (IQR = 44.75–75.00), P < 0.001) and at 2 year follow-up (Health of Nation Outcome Scales total score median initial visit: 13.00 (IQR = 9.00–15.00); 2 year follow-up: 8.00 (IQR = 3.00–13.00), P = 0.023).
These findings indicate that community initiation of clozapine is feasible and is associated with significant reductions in costs, service use and symptom severity.
OBJECTIVES/GOALS: We aimed to determine if GLP-1 receptor agonists exert beneficial effects on surrogate measures of cardiovascular function independently of weight loss. Our objective was to compare the outcomes between GLP-1 receptor agonist treatment versus a similar drug without cardiovascular benefit versus weight loss through diet alone. METHODS/STUDY POPULATION: We enrolled 88 individuals with obesity (BMI â‰¥ 30kg/m2) and pre-diabetes and randomized them in a 2:1:1 ratio to 14 weeks of the GLP-1 receptor agonist liraglutide, the dipeptidyl peptidase-4 inhibitor sitagliptin, or hypocaloric diet. Sitagliptin blocks degradation of endogenous GLP-1 but does not cause weight loss or lower adverse cardiovascular outcomes. Treatment was double-blinded and placebo-controlled for drug, and unblinded for diet. Primary endpoints were flow-mediated dilation (FMD) to assess endothelial vasodilatory function, and plasminogen activator inhibitor-1 (PAI-1) to assess endothelial fibrinolytic function. We used a general linear model for each outcome and included gender as a covariate for FMD. Baseline characteristics were similar. Mean age was 50, with 32% men and 13% black. RESULTS/ANTICIPATED RESULTS: At 14 weeks, diet and liraglutide caused weight loss (diet -4.3 Â± 3.2 kg, P<0.01; liraglutide -2.7 Â± 3.2, P<0.01), while sitagliptin did not (-0.7 Â± 2.0, P=0.17). Diet did not improve FMD at 14 weeks compared to baseline (+0.9%, 95% CI [-1.5, 3.3], P=0.46). FMD tended to increase after liraglutide and sitagliptin but was not significant (liraglutide +1.2 [-0.3, 2.8], P=0.12; sitagliptin +1.6 [-0.6, 3.8], P=0.15). Given that liraglutide and sitagliptin work through the same GLP-1 pathway, we combined the liraglutide and sitagliptin groups for overall effect on FMD, which was significantly improved from baseline (+1.4 [0.1, 2.8], P=0.04). Diet and liraglutide improved PAI-1 at 14 weeks (diet -4.4U/mL, [-8.5, -0.2], P=0.04; liraglutide -3.4 [-6.0, -0.7], P=0.01), while sitagliptin did not (-1.4 [-5.1, 2.3], P=0.46). DISCUSSION/SIGNIFICANCE: Activation of the GLP-1 pathway by liraglutide or sitagliptin improves FMD independent of weight loss, while PAI-1 improvement is weight-loss dependent and is only seen after liraglutide or diet. Our study suggests the cardiovascular benefit of liraglutide may be due to combined improvements in endothelial vasodilatory and fibrinolytic function.
The 2016–17 European outbreak of H5N8 HPAIV (Clade 126.96.36.199b) affected a wider range of avian species than the previous H5N8 outbreak (2014–15), including an incursion of H5N8 HPAIV into gamebirds in England. Natural infection of captive-reared pheasants (Phasianus colchicus) led to variable disease presentation; clinical signs included ruffled feathers, reluctance to move, bright green faeces, and/or sudden mortality. Several birds exhibited neurological signs (nystagmus, torticollis, ataxia). Birds exhibiting even mild clinical signs maintained substantial levels of virus replication and shedding, with preferential shedding via the oropharyngeal route. Gross pathology was consistent with HPAIV, in gallinaceous species but diphtheroid plaques in oropharyngeal mucosa associated with necrotising stomatitis were novel but consistent findings. However, minimal or modest microscopic pathological lesions were detected despite the systemic dissemination of the virus. Serology results indicated differences in the timeframe of exposure for each case (n = 3). This supported epidemiological conclusions confirming that the movement of birds between sites and other standard husbandry practices with limited hygiene involved in pheasant rearing (including several fomite pathways) contributed to virus spread between premises.
The transition from the Late Archaic to the Late Early Formative period witnessed profound changes in the Maya lowlands. In addition to the establishment of the first settlements and agrarian communities, this critical phase of cultural development heralded the introduction of ceramics, saw changes in lithic technology, gave rise to inter-regional trade and exchange, and witnessed the introduction of a complex symbolic system expressed on portable objects. In this article, we synthesize data collected over the past several decades by various archaeological projects in western Belize to provide an overview of the cultural changes that unfolded during the Late Archaic to Late Early Formative period in the Upper Belize River Valley. We also provide evidence indicating that it was during this critical transitional period that we begin to see the establishment of several cultural traditions that became uniquely lowland Maya.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
rms at a spatial resolution of
11–18 arcsec, resulting in a catalogue of
220 000 sources, of which
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
The number of people over the age of 65 attending Emergency Departments (ED) in the United Kingdom (UK) is increasing. Those who attend with a mental health related problem may be referred to liaison psychiatry for assessment. Improving responsiveness and integration of liaison psychiatry in general hospital settings is a national priority. To do this psychiatry teams must be adequately resourced and organised. However, it is unknown how trends in the number of referrals of older people to liaison psychiatry teams by EDs are changing, making this difficult.
We performed a national multi-centre retrospective service evaluation, analysing existing psychiatry referral data from EDs of people over 65. Sites were selected from a convenience sample of older peoples liaison psychiatry departments. Departments from all regions of the UK were invited to participate via the RCPsych liaison and older peoples faculty email distribution lists. From departments who returned data, we combined the date and described trends in the number and rate of referrals over a 7 year period.
Referral data from up to 28 EDs across England and Scotland over a 7 year period were analysed (n = 18828 referrals). There is a general trend towards increasing numbers of older people referred to liaison psychiatry year on year. Rates rose year on year from 1.4 referrals per 1000 ED attenders (>65 years) in 2011 to 4.5 in 2019 . There is inter and intra site variability in referral numbers per 1000 ED attendances between different departments, ranging from 0.1 - 24.3.
To plan an effective healthcare system we need to understand the population it serves, and have appropriate structures and processes within it. The overarching message of this study is clear; older peoples mental health emergencies presenting in ED are common and appear to be increasingly so. Without appropriate investment either in EDs or community mental health services, this is unlikely to improve.
The data also suggest very variable inter-departmental referral rates. It is not possible to establish why rates from one department to another are so different, or whether outcomes for the population they serve are better or worse. The data does however highlight the importance of asking further questions about why the departments are different, and what impact that has on the patients they serve.
Early assessment, diagnosis and management for people living with dementia is essential, both for the patient and their carers. We recognised delays in established local pathways when patients had unplanned acute hospital admissions preventing them from attending memory diagnostic appointments. The Psychiatric Liaison Team (PLT) Memory Pathway was introduced as we had the skills and expertise to resume the process and to find new undetected patients.
Our aim was to determine how well the newly implemented PLT Memory Pathway follows the standards outlined in the National Institute of Health & Care Excellence (NICE) Clinical Guideline 97 (CG97): Assessment, management and support for people living with dementia and their carers.
A retrospective analysis of all PLT referrals from July 2018 to February 2020 (20 months) was performed to identify patients on the community memory pathway and those with possible undetected cognitive impairment. Data were collected from electronic patient records which included demographics, primary and collateral history, cognitive testing and imaging, dementia type among others. Results were analysed using Microsoft Excel.
41 patients were included (59% female). 80% of patients were referred for memory problems or confusion. 63% had previous referrals to a memory service and was on the community memory pathway at the time of the referral. 34% were on anticholinergic medication but in only 14% were this documented as reviewed. 100 % were offered and had head imaging. A finding worthy of note was the absence of any from the ethnic minority background. 63% of patients were given a memory diagnosis and 34% had anti-dementia medication started. Patients’ families were made aware of the diagnosis in 83% of cases, due to the absence of next of kin details in the patient record. Primary Care was made aware in 100% of cases; post-diagnostic support was 100%.
The PLT is well placed to bridge the service gap between the acute care trust and established community memory services when dealing with patients with dementia. A dedicated Memory Pathway has helped to close this gap and adherence to NICE CG97 standards was good, but there is room for improvement. A particular focus will be on improving documentation of anticholinergic medication review and exploration for the absence of ethnic minority patients. Aiming to achieve 100% family involvement is also recommended.
This study has been submitted to the Royal College of Psychiatrists' Faculty of Old Age Annual Conference 2021.
Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.
ABSTRACT IMPACT: This study will provide the essential characterization of intrinsic neural activity in human brain organoids, both at the single cell and network levels, to harness for translational purposes. OBJECTIVES/GOALS: Brain organoids are 3D, stem cell-derived neural tissues that recapitulate neurodevelopment. However, to levy their full translational potential, a deeper understanding of their intrinsic neural activity is essential. Here, we present our preliminary analysis of maturing neural activity in human forebrain organoids. METHODS/STUDY POPULATION: Forebrain organoids were generated from human iPSC lines derived from healthy volunteers. Linear microelectrode probes were employed to record spontaneous electrical activity from day 77, 100, and 130 organoids. Single unit recordings were collected during hour-long recordings, involving baseline recordings followed by glutamatergic blockade. Subsequently, tetrodotoxin, was used to abolish action potential firing. Single units were identified via spike sorting, and the spatiotemporal evolution of baseline neural properties and network dynamics was characterized. RESULTS/ANTICIPATED RESULTS: Nine organoids were recorded successfully (n=3 per timepoint). A significant difference in number of units was seen across age groups (F (2,6) = 6.4178, p = 0.0323). Post hoc comparisons by the Tukey HSD test showed significantly more units in day 130 (51.67 ±14.15) than day 77 (16.33 ±14.98) organoids. Mean firing rates were significantly different in organoids based on age, with drug condition also trending toward significance (F (6,12) = 9.97; p = 0.0028 and p = 0.08 respectively). Post hoc comparisons showed a higher baseline firing rate in day 130 (0.99Hz ±0.30) organoids than their day 77 counterparts at baseline (0.31Hz ±0.066) and glutamate blockade (0.31Hz ±0.045). Preliminary network analysis showed no modularity or small-world features; however, these features are expected to emerge as organoids mature. DISCUSSION/SIGNIFICANCE OF FINDINGS: Initial analysis of brain organoid activity demonstrates changes in single unit properties as they mature. Additional work in this area, as well as further network analyses, will confer better sense of how to rationally utilize brain organoids for translational purposes.
Intracerebral haemorrhage and subarachnoid haemorrhage are associated with considerable morbidity and mortality. Too often the focus is on acute treatment after a haemorrhage has occurred, instead of primary and secondary prevention. Medical therapies to control hypertension, achieve tobacco abstinence, and avoid excessive alcohol consumption can confer broad reductions in haemorrhage risk across pathophysiological subtypes. Judicious restriction of antiplatelet and anticoagulant therapies to only those individuals and those intensities for which they are indicated also can substantially reduce haemorrhagic stroke frequency. Specific endovascular and surgical therapies, judiciously employed, will further reduce risk of first or recurrent haemorrhage from structural vascular anomalies, including arteriovenous malformation, cavernous malformations, and saccular aneurysms. For unruptured intracranial aneurysms, features that favour consideration of preventive occlusion include include younger patient age, prior subarachnoid haemorrhage from a different aneurysm, familial intracranial aneurysms, large aneurysm size, irregular shape, basilar or vertebral artery location, and aneurysm growth on serial imaging. Among individuals who are technical candidates for either coiling or clipping, endovascular coiling is associated with a reduction in procedural morbidity and mortality but has a higher risk of recurrence.
To quantify the impact of clinical guidance and rapid respiratory and meningitis/encephalitis multiplex polymerase chain reaction (mPCR) testing on the management of infants.
Before-and-after intervention study.
Tertiary-care children’s hospital.
Infants ≤90 days old presenting with fever or hypothermia to the emergency department (ED).
The study spanned 3 periods: period 1, January 1, 2011, through December 31, 2014; period 2, January 1, 2015, through April 30, 2018; and period 3, May 1, 2018, through June 15, 2019. During period 1, no standardized clinical guideline had been established and no rapid pathogen testing was available. During period 2, a clinical guideline was implemented, but no rapid testing was available. During period 3, a guideline was in effect, plus mPCR testing using the BioFire FilmArray respiratory panel 2 (RP 2) and the meningitis encephalitis panel (MEP). Outcomes included antimicrobial and ancillary test utilization, length of stay (LOS), admission rate, 30-day mortality. Outcomes were compared across periods using Kruskal-Wallis and Pearson tests and interrupted time series analysis.
Overall 5,317 patients were included: 2,514 in period 1, 2,082 in period 2, and 721 in period 3. Over the entire study period, we detected reductions in the use of chest radiographs, lumbar punctures, LOS, and median antibiotic duration. After adjusting for temporal trends, we observed that the introduction of the guideline was associated with reductions in ancillary tests and lumbar punctures. Use of mPCR testing with the febrile infant clinical guideline was associated with additional reductions in ancillary testing for all patients and a higher proportion of infants 29–60 days old being managed without antibiotics.
Use of mPCR testing plus a guideline for young infant evaluation in the emergency department was associated with less antimicrobial and ancillary test utilization compared to the use of a guideline alone.
The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.
The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.
Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).
At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).
Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.
The National Institute of Standards and Technology (NIST) certifies a suite of Standard Reference Materials (SRMs) to evaluate specific aspects of instrument performance of both X-ray and neutron powder diffractometers. This report describes SRM 660c, the fourth generation of this powder diffraction SRM, which is used primarily for calibrating powder diffractometers with respect to line position and line shape for the determination of the instrument profile function (IPF). It is certified with respect to lattice parameter and consists of approximately 6 g of lanthanum hexaboride (LaB6) powder. So that this SRM would be applicable for the neutron diffraction community, the powder was prepared from an isotopically enriched 11B precursor material. The microstructure of the LaB6 powder was engineered specifically to yield a crystallite size above that where size broadening is typically observed and to minimize the crystallographic defects that lead to strain broadening. A NIST-built diffractometer, incorporating many advanced design features, was used to certify the lattice parameter of the LaB6 powder. Both Type A, statistical, and Type B, systematic, uncertainties have been assigned to yield a certified value for the lattice parameter at 22.5 °C of a = 0.415 682 6 ± 0.000 008 nm (95% confidence).
− Agency is one of five core analytical problems in the Earth System Governance (ESG) Project’s research framework, which offers a unique approach to the study of environmental governance. − Agency in Earth System Governance draws lessons from ESG–Agency research through a systematic review of 322 peer-reviewed journal articles published between 2008 and 2016 and contained in the ESG–Agency Harvesting Database.− ESG–Agency research draws on diverse disciplinary perspectives with distinct clusters of scholars rooted in the fields of global environmental politics, policy studies, and socio-ecological systems. − Collectively, the chapters in Agency in Earth System Governance provide an accessible synthesis of some of the field’s major questions and debates and a state-of-the-art understanding of how diverse actors engage with and exercise authority in environmental governance.
Carers of people experiencing a first episode of psychosis are at an increased risk of developing their own physical and mental health problems. Psychoeducation has been found to improve carer wellbeing and reduce distress. However, few psychoeducation interventions have considered the resource constraints on mental health services and the impact that these can have on the implementation of any such interventions. The present service evaluation aimed to evaluate an abbreviated version (sole session) of a previously tested psychoeducation intervention (three sessions) that targets less adaptive illness beliefs (n = 17). Pre–post effect sizes reveal that all of the carers’ illness beliefs changed in the desired direction, with four out of the 10 illness beliefs associated with large to moderate improvements. When compared with the outcomes obtained in our evaluation of the more intensive, three-session version of the intervention, the between-group effects largely favoured the three-session version but were mostly small. Moderate to large effects in favour of the three-session version were found for two of the 10 illness beliefs. These findings support the further investigation of the sole session psychoeducation intervention as part of a randomised controlled trial.
Key learning aims
(1) To evaluate the impact of a sole-session psychoeducation intervention on illness beliefs.
(2) To compare the outcomes of the sole-session psychoeducation intervention to the previous, more intensive (three-session) version of the same intervention.
(3) To consider the value of research approaches to evaluating psychoeducation interventions for carers of people with psychosis.