Publications by authors named "David J Wright"

194 Publications

Combined plate and nail fixation of bicondylar tibial plateau fractures.

Injury 2021 Jul 9. Epub 2021 Jul 9.

Associate Professor, University of California, Irvine, 101 The City Drive South, Building 29A, Pavilion III - 2nd Floor, Irvine, Orange, CA, 92868, USA. Electronic address:

Introduction: Bicondylar tibial plateau fractures with meta-diaphyseal comminution commonly have a compromised soft tissue envelope. Combined plate-nail fixation is an emerging technique that utilizes a limited anterolateral approach for plate application and percutaneous incisions for placement of an intramedullary nail. This technique alleviates the need for a separate medial approach to the proximal tibia. We report a series of patients treated with this approach and outline the steps for implementation.

Methods: We performed a retrospective review of 18 consecutive patients treated with combination lateral locked plating and intramedullary nailing at a single academic institution from 2016 to 2019. Of these, 16 patients met inclusion criteria and were included in this study. All patients had AO/OTA type 41C2/C3 fractures. Primary outcomes included coronal plane and sagittal plane alignment at latest follow up, rate of articular subsidence at latest follow up, and rate of postoperative infection.

Results: Of the 16 patients included, average followup was 8.2 months (range 0.1-29.7 months). At latest follow-up, average coronal alignment ranged from 0.8±1.2 degrees of varus (maximum 4.0 degrees) to 1.4±1.7 degrees of valgus (maximum 4.0 degrees). Average sagittal alignment ranged from 0.8±1.1 degrees of procurvatum (maximum 3.0 degrees) to 0.6±1.2 degrees of recurvatum (maximum 4.0 degrees). There was no radiographic evidence of articular subsidence at latest follow up for any patient. One patient (5.9%) presented at 141 days postoperatively with a draining wound and infection.

Conclusions: Combination plate-nail fixation is a viable option for treating patients with select bicondylar tibial plateau fractures with meta-diaphyseal comminution. This case series with short-term followup demonstrates acceptable radiographic and clinical outcomes, as well as rates of postoperative infection and implant removal similar to those currently reported in the literature for other techniques used to treat these fractures.
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http://dx.doi.org/10.1016/j.injury.2021.07.010DOI Listing
July 2021

Cost-Effectiveness Analyses of an Absorbable Antibacterial Envelope for Use in Patients at Increased Risk of Cardiac Implantable Electronic Device Infection in Germany, Italy, and England.

Value Health 2021 Jul 1;24(7):930-938. Epub 2021 Apr 1.

Cleveland Clinic, Cleveland, OH, USA.

Objectives: To model the cost-effectiveness of the TYRX Absorbable Antibacterial Envelope when used in patients at increased risk of cardiac implantable electronic device (CIED) infection in the context of 3 European healthcare systems: Germany, Italy, and England.

Methods: A decision tree model with a lifetime horizon was populated using data from the Worldwide Randomized Antibiotic Envelope Infection Prevention Trial, a large multicenter randomized controlled trial. Use of the antibacterial envelope adjunctive to standard of care was compared to standard of care infection prevention alone. Patients in the model were divided into subgroups based on presence of factors known to increase infection risk.

Results: The antibacterial envelope had the most favorable cost-effectiveness profile when patients had previously experienced CIED infection, had a history of immunosuppressive therapy, or had a Prevention of Arrhythmia Device Infection Trial (PADIT) score indicating high risk of infection (scores ≥6) at cost-effectiveness thresholds of €50 000 in Germany (assumed in the absence of an official threshold), €40 000 in Italy, and £30 000 in England. Probabilistic sensitivity analysis indicated that the antibacterial envelope was likely to be cost-effective in patients with other risk factors (including replacement of high power CIEDs, generator replacement with lead modification, and PADIT scores indicating intermediate risk of infection) when used with some device types and in some countries.

Conclusions: The absorbable antibacterial envelope was associated with cost-effectiveness ratios below European benchmarks in selected patients at increased risk of infection, suggesting the envelope provides value for European healthcare systems by reducing CIED infections.
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http://dx.doi.org/10.1016/j.jval.2020.12.021DOI Listing
July 2021

Quantitative EEG and cholinergic basal forebrain atrophy in Parkinson's disease and mild cognitive impairment.

Neurobiol Aging 2021 Jun 5;106:37-44. Epub 2021 Jun 5.

Department of Psychology, Health, Psychology, and Communities Research Centre, Manchester Metropolitan University, Manchester, UK.

Cholinergic degeneration is a key feature of dementia in neurodegenerative conditions including Alzheimer's disease (AD) and Parkinson's disease (PD). Quantitative electro-encephalography (EEG) metrics are altered in both conditions from early stages, and recent research in people with Lewy body and AD dementia suggests these changes may be associated with atrophy in cholinergic basal forebrain nuclei (cBF). To determine if these relationships exist in predementia stages of neurodegenerative conditions, we studied resting-state EEG and in vivo cBF volumes in 31 people with PD (without dementia), 21 people with mild cognitive impairment (MCI), and 21 age-matched controls. People with PD showed increased power in slower frequencies and reduced alpha reactivity compared to controls. Volumes of cholinergic cell clusters corresponding to the medial septum and vertical and horizontal limb of the diagonal band, and the posterior nucleus basalis of Meynert, correlated positively with; alpha reactivity in people with PD (p< 0.01); and pre-alpha power in people with MCI (p< 0.05). These results suggest that alpha reactivity and pre-alpha power are related to changes in cBF volumes in MCI and PD without dementia.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.05.023DOI Listing
June 2021

Exercise-based cardiac rehabilitation for cardiac implantable electronic device recipients.

Eur J Prev Cardiol 2021 Jun 21. Epub 2021 Jun 21.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK.

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http://dx.doi.org/10.1093/eurjpc/zwab103DOI Listing
June 2021

Use of U.S. Blood Donors for National Serosurveillance of SARS-CoV-2 Antibodies: Basis for an Expanded National Donor Serosurveillance Program.

Clin Infect Dis 2021 Jun 10. Epub 2021 Jun 10.

Vitalant Research Institute, San Francisco, CA, USA.

Introduction: The REDS-IV-P Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE) seroprevalence study conducted monthly cross-sectional testing for SARS-CoV-2 antibodies on blood donors in six U.S. metropolitan regions to estimate the extent of SARS-COV-2 infections over time.

Study Design/methods: During March-August 2020, approximately ≥1,000 serum specimens were collected monthly from each region and tested for SARS-CoV-2 antibodies using a well-validated algorithm. Regional seroprevalence estimates were weighted based on demographic differences with the general population. Seroprevalence was compared with reported COVID-19 case rates over time.

Results/findings: For all regions, seroprevalence was <1.0% in March 2020. New York experienced the biggest increase (peak seroprevalence, 15.8 % in May). All other regions experienced modest increases in seroprevalence(1-2% in May-June to 2-4% in July-August). Seroprevalence was higher in younger, non-Hispanic Black, and Hispanic donors. Temporal increases in donor seroprevalence correlated with reported case rates in each region. In August, 1.3-5.6 estimated cumulative infections (based on seroprevalence data) per COVID-19 case reported to CDC.

Conclusion: Increases in seroprevalence were found in all regions, with the largest increase in New York. Seroprevalence was higher in non-Hispanic Black and Hispanic blood donors than in non-Hispanic White blood donors. SARS-CoV-2 antibody testing of blood donor samples can be used to estimate the seroprevalence in the general population by region and demographic group. The methods derived from the RESPONSE seroprevalence study served as the basis for expanding SARS-CoV-2 seroprevalence surveillance to all 50 states and Puerto Rico.
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http://dx.doi.org/10.1093/cid/ciab537DOI Listing
June 2021

Combined action observation and motor imagery: An intervention to combat the neural and behavioural deficits associated with developmental coordination disorder.

Neurosci Biobehav Rev 2021 Aug 19;127:638-646. Epub 2021 May 19.

Research Centre for Health, Psychology and Communities, Department of Psychology, Faculty of Health, Psychology and Social Care, Manchester Metropolitan University, Manchester, UK.

Action observation (AO) and motor imagery (MI) have been used separately across different populations to alleviate movement impairment. Recently these two forms of covert motor simulation have been combined (combined action observation and motor imagery; AOMI), resulting in greater neurophysiological activity in the motor system, and more favourable behavioural outcomes when compared to independent AO and MI. This review aims to outline how some of the neural deficits associated with developmental coordination disorder (DCD) are evident during AO and MI, and highlight how these motor simulation techniques have been used independently to improve motor skill learning in children in this population. The growing body of evidence indicating that AOMI is superior to the independent use of either AO and MI is then synthesised and discussed in the context of children with DCD. To conclude, recommendations to optimise the delivery of AOMI for children with DCD are provided and future avenues for research are highlighted.
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http://dx.doi.org/10.1016/j.neubiorev.2021.05.015DOI Listing
August 2021

Development and feasibility testing of an evidence-based training programme for pharmacist independent prescribers responsible for the medicines-related activities within care homes.

Int J Pharm Pract 2021 May 21. Epub 2021 May 21.

Leicester Medical School, University of Leicester, Leicester, UK.

Introduction: The UK pharmacists with independent prescribing rights (pharmacist independent prescribers [PIPs]) are authorised to prescribe within their areas of competence. To enable PIPs to provide pharmaceutical care to residents in care homes and assume responsibility for medicines management, a process for development and assessment of competence is required. The aim of this research was to develop a training and accreditation process (training programme) to enable PIPs to operate safely and effectively within care homes.

Methods: Located in England, Scotland and Northern Ireland across four sites and based on a systematic review, it consisted of four phases: (1) initial stakeholder engagement, (2) uni-professional focus groups and interviews, (3) expert panel consensus and (4) feasibility testing. Four PIPs were trained each to provide pharmaceutical care to 10 care home residents. An expert panel synthesised the evidence at each stage to develop each iteration of the training programme. Content analysis was used throughout.

Results: Differences in baseline knowledge of PIPs required inclusion of a Personal Development Framework and the provision of a mentor. Face-to-face training focussed on managing medicines for a complex older person, minimising prescribing costs and supporting people without capacity. Provision of time to understand local context and develop relationships with care homes and general practitioners was identified as a central requirement. PIPs were assessed for competency via viva. Feasibility testing demonstrated that the derived training programme was acceptable, practical and effective.

Discussion: The model seemed to work, but due to small numbers, larger-scale testing of the training programme is now required.
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http://dx.doi.org/10.1093/ijpp/riab025DOI Listing
May 2021

Muscular forces responsible for proximal humeral deformity following fracture.

J Orthop Trauma 2021 May 14. Epub 2021 May 14.

University of California Irvine School of Medicine University of California Irvine, Department of Orthopedic Surgery Cornell University Orthopaedic Biomechanics Laboratory, Congress Medical Foundation.

Objectives: To evaluate the contribution of each of the rotator cuff muscles and deltoid to fracture deformity in a two-part proximal humerus fracture model. Our hypothesis was that superior cuff muscles would have the greatest contribution to coronal plane deformity while muscles with anterior and posterior attachments would have the greatest contribution to axial and sagittal plane deformity.

Methods: A medial wedge osteotomy was created in eight cadaveric shoulder specimens. A custom shoulder testing system was used load to each rotator cuff muscle and deltoid under increasing loading conditions. Fracture displacement was measured using a Microscribe digitizing system. The primary outcome was the contribution of each muscle to varus collapse. Secondary outcomes included contributions of each muscle to apex anterior/posterior deformity and humeral head anteversion/retroversion.

Results: Unbalanced loading of the supraspinatus resulted in the greatest varus deformity (34.5±2.3°) followed by the infraspinatus (22.3±3.6°) and subscapularis (21.7±3.1°) (p<0.05). Unbalanced loading of the subscapularis induced the greatest apex posterior (27.5±4.8°, p<0.05) and retroversion (39.0±5.6°, p<0.05) deformity while the infraspinatus induced the greatest apex anterior (8.7±3.4°, p>0.05) and anteversion (17.7±5.7°, p>0.05) deformity.

Conclusions: In this proximal humerus fracture model, the supraspinatus was the primary driver of varus deformity while the subscapularis and infraspinatus contributed to apex posterior/retroversion and apex anterior/anteversion, respectively. The subscapularis and infraspinatus are also important secondary drivers of varus deformity. This study establishes a physiologically relevant fracture model that mimics in vivo conditions for future biomechanical testing.
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http://dx.doi.org/10.1097/BOT.0000000000002142DOI Listing
May 2021

Modern Principles in the Acute Surgical Management of Open Distal Tibial Fractures.

J Am Acad Orthop Surg 2021 Jun;29(11):e536-e547

From the Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD (Shafiq), the Department of Orthopaedic Surgery, New York University School of Medicine, New York, NY (Hacquebord), and the Department of Orthopaedic Surgery, University of California, School of Medicine, Los Angeles, CA (Wright and Gupta).

Over the past two decades, management of open distal tibial fractures has evolved such that a staged approach, with external fixation and débridement during the index procedure, followed by definitive fixation and wound closure at a later date, is often considered the standard of care. Although definitive treatment of these complex injuries is often done by a multidisciplinary team of surgeons well versed in periarticular fracture repair and soft-tissue coverage in the distal extremity, the on-call orthopaedic surgeon doing the index procedure must understand the principles and rationale of the staged treatment algorithm to avoid compromising definitive treatment options and ensure the best possible patient outcome. The mechanism of injury, neurovascular status, size and location of soft-tissue injury, fracture pattern, and concomitant injuries in the polytraumatized patient should direct the treatment plan and anticipated outcomes. This review focuses on evaluation and management of these complex injuries with an emphasis on early aggressive débridement, principles of initial fracture fixation, and modern options for soft-tissue coverage, including local and free tissue transfer.
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http://dx.doi.org/10.5435/JAAOS-D-20-00502DOI Listing
June 2021

Low-temperature electrocautery reduces adverse effects from secondary cardiac implantable electronic device procedures: Insights from the WRAP-IT trial.

Heart Rhythm 2021 Jul 27;18(7):1142-1150. Epub 2021 Mar 27.

Cleveland Clinic, Cleveland Ohio.

Background: Cardiac device procedures require tissue dissection to free existing device lead(s). Common techniques include blunt dissection, standard electrocautery, and low-temperature electrocautery (PlasmaBlade, Medtronic); however, data on the type of electrosurgical tool used and the development of procedure- or lead-related adverse events are limited.

Objective: The purpose of this study was to determine whether standard or low-temperature electrocautery impacts the development of an adverse event.

Methods: We evaluated patients enrolled in WRAP-IT (Worldwide Randomized Antibiotic EnveloPe Infection PrevenTion Trial) undergoing cardiac implantable electronic device (CIED) revision, upgrade, or replacement. All adverse events were adjudicated by an independent physician committee. Data were analyzed using Cox proportional hazard regression modeling.

Results: In total, 5641 patients underwent device revision/upgrade/replacement. Electrocautery was used in 5205 patients (92.3%) (mean age 70.6 ± 12.7 years; 28.8% female), and low-temperature electrocautery was used in 1866 patients (35.9%). Compared to standard electrocautery, low-temperature electrocautery was associated with a 23% reduction in the incidence of a procedure- or lead-related adverse event through 3 years of follow up (hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.65-0.91; P = .002). After controlling for the number of active leads, degree of capsulectomy, degree of lead dissection, and renal dysfunction, low-temperature electrocautery was associated with a 32% lower risk of lead-related adverse events (HR 0.68; 95% CI 0.52-0.89; P = .004). These effects were consistent across a spectrum of lead-related adverse event types.

Conclusion: This study represents one of the largest assessments of electrocautery use in patients undergoing CIED revision, upgrade, or replacement procedures. Compared to standard electrocautery, low-temperature electrocautery significantly reduces adverse effects from these procedures.
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http://dx.doi.org/10.1016/j.hrthm.2021.03.033DOI Listing
July 2021

Implementation of a Pharmacogenomic Testing Service through Community Pharmacy in the Netherlands: Results from an Early Service Evaluation.

Pharmacy (Basel) 2021 Feb 12;9(1). Epub 2021 Feb 12.

University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.

Community pharmacy services have evolved to include medical and pharmaceutical interventions alongside dispensing. While established pharmacogenomic (PGx) testing is available throughout the Netherlands, this is primarily based in hospital environments and for specialist medicines. The aim of this work was to describe how best to implement PGx services within community pharmacy, considering potential barriers and enablers to service delivery and how to address them. The service was implemented across a selection of community pharmacies in the Netherlands. Data were captured on test outcomes and through a pharmacist survey. Following testing, 17.8% of the clinical samples were recommended to avoid certain medication (based on their current medicines use), and 14.0% to have their dose adjusted. Pre-emptive analysis of genotyped patients showed that the majority (99.2%) had actionable variants. Pharmacists felt confident in their operational knowledge to deliver the service, but less so in applying that knowledge. Delivering the service was believed to improve relationships with other healthcare professionals. These results add to the evidence in understanding how PGx can be delivered effectively within the community pharmacy environment. Training pharmacists in how to respond to patient queries and make clinical recommendations may enhance service provision further.
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http://dx.doi.org/10.3390/pharmacy9010038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930936PMC
February 2021

Structured block placements of hospital pre-registration trainee pharmacists in primary care medical practices across the United Kingdom: Lessons from a pilot scheme.

Curr Pharm Teach Learn 2021 Mar 1;13(3):302-311. Epub 2020 Nov 1.

Professor in Pharmacy Practice, University of East Anglia School of Pharmacy, Earlham Research Park, Norwich NR4 7TJ, United Kingdom. Electronic address:

Background And Purpose: There is increasing demand for suitably trained pharmacists to undertake clinical roles in primary care general practices across the United Kingdom. This necessitates development of sustainable training opportunities to both better prepare future registrants for such roles and raise awareness of the new career pathway. Educational activity and setting: Hospital pre-registration trainee pharmacists undertook four or eight-week placements in general practice as part of their training year. Trainees attended an introductory session and received educational support tools six weeks prior to their placements. Each trainee had an allocated clinical supervisor in general practice and maintained communication with their hospital tutor. On completion of all placements, trainees and general practice staff were asked to share perceptions and outcomes via online questionnaires.

Findings: Most trainees reported that the clinical supervision arrangements were satisfactory and found the placement workbook useful for guiding daily activities. Key benefits from the placements included enhanced understanding of the patient journey across healthcare sectors, increased confidence, and raised awareness of general practice as a career option. Main limitations included restricted opportunities to engage in patient-centred activities and lack of integration with general practice teams. All trainees stated that the presence of a general practice pharmacist was essential for learning support.

Summary: This model demonstrated the feasibility of structured block placements of trainee pharmacists in general practice with identified benefits for trainees and pharmacy workforce requirements. Future research:Identified key limitations to this model need further investigation, to improve the design of future placements.
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http://dx.doi.org/10.1016/j.cptl.2020.10.009DOI Listing
March 2021

No severe genetic bottleneck in a rapidly range-expanding bumblebee pollinator.

Proc Biol Sci 2021 02 10;288(1944):20202639. Epub 2021 Feb 10.

School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, UK.

Genetic bottlenecks can limit the success of populations colonizing new ranges. However, successful colonizations can occur despite bottlenecks, a phenomenon known as the genetic paradox of invasion. Eusocial Hymenoptera such as bumblebees ( spp.) should be particularly vulnerable to genetic bottlenecks, since homozygosity at the sex-determining locus leads to costly diploid male production (DMP). The Tree Bumblebee () has rapidly colonized the UK since 2001 and has been highlighted as exemplifying the genetic paradox of invasion. Using microsatellite genotyping, combined with the first genetic estimates of DMP in UK , we tested two alternative genetic hypotheses ('bottleneck' and 'gene flow' hypotheses) for 's colonization of the UK. We found that the UK population has not undergone a recent severe genetic bottleneck and exhibits levels of genetic diversity falling between those of widespread and range-restricted species. Diploid males occurred in 15.4% of reared colonies, leading to an estimate of 21.5 alleles at the sex-determining locus. Overall, the findings show that this population is not bottlenecked, instead suggesting that it is experiencing continued gene flow from the continental European source population with only moderate loss of genetic diversity, and does not exemplify the genetic paradox of invasion.
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http://dx.doi.org/10.1098/rspb.2020.2639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893223PMC
February 2021

Estimating the potential impact of implementing pre-emptive pharmacogenetic testing in primary care across the UK.

Br J Clin Pharmacol 2021 Jul 19;87(7):2907-2925. Epub 2021 Jan 19.

Boots UK, Thane Road, Nottingham, UK.

Aims: Pharmacogenetics (PGx) in the UK is currently implemented in secondary care for a small group of high-risk medicines. However, most prescribing takes place in primary care, with a large group of medicines influenced by commonly occurring genetic variations. The goal of this study is to quantitatively estimate the volumes of medicines impacted by implementation of a population-level, pre-emptive pharmacogenetic screening programme for nine genes related to medicines frequently dispensed in primary care in 2019.

Methods: A large community pharmacy database was analysed to estimate the national incidence of first prescriptions for 56 PGx drugs used in the UK for the period 1 January-31 December 2019. These estimated prescription volumes were combined with phenotype frequency data to estimate the occurrence of actionable drug-gene interactions (DGI) in daily practice in community pharmacies.

Results: In between 19.1 and 21.1% (n = 5 233 353-5 780 595) of all new prescriptions for 56 drugs (n = 27 411 288 new prescriptions/year), an actionable drug-gene interaction (DGI) was present according to the guidelines of the Dutch Pharmacogenetics Working Group and/or the Clinical Pharmacogenetics Implementation Consortium. In these cases, the DGI would result in either increased monitoring, guarding against a maximum ceiling dose or an optional or immediate drug/dose change. An immediate dose adjustment or change in drug regimen accounted for 8.6-9.1% (n = 2 354 058-2 500 283) of these prescriptions.

Conclusions: Actionable drug-gene interactions frequently occur in UK primary care, with a large opportunity to optimise prescribing.
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http://dx.doi.org/10.1111/bcp.14704DOI Listing
July 2021

Optimal Fixation of the Capitellar Fragment in Distal Humerus Fractures.

J Orthop Trauma 2021 07;35(7):e228-e233

Department of Orthopedic Surgery, University of California Irvine, Orange, CA; and.

Objectives: To determine if orthogonal or parallel plate position provides superior fixation of the separate capitellar fragment often present in intra-articular distal humerus fractures. We hypothesized that orthogonal plating would provide stiffer fixation given a greater number of opportunities for capitellar fixation and screw trajectories perpendicular to the fracture plane offered by a posterolateral plate compared with a parallel plate construct.

Methods: Ten matched pairs of cadaveric distal humeri were used to compare parallel and orthogonal plating in a fracture gap model with an isolated capitellar fragment. The capitellum was loaded in 20 degrees of flexion using a cyclic, ramp-loading protocol. Fracture displacement was measured using video tracking software. The primary outcome was axial stiffness for each construct. Secondary outcomes included maximum axial and angular fracture displacement.

Results: The parallel plate construct was more than twice as stiff as the orthogonal plate construct averaged across all loads (1464.8 ± 224.0 N/mm vs. 526.3 ± 90.8 N/mm, P < 0.001). Average axial fracture displacement was 0.15 ± 0.03 mm versus 0.53 ± 0.10 mm for parallel versus orthogonal plating, respectively (P = 0.003). Angular fracture displacement was minimal for both constructs (0.009 ± 0.001 degrees vs. 0.028 ± 0.006 degrees for parallel vs. orthogonal constructs).

Conclusions: Despite fewer points of fixation, a parallel plate construct provided stiffer fixation with less displacement of the simulated capitellar fracture fragment than an orthogonal plate construct in this biomechanical study. In the setting of an articular fracture, in which absolute stability and primary bone healing are desirable, parallel fixation should be considered even in fractures with a separate capitellar fragment if the size of fragment and fracture orientation allows.
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http://dx.doi.org/10.1097/BOT.0000000000002012DOI Listing
July 2021

Human TRPC5 structures reveal interaction of a xanthine-based TRPC1/4/5 inhibitor with a conserved lipid binding site.

Commun Biol 2020 11 23;3(1):704. Epub 2020 Nov 23.

Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, LS2 9JT, UK.

TRPC1/4/5 channels are non-specific cation channels implicated in a wide variety of diseases, and TRPC1/4/5 inhibitors have recently entered clinical trials. However, fundamental and translational studies require a better understanding of TRPC1/4/5 channel regulation by endogenous and exogenous factors. Although several potent and selective TRPC1/4/5 modulators have been reported, the paucity of mechanistic insights into their modes-of-action remains a barrier to the development of new chemical probes and drug candidates. Xanthine-based modulators include the most potent and selective TRPC1/4/5 inhibitors described to date, as well as TRPC5 activators. Our previous studies suggest that xanthines interact with a, so far, elusive pocket of TRPC1/4/5 channels that is essential to channel gating. Here we report the structure of a small-molecule-bound TRPC1/4/5 channel-human TRPC5 in complex with the xanthine Pico145-to 3.0 Å. We found that Pico145 binds to a conserved lipid binding site of TRPC5, where it displaces a bound phospholipid. Our findings explain the mode-of-action of xanthine-based TRPC1/4/5 modulators, and suggest a structural basis for TRPC1/4/5 modulation by endogenous factors such as (phospho)lipids and Zn ions. These studies lay the foundations for the structure-based design of new generations of TRPC1/4/5 modulators.
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http://dx.doi.org/10.1038/s42003-020-01437-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683545PMC
November 2020

The role of behavioural science in changing deprescribing practice.

Br J Clin Pharmacol 2021 01 5;87(1):39-41. Epub 2020 Nov 5.

School of Pharmacy, University of East Anglia, Norwich, UK.

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http://dx.doi.org/10.1111/bcp.14595DOI Listing
January 2021

Establishing Validity of a Comprehensive Hand Surgical Training and Educational Platform (STEP).

J Hand Surg Am 2020 Dec 30;45(12):1105-1114. Epub 2020 Sep 30.

Departments of Orthopaedic Surgery, University of California, Irvine, Irvine, CA.

Purpose: The purpose of this study was to develop and perform the initial validation for the Surgical Training and Educational Platform (STEP), a cost-effective psychomotor training and assessment instrument designed to teach and evaluate fundamental skills considered critical to competency in hand surgery.

Methods: An American Society for Surgery of the Hand (ASSH) taskforce of 13 board-certified hand surgeons developed 8 skills considered fundamental to competency in hand surgery including: (1) lag screw fixation of an oblique fracture, (2) depth of plunge during bicortical drilling, (3) central axis scaphoid fixation, (4) phalangeal fracture pinning, (5) flexor tendon repair, (6) microsurgical suturing, (7) full-thickness skin graft harvest, and (8) wrist arthroscopy. The tasks were developed from commercially available, nonclinical supplies at low cost. The startup cost for the entire system was less than $600 USD, with a cost-per-trainee-assessment of approximately $25 USD. After the tasks were finalized, 2 examiners traveled to 8 sites around the country to evaluate 93 surgeons, including 57 board-certified hand surgeons and 36 first-year orthopedic and plastic surgical residents. Scoring criteria for each task were based on a combination of time and clinically relevant quality metrics.

Results: Board-certified hand surgeons significantly outperformed surgical trainees on all 8 tasks, demonstrating that the STEP appropriately differentiates the skill level of expert and novice hand surgeons.

Conclusions: The STEP is an effective simulator that encompasses a wide range of fundamental psychomotor skills considered critical to competency in hand surgery. Although the STEP tasks are a valuable surgical training tool, further work is required to evaluate and refine the scoring system prior to using it as a critical evaluation of performance.

Clinical Relevance: The STEP simulator is a valuable, validated instrument for resident and fellow education and evaluation in hand surgery outside of the operating room.
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http://dx.doi.org/10.1016/j.jhsa.2020.07.019DOI Listing
December 2020

Human motor endplate remodeling after traumatic nerve injury.

J Neurosurg 2020 Sep 18:1-8. Epub 2020 Sep 18.

4Reeve-Irvine Research Center, University of California, Irvine, California.

Objective: Current management of traumatic peripheral nerve injuries is variable with operative decisions based on assumptions that irreversible degeneration of the human motor endplate (MEP) follows prolonged denervation and precludes reinnervation. However, the mechanism and time course of MEP changes after human peripheral nerve injury have not been investigated. Consequently, there are no objective measures by which to determine the probability of spontaneous recovery and the optimal timing of surgical intervention. To improve guidance for such decisions, the aim of this study was to characterize morphological changes at the human MEP following traumatic nerve injury.

Methods: A prospective cohort (here analyzed retrospectively) of 18 patients with traumatic brachial plexus and axillary nerve injuries underwent biopsy of denervated muscles from the upper extremity from 3 days to 6 years after injury. Muscle specimens were processed for H & E staining and immunohistochemistry, with visualization via confocal and two-photon excitation microscopy.

Results: Immunohistochemical analysis demonstrated varying degrees of fragmentation and acetylcholine receptor dispersion in denervated muscles. Comparison of denervated muscles at different times postinjury revealed progressively increasing degeneration. Linear regression analysis of 3D reconstructions revealed significant linear decreases in MEP volume (R = -0.92, R2 = 0.85, p = 0.001) and surface area (R = -0.75, R2 = 0.56, p = 0.032) as deltoid muscle denervation time increased. Surprisingly, innervated and structurally intact MEPs persisted in denervated muscle specimens from multiple patients 6 or more months after nerve injury, including 2 patients who had presented > 3 years after nerve injury.

Conclusions: This study details novel and critically important data about the morphology and temporal sequence of events involved in human MEP degradation after traumatic nerve injuries. Surprisingly, human MEPs not only persisted, but also retained their structures beyond the assumed 6-month window for therapeutic surgical intervention based on previous clinical studies. Preoperative muscle biopsy in patients being considered for nerve transfer may be a useful prognostic tool to determine MEP viability in denervated muscle, with surviving MEPs also being targets for adjuvant therapy.
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http://dx.doi.org/10.3171/2020.8.JNS201461DOI Listing
September 2020

A practitioner behaviour change intervention for deprescribing in the hospital setting.

Age Ageing 2021 02;50(2):581-586

School of Pharmacy, University of East Anglia, Norwich, NR4 7TJ, UK.

Background: hospital deprescribing trials have demonstrated marginal increases in deprescribing activity that are not sustained beyond the trial period. The hospital deprescribing implementation framework (hDIF) links barriers and enablers of deprescribing in hospital with 44 potential intervention components. This study aimed to support geriatricians and pharmacists to select and characterise hDIF components according to affordability, practicability, effectiveness, acceptability, safety and equity (APEASE) to design a deprescribing intervention in the English hospital setting.

Methods: we convened a modified Nominal Group Technique with a panel of nine geriatricians and pharmacists representing five English hospitals. Panel members selected and characterised intervention components from the hDIF based on the APEASE criteria. We set a consensus threshold of 80% agreement per APEASE criterion in order for the intervention component to be included.

Results: the panel selected five intervention components supporting engagement with deprescribing: an organisational action plan to prioritise deprescribing, two training activities to address pharmacists' beliefs about negative deprescribing consequences, restructuring pharmacists' working patterns to facilitate their contribution to deprescribing decisions, and sharing experiences of successfully engaging patients/family in deprescribing conversations to support others to do the same. A sixth component was selected to sustain engagement with deprescribing through measuring and sharing deprescribing activity achieved between teams.

Conclusions: deprescribing interventions targeting geriatricians' and pharmacists' behaviour in the English hospital context should include the six characterised components. A component to sustain deprescribing activity is a notable omission from previously reported deprescribing interventions and may explain their failure to maintain efficacy beyond the short-term trial period.
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http://dx.doi.org/10.1093/ageing/afaa169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936025PMC
February 2021

Improving guideline-mandated care of patients with implantable cardiac defibrillators.

Br J Hosp Med (Lond) 2020 Aug 4;81(8):1-10. Epub 2020 Aug 4.

Department of Cardiology, Liverpool Heart and Chest Hospital, Liverpool, UK.

Background/aims: Implantable cardiac defibrillators reduce the risk of sudden cardiac death in selected patients. The value of an implantable cardiac defibrillator declines as the patient's disease progresses. Guidelines suggest that the appropriateness of maintaining implantable cardiac defibrillator therapy be regularly reviewed as part of monitoring of the patient's disease trajectory. It is recommended that implantable cardiac defibrillators are deactivated as patients approach the end of life. Patients with a better understanding of their current state of health and the role that the implantable cardiac defibrillator plays within it are more likely to make informed decisions about the timing of deactivation.

Methods: A quality improvement project was undertaken on appropriate deactivation of implantable cardiac defibrillators within a large tertiary cardiac centre. This was driven by audit data showing inadequate patient communication and documentation around deactivation. Drivers for change included the introduction of electronic data records, clinical review of comorbid patients approaching elective battery change and an ongoing forum for patient and carer education. Measured outcomes included the number of deactivations performed, evidence of patient discussion and consent, and timing of deactivation of the implantable cardiac defibrillator.

Results: There were increased numbers of timely device deactivations undertaken following the interventions with improved documented evidence of patient discussion and consent. The educational forum was received favourably.

Conclusions: Focused multidisciplinary interventions can impact favourably on appropriate implantable cardiac defibrillator deactivation and improve patient engagement.
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http://dx.doi.org/10.12968/hmed.2020.0259DOI Listing
August 2020

Need for Speed: Examining Protein Behavior during CryoEM Grid Preparation at Different Timescales.

Structure 2020 11 18;28(11):1238-1248.e4. Epub 2020 Aug 18.

School of Biomedical Sciences, Faculty of Biological Sciences & Astbury Centre for Structural and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. Electronic address:

A host of new technologies are under development to improve the quality and reproducibility of cryoelectron microscopy (cryoEM) grid preparation. Here we have systematically investigated the preparation of three macromolecular complexes using three different vitrification devices (Vitrobot, chameleon, and a time-resolved cryoEM device) on various timescales, including grids made within 6 ms (the fastest reported to date), to interrogate particle behavior at the air-water interface for different timepoints. Results demonstrate that different macromolecular complexes can respond to the thin-film environment formed during cryoEM sample preparation in highly variable ways, shedding light on why cryoEM sample preparation can be difficult to optimize. We demonstrate that reducing time between sample application and vitrification is just one tool to improve cryoEM grid quality, but that it is unlikely to be a generic "silver bullet" for improving the quality of every cryoEM sample preparation.
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http://dx.doi.org/10.1016/j.str.2020.07.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652391PMC
November 2020

Subcutaneous or Transvenous Defibrillator Therapy.

N Engl J Med 2020 08;383(6):526-536

From the Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, University of Amsterdam (R.E.K., L.R.A.O.N., L.V.A.B., T.F.B., A.-F.B.E.Q., L.S., W.S., A.W., K.C.W., J.R.G., K.M.K., M.C.B., J.G.P.T., A.A.M.W.), ERN GUARD-Heart (E.R.B., P.D.L., A.A.M.W.), and the Department of Cardiology, OLVG (J.S.S.G.J.), Amsterdam, the Department of Cardiology, Isala Heart Centre, Zwolle (P.-P.H.M.D.), the Department of Cardiology, St. Antonius Hospital, Nieuwegein (L.V.A.B.), the Department of Cardiology, Flevoziekenhuis, Almere (N.R.B.), the Department of Cardiology, Radboud University Medical Center, Nijmegen (M.A.B.), the Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht (K.V.), the Department of Cardiology, Amphia Hospital, Breda (M.A.), Werkgroep Cardiologische Centra Nederland, Utrecht (M.A.), and the Department of Electrophysiology, Catharina Hospital, Eindhoven (F.A.L.E.B.) - all in the Netherlands; the First Department of Medicine-Cardiology, University Medical Center Mannheim, and the German Center for Cardiovascular Research Partner Site Heidelberg-Mannheim, Mannheim (J.K.), Klinik für Innere Medizin III, Schwerpunkt Kardiologie und Angiologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel (H.B.), the Department of Medicine I, Ludwig-Maximilians University Hospital, and the German Center for Cardiovascular Research, Munich Heart Alliance, Munich (S.K.), and the Department of Electrophysiology, Heart Center at University of Leipzig, Leipzig (S.R.) - all in Germany; the Division of Cardiology Section of Electrophysiology, Emory University, Atlanta (M.F.E.-C.); the Cardiology Clinical Academic Group, St. George's, University of London and St. George's University Hospitals NHS Foundation Trust London (E.R.B.), and Office of the Director of Clinical Electrophysiology Research and Lead for Inherited Arrhythmia Specialist Services, University College London and Barts Heart Centre (P.D.L.), London, the Oxford Biomedical Research Centre, Oxford University Hospitals NHS Trust, Oxford (T.R.B.), and Liverpool Heart and Chest Hospital, Liverpool (D.J.W.) - all in the United Kingdom; Valley Health System, Ridgewood, NJ (S.M.); the Department of Cardiology, Homolka Hospital, Prague, Czech Republic (P.N.); and CorVita Science Foundation, Chicago (M.C.B.).

Background: The subcutaneous implantable cardioverter-defibrillator (ICD) was designed to avoid complications related to the transvenous ICD lead by using an entirely extrathoracic placement. Evidence comparing these systems has been based primarily on observational studies.

Methods: We conducted a noninferiority trial in which patients with an indication for an ICD but no indication for pacing were assigned to receive a subcutaneous ICD or transvenous ICD. The primary end point was the composite of device-related complications and inappropriate shocks; the noninferiority margin for the upper boundary of the 95% confidence interval for the hazard ratio (subcutaneous ICD vs. transvenous ICD) was 1.45. A superiority analysis was prespecified if noninferiority was established. Secondary end points included death and appropriate shocks.

Results: A total of 849 patients (426 in the subcutaneous ICD group and 423 in the transvenous ICD group) were included in the analyses. At a median follow-up of 49.1 months, a primary end-point event occurred in 68 patients in the subcutaneous ICD group and in 68 patients in the transvenous ICD group (48-month Kaplan-Meier estimated cumulative incidence, 15.1% and 15.7%, respectively; hazard ratio, 0.99; 95% confidence interval [CI], 0.71 to 1.39; P = 0.01 for noninferiority; P = 0.95 for superiority). Device-related complications occurred in 31 patients in the subcutaneous ICD group and in 44 in the transvenous ICD group (hazard ratio, 0.69; 95% CI, 0.44 to 1.09); inappropriate shocks occurred in 41 and 29 patients, respectively (hazard ratio, 1.43; 95% CI, 0.89 to 2.30). Death occurred in 83 patients in the subcutaneous ICD group and in 68 in the transvenous ICD group (hazard ratio, 1.23; 95% CI, 0.89 to 1.70); appropriate shocks occurred in 83 and 57 patients, respectively (hazard ratio, 1.52; 95% CI, 1.08 to 2.12).

Conclusions: In patients with an indication for an ICD but no indication for pacing, the subcutaneous ICD was noninferior to the transvenous ICD with respect to device-related complications and inappropriate shocks. (Funded by Boston Scientific; PRAETORIAN ClinicalTrials.gov number, NCT01296022.).
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http://dx.doi.org/10.1056/NEJMoa1915932DOI Listing
August 2020

Clinical and cost effectiveness of a multi-professional medication reviews in care homes (CAREMED).

Int J Pharm Pract 2020 Dec 14;28(6):626-634. Epub 2020 Jul 14.

School of Pharmacy, University of East Anglia, Norfolk, UK.

Objectives: With 70% of care home residents experiencing a medication error every day in the UK, better multi-professional working between medical practitioners, pharmacists and care homes was recommended. The aim of this study was to determine the effectiveness (falls reduction) and cost-effectiveness, of a multi-professional medication review (MPMR) service in care homes for older people.

Method: A total of care homes in the East of England were cluster randomised to 'usual care' or two multi-professional (General practitioner, clinical pharmacist and care homes staff) medication reviews during the 12-month trial period. Target recruitment was 900 residents with 10% assumed loss to follow-up. Co-primary outcome measures were number of falls and potentially inappropriate prescribing assessed by the Screening Tool of Older Persons Prescriptions.

Key Findings: A total of 826 care home residents were recruited with 324 lost to follow-up for at least one primary outcome measure. The mean number of falls per resident per annum was 3.3 for intervention and 3.0 for control (P = 0.947). Each resident was found to be prescribed 0.69 (intervention) and 0.85 (control) potentially inappropriate medicines after 12 months (P = 0.046). No significant difference identified in emergency hospital admissions or deaths. Estimated unadjusted incremental mean cost per resident was £374.26 higher in the intervention group.

Conclusions: In line with other medication review based interventions in care homes, two MPMRs improved medication appropriateness but failed to demonstrate improvements in clinical outcomes. From a health system perspective costs where estimated to increase overall and therefore a different model of medicines management is required.
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http://dx.doi.org/10.1111/ijpp.12656DOI Listing
December 2020

Posterior Inferior Comminution Significantly Influences Torque to Failure in Vertically Oriented Femoral Neck Fractures: A Biomechanical Study.

J Orthop Trauma 2020 12;34(12):644-649

University of California Irvine Department of Orthopedic Surgery, Orange, CA.

Objectives: To evaluate axial fracture obliquity and posterior inferior comminution in vertically oriented femoral neck fractures (FNFs) in the physiologically young patient. A biomechanical investigation was designed to evaluate the impact of these fracture elements on torque to failure using cannulated screw (CS) and sliding hip screw fixation.

Methods: Four Pauwels III FNF models were established in synthetic femurs: (1) vertically oriented in the coronal plane (COR), (2) coronal plane with axial obliquity (AX), (3) coronal plane with posterior inferior comminution (CCOM), and (4) coronal plane with axial obliquity and posterior inferior comminution (ACOM). In each group (n = 10), specimens were fixed using either 3 CSs or a sliding hip screw with supplemental antirotation screw (SHS). Quasistatic cyclic ramp-loading to failure was performed using a custom testing jig combining axial preloading and torsional ramp-loading. The primary outcome was torque to failure, defined as angular displacement ≥5 degrees.

Results: In the CS group, torque to failure was 40.2 ± 2.6 Nm, 35.0 ± 1.4 Nm, 29.8 ± 1.5 Nm, and 31.8 ± 2.2 Nm for the COR, AX, CCOM, and ACOM fracture groups, respectively (P < 0.05). In the SHS group, torque to failure was 28.6 ± 1.3 Nm, 24.2 ± 1.4 Nm, 21.4 ± 1.2 Nm, and 21.0 ± 0.9 Nm for the COR, AX, CCOM, and ACOM fracture groups, respectively (P < 0.05). In both constructs, groups with posterior inferior comminution demonstrated significantly lower torque to failure compared to the COR group (P < 0.05). The CS construct demonstrated higher torque to failure in all groups when compared to the SHS construct (P < 0.01).

Conclusions: Posterior inferior comminution significantly affects torque to failure in vertically oriented FNFs. Three peripherally placed CSs may resist combined axial and torsional loading better than a sliding hip screw construct.
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http://dx.doi.org/10.1097/BOT.0000000000001846DOI Listing
December 2020

Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society.

Eur J Heart Fail 2020 11 6;22(11):1945-1960. Epub 2020 Aug 6.

Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies.
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http://dx.doi.org/10.1002/ejhf.1920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019326PMC
November 2020

Prevention of the cytokine storm in COVID-19.

Authors:
David J M Wright

Lancet Infect Dis 2021 01 7;21(1):25-26. Epub 2020 May 7.

Emeritus Reader in Medical Microbiology, Imperial College London, London SW7 7BU, UK. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(20)30376-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252095PMC
January 2021

Prevalence and prognostic significance of device-detected subclinical atrial fibrillation in patients with heart failure and reduced ejection fraction.

Int J Cardiol 2020 08 3;312:64-70. Epub 2020 Mar 3.

Imperial College London (Royal Brompton Hospital), United Kingdom. Electronic address:

Background: Cardiac implanted electronic devices (CIEDs) can detect short durations of previously unrecognised atrial fibrillation (AF). The prognostic significance of device-detected subclinical AF, in the context of contemporary heart failure (HF) therapy, is unclear.

Methods: Amongst patients enrolled in the Remote Monitoring in HF with implanted devices (REM-HF) trial, three categories were defined based on total AF duration in the first year of follow-up: no AF, subclinical AF (≥6 min to ≤24 h), and AF >24 h. All-cause mortality, stroke, and cardiovascular hospitalisation were assessed.

Results: 1561 patients (94.6%) had rhythm data: 71 (4.6%) had subclinical AF (median of 4 episodes, total duration 3.1 h) and 279 (17.9%) had AF >24 h. During 2.8 ± 0.8 years' follow-up, 39 (2.5%) patients had a stroke. Stroke rate was highest amongst patients with subclinical AF (2.0 per 100-person years) versus no AF or AF >24 h (0.8 and 1.0 per 100-person years, respectively). In the overall cohort, AF >24 h was not an independent predictor of stroke. However, amongst patients with no history of AF (n = 932), new-onset subclinical AF conferred a three-fold higher stroke risk (adjusted HR 3.35, 95%CI 1.15-9.77, p = 0.027). AF >24 h was associated with more frequent emergency cardiovascular hospitalisation (adjusted HR 1.46, 95%CI 1.19-1.79, p < 0.0005). Neither AF classification was associated with mortality.

Conclusions: In patients with HF and a CIED, subclinical AF was infrequent but, as a new finding, was associated with an increased risk of stroke. Anticoagulation remains an important consideration in this population, particularly when the clinical profile indicates a high stroke risk.
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http://dx.doi.org/10.1016/j.ijcard.2020.03.008DOI Listing
August 2020

Optimising Medicines Administration for Patients with Dysphagia in Hospital: Medical or Nursing Responsibility?

Geriatrics (Basel) 2020 Feb 19;5(1). Epub 2020 Feb 19.

Senior Lecturer in Law, College of Human and Health Sciences, Swansea University, Swansea SA2 8PP, UK.

Dysphagia is common-not only associated with stroke, dementia, Parkinson's but also in many non-neurological medical problems-and is increasingly prevalent in ageing patients, where malnutrition is common and pneumonia is frequently the main cause of death. To improve the care of people with dysphagia (PWD) and minimise risk of aspiration and choking, the textures of food and drinks are frequently modified. Whilst medicines are usually concurrently prescribed for PWD, their texture is frequently not considered and therefore any minimisation of risk with respect to food and drink may be being negated when such medicines are administered. Furthermore, evidence is starting to emerge that mixing thickeners with medicines can, in certain circumstances, significantly affect drug bioavailability and therefore amending the texture of a medicine may not be straightforward. Research across a number of hospital trusts demonstrated that PWD are three times more likely to experience medication administration errors than those without dysphagia located on the same ward. Errors more commonly seen in PWD were missed doses, wrong formulation and wrong preparation through medicines alteration. Researchers also found that the same patient with dysphagia would be given their medicines in entirely different ways depending on the person administering the medicine. The alteration of medicines prior to administration has potential for patient harm, particularly if the medicine has been designed to release medicines at a pre-defined rate or within a pre-defined location. Alteration of medicines can have significant legal implications and these are frequently overlooked. Dispersing, crushing or mixing medicines can be part of, or misconstrued as, covert administration, thus introducing a further raft of legislation. Guidance within the UK recommends that following identification of dysphagia, the ongoing need for the medicine should be considered, as should the most appropriate route and formulation, with medicines alteration used as a last resort. The patient should be at the centre of any decision making. Evidence suggests that in the UK this guidance is not being followed. This article considers the clinical and legal issues surrounding administration of medicines to PWD from a UK perspective and debates whether medicines optimisation should be the primary responsibility of the prescriber when initiating therapy on the ward or the nurse who administers the medicine.
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http://dx.doi.org/10.3390/geriatrics5010009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151233PMC
February 2020

Effect of biceps rerouting technique to restore glenohumeral joint stability for large irreparable rotator cuff tears: a cadaveric biomechanical study.

J Shoulder Elbow Surg 2020 Jul 17;29(7):1425-1434. Epub 2020 Feb 17.

Department of Orthopedic Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:

Background: The concept of stabilizing the humerus has taken on an important role in the treatment of irreparable cuff tears, and the biceps rerouting (BR) method is considered one of the most effective treatments in this field. The study aimed to evaluate the biomechanical effects of BR for large irreparable rotator cuff tears (LICTs).

Methods: A total of 8 cadaveric shoulders were used for testing under 5 conditions: intact shoulder, LICT, partial repair (PR), BR, and biceps rerouting with side-to-side repair (BRSS). Total rotational range of motion was measured at 40°, then 20°, and finally 0° of glenohumeral (GH) abduction. Superior humeral translation and subacromial contact pressure were measured at 0°, 30°, 60°, and 90° of external rotation at each abduction angle. Repeated-measures analyses of variance with Tukey post hoc tests were used for statistical comparisons.

Results: Superior humeral translation was significantly decreased in the BR and BRSS conditions compared with the LICT and PR conditions at 0° and 20° of GH abduction (P < .001). BR and BRSS significantly reduced subacromial contact pressure compared with LICT and PR at 0° of GH abduction (P < .001). There was no significant decrease in total rotational range of motion after BR at any abduction angle.

Conclusion: BR biomechanically restored shoulder stability without overconstraining range of motion in an LICT model.
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http://dx.doi.org/10.1016/j.jse.2019.11.015DOI Listing
July 2020
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