Publications by authors named "Andrew Hill"

1,036 Publications

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Do Athlete and Coach Performance Perfectionism Predict Athlete Burnout?

Eur J Sport Sci 2021 Apr 12:1-33. Epub 2021 Apr 12.

York St John University, UK.

Research has illustrated that athlete perfectionism predicts athlete burnout. The present study sought to build on existing research in two ways. First, we provide the first test of the relationship between performance perfectionism and athlete burnout. That is, whether the degree to which athlete's expect their own or others' sport performances to be perfect, predicts burnout. Second, we broaden the examination of the perfectionism-burnout relationship to include coaches by testing the incremental predictive ability of perceptions of coach other-oriented performance perfectionism (the degree to which coaches were perceived to expect perfect performances from others). A sample of 190 competitive adult athletes ( age = 20.54) completed measures of their own performance perfectionism (self-oriented, socially prescribed, and other-oriented performance perfectionism), perceived coach other-oriented performance perfectionism, and burnout symptoms. Regression analyses indicated that both athlete self-oriented and socially prescribed performance perfectionism positively predicted athlete burnout. In addition, after controlling for all dimensions of athlete performance perfectionism, perceived coach other-oriented performance perfectionism positively predicted athlete burnout. The findings suggest that, in addition to their own perfectionism, when athletes perceive their coaches to be more perfectionistic towards others, they are more likely to experience burnout.
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http://dx.doi.org/10.1080/17461391.2021.1916080DOI Listing
April 2021

Effectiveness of Quality Improvement Processes, Interventions, and Structure in Trauma Systems in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis.

World J Surg 2021 Apr 9. Epub 2021 Apr 9.

Department of Surgery, The University of Auckland, Auckland, New Zealand.

Background: Trauma mortality in low- and middle-income countries (LMICs) remains high compared to high-income countries. Quality improvement processes, interventions, and structure are essential in the effort to decrease trauma mortality.

Methods: A systematic review and meta-analysis of interventional studies assessing quality improvement processes, interventions, and structure in developing country trauma systems was conducted from November 1989 to August 2020 according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included if they were conducted in an LMIC population according to World Bank Income Classification, occurred in a trauma setting, and measured the effect of implementation and its impact. The primary outcome was trauma mortality.

Results: Of 37,575 search results, 30 studies were included from 15 LMICs covering five WHO regions in a qualitative synthesis. Twenty-seven articles were included in a meta-analysis. Implementing a pre-hospital trauma system reduced overall trauma mortality by 45% (risk ratio (RR) 0.55, 95% CI 0.4 to 0.75). Training first responders resulted in an overall decrease in mortality (RR 0.47, 95% CI 0.28 to 0.78). In-hospital trauma training with certified courses resulted in a reduction of mortality (RR 0.71, 95% CI 0.62 to 0.78). Trauma audits and trauma protocols resulted in varying improvements in trauma mortality.

Conclusion: There is evidence that quality improvement processes, interventions, and structure can improve mortality in the trauma systems in LMICs.
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http://dx.doi.org/10.1007/s00268-021-06065-9DOI Listing
April 2021

membrane vesicles contain immunostimulatory DNA, RNA and peptidoglycan that activate innate immune receptors and induce autophagy.

J Extracell Vesicles 2021 Apr 1;10(6):e12080. Epub 2021 Apr 1.

Department of Physiology Anatomy and Microbiology La Trobe University Melbourne Victoria 3086 Australia.

Gram-positive bacteria ubiquitously produce membrane vesicles (MVs), and although they contribute to biological functions, our knowledge regarding their composition and immunogenicity remains limited. Here we examine the morphology, contents and immunostimulatory functions of MVs produced by three strains; a methicillin resistant clinical isolate, a methicillin sensitive clinical isolate and a laboratory-adapted strain. We observed differences in the number and morphology of MVs produced by each strain and showed that they contain microbe-associated molecular patterns (MAMPs) including protein, nucleic acids and peptidoglycan. Analysis of MV-derived RNA indicated the presence of small RNA (sRNA). Furthermore, we detected variability in the amount and composition of protein, nucleic acid and peptidoglycan cargo carried by MVs from each strain. MVs activated Toll-like receptor (TLR) 2, 7, 8, 9 and nucleotide-binding oligomerization domain containing protein 2 (NOD2) signalling and promoted cytokine and chemokine release by epithelial cells, thus identifying that MV-associated MAMPs including DNA, RNA and peptidoglycan are detected by pattern recognition receptors (PRRs). Moreover, MVs induced the formation of and colocalized with autophagosomes in epithelial cells, while inhibition of lysosomal acidification using bafilomycin A1 resulted in accumulation of autophagosomal puncta that colocalized with MVs, revealing the ability of the host to degrade MVs via autophagy. This study reveals the ability of DNA, RNA and peptidoglycan associated with MVs to activate PRRs in host epithelial cells, and their intracellular degradation via autophagy. These findings advance our understanding of the immunostimulatory roles of Gram-positive bacterial MVs in mediating pathogenesis, and their intracellular fate within the host.
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http://dx.doi.org/10.1002/jev2.12080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015888PMC
April 2021

State-level prevalence estimates of latent tuberculosis infection in the United States by medical risk factors, demographic characteristics and nativity.

PLoS One 2021 1;16(4):e0249012. Epub 2021 Apr 1.

Consortium to Assess Prevention Economics, Philip R Lee Institute for Health Policy Studies, University of California San Francisco, San Francisco, California, United States of America.

Introduction: Preventing tuberculosis (TB) disease requires treatment of latent TB infection (LTBI) as well as prevention of person-to-person transmission. We estimated the LTBI prevalence for the entire United States and for each state by medical risk factors, age, and race/ethnicity, both in the total population and stratified by nativity.

Methods: We created a mathematical model using all incident TB disease cases during 2013-2017 reported to the National Tuberculosis Surveillance System that were classified using genotype-based methods or imputation as not attributed to recent TB transmission. Using the annual average number of TB cases among US-born and non-US-born persons by medical risk factor, age group, and race/ethnicity, we applied population-specific reactivation rates (and corresponding 95% confidence intervals [CI]) to back-calculate the estimated prevalence of untreated LTBI in each population for the United States and for each of the 50 states and the District of Columbia in 2015.

Results: We estimated that 2.7% (CI: 2.6%-2.8%) of the U.S. population, or 8.6 (CI: 8.3-8.8) million people, were living with LTBI in 2015. Estimated LTBI prevalence among US-born persons was 1.0% (CI: 1.0%-1.1%) and among non-US-born persons was 13.9% (CI: 13.5%-14.3%). Among US-born persons, the highest LTBI prevalence was in persons aged ≥65 years (2.1%) and in persons of non-Hispanic Black race/ethnicity (3.1%). Among non-US-born persons, the highest LTBI prevalence was estimated in persons aged 45-64 years (16.3%) and persons of Asian and other racial/ethnic groups (19.1%).

Conclusions: Our estimations of the prevalence of LTBI by medical risk factors and demographic characteristics for each state could facilitate planning for testing and treatment interventions to eliminate TB in the United States. Our back-calculation method feasibly estimates untreated LTBI prevalence and can be updated using future TB disease case counts at the state or national level.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249012PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016318PMC
April 2021

Distribution of microRNA profiles in pre-clinical and clinical forms of murine and human prion disease.

Commun Biol 2021 Mar 25;4(1):411. Epub 2021 Mar 25.

Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.

Prion diseases are distinguished by long pre-clinical incubation periods during which prions actively propagate in the brain and cause neurodegeneration. In the pre-clinical stage, we hypothesize that upon prion infection, transcriptional changes occur that can lead to early neurodegeneration. A longitudinal analysis of miRNAs in pre-clinical and clinical forms of murine prion disease demonstrated dynamic expression changes during disease progression in the affected thalamus region and serum. Serum samples at each timepoint were collected whereby extracellular vesicles (EVs) were isolated and used to identify blood-based biomarkers reflective of pathology in the brain. Differentially expressed EV miRNAs were validated in human clinical samples from patients with human sporadic Creutzfeldt-Jakob disease (sCJD), with the molecular subtype at codon 129 either methionine-methionine (MM, n = 14) or valine-valine (VV, n = 12) compared to controls (n = 20). EV miRNA biomarkers associated with prion infection predicted sCJD with an AUC of 0.800 (85% sensitivity and 66.7% specificity) in a second independent validation cohort (n = 26) of sCJD and control patients with MM or VV subtype. This study discovered clinically relevant miRNAs that benefit diagnostic development to detect prion-related diseases and therapeutic development to inhibit prion infectivity.
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http://dx.doi.org/10.1038/s42003-021-01868-xDOI Listing
March 2021

Taking a local government perspective for economic evaluation of a population-level programme to promote exercise.

Health Policy 2021 Mar 4. Epub 2021 Mar 4.

Centre for Health Economics, University of York, YO105DD Heslington, UK.

Background: In order to tackle the issue of physical inactivity, local governments have implemented population-level programmes to promote exercise. While evidence is accumulating on the cost-effectiveness of these interventions, studies have typically adopted a health sector perspective for economic evaluation. This approach has been challenged as it does not allow for key concerns by local governments, which are primary stakeholders, to be addressed.

Objectives: To show how taking a local government perspective for economic evaluation can be implemented in practice and this may affect the economic conclusions.

Methods: Based on data from a case study, the health equity impact of the intervention and its opportunity cost from a service provider viewpoint were assessed. The cost-effectiveness implications of a change in perspective were subsequently estimated by means of scenario analysis.

Findings: The intervention was found to provide adult residents living in the most deprived city areas with greater health benefits compared with the rest of the population. However, a negative net equity impact was found in the short-term. The opportunity cost of the intervention was estimated to be substantially lower than its financial cost (£2.77 per person/year), with significant implications for decision-making.

Conclusions: Taking a local government perspective can affect the conclusions drawn from the economic evaluation of population-level programmes to promote exercise, and therefore influence decision making.
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http://dx.doi.org/10.1016/j.healthpol.2021.02.012DOI Listing
March 2021

Enhanced recovery after surgery: tips and tricks for success.

Authors:
Andrew G Hill

ANZ J Surg 2021 03;91(3):228-229

Department of Surgery, University of Auckland, Middlemore Hospital, Auckland, New Zealand.

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http://dx.doi.org/10.1111/ans.16533DOI Listing
March 2021

NEXUS Arch: A Multicenter Study Evaluating the Initial Experience with a Novel Aortic Arch Stent Graft System.

Ann Surg 2021 Mar 4. Epub 2021 Mar 4.

Heart Institute, Hadassah - Hebrew University Medical Center, Jerusalem, Israel Ospedale San Camillo-Forlanini, Roma, Italy Ospedale San Filippo Neri, Roma, Italy Peter Munk Cardiac Centre Toronto General Hospital, Toronto, Canada Department of Cardiac, Thoracic, Vascular Sciences and Public health, University of Padua, Italy Universitätsklinik für Gefäß- und Endovaskularchirurgie, Düsseldorf, Germany Aortic and Vascular Center, Clinic Hirslanden, Zürich, Switzerland Clinic for cardiac and vascular surgery, university hospital Zürich, Zürich, Switzerland Auckland Hospital, Auckland, New Zealand Endospan Ltd., Herzlia, Israel University of Palermo, Vascular Surgery Unit, AOUP "P. Giaccone", Palermo, Italy.

Objective: To assess the initial clinical experience with a novel endograft system (NEXUS Aortic Arch Stent Graft System) designed to treat aortic arch pathologies and address the morphology and hemodynamic challenges of the aortic arch.

Summary Background Data: The aortic arch remains the most challenging part of the aorta for both open and endovascular repair. Transcatheter aortic arch repair has the potential to significantly reduce surgical risks.

Methods: Patients underwent transcatheter aortic arch repair with a single branch, two stent graft system, implanted over a through-and-through guidewire from the brachiocephalic trunk, to the descending aorta with an ascending aorta stent graft. The ascending aorta stent graft is deployed into a designated docking sleeve to connect the two stent grafts and isolate the aortic arch pathology. Proximal landing zone in all cases was in Zone 0. Anatomical inclusion criteria included adequate landing zone in the ascending aorta, brachiocephalic trunk and descending thoracic aorta. Preparatory debranching procedure was performed in all patients with carotid - carotid crossover bypass and left carotid to left subclavian bypass, or parallel graft from descending aorta to left subclavian artery. Safety and performance were evaluated through one year. Survival analysis used the Kaplan-Meier method.

Results: Twenty-eight patients, 79% males, with a mean age of 72.2 ± 6.2 years were treated with 100% procedural success. Isolated aortic arch aneurysm was the principle pathology in 17 (60.7%) of patients while chronic aortic dissection was the principle pathology in 6 (21.4%) of patients. The remaining 5(17.8%) had combined or other pathologies. At one month, the vascular pathology was excluded in 25 of 26 alive patients (96.1%). The 30 days mortality rate was 7.1%, stroke rate was 3.6% (all non-disabling) and combined mortality/stroke rate was 10.7%. One year mortality was 10.7%, without device or aneurysm related death. Two patients (7.1%) reported stroke or transient ischemic attack at one year that recovered completely. One year combined mortality/stroke rate was 17.8%. There were three patients (10.7%) that had device related unplanned reinterventions through one year.

Conclusions: The NEXUS Aortic Arch Stent Graft System, a novel single branch, two stent graft system used for endovascular aortic arch repair that requires landing in the ascending aorta, demonstrates a high success rate with excellent one year safety and performance.
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http://dx.doi.org/10.1097/SLA.0000000000004843DOI Listing
March 2021

Self-Reported Engagement in Care among U.S. Residents with Latent Tuberculosis Infection - 2011-2012.

Ann Am Thorac Soc 2021 Mar 8. Epub 2021 Mar 8.

Centers for Disease Control and Prevention, 1242, Atlanta, Georgia, United States.

Rationale: A central strategy of tuberculosis (TB) control in the United States is reducing the burden of latent TB infection (LTBI) through targeted testing and treatment of persons with untreated LTBI.

Objectives: The objective of the study was to provide estimates of and risk factors for engagement in LTBI care in the overall U.S. population and among specific risk groups.

Methods: We used nationally representative data from 7,080 participants in the 2011-2012 National Health and Nutrition Examination Survey. Engagement in LTBI care was assessed by estimating the proportion with a history of testing, diagnosis, treatment initiation and treatment completion. Weighted methods were used to account for the complex survey design and to derive national estimates.

Results: Only 1.4 million (10%) of an estimated 14.0 million individuals with LTBI had previously completed treatment. Of the 12.6 million who did not complete LTBI treatment, 3.7 million (29%) had never been tested and 7.2 million (57%) received testing but had no history of diagnosis. High-risk groups showed low levels of engagement, including TB contacts and persons born outside the United States.

Conclusions: There is a reservoir of more than 12 million individuals in the U.S. who may be at risk for progression to TB disease and potential transmission. TB control programs and community providers should consider focused efforts to increase testing, diagnosis, and treatment for LTBI.
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http://dx.doi.org/10.1513/AnnalsATS.202009-1153OCDOI Listing
March 2021

Delayed presentation of an iatrogenic, traumatic brachio-brachial fistula.

Trauma Case Rep 2021 Apr 18;32:100438. Epub 2021 Feb 18.

Vascular Department, Auckland City Hospital, ADHB, New Zealand.

Iatrogenic arteriovenous fistulae are rare occurrences after venepuncture, line placement or trauma. Presentations and symptoms can vary but they are usually identified soon after the causative injury due to the development of a visible, palpable, and pulsatile lump that can be concerning for patients. We describe the presentation and management of an unusual case of delayed presentation of an iatrogenic, traumatic brachio-brachial fistula.
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http://dx.doi.org/10.1016/j.tcr.2021.100438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907532PMC
April 2021

A human factors approach to subcutaneous insulin chart design improves user-performance: An experimental study.

Appl Ergon 2021 Feb 26;94:103389. Epub 2021 Feb 26.

Clinical Skills Development Service, Metro North Hospital and Health Service, Herston, Brisbane, Queensland, 4006, Australia; School of Psychology, The University of Queensland, St Lucia, Brisbane, Queensland, 4072, Australia; School of Medicine, The University of Queensland, Herston, Brisbane, Queensland, 4006, Australia.

Insulin is a high-risk medicine that has been implicated in serious adverse events for hospital inpatients, including medication-error related deaths. Most insulin errors occur during administration, and "wrong dose" is the most common type. A paper-based subcutaneous insulin chart (the "NSIC") was developed for the Australian Commission on Safety and Quality in Health Care, using a range of human factors methods, with the aim of reducing the opportunity for errors. The present lab-based study empirically assessed whether the NSIC's human factors design translates into improved user-performance in the determination of insulin doses, compared with a pre-existing chart. Forty-one experienced nurses and 48 novice chart-users completed 60 experimental trials (30 per chart), in which they determined doses to administer to patients. Both groups determined insulin doses faster, and made fewer dose errors, when using the NSIC. These results support the utility of the usability heuristics employed in developing the chart.
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http://dx.doi.org/10.1016/j.apergo.2021.103389DOI Listing
February 2021

Fluoroscopically Guided Facet Cyst Rupture: Rate of Conversion to Surgery and Risk Factor Analysis.

Clin Spine Surg 2021 Feb 24. Epub 2021 Feb 24.

Departments of Orthopaedic Surgery Radiology, University of Virginia, Charlottesville, VA.

Study Design: Retrospective case series at a single academic medical center.

Objective: The aim was to determine if specific clinical, radiologic, and procedural factors are associated with conversion to surgery after fluoroscopically guided cyst rupture.

Summary Of Background Data: Percutaneous fluoroscopic rupture of facet cysts can often be the definitive treatment; however, it is unknown before the procedure who will ultimately proceed to formal surgical decompression. Differences in clinical, radiographic, and procedural factors of facet cysts may relate to the difference in efficacy of fluoroscopically guided cyst rupture.

Methods: A continuous cohort of 45 patients who underwent fluoroscopically guided cyst rupture was evaluated. The primary outcome measured rate of conversion to surgery and of those that underwent surgery, the rate of decompression and fusion compared with fusion alone was noted. Secondary outcomes included analysis of clinical, radiologic, and procedural variables to determine if there were risk factors associated with conversion to surgery.

Results: Twenty-nine percent of patients eventually underwent a surgical procedure with an average interval to surgery of 95 days after attempted rupture. Thirty-eight percent of patients that underwent surgery had a decompression and fusion. Failure of percutaneous cyst rupture trended toward significance for a future surgical decompression (P=0.08).

Conclusions: Percutaneous facet cyst rupture is potentially a definitive treatment for this condition; however, it is unknown ahead of time who will proceed to definitive surgical decompression. On the basis of the data in this study, less than one-third of patients who had a fluoroscopically guided facet cyst rupture went on to surgery. There were no clinical, radiographic, or procedural details which could be used to robustly predict failure of percutaneous treatment. At this time, it is recommended to continue to attempt this nonoperative treatment intervention when there is a clinical indication after discussion of the risks and benefits with the patient.
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http://dx.doi.org/10.1097/BSD.0000000000001146DOI Listing
February 2021

Coronary healing patterns following stenting in patients with diabetes as assessed by optical coherence tomography.

Cardiovasc Revasc Med 2021 Feb 23. Epub 2021 Feb 23.

Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, USA. Electronic address:

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http://dx.doi.org/10.1016/j.carrev.2021.02.012DOI Listing
February 2021

Intravenous Local Anesthetic Compared with Intraperitoneal Local Anesthetic in Laparoscopic Colectomy: A Double-Blind Randomized Controlled Trial.

Ann Surg 2021 Jan 15. Epub 2021 Jan 15.

*Department of Surgery, South Auckland Clinical Campus, The University of Auckland, Auckland, New Zealand †Department of Anesthesia and Pain Medicine, Middlemore Hospital, Auckland, New Zealand ‡Department of Surgery, Middlemore Hospital, Auckland, New Zealand §School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.

Introduction: Controlling perioperative pain is essential to improving patient experience and satisfaction following surgery. Traditionally opioids have been frequently utilised for postoperative analgesia. Although they are effective at controlling pain, they are associated with adverse effects, including postoperative nausea, vomiting, ileus and long-term opioid dependency.Following laparoscopic colectomy, the use of intravenous or intraperitoneal infusions of lidocaine (IVL, IPL) are promising emerging analgesic options. Although both techniques are promising, there have been no direct, prospective randomized comparisons in patients undergoing laparoscopic colon resection. The purpose of this study was to compare IPL with IVL.

Methods: Double blinded, randomized controlled trial of patients undergoing laparoscopic colonic resection. The two groups received equal doses of either IPL or IVL which commenced intra-operatively with a bolus followed by a continuous infusion for 3 days postoperatively. Patients were cared for through a standardized ERAS program. The primary outcome was total post-operative opioid consumption over the first three post-operative days. Patients were followed for 60 days.

Results: Fifty-six patients were randomized in a 1:1 fashion to the IVL or IPL groups. Total opioid consumption over the first three post-operative days was significantly lower in the IPL group (70.9 mg vs 157.8 mg p < 0.05) and overall opioid consumption during the total length of stay was also significantly lower (80.3 mg vs 187.36 mg p < 0.05. Pain scores were significantly lower at two hours post-operatively in the IPL group, however, all other time points were not significant. There were no differences in complications between the two groups.

Conclusion: Perioperative use of IPL results in a significant reduction in opioid consumption following laparoscopic colon surgery when compared to IVL. This suggests that the peritoneal cavity/compartment is a strategic target for local anesthetic administration. Future ERAS recommendations should consider IPL as an important component of a multimodal pain strategy following colectomy.
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http://dx.doi.org/10.1097/SLA.0000000000004758DOI Listing
January 2021

Risks of metabolic syndrome and diabetes with integrase inhibitor-based therapy: Republication.

Curr Opin HIV AIDS 2021 Mar;16(2):106-114

Department of Translational Medicine, Liverpool University, Pharmacology, Liverpool, UK.

Purpose Of Review: A growing body of evidence suggests that integrase inhibitors (INSTIs) are significantly associated with weight gain and obesity. Obesity is a significant risk factor for metabolic syndrome and diabetes. This article comprehensively reviews recent available evidence weight gain and the risks of metabolic syndrome and diabetes associated with INSTIs.

Recent Findings: Recent evidence continues to contribute to the evidence for weight gain associated with INSTIs, especially when used with newer nucleoside reverse transcriptase inhibitor, tenofovir alafenamide (TAF). Although the literature suggests a neutral effect on lipids, there is evidence that INSTIs are associated with metabolic syndrome due to treatment-emergent obesity. The literature for short-term treatment-emergent diabetes and insulin resistance remains inconsistent, but there is some evidence that weight gain could lead to an increased risk of developing diabetes in the future.

Summary: Longer term studies are required to understand the metabolic impact of INSTIs, secondary to weight gain. Evidence suggests that INSTIs, when used with TAF, contribute to metabolic syndrome and may have long-term risks of diabetes. INSTIs, when used with tenofovir disoproxil fumarate, have fewer metabolic implications. Clinicians must monitor for weight gain and metabolic effects, especially in those with underlying risk factors.
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http://dx.doi.org/10.1097/COH.0000000000000671DOI Listing
March 2021

Efficacy, safety and central nervous system effects after switch from efavirenz/tenofovir/emtricitabine to doravirine/tenofovir/lamivudine.

AIDS 2021 04;35(5):759-767

Merck & Co., Inc., Kenilworth, New Jersey, USA.

Objective: Doravirine is an alternative treatment option for individuals who do not tolerate efavirenz. We assessed efficacy, safety, and CNS effects in adults with HIV-1 and CNS complaints who switched from an efavirenz-based regimen to a doravirine-based regimen.

Design: Multicenter, double-blind, randomized trial (NCT02652260).

Methods: Virologically suppressed adults receiving efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF), or its components, with ongoing EFV-associated CNS toxicity grade 2 or higher (DAIDS criteria) were switched to doravirine/lamivudine/tenofovir (DOR/3TC/TDF) on day 1 (Immediate Switch Group [ISG]) or after 12 weeks (Deferred Switch Group [DSG]). CNS toxicity data were collected by self-administered questionnaire. The primary endpoint was the proportion of participants with any grade 2 or higher CNS toxicity at week 12. Secondary endpoints included virologic response and effect on fasting lipids.

Results: Eighty-six participants (58% men, 56% black, median age 41 years, median 4 years on prior EFV regimen) were enrolled (43 ISG, 43 DSG) and included in the analyses. At week 12, 42% of ISG and 37% of DSG had at least 1 grade 2 or higher CNS toxicity [difference 4.7%, 95% CI (-16 to 25%); P = 0.33]. At 24 weeks postswitch, HIV-1 RNA less than 50 copies/ml was maintained in 95.3% of participants, and fasting lipids were significantly decreased (LDL-cholesterol -11.0, non-HDL-cholesterol -13.2, HDL-cholesterol -7.7, total cholesterol -20.9, and triglycerides -13.0 mg/dl).

Conclusion: In participants who had CNS complaints while receiving EFV/FTC/TDF, improvement in CNS toxicities attributable to EFV was not significantly different after switching to DOR/3TC/TDF compared with remaining on EFV/FTC/TDF. Virologic efficacy was maintained and lipid profiles improved after switching to DOR/3TC/TDF.
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http://dx.doi.org/10.1097/QAD.0000000000002804DOI Listing
April 2021

Potential approaches for the pricing of cancer medicines across Europe to enhance the sustainability of healthcare systems and the implications.

Expert Rev Pharmacoecon Outcomes Res 2021 Mar 11:1-14. Epub 2021 Mar 11.

Health Data Science, Institute of Population Health Liverpool Reviews and Implementation Group, Whelan Building, University of Liverpool, Liverpool, UK.

: There are growing concerns among European health authorities regarding increasing prices for new cancer medicines, prices not necessarily linked to health gain and the implications for the sustainability of their healthcare systems.: Narrative discussion principally among payers and their advisers regarding potential approaches to the pricing of new cancer medicines.: A number of potential pricing approaches are discussed including minimum effectiveness levels for new cancer medicines, managed entry agreements, multicriteria decision analyses (MCDAs), differential/tiered pricing, fair pricing models, amortization models as well as de-linkage models. We are likely to see a growth in alternative pricing deliberations in view of ongoing challenges. These include the considerable number of new oncology medicines in development including new gene therapies, new oncology medicines being launched with uncertainty regarding their value, and continued high prices coupled with the extent of confidential discounts for reimbursement. However, balanced against the need for new cancer medicines. This will lead to greater scrutiny over the prices of patent oncology medicines as more standard medicines lose their patent, calls for greater transparency as well as new models including amortization models. We will be monitoring these developments.
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http://dx.doi.org/10.1080/14737167.2021.1884546DOI Listing
March 2021

Atrial Fibrillation and Stroke.

Card Electrophysiol Clin 2021 03;13(1):243-255

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Thomas Drive, Liverpool L14 3PE, UK; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Sondra Skovvej, 15, Aalborg 9000, Denmark. Electronic address:

Atrial fibrillation (AF) is the most common cardiac arrythmia and a major cause of stroke, heart failure, sudden death, and cardiovascular morbidity. AF increases risk of thromboembolic stroke via stasis in the left atrium and subsequent embolization to the brain. In patients with acute ischemic stroke, it is essential that clinicians undertake careful investigation to search for AF. In these patients, up to 23.7% eventually are found to have underlying AF. Oral anticoagulation is effective in prevention of strokes secondary to AF, reducing overall stroke numbers by approximately 64%. Left atrial appendage occlusion is promising for prevention of stroke in AF.
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http://dx.doi.org/10.1016/j.ccep.2020.11.003DOI Listing
March 2021

New Zealand and Australia emergency laparotomy mortality rates compare favourably to international outcomes: a systematic review.

ANZ J Surg 2021 Jan 28. Epub 2021 Jan 28.

Department of Surgery, University of Otago, Christchurch Hospital, Christchurch, New Zealand.

Background: Almost 20 000 people undergo an emergency laparotomy each year in New Zealand and Australia. Common indications include small and large bowel obstruction, and intestinal perforation. Considered a high-risk procedure, emergency laparotomy is associated with significantly high morbidity and mortality. The aim of this review was to identify and compare 30-day, 90-day and 1-year mortality rates following emergency laparotomy in New Zealand and Australia.

Methods: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Electronic searches were performed in Medline, Embase, PubMed and Scopus in April 2020.

Results: Thirty-three papers met the inclusion criteria. Studies ranged in size from 58 to 75 280 patients. Weighted mean 30-day mortality was 8.40% (8.39-8.41). Mortality rates increased with longer postoperative follow up with 90-day weighted mortality rate of 14.14% (14.13-14.15) and the weighted mortality rate at 1 year of 24.60% (24.56-24.66). There was significant variability in mortality rates between countries.

Conclusion: There is a wide variability of 30-day, 90-day and 1-year mortality rates internationally. Lowering postoperative mortality rates following emergency laparotomy through quality improvement initiatives could result in up to 120 lives in New Zealand and over 250 lives in Australia being saved each year. The continued work of the Australian and New Zealand Emergency Laparotomy Audit - Quality Improvement is crucial to improving emergency laparotomy mortality rates further in New Zealand and Australia.
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http://dx.doi.org/10.1111/ans.16563DOI Listing
January 2021

A thousand years of crash experience in three hours: An online hazard perception training course for drivers.

Accid Anal Prev 2021 Mar 23;152:105969. Epub 2021 Jan 23.

School of Psychology, The University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia.

A key goal of driver training is to teach drivers to avoid crashes. However, in traditional driver training, drivers are unlikely to see even a single example of the class of event that we want them to learn to avoid. We developed a six-session automated online hazard perception training course for drivers, which incorporates a range of evidence-based strategies and employs extensive video footage of real crashes. We evaluated this course in a randomized control trial by examining its effects on previously-validated computer-based measures of hazard perception, hazard prediction, speed choice, following distance, and gap acceptance propensity, as well as self-rated measures of driver skill, safety, and real world transfer. We found that the course resulted in significant improvements in hazard perception response time and hazard prediction scores, and significantly longer vehicle following distances. Additionally, all participants in the trained group reported that their real world driving behaviour had improved. No significant training effects were found for the other measures. The results suggest that the course can improve key behaviours associated with crash risk.
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http://dx.doi.org/10.1016/j.aap.2020.105969DOI Listing
March 2021

Patient Experiences of the Emergency Laparotomy Pathway: A Qualitative Study.

World J Surg 2021 May 21;45(5):1362-1369. Epub 2021 Jan 21.

Department of Surgery, South Auckland Clinical Campus, Middlemore Hospital, University of Auckland, Private Bag 93311, Otahuhu, Auckland, New Zealand.

Introduction: Emergency laparotomy (EL) is a commonly performed operation with high rates of morbidity and mortality. Despite a growing body of literature on outcomes from EL, there is sparse literature on the patient experience. The aim of this study is to capture the perspective of patients on their EL experience. Qualitative methodology is used as a platform to allow patients to express their personal experiences and ideas around the EL process.

Materials And Method: Participants were consented as a part of a large observational study, established across the three public teaching hospitals in Auckland, New Zealand. Patients who had an EL within the past 4 months were recruited. A recorded interview was conducted either face-to-face or over the telephone, using questions formulated from a previous systematic review on EL outcomes. Transcripts were transported to NVivo and thematically analysed by two reviewers.

Results: Fifteen participants were interviewed. The majority of participants were female, New Zealand European and 65 or older. Five important themes were identified. Overall, participants expressed satisfaction with their interactions with hospital staff. However, they wanted more information about their condition, operation and what outcomes might occur. Participants also described post-operative priorities in the acute setting, as well as long-standing physical and emotional impacts.

Conclusion: This study provides a better understanding of what is important to patients during the EL process. This information is important when considering ways to improve care and communication with patients undergoing EL.
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http://dx.doi.org/10.1007/s00268-020-05936-xDOI Listing
May 2021

Copula Models for Addressing Sample Selection in the Evaluation of Public Health Programmes: An Application to the Leeds Let's Get Active Study.

Appl Health Econ Health Policy 2021 Jan 11. Epub 2021 Jan 11.

Department of Applied Health Research, University College London, London, UK.

Sample selectivity is a recurrent problem in public health programmes and poses serious challenges to their evaluation. Traditional approaches to handle sample selection tend to rely on restrictive assumptions. The aim of this paper is to illustrate a copula-based selection model to handle sample selection in the evaluation of public health programmes. Motivated by a public health programme to promote physical activity in Leeds (England), we describe the assumptions underlying the copula selection, and its relative advantages compared with commonly used approaches to handle sample selection, such as inverse probability weighting and Heckman's selection model. We illustrate the methods in the Leeds Let's Get Active programme and show the implications of method choice for estimating the effect on individual's physical activity. The programme was associated with increased physical activity overall, but the magnitude of its effect differed according to adjustment method. The copula selection model led to a similar effect to the Heckman's approach but with relatively narrower 95% confidence intervals. These results remained relatively similar when different model specifications and alternative distributional assumptions were considered. The copula selection model can address important limitations of traditional approaches to address sample selection, such as the Heckman model, and should be considered in the evaluation of public health programmes, where sample selection is likely to be present.
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http://dx.doi.org/10.1007/s40258-020-00629-xDOI Listing
January 2021

Are New Antiretroviral Treatments Increasing the Risk of Weight Gain?

Drugs 2021 Feb;81(3):299-315

Department of Translational Medicine, Liverpool University, Pharmacology, Liverpool, UK.

There is a growing body of evidence from both observational and randomised trials implicating integrase inhibitors, particularly dolutegravir and bictegravir, with the development of weight gain and obesity in people living with HIV. Evidence with cabotegravir, the newest integrase inhibitor, is limited. Reasons for weight gain are currently unknown. Proposed mechanisms include improved tolerability, direct impact on adipogenesis, and gut microbiome disturbance. Clinical trials have found that weight gain with integrase inhibitors is greatest for women and people of Black ethnicity. Evidence suggests that the nucleoside reverse transcriptase backbone has additional effects on weight gain, with tenofovir alafenamide potentially enhancing the weight gain effect. Weight gain and obesity have long-term consequences, including metabolic syndrome, development of type 2 diabetes mellitus, cardiovascular disease and adverse birth outcomes. However, the current evidence for the medium and long-term effects of weight gain associated with integrase inhibitors is limited. There is an urgent need for clinical trials with longer follow-up periods and standardised endpoints to evaluate these effects. New thresholds for weight gain should be established as guidance for clinicians to stop treatment where weight gain is excessive. Novel treatments such as doravirine could offer a suitable therapy alternative, with current evidence showing efficacy with limited effect on weight gain.
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http://dx.doi.org/10.1007/s40265-020-01457-yDOI Listing
February 2021

Pilonidal sinus: is histological examination necessary?

ANZ J Surg 2020 Dec 28. Epub 2020 Dec 28.

Department of Surgery, Middlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand.

Background: Pilonidal sinus is a common pathology occurring in a number of sites including the gluteal cleft between the buttocks. Surgery is the principal mode of treatment with a variety of techniques proposed to cure the disease and prevent recurrence. The rate of malignant degeneration is estimated at 0.1% in patients with chronic pilonidal disease. A case series study of pilonidal sinus found that most patients with malignancy were over the age of 50 years and had had chronic pilonidal disease for several years. This study aimed to review the value of histological analysis of pilonidal sinus specimens.

Methods: A retrospective observational study was conducted of all patients who have undergone pilonidal sinus excision by the Department of General Surgery at Counties Manukau District Health Board in the past 10 years.

Results: This study reviewed 1324 admissions with a pilonidal disease requiring surgical management. There were 325 pilonidal resections with 320 histological specimens analysed. Pilonidal sinus was detected in 312 specimens, eight others were benign and there were no specimens with malignancy.

Conclusion: No cases of malignancy were found in all pilonidal specimens that were sent for histological review. Routine histological examination of pilonidal sinus specimens appears to be unnecessary; however, it should be considered in patients over the age of 50 years.
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http://dx.doi.org/10.1111/ans.16446DOI Listing
December 2020

Safety and feasibility report on nonimplantable endovenous valve formation for the treatment of deep vein reflux.

J Vasc Surg Venous Lymphat Disord 2021 Jan 19. Epub 2021 Jan 19.

Department of Surgery, Prince of Wales Hospital and Faculty of Medicine, University of New South Wales, Sydney, Australia. Electronic address:

Objective: Definitive treatment techniques for symptomatic deep venous reflux have been relegated to complex and invasive open surgery which is rarely performed today. The BlueLeaf System provides an endovenous method for the formation of deep venous valves without an implant, avoiding the complications associated with permanent foreign materials. The system has the adaptability to form valves within the femoral and popliteal veins at multiple levels in a single procedure. The aim was to determine the midterm safety and efficacy of this novel device in an early feasibility study.

Methods: Feasibility of endovenous deep venous valve formation was assessed in patients with chronic venous insufficiency (Clinical, Etiologic, Anatomic, Pathophysiologic [CEAP] 4-6). Follow-up was completed through 1 year, assessing vein patency and reflux time (RT) with duplex ultrasound examination. Venous clinical improvement was evaluated using the revised Venous Clinical Severity Scale.

Results: Of the 14 patients, 13 (93%) had successful formation of at least one monocuspid valve, with a mean number of 1.4 valves (range, 0-3 valves) per patient. There were no device-related serious adverse events during the index procedure. There were no deep venous thromboses reported at any time point, including 10 patients through the 1-year follow-up. In patients with at least one valve formed, site reported duplex ultrasound examination measured the average RT in the popliteal vein below valve formations, was 3.0 ± 1.0 seconds at baseline, 3.9 ± 3.1 seconds at 30 days, and 3.6 ± 2.1 seconds at 360 days. The revised Venous Clinical Severity Scale improved in all 13 successfully treated patients, decreasing from 15.0 ± 6.0 at baseline to 11.6 ± 5.5 at 30 days, 10.7 ± 5.3 at 210 days, and 9.4 ± 5.0 at 360 days (P = .0002; baseline to 360 days). Among the five patients with an ulcer who reached the 360-day follow-up visit, all (100%) healed at least one ulcer. Two patients (40%) healed all ulcers and three patients (60%) had a decrease in ulcers number but remained at C6 at 360 days. The five patients with a total of nine active ulcers at baseline had four active ulcers at 360 days.

Conclusions: The BlueLeaf System holds promise as a minimally invasive means to safely form fully autogenous deep venous valves. Reconstructed deep veins remained patent, without deep venous thrombosis and symptomatic improvement was consistently observed; however, a decrease in the RT was not. Incremental device design improvements have been undertaken to improve valve function. The results of these iterations await further clinical evaluation.
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http://dx.doi.org/10.1016/j.jvsv.2020.12.073DOI Listing
January 2021

Sofosbuvir and daclatasvir for the treatment of COVID-19 outpatients: a double-blind, randomized controlled trial.

J Antimicrob Chemother 2021 02;76(3):753-757

Gastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.

Introduction: Effective treatments are urgently needed to tackle the novel coronavirus disease 2019 (COVID-19). This trial aims to evaluate sofosbuvir and daclatasvir versus standard care for outpatients with mild COVID-19 infection.

Methods: This was a randomized controlled clinical trial in outpatients with mild COVID-19. Patients were randomized into a treatment arm receiving sofosbuvir/daclatasvir plus hydroxychloroquine or a control arm receiving hydroxychloroquine alone. The primary endpoint of the trial was symptom alleviation after 7 days of follow-up. The secondary endpoint of the trial was hospital admission. Fatigue, dyspnoea and loss of appetite were investigated after 1 month of follow-up. This study is registered with the IRCT.ir under registration number IRCT20200403046926N1.

Results: Between 8 April 2020 and 19 May 2020, 55 patients were recruited and allocated to either the sofosbuvir/daclatasvir treatment arm (n = 27) or the control arm (n = 28). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms at Day 7. One patient was admitted to hospital in the sofosbuvir/daclatasvir arm and four in the control arm, but the difference was not significant. After 1 month of follow-up, two patients reported fatigue in the sofosbuvir/daclatasvir arm and 16 in the control arm; P < 0.001.

Conclusions: In this study, sofosbuvir/daclatasvir did not significantly alleviate symptoms after 7 days of treatment compared with control. Although fewer hospitalizations were observed in the sofosbuvir/daclatasvir arm, this was not statistically significant. Sofosbuvir/daclatasvir significantly reduced the number of patients with fatigue and dyspnoea after 1 month. Larger, well-designed trials are warranted.
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http://dx.doi.org/10.1093/jac/dkaa501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798988PMC
February 2021

Improving E. coli Bactofection by Expression of Bacteriophage ΦX174 Gene E.

Methods Mol Biol 2021 ;2211:3-14

Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY, USA.

Bactofection, a bacterial-mediated form of genetic transfer, is highlighted as an alternative mechanism for gene therapy. A key advantage of this system for immune-reactivity purposes stems from the nature of the bacterial host capable of initiating an immune response by attracting recognition and cellular uptake by antigen-presenting cells (APCs). The approach is also a suitable technique to deliver larger genetic constructs more efficiently as it can transfer plasmids of varying sizes into target mammalian cells. Given these advantages, bacterial vectors are being studied as potential carriers for the delivery of plasmid DNA into target cells to enable expression of heterologous proteins. The bacteria used for bactofection are generally nonpathogenic; however, concerns arise due to the use of a biological agent. To overcome such concerns, enhanced bacterial degradation has been engineered as an attenuation and safety feature for bactofection vectors. In particular, the ΦX174 lysis E (LyE) gene can be repurposed to both minimize bacterial survival within mammalian hosts while also improving overall gene delivery. More specifically, an engineered bacterial vector carrying the LyE gene showed improved gene delivery and safety profiles when tested with murine RAW264.7 macrophage APCs. This chapter outlines steps taken to engineer E. coli for LyE expression as a safer and more effective genetic antigen delivery bactofection vehicle in the context of vaccine utility.
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http://dx.doi.org/10.1007/978-1-0716-0943-9_1DOI Listing
March 2021