Generalizability of a Musculoskeletal Therapist Electronic Health Record for Modelling Outcomes to Work-Related Musculoskeletal Disorders.

PURPOSE: Electronic Health Records (EHRs) can contain vast amounts of clinical information that could be reused in modelling outcomes of work-related musculoskeletal disorders (WMSDs). Determining the generalizability of an EHR dataset is an important step in determining the appropriateness of its reuse. The study aims to describe the EHR dataset used by occupational musculoskeletal therapists and determine whether the EHR dataset is generalizable to the Australian workers' population and injury characteristics seen in workers' compensation claims. METHODS: Variables were considered if they were associated with outcomes of WMSDs and variables data were available. Completeness and external validity assessment analysed frequency distributions, percentage of records and confidence intervals. RESULTS: There were 48,434 patient care plans across 10 industries from 2014 to 2021. The EHR collects information related to clinical interventions, health and psychosocial factors, job demands, work accommodations as well as workplace culture, which have all been shown to be valuable variables in determining outcomes to WMSDs. Distributions of age, duration of employment, gender and region of birth were mostly similar to the Australian workforce. Upper limb WMSDs were higher in the EHR compared to workers' compensation claims and diagnoses were similar. CONCLUSION: The study shows the EHR has strong potential to be used for further research into WMSDs as it has a similar population to the Australian workforce, manufacturing industry and workers' compensation claims. It contains many variables that may be relevant in modelling outcomes to WMSDs that are not typically available in existing datasets.

Electronic Health Records for Predicting Outcomes to Work-Related Musculoskeletal Disorders: A Scoping Review.

PURPOSE: Through electronic health records (EHRs), musculoskeletal (MSK) therapists such as chiropractors and physical therapists, as well as occupational medicine physicians could collect data on many variables that can be traditionally challenging to collect in managing work-related musculoskeletal disorders (WMSDs). The review's objectives were to explore the extent of research using EHRs in predicting outcomes of WMSDs by MSK therapists. METHOD: A systematic search was conducted in Medline, PubMed, CINAHL, and Embase. Grey literature was searched. 2156 unique papers were retrieved, of which 38 were included. Three themes were explored, the use of EHRs to predict outcomes to WMSDs, data sources for predicting outcomes to WMSDs, and adoption of standardised information for managing WMSDs. RESULTS: Predicting outcomes of all MSK disorders using EHRs has been researched in 6 studies, with only 3 focusing on MSK therapists and 4 addressing WMSDs. Similar to all secondary data source research, the challenges include data quality, missing data and unstructured data. There is not yet a standardised or minimum set of data that has been defined for MSK therapists to collect when managing WMSD. Further work based on existing frameworks is required to reduce the documentation burden and increase usability. CONCLUSION: The review outlines the limited research on using EHRs to predict outcomes of WMSDs. It highlights the need for EHR design to address data quality issues and develop a standardised data set in occupational healthcare that includes known factors that potentially predict outcomes to help regulators, research efforts, and practitioners make better informed clinical decisions.

Appropriateness of acute-care antibiotic prescriptions for community-acquired infections and surgical antibiotic prophylaxis in England: analysis of 2016 national point prevalence survey data.

BACKGROUND: Estimates of inappropriate prescribing can highlight key target areas for antimicrobial stewardship (AMS) and inform national targets. OBJECTIVES: To (1) define and (2) produce estimates of inappropriate antibiotic prescribing levels within acute hospital trusts in England. METHODS: The 2016 national Healthcare-Associated Infections (HAI), Antimicrobial Use (AMU) and AMS point prevalence survey (PPS) was used to derive estimates of inappropriate prescribing, focusing on the four most reported community-acquired antibiotic indications (CAIs) in the PPS and surgical prophylaxis. Definitions of appropriate antibiotic therapy for each indication were developed through the compilation of national treatment guidelines. A Likert-scale system of appropriateness coding was validated and refined through a two-stage expert review process. RESULTS: Antimicrobial usage prevalence data were collected for 25,741 individual antibiotic prescriptions, representing 17,884 patients and 213 hospitals in England. 30.4% of prescriptions for the four CAIs of interest were estimated to be inappropriate (2054 prescriptions). The highest percentage of inappropriate prescribing occurred in uncomplicated cystitis prescriptions (62.5%), followed by bronchitis (48%). For surgical prophylaxis, 30.8% of prescriptions were inappropriate in terms of dose number, and 21.3% in terms of excess prophylaxis duration. CONCLUSIONS: The 2016 prevalence of inappropriate antibiotic prescribing in hospitals in England was approximated to be 30.4%; this establishes a baseline prevalence and provided indication of where AMS interventions should be prioritized. Our definitions appraised antibiotic choice, treatment duration and dose number (surgical prophylaxis only); however, they did not consider other aspects of appropriateness, such as combination therapy - this is an important area for future work.

Intermittent point prevalence surveys on healthcare-associated infections, 2011 and 2016, in England: what are the surveillance and intervention priorities?

BACKGROUND: Point prevalence surveys are an important surveillance method for determining the burden of healthcare-associated infections (HCAIs). AIM: To outline the key results of two point prevalence surveys in England (2011 and 2016). METHODS: All National Health Service and independent sector hospitals in England were eligible to participate. Data were collected between September and November in both 2011 and 2016 based on the protocol and codebook devised by the European Centre for Disease Prevention and Control. Analysis was performed using Stata Version 13 and SAS Version 9.3. A mixed-effects model was applied, which allowed estimation of organization-specific means and accounted for the heterogeneity in the responses from different organizations. FINDINGS: A total of 100,755 case records were included (52,433 in 2011 and 48,312 in 2016). The estimated prevalence of HCAIs was slightly higher in 2016 [6.89%, 95% confidence interval (CI) 6.21-7.57%] than in 2011 (6.41%, 95% CI 5.75-7.06%). In both surveys, the prevalence of HCAIs was highest in adult intensive care units (23.1% in 2011, 21.2% in 2016), and pneumonia/lower respiratory tract infections was the most common cause of HCAIs (22.7% in 2011 vs 29.2% in 2016). Inpatients in acute hospitals were older and had higher risk of dying in 2016 compared with 2011; however, the proportion of inpatients with HCAIs or on antibiotics did not differ significantly. CONCLUSION: The burden of HCAIs in English hospitals increased slightly between 2011 and 2016. However, the proportion of inpatients with HCAIs or on antibiotics did not differ significantly.

British Society for Immunology and United Kingdom Primary Immunodeficiency Network (UKPIN) consensus guideline for the management of immunoglobulin replacement therapy.

Currently, there is no guideline to support the use of immunoglobulin replacement therapy (IgRT) in primary and secondary immunodeficiency disorders in UK. The UK Primary Immunodeficiency Network (UK-PIN) and the British Society of Immunology (BSI) joined forces to address this need. Given the paucity of evidence, a modified Delphi approach was used covering statements for the initiation, monitoring, discontinuation of IgRT as well as home therapy programme. A group of six consultant immunologists and three nurse specialists created the statements, reviewed responses and feedback and agreed on final recommendations. This guideline includes 22 statements for initiation, 22 statements for monitoring, 11 statement for home therapy, and 19 statements for discontinuation of IgRT. Further areas of research are proposed to improve future delivery of care.

The Mechanical Response and Tolerance of the Anteriorly-Tilted Human Pelvis Under Vertical Loading.

Military vehicle underbody blast (UBB) is the cause of many serious injuries in theatre today; however, the effects of these chaotic events on the human body are not well understood. The purpose of this research was to replicate UBB loading conditions on the human pelvis and investigate the resulting response in a controlled laboratory setting. In addition to better understanding the response of the human pelvis to high rate vertical loading, this test series also aimed to identify high rate injury thresholds. Twenty-seven post mortem human surrogate (PMHS) component pelvis tests were completed using the University of Virginia's (UVa) simulated blast rig under a range of loading conditions and postures. Of those tests, 17 were in the anteriorly-tilted posture and used to construct the human injury probability curve. Average seat pan (rigid) accelerations for this subset of tests ranged from 300 to 2400 g over 2 to 3 ms of positive phase duration. Post-test computed tomography (CT) scans and necropsies were performed to determine injuries and revealed a frequent occurrence of anterior and posterior injuries, resulting in unstable pelvis ring fractures. The resulting Human Injury Probability Curve (HIPC) yielded mean forces of 5529, 8516, and 12431 N as measured by mass compensated seat platen loadcells applied through the rigid seat to the bilateral ischium are associated with a 10, 25, and 50% risk for unstable pelvic ring sacrum fractures in an anteriorly-tilted pelvis (28° from vertical), respectively.

Second international guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications. The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved. The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.

A meta-synthesis of competency standards suggest allied health are not preparing for a digital health future.

OBJECTIVE: This study reviewed the competency and threshold standards for allied health professionals to identify the inclusion of digital health competencies. MATERIALS AND METHODS: A nine-stage, sequential meta-synthesis of professional standards was undertaken. Statements relevant to digital health were extracted, categorised by discipline, and coded to the level in the standards, skills or knowledge and level of learning. RESULTS: Eighteen standards were analysed. Of these, fourteen standards contained a total of thirty-five statements related to digital health in the themes of data governance and technologies, but not data translation. Only four disciplines included more than two statements related to digital health. DISCUSSION: The study highlighted four key gaps in the Standards. Statements in competency and threshold standards for allied health professionals lack reference to digital health, with predominantly information management statements. The statements are ambiguously worded, and could be interpreted to only refer to paper records management, and when there is a reference to digital health, it is more likely to be a skill as opposed to knowledge, typically at the indicator or cue level, and largely a lower level of learning (Bloom's). The lack of digital health in standards may result in limited instruction in already full tertiary education curriculum. CONCLUSION: Digital health represents a major gap in competency statements for all allied health disciplines, signifying the need for a national approach to developing quality and specific digital health competencies, to support allied health graduates being prepared to work in the digital health age.

Observation of persistent species temperature separation in inertial confinement fusion mixtures.

The injection and mixing of contaminant mass into the fuel in inertial confinement fusion (ICF) implosions is a primary factor preventing ignition. ICF experiments have recently achieved an alpha-heating regime, in which fusion self-heating is the dominant source of yield, by reducing the susceptibility of implosions to instabilities that inject this mass. We report the results of unique separated reactants implosion experiments studying pre-mixed contaminant as well as detailed high-resolution three-dimensional simulations that are in good agreement with experiments. At conditions relevant to mixing regions in high-yield implosions, we observe persistent chunks of contaminant that do not achieve thermal equilibrium with the fuel throughout the burn phase. The assumption of thermal equilibrium is made in nearly all computational ICF modeling and methods used to infer levels of contaminant from experiments. We estimate that these methods may underestimate the amount of contaminant by a factor of two or more.

Cross-sectional study of the prevalence, causes and management of hospital-onset diarrhoea.

BACKGROUND: The National Health Service in England advises hospitals collect data on hospital-onset diarrhoea (HOD). Contemporaneous data on HOD are lacking. AIM: To investigate prevalence, aetiology and management of HOD on medical, surgical and elderly-care wards. METHODS: A cross-sectional study in a volunteer sample of UK hospitals, which collected data on one winter and one summer day in 2016. Patients admitted ≥72 h were screened for HOD (definition: ≥2 episodes of Bristol Stool Type 5-7 the day before the study, with diarrhoea onset >48 h after admission). Data on HOD aetiology and management were collected prospectively. FINDINGS: Data were collected on 141 wards in 32 hospitals (16 acute, 16 teaching). Point-prevalence of HOD was 4.5% (230/5142 patients; 95% confidence interval (CI) 3.9-5.0%). Teaching hospital HOD prevalence (5.9%, 95% CI 5.1-6.9%) was twice that of acute hospitals (2.8%, 95% CI 2.1-3.5%; odds ratio 2.2, 95% CI 1.7-3.0). At least one potential cause was identified in 222/230 patients (97%): 107 (47%) had a relevant underlying condition, 125 (54%) were taking antimicrobials, and 195 (85%) other medication known to cause diarrhoea. Nine of 75 tested patients were Clostridium difficile toxin positive (4%). Eighty (35%) patients had a documented medical assessment of diarrhoea. Documentation of HOD in medical notes correlated with testing for C. difficile (78% of those tested vs 38% not tested, P<0.001). One-hundred and forty-four (63%) patients were not isolated following diarrhoea onset. CONCLUSION: HOD is a prevalent symptom affecting thousands of patients across the UK health system each day. Most patients had multiple potential causes of HOD, mainly iatrogenic, but only a third had medical assessment. Most were not tested for C. difficile and were not isolated.

Borrelia burgdorferi Transcriptome Analysis by RNA-Sequencing.

Next-Generation Sequencing (NGS) has revolutionized transcriptomics studies in the last decade. Transcriptome analysis experiments using NGS-based RNA-sequencing have several advantages over DNA microarray analysis. Novel unannotated transcripts and transcriptional start sites can be identified. Differential gene expression can be determined on novel and annotated transcripts simultaneously, whereas DNA microarray analysis can only quantify changes of known genes. In the protocol below we describe an Illumina compatible ligation-based method for generating stranded cDNA libraries for total RNA and small RNA transcriptomes in Borrelia burgdorferi.

Health Information Management: Changing with Time.

Objective: With the evolution of patient medical records from paper to electronic media and the changes to the way data is sourced, used, and managed, there is an opportunity for health information management (HIM) to learn and facilitate the increasing expanse of available patient data. Methods: This paper discusses the emerging trends and lessons learnt in relation with the following four areas: 1) data and information governance, 2) terminology standards certification, 3) International Classification of Diseases, 11th edition (ICD-11), and 4) data analytics and HIM. Results: The governance of patient data and information increasingly requires the HIM profession to incorporate the roles of data scientists and data stewards into its portfolio to ensure data analytics and digital transformation is appropriately managed. Not only are terminology standards required to facilitate the structure and primary use of this data, developments in Canada in relation with the standards, role descriptions, framework and curricula in the form of certification provide one prime example of ensuring the quality of the secondary use of patient data. The impending introduction of ICD-11 brings with it the need for the HIM profession to manage the transition between ICD versions and country modifications incorporating changes to standards and tools, and the availability and type of patient data available for secondary use. Conclusions: In summary, the health information management profession now requires abilities in leadership, data, and informatics in addition to health information science and coding skills to facilitate the expanding secondary use of patient data.

School breakfast and body mass index: a longitudinal observational study of middle school students.

OBJECTIVES: The objectives are to identify breakfast location patterns (frequency and place of breakfast consumption) and explore the association between breakfast patterns and weight status over time among preadolescents. METHODS: Surveys and physical measurements were completed among students from 12 randomly selected schools in a medium-sized urban school district. All students were followed from fifth (Fall, 2011) to seventh grade (Fall, 2013). Latent transition analysis and longitudinal analyses were used in the study. RESULTS: Six distinct breakfast location patterns emerged at baseline (1) frequent skippers; (2) inconsistent school eaters; (3) inconsistent home eaters; (4) regular home eaters; (5) regular school eaters and (6) double breakfast eaters. Results from the longitudinal analyses revealed that there was an increased odds of overweight/obesity among frequent skippers compared with double breakfast eaters after adjusting for school, year and students' race/ethnicity (AOR: 2.66, 95% CI: 1.67, 4.24). Weight changes from year to year were similar between double breakfast eaters and other students. CONCLUSIONS: Concerns that a second breakfast at school increases risk of excessive weight gain are unsupported. Students who regularly consumed breakfasts at school, including double breakfast eaters, were more likely to exhibit a healthy weight trajectory. Additional research is needed to understand the impact of universal school breakfast on students' overall diets.

Anticholinergic medicines in an older primary care population: a cross-sectional analysis of medicines' levels of anticholinergic activity and clinical indications.

WHAT IS KNOWN AND OBJECTIVES: Adverse clinical outcomes have been associated with cumulative anticholinergic burden (to which low-potency as well as high-potency anticholinergic medicines contribute). The clinical indications for which anticholinergic medicines are prescribed (and thus the 'phenotype' of patients with anticholinergic burden) have not been established. We sought to establish the overall prevalence of prescribing of anticholinergic medicines, the prevalence of prescribing of low-, medium- and high-potency anticholinergic medicines, and the clinical indications for which the medicines were prescribed in an older primary care population. METHODS: This was a cross-sectional analysis of a cohort study of Australian early-career general practitioners' (GPs') clinical consultations - the Registrar Clinical Encounters in Training (ReCEnT) study. In ReCEnT, GPs collect detailed data (including medicines prescribed and their clinical indication) for 60 consecutive patients, on up to three occasions 6 months apart. Anticholinergic medicines were categorized as levels 1 (low-potency) to 3 (high-potency) using the Anticholinergic Drug Scale (ADS). RESULTS: During 2010-2014, 879 early-career GPs (across five of Australia's six states) conducted 20 555 consultations with patients aged 65 years or older, representing 35 506 problems/diagnoses. Anticholinergic medicines were prescribed in 10·4% [95% CIs 9·5-10·5] of consultations. Of the total anticholinergic load of prescribed medicines ('community anticholinergic load') 72·7% [95% CIs 71·0-74·3] was contributed by Level 1 medicines, 0·8% [95% CIs 0·5-1·3] by Level 2 medicines and 26·5% [95% CIs 24·8-28·1] by Level 3 medicines. Cardiac (40·0%), Musculoskeletal (16·9%) and Respiratory (10·6%) were the most common indications associated with Level 1 anticholinergic prescription. For Level 2 and 3 medicines (combined data), Psychological (16·1%), Neurological (16·1%), Musculoskeletal (15·7%) and Urological (11·1%) indications were most common. WHAT IS NEW AND CONCLUSION: Anticholinergic medicines are frequently prescribed in Australian general practice, and the majority of the 'community' anticholinergic burden is contributed by 'low'-anticholinergic potency medicines whose anticholinergic effects may be largely 'invisible' to prescribing GPs. Furthermore, the clinical 'phenotype' of the patient with high anticholinergic burden may be very different to common stereotypes (patients with urological, psychological or neurological problems), potentially making recognition of risk of anticholinergic adverse effects additionally problematic for GPs.

Emergency readmissions to paediatric surgery and urology: The impact of inappropriate coding.

Introduction In England, emergency readmissions within 30 days of hospital discharge after an elective admission are not reimbursed if they do not meet Payment by Results (PbR) exclusion criteria. However, coding errors could inappropriately penalise hospitals. We aimed to assess the accuracy of coding for emergency readmissions. Methods Emergency readmissions attributed to paediatric surgery and urology between September 2012 and August 2014 to our tertiary referral centre were retrospectively reviewed. Payment by Results (PbR) coding data were obtained from the hospital's Family Health Directorate. Clinical details were obtained from contemporaneous records. All readmissions were categorised as appropriately coded (postoperative or nonoperative) or inappropriately coded (planned surgical readmission, unrelated surgical admission, unrelated medical admission or coding error). Results Over the 24-month period, 241 patients were coded as 30-day readmissions, with 143 (59%) meeting the PbR exclusion criteria. Of the remaining 98 (41%) patients, 24 (25%) were inappropriately coded as emergency readmissions. These readmissions resulted in 352 extra bed days, of which 117 (33%) were attributable to inappropriately coded cases. Conclusions One-quarter of non-excluded emergency readmissions were inappropriately coded, accounting for one-third of additional bed days. As a stay on a paediatric ward costs up to £500 a day, the potential cost to our institution due to inappropriate readmission coding was over £50,000. Diagnoses and the reason for admission for each care episode should be accurately documented and coded, and readmission data should be reviewed at a senior clinician level.

Quantifying the Burden of Hospital-Acquired Bloodstream Infection in Children in England by Estimating Excess Length of Hospital Stay and Mortality Using a Multistate Analysis of Linked, Routinely Collected Data.

BACKGROUND: Hospital-acquired bloodstream infection (HA-BSI) is associated with substantial morbidity, mortality, and healthcare costs in all patient populations. Young children have been shown to have a high rate of healthcare-associated infections compared with the adult population. We aimed to quantify the excess mortality and length of stay in pediatric patients from HA-BSI. METHODS: We analyzed data collected retrospectively from a probabilistically linked national database of pediatric (aged 1 month-18 years) in-patients with a microbiologically confirmed HA-BSI in England between January and March 2009. A time-dependent Cox regression model was fit to determine the presence of any effect. Furthermore, a multistate model, adjusted for the time to onset of HA-BSI, was used to compare outcomes in patients with HA-BSI to those without HA-BSI. We further adjusted for patients' characteristics as recorded in hospital admission data. RESULTS: The dataset comprised 333 605 patients, with 214 cases of HA-BSI. After adjustment for time to HA-BSI and comorbidities, the hazard for discharge (dead or alive) from hospital for patients with HA-BSI was 0.9 times (95% confidence interval [CI], .8-1.1) that of noninfected patients. Excess length of stay associated with all-cause HA-BSI was 1.6 days (95% CI, .2-3.0), although this duration varied by pathogen. Patients with HA-BSI had a 3.6 (95% CI, 1.3-10.4) times higher hazard for in-hospital death than noninfected patients. CONCLUSIONS: Hospital-acquired bloodstream infection increased the length of stay and mortality of pediatric inpatients. The results of this study provide an evidence base to judge the health and economic impact of programs to prevent and control HA-BSI in children.

Timing of positive blood samples does not differentiate pathogens causing healthcare-associated from community-acquired bloodstream infections in children in England: a linked retrospective cohort study.

Paediatricians recognize that using the time-dependent community-acquired vs. hospital-acquired bloodstream infection (BSI) dichotomy to guide empirical treatment no longer distinguishes between causative pathogens due to the emergence of healthcare-associated BSIs. However, paediatric epidemiological evidence of the aetiology of BSIs in relation to hospital admission in England is lacking. For 12 common BSI-causing pathogens in England, timing of laboratory reports of positive paediatric (3 months to 5 years) bacterial blood isolates were linked to in-patient hospital data and plotted in relation to hospital admission. The majority (88·6%) of linked pathogens were isolated <2 days after hospital admission, including pathogens widely regarded as hospital acquired: Enterococcus spp. (67·2%) and Klebsiella spp. (88·9%). Neisseria meningitidis, Streptococcus pneumoniae, group A streptococcus and Salmonella spp. were unlikely to cause hospital-acquired BSI. Pathogens commonly associated with hospital-acquired BSI are being isolated <2 days after hospital admission alongside pathogens commonly associated with community-acquired BSI. We confirm that timing of blood samples alone does not differentiate between bacterial pathogens. Additional factors including clinical patient characteristics and healthcare contact should be considered to help predict the causative pathogen and guide empirical antibiotic therapy.

The United Kingdom Primary Immune Deficiency (UKPID) Registry: report of the first 4 years' activity 2008-2012.

This report summarizes the establishment of the first national online registry of primary immune deficency in the United Kingdom, the United Kingdom Primary Immunodeficiency (UKPID Registry). This UKPID Registry is based on the European Society for Immune Deficiency (ESID) registry platform, hosted on servers at the Royal Free site of University College, London. It is accessible to users through the website of the United Kingdom Primary Immunodeficiency Network (www.ukpin.org.uk). Twenty-seven centres in the United Kingdom are actively contributing data, with an additional nine centres completing their ethical and governance approvals to participate. This indicates that 36 of 38 (95%) of recognized centres in the United Kingdom have engaged with this project. To date, 2229 patients have been enrolled, with a notable increasing rate of recruitment in the past 12 months. Data are presented on the range of diagnoses recorded, estimated minimum disease prevalence, geographical distribution of patients across the United Kingdom, age at presentation, diagnostic delay, treatment modalities used and evidence of their monitoring and effectiveness.

Intermittent hypoxia-induced increases in reactive oxygen species activate NFATc3 increasing endothelin-1 vasoconstrictor reactivity.

Sleep apnea (SA), defined as intermittent respiratory arrest during sleep, is associated with increased incidence of hypertension, peripheral vascular disease, stroke, and sudden cardiac death. We have shown that intermittent hypoxia with CO2 supplementation (IH), a model for SA, increases blood pressure and circulating ET-1 levels, upregulates lung pre-pro ET-1 mRNA, increases vasoconstrictor reactivity to ET-1 in rat small mesenteric arteries (MA) and increases vascular reactive oxygen species (ROS). NFAT activity is increased in the aorta (AO) and MA of mice exposed to IH in an ET-1-dependent manner, and the genetic ablation of the isoform NFATc3 prevents IH-induced hypertension. We hypothesized that IH causes an increase in arterial ROS generation, which activates NFATc3 to increase vasoconstrictor reactivity to ET-1. In support of our hypothesis, we found that IH increases ROS in AO and MA. In vivo administration of the SOD mimetic tempol during IH exposure prevents IH-induced increases in NFAT activity in mouse MA and AO. We found that IH causes an NFATc3-dependent increase in vasoconstrictor reactivity to ET-1, accompanied by an increase in vessel wall [Ca²âº]. Our results indicate that IH exposure causes an increase in arterial ROS to activate NFATc3, which then increases vasoconstrictor reactivity and Ca²âº response to ET-1. These studies highlight a novel regulatory pathway, and demonstrate the potential clinical relevance of NFAT inhibition to prevent hypertension in SA patients.

A framework to aid adoption of automated rehabilitation devices into clinical practice: synthesising and Interpreting Language for Clinical Kinematics (SILCK).

The Synthesising and Interpreting Language for Clinical Kinematics (SILCK) is an informatic framework for developing software to control automated rehabilitation devices. It aids adoption of devices into rehabilitation practice, by bridging the gap between clinical practice and internal device operation. SILCK defines data entities and processes for capturing clinical observations of patients and their rehabilitation goals in formats which can be used to direct the tailoring of device parameters to the individual patient's needs.