Publications by authors named "Andrew Hughes"

252 Publications

The majority of athletes fail to return to play following anterior cruciate ligament reconstruction due to reasons other than the operated knee.

Knee Surg Sports Traumatol Arthrosc 2021 Jan 28. Epub 2021 Jan 28.

Sports Surgery Clinic, Northwood Avenue, Santry, Santry Demesne, Dublin 9, Ireland.

Purpose: The purpose of this study is to evaluate the reasons why athletes do not return to play (RTP) following anterior cruciate ligament (ACL) reconstruction from a large single-centre database.

Methods: The institutional ACL registry was screened for patients that had undergone a primary ACLR and had RTP status reported at 24-month follow-up. The reasons that patients were unable to RTP at 24 months were evaluated. The ACL-Return to Sport Index (ACL-RSI) was evaluated at baseline and 24-month follow-up to evaluate psychological ability to RTP.

Results: At 2 years, 1140 patients returned to play, and 222 had not returned to play. The most common reasons athletes were unable to return was fear of reinjury (27.5%), lack of confidence in performance on return (19.4%) and external life factors (16.6%), i.e. work commitments and family reasons. Other reasons for athletes not returning to play were residual knee pain (10%) and subsequent injury (5%). The ACL-RSI score was significantly lower at diagnosis (40.3 vs. 49.3; p = 0.003) and 2 years (41.8 vs. 78.7; p < 0.0001) in athletes who did not return to play vs. those that did RTP.

Conclusion: The majority of patients that report they have not returned to play do so due to external life and psychological factors associated with their injury, including fear of reinjury and lack of confidence in performance. A small minority of patients were unable to return due to residual knee symptoms or reinjury. Pre-operative psychological assessment and intervention may identify those less likely to RTP and provide an opportunity for targeted interventions to further improve RTP outcomes.

Level Of Evidence: III.
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http://dx.doi.org/10.1007/s00167-020-06407-5DOI Listing
January 2021

Hip fracture care during Covid-19: a regional trauma centre's experience.

Ir J Med Sci 2021 Jan 3. Epub 2021 Jan 3.

Department of Trauma and Orthopaedics, Midland Regional Hospital, Tullamore, Co Offaly, Ireland.

Introduction: The Covid-19 pandemic has caused worldwide upheaval from early 2020. Trauma and orthopaedic services are no different. A fundamentally important and significant portion of trauma services is the treatment of fragility fractures of the proximal femur, otherwise known as hip fractures. The hip fracture "Blue book Standards", the key performance indicators (KPIs) associated with appropriate hip fracture care are challenging during non-crisis times. We aim to review Blue Book compliance during the Covid-19 crisis and review outcomes of hip fractures, including Covid-19 infection rates.

Methods: We retrospectively reviewed IHFD data to collection demographic data, IHFD standards of care, 30-day mortality rates and complications between 23rd March and 20th May 2020 and 2019. Covid-19 rates in 2020 were also recorded.

Results: A total of 36 hip fractures were recorded in 2020, compared with 45 in 2019, resulting in a 20% reduction in presentations. Thirty-day mortality in hip fractures during the Covid-19 crisis was 8.3% compared with 2.2% in 2020. Covid-19 infection was statistically associated with 30-day mortality in the 2020 cohort. Statistically significant improvements in time-dependent KPIs (time to ward and time to surgery) were noted in the 2020 cohort.

Conclusions: Despite improvements in hip fracture care KPIs, the Covid-19 crisis was associated with increased 30-day mortality in hip fracture patients. A positive Covid-19 swab was associated with higher mortality. These observations are of paramount importance to ensure adequate service planning and provision in the face of a potential "second wave" of Covid-19 infections leading into the winter months of 2020.
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http://dx.doi.org/10.1007/s11845-020-02476-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779090PMC
January 2021

The impact of comorbidities on post-operative complications following colorectal cancer surgery.

PLoS One 2020 23;15(12):e0243995. Epub 2020 Dec 23.

Department of General Surgery, The Prince Charles Hospital, Brisbane, Queensland, Australia.

Background: Colorectal cancer surgery is complex and can result in severe post-operative complications. Optimisation of surgical outcomes requires a thorough understanding of the background complexity and comorbid status of patients.

Aim: The aim of this study is to determine whether certain pre-existing comorbidities are associated with high grade post-operative complications following colorectal cancer surgery. The study also aims to define the prevalence of demographic, comorbid and surgical features in a population undergoing colorectal cancer resection.

Method: A colorectal cancer database at The Prince Charles Hospital was established to capture detailed information on patient background, comorbidities and clinicopathological features. A single-centre retrospective study was undertaken to assess the effect of comorbidities on post-operative outcomes following colorectal cancer resection. Five hundred and thirty-three patients were reviewed between 2010-2018 to assess if specific comorbidities were associated with higher grade post-operative complications. A Clavien-Dindo grade of three or higher was defined as a high grade complication.

Results: Fifty-eight percent of all patients had an ASA grade of ASA III or above. The average BMI of patients undergoing resection was 28 ± 6.0. Sixteen percent of all patients experienced a high grade complications. Patients with high grade complications had a higher mean average age compared to patients with low grade or no post-operative complications (74 years vs 70 years, p = 0.01). Univariate analysis revealed patients with atrial fibrillation, COPD, ischaemic heart disease and heart failure had an increased risk of high grade complications. Multivariate analysis revealed pre-existing atrial fibrillation (OR 2.70, 95% CI 1.53-4.89, p <0.01) and COPD (OR 2.02 1.07-3.80, p = 0.029) were independently associated with an increased risk of high grade complications.

Conclusion: Pre-existing atrial fibrillation and COPD are independent risk factors for high grade complications. Targeted perioperative management is necessary to optimise outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243995PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757883PMC
February 2021

Challenges faced by orthopaedic trainees during the Covid-19 pandemic - An Irish perspective.

Surgeon 2020 Nov 14. Epub 2020 Nov 14.

Trauma & Orthopaedic Surgery, Midland Regional Hospital, Tullamore, Co. Offaly, Ireland. Electronic address:

Background: The recent SARS-CoV2/COVID-19 pandemic has caused a change in most aspects of our daily lives. Our health systems have had to adjust at an unprecedented rate to accommodate care for patients affected by the virus. As a result there has been widespread disruption to trauma and elective services throughout the Orthopaedic community Worldwide. We discuss the changes facing orthopaedic residents in training and the adaptations that have been made.

Methods: We discuss the challenges posed from a reduction in caseload to surgeons in training, teaching activities, patient interaction, workforce reinforcement and support networks in Ireland.

Results: A structured deployment of residents has taken place ensuring maximum exposure to operative cases to maintain competency. Teaching activities have been virtualised into a new curriculum that provides trainees with convenient access to a wide range of specialists at defined time periods during the week. Strategies have been employed to reinforce the workforce in anticipation of an acute reduction in staff due to the Covid-19 virus.

Conclusions: The changes have been rapid and despite many of these adjustments being borne out of necessity, the innovation displayed will almost certainly alter how training is ultimately delivered long after the crisis has ceased.
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http://dx.doi.org/10.1016/j.surge.2020.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666556PMC
November 2020

Remote Delivery of the Satellite Virtual Fracture Clinic - a Pilot Report of the First 500 Cases.

Injury 2020 Nov 21. Epub 2020 Nov 21.

Department of Trauma and Orthopaedic Surgery, Dublin Midlands Hospital Group, Tullamore, Co. Offaly, Ireland; School of Medicine, University of Limerick, Co. Limerick, Ireland.

Presenting to the fracture clinic carries economic, social and societal consequences. The virtual fracture clinic (VFC) has proven to be a safe, patient-focused, cost-effective means of delivering trauma care, whilst reducing unnecessary clinic attendances. Within our institution, a Satellite VFC was established, so as to accommodate an offsite referring emergency department. The VFC database was accessed to identify the first 500 patients who were referred to the Satellite VFC. The decision made for each patient, the rate of returns to the clinic, and the rate of referrals requiring surgical intervention, following discussion at the VFC, ,were identified. A cost analysis and cost comparison was carried out between the Satellite VFC and the traditional "face to face" fracture clinic. There were 500 patients referred to the Satellite VFC within the study period. Of such patients, 288 (58%) were discharged directly following review at the Satellite VFC, 141 patients (28%) were referred to physiotherapy, 50 (10%) were redirected to the trauma clinic, 11 (2%) were sent directly to hand therapy, and 10 (2%) were sent to the ED review clinic. Patients who returned to the fracture clinic accounted for 3.8% of all referrals, and 0.2% of all referrals necessitated surgical intervention. This pilot initiative saved the Dublin Midlands Hospital Group over €50,000. The Satellite VFC is the first of its kind in the literature. Rural communities worldwide would benefit from remote orthopaedic management of suitable fracture patterns. The true value of the Satellite VFC process comes from its use of robust patient care pathways, rationalising resource use and minimising patient travel, whilst demonstrating reliable outcomes and promoting safety.
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http://dx.doi.org/10.1016/j.injury.2020.11.055DOI Listing
November 2020

Role of transoesophageal echocardiography in detecting patent foramen ovale in stroke patients aged ≤60 years: A retrospective study.

PLoS One 2020 30;15(11):e0242885. Epub 2020 Nov 30.

Australian National University Medical School, Australian National University, Acton, ACT, Australia.

Background: The underlying aetiology of ischaemic strokes is unknown in as many as 50% of cases. Patent foramen ovale (PFO) has become an increasingly recognised cause of ischaemic strokes in young patients. The present study aimed (1) to assess the frequency of transoesophageal echocardiography (TOE) performed and the proportion of PFOs detected in patients aged ≤60 years and (2) examine the effect of PFO closure on reducing stroke reoccurrence.

Methods: This was a retrospective clinical audit based on de-identified, secure medical records of the Canberra Hospital, Australia. A review of records was conducted on discharged patients aged 18-60 years admitted to the stroke unit following an ischaemic stroke episode between January 1, 2015, and December 31, 2018.

Results: A total of 214 acute ischaemic stroke patients were admitted to the stroke unit (mean age, 49.2 ± 9.7 years). Concerning aetiology, 47.2% were cryptogenic in origin, whereas 52.8% had a stroke of a determined cause. 12 patients were diagnosed with a PFO and 7 venous thromboembolic events were identified, 1 in the cryptogenic group and 6 in the determined cause group. 91.7% of PFOs were diagnosed in patients with a cryptogenic stroke. Trans-thoracic echocardiography (TTE) was performed in 37.3% of patients and had detected 4 PFOs (sensitivity 27.3%, specificity 92.5%). TOE was performed in 26.2% of patients and had detected 11 PFOs (sensitivity 90.0%, specificity 100%). The number needed to treat to prevent the occurrence of an ischaemic stroke through PFO closure was estimated at 30.

Conclusions: An inverse association between age and PFO presence was found in patients aged 18-60 years. Additionally, TOE was superior to TTE for detecting PFO, particularly in those with stroke of an undetermined cause. Our results suggest an increased need for TOE as a routine imaging procedure for acute ischaemic stroke patients aged ≤60.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242885PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703908PMC
January 2021

Quantifying the impact of the COVID-19 pandemic on orthopaedic trainees: a national perspective.

Bone Jt Open 2020 Oct 19;1(10):645-652. Epub 2020 Oct 19.

Orthopaedic Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland.

Aims: We aim to objectively assess the impact of COVID-19 on mean total operative cases for all indicative procedures (as outlined by the Joint Committee on Surgical Training (JCST)) experienced by orthopaedic trainees in the deanery of the Republic of Ireland. Subjective experiences were reported for each trainee using questionnaires.

Methods: During the first four weeks of the nationwide lockdown due to COVID-19, the objective impact of the pandemic on each trainee's surgical caseload exposure was assessed using data from individual trainee logbook profiles in the deanery of the Republic of Ireland. Independent predictor variables included the trainee grade (ST 3 to 8), the individual trainee, the unit that the logbook was reported from, and the year in which the logbook was recorded. We used the analysis of variance (ANOVA) test to assess for any statistically significant predictor variables. The subjective experience of each trainee was captured using an electronic questionnaire.

Results: The mean number of total procedures per trainee over four weeks was 36.8 (7 to 99; standard deviation (SD) 19.67) in 2018, 40.6 (6 to 81; SD 17.90) in 2019, and 18.3 (3 to 65; SD 11.70) during the pandemic of 2020 (p = 0.043). Significant reductions were noted for all elective indicative procedures, including arthroplasty (p = 0.019), osteotomy (p = 0.045), nerve decompression (p = 0.024) and arthroscopy (p = 0.024). In contrast, none of the nine indicative procedures for trauma were reduced. There was a significant inter-unit difference in the mean number of total cases (p = 0.029) and indicative cases (p = 0.0005) per trainee. We noted that 7.69% (n = 3) of trainees contracted COVID-19.

Conclusion: During the COVID-19 pandemic, the mean number of operative cases per trainee has been significantly reduced for four of the 13 indicative procedures, as outlined by the JCST. Reassignment of trainees to high-volume institutions in the future may be a plausible approach to mitigate significant training deficits in those trainees worst impacted by the reduction in operative exposure.
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http://dx.doi.org/10.1302/2633-1462.110.BJO-2020-0149.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659703PMC
October 2020

Infographics Improve Comprehension and Recall at the Orthopaedic Journal Club.

J Surg Educ 2020 Nov 16. Epub 2020 Nov 16.

Department of Orthopaedic Surgery, National Orthopaedic Hospital Cappagh, Dublin, Ireland.

Information graphics, abbreviated to infographics, convey information using visualisations and images. This format of presenting research has been shown to be preferred by 80% of clinicians when compared to text articles. The weekly Journal Club was audited within our institution over a period of 10 weeks. Five weeks of article presentations using plain text abstract displays preceded 5 weeks of infographic display. A multiple-choice questionnaire was constructed weekly so as to test the attendees' recall and comprehension. A total of 1036 multiple-choice questions were answered across the 10 weeks, which included 553 questions (53.4%) based on the standard Journal Club format, and 483 questions (46.6%) on infographic displays. The use of infographics saw significantly improved test results from 42% to 65.8% (p < 0.001). Questions were answered correctly 1.5 times more often following infographic introduction. Infographics were preferred over plain text abstracts by 78% of team members. Infographics enhanced the audience's comprehension and recall of orthopaedic research when used as a presentation tool at the Journal Club. The majority of clinicians preferred infographic displays to plain text abstracts. Research was perceived as being more engaging, and thus more suitable for dissemination, such that key messages could be shared with surgeons, researchers and patients worldwide.
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http://dx.doi.org/10.1016/j.jsurg.2020.10.012DOI Listing
November 2020

Multinutrients for the Treatment of Psychiatric Symptoms in Clinical Samples: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Nutrients 2020 Nov 4;12(11). Epub 2020 Nov 4.

School of Psychology, Speech and Hearing, University of Canterbury, Christchurch 8140, New Zealand.

This systematic review and meta-analysis focused on randomized controlled trials (RCT) of multinutrients consisting of at least four vitamins and/or minerals as interventions for participants with psychiatric symptoms. A systematic search identified 16 RCTs that fit the inclusion criteria ( = 1719 participants) in six psychiatric categories: depression, post-disaster stress, antisocial behavior, behavioral deficits in dementia, attention-deficit/hyperactivity disorder, and autism. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to rate the evidence base. Significant clinical benefit was assessed using minimal clinically important differences (MIDs). Due to heterogeneity in participants, multinutrient formulas, outcome measures, and absence of complete data, only the Attention-Deficit/Hyperactivity Disorder (ADHD) category was eligible for meta-analyses. In ADHD populations, statistically and clinically significant improvements were found in global functioning, Mean Difference (MD) -3.3, = 0.001, MID -3.26; Standardized Mean Difference (SMD) -0.49 = 0.001 MD -0.5), clinician ratings of global improvement (MD -0.58, = 0.001, MID -0.5) and ADHD improvement (MD -0.54, = 0.002, MID -0.5), and clinician (but not observer) measures of ADHD inattentive symptoms (MD -1.53, = 0.05, MID -0.5). Narrative synthesis also revealed a pattern of benefit for global measures of improvement, for example: in autism, and in participants with behavioral deficits in dementia. Post-natural disaster anxiety and the number of violent incidents in prison populations also improved. Broad-spectrum formulas (vitamins + minerals) demonstrated more robust effects than formulas with fewer ingredients. This review highlights the need for robust methodology-RCTs that report full data, including means and standard deviations for all outcomes-in order to further elucidate the effects of multinutrients for psychiatric symptoms.
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http://dx.doi.org/10.3390/nu12113394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694278PMC
November 2020

Ventilator dependence complications in motor neuron disease.

BMJ Support Palliat Care 2020 Sep 21. Epub 2020 Sep 21.

Palliative Medicine, St Oswald's Hospice, Newcastle, UK.

Long-term dependence on non-invasive ventilation (NIV) without time for advance care planning can result in significant complications that may require innovative management strategies. We present the case of a man who was admitted with respiratory failure and required NIV. Despite effective treatment for community acquired pneumonia, attempts to wean NIV failed. While dependent on NIV, a diagnosis of motor neuron disease was made. Time without ventilation was not tolerated and consequently complications of: facial pressure ulceration, nasal septal prolapse, inspissated secretions and failure to feed occurred. This case illustrates the severity of complications that can result from NIV dependence; however, it also details how these can be effectively managed by the hospice multidisciplinary team, with support from experts both within and external to the hospice enabling the acquisition of appropriate skills and knowledge.
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http://dx.doi.org/10.1136/bmjspcare-2020-002560DOI Listing
September 2020

Elements of the New Conversation.

J Am Acad Child Adolesc Psychiatry 2020 Dec 17;59(12):1310-1311. Epub 2020 Sep 17.

University of Washington, Seattle.

These comments include established behavioral treatment preceding and augmenting stimulant use to prevent or reduce dosing, nutritional approaches with placebo-controlled evidence, and possible effects of stimulant on micronutrient levels.
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http://dx.doi.org/10.1016/j.jaac.2020.08.438DOI Listing
December 2020

Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: Analysis of data from the United Kingdom National Alkaptonuria Centre.

JIMD Rep 2020 Sep 22;55(1):75-87. Epub 2020 Jun 22.

Institute of Ageing and Chronic Disease, Musculoskeletal Biology I, William Henry Duncan Building Liverpool UK.

Background: Increased homogentisic acid (HGA) causes ochronosis. Nitisinone decreases HGA. The aim was to study the effect of nitisinone on the ochronosis progression.

Methods: Photographs of the eyes and ears were acquired from patients attending the National Alkaptonuria Centre (NAC) at V-1 (pre-baseline visit), V0 (baseline visit when 2 mg nitisinone was commenced), and yearly at V1, V2, and V3 visits. Photographs were inspected for evolution of ochronotic pigment and also scored categorically to derive eye, ear, and combined ochronosis scores. An ear cartilage biopsy was also carried out at V0 and one year after V3 (V4) and ochronotic pigment was assessed and quantitated. Visits were compared for changes in pigment. Fasting blood and 24-hour urine samples were collected for measurement of HGA.

Results: There were 80 AKU patients at V0, and 52, 47, and 40 at V1, V2, and V3 in the group with variable numbers (VAR Group) respectively; 23 patients attended once before V0, in the V-1 visit. Photographs of patients show increase in eye pigment between V-1 and V0, followed by decrease post-nitisinone at V1, V2, and V3. Ear and combined ochronosis semiquantitative scoring showed an increase between V-1 and V0 ( < .01), followed by a decrease at V1, V2, and V3, in the VAR group ( < .01). Ochronotic pigment in ear biopsy between V0 and V4 showed a 19.1% decrease ( < .05).

Conclusions: Nitisinone decreases HGA and partially reverses ochronosis.
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http://dx.doi.org/10.1002/jmd2.12137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463057PMC
September 2020

Efficacy and safety of once-daily nitisinone for patients with alkaptonuria (SONIA 2): an international, multicentre, open-label, randomised controlled trial.

Lancet Diabetes Endocrinol 2020 09 18;8(9):762-772. Epub 2020 Aug 18.

Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

Background: Alkaptonuria is a rare, genetic, multisystem disease characterised by the accumulation of homogentisic acid (HGA). No HGA-lowering therapy has been approved to date. The aim of SONIA 2 was to investigate the efficacy and safety of once-daily nitisinone for reducing HGA excretion in patients with alkaptonuria and to evaluate whether nitisinone has a clinical benefit.

Methods: SONIA 2 was a 4-year, open-label, evaluator-blind, randomised, no treatment controlled, parallel-group study done at three sites in the UK, France, and Slovakia. Patients aged 25 years or older with confirmed alkaptonuria and any clinical disease manifestations were randomly assigned (1:1) to receive either oral nitisinone 10 mg daily or no treatment. Patients could not be masked to treatment due to colour changes in the urine, but the study was evaluator-blinded as far as possible. The primary endpoint was daily urinary HGA excretion (u-HGA) after 12 months. Clinical evaluation Alkaptonuria Severity Score Index (cAKUSSI) score was assessed at 12, 24, 36, and 48 months. Efficacy variables were analysed in all randomly assigned patients with a valid u-HGA measurement at baseline. Safety variables were analysed in all randomly assigned patients. The study was registered at ClinicalTrials.gov (NCT01916382).

Findings: Between May 7, 2014, and Feb 16, 2015, 139 patients were screened, of whom 138 were included in the study, with 69 patients randomly assigned to each group. 55 patients in the nitisinone group and 53 in the control group completed the study. u-HGA at 12 months was significantly decreased by 99·7% in the nitisinone group compared with the control group (adjusted geometric mean ratio of nitisinone/control 0·003 [95% CI 0·003 to 0·004], p<0·0001). At 48 months, the increase in cAKUSSI score from baseline was significantly lower in the nitisinone group compared with the control group (adjusted mean difference -8·6 points [-16·0 to -1·2], p=0·023). 400 adverse events occurred in 59 (86%) patients in the nitisinone group and 284 events occurred in 57 (83%) patients in the control group. No treatment-related deaths occurred.

Interpretation: Nitisinone 10 mg daily was well tolerated and effective in reducing urinary excretion of HGA. Nitisinone decreased ochronosis and improved clinical signs, indicating a slower disease progression.

Funding: European Commission Seventh Framework Programme.
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http://dx.doi.org/10.1016/S2213-8587(20)30228-XDOI Listing
September 2020

Upscaling Virtual Fracture Clinic Use Is a Safe, Effective Measure in the Delivery of Trauma Care.

J Orthop Trauma 2020 Sep;34(9):e349-e352

Department of Trauma and Orthopaedic Surgery, Midlands Regional Hospital Tullamore, Co. Offaly, Ireland; and.

The Virtual Fracture Clinic (VFC) has proved beneficial in reducing footfall within the hospital setting, improving the cost of running a trauma service, while satisfying the majority of referred patients. The mandatory upscaling of telemedicine use, specifically the enhancement of the VFC, amidst the COVID-19 pandemic, was analyzed. The remit of the VFC within our hospital was expanded so as to include all referred ambulatory trauma. Outcomes of our VFC review over the 6-week period following the introduction of the national Irish COVID-19-related restrictions were gathered. These outcomes were analyzed and compared with the corresponding 6-week period from 2019. A 77.2% increase in the VFC referral volume was observed throughout the COVID-19-related period. Patients were directly discharged in 55.2% of cases in 2020, as opposed to 47.8% in 2019 (P = 0.044); referred directly for physiotherapy in 32.9% of cases in 2020, as opposed to 28.9% in 2019 (P = 0.173); and referred to a fracture clinic in 11.9% of cases in 2020, as opposed to 23.7% in 2019 (P < 0.001). Also, 3.0% of patients returned to the clinic after discharge in 2020, compared with 4.4% in 2019 (P = 0.237); 4.5% of patients were referred for surgery in 2020, as opposed to 2.2% in 2019 (P = 0.105). The VFC proved to be an efficient tool in managing ambulatory trauma throughout the pandemic. Upscaling the VFC to include all ambulatory trauma is a safe, effective method in reducing clinic attendances and hospital footfall, whilst ensuring that high care standards are maintained. LEVEL OF EVIDENCE:: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.1097/BOT.0000000000001894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446992PMC
September 2020

Evaluation of drugs for potential repurposing against COVID-19 using a tier-based scoring system.

Antivir Ther 2020 Aug 3. Epub 2020 Aug 3.

Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.

Background: As the coronavirus disease 2019 (COVID-19) pandemic grows daily, we remain with no prophylactic and only minimal therapeutic interventions to prevent or ameliorate severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Prior to SARS-CoV-2 emergence, high throughput screens utilizing clinically developed drugs identified compounds with in vitro inhibitory effect on human coronaviruses that may have potential for repurposing as treatment options for COVID-19. However, caution should be applied to repurposing of these drugs when they are taken out of context of human pharmacokinetic parameters associated with normal therapeutic use.

Methods: Our aim was to provide a tier-based scoring system to interrogate this data set and match each drug with its human pharmacokinetic criteria, such as route of administration, therapeutic plasma levels and half-life, tissue distribution and safety.

Results: Our analysis excluded most previously identified drugs but identified members of four drug classes (antimalarial amino-quinolones, selective estrogen receptor modulators [SERMs], low potency tricyclic antipsychotics and tricyclic antidepressants) as potential drug candidates for COVID-19. Two of them, the tricyclic antipsychotics and tricyclic antidepressants were further excluded based on a high adverse event profile.

Conclusions: In summary, our findings using a new pharmacokinetic-based scoring system supports efficacy testing of only a minority of candidates against SARS-CoV-2 infection.
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http://dx.doi.org/10.3851/IMP3368DOI Listing
August 2020

Intraosseous schwannoma of the femur in a patient with monoclonal gammopathy of undetermined significance.

Int J Surg Case Rep 2020 13;72:494-498. Epub 2020 Jun 13.

Department of Trauma and Orthopaedics, Midland Regional Hospital Tullamore, Tullamore, Co. Offaly, Ireland.

Introduction: Schwannomas are slow-growing, benign tumours normally originating from the schwann cells of the nerve sheath. Intraosseous schwannomas account for 0.175% of primary bone tumours and are extremely rare, especially outside the axial skeleton. Monoclonal gammopathy has been associated with soft tissue schwannomas but never with the intraosseous variety.

Presentation Of Case: A 55-year-old woman with a background of monoclonal gammopathy of undetermined significance (MGUS) presented with a 2-year history of right thigh pain. CT scan showed a well defined, lytic lesion with a thin peripheral rim of sclerosis in the midshaft of the femur. MRI displayed a hyperintense, well marginated and homogenous lesion. Definitive diagnosis was made based on the classical histopathological appearance of schwannoma. We managed our patient with local curettage and prophylactic cephalomedullary nailing based on her high mirel score.

Discussion: Intraosseous schwannomas are poorly understood but most commonly reported in middle-aged women. Radiologically, their differential diagnosis includes malignant bone tumours, solitary bone cysts, aneurysmal bone cysts and giant cell tumours. As a result, they are usually diagnosed incidentally on histology. Although malignant transformation is possible in soft tissue schwannomas, all intraosseous schwannomas reported to date have been benign.

Conclusion: This case demonstrates the importance of suspecting intraosseous schwannoma as a differential diagnosis for lytic bone lesions to avoid the overtreatment of patients. We also highlight monoclonal gammopathy of undetermined significance as a potential risk factor for a poorly understood disease and make recommendations about the appropriate management of these lesions.
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http://dx.doi.org/10.1016/j.ijscr.2020.06.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322230PMC
June 2020

Risk Factors Associated with Antibiotic Treatment Failure of Buruli Ulcer.

Antimicrob Agents Chemother 2020 08 20;64(9). Epub 2020 Aug 20.

Barwon Health, University Hospital Geelong, Geelong, Australia.

Combination antibiotic therapy is highly effective in curing Buruli ulcer (BU) caused by Treatment failures have been uncommonly reported with the recommended 56 days of antibiotics, and little is known about risk factors for treatment failure. We analyzed treatment failures among BU patients treated with ≥56 days of antibiotics from a prospective observational cohort at Barwon Health, Victoria, from 1 January 1998 to 31 December 2018. Treatment failure was defined as culture-positive recurrence within 12 months of commencing antibiotics under the following conditions: (i) following failure to heal the initial lesion or (ii) a new lesion developing at the original or at a new site. A total of 430 patients received ≥56 days of antibiotic therapy, with a median duration of 56 days (interquartile range [IQR], 56 to 80). Seven (1.6%) patients experienced treatment failure. For six adult patients experiencing treatment failure, all were male, weighed >90 kg, did not have surgery, and received combination rifampin-clarithromycin (median rifampin dose, 5.6 mg per kg of body weight per day; median clarithromycin dose, 8.1 mg/kg/day). When compared to those who did not fail treatment on univariate analysis, treatment failure was significantly associated with a weight of >90 kg ( < 0.001), male gender ( = 0.02), immune suppression ( = 0.04), and a first-line regimen of rifampin-clarithromycin compared to a regimen of rifampin-fluoroquinolone ( = 0.05). There is a low rate of treatment failure in Australian BU patients treated with rifampin-based oral combination antibiotic therapy. Our study raises the possibility that treatment failure risk may be increased in males, those with a body weight of >90 kg, those with immune suppression, and those taking rifampin-clarithromycin antibiotic regimens, but future pharmacokinetic and pharmacodynamics studies are required to determine the validity of these hypotheses.
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http://dx.doi.org/10.1128/AAC.00722-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449191PMC
August 2020

Cardiac Magnetic Resonance Feature Tracking Global Longitudinal Strain and Prognosis After Heart Transplantation.

JACC Cardiovasc Imaging 2020 Sep 17;13(9):1934-1942. Epub 2020 Jun 17.

Section of Cardiology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.

Objectives: This study determined the long-term prognostic significance of GLS assessed using CMR-FT in a large cohort of heart transplant recipients.

Background: In heart transplant recipients, global longitudinal strain (GLS) assessed using echocardiography has shown promise in the prediction of clinical outcomes. We hypothesized that CMR feature tracking (CMR-FT) GLS is independently associated with long-term outcomes in heart transplant recipients.

Methods: In a cohort of consecutive heart transplant recipients who underwent routine CMR for clinical surveillance, CMR-FT GLS was calculated from 3 long-axis cine CMR images. Associations between GLS and a composite endpoint of death or major adverse cardiac events (MACE), including retransplantation, nonfatal myocardial infarction, coronary revascularization, and heart failure hospitalization, were investigated.

Results: A total of 152 heart transplant recipients (age 54 ± 15 years; 29% women; 5.0 ± 5.4 years after heart transplantation) were included. The median GLS was -11.6% (interquartile range: -13.6% to -9.2%). Over a median follow-up of 2.6 years, 59 recipients reached the composite endpoint. On Kaplan-Meier analyses, recipients with GLS worse than the median had a higher estimated cumulative incidence of the composite endpoint compared with recipients with GLS better than the median (log rank p = 0.004). On multivariate Cox proportional hazards regression, GLS was independently associated with the composite endpoint after adjustment for cardiac allograft vasculopathy, history of rejection, left ventricular ejection fraction (LVEF), right ventricular EF, and presence of myocardial fibrosis, with a hazard ratio of 1.15 for every 1% worsening in GLS (95% confidence interval: 1.06 to 1.24; p < 0.001). Similar results were seen in subgroups of recipients with LVEF >50% and with no myocardial fibrosis. GLS provided incremental prognostic value over other variables in the multivariate model as determined by the log-likelihood chi-squared test.

Conclusions: In a large cohort of heart transplant recipients, CMR-FT GLS was independently associated with the long-term risk of death or MACE.
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http://dx.doi.org/10.1016/j.jcmg.2020.04.004DOI Listing
September 2020

Thyroid hormone receptors mediate two distinct mechanisms of long-wavelength vision.

Proc Natl Acad Sci U S A 2020 06 15;117(26):15262-15269. Epub 2020 Jun 15.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;

Thyroid hormone (TH) signaling plays an important role in the regulation of long-wavelength vision in vertebrates. In the retina, () is required for expression of long-wavelength-sensitive opsin () in red cone photoreceptors, while in retinal pigment epithelium (RPE), TH regulates expression of a cytochrome P450 enzyme, , that converts vitamin A into vitamin A to produce a red-shifted chromophore. To better understand how TH controls these processes, we analyzed the phenotype of zebrafish with mutations in the three known TH nuclear receptor transcription factors (, , ). We found that no single TH nuclear receptor is required for TH-mediated induction of but that deletion of all three ( ) completely abrogates its induction and the resulting conversion of A- to A-based retinoids. In the retina, loss of resulted in an absence of red cones at both larval and adult stages without disruption of the underlying cone mosaic. RNA-sequencing analysis revealed significant down-regulation of only five genes in adult retina, of which three (, , and ) occur in a single syntenic cluster. In the retina, retinal progenitors destined to become red cones were transfated into ultraviolet (UV) cones and horizontal cells. Taken together, our findings demonstrate cooperative regulation of by TH receptors and a requirement for in red cone fate determination. Thus, TH signaling coordinately regulates both spectral sensitivity and sensory plasticity.
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http://dx.doi.org/10.1073/pnas.1920086117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334509PMC
June 2020

The nutritional status of people with alkaptonuria: An exploratory analysis suggests a protein/energy dilemma.

JIMD Rep 2020 May 17;53(1):45-60. Epub 2020 Mar 17.

Department of Clinical Biochemistry and Metabolic Medicine Liverpool Clinical Laboratories, Royal Liverpool University Hospital Liverpool UK.

Background: Alkaptonuria (AKU) is a disorder of tyrosine/protein metabolism leading to accumulation of homogentisic acid. Clinical management historically recommended reducing dietary protein intake, especially in childhood, which has since been discredited in the literature. For the first time, analysis of baseline cross-sectional nutritional surveillance data from a large cohort of AKU patients is presented, which has clinical implications in all aspects of treatment planning.

Method: Seventy-four patients (mean 55 years) admitted to the National Alkaptonuria Centre (NAC), underwent a global nutritional assessment, which included objective anthropometry, bioimpedance measures, habitual nutritional intake using a 7-day food diary and key nutritional biomarkers, including 24 hours urinary nitrogen, serum albumin, total protein and total 25-hydroxy vitamin D. All data was compared with cohort norms or recommended nutrient intakes for health (RNI). The potential beneficial impact of protein and anti-inflammatory nutrients such as vitamin C, selenium, and zinc were statistically interrogated against the AKU severity score index (AKUSSI)-a validated measure of disease progression stratified by age.

Results: Fifty percent of AKU patients reported some level of protein restriction at some point in their lives. In comparison with national data sets, AKU patients present with significantly lower than predicted mid-upper arm circumference, grip strength, BMI, total energy and protein intake, and higher than predicted percentage body fat. They therefore meet the ESPEN criteria as "clinically undernourished." Severity fluctuates over the life course. No statistical association is identified between protein intake, expressed as %RNI or g/kg, or anti-inflammatory nutrients, including vitamin C as a high dose supplement on the severity of the disease, when correlated against the validated AKUSSI score.

Conclusion: AKU patients are at risk of protein depletion associated with a "perfect storm" of risk factors: historical, poorly evidenced recommendations to reduce total protein intake; limited mobility as the condition progresses, compromising muscle integrity; frequent hospital admissions for major surgery associated with multiple joint replacements, creating pinch points of high metabolic demand and the potential impact of the disease itself. As this is the first time this risk has been identified, the authors consider the dietetic implications of nitisinone treatment, which requires dietary protein control to manage the acquired tyrosinaemia. The lack of statistically significant evidence to support dietary manipulation of any kind to impede disease progression in AKU is demonstrated.
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http://dx.doi.org/10.1002/jmd2.12084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203650PMC
May 2020

Do Equivalence Trials Display Superiority Over the Traditional Comparative Study Methods in Orthopedic Surgery?

Clin Spine Surg 2020 06;33(5):201-204

National Spinal Injuries Unit, Department of Trauma & Orthopaedic Surgery, Mater Misericordiae University Hospital.

Superiority and equivalence trials are 2 commonly encountered methods of designing randomized controlled trials. Traditionally, the goal of a randomized controlled trial is to show superiority. However, in more recent times, there has been a tendency to show equivalence in clinical randomized trials. These differing conclusions at first glance seem to be drawn on the basis of the results of the respective trials. However, to accurately reach these conclusions, there are stark contrasts in the methodologies of these different study types. This article provides a brief overview of superiority and equivalence trials, highlights the differences between the 2, and their relevance to orthopedic surgery.
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http://dx.doi.org/10.1097/BSD.0000000000000978DOI Listing
June 2020

Management of bile duct stones at cholecystectomy: an Australian single-centre experience over 2 years.

Surg Endosc 2021 Mar 9;35(3):1247-1253. Epub 2020 Mar 9.

Department of General Surgery, The Prince Charles Hospital, Chermside, QLD, Australia.

Background: Bile duct stones with an intact gallbladder can be treated with either bile duct exploration at cholecystectomy or endoscopic retrograde cholangiopancreatography (ERCP) before or after cholecystectomy. The aim of this study was to evaluate the management of bile duct stones at cholecystectomy at our institution. We also aimed to identify risk factors for failure of ductal clearance in our series.

Methods: A retrospective review of 690 laparoscopic cholecystectomies over a 2-year period was performed. Patients who underwent laparoscopic bile duct exploration formed the study population.

Results: Of 69 patients with suspected bile duct stones at cholecystectomy 67 (97%) patients underwent laparoscopic bile duct exploration upfront. Complete ductal clearance was achieved in 52 (78%) patients. Postoperative complications (10/67, 15%) included postoperative bleeding (2/67, 3%), bile leak (1/67, 1%), and superficial wound infection (1/67, 1%). There was no mortality. The mean operative time was 126 min and the median length of stay was 2 (1-4) days. A wider common bile duct (CBD) (≥ 8 mm) increased the risk of failed ductal clearance (OR 4.50; 95% confidence interval (CI) 1.15-19.23).

Conclusion: This study found that laparoscopic bile duct exploration can effectively and safely treat bile duct stones suspected at cholecystectomy.
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http://dx.doi.org/10.1007/s00464-020-07495-7DOI Listing
March 2021

Nitisinone causes acquired tyrosinosis in alkaptonuria.

J Inherit Metab Dis 2020 09 5;43(5):1014-1023. Epub 2020 Mar 5.

Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospitals Trust, Liverpool, UK.

For over two decades, nitisinone (NTBC) has been successfully used to manipulate the tyrosine degradation pathway and save the lives of many children with hereditary tyrosinaemia type 1. More recently, NTBC has been used to halt homogentisic acid accumulation in alkaptonuria (AKU) with evidence suggesting its efficacy as a disease modifying agent. NTBC-induced hypertyrosinaemia has been associated with cognitive impairment and potentially sight-threatening keratopathy. In the context of a non-lethal condition (ie, AKU), these serious risks call for an evaluation of the wider impact of NTBC on the tyrosine pathway. We hypothesised that NTBC increases the tyrosine pool size and concentrations in tissues. In AKU mice tyrosine concentrations of tissue homogenates were measured before and after treatment with NTBC. In humans, pulse injection with l-[ C ]tyrosine and l-[d ]phenylalanine was used along with compartmental modelling to estimate the size of tyrosine pools before and after treatment with NTBC. We found that NTBC increased tyrosine concentrations in murine tissues by five to nine folds. It also significantly increased the tyrosine pool size in humans (P < .001), suggesting that NTBC increases tyrosine not just in serum but also in tissues (ie, acquired tyrosinosis). This study provides, for the first time, the experimental proof for the magnitude of NTBC-related acquired tyrosinosis which should be overcome to ensure the safe use of NTBC in AKU.
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http://dx.doi.org/10.1002/jimd.12229DOI Listing
September 2020

Peer teacher training (PTT) in action.

Clin Teach 2020 10 20;17(5):531-537. Epub 2020 Feb 20.

University Hospitals of Leicester, Leicester, UK.

Background: The benefits of peer teaching for tutors, students and institutions are well documented. Skills in peer teaching, assessment and feedback are cited as important graduate attributes by international medical councils; however, the literature on preparation for this role, specifically peer teacher training (PTT), is sparse. This study evaluated the implementation of a PTT programme adopted from the Medical School at the University of Sydney in 2016. The programme was adopted to support the development of skills in UK medical undergraduates. The training was accessed by students studying at the University of Leicester in 2017 and 2018.

Methods: The course was evaluated using mixed methods. Students completed pre- and post-course self-rated questionnaires. Semi-structured focus groups were conducted after each course to investigate students' perceptions.

Results: Twenty fourth-year medical students attended the PTT. Students reported improvements in their understanding of educational principles, confidence in teaching and feedback skills, and an increased likelihood of volunteering to teach. Focus groups revealed potential benefits for future patient interaction and preparation for educator roles.

Discussion: The PTT provided an effective approach for medical students to gain perceived competence and confidence in teaching and giving feedback. Students reported an increased propensity for teaching when qualified. Students with lower self-reported teaching ability reported greater improvements following the course. Students reported unanticipated perceived benefits for improving patient education and obtaining teaching accreditation for their portfolio and future clinical roles. They perceived potential value if the training were to be made interprofessional on future courses. Furthermore, this study demonstrates the transferability of the PTT programme across university settings.
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http://dx.doi.org/10.1111/tct.13142DOI Listing
October 2020

Superior patient reported outcome measures reported post Articular Surface Replacement (ASR) revision arthroplasty in the setting of an objective surgical indication.

J Orthop 2020 Sep-Oct;21:31-34. Epub 2020 Feb 4.

Department of Trauma and Orthopaedic Surgery, Galway University Hospitals, Galway, Ireland.

The Articular Surface Replacement (ASR) hip system displayed unexpectedly high failure rates. All patients who underwent revision arthroplasty at our institution were identified. Indications for revision were classified as objectively identifiable or performed for unexplained pain. Clinical outcomes, post ASR revision, were superior in cases where the aetiology for failure was identifiable. Pain and function improved reliably when a targeted objective indication was identified pre-revision, but failed to do so in cases of unexplained pain. Surgeons familiar with the results of this study will be empowered to discuss expectations and realistic outcomes with their patients undergoing complex revision arthroplasty cases.
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http://dx.doi.org/10.1016/j.jor.2020.01.052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016020PMC
February 2020

Defining the exploitation patterns of groundwater heat pump systems.

Sci Total Environ 2020 Mar 3;710:136425. Epub 2020 Jan 3.

Geological Survey of Spain (IGME), C/Ríos Rosas 23, 28003 Madrid, Spain.

Shallow geothermal systems are the most efficient and clean technology for the air-conditioning of buildings and constitutes an emergent renewable energy resource in the worldwide market. Undisturbed systems are capable of efficiently exchanging heat with the subsurface and transferring it to human infrastructures, providing the basis for the successful decarbonisation of heating and cooling demands of cities. Unmanaged intensive use of groundwater for thermal purposes as a shallow geothermal energy (SGE) resource in urban environments threatens the resources' renewability and the systems' performance, due to the thermal interferences created by a biased energy demand throughout the year. The exploitation regimes of 27 groundwater heat pump systems from an alluvial aquifer were firstly examined using descriptive statistics. Linear relationships between abstraction and injection temperatures of the systems were assessed by calculating Pearson's r correlation coefficient, and used as an evidence of thermal interferences. Then, time series of flow rate, operation temperature and energy transfer were modelled by means of spectral analysis and sinusoidal regression methods, followed by the definition of the relative exploitation patterns. The exploitation regimes examined presented a clear cooling bias and a similar cyclicality. The amplitudes correlated with the different end-user's activities (e.g. medical centres) when high frequency cycles were observed, while climatization strategies (e.g. constant flow rates and modulation of injection temperatures) did so when low frequency cycles were detected. The time series models allowed defining the relative operational pattern of a system and the groups of systems following such patterns. The biases in exploitation regimes of groundwater heat pump systems existing in Mediterranean areas require correction measures to ensure a more balanced exploitation of the SGE resources. The definition of the characteristic exploitation pattern proposed could be applied to guide resource managers by identifying unbalanced systems, understanding existent exploitation strategies and proposing corrective alternative plans.
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http://dx.doi.org/10.1016/j.scitotenv.2019.136425DOI Listing
March 2020