718 results on '"Andrew, Hill"'
Search Results
2. Further down the road: The enduring effect of an online training course on novice drivers’ hazard perception skill
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Mark S. Horswill, Andrew Hill, Lisa Buckley, Genevieve Kieseker, and Francine Elrose
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Automotive Engineering ,Transportation ,Applied Psychology ,Civil and Structural Engineering - Published
- 2023
3. Estimated minimum prices and lowest available national prices for antiobesity medications: Improving affordability and access to treatment
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Jacob Levi, Junzheng Wang, Francois Venter, and Andrew Hill
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Nutrition and Dietetics ,Endocrinology ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) - Published
- 2023
4. Initial Supplementary Dose of Dolutegravir in Second-Line Antiretroviral Therapy: A Noncomparative, Double-Blind, Randomized Placebo-Controlled Trial
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Ying Zhao, Rulan Griesel, Zaayid Omar, Bryony Simmons, Andrew Hill, Gert van Zyl, Claire Keene, Gary Maartens, and Graeme Meintjes
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Microbiology (medical) ,Infectious Diseases ,RA0421 Public health. Hygiene. Preventive Medicine - Abstract
Background Dolutegravir concentrations are reduced by efavirenz induction effect necessitating twice-daily dolutegravir dosing when coadministered. Efavirenz induction persists for several weeks after stopping, which could potentially select for dolutegravir resistance if switching occurred with unsuppressed human immunodeficiency virus type 1 (HIV-1) RNA levels and standard dolutegravir dosing. We evaluated the need for a lead-in supplementary dolutegravir dose in adults failing first-line tenofovir-emtricitabine-efavirenz (TEE). Methods We conducted a randomized, double-blind, placebo-controlled, phase 2 trial in Khayelitsha, South Africa. Eligible patients had virologic failure (2 consecutive HIV-1 RNA ≥1000 copies/mL) on first-line TEE. Participants were randomly assigned (1:1) to switch to tenofovir-lamivudine-dolutegravir (TLD) with a supplementary 50 mg dolutegravir dose or placebo taken 12 hours later for 14 days. Primary outcome was proportion with HIV-1 RNA Results One hundred thirty participants were randomized (65 to each arm). Median baseline HIV-1 RNA was 4.0 log10 copies/mL and 76% had baseline resistance to both tenofovir and lamivudine. One participant died and 2 were lost to follow-up. At week 24, 55 of 64 (86% [95% confidence interval {CI}: 75%–93%]) in the supplementary dolutegravir arm and 53 of 65 (82% [95% CI: 70%–90%]) in the placebo arm had HIV-1 RNA Conclusions Our findings do not support the need for initial dolutegravir dose adjustment in patients switching to TLD who failed first-line TEE. Clinical Trials Registration NCT03991013.
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- 2023
5. Assessing speeding propensity via self-report: An on-road validation study of the Driver Behaviour Questionnaire and three speeding-specific measures
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Andrew Hill, Mark S. Horswill, John Whiting, and Marcus O. Watson
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Automotive Engineering ,Transportation ,Applied Psychology ,Civil and Structural Engineering - Published
- 2023
6. The dangers of non-randomized, observational studies: experience from the COVID-19 epidemic
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Andrew, Hill and Manya, Mirchandani
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Pharmacology ,Microbiology (medical) ,Infectious Diseases ,Pharmacology (medical) - Abstract
In regulatory evaluations, high-quality randomized controlled trials (RCTs) are considered the gold standard for assessing the efficacy of medical interventions. However, during the COVID-19 pandemic, the urgent need for treatment options led to regulatory approvals being made based on evidence from non-randomized, observational studies. In this study we contrast results from observational studies and RCTs of six drugs to treat COVID-19 infection. Across a range of studies evaluating hydroxychloroquine, remdesivir, ivermectin, aspirin, molnupiravir and tenofovir for COVID-19, there was statistically significant evidence of benefit from non-randomized observational studies, which was then not seen in RCTs. We propose that all observational studies need to be labelled as ‘non-randomized’ in the title. This should indicate that they are not as reliable for evaluating the efficacy of a drug and should not be used independently for regulatory approval decisions.
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- 2022
7. Hazard Perception Skill and Driver Behavior in Patients With Functional Neurologic Disorders
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Tjerk J. Lagrand, Atiyeh Vaezipour, Andrew Hill, Mark S. Horswill, and Alexander C. Lehn
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Neurology (clinical) ,Research Article - Abstract
Background and ObjectivesDriving in patients with functional neurologic disorders (FND) is a major concern, but current guidelines (where they exist) are based on expert consensus only due to a lack of relevant empirical evidence. This study aimed to provide such evidence by comparing drivers with FND with healthy controls on aspects of driving performance and behavior important to crash risk, including hazard perception skill.MethodsParticipants completed validated self-report questionnaires of driving behaviors (assessing lapses, errors, violations, and attentional issues) and 2 computer-based measures of hazard perception skill (both known to be associated with crash risk).ResultsWe compared 43 patients who experience dissociative attacks or functional motor symptoms and 43 healthy controls. Patients with FND self-reported significantly more driving lapses and driving errors compared with healthy controls. However, there were no significant between-group differences in self-reports of ordinary violations, aggressive violations, or attention-related errors. Participants in the FND group and healthy controls exhibited a similar performance on a response timehazard perception test(6.27 vs 5.51 seconds,p= 0.245). However, participants with FND remarkably outperformed the controls in the number of plausible predictions they made in a verbal responsehazard prediction test(1.55 vs 1.18 predictions per clip,p= 0.006).DiscussionOur findings suggest that the ability of drivers with FND to predict traffic hazards in between attacks or flares is not worse than that of healthy individuals, with the possibility that it might even be better under some circumstances. Further studies with various populations are needed to replicate our findings.
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- 2022
8. Weight and Metabolic Changes After Switching From Tenofovir Alafenamide/Emtricitabine (FTC)+Dolutegravir (DTG), Tenofovir Disoproxil Fumarate (TDF)/FTC + DTG, and TDF/FTC/Efavirenz to TDF/Lamivudine/DTG
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Bronwyn Bosch, Godspower Akpomiemie, Nomathemba Chandiwana, Simiso Sokhela, Andrew Hill, Kaitlyn McCann, Ambar Qavi, Manya Mirchandani, and Willem Daniel Francois Venter
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Microbiology (medical) ,Infectious Diseases - Abstract
Participants randomized to first-line tenofovir alafenamide (TAF)/emtricitabine (FTC)+dolutegravir (DTG), tenofovir disoproxil fumarate (TDF)/FTC + DTG, or TDF/FTC/efavirenz (EFV) for 192 weeks were then switched to TDF/lamivudine (3TC)/DTG for 52 weeks. Participants switching either TAF/FTC + DTG or TDF/FTC/EFV to TDF/3TC/DTG showed statistically significant reductions in weight, low-density lipoprotein, triglycerides, glucose and glycated hemoglobin.
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- 2022
9. Systematic Review and Meta-Analysis of the Effect of Augmenting Bariatric Surgery with Vagotomy
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Hanson Unasa, James Jin, Melbourne Mauiliu-Wallis, and Andrew Hill
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Medical–Surgical Nursing ,Nutrition and Dietetics ,Surgery - Published
- 2022
10. Can Targeting Sphincter Spasm Reduce Post-Haemorrhoidectomy Pain? A Systematic Review and Meta-Analysis
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James Jin, Hanson Unasa, Praharsh Bahl, Melbourne Mauiliu-Wallis, Darren Svirskis, and Andrew Hill
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Surgery - Abstract
Background Haemorrhoidectomy is often complicated by significant post-operative pain, to which spasm of the internal anal sphincter is thought to be a contributing factor. This study appraises the evidence behind interventions aimed at lowering sphincter spasm to relieve post-haemorrhoidectomy pain. Methods A Preferred Reporting Items for Systematic Reviews and Meta-analyses compliant systematic review was conducted. Medline, EMBASE, and CENTRAL databases were systematically searched. All RCTs which compared interventions targeting the internal anal sphincter to relieve pain post excisional haemorrhoidectomy were included. The primary outcome measure was pain on the visual analogue scale. Results Of the initial 10,221 search results, 39 articles were included in a qualitative synthesis, and 33 studies were included in a meta-analysis. Topical glyceryl trinitrate (GTN) reduced pain on day 7 (7 studies, 485 participants), with a mean difference and 95% confidence interval (MD, 95% CI) of −1.34 (−2.31; −0.37), I2 = 91%. Diltiazem reduced pain on day 3 on the VAS, and the MD was −2.75 (−398; −1.51) shown in five studies (n = 227). Botulinum toxin reduced pain on day 7, in four studies with 178 participants, MD −1.43 (−2.50; −0.35) I2 = 62%. The addition of Lateral Internal Sphincterotomy to haemorrhoidectomy reduced pain on day 2 in three studies with 275 participants, MD of −2.13 (−3.49; −0.77) I2 = 92%. The results were limited by high heterogeneity and risk of bias. Conclusion Evidence suggests that lateral sphincterotomy, administration of botulinum toxin and the application of topical diltiazem or GTN can reduce post-operative pain after haemorrhoidectomy. Lateral sphincterotomy should not be routinely used due to the risk of incontinence.
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- 2022
11. The need for speed: Scores on a new video-based measure of speeding propensity, suitable for use in online research, correlate with drivers’ on-road speeding behaviour
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Mark S. Horswill, Andrew Hill, and Chiara Santomauro
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Automotive Engineering ,Transportation ,Applied Psychology ,Civil and Structural Engineering - Published
- 2022
12. Short-Term Weather Forecast Skill of Artificial Neural Networks
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Christopher C. Hennon, Andrew Coleman, and Andrew Hill
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Atmospheric Science - Abstract
We evaluate the short-term weather forecast performance of three flavors of artificial neural networks (NNs): feed forward back propagation, radial basis function, and generalized regression. To prepare the application of the NNs to an operational setting, we tune NN hyperparameters using over two years of historical data. Five objective guidance products serve as predictors to the NNs: North American Mesoscale and Global Forecast System model output statistics (MOS) forecasts, the High-Resolution Rapid Refresh (HRRR) model, National Weather Service forecasts, and the National Blend of Models product. We independently test NN performance using 96 real-time forecasts of temperature, wind, and precipitation across 11 U.S. cities made during the WxChallenge, a weather forecasting competition. We demonstrate that all NNs significantly improve short-range weather forecasts relative to the traditional objective guidance aids used to train the networks. For example, 1-day maximum and minimum temperature forecast error is 20%–30% lower than MOS. However, NN improvement over multiple linear regression for short-term forecasts is not significant. We suggest this may be attributed to the small number of training samples, the operational nature of the experiment, and the short forecast lead times. Regardless, our results are consistent with previous work suggesting that applying NNs to model forecasts can have a positive impact on operational forecast skill and will become valuable tools when integrated into the forecast enterprise. Significance Statement We used approximately two years of historical weather data and objective forecasts for a number of cities to tune a series of artificial neural networks (NNs) to forecast 1-day values of maximum and minimum temperature, maximum sustained wind speed, and quantitative precipitation. We compare forecast error against common objective guidance and multiple linear regression. We found that the NNs exhibit about 25% lower error than common objective guidance for temperature forecasting and 50% lower error for wind speed. Our results suggest that NNs will be a valuable contributor to improving weather forecast skill when adopted into the existing forecast enterprise.
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- 2022
13. Randomized clinical trial of nitazoxanide or sofosbuvir/daclatasvir for the prevention of SARS-CoV-2 infection
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Simiso Sokhela, Bronwyn Bosch, Andrew Hill, Bryony Simmons, Joana Woods, Hilary Johnstone, Godspower Akpomiemie, Leah Ellis, Andrew Owen, Carmen Perez Casas, and Willem Daniel Francois Venter
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Pharmacology ,Microbiology (medical) ,Pyrrolidines ,SARS-CoV-2 ,Imidazoles ,COVID-19 ,Valine ,Nitro Compounds ,Antiviral Agents ,HV Social pathology. Social and public welfare. Criminology ,RM Therapeutics. Pharmacology ,South Africa ,Thiazoles ,Treatment Outcome ,Infectious Diseases ,RA0421 Public health. Hygiene. Preventive Medicine ,Humans ,Pharmacology (medical) ,Carbamates ,Sofosbuvir - Abstract
Background The COVER trial evaluated whether nitazoxanide or sofosbuvir/daclatasvir could lower the risk of SARS-CoV-2 infection. Nitazoxanide was selected given its favourable pharmacokinetics and in vitro antiviral effects against SARS-CoV-2. Sofosbuvir/daclatasvir had shown favourable results in early clinical trials. Methods In this clinical trial in Johannesburg, South Africa, healthcare workers and others at high risk of infection were randomized to 24 weeks of either nitazoxanide or sofosbuvir/daclatasvir as prevention, or standard prevention advice only. Participants were evaluated every 4 weeks for COVID-19 symptoms and had antibody and PCR testing. The primary endpoint was positive SARS-CoV-2 PCR and/or serology ≥7 days after randomization, regardless of symptoms. A Poisson regression model was used to estimate the incidence rate ratios of confirmed SARS-CoV-2 between each experimental arm and control. Results Between December 2020 and January 2022, 828 participants were enrolled. COVID-19 infections were confirmed in 100 participants on nitazoxanide (2234 per 1000 person-years; 95% CI 1837–2718), 87 on sofosbuvir/daclatasvir (2125 per 1000 person-years; 95% CI 1722–2622) and 111 in the control arm (1849 per 1000 person-years; 95% CI 1535–2227). There were no significant differences in the primary endpoint between the treatment arms, and the results met the criteria for futility. In the safety analysis, the frequency of grade 3 or 4 adverse events was low and similar across arms. Conclusions In this randomized trial, nitazoxanide and sofosbuvir/daclatasvir had no significant preventative effect on infection with SARS-CoV-2 among healthcare workers and others at high risk of infection.
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- 2022
14. Making Statistical Sense of the Molnupiravir MOVe-OUT Clinical Trial
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Kristian Thorlund, Kyle Sheldrick, Gideon Meyerowitz-Katz, Sonal Singh, and Andrew Hill
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Infectious Diseases ,Virology ,Parasitology - Abstract
Oral therapies for the early treatment of COVID-19 may prevent disease progression and health system overcrowding. A new oral therapeutic named molnupiravir has been promoted as providing an approximately 50% reduction in death or the need for hospitalization. The clinical trial evaluating this drug was stopped early at the recommendation of the Data Safety and Monitoring Board after approximately 50% of the sample had been recruited. At the point of discontinuing the trial, approximately 90% of the planned sample had been recruited and had available follow-up data accessible. We discuss issues about the study conduct, analysis, and interpretation, including 1) the authors and sponsors presented the interim analysis as the primary analysis; 2) communication between sponsors and the Data Safety and Monitoring Board was insufficient; 3) the treatment effects reverse when examining only the post-interim analysis population, and are substantially attenuated when examining the full data; 4) the choice of primary analysis is incorrect; 5) analysis of lost-to-follow-up patients favors the study drug; and 6) other known molnupiravir trials were not presented in the primary study findings. As a result of methodological and statistical concerns, it seems that external trials, separate from those supported by the sponsoring company, are required to determine the utility of this drug.
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- 2022
15. In situ gelling system for sustained intraarticular delivery of bupivacaine and ketorolac in sheep
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Hani Abdeltawab, Scott M. Bolam, Jagdish K. Jaiswal, Sue R. McGlashan, Simon W Young, Andrew Hill, Darren Svirskis, and Manisha Sharma
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Pain, Postoperative ,Sheep ,Animals ,Pharmaceutical Science ,Poloxamer ,General Medicine ,Bupivacaine ,Gels ,Ketorolac ,Ketorolac Tromethamine ,Biotechnology - Abstract
Suboptimal control of postoperative pain following knee arthroplasty can slow recovery and reduce patient satisfaction. Intraarticular (IA) administration of bupivacaine and ketorolac offers efficient pain control and minimizes opioid consumption. However, the clinical benefits of this approach are short lived due to rapid clearance of drugs from the joint cavity. Here, we describe a poloxamer based thermoresponsive in situ gelling system for the sustained IA delivery of bupivacaine hydrochloride (BH) and ketorolac tromethamine (KT) following knee surgery in an ovine model. Drug loaded formulations were prepared using poloxamer 407, poloxamer 188 and sodium chloride. In vitro characterization was conducted, followed by in vivo evaluation of sustained drug release and safety in an ovine model of knee joint surgery. Rheological studies revealed a Newtonian-like flow of the developed formulation at room temperature, confirming its injectability, followed by a transition to a viscous gel as temperature approached body temperature. The developed formulation successfully sustained the in vivo release of BH for 72 h and KT for 48 h, as determined by circulating drug levels, compared to 24 and 8 h for marketed drug solutions. The concentrations of BH and KT in the synovial fluids at 72 h were 11.5 and 1.8 times that of marketed products, suggesting a significant increase in the IA residence time. The developed formulation induced a comparable inflammatory response compared to the marketed drug solutions, however a significantly higher chondrotoxicity was observed following administration of the gel formulations. Poloxamers based in situ gelling systems are promising delivery platforms for the sustained and localised IA delivery of BH and KT, with potential clinical benefits in managing the postoperative pain following knee arthroplasty.
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- 2022
16. An online hazard perception training course reduces heavy braking, speeding, and over-revving rates during everyday driving
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Mark S. Horswill, Andrew Hill, Lisa Buckley, Genevieve Kieseker, and Francine Elrose
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Automotive Engineering ,Transportation ,Applied Psychology ,Civil and Structural Engineering - Published
- 2022
17. Developing Record Linkage Methods to Improve Data Quality
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Toan Ong, Chan Voong, Bethany Kwan, Jenna Reno, Tessa Crumel, Shaun Grannis, Andrew Hill, Joshva Silvasstar, Lisa Schilling, and Michael Kahn
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- 2023
18. Adapting an online guided self‐help intervention for the management of binge eating in adults with type 2 diabetes: The <scp>POSE‐D</scp> study
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Eleanor Coales, Andrew Hill, Suzanne Heywood‐Everett, Jinan Rabbee, Michael Mansfield, Clare Grace, Ian Beeton, and Gemma Traviss‐Turner
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Endocrinology ,Endocrinology, Diabetes and Metabolism ,Internal Medicine - Published
- 2023
19. Evaluation of Huawei smart wearables for detection of atrial fibrillation in patients following ischemic stroke:The Liverpool-Huawei Stroke Study
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Stephanie L. Harrison, Benjamin J.R. Buckley, Yalin Zheng, Andrew Hill, Thant Hlaing, Ruth Davies, Yutao Guo, Deirdre A. Lane, Gregory Y.H. Lip, Sylvia Choi, Sandra Elsheikh, Dimitrios Sagris, Martha Joddrell, Muath Alobaida, E. McCarthy, Elizabeth McCarthy, I. Eustace, Ian Eustace, K. Hoad, S.J. Katie Hoad, Sunil Jit R.J. Logantha, Garry McDowell, Alena Shantsila, Ying Gue, M Isanejad, I. Jones, Masoud Isanejad, and Ian Jones
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Cardiology and Cardiovascular Medicine - Abstract
BACKGROUND: Atrial fibrillation (AF) often remains undetected following stroke. Documenting AF is critical to initiate oral anticoagulation, which has proven benefit in reducing recurrent stroke and mortality in patients with AF. The accuracy and acceptability of using smart wearables to detect AF in patients following stroke is unknown.METHODS: The aims of the Liverpool-Huawei Stroke Study are to determine the effectiveness, cost-effectiveness and patient and staff acceptability of using Huawei smart wearables to detect AF following ischemic stroke. The study plans to recruit 1,000 adults aged ≥18 years following ischemic stroke from participating hospitals over 12 months. All participants will be asked to wear a Huawei smart band for 4 weeks postdischarge. If participants do not have access to a compatible smartphone required for the study, they will be provided with a smartphone for the 4-week AF monitoring period.RESULTS: Participants with suspected AF detected by the smart wearables, without previous known AF, will be referred for further evaluation. To determine the effectiveness of the Huawei smart wearables to detect AF, the positive predictive value will be determined. Patient acceptability of using this technology will also be examined. Additional follow-up assessments will be conducted at 6 and 12 months, and clinical outcomes recorded in relation to prevalent and incident AF post-stroke. The study opened for recruitment on May 30, 2022, and is currently open at 4 participating hospitals; the first 106 participants have been recruited. One further hospital is preparing to open for recruitment.CONCLUSIONS: This prospective study will examine the effectiveness and acceptability of the use of smart wearables in patients following ischemic stroke. This could have important implications for detection of AF and therefore, earlier prophylaxis for recurrent stroke. The study is registered on https://www.isrctn.com/ (Identifier ISRCTN30693819).
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- 2023
20. Endovascular treatment for ischemic stroke patients with and without atrial fibrillation, and the effects of adjunctive pharmacotherapy:a narrative review
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Muath Alobaida, Gregory Y H Lip, Deirdre A Lane, Dimitrios Sagris, Andrew Hill, and Stephanie L Harrison
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Pharmacology ,pharmacological ,Brain Ischemia/drug therapy ,General Medicine ,endovascular thrombectomy ,clinical outcomes ,Stroke ,Treatment Outcome ,Ischemic Stroke/etiology ,Thrombectomy/adverse effects ,Humans ,Pharmacology (medical) ,atrial fibrillation ,Endovascular Procedures/adverse effects ,Thrombolytic Therapy ,Stroke/drug therapy ,Atrial Fibrillation/complications - Abstract
Introduction: Endovascular thrombectomy (EVT) is associated with good clinical outcomes in patients with ischemic stroke, but the impact of EVT on clinical outcomes in patients with ischemic stroke with and without atrial fibrillation (AF), and the effect of adjunctive pharmacological therapies with EVT, remains unclear. Areas covered: The goal of this narrative review is to provide an overview of studies which have examined: 1) associations between EVT and outcomes for patients following ischemic stroke, 2) associations between EVT and outcomes for patients following ischemic stroke with and without AF, including function, reperfusion, hemorrhage, and mortality, 3) the effect of adjunctive pharmacological therapies peri- and post-thrombectomy, and 4) integration of prehospital care on endovascular treatment outcomes. Expert opinion: There is little evidence from randomized controlled trials on the effect of AF on stroke outcomes following EVT and the safety and efficacy of AF treatment in the peri-EVT such as tirofiban or Intravenous thrombolysis with Non-vitamin K Antagonist Oral Anticoagulant. The available evidence from observational studies on AF and EVT outcomes is inconsistent, but factors such as procedural EVT devices, the center volume, clinician experience, stroke recognition, and inclusion criteria of studies have all been associated with poorer clinical outcomes. Enhancing the clinical network among prehospital and hospitals will facilitate direct transfer to EVT centers, reducing stroke onset to EVT time and optimizing stroke outcomes.
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- 2023
21. Outcomes in patients with ischaemic stroke undergoing endovascular thrombectomy:Impact of atrial fibrillation
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Muath Alobaida, Stephanie L. Harrison, Deirdre A. Lane, Paula Underhill, Andrew Hill, and Gregory Y.H. Lip
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Male ,Adult ,Adolescent ,Brain Ischemia/therapy ,Cerebral Hemorrhage/diagnostic imaging ,endovascular thrombectomy ,Humans ,atrial fibrillation ,Endovascular Procedures/adverse effects ,Aged ,Retrospective Studies ,Aged, 80 and over ,ischaemic stroke ,Atrial Fibrillation/drug therapy ,Rehabilitation ,intracerebral haemorrhage ,Middle Aged ,Stroke/diagnosis ,clinical outcomes ,Treatment Outcome ,Ischemic Stroke/etiology ,Thrombectomy/adverse effects ,Surgery ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine - Abstract
OBJECTIVES: Endovascular thrombectomy (EVT) is associated with good clinical outcomes in ischaemic stroke, but the risk of intracerebral haemorrhage (ICH) and mortality remains common following ischaemic stroke. The effect of concomitant atrial fibrillation (AF) on clinical outcomes following acute ischaemic stroke in patients receiving EVT remains unclear. The aim is to investigate associations between AF and intracerebral haemorrhage and all-cause mortality at 90 days in patients with ischaemic stroke undergoing EVT.MATERIALS AND METHODS: A retrospective cohort was conducted using TriNetX, a global health research network. The network was searched for people aged ≥18 years with ischaemic stroke, EVT and AF recorded in electronic medical records between 01/09/2018 and 01/09/2021. These patients were compared to controls with ischaemic stroke, EVT and no AF. Propensity score matching for age, sex, race, comorbidities, National Institutes of Health Stroke Scale (NIHSS) scores, and prior use of anticoagulation was used to balance the cohorts with and without AF.RESULTS: In total 3,106 patients were identified with history of ischaemic stroke treated by EVT. After propensity-score matching, 832 patients (mean age 68 ± 13; 47% female) with ischaemic stroke, EVT and AF, were compared to 832 patients (mean age 67 ± 12; 47% female) with ischaemic stroke, EVT and no history of AF. In the cohort with AF, 11.5% (n = 96) experienced ICH within 90 days following EVT, compared with 12.3% (n = 103) in patients without AF (Odds Ratio (OR) 0.92, 95% confidence interval (CI) 0.68-1.24; p = 0.59). In the patients with AF, mortality within 90 days following EVT was 18.7% (n = 156), compared with 22.5% in patients without AF (n = 187) (OR 0.79, 95% CI 0.63-1.01; p = 0.06).CONCLUSION: In patients with ischaemic stroke undergoing EVT, AF was not significantly associated with intracerebral haemorrhage or all-cause mortality at 90-day follow-up.
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- 2023
22. Recommendations from a Working Group on Obesity Care Competencies for Healthcare Education in the UK: A Report by the Steering Committee
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Matthew S. Capehorn, Nigel Hinchliffe, Deborah Cook, Andrew Hill, Mary O’Kane, Abd A. Tahrani, Ann Vincent, Simon Williams, and John Feenie
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COVID-19 ,Humans ,Pharmacology (medical) ,Clinical Competence ,Health Status Disparities ,Obesity ,General Medicine ,Delivery of Health Care ,United Kingdom - Abstract
Obesity significantly increases the risk of developing (or worsening) more than 200 chronic diseases, and it is also a risk factor for severe COVID-19. With the rising prevalence of obesity in the UK, there is a need to develop obesity care competencies that apply to healthcare professionals (HCPs) at all levels of the health service, to increase the capacity for contemporary, evidence-based treatment that is effective, compassionate, and avoids stigmatising patients.A UK Obesity Care Competencies Working Group consisting of experts by profession and experts by experience was created to provide a framework of obesity care competencies for HCPs involved in specialist obesity care (tiers 2-4 in the UK). The framework was adapted from a set of competencies recently published by the USA-based Obesity Medicine Education Collaborative (OMEC) and was intended to be adaptable to nurses and allied health professionals, as well as physicians, owing to the multidisciplinary team approach used in healthcare in the UK.The UK Obesity Care Competencies Working Group developed a set of 29 competencies, divided into five focal areas, namely obesity knowledge, patient care and procedural skills, practice-based learning and improvement, professionalism and interpersonal communication skills, and systems-based practice. The working group recommends that the obesity care competencies are targeted at HCPs training as specialists. The competencies could be imported into existing training programmes to help standardise obesity-related medical education and could also be used to direct a new General Practitioner with Extended Role (GPwER) qualification.This list of obesity care competencies aims to provide an initial framework to improve education for HCPs and therefore to improve patient care in obesity. The acceptance and integration of these competencies into the healthcare system should provide a stepping stone toward addressing trends in health inequality.
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- 2022
23. Therapeutically harnessing extracellular vesicles
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Lesley Cheng and Andrew Hill
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Pharmacology ,Drug Discovery ,General Medicine - Published
- 2022
24. Ivermectin for the prevention of COVID-19: addressing potential bias and medical fraud
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Andrew Hill, Manya Mirchandani, Leah Ellis, and Victoria Pilkington
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Pharmacology ,Microbiology (medical) ,2019-20 coronavirus outbreak ,medicine.medical_specialty ,Ivermectin ,Antiparasitic Agents ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Fraud ,Poor quality ,COVID-19 Drug Treatment ,Clinical trial ,Treatment Outcome ,Infectious Diseases ,parasitic diseases ,medicine ,Humans ,Pharmacology (medical) ,Intensive care medicine ,business ,Randomized Controlled Trials as Topic ,medicine.drug - Abstract
Background Ivermectin is an antiparasitic drug being investigated in clinical trials for the prevention of COVID-19. However, there are concerns about the quality of some of these trials. Objectives To conduct a meta-analysis with randomized controlled trials of ivermectin for the prevention of COVID-19, while controlling for the quality of data. The primary outcome was RT–PCR-confirmed COVID-19 infection. The secondary outcome was rate of symptomatic COVID-19 infection. Methods We conducted a subgroup analysis based on the quality of randomized controlled trials evaluating ivermectin for the prevention of COVID-19. Quality was assessed using the Cochrane risk of bias measures (RoB 2) and additional checks on raw data, where possible. Results Four studies were included in the meta-analysis. One was rated as being potentially fraudulent, two as having a high risk of bias and one as having some concerns for bias. Ivermectin did not have a significant effect on preventing RT–PCR-confirmed COVID-19 infection. Ivermectin had a significant effect on preventing symptomatic COVID-19 infection in one trial with some concerns of bias, but this result was based on post hoc analysis of a multi-arm study. Conclusions In this meta-analysis, the use of ivermectin was not associated with the prevention of RT–PCR-confirmed or symptomatic COVID-19. The currently available randomized trials evaluating ivermectin for the prevention of COVID-19 are insufficient and of poor quality.
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- 2022
25. Antiplatelet Agents and Oral Anticoagulant Use in Patients with Atrial Fibrillation and Carotid Artery Disease After First-Time Ischaemic Stroke
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Stephanie L. Harrison, Benjamin J.R. Buckley, Deirdre A. Lane, Elnara Fazio-Eynullayeva, Paula Underhill, Andrew Hill, David J. Werring, and Gregory Y.H. Lip
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Stroke ,Pharmacology ,Carotid artery disease ,Antiplatelet agents ,Anticoagulants ,Pharmacology (medical) ,General Medicine ,Cardiology and Cardiovascular Medicine ,Atrial fibrillation - Abstract
Introduction People with atrial fibrillation (AF) frequently have competing mechanisms for ischaemic stroke, including extracranial carotid atherosclerosis. The objective of this study was to determine associations between use of oral anticoagulants (OACs) plus antiplatelet agents (APA) after ischaemic stroke and outcomes for patients with AF and carotid artery disease. Patients and Methods A retrospective cohort study was conducted. Participants receiving OACs with or without APA were propensity score–matched for age, sex, ethnicity, co-morbidities and presence of cardiac and vascular implants and grafts. Outcomes were 1-year mortality, recurrent stroke and major bleeding. Results Of 5708 patients, 24.1% (n=1628) received non-vitamin K antagonist OACs (NOACs) with no APA, 26.0% (n=1401) received NOACs plus APA, 20.7% (n=1243) received warfarin without APA and 29.2% (n=1436) received warfarin plus APA. There was no significant difference in risk of recurrent stroke between the groups. Compared to receiving NOACs without APA, receiving warfarin plus APA was associated with a higher risk of mortality (hazard ratio (HR) 1.51 (95% confidence interval (CI) 1.20, 1.89)) and major bleeding (HR 1.66 (95% CI 1.40, 1.96)). Receiving NOACs plus APA was also associated with a higher risk of major bleeding compared to NOACs without APA (HR 1.27 (95% CI 1.07, 1.51), respectively). Conclusions The results suggest for patients with AF and carotid artery disease after ischaemic stroke, receiving NOACs without APA is associated with a lower risk of major bleeding with no negative impact on recurrent stroke or mortality. Evidence from randomised trials is needed to confirm this finding.
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- 2023
26. Neuroinflammatory Modulation of Extracellular Vesicle Biogenesis and Cargo Loading
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Natasha Vassileff, Jereme Spiers, and Andrew Hill
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Cellular and Molecular Neuroscience ,Extracellular Vesicles ,MicroRNAs ,Neurology ,FOS: Clinical medicine ,Biochemistry and cell biology ,Neurosciences ,Molecular Medicine ,Cytokines ,Cell Communication ,Microglia - Abstract
Increasing evidence suggests neuroinflammation is a highly coordinated response involving multiple cell types and utilising several different forms of cellular communication. In addition to the well documented cytokine and chemokine messengers, extracellular vesicles (EVs) have emerged as key regulators of the inflammatory response. EVs act as vectors of intercellular communication, capable of travelling between different cells and tissues to deliver selectively packaged protein, miRNA, and lipids from the parent cell. During neuroinflammation, EVs transmit specific inflammatory mediators, particularly from microglia, to promote inflammatory resolution. This mini-review will highlight the novel neuroinflammatory mechanisms contributing to the biogenesis and selective packaging of EVs.
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- 2023
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27. Adherence, resistance, and viral suppression on dolutegravir in sub-Saharan Africa: implications for the TLD era
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Suzanne M. McCluskey, Ravindra K. Gupta, Andrew Hill, Mark J. Siedner, Toby Pepperrell, and Willem D F Venter
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medicine.medical_specialty ,Efavirenz ,Sub saharan ,Anti-HIV Agents ,Pyridones ,Immunology ,HIV Infections ,Article ,Piperazines ,chemistry.chemical_compound ,Oxazines ,medicine ,Humans ,Immunology and Allergy ,Viral suppression ,Intensive care medicine ,business.industry ,Antiretroviral therapy ,VIROLOGIC FAILURE ,Clinical trial ,Infectious Diseases ,chemistry ,Dolutegravir ,business ,Heterocyclic Compounds, 3-Ring ,HIV drug resistance - Abstract
Dolutegravir (DTG) is now a component of preferred first-line antiretroviral therapy (ART) worldwide. ADVANCE and NAMSAL were two landmark clinical trials conducted exclusively in sub-Saharan Africa, which studied the effectiveness of DTG-based first-line regimens for ART-naive individuals. In this review, we examine the data from these studies to consider the contributions of adherence and HIV drug resistance to treatment failure on DTG-based ART, as compared with efavirenz (EFV)-based ART, which has a lower genetic barrier to resistance. We also discuss the implications of virologic failure on DTG and consolidate currently available data to conclude with recommendations for virologic monitoring on DTG-based ART.
- Published
- 2021
28. Impact of long-acting therapies on the global HIV epidemic
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Nomathemba Chandiwana, Andrew Hill, Carmen Pérez Casas, Charles Flexner, Celicia Serenata, Steve P. Rannard, Cherise Scott, Andrew Owen, and Polly Clayden
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medicine.medical_specialty ,Anti-HIV Agents ,business.industry ,Social Stigma ,Immunology ,Hiv epidemic ,Human immunodeficiency virus (HIV) ,Stigma (botany) ,Treatment options ,HIV Infections ,medicine.disease_cause ,Infectious Diseases ,Long acting ,Tolerability ,Humans ,Immunology and Allergy ,Medicine ,Pre-Exposure Prophylaxis ,Dosing ,Epidemics ,business ,Intensive care medicine ,Oral therapy - Abstract
Long-acting antiretroviral drugs have emerged as exciting treatment and preexposure prophylaxis (PrEP) options for people with HIV and at risk of HIV. Long-acting regimens may improve dosing convenience, tolerability and cost compared with current daily-based oral therapy. They can also circumvent stigma associated with oral therapy for both treatment and PrEP, thereby improving adherence and outcomes. Yet, multiple challenges remain, many specific to low-income and middle-income countries (LMICs), where the epidemic is most concentrated and HIV prevention and treatment options are limited. To optimize the use of long-acting formulations, key outstanding questions must be addressed. Uncertain costing, scale-up manufacturing, complex delivery systems and implementation challenges are potential barriers when considering the scalability of long-acting ARVs for global use.
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- 2021
29. Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER)
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Atefeh Bonyadi, Fariborz Mansour-Ghanaei, Farhang Babamahmoodi, Esmat Radmanesh, Hadiseh Hosamirudsari, Javad Khodadadi, Sara Sayar, Zeinab Mehrabi, Amir Reza Bahadori, Shahin Merat, Minoo Moghimi, Gholamali Eslami, Hashem Mousavi, Lotfollah Davoodi, Mona Ebrahimzadeh, Farahnaz Joukar, Amir Anushiravani, Ali Ali Asgari, Ali Reza Davoudi Badabi, Elham Barahimi, Saeed Jelvay, Zahra Poormontaseri, Aida Zeinali, Nasim Khajavirad, Minoosh Shabani, Hamideh Abbaspour Kasgari, Zohreh Azarkar, Rohollah Moslemi, Ahmad Hormati, Azadeh Ebrahimzadeh, Hani Esmaeilian, Shokrollah Salmanzadeh, Elham Akbarpour, Lili Rezaie Keikhaie, Kaitlyn McCann, Amir Mohammad Shabani, Abdolali Tousi, Mohammad Abdollahi, Sara Mobarak, Mohammadreza Naghipour, Hadi Mirzaei, Mohammadreza Salehi, Shervin Shokouhi, Bryony Simmons, Morteza Mobarak, Helia Nateghi Baygi, Jacob Levi, Mehdi Hassaniazad, Andrew Hill, Zahra Arizavi, Nasrollah Hasooni Bahrini, Seyed Ali Dehghan Manshadi, Fatemeh Dehghani, Hannah Wentzel, Hossein Pourmasoomi, Masoome Noori Jangi, Shoeleh Yaghoubi, Alireza Nateghi Baygi, Mehdi Salasi, Farnaz Zolfaghari, Sara Yeganeh, Elmira Azimi, Jalal Karimi, Hafez Fakheri, Mahdi Afshari, Tofigh Yaghubi Kalurazi, Anahita Sadeghi, Farshid Abedi, Sajedeh Mousaviasl, Zahra Nekoukar, Dorsa Merat, and Masood Ziaee
- Subjects
Adult ,Microbiology (medical) ,medicine.medical_specialty ,Pyrrolidines ,Randomization ,Daclatasvir ,Coronavirus disease 2019 (COVID-19) ,Sofosbuvir ,Placebo ,Antiviral Agents ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,Clinical endpoint ,AcademicSubjects/MED00740 ,Humans ,Medicine ,Pharmacology (medical) ,Original Research ,Pharmacology ,SARS-CoV-2 ,business.industry ,Imidazoles ,COVID-19 ,Valine ,Institutional review board ,Clinical trial ,AcademicSubjects/MED00290 ,Treatment Outcome ,Infectious Diseases ,Relative risk ,Carbamates ,AcademicSubjects/MED00230 ,business ,medicine.drug - Abstract
Background: The combination of sofosbuvir (SOF) and daclatasvir (DCV) has shown preliminary efficacy for patients with COVID-19 in five open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir and daclatasvir to standard care improved clinical endpoints in hospitalized patients with moderate or severe COVID-19. Methods: This was a placebo-controlled, randomized clinical trial in adults with moderate or severe COVID-19 admitted to 19 hospitals in Iran. Patients were randomized to SOF/DCV 400/60mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O 2 saturation
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- 2021
30. Atrial fibrillation and stroke
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Sylvia E. Choi, Dimitrios Sagris, Andrew Hill, Gregory Y.H. Lip, and Azmil H. Abdul-Rahim
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oral anticoagulation ,rhythm control ,Incidence ,General Medicine ,integrated care approach ,Stroke/epidemiology ,Anticoagulants/therapeutic use ,Risk Factors ,embolic stroke ,Internal Medicine ,cryptogenic stroke ,Humans ,atrial fibrillation ,stroke prevention ,Cardiology and Cardiovascular Medicine ,Atrial Fibrillation/complications ,Ischemic Stroke - Abstract
INTRODUCTION: Stroke is one of the leading causes of mortality and morbidity globally. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It is set to reach epidemic proportions. AF is associated with a five-fold increase in risk of stroke. Strokes caused by AF more often are fatal or result in severe disability. Even though the incidence of stroke has been significantly reduced by oral anticoagulation, AF is thought to account for a significant proportion of cryptogenic strokes where no etiology is identified.AREAS COVERED: This article reviews the literature related to AF and stroke, pathophysiological insights, diagnosis of AF in stroke patients, and its management (Graphical Abstract).EXPERT OPINION: The pathophysiology of thrombogenesis that links AF and stroke is not well understood and is an area of active research to identify new therapeutic targets to prevent AF and stroke. As the nature of AF and stroke is multifaceted, an integrated care approach to managing AF and stroke is increasingly essential.
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- 2022
31. Semi-supervised Embedding for Scalable and Accurate Time Series Clustering
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Andrew Hill, Russell Bowler, Katerina Kechris, and Farnoush Banaei-Kashani
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- 2022
32. 1946. Efficacy of Approved versus Unapproved Vaccines for SARS-CoV-2 Infection in Randomised Blinded Clinical Trials
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Andrea Perez Navarro, Victoria Pilkington, Andrew Hill, and Toby Pepperrell
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Infectious Diseases ,Oncology - Abstract
Background Five SARS-CoV-2 vaccines are approved in North America and/or Europe: Pfizer/BioNTech, Moderna, Janssen, Oxford-AstraZeneca and Novavax. Other vaccines have been developed, including Sinopharm, SinoVac, QazVac, Covaxin, Soberana, Corbevac, Medicago, Clover and Cansino, but are not approved in high income countries. This meta-analysis compared the efficacy of approved and unapproved vaccines in randomised clinical trials (RCTs). Methods A systematic review of clinical trial registries, PUBMED and EMBASE identified placebo-controlled RCTs of SARS-CoV-2 vaccines prospectively evaluating risks of symptomatic or severe infection with clearly defined endpoints. For each trial, risk of bias was assessed using Cochrane tool 2.0 and the CONSORT checklist. In the pre-defined meta-analysis, relative risks of symptomatic infection and severe disease were compared for each vaccine versus placebo, using Cochrane-Mantel Haenszel Tests (random effects method). Results There were 21 RCTs assessing efficacy of the COVID-19 vaccines identified. One RCT was excluded for high risk of bias. Ten RCTs in 206,667 participants evaluated 5 approved vaccines; 10 RCTs in 158,599 participants evaluated 8 unapproved vaccines. In the meta-analysis, prevention of symptomatic infection was 84% (95% C.I. 68-92%) for approved vaccines versus 72% (95% C.I. 65-77%) for unapproved vaccines, with no significant difference between vaccine types (p=0.13). Prevention of severe SARS-CoV-2 infection was 95% (95% C.I. 78-99%) for approved vaccines versus 84% (95% C.I. 72-91%) for unapproved vaccines (p=0.12). In addition, the risk of serious adverse events was similar between vaccine types (p=0.49). Efficacy of approved and unapproved SARS-CoV-2 vaccines Percentage efficacy of approved and unapproved SARS-CoV-2 vaccines against symptomatic infection (Panel A) and severe disease (Panel B). Vaccines are arranged by approval-status (approved vaccines to the left and unapproved vaccines to the right of discontinuous line) and colour-coded by vaccine type. Error bars represent 95% confidence intervals. RIBSP, Research Institute for Biological Safety Problems; IFV, Instituto Finlay de Vacunas. Conclusion This meta-analysis of 20 RCTs in 365,266 participants, showed no significant difference in efficacy between the approved and unapproved SARS-CoV-2 vaccines for endpoints of either symptomatic or severe infection. Differences in study design, end-point definitions, variants and prevalence of infection may have influenced the results. Head-to-head RCTs will be required to make definitive conclusions. If efficacy is proved definitively, new patent-free vaccines could lower costs of worldwide SARS-CoV-2 vaccination campaigns significantly. Disclosures All Authors: No reported disclosures.
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- 2022
33. Qualitative exploration of patient and healthcare professional perspectives on barriers and facilitators to foot self-care behaviors in diabetes
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Andrew Hill, Mairghread Ellis, and Fiona Gillison
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Attitude of Health Personnel ,Endocrinology, Diabetes and Metabolism ,foot ulcer ,Self Care ,health behavior ,SDG 3 - Good Health and Well-being ,General Practitioners ,self care ,Diabetes Mellitus ,Humans ,Qualitative Research ,diabetic foot - Abstract
IntroductionDiabetic foot ulcers contribute significantly to morbidity and mortality associated with diabetes, but are preventable with good foot self-care. This study sought to explore the perspectives of patients and healthcare professionals (HCPs) on barriers and/or facilitators to foot self-care behaviors in diabetes and areas of consensus and/or tension between patient and HCP perspectives.Research design and methodsThis was a sequential, qualitative study that used a hermeneutic phenomenological approach. Phase I involved nine in-depth, semi-structured patient interviews. Phase II involved seven in-depth semi-structured interviews with HCPs (podiatrists, diabetes nurses, foot health practitioners (FHPs) and general practitioners (GPs)). In phase III, findings from phases I and II were brought back to two patient interview groups (five patients in total) to try and identify any areas of consensus and tension between HCP and patient perspectives.ResultsPatient and HCP perspectives had several areas of alignment: concerns over consequences of diabetes complications; the importance of patient education and frustrations around aspects of health service delivery. There were also some notable tensions identified: mixed messaging from HCPs around whose responsibility patient foot health is; and who patients should initially consult following the development of a foot problem. Overall, patients expressed that motivation to undertake good foot self-care behaviors was generated from their lived experiences, and was enhanced when this aligned with the information they received from HCPs. HCPs appeared to attribute lack of patient motivation to lack of knowledge, which was not raised by patients.ConclusionsThis study has identified points of misalignment between the views of patients and practitioners that may help to explain why adherence to foot self-care among patients with diabetes is low. Our results suggest that better outcomes may stem from HCPs focusing on supporting autonomous motivation for self-care and enhancing the rationale through referencing patients’ own experience rather than focussing on increasing patient knowledge. Renewed focus on consistency of messaging by HCPs around the roles and responsibilities relating to foot health in diabetes, and the benefit of foot-specific training being provided to non-foot specialist HCPs may also help to improve uptake and adherence to foot self-care behaviors in diabetes.
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- 2022
34. Survival After Endovascular Aneurysm Sealing Compared With Endovascular Aneurysm Repair
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Clark J. Zeebregts, Arshad Sheriff, Andrew Holden, Andrew Hill, Aleksandra C. Zoethout, Michel M.P.J. Reijnen, Multi-Modality Medical Imaging, TechMed Centre, and Man, Biomaterials and Microbes (MBM)
- Subjects
medicine.medical_specialty ,Time Factors ,Inflammatory response ,medicine.medical_treatment ,Prosthesis Design ,Endovascular aneurysm repair ,survival ,endovascular aneurysm repair ,Blood Vessel Prosthesis Implantation ,Aneurysm ,abdominal aortic aneurysm ,THROMBUS ,Risk Factors ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Retrospective Studies ,endovascular aneurysm sealing ,business.industry ,Endovascular Procedures ,INFLAMMATORY RESPONSE ,CYTOKINES ,medicine.disease ,Abdominal aortic aneurysm ,Surgery ,Blood Vessel Prosthesis ,Treatment Outcome ,VOLUME ,Stents ,Cardiology and Cardiovascular Medicine ,business ,Aortic Aneurysm, Abdominal - Abstract
Introduction Endovascular aneurysm sealing (EVAS) is a sac-filling device with a blunted systemic inflammatory response compared to conventional endovascular aneurysm repair (EVAR), with a suggested impact on all-cause mortality. This study compares mortality after both EVAS and EVAR. Materials and Methods This is a retrospective observational study including data from 2 centres, with ethical approval. Elective procedures on asymptomatic infrarenal aneurysms performed between January 2011 until April 2018 were enrolled. Laboratory values (serum creatinine, haemoglobin, white blood cell count, platelet count) were measured pre- and postoperatively and at 1 and 2 years, respectively. Mortality and cause of death were recorded during follow-up. Results A total of 564 patients were included (225 EVAS, 369 EVAR), after propensity score matching there were 207 patients in both groups. Baseline characteristics were similar, except for larger neck angulation and more pulmonary disease in the EVAR group. The median follow-up time was 49 (EVAS) and 44 (EVAR) months. No significant differences regarding creatinine and haemoglobin were observed. Preoperative white blood cell count was higher in the EVAR group (p=0.011), without significant differences during follow-up. Median platelet count was lower in the EVAR group preoperatively (p=0.001), but was significantly higher at 1 year follow-up (p=0.003). There were 43 deaths within the EVAS group (20.8%) and 52 within the EVAR group (25.1%) (p=0.293). Of these, 4 were aneurysm related (EVAS n=3, EVAR n=1; p=0.222) and 14 cardiovascular (EVAS n=6, EVAR n=8, p=0.845). For the EVAS cohort, survival was 95.5% at 1 year and 74.9% at 5 years. For the EVAR cohort, this was 93.3% at 1 year and 75.5% at 5 years. No significant differences were observed in causes of death. Conclusion This study showed comparable survival rates through 5 years between EVAS and EVAR with a tendency toward higher inflammatory response in the EVAR patients through the first 2 years.
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- 2021
35. Cabotegravir – global access to long-acting pre-exposure prophylaxis for HIV
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Toby Pepperrell, Samuel Cross, and Andrew Hill
- Abstract
A novel injectable pre-exposure prophylaxis, cabotegravir, has greater efficacy and acceptability than oral TDF/FTC for prevention of HIV infection. Cabotegravir is currently priced at $22,200 per year, 370-times higher than the potential $60 estimated cost-effectiveness threshold for MICs. Following civil society pressure, ViiV agreed access to generic versions in 90 countries with the Medicines Patent Pool (MPP), including all African nations. However, several MICs outside Africa have rapidly growing HIV epidemics. We analysed the ViiV-MPP deal to assess population covered and Gross Domestic Product (GDP) per capita. There were 38 countries excluded from the ViiV-MPP deal despite having a GDP per Capita lower than the highest earning African country. These countries include 2.4 billion people (30% global population), with an incidence of 122 thousand (8%). For cabotegravir to have a significant impact on HIV infections, millions will need to be treated at affordable prices in a wide range of countries.
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- 2022
36. Weight and metabolic changes after switching from tenofovir alafenamide (TAF)/emtricitabine (FTC)+dolutegravir (DTG), tenofovir disoproxil fumarate (TDF)/FTC+DTG and TDF/FTC/efavirenz (EFV) to TDF/lamivudine (3TC)/DTG
- Author
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Bronwyn, Bosch, Godspower, Akpomiemie, Nomathemba, Chandiwana, Simiso, Sokhela, Andrew, Hill, Kaitlyn, McCann, Ambar, Qavi, Manya, Mirchandani, and Willem Daniel Francois, Venter
- Abstract
Participants randomised to first-line tenofovir alafenamide (TAF)/emtricitabine (FTC)+dolutegravir (DTG), tenofovir disoproxil fumarate (TDF)/FTC+DTG or TDF/FTC/efavirenz (EFV) for 192 weeks were then switched to TDF/lamivudine (3TC)/DTG for 52 weeks. Participants switching either TAF/FTC+DTG or TDF/FTC/EFV to TDF/3TC/DTG showed statistically significant reductions in weight, low density lipoprotein, triglycerides, glucose and glycated haemoglobin.
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- 2022
37. The Benefit of the Gift
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Mark Andrew Hill
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- 2022
38. Response to comments by Taramasso and colleagues on weight gain stopping/switch rules for antiretroviral clinical trials
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Francois Venter, Simiso Sokhela, Alexandra Calmy, Mark J. Siedner, Saye Khoo, Polly Clayden, Luckyboy Mkhondwane, Bronwyn Bosch, Nomathemba Chandiwana, Andrew Hill, Vincent C. Marconi, Marta Boffito, Kenly Sekwese, Mohammed Ali, Eric Delaporte, Anton Pozniak, Nkuli Mashabane, Samanta Lalla-Edwards, Mary Carman, and Simon Collins
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Infectious Diseases ,Immunology ,Immunology and Allergy - Published
- 2022
39. Evaluation of publication bias for 12 clinical trials of molnupiravir to treat SARS-CoV-2 infection in 13 694 patients with meta-analysis
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Jack M Lawrence, Manya Mirchandani, and Andrew Hill
- Subjects
Pharmacology ,Microbiology (medical) ,Infectious Diseases ,Pharmacology (medical) - Abstract
In response to the COVID-19 pandemic, Merck Sharp & Dohme (MSD) acquired the global licensing rights for the antiviral molnupiravir, promising affordable access via licensing deals. Numerous Indian pharmaceutical companies subsequently conducted trials of the drug. Registered trials of molnupiravir were searched on the Clinical Trials Registry–India (CTRI) and efforts made to detect resulting public data. Per the CTRI, 12 randomized trials of molnupiravir were conducted in 13 694 Indian patients, from mid-2021. By August 2022, only a preprint and medical conference presentation had resulted. Additionally, two trials were mentioned in press releases suggesting failure of treatment. The available data contain unexplained results that differ significantly from both the PANORAMIC and MSD MOVe-OUT trials. Approximately one-third of the global data on molnupiravir remain unpublished. We conducted a meta-analysis with four studies that provided results and observed that molnupiravir does not have a significant benefit for hospitalizations.
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- 2022
40. Feasibility of transcaval access TAVI in morbidly obese patients: A single-center experience
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Michael Michail, James Cockburn, Kristoffer Vincent P. Tanseco, Sandeep Arunothayaraj, Andrew Hill, Uday Trivedi, and David Hildick‐Smith
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Radiology, Nuclear Medicine and imaging ,General Medicine ,Cardiology and Cardiovascular Medicine - Abstract
We report a single-center experience in utilizing the transcaval-access transcatheter aortic valve implantation (TAVI) as an alternative approach in morbidly obese patients.Morbidly obese patients present frequently for TAVI. Transfemoral arterial access TAVI in these patients is technically challenging due to deep arterial access, resulting in a higher risk of vascular complications. Transcaval access TAVI is increasingly used in patients with prohibitive iliofemoral arterial access.We used the transcaval approach for eight morbidly obese patients who had otherwise technically feasible femoral arterial access. This technique provides an alternative arterial access point that potentially circumvents some of the challenges relating to femoral arterial access.We report eight morbidly obese patients with a mean body mass index of 42.3 ± 6.2 kg/mTranscaval access TAVI is a feasible alternative for morbidly obese patients and may reduce vascular complications. Further data are required to evaluate the safety of this approach.
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- 2022
41. Comparing Prospective Incident Severe Acute Respiratory Syndrome Coronavirus 2 Infection Rates During Successive Waves of Delta and Omicron in Johannesburg, South Africa
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Simiso Sokhela, Bronwyn Bosch, Andrew Hill, Bryony Simmons, Joana Woods, Hilary Johnstone, Shabir Madhi, Ambar Qavi, Leah Ellis, Godspower Akpomiemie, Esther Bhaskar, Jacob Levi, Jonathan Falconer, Manya Mirchandani, Carmen Perez Casas, Karlien Moller, Victoria Pilkington, Toby Pepperrell, and Willem Daniel Francois Venter
- Subjects
Infectious Diseases ,Oncology - Abstract
In high-risk individuals in Johannesburg, during the Delta coronavirus disease 2019 wave, 22% (125/561) were positive, with 33% symptomatic (2 hospitalizations; 1 death). During Omicron, 56% (232/411) were infected, with 24% symptomatic (no hospitalizations or deaths). The remarkable speed of infection of Omicron over Delta poses challenges to conventional severe acute respiratory syndrome coronavirus 2 control measures.
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- 2022
42. Evaluation of publication bias for 12 clinical trials of molnupiravir to treat SARS-CoV-2 infection in 13,694 patients
- Author
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Jack Lawrence, Manya Mirchandani, and Andrew Hill
- Abstract
Introduction: During the COVID-19 pandemic, Merck Sharp and Dohme (MSD) acquired the global licensing rights for molnupiravir. MSD allowed Indian manufacturers to produce the drug under voluntary license. Indian companies conducted local clinical trials to evaluate the efficacy and safety of molnupiravir. Methods Searches of the Clinical Trials Registry-India (CTRI) were conducted to find registered trials of molnupiravir in India. Subsequent investigations were performed to assess which clinical trials had been presented or published. Results According to the CTRI, 12 randomised trials of molnupiravir were conducted in India, in 13,694 patients, starting in late May 2021. By July 2022, none of the 12 trials has been published, one was presented at a medical conference, and two were announced in press releases suggesting failure of treatment. Results from three trials were shared with the World Health Organisation. One of these three trials had many unexplained results, with effects of treatment significantly different from the MSD MOVE-OUT trial in a similar population. Discussion The lack of results runs counter to established practices and leaves a situation where approximately 90% of the global data on molnupiravir has not been published in any form. Access to patient-level databases is required to investigate risks of bias or medical fraud.
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- 2022
43. Supporting Weight Management during COVID-19 (SWiM-C): Twelve-month follow-up of a randomised controlled trial of a web-based, ACT-based, guided self-help intervention
- Author
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Julia Mueller, Rebecca Richards, Rebecca Jones, Fiona Whittle, Jennifer Woolston, Marie Stubbings, Stephen Sharp, Simon Griffin, Jennifer Bostock, Carly Hughes, Andrew Hill, Clare Boothby, and Amy Ahern
- Abstract
Objectives: We developed a guided self-help intervention (Supporting Weight Management during COVID-19, “SWiM-C”) to support adults with overweight or obesity in their weight management during the COVID-19 pandemic. This study evaluated the effect of SWiM-C on weight and determinants of weight management over twelve months.Methods: Participants (≥18 years, body-mass-index ≥25kg/m2) were randomised to the SWiM-C intervention or to a standard advice group. Participants completed online questionnaires at baseline, four months, and twelve months. The primary outcome was change in self-reported weight from baseline to twelve months; secondary outcomes were eating behaviour (uncontrolled eating, emotional eating, cognitive restraint of food intake), experiential avoidance/psychological flexibility, mental health (depression, anxiety, stress), wellbeing and physical activity. Interventions: SWiM-C is based on acceptance and commitment therapy (ACT). Participants had access to an online web platform with 12 weekly modules and limited email and telephone contact with a trained, non-specialist coach. Standard advice was a leaflet on managing weight and mood during the COVID-19 pandemic. Results: 388 participants were randomised (SWiM-C: n=192, standard advice: n=196). The baseline-adjusted difference in weight change between SWiM-C and standard advice participants was -0.81kg (95% CI: -2.24 to 0.61kg). SWiM-C participants reported a greater reduction in experiential avoidance (-2.45, 95% CI: -4.75 to -0.15), uncontrolled eating (-3.36, 95% CI: -5.66 to -1.06), and emotional eating (-4.14, 95% CI: -7.25 to -1.02) and an increase in physical activity (8.96, 95% CI: 0.29 to 17.62) compared to standard advice participants.Conclusions: Whilst the effect of the SWiM-C intervention on weight was inconclusive, SWiM-C improved eating behaviours, psychological flexibility and physical activity. These factors have been previously identified as determinants of successful weight management. Further refinement of the SWiM-C intervention is necessary to ensure meaningful effects on weight prior to implementation in practice.
- Published
- 2022
44. Jacks (and Jills) of all trades: the gentle art of policing rural Iceland
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Thoroddur Bjarnason, Andrew Hill, and Guðmundur Oddsson
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Law - Published
- 2021
45. Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line antiretroviral therapy in adults failing a tenofovir-based first-line regimen
- Author
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Kaneez Sayed, Rene Goliath, Claire Keene, Rulan Griesel, Gert U. van Zyl, Eric Goemaere, Olina Ngwenya, Graeme Meintjes, Andrew Hill, Ying Zhao, Tracy Flowers, Tali Cassidy, Lubbe Wiesner, Gary Maartens, Zimasa Gcwabe, Charlotte Schutz, Amanda Jackson, and Bryony Simmons
- Subjects
Adult ,0301 basic medicine ,medicine.medical_specialty ,Efavirenz ,Nevirapine ,Anti-HIV Agents ,Pyridones ,Immunology ,HIV Infections ,Emtricitabine ,Piperazines ,South Africa ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Oxazines ,Humans ,Immunology and Allergy ,Medicine ,Prospective Studies ,030212 general & internal medicine ,Tenofovir ,Adverse effect ,business.industry ,virus diseases ,Lamivudine ,Viral Load ,Regimen ,030104 developmental biology ,Infectious Diseases ,chemistry ,Dolutegravir ,HIV-1 ,business ,Heterocyclic Compounds, 3-Ring ,Viral load ,medicine.drug - Abstract
Objective: Recycling tenofovir and lamivudine/emtricitabine (XTC) with dolutegravir would provide a more tolerable, affordable, and scalable second-line regimen than dolutegravir with an optimized nucleoside reverse transcriptase inhibitor (NRTI) backbone. We evaluated efficacy of tenofovir/lamivudine/dolutegravir (TLD) in patients failing first-line tenofovir/XTC/efavirenz or nevirapine. Design: Single arm, prospective, interventional study. Setting: Two primary care clinics in Khayelitsha, South Africa. Participants: Sixty adult patients with two viral loads greater than 1000 copies/ml. Intervention: Participants were switched to TLD with additional dolutegravir (50 mg) for 2 weeks to overcome efavirenz induction. Primary outcome: Proportion achieving viral load less than 50 copies/ml at week 24 using the FDA snapshot algorithm. Results: Baseline median CD4+ cell count was 248 cells/μl, viral load 10 580 copies/ml and 48 of 54 (89%) had resistance (Stanford score ≥15) to one or both of tenofovir and XTC. No participants were lost to follow-up. At week 24, 51 of 60 [85%, 95% confidence interval (CI) 73-93%] were virologically suppressed, six had viral load 50-100 copies/ml, one had viral load 100-1000 copies/ml, one no viral load in window, and one switched because of tenofovir-related adverse event. No integrase mutations were detected in the one participant meeting criteria for resistance testing. Virological suppression was achieved by 29 of 35 (83%, 95% CI 66-93%) with resistance to tenofovir and XTC, 11 of 13 (85%, 95% CI 55-98%) with resistance to XTC, and six of six (100%, 95% CI 54-100%) with resistance to neither. Conclusion: A high proportion of adults switching to second-line TLD achieved virologic suppression despite substantial baseline NRTI resistance and most not suppressed had low-level viraemia (≤100 copies/ml). This suggests recycling tenofovir and XTC with dolutegravir could provide an effective second-line option.
- Published
- 2021
46. Modeling the Population Health Impacts of Heated Tobacco Products in Japan
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Joshua D. Jones, Oscar M. Camacho, Stacy Fiebelkorn, Andrew Hill, Christopher Proctor, James Murphy, and Krishna Prasad
- Subjects
Health (social science) ,Geography ,Health Policy ,Environmental health ,Public Health, Environmental and Occupational Health ,Population health - Abstract
Objective: We evaluated the potential population health impact of launching heated tobacco products (HTP) in Japan. Method: We use a modeling approach to project the effects of HTP use in overall mortality up to 2100 and compare those projections against a baseline scenario based on smoking rates pre-HTP launch, ie, smoking only. The model was informed using data from publicly available sources and the literature, including population size, yearly deaths, and smoking prevalence with the initial year of 2004, and births and migration from 2004 to 2065. Transitions between products were estimated from cross-sectional population surveys in Japan. Result: In a worst-case scenario, population health gains would be seen with HTPs risk about 50% lower risk than smoking. Assuming equal risk for dual use and smoking, HTP risk would need to be at least 10% lower than smoking to achieve a population health benefit by 2100. Potential reduction in life-years lost with the introduction of HTPs was 13 million by 2100 compared with smoking only. Conclusions: In credible scenarios, substantial population harm reduction will follow the introduction of HTPs in Japan.
- Published
- 2021
47. Difficult diagnosis and management of a complicated Nellix graft infection
- Author
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Jin Xin Lin, Sam Frank Taylor, Cassandra Hidajat, and Andrew Hill
- Subjects
medicine.medical_specialty ,Complications ,RD1-811 ,medicine.medical_treatment ,Computed tomography ,030204 cardiovascular system & hematology ,030218 nuclear medicine & medical imaging ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Laparotomy ,Case report ,Diseases of the circulatory (Cardiovascular) system ,Medicine ,medicine.diagnostic_test ,business.industry ,Infected stent-graft ,medicine.disease ,surgical procedures, operative ,Positron emission tomography ,RC666-701 ,Surgery ,Surgical history ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,Nellix - Abstract
An 81-year-old man, with a complex vascular surgical history, presents with sepsis from an infected Nellix stent-graft. He required an urgent laparotomy, explantation of the graft, and extra-anatomical repair. Although now widely used for this indication, the preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography was nondiagnostic for his stent-graft infection. We describe our management of a complicated Nellix graft infection and discuss the utility of positron emission tomography/computed tomography for stent-graft infections.
- Published
- 2021
48. Amplatzer Post-Infarction Ventricular Septal Defect Closure via Retrograde Transarterial Access: Easier and Better
- Author
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Natalia Briceno, Thomas R. Keeble, James Cockburn, Andrew Hill, Gerald J. Clesham, Arionilson Gomes, Osama Alsanjari, and David Hildick-Smith
- Subjects
medicine.medical_specialty ,Percutaneous ,business.industry ,Closure (topology) ,medicine.disease ,Post-infarction ventricular septal defect ,Internal medicine ,cardiovascular system ,medicine ,Cardiology ,cardiovascular diseases ,Myocardial infarction ,Cardiology and Cardiovascular Medicine ,business - Abstract
Percutaneous closure of postinfarction ventricular septal defect (PIVSD) after myocardial infarction is one of the most demanding interventional procedures. Patients are usually hemodynamically bri...
- Published
- 2021
49. What we have learned from antiretroviral treatment optimization efforts over the last 5 years?
- Author
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Celicia Serenata, Polly Clayden, Toby Pepperrell, Kenly Sikwese, Ambar Qavi, Meg Doherty, Martina Penazzato, Luckyboy Mkhondwane, W D Francois Venter, Andrew Hill, and Marco Vitoria
- Subjects
medicine.medical_specialty ,Anti-HIV Agents ,business.industry ,Public health ,Immunology ,Hiv epidemic ,MEDLINE ,HIV Infections ,Antiretroviral therapy ,Regimen ,Infectious Diseases ,Anti-Retroviral Agents ,medicine ,Antiretroviral treatment ,Humans ,Immunology and Allergy ,Epidemics ,business ,Intensive care medicine ,Selection (genetic algorithm) - Abstract
Progression in the development of antiretroviral therapy has been remarkable, with new agents continuing to appear as options for modern regimens, including in low-and-middle income countries where the HIV epidemic is concentrated. Here, we reflect on progress made in guiding regimen changes to public health programmes, and the challenges facing selection of newer agents.
- Published
- 2021
50. Safety and efficacy of four drug regimens versus standard-of-care for the treatment of symptomatic outpatients with COVID-19: A randomised, open-label, multi-arm, phase 2 clinical trial
- Author
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Nomathemba Chandiwana, Chelsea Kruger, Hilary Johnstone, Mohamed Farouk Chughlay, Chung Ju, Byungsu Kim, Yengiwe Dineka, Sarah Arbe-Barnes, Robert Miller, Andrew Owen, Andrew Hill, Daniel Windgassen, Nada Abla, Anne Claire Marrast, Stephan Duparc, and Willem Daniel Francois Venter
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General Medicine ,General Biochemistry, Genetics and Molecular Biology - Abstract
This exploratory study investigated four repurposed anti-infective drug regimens in outpatients with COVID-19.This phase 2, single centre, randomised, open-label, clinical trial was conducted in South Africa between 3rd September 2020 and 23rd August 2021. Symptomatic outpatients aged 18-65 years, with RT-PCR confirmed SARS-CoV-2 infection were computer randomised (1:1:1:1:1) to standard-of-care (SOC) with paracetamol, or SOC plus artesunate-amodiaquine (ASAQ), pyronaridine-artesunate (PA), favipiravir plus nitazoxanide (FPV + NTZ), or sofosbuvir-daclatasvir (SOF-DCV). The primary endpoint was the incidence of viral clearance, i.e., the proportion of patients with a negative SARS-CoV-2 RT-PCR on day 7, compared to SOC using a log-binomial model in the modified intention-to-treat (mITT) population.The mITT population included 186 patients: mean age (SD) 34.9 (10.3) years, body weight 78.2 (17.1) kg. Day 7 SARS-CoV-2 clearance rates (n/N; risk ratio [95% CI]) were: SOC 34.2% (13/38), ASAQ 38.5% (15/39; 0.80 [0.44, 1.47]), PA 30.3% (10/33; 0.69 [0.37, 1.29]), FPV + NTZ 27.0% (10/37; 0.60 [0.31, 1.18]) and SOF-DCV 23.5% (8/34; 0.47 [0.22, 1.00]). Three lower respiratory tract infections occurred (PA 6.1% [2/33]; SOF-DCV 2.9% [1/34]); two required hospitalisation (PA, SOF-DCV). There were no deaths. Adverse events occurred in 55.3% (105/190) of patients, including one serious adverse event (pancytopenia; FPV + NTZ).There was no statistical difference in viral clearance for any regimen compared to SOC. All treatments were well tolerated.Medicines for Malaria Venture, with funding from the UK Foreign, Commonwealth and Development Office, within the Covid-19 Therapeutics Accelerator in partnership with Wellcome, the Bill and Melinda Gates Foundation, and Mastercard.
- Published
- 2022
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