Immunization of turkeys with Clostridium septicum alpha toxin-based recombinant subunit proteins can confer protection against experimental Clostridial dermatitis.

Clostridial dermatitis (CD), caused by Clostridium septicum, is an emerging disease of increasing economic importance in turkeys. Currently, there are no effective vaccines for CD control. Here, two non-toxic domains of C. septicum alpha toxin, namely ntATX-D1 and ntATX-D2, were identified, cloned, and expressed in Escherichia coli as recombinant subunit proteins to investigate their use as potential vaccine candidates. Experimental groups consisted of a Negative control (NCx) that did not receive C. septicum challenge, while the adjuvant-only Positive control (PCx), ntATX-D1 immunization (D1) and ntATX-D2 immunization (D2) groups received C. septicum challenge. Turkeys were immunized subcutaneously with 100 µg of protein at 7, 8 and 9 weeks of age along with an oil-in-water nano-emulsion adjuvant, followed by C. septicum challenge at 11 weeks of age. Results showed that while 46.2% of birds in the PCx group died post-challenge, the rate of mortality in D1- or D2-immunization groups was 13.3%. The gross and histopathological lesions in the skin, muscle and spleen showed that the disease severity was highest in PCx group, while the D2-immunized birds had significantly lower lesion scores when compared to PCx. Gene expression analysis revealed that PCx birds had significantly higher expression of pro-inflammatory cytokine genes in the skin, muscle and spleen than the NCx group, while the D2 group had significantly lower expression of these genes compared to PCx. Peripheral blood cellular analysis showed increased frequencies of activated CD4+ and/or CD8+ cells in the D1 and D2-immunized groups. Additionally, the immunized turkeys developed antigen-specific serum IgY antibodies. Collectively, these findings indicate that ntATX proteins, specifically the ntATX-D2 can be a promising vaccine candidate for protecting turkeys against CD and that the protection mechanisms may include downregulation of C. septicum-induced inflammation and increased CD4+ and CD8+ cellular activation.

Magnitude and time to peak oxygenation effect of prone positioning in ventilated adults with COVID-19 related acute hypoxemic respiratory failure.

BACKGROUND: Prone positioning may improve oxygenation in acute hypoxemic respiratory failure and was widely adopted in COVID-19 patients. However, the magnitude and timing of its peak oxygenation effect remain uncertain with the optimum dosage unknown. Therefore, we aimed to investigate the magnitude of the peak effect of prone positioning on the PaO2 :FiO2 ratio during prone and secondly, the time to peak oxygenation. METHODS: Multi-centre, observational study of invasively ventilated adults with acute hypoxemic respiratory failure secondary to COVID-19 treated with prone positioning. Baseline characteristics, prone positioning and patient outcome data were collected. All arterial blood gas (ABG) data during supine, prone and after return to supine position were analysed. The magnitude of peak PaO2 :FiO2 ratio effect and time to peak PaO2 :FIO2 ratio effect was measured. RESULTS: We studied 220 patients (mean age 54 years) and 548 prone episodes. Prone positioning was applied for a mean (±SD) 3 (±2) times and 16 (±3) hours per episode. Pre-proning PaO2 :FIO2 ratio was 137 (±49) for all prone episodes. During the first episode. the mean PaO2 :FIO2 ratio increased from 125 to a peak of 196 (p < .001). Peak effect was achieved during the first episode, after 9 (±5) hours in prone position and maintained until return to supine position. CONCLUSIONS: In ventilated adults with COVID-19 acute hypoxemic respiratory failure, peak PaO2 :FIO2 ratio effect occurred during the first prone positioning episode and after 9 h. Subsequent episodes also improved oxygenation but with diminished effect on PaO2 :FIO2 ratio. This information can help guide the number and duration of prone positioning episodes.

Neuromuscular blockade and oxygenation changes during prone positioning in COVID-19.

PURPOSE: Neuromuscular blockers (NMBs) are often used during prone positioning to facilitate mechanical ventilation in COVID-19 related ARDS. However, their impact on oxygenation is uncertain. METHODS: Multi-centre observational study of invasively ventilated COVID-19 ARDS adults treated with prone positioning. We collected data on baseline characteristics, prone positioning, NMB use and patient outcome. We assessed arterial blood gas data during supine and prone positioning and after return to the supine position. RESULTS: We studied 548 prone episodes in 220 patients (mean age 54 years, 61% male) of whom 164 (75%) received NMBs. Mean PaO2:FiO2 (P/F ratio) during the first prone episode with NMBs reached 208 ± 63 mmHg compared with 161 ± 66 mmHg without NMBs (Δmean = 47 ± 5 mmHg) for an absolute increase from baseline of 76 ± 56 mmHg versus 55 ± 56 mmHg (padj < 0.001). The mean P/F ratio on return to the supine position was 190 ± 63 mmHg in the NMB group versus 141 ± 64 mmHg in the non-NMB group for an absolute increase from baseline of 59 ± 58 mmHg versus 34 ± 56 mmHg (padj < 0.001). CONCLUSION: During prone positioning, NMB is associated with increased oxygenation compared to non-NMB therapy, with a sustained effect on return to the supine position. These findings may help guide the use of NMB during prone positioning in COVID-19 ARDS.

Utilising routine clinical laboratory data to support quality improvement in health care: Application of a national acute kidney injury alert system as a proof of concept.

BACKGROUND: Acute kidney injury (AKI) is a global health issue known to cause avoidable harm and death. Improvement in its prevention and management is therefore considered an important goal for the health-care sector. The work here aimed to develop a tool which could be used to robustly and reliably measure, monitor, and compare the effectiveness of health-care interventions related to AKI across the Welsh NHS, a mechanism which did not exist previously. METHODS: Using serum creatinine (SCr) as a biomarker for AKI and a validated national data-set collected from the all Wales Laboratory Information Management System, work involved applying Donabedian's framework to develop indicators with which to measure outcomes related to AKI, and exploring the potential of statistical process control (SPC) techniques for analysing data on these indicators. RESULTS: Rate of AKI incidence and 30-day AKI-associated mortality are proposed as valid, feasible indicators with which to measure the effectiveness of health-care interventions related to AKI. The control chart, funnel plot, and Pareto chart are proposed as appropriate, robust SPC techniques to analyse and visualise variation in AKI-related outcomes. CONCLUSIONS: This work demonstrates that routinely collected large SCr data offer a significant opportunity to monitor and therefore inform improvement in patient outcomes related to AKI. Moreover, while this work concerns utilisation of SCr data for improvement in AKI strategies, it is a proof of concept which could be replicated for other routinely collected clinical laboratory data, to improve the prevention and/or management of the conditions to which they relate.

Identifying thresholds for clinically meaningful change among clients of drug and alcohol services using the Australian Treatment Outcomes Profile.

AIMS: The Austraian Treatment Outcomes Profile (ATOP) is a brief clinical outcomes tool used widely in the Australian alcohol and other drugs treatment sector to monitor clients' substance use, health, wellbeing and clinical risk factors. It has demonstrated reliability and validity, and has recommended clinical cut-offs for assessing single-occasion client-rated health scores. This study determined clinically meaningful change thresholds for ATOP substance use and health and wellbeing variables for use by clinicians in monitoring client progress, and for quality improvement and service evaluation. DESIGN, SETTING AND PARTICIPANTS: A framework for assessing clinically meaningful changes scores was developed by (1) calculating statistically reliable change thresholds using data-driven techniques with a reference sample of clinical ATOP data and (2) conducting a multi-disciplinary subject matter expert group to review the utility and validity of data-derived clinically meaningful change. The study was conducted within Outpatient Alcohol and Other Drug treatment services in New South Wales, Australia. The reference sample comprised 6100 ATOPs from clients at entry to public outpatient Alcohol and Other Drug treatment services; the subject matter expert group comprised 29 key stakeholders from the specialist alcohol and other drug treatment sector. MEASUREMENTS AND FINDINGS: We used the Reliable Change Index method to calculate clinically meaningful change thresholds for ATOP variables. For substance use variables, a change of 30% in days of use in the last 28 (minimum 4 days) was the threshold for clinically meaningful change for substance use; for health and wellbeing variables, a change of 2 or more points in psychological health, physical health or quality of life scores (measured on 0-10 scales) was the minimum clinically meaningful change. CONCLUSIONS: Clinically meaningful change thresholds have been proposed for Australian Treatment Outcomes Profile substance use and health and wellbeing items, based on statistical reliability and subject matter expert assessment. These will be used in the development of an outcomes metric for assessing change and assigning meaning in aggregated data for evaluation of services.

Substance use, socio-demographic characteristics, and self-rated health of people seeking alcohol and other drug treatment in New South Wales: baseline findings from a cohort study.

OBJECTIVE: To investigate the demographic characteristics, substance use, and self-rated health of people entering treatment in New South Wales public health services for alcohol, amphetamine-type stimulants, cannabis, cocaine, or opioids use, by principal drug of concern. DESIGN: Baseline findings of a cohort study; analysis of data in patient electronic medical records and NSW minimum data set for drug and alcohol treatment services. SETTING, PARTICIPANTS: People completing initial Australian Treatment Outcomes Profile (ATOP) assessments on entry to publicly funded alcohol and other drug treatment services in six NSW local health districts/networks, 1 July 2016 - 30 June 2019. MAIN OUTCOME MEASURES: Socio-demographic characteristics, and substance use and self-rated health (psychological, physical, quality of life) during preceding 28 days, by principal drug of concern. RESULTS: Of 14 087 people included in our analysis, the principal drug of concern was alcohol for 6051 people (43%), opioids for 3158 (22%), amphetamine-type stimulants for 2534 (18%), cannabis for 2098 (15%), and cocaine for 246 (2%). Most people commencing treatment were male (9373, 66.5%), aged 20-39 years (7846, 50.4%), and were born in Australia (10 934, 86.7%). Polysubstance use was frequently reported, particularly by people for whom opioids or amphetamine-type stimulants were the principal drugs of concern. Large proportions used tobacco daily (53-82%, by principal drug of concern group) and reported poor psychological health (47-59%), poor physical health (32-44%), or poor quality of life (43-52%). CONCLUSIONS: The prevalence of social disadvantage and poor health is high among people seeking assistance with alcohol, amphetamine-type stimulants, cannabis, cocaine, or opioids use problems. Given the differences in these characteristics by principal drug of concern, health services should collect comprehensive patient information during assessment to facilitate more holistic, tailored, and person-centred care.

The DACRIN data project: A process for harmonising data collection for clinical research in alcohol and other drugs services in New South Wales.

INTRODUCTION: Standardised data collection processes allow for harmonisation and comparison of data across different studies and services. This project aimed to develop a 'core dataset' to serve as the default collection when designing future studies and evaluations, building upon data routinely collected in clinical alcohol and other drugs (AOD) settings in NSW, Australia. METHODS: A working group was established, comprising clinicians, researchers, data managers and consumers from public sector and non-government organisation AOD services in the NSW Drug and Alcohol Clinical Research and Improvement Network. A series of Delphi meetings occurred to reach consensus on the data items to be included in the core dataset for three domains: demographics, treatment activity and substance use variables. RESULTS: There were 20-40 attendees at each meeting. An initial consensus criterion of having received >70% of the vote was established. Given the difficulty in reaching consensus for most items, subsequently, this was changed to eliminate items that received <5 votes, after which the item receiving the most votes would be selected. DISCUSSIONS AND CONCLUSIONS: This important process received considerable interest and buy-in across the NSW AOD sector. Ample opportunity for discussion and voting was provided for the three domains of interest, allowing participants to contribute their expertise and experience to inform decisions. As such, we believe the core dataset includes the best options currently available to collect data for these domains in the NSW AOD context, and potentially more broadly. This foundational study may inform other attempts to harmonise data across AOD services.

Early childhood naps initiate emotional memory processing in preparation for enhanced overnight consolidation.

Early childhood naps support emotional memory, but benefits are only observed after overnight sleep. Whether emotional memory consolidation occurs during naps, or whether napping only prepares memories for overnight consolidation is unknown. We investigated whether naps protect emotional memories from interference, indicating consolidation. Between 2018 and 2020, 63 children in western Massachusetts preschools (30 female, 33 male; 33-67 months; 23.8% Hispanic, 87.3% White) learned faces paired with negative or neutral descriptions, followed by nap or wake. Before delayed recognition, half completed an interference task. Without interference, napping benefited recognition. With interference, children recognized fewer negative faces post-nap (compared to wake), with overnight sleep attenuating this difference. Results suggest that naps initially destabilize emotional memories, possibly reflecting partial processing that promotes long-term consolidation.

Health and social characteristics of clients reporting amphetamine type substance use at entry to public alcohol and other drug services in New South Wales, Australia, 2016-2019.

INTRODUCTION: Amphetamine type substances (ATS) are commonly used by Australian alcohol and other drug service entrants. We describe demographic characteristics, patterns of ATS and other substance use, health and social conditions among clients entering New South Wales (NSW) public alcohol and other drug services. METHODS: Retrospective cohort of 13,864 records across six health districts (2016-2019) for clients seeking substance use treatment. These districts service approximately 44% of the NSW population aged 15 years and over. Multivariate analysis was conducted on a subsample for whom full data were available (N = 9981). Data included NSW Minimum Data Set for drug and alcohol treatment services and Australian Treatment Outcomes Profile items. RESULTS: Over the preceding 4 weeks, 77% (n = 10,610) of clients (N = 13,864) reported no recent ATS use, 15% (n = 2109) reported 'low frequency' (1-12 days) and 8% (n = 1145) 'high frequency' (13-28 days) use. ATS use was most common among people attending for ATS or opioids as primary drug of concern. A multinomial regression (N = 9981) identified that clients reporting recent arrest (aOR 1.74, 95% CI 1.36, 2.24), higher cannabis use frequency (aOR 1.01, 95% CI 1.00, 1.02), lower opioid use frequency (aOR 0.98, 95% CI 0.97, 0.99) and poorer quality of life (aOR 0.91, 95% CI 0.86, 0.97) were more likely to report 'high frequency' rather than 'low frequency' ATS use. DISCUSSION AND CONCLUSIONS: People who use ATS experience health and social issues that may require targeted responses. These should be integrated across all services, not only for clients with ATS as principal drug of concern.

Myeloid cell MHC I expression drives CD8+ T cell activation in nonalcoholic steatohepatitis.

Background & aims: Activated CD8+ T cells are elevated in Nonalcoholic steatohepatitis (NASH) and are important for driving fibrosis and inflammation. Despite this, mechanisms of CD8+ T cell activation in NASH are largely limited. Specific CD8+ T cell subsets may become activated through metabolic signals or cytokines. However, studies in NASH have not evaluated the impact of antigen presentation or the involvement of specific antigens. Therefore, we determined if activated CD8+ T cells are dependent on MHC class I expression in NASH to regulate fibrosis and inflammation. Methods: We used H2Kb and H2Db deficient (MHC I KO), Kb transgenic mice, and myeloid cell Kb deficient mice (LysM Kb KO) to investigate how MHC class I impacts CD8+ T cell function and NASH. Flow cytometry, gene expression, and histology were used to examine hepatic inflammation and fibrosis. The hepatic class I immunopeptidome was evaluated by mass spectrometry. Results: In NASH, MHC class I isoform H2Kb was upregulated in myeloid cells. MHC I KO demonstrated protective effects against NASH-induced inflammation and fibrosis. Kb mice exhibited increased fibrosis in the absence of H2Db while LysM Kb KO mice showed protection against fibrosis but not inflammation. H2Kb restricted peptides identified a unique NASH peptide Ncf2 capable of CD8+ T cell activation in vitro. The Ncf2 peptide was not detected during fibrosis resolution. Conclusion: These results suggest that activated hepatic CD8+ T cells are dependent on myeloid cell MHC class I expression in diet induced NASH to promote inflammation and fibrosis. Additionally, our studies suggest a role of NADPH oxidase in the production of Ncf2 peptide generation.

Associations of activity, sedentary, and sleep behaviors with cognitive and social-emotional health in early childhood.

Background: Early childhood is important for cognitive and social-emotional development, and a time in which to promote healthy movement behaviors (sedentary behavior, physical activity, and sleep). Movement behaviors may have interactive influences on cognition and social-emotional factors in young children, but most previous research has explored them independently. The purpose of this study was to determine if movement behaviors are associated with measures of cognitive and social-emotional health in young children and if so, to describe optimal compositions of movement behaviors of a daily cycle for such outcomes. Methods: Children (n = 388, 33 to 70 months, 44.6% female) from a clinical trial (ClinicalTrials.gov ID: NCT03285880, first posted September 18, 2017) wore accelerometers on their wrists for 24-h for 9.56 ± 3.3 days. Movement behavior compositions consisted of time spent in sedentary behaviors, light intensity physical activity, moderate to vigorous intensity physical activity (MVPA), and sleep. Outcomes were cognitive (receptive vocabulary, declarative and procedural memory, and executive attention) and social-emotional measures (temperament and behavioral problems). Compositional linear regression models with isometric log ratios were used to investigate the relations between the movement behavior composition and the cognitive and social-emotional health measures. If a significant association was found between the composition and an outcome, we further explored the "optimal" 24-h time-use for said outcome. Results: Movement behavior compositions were associated with receptive vocabulary. The composition associated with the predicted top five percent of vocabulary scores consisted of 12.1 h of sleep, 4.7 h of sedentary time, 5.6 h of light physical activity, and 1.7 h of MVPA. Conclusions: While behavior compositions are related to vocabulary ability in early childhood, our findings align with the inconclusiveness of the current evidence regarding other developmental outcomes. Future research exploring activities within these four movement behaviors, that are meaningful to cognitive and social-emotional development, may be warranted. Supplementary Information: The online version contains supplementary material available at 10.1186/s44167-023-00016-6.

Temporal Associations between Actigraphy-Measured Daytime Movement Behaviors and Nap Sleep in Early Childhood.

The purpose of this micro-longitudinal study was to explore daily associations between daytime movement behaviors (sedentary time and physical activity) and nap sleep in young children. In 298 children (age = 51.0 ± 9.6 months, 43.6% female), wrist-based actigraphy (mean wear time = 10 days) assessed sedentary time, total physical activity, and provided an estimate of nap sleep duration and efficiency. Multilevel logistic and linear regression models were used to examine temporal within-person relations between wake behaviors and nap sleep, and adjusted for overnight sleep duration between days of interest, age, sex, and socioeconomic status. Movement behaviors were not related to the likelihood of next-day napping, but when children were less sedentary (OR = 0.96; p < 0.001) or more active (OR = 1.01; p = 0.001) in the morning, they were more likely to nap that same day. Movement behaviors were not associated with nap sleep duration or efficiency. Conversely, on days children napped, they were less sedentary (B = -2.09, p < 0.001) and more active (B = 25.8, p < 0.001) the following day. Though napping and movement behaviors had some reciprocal relations, effect sizes in the present study were small. Further studies should examine children with more diverse sleep health and from different childcare settings.

Cost-effectiveness of an Emergency Department-Based Intensive Care Unit.

Importance: Value in health care is quality per unit cost (V = Q/C), and an emergency department-based intensive care unit (ED-ICU) model has been associated with improved quality. To assess the value of this care delivery model, it is essential to determine the incremental direct cost of care. Objective: To determine the association of an ED-ICU with inflation-adjusted change in mean direct cost of care, net revenue, and direct margin per ED patient encounter. Design, Setting, and Participants: This retrospective economic analysis evaluated the cost of care delivery to patients in the ED before and after deployment of the Joyce and Don Massey Family Foundation Emergency Critical Care Center, an ED-ICU, on February 16, 2015, at a large academic medical center in the US with approximately 75 000 adult ED visits per year. The pre-ED-ICU cohort was defined as all documented ED visits by patients 18 years or older with a complete financial record from September 8, 2012, through June 30, 2014 (660 days); the post-ED-ICU cohort, all visits from July 1, 2015, through April 21, 2017 (660 days). Fiscal year 2015 was excluded from analysis to phase in the new care model. Statistical analysis was performed March 1 through December 30, 2021. Exposures: Implementation of an ED-ICU. Main Outcomes and Measures: Inflation-adjusted direct cost of care, net revenue, and direct margin per patient encounter in the ED. Results: A total of 234 884 ED visits during the study period were analyzed, with 115 052 patients (54.7% women) in the pre-ED-ICU cohort and 119 832 patients (54.5% women) in the post-ED-ICU cohort. The post-ED-ICU cohort was older (mean [SD] age, 49.1 [19.9] vs 47.8 [19.6] years; P < .001), required more intensive respiratory support (2.2% vs 1.1%; P < .001) and more vasopressor use (0.5% vs 0.2%; P < .001), and had a higher overall case mix index (mean [SD], 1.7 [2.0] vs 1.5 [1.7]; P < .001). Implementation of the ED-ICU was associated with similar inflation-adjusted total direct cost per ED encounter (pre-ED-ICU, mean [SD], $4875 [$15 175]; post-ED-ICU, $4877 [$17 400]; P = .98). Inflation-adjusted net revenue per encounter increased by 7.0% (95% CI, 3.4%-10.6%; P < .001), and inflation-adjusted direct margin per encounter increased by 46.6% (95% CI, 32.1%-61.2%; P < .001). Conclusions and Relevance: Implementation of an ED-ICU was associated with no significant change in inflation-adjusted total direct cost per ED encounter. Holding delivery costs constant while improving quality demonstrates improved value via the ED-ICU model of care.

Temporal relationships between device-derived sedentary behavior, physical activity, and sleep in early childhood.

STUDY OBJECTIVES: Understanding the ideal composition of a child's day requires a better understanding of the relations between wake behaviors (sedentary behavior [SB], physical activity [PA]) and sleep. Here, we examine between- and within-person temporal associations between daytime wake behaviors and overnight sleep in early childhood, an important age when healthy behaviors are initiated and 24-hour behaviors are largely determined by caregivers. METHODS: Daily, repeated measures of wake behavior and overnight sleep were assessed via wrist-worn actigraphy (mean = 9 days/nights) in 240 children (50.8 ± 9.8 months). Multilevel models with lagged effects were used to examine the temporal associations between wake and overnight sleep measures and adjusted for daily nap duration, age, sex, and socioeconomic status. RESULTS: Between-person associations for sleep outcomes were negative between moderate-to vigorous-intensity PA (MVPA) and total activity for sleep efficiency (SE). Between-person associations for wake outcomes were positive between sleep duration and light PA, and negative between SE and both MVPA and total PA. When children obtained higher SE relative to their individual average, they were more likely to engage in less SB and greater MVPA and total PA the next day. CONCLUSIONS: Generally, days with greater activity or sleep were not associated with greater subsequent sleep or PA. Most subsequent behaviors were not influenced by children achieving higher activity or sleep relative to their individual average levels, although higher SE was beneficially associated with next day wake behaviors. Future analyses with young children should consider within-person associations and could investigate lagged effects beyond one day.

Current costs of dialysis modalities: A comprehensive analysis within the United Kingdom.

BACKGROUND: Previous evidence suggests home-based dialysis to be more cost-effective than unit-based or hospital-based dialysis. However, previous analyses to quantify the costs of different dialysis modalities have used varied perspectives, different methods, and required assumptions due to lack of available data. The National Institute for Health and Care Excellence reports uncertainty about the differences in costs between home-based and unit-based dialysis. This uncertainty limits the ability of policy makers to make recommendations based on cost effectiveness, which also impacts on the ability of budget holders to model the impact of any service redesign and to understand which therapies deliver better value. The aim of our study was to use a combination of top-down and bottom-up costing methods to determine the direct medical costs of different dialysis modalities in one UK nation (Wales) from the perspective of the National Health Service (NHS). METHODS: Detailed hybrid top-down and bottom-up micro-costing methods were applied to estimate the direct medical costs of dialysis modalities across Wales. Micro-costing data was obtained from commissioners of the service and from interviews with renal consultants, nurses, accountants, managers and allied health professionals. Top-down costing information was obtained from the Welsh Renal Clinical Network (who commission renal services across Wales) and the Welsh Ambulance Service Trust. RESULTS: The annual direct cost per patient for home-based modalities was £16,395 for continuous ambulatory peritoneal dialysis (CAPD), £20,295 for automated peritoneal dialysis (APD) and £23,403 for home-based haemodialysis (HHD). The annual cost per patient for unit-based modalities depended on whether or not patients required ambulance transport. Excluding transport, the cost of dialysis was £19,990 for satellite units run in partnership with independent sector providers and £23,737 for hospital units managed and staffed by the NHS. When ambulance transport was included, the respective costs were £28,931 and £32,678, respectively. CONCLUSION: Our study is the most comprehensive analysis of the costs of dialysis undertaken thus far in the United Kingdom and clearly demonstrate that CAPD is less costly than other dialysis modalities. When ambulance transport costs are included, other home therapies (APD and HHD) are also less costly than unit-based dialysis. This detailed analysis of the components that contribute to dialysis costs will help inform future cost-effectiveness studies, inform healthcare policy and drive service redesign.

Determining clinical cutoff scores for the Australian Treatment Outcomes Profile psychological health, physical health and quality of life questions.

INTRODUCTION: The Australian Treatment Outcomes Profile (ATOP) is a brief instrument that measures self-reported substance use, health, and wellbeing in the previous 28 days for people in alcohol and other drug treatment. Previous studies have established the concurrent validity, inter-rater, and test-retest reliability of the tool. The current study sought to identify recommended cutoff scores for ATOP items for psychological health, physical health and quality of life that identify clients reporting clinically significant problems warranting further assessment and/or intervention, compared to cutoffs used by 'gold-standard' measures for these domains. METHODS: Clients attending for treatment for problems with opioid (n = 144) or alcohol use (n = 134) completed the ATOP and comparison standardised questionnaires (Kessler-10, Short Form Survey 12 and the Personal Wellbeing Index) with a researcher. Receiver operating characteristics analysis, along with clinician perspectives, were used to recommend cutoff scores for ATOP items indicative of clinically significant problems. RESULTS: A cutoff score of 5 or less out of 10 was identified as an optimal pragmatic cutoff for ATOP items relating to psychological health, physical health and quality of life items with regards to balancing sensitivity, specificity, and application in a treatment setting. DISCUSSION AND CONCLUSIONS: The recommended clinical cutoffs will support clinicians and treatment services to identify clients who require further assessment and follow up for their psychological health, physical health and quality of life. The current study provides further evidence for the utility of the ATOP for individual clinical review, service planning and research.

Predicting Direct-Specimen SARS-CoV-2 Assay Performance Using Residual Patient Samples.

BACKGROUND: Diagnostic sensitivities of point-of-care SARS-CoV-2 assays depend on specimen type and population-specific viral loads. Evaluation of these assays require "direct" specimens from paired-swab studies rather than more accessible residual specimens in viral transport media (VTM). METHODS: Residual VTM and limit-of-detection studies were conducted on Abbott ID NOW™ COVID-19, Quidel Sofia 2™ SARS Antigen FIA, and DiaSorin Simplexa™ COVID-19 Direct assays, with cycle threshold (CT) adjustments to approximate direct-specimen testing based on gene-target doubling each PCR cycle. Logistic regression was used to model assay performance by specimen CT. These models were applied to CT distributions of symptomatic and asymptomatic populations presenting to emergency services to predict the percentage of specimens that would be detected by each assay. A 96-sample paired-swab study was conducted to confirm model results. RESULTS: When using direct nasopharyngeal samples and fit with either VTM or limit-of-detection data, percent positivities for ID NOW (symptomatic 94.9%/97.4%; asymptomatic 88.4.0%/89.6%) and Simplexa (symptomatic 97.8%/97.2%; asymptomatic 91.1%/90.8%) were predicted to be similar. Likewise, percent positivities for ID NOW with direct nasal specimens (symptomatic 77.8%; asymptomatic 64.5%) and, fit with VTM data, Sofia 2 with direct nasopharyngeal specimens (symptomatic 76.6%, asymptomatic 60.3%) were similar. The paired-swab study comparing direct nasopharyngeal specimens on ID NOW and nasopharyngeal VTM specimens on Simplexa showed 99% concordance. CONCLUSIONS: Assay performance can be modeled as dependent on viral load, fit using laboratory bench study results, and adjusted to account for direct-specimen testing. When using nasopharyngeal specimens, direct testing on Abbott ID NOW and VTM testing on DiaSorin Simplexa have similar performance.

Development of Reaching, Grasping & Manipulation indicators to advance the quality of spinal cord injury rehabilitation: SCI-High Project.

OBJECTIVE: To describe the development of structure, process, and outcome indicators aimed to advance the quality of Reaching, Grasping & Manipulation (RG&M) rehabilitation for Canadians living with spinal cord injury or disease (SCI/D). METHOD: Upper extremity rehabilitation experts developed a framework of indicators for evaluation of RG&M rehabilitation quality. A systematic search of the literature identified potential upper extremity indicators that influence RG&M outcomes. A Driver diagram summarized factors influencing upper extremity outcomes to inform the selection of structure and process indicators. Psychometric properties, clinical utility, and feasibility of potential upper extremity measures were considered when selecting outcome indicators. RESULTS: The selected structure indicator is the number of occupational and physical therapists with specialized certification, education, training and/or work experience in upper extremity therapy related to RG&M at a given SCI/D rehabilitation center. The process indicator is the total hours of upper extremity therapies related to RG&M and the proportion of this time allocated to neurorestorative therapy for each individual with tetraplegia receiving therapy. The outcome indicators are the Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) strength and Spinal Cord Independence Measure III (SCIM III) Self-Care subscores implemented at rehabilitation admission and discharge, and SCIM III Self-Care subscore only at 18 months post-admission. CONCLUSION: The selected indicators align with current practice, will direct the timing of routine assessments, and enhance the volume and quality of RG&M therapy delivered, with the aim to ultimately increase the proportion of individuals with tetraplegia achieving improved upper extremity function by 18 months post-rehabilitation.

Sleep and Coping in Early Childhood During the COVID-19 Pandemic.

Sleep disturbances in early childhood are associated with mood and anxiety disorders. Children also exhibit sleep disruptions, such as nighttime awakenings, nightmares, and difficulties falling asleep, in conjunction with adverse events and stress. Prior studies have examined independently the role of sleep on adaptive processing, as well as the effects of stress on sleep. However, how childhood sleep and children's adaptive behavior (i.e., coping strategies) bidirectionally interact is currently less known. Using a within-subjects design and actigraphy-measured sleep from 16 preschool-aged children (Mage = 56.4 months, SD = 10.8, range: 36-70 months), this study investigated how prior sleep patterns relate to children's coping during a potentially stressful event, the COVID-19 pandemic, and how prior coping skills may influence children's sleep during the pandemic. Children who woke earlier had greater negative expression both before and during the pandemic. During the pandemic, children slept longer and woke later on average compared to before the pandemic. Additionally, for children engaged in at-home learning, sleeping longer was associated with less negative expression. These findings highlight how sleep behaviors and coping strategies are related, and the stability of this relationship under stress.

High-resolution characterization of the structural features and genetic variation of six feline leukocyte antigen class I loci via single molecule, real-time (SMRT) sequencing.

Of the 12 full-length feline leukocyte antigen class I (FLAI) loci, 3 are presumed to be classical: FLAI-E, FLAI-H, and FLAI-K. As diversity is a class Ia hallmark, multi-allelism is an important surrogate supporting a classical designation, in the absence of direct demonstration of T-cell restriction. Conversely, limited polymorphism at an expressed locus suggests regulation of immune effectors with invariant receptors, and non-classical status. FLAI-A, FLAI-J, FLAI-L, and FLAI-O are putative class Ib genes in cats. For both classes, identifying prevalent variants across outbred populations can illuminate specific genotypes to be prioritized for immune studies, as shared alleles direct shared responses. Since variation is concentrated in exons 2 and 3, which encode the antigen-binding domains, partial-length cloning/sequencing can be used for allele discovery, but is laborious and occasionally ambiguous. Here we develop a targeted approach to FLAI genotyping, using the single-molecule real-time (SMRT) platform, which allows full-length (3.4-kb) reads without assembly. Consensus sequences matched full-length Sanger references. Thirty-one new class Ia genes were found in 17 cats. Alleles segregated strongly by loci, and the origins of formerly difficult-to-assign sequences were resolved. Although not targeted, FLAI-L and FLAI-J, and the pseudogene FLAI-F, were also returned. Eighteen class Ib alleles were identified. Diversity was restricted and outside hypervariable regions. Both class Ib genes were transcriptionally active. Novel alternative splicing of FLAI-L was observed. SMRT sequencing of FLAI amplicons is useful for full-length genotyping at feline class Ia loci. High-throughput sequencing could allow highly accurate allele surveys in large cat cohorts.