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Multimorbidity in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Results From a Longitudinal, Multicenter Data Linkage Study.
No full textOBJECTIVE
Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is considered a chronic, relapsing condition. To date, no studies have investigated multimorbidity in AAV nationally. This study was undertaken to characterize temporal trends in multimorbidity and report excess health care expenditures associated with multimorbidities in a national AAV cohort from Scotland.
METHODS
Eligible patients with AAV were diagnosed between 1997 and 2017. Each patient was matched with up to 5 general population controls. Linked morbidity and health care expenditure data were retrieved from a Scottish national hospitalization repository and from published national cost data. Multimorbidity was defined as the development of ≥2 disorders. Prespecified morbidities, individually and together, were analyzed for risks and associations over time using modified Poisson regression, discrete interval analysis, and chi-square test for trend. The relationship between multimorbidities and health care expenditure was investigated using multivariate linear regression.
RESULTS
In total, 543 patients with AAV (median age 58.7 years [range 48.9-68.0 years]; 53.6% male) and 2,672 general population controls (median age 58.7 years [range 48.9-68.0 years]; 53.7% male) were matched and followed up for a median of 5.1 years. AAV patients were more likely to develop individual morbidities at all time points, but especially <2 years after diagnosis. The highest proportional risk observed was for osteoporosis (adjusted incidence rate ratio 8.0, 95% confidence interval [95% CI] 4.5-14.2). After 1 year, 23.0% of AAV patients and 9.3% of controls had developed multimorbidity (P < 0.0001). After 10 years, 37.0% of AAV patients and 17.3% of controls were reported to have multimorbidity (P < 0.0001). Multimorbidity was associated with disproportionate increases in health care expenditures in AAV patients. Health care expenditure was highest for AAV patients with ≥3 morbidities (3.89-fold increase in costs, 95% CI 2.83-5.31; P < 0.001 versus no morbidities).
CONCLUSION
These findings emphasize the importance of holistic care in patients with AAV, and may identify a potentially critical opportunity to consider early screening
An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.
No full textBACKGROUNDS & AIMS
Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening.
METHODS
We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts.
RESULTS
We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57 genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (T)1 and T17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders.
CONCLUSIONS
This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders.
LAY SUMMARY
Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these 'candidate genes' to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC
Relationship Between Clinical Features and the Arc and Length of Dehiscence in SCDS: A Single Center Review of 42 Cases.
No full textINTRODUCTION
Superior canal dehiscence syndrome (SCDS) is a rare disorder characterized by an array of audiovestibular symptoms due to a dehiscence of bone overlying the superior semicircular canal (SSC). In the presence of debilitating symptoms, surgical management, to plug or resurface the SCC is performed. Although computed tomography (CT) may overestimate the size or presence of a dehiscence due to a partial volume effect, it remains an invaluable diagnostic tool.
OBJECTIVES
To assess for correlation between the arc and length of dehiscence and clinical symptomology.
METHOD
A single-center, single-operator retrospective analysis of 42 patients who underwent trans mastoid plugging of SCC with confirmed radiological dehiscence of their SSC between January 2008 and July 2019 was undertaken. Patients were assessed based on seven predefined clinical symptoms. Length and arc of dehiscence's were evaluated by means of high resolution (0.5 mm) CT (HRCT), using multiplanar reconstruction (MPR). Receiver operating characteristics (ROC), and more specifically the area under the ROC curve (AUROC) were used to assess for statistical significance.
RESULTS
Our results demonstrate overall very little correlation between the arc and size of the dehiscence and symptoms. The only statistically significant correlation we found was between length of dehiscence and the presence of aural fullness.
CONCLUSION
SCDS is a debilitating condition with an array of symptoms on presentation. While dehiscence length demonstrated a correlation with aural fullness, no other symptomology in patients with radiologically evident SCDS demonstrated a statistically significant correlation either against the length or arc of dehiscence
Management of Seymour Fractures in Children and Adolescents: A Systematic Review and Meta-Analysis.
No full textPURPOSE
Seymour fractures are injuries with a potentially high risk of infection and osteomyelitis. The optimal management of this pediatric open fracture is unknown. We performed a systematic review and meta-analysis to summarize the best evidence for these fractures and determine their optional management based on primary clinical studies.
METHODS
A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review and meta-analysis was performed. A comprehensive search strategy was applied to the MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and gray literature databases (from May 1966 to April 15, 2020). Studies describing patients under the age of 18 years with Seymour fractures were included. Treatment was grouped based on debridement and antibiotic status as well as the timing of these interventions. The primary outcome was infection. The secondary outcomes included malunion, physeal disturbance, and nail dystrophy.
RESULTS
The searches helped identify 56 records, of which 10 nonrandomized studies met our inclusion criteria, comprising 352 patients and 355 fractures. Early (<48 hours) debridement was associated with significantly less risk of infection (risk ratio [RR] = 0.28 [95% CI, 0.12-0.64]) and malunion (RR = 0.25 [95% CI, 0.07-0.99]). Prophylactic (<24 hours) antibiotics significantly reduced the risk of infection (RR = 0.21 [95% CI, 0.10-0.43]). In addition, prophylactic antibiotics and debridement were associated with a 70% reduction in the risk of infection (RR = 0.30 [95% CI, 0.11-0.83]). Over one-third of patients with delayed presentation (median 8.5 days) were infected at presentation.
CONCLUSIONS
The high-risk nature of Seymour fractures may be mitigated by prompt recognition and early, basic interventions, which can usually be performed in any setting.
TYPE OF STUDY/LEVEL OF EVIDENCE
Therapeutic IV
Long term outcomes of participants in the PARAMEDIC2 randomised trial of adrenaline in out-of-hospital cardiac arrest.
No full textAIMS
We recently reported early outcomes in patients enrolled in a randomised trial of adrenaline in out-of-hospital cardiac arrest: the PARAMEDIC2 (Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest) trial. The purpose of the present paper is to report long-term survival, quality of life, functional and cognitive outcomes at 3, 6 and 12-months.
METHODS
PARAMEDIC2 was a pragmatic, individually randomised, double blind, controlled trial with an economic evaluation. Patients were randomised to either adrenaline or placebo. This paper reports results on the modified Rankin Scale scores at 6-months, survival at 6 and 12-months, as well as other cognitive, functional and quality of life outcomes collected at 3 and 6 months (Two Simple Questions, the Mini Mental State Examination, the Informant Questionnaire on Cognitive Decline Evaluation for Cardiac Arrest, Hospital Anxiety and Depression Scale, the Post Traumatic Stress Disorder Checklist - Civilian Version, Short-Form 12-item Health Survey and the EuroQoL EQ-5D-5L).
RESULTS
8,014 patients were randomised with confirmed trial drug administration. At 6-months, 78 (2.0%) of the patients in the adrenaline group and 58 (1.5%) of patients in the placebo group had a favourable neurological outcome (adjusted odds ratio 1.35 [95% confidence interval: 0.93, 1.97]). 117 (2.9%) patients were alive at 6-months in the adrenaline group compared with 86 (2.2%) in the placebo group (1.43 [1.05, 1.96], reducing to 107 (2.7%) and 80 (2.0%) respectively at 12-months (1.38 [1.00, 1.92]). Measures of 3 and 6-month cognitive, functional and quality of life outcomes were reduced, but there was no strong evidence of differences between groups.
CONCLUSION
Adrenaline improved survival through to 12-months follow-up. The study did not find evidence of improvements in favourable neurological outcomes. (ISCRTN 73485024)
A fast, accurate, and generalisable heuristic-based negation detection algorithm for clinical text.
No full textNegation detection is an important task in biomedical text mining. Particularly in clinical settings, it is of critical importance to determine whether findings mentioned in text are present or absent. Rule-based negation detection algorithms are a common approach to the task, and more recent investigations have resulted in the development of rule-based systems utilising the rich grammatical information afforded by typed dependency graphs. However, interacting with these complex representations inevitably necessitates complex rules, which are time-consuming to develop and do not generalise well. We hypothesise that a heuristic approach to determining negation via dependency graphs could offer a powerful alternative. We describe and implement an algorithm for negation detection based on grammatical distance from a negatory construct in a typed dependency graph. To evaluate the algorithm, we develop two testing corpora comprised of sentences of clinical text extracted from the MIMIC-III database and documents related to hypertrophic cardiomyopathy patients routinely collected at University Hospitals Birmingham NHS trust. Gold-standard validation datasets were built by a combination of human annotation and examination of algorithm error. Finally, we compare the performance of our approach with four other rule-based algorithms on both gold-standard corpora. The presented algorithm exhibits the best performance by f-measure over the MIMIC-III dataset, and a similar performance to the syntactic negation detection systems over the HCM dataset. It is also the fastest of the dependency-based negation systems explored in this study. Our results show that while a single heuristic approach to dependency-based negation detection is ignorant to certain advanced cases, it nevertheless forms a powerful and stable method, requiring minimal training and adaptation between datasets. As such, it could present a drop-in replacement or augmentation for many-rule negation approaches in clinical text-mining pipelines, particularly for cases where adaptation and rule development is not required or possible
COVID-19 in haematology patients: a multicentre West Midlands clinical outcomes analysis on behalf of the West Midlands Research Consortium.
No full textRehabilitation Exercise and psycholoGical support After covid-19 InfectioN' (REGAIN): a structured summary of a study protocol for a randomised controlled trial.
No full textOBJECTIVES
The primary objective is to determine which of two interventions: 1) an eight week, online, home-based, supervised, group rehabilitation programme (REGAIN); or 2) a single online session of advice (best-practice usual care); is the most clinically and cost-effective treatment for people with ongoing COVID-19 sequelae more than three months after hospital discharge.
TRIAL DESIGN
Multi-centre, 2-arm (1:1 ratio) parallel group, randomised controlled trial with embedded process evaluation and health economic evaluation.
PARTICIPANTS
Adults with ongoing COVID-19 sequelae more than three months after hospital discharge Inclusion criteria: 1) Adults ≥18 years; 2) ≥ 3 months after any hospital discharge related to COVID-19 infection, regardless of need for critical care or ventilatory support; 3) substantial (as defined by the participant) COVID-19 related physical and/or mental health problems; 4) access to, and able/supported to use email and internet audio/video; 4) able to provide informed consent; 5) able to understand spoken and written English, Bengali, Gujarati, Urdu, Punjabi or Mandarin, themselves or supported by family/friends.
EXCLUSION CRITERIA
1) exercise contraindicated; 2) severe mental health problems preventing engagement; 3) previous randomisation in the present study; 4) already engaged in, or planning to engage in an alternative NHS rehabilitation programme in the next 12 weeks; 5) a member of the same household previously randomised in the present study.
INTERVENTION AND COMPARATOR
Intervention 1: The Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) programme: an eight week, online, home-based, supervised, group rehabilitation programme. Intervention 2: A thirty-minute, on-line, one-to-one consultation with a REGAIN practitioner (best-practice usual care).
MAIN OUTCOMES
The primary outcome is health-related quality of life (HRQoL) - PROMIS® 29+2 Profile v2.1 (PROPr) - measured at three months post-randomisation. Secondary outcomes include dyspnoea, cognitive function, health utility, physical activity participation, post-traumatic stress disorder (PTSD) symptom severity, depressive and anxiety symptoms, work status, health and social care resource use, death - measured at three, six and 12 months post-randomisation.
RANDOMISATION
Participants will be randomised to best practice usual care or the REGAIN programme on a 1:1.03 basis using a computer-generated randomisation sequence, performed by minimisation and stratified by age, level of hospital care, and case level mental health symptomatology. Once consent and baseline questionnaires have been completed by the participant online at home, randomisation will be performed automatically by a bespoke web-based system.
BLINDING (MASKING)
To ensure allocation concealment from both participant and REGAIN practitioner at baseline, randomisation will be performed only after the baseline questionnaires have been completed online at home by the participant. After randomisation has been performed, participants and REGAIN practitioners cannot be blind to group allocation. Follow-up outcome assessments will be completed by participants online at home.
NUMBERS TO BE RANDOMISED (SAMPLE SIZE)
A total of 535 participants will be randomised: 263 to the best-practice usual care arm, and 272 participants to the REGAIN programme arm.
TRIAL STATUS
Current protocol: Version 3.0 (27th October 2020) Recruitment will begin in December 2020 and is anticipated to complete by September 2021.
TRIAL REGISTRATION
ISRCTN:11466448 , 23rd November 2020 FULL PROTOCOL: The full protocol Version 3.0 (27th October 2020) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interests of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines
Incidents in Molecular Pathology: Frequency and Causes During Routine Testing.
No full textCONTEXT.—
Errors in laboratory medicine could compromise patient safety. Good laboratory practice includes identifying and managing nonconformities in the total test process. Varying error percentages have been described in other fields but are lacking for molecular oncology.
OBJECTIVES.—
To gain insight into incident causes and frequency in the total test process from 8 European institutes routinely performing biomarker tests in non-small cell lung cancer and colorectal cancer.
DESIGN.—
All incidents documented in 2018 were collected from all hospital services for pre-preanalytical entries before the biomarker test, as well as specific incidents for biomarker tests.
RESULTS.—
There were 5185 incidents collected, of which 4363 (84.1%) occurred in the pre-preanalytical phase (all hospital services), 2796 of 4363 (64.1%) related to missing or incorrect request form information. From the other 822 specific incidents, 166 (20.2%) were recorded in the preanalytical phase, 275 (33.5%) in the analytical phase, and 194 (23.6%) in the postanalytical phase, mainly due to incorrect report content. Only 47 of 822 (5.7%) incidents were recorded in the post-postanalytical phase, and 123 (15.0%) in the complete total test process. For 17 of 822 (2.1%) incidents the time point was unknown. Pre-preanalytical incidents were resolved sooner than incidents on the complete process (mean 6 versus 60 days). For 1215 of 5168 (23.5%) incidents with known causes a specific action was undertaken besides documenting them, not limited to accredited institutes.
CONCLUSIONS.—
There was a large variety in the number and extent of documented incidents. Correct and complete information on the request forms and final reports are highly error prone and require additional focus
Mechanical circulatory support in paediatric population.
No full textExtra-corporeal membrane oxygenation is a life-saving modality to support the cardiac and/or pulmonary system as a form of life support in resuscitation, post-cardiotomy, as a bridge to cardiac transplantation and in respiratory failure. Its use in the paediatric and neonatal population has proven incredibly useful. However, extra-corporeal membrane oxygenation is also associated with a greater rate of mortality and complications, particularly in those with co-morbidities. As a result, interventions such as ventricular assist devices have been trialled in these patients. In this review, we provide a comprehensive analysis of the current literature on extra-corporeal membrane oxygenation for cardiac support in the paediatric and neonatal population. We evaluate its effectiveness in comparison to other forms of mechanical circulatory support and focus on areas for future development