Recent Submissions

  • Reply to: Inaccuracy of pulse oximetry in darker-skinned patients is unchanged across 32 years

    Crooks, Colin J.; Joe, West; Card, Tim; Shaw, Dominick; Simmonds, Mark (2022)
    We thank M.J. Tobin and A. Jubran for their interest in our data [1]. As they state, it is an extension of a body of work that they helped establish over 30 years ago.
  • Nitric oxide for the prevention and treatment of viral, bacterial, protozoal and fungal infections

    Bath, Philip M.; Lim, Wei Shen (2021)
    Although the antimicrobial potential of nitric oxide (NO) is widely published, it is little used clinically. NO is a key signalling molecule modulating vascular, neuronal, inflammatory and immune responses. Endogenous antimicrobial activity is largely mediated by high local NO concentrations produced by cellular inducible nitric oxide synthase, and by derivative reactive nitrogen oxide species including peroxynitrite and S-nitrosothiols. NO may be taken as dietary substrate (inorganic nitrate, L-arginine), and therapeutically as gaseous NO, and transdermal, sublingual, oral, intranasal and intravenous nitrite or nitrate. Numerous preclinical studies have demonstrated that NO has generic static and cidal activities against viruses (including beta-coronaviruses such as SARS-CoV-2), bacteria, protozoa and fungi/yeasts in vitro. Therapeutic effects have been seen in animal models in vivo, and phase II trials have demonstrated that NO donors can reduce microbial infection. Nevertheless, excess NO, as occurs in septic shock, is associated with increased morbidity and mortality. In view of the dose-dependent positive and negative effects of NO, safety and efficacy trials of NO and its donors are needed for assessing their role in the prevention and treatment of infections. Trials should test dietary inorganic nitrate for pre- or post-exposure prophylaxis and gaseous NO or oral, topical or intravenous nitrite and nitrate for treatment of mild-to-severe infections, including due to SARS-CoV-2 (COVID-19). This review summarises the evidence base from in vitro, in vivo and early phase clinical studies of NO activity in viral, bacterial, protozoal and fungal infections. Copyright: © 2021 Bath PM et al.
  • TIPSS as a bridge to extrahepatic abdominal surgery: A case report

    Kapeleris, Audrey Pamela; Venkatachalapathy, Suresh (2022)
    Severe portal hypertension in cirrhosis is a relative contraindication to major surgical intervention. Pre-surgical placement of a transjugular intrahepatic portosystemic shunt (TIPSS) can potentially reduce portal hypertension and the risk of intraoperative bleeding. Two patients in our service, with cirrhosis and portal hypertension, required abdominal surgery and underwent TIPSS placement as a potential bridging therapy. Patient 1, a 56-year-old female, successfully underwent surgery with no intraoperative complications. Patient 2, a 36-year-old male, experienced liver decompensation post-TIPSS and is currently awaiting a liver and bowel transplant. Prophylactic TIPSS placement may allow some patients with decompensated cirrhosis to successfully undergo major extrahepatic abdominal surgery. However, careful patient selection and preoperative counselling for decompensation is necessary. Copyright © The Author(s) 2022. Published by Oxford University Press.
  • QOL - 26. Exploring the experience of young people receiving remotely delivered acceptance and commitment therapy following treatment for a brain tumour

    Powers, Katie; Thomas, Sophie; Davies, Nicholas (2022)
    Despite high survival rates of children and young people diagnosed with a brain tumour, survival is often associated with poor psychological, physical, and social outcomes. Acceptance and Commitment Therapy (ACT) is an evidence-based psychological intervention shown to improve psychological and physical outcomes in adults and children with chronic disease, including cancer. The ACT Now study investigates the feasibility of ACT delivered remotely with young people who have experienced a brain tumour. This study aims to describe participant experience whilst better understanding the impact of therapy and capturing the barriers and facilitators to engagement. Participants of the ACT Now study were invited to take part in a semi-structured interview with questions covering experience of study initiation, receipt of ACT, remote delivery and overall impact of ACT. Ten participants who had previously undergone treatment for a brain tumour have been interviewed to date. Interviews were transcribed verbatim and coded into broad themes. We found that pre-therapy mood and altruism served as motivation for interviewees' involvement in the study. Interviewees reported hoping to learn coping techniques to navigate fluctuating moods and the pressures of young adult life. Despite the technology used for remote delivery occasionally malfunctioning, interviewees reported increased ability to access therapy via this method. However, an overall preference for face-to-face therapy delivery was reported with interviewees describing that they felt communication might have been easier in person. The therapeutic relationship and the therapists' flexible schedules were seen as facilitators to session attendance. Barriers to attendance were scarcely reported but included scheduling conflicts due to work or school. ACT was highly regarded amongst interviewees and provided an opportunity for them to learn about themselves and how they can live in accordance with their personal values. Interviewees benefitted from ACT psychologically, physically, and socially and reported an overall positive experience of study involvement.
  • QOL - 34. The relationship between psychological flexibility, quality-of-life and psychological health

    Davies, Nicholas; Powers, Katie; Grundy, Richard; Malins, Sam; Thomas, Sophie (2022)
    Despite increasing survival rates in young people who have experienced a brain tumour, this patient group have the poorest reported quality-of-life (QoL) of all cancer survivors. QoL is defined as an individual's perception of their position in life in relation to their goals, expectations and standards. QoL can be influenced by physical functioning but one of its strongest predictors is psychological health. A concept that has a large impact on psychological health is Psychological Flexibility (PF). PF refers to the ability to recognise and adapt to situations, shift cognitive and behavioural repertoires which are impacting negatively on personal and social functioning and commit to behaviours that are in line with strongly held values. Studies have demonstrated a relationship between PF and QoL in other patient populations such as chronic pain and breast cancer survivors. In this study we explored the relationship between PF and QoL at baseline in a sample of young people enrolled in a randomised controlled trial of Acceptance and Commitment Therapy (ACT) for young people who have experienced a brain tumour. We found that higher PF was associated with higher QoL in both 11-15 year olds (R2 = .69, p = .24, ps < .01) which was also associated with higher levels of QoL (R2 = .49 , p < .01). The results suggest assessing and providing support to increase PF is important for young people who have experienced a brain tumour. It highlights that interventions found to increase PF, such as ACT, could be helpful in improving psychological health in this population.
  • Serum levels of proinflammatory lipid mediators and specialized proresolving molecules are increased in patients with severe acute respiratory syndrome coronavirus 2 and correlate with markers of the adaptive immune response

    Turnbull, James; Jha, Rakesh R.; Lunt, Eleanor; Irving, William L.; Gohir, Sameer A.; Valdes, Ana M.; Tarr, Alexander W.; Barrett, David A.; Chapman, Victoria (2022)
    Abstract Background Specialized proresolution molecules (SPMs) halt the transition to chronic pathogenic inflammation. We aimed to quantify serum levels of pro- and anti-inflammatory bioactive lipids in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients, and to identify potential relationships with innate responses and clinical outcome. Methods Serum from 50 hospital admitted inpatients (22 female, 28 male) with confirmed symptomatic SARS-CoV-2 infection and 94 age- and sex-matched controls collected prior to the pandemic (SARS-CoV-2 negative), were processed for quantification of bioactive lipids and anti-nucleocapsid and anti-spike quantitative binding assays. Results SARS-CoV-2 serum had significantly higher concentrations of omega-6–derived proinflammatory lipids and omega-6– and omega-3–derived SPMs, compared to the age- and sex-matched SARS-CoV-2–negative group, which were not markedly altered by age or sex. There were significant positive correlations between SPMs, proinflammatory bioactive lipids, and anti-spike antibody binding. Levels of some SPMs were significantly higher in patients with an anti-spike antibody value >0.5. Levels of linoleic acid and 5,6-dihydroxy-8Z,11Z,14Z-eicosatrienoic acid were significantly lower in SARS-CoV-2 patients who died. Conclusions SARS-CoV-2 infection was associated with increased levels of SPMs and other pro- and anti-inflammatory bioactive lipids, supporting the future investigation of the underlying enzymatic pathways, which may inform the development of novel treatments.
  • Development and validation of a prognostic model for leflunomide discontinuation with abnormal blood tests during long-term treatment: Cohort study using data from the clinical practice research datalink gold and aurum

    Aithal, Guruprasad P.; Fox, Christopher P.; Abhishek, Abhishek (2022)
    OBJECTIVE: To develop and validate a prognostic model for LEF discontinuation with abnormal blood test results. METHODS: Data from the Clinical Practice Research Datalink Gold and Aurum were used for model development and external validation, respectively. Participants prescribed LEF between 1 January 2007 and 31 December 2019 were followed up from 6 months after the first general practitioner prescription to the earliest of date of outcome, death, 5 year follow-up or 31 December 2019. Candidate prognostic factors were ascertained using theory and data-driven approaches. Penalized Cox regression was performed to develop the risk equation, followed by internal validation using 500 bootstraps to correct for optimism. Multiple imputation was applied to handle missing data. Model performance was assessed in terms of calibration and discrimination. RESULTS: Data for 1487 and 2329 participants contributing 3140 and 5246 person-years follow-up were included in the development and validation cohorts, respectively. Thirteen candidate predictors were included in the model. Epilepsy and either cytopenia or elevated liver enzymes during the first 6 months of shared-care LEF prescription were strong predictors of drug discontinuation with a hazard ratio of 4.39 (95% CI 1.74, 11.06) and 3.06 (2.15, 4.35), respectively. The unadjusted and optimism-adjusted calibration slope in development data was 1.00 (95% CI 0.75, 1.25) and 0.72 (95% CI 0.47, 0.97), respectively. The calibration slope in validation data was 0.91 (95% CI 0.74, 1.07). The model showed prognostic separation with an optimism-adjusted Royston D statistic of 0.73 (95% CI 0.44, 1.02). CONCLUSION: We have developed and externally validated an easy-to-use prognostic model that may be used to risk stratify monitoring for LEF toxicity and to make informed choices about risks when choosing treatments. Copyright © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.
  • Foot and ankle osteoarthritis and cognitive impairment in retired UK soccer players (FOCUS): Protocol for a cross-sectional comparative study with general population controls

    Batt, Mark (2022)
    INTRODUCTION: Professional footballers commonly experience sports-related injury and repetitive microtrauma to the foot and ankle, placing them at risk of subsequent chronic pain and osteoarthritis (OA) of the foot and ankle. Similarly, repeated heading of the ball, head/neck injuries and concussion have been implicated in later development of neurodegenerative diseases such as dementia. A recent retrospective study found that death from neurodegenerative diseases was higher among former professional soccer players compared with age matched controls. However, well-designed lifetime studies are still needed to provide evidence regarding the prevalence of these conditions and their associated risk factors in retired professional football players compared with the general male population. OBJECTIVES: To determine whether former professional male footballers have a higher prevalence than the general male population of: (1) foot/ankle pain and radiographic OA; and (2) cognitive and motor impairments associated with dementia and Parkinson's disease. Secondary objectives are to identify specific football-related risk factors such as head impact/concussion for neurodegenerative conditions and foot/ankle injuries for chronic foot/ankle pain and OA. METHODS AND ANALYSIS: This is a cross-sectional, comparative study involving a questionnaire survey with subsamples of responders being assessed for cognitive function by telephone assessment, and foot/ankle OA by radiographic examination. A sample of 900 adult, male, ex professional footballers will be recruited and compared with a control group of 1100 age-matched general population men between 40 and 100 years old. Prevalence will be estimated per group. Poisson regression will be performed to determine prevalence ratio between the populations and logistic regression will be used to examine risk factors associated with each condition in footballers. ETHICS AND DISSEMINATION: This study was approved by the East Midlands-Leicester Central Research Ethics Committee on 23 January 2020 (REC ref: 19/EM/0354). The study results will be disseminated at national and international meetings and submitted for peer-review publication. Copyright © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
  • Italian guidelines for the management of irritable bowel syndrome: Joint consensus from the Italian societies of: Gastroenterology and Endoscopy (SIGE), Neurogastroenterology and Motility (SINGEM), Hospital Gastroenterologists and Endoscopists (AIGO), Digestive Endoscopy (SIED), General Medicine (SIMG), Gastroenterology, Hepatology and Pediatric Nutrition (SIGENP) and Pediatrics (SIP)

    Corsetti, Maura (2023)
    The irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction. IBS is still associated with areas of uncertainties, especially regarding the optimal diagnostic work-up and the more appropriate management. Experts from 7 Italian Societies conducted a Delphi consensus with literature summary and voting process on 27 statements. Recommendations and quality of evidence were evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was defined as >80% agreement and reached for all statements. In terms of diagnosis, the consensus supports a positive diagnostic strategy with a symptom-based approach, including the psychological comorbidities assessment and the exclusion of alarm symptoms, together with the digital rectal examination, full blood count, C-reactive protein, serology for coeliac disease, and fecal calprotectin assessment. Colonoscopy should be recommended in patients with alarm features. Regarding treatment, the consensus strongly supports a dietary approach for patients with IBS, the use of soluble fiber, secretagogues, tricyclic antidepressants, psychologically directed therapies and, only in specific IBS subtypes, rifaximin. A conditional recommendation was achieved for probiotics, polyethylene glycol, antispasmodics, selective serotonin reuptake inhibitors and, only in specific IBS subtypes, 5-HT3 antagonists, 5-HT4 agonists, bile acid sequestrants. Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
  • The rs429358 locus in apolipoprotein E is associated with hepatocellular carcinoma in patients with cirrhosis

    Guha, Indra Neil; Irving, William L.; Benselin, Jennifer; Morling, Joanne R. (2022)
    The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol-3-phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol-related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case-control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP-HCV), and one alcohol-related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed-effect meta-analysis was used to determine the pooled effect size across all data sets. Across four case-control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61-0.84; P = 2.9 x 10-5). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45-2.86; P = 3.1 x 10-6). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90-1.13; P = 0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84-1.00; P = 0.043). Conclusion(s): This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis.Copyright © 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.
  • Semantic segmentation of spontaneous intracerebral hemorrhage, intraventricular hemorrhage, and associated edema on CT images using deep learning

    Krishnan, Kailash; Bath, Philip M.; Sprigg, Nikola; Dineen, Robert A. (2022)
    This study evaluated deep learning algorithms for semantic segmentation and quantification of intracerebral hemorrhage (ICH), perihematomal edema (PHE), and intraventricular hemorrhage (IVH) on noncontrast CT scans of patients with spontaneous ICH. Models were assessed on 1732 annotated baseline noncontrast CT scans obtained from the Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (ie, TICH-2) international multicenter trial (ISRCTN93732214), and different loss functions using a three-dimensional no-new-U-Net (nnU-Net) were examined to address class imbalance (30% of participants with IVH in dataset). On the test cohort (n = 174, 10% of dataset), the top-performing models achieved median Dice similarity coefficients of 0.92 (IQR, 0.89-0.94), 0.66 (0.58-0.71), and 1.00 (0.87-1.00), respectively, for ICH, PHE, and IVH segmentation. U-Net-based networks showed comparable, satisfactory performances on ICH and PHE segmentations (P . .05), but all nnU-Net variants achieved higher accuracy than the Brain Lesion Analysis and Segmentation Tool for CT (BLAST-CT) and DeepLabv31 for all labels (P, .05). The Focal model showed improved performance in IVH segmentation compared with the Tversky, two-dimensional nnU-Net, U-Net, BLAST-CT, and DeepLabv31 models (P, .05). Focal achieved concordance values of 0.98, 0.88, and 0.99 for ICH, PHE, and ICH volumes, respectively. The mean volumetric differences between the ground truth and prediction were 0.32 mL (95% CI: -8.35, 9.00), 1.14 mL (-9.53, 11.8), and 0.06 mL (-1.71, 1.84), respectively. In conclusion, U-Net-based networks provide accurate segmentation on CT images of spontaneous ICH, and Focal loss can address class imbalance. International Clinical Trials Registry Platform (ICTRP) no. ISRCTN93732214.Copyright © RSNA, 2022.
  • Matching the outcomes to treatment targets of exercise for low back pain: Does it make a difference? Results of secondary analyses from individual patient data of randomised controlled trials and pooling of results across trials in comparative meta-analysis

    Wood, Lianne (2023)
    OBJECTIVE: To explore whether using a single matched or composite outcome might affect the results of previous randomized controlled trials (RCTs) testing exercise for non-specific low back pain (NSLBP). The first objective was to explore whether a single matched outcome generated greater standardized mean differences (SMDs) when compared with the original unmatched primary outcome SMD. The second objective was to explore whether a composite measure, composed of matched outcomes, generated a greater SMD when compared with the original primary outcome SMD. DESIGN: We conducted exploratory secondary analyses of data. SETTING: Seven RCTs were included, of which 2 were based in the USA (University research clinic, Veterans Affairs medical center) and the UK (primary care clinics, nonmedical centers). One each were based in Norway (clinics), Brazil (primary care), and Japan (outpatient clinics). PARTICIPANTS: The first analysis comprised 1) 5 RCTs (n=1033) that used an unmatched primary outcome but included (some) matched outcomes as secondary outcomes, and the second analysis comprised 2) 4 RCTs (n=864) that included multiple matched outcomes by developing composite outcomes (N=1897). INTERVENTION: Exercise compared with no exercise. MAIN OUTCOME MEASURES: The composite consisted of standardized averaged matched outcomes. All analyses replicated the RCTs' primary outcome analyses. RESULTS: Of 5 RCTs, 3 had greater SMDs with matched outcomes (pooled effect SMD 0.30 [95% confidence interval {CI} 0.04, 0.56], P=.02) compared with an unmatched primary outcome (pooled effect SMD 0.19 [95% CI -0.03, 0.40] P=.09). Of 4 composite outcome analyses, 3 RCTs had greater SMDs in the composite outcome (pooled effect SMD 0.28 [95% CI 0.05, 0.51] P=.02) compared with the primary outcome (pooled effect SMD 0.24 [95% CI -0.04, 0.53] P=.10). CONCLUSIONS: These exploratory analyses suggest that using an outcome matched to exercise treatment targets in NSLBP RCTs may produce greater SMDs than an unmatched primary outcome. Composite outcomes could offer a meaningful way of investigating superiority of exercise than single domain outcomes. Copyright © 2022 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
  • Functional bowel disorders with diarrhoea: Clinical guidelines of the united European gastroenterology and European society for neurogastroenterology and motility

    Corsetti, Maura (2022)
    Irritable bowel syndrome with diarrhoea (IBS-D) and functional diarrhoea (FDr) are the two major functional bowel disorders characterized by diarrhoea. In spite of their high prevalence, IBS-D and FDr are associated with major uncertainties, especially regarding their optimal diagnostic work-up and management. A Delphi consensus was performed with experts from 10 European countries who conducted a literature summary and voting process on 31 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation criteria. Consensus (defined as >80% agreement) was reached for all the statements. The panel agreed with the potential overlapping of IBS-D and FDr. In terms of diagnosis, the consensus supports a symptom-based approach also with the exclusion of alarm symptoms, recommending the evaluation of full blood count, C-reactive protein, serology for coeliac disease, and faecal calprotectin, and consideration of diagnosing bile acid diarrhoea. Colonoscopy with random biopsies in both the right and left colon is recommended in patients older than 50 years and in presence of alarm features. Regarding treatment, a strong consensus was achieved for the use of a diet low fermentable oligo-, di-, monosaccharides and polyols, gut-directed psychological therapies, rifaximin, loperamide, and eluxadoline. A weak or conditional recommendation was achieved for antispasmodics, probiotics, tryciclic antidepressants, bile acid sequestrants, 5-hydroxytryptamine-3 antagonists (i.e. alosetron, ondansetron, or ramosetron). A multinational group of European experts summarized the current state of consensus on the definition, diagnosis, and management of IBS-D and FDr. Copyright © 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.
  • Dynamic susceptibility-contrast magnetic resonance imaging with contrast agent leakage correction aids in predicting grade in pediatric brain tumours: A multicenter study

    Morgan, Paul S.; Auer, Dorothee P. (2022)
    BACKGROUND: Relative cerebral blood volume (rCBV) measured using dynamic susceptibility-contrast MRI can differentiate between low- and high-grade pediatric brain tumors. Multicenter studies are required for translation into clinical practice. OBJECTIVE: We compared leakage-corrected dynamic susceptibility-contrast MRI perfusion parameters acquired at multiple centers in low- and high-grade pediatric brain tumors. MATERIALS AND METHODS: Eighty-five pediatric patients underwent pre-treatment dynamic susceptibility-contrast MRI scans at four centers. MRI protocols were variable. We analyzed data using the Boxerman leakage-correction method producing pixel-by-pixel estimates of leakage-uncorrected (rCBVuncorr) and corrected (rCBVcorr) relative cerebral blood volume, and the leakage parameter, K2. Histological diagnoses were obtained. Tumors were classified by high-grade tumor. We compared whole-tumor median perfusion parameters between low- and high-grade tumors and across tumor types. RESULTS: Forty tumors were classified as low grade, 45 as high grade. Mean whole-tumor median rCBVuncorr was higher in high-grade tumors than low-grade tumors (mean +/- standard deviation [SD] = 2.37+/-2.61 vs. -0.14+/-5.55; P was higher in high-grade tumors than low-grade tumors (mean +/- standard deviation [SD] = 2.37+/-2.61 vs. -0.14+/-5.55; P2=0.017+/-0.049 vs. 0.002+/-0.017). Parameters varied with tumor type but not center. Median rCBVuncorr was higher (mean = 1.49 vs. 0.49; P=0.015) and K2 lower (mean = 0.005 vs. 0.016; P=0.013) in children who received a pre-bolus of contrast agent compared to those who did not. Leakage correction removed the difference. CONCLUSION: Dynamic susceptibility-contrast MRI acquired at multiple centers helped distinguish between children's brain tumors. Relative cerebral blood volume was significantly higher in high-grade compared to low-grade tumors and differed among common tumor types. Vessel leakage correction is required to provide accurate rCBV, particularly in low-grade enhancing tumors. Copyright © 2022. The Author(s).
  • The UN decade of healthy ageing: Strengthening measurement for monitoring health and wellbeing of older people

    Harwood, Rowan H. (2022)
    Over the past 100 years, life expectancy has increased dramatically in nearly all nations. Yet, these extra years of life gained have not all been healthy, particularly for older people aged 60 years and over. In 2020, the World Health Organisation (WHO) and United Nations (UN) member states embraced a sweeping 10-year global plan of action to ensure all older people can live long and healthy lives, formally known as the UN Decade of Healthy Ageing (2021-2030). With the adoption of the UN Decade of Healthy Ageing resolution, countries are committed to implementing collaborative actions to improve the lives of older people, their families and the communities in which they reside. The Decade addresses four interconnected areas of action. Adopting the UN's resolution on the Decade of Healthy Ageing has caused excitement, but a question that has weighed on everyone's mind is how governments will be held accountable? Besides, there have been no goals or targets set for the UN Decade of Healthy Ageing from a programmatic perspective for the action areas, and guidance on measures, data collection, analysis and reporting are urgently needed to support global, regional and national monitoring of the national strategies, programmes and policies. To this end, WHO in collaboration with UN agencies and international agencies established a Technical Advisory Group for Measurement of Healthy Ageing (TAG4MHA) to provide advice on the measurement, monitoring and evaluation of the UN Decade of Healthy Ageing at the global, regional and national levels. Copyright © 2022 The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.
  • Real-world outcomes of direct-acting antiviral treatment and retreatment in United Kingdom-based patients infected with hepatitis C virus genotypes/subtypes endemic in Africa

    McClure, C. Patrick; Irving, William L.; Adeboyejo, Kazeem; Ball, Jonathan K. (2022)
    BACKGROUND: Chronic hepatitis C virus (HCV) infection affects 71 million individuals, mostly residing in low- and middle-income countries (LMICs). Direct-acting antivirals (DAAs) give high rates of sustained virological response (SVR) in high-income countries where a restricted range of HCV genotypes/subtypes circulate. METHODS: We studied United Kingdom-resident patients born in Africa to examine DAA effectiveness in LMICs where there is far greater breadth of HCV genotypes/subtypes. Viral genome sequences were determined from 233 patients. RESULTS: Full-length viral genomic sequences for 26 known subtypes and 5 previously unidentified isolates covering 5 HCV genotypes were determined. From 149 patients who received DAA treatment/retreatment, the overall SVR was 93%. Treatment failure was associated primarily with 2 subtypes, gt1l and gt4r, using sofosbuvir/ledipasvir. These subtypes contain natural resistance-associated variants that likely contribute to poor efficacy with this drug combination. Treatment failure was also significantly associated with hepatocellular carcinoma. CONCLUSIONS: DAA combinations give high SVR rates despite the high HCV diversity across the African continent except for subtypes gt1l and gt4r, which respond poorly to sofosbuvir/ledipasvir. These subtypes are widely distributed across Western, Central, and Eastern Africa. Thus, in circumstances where accurate genotyping is absent, ledipasvir and its generic compounds should not be considered as a recommended treatment option. Copyright © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.
  • The core rehabilitation outcome set for single-sided deafness (CROSSSD) study: International consensus on outcome measures for trials of interventions for adults with single-sided deafness

    Horobin, Adele (2022)
    BACKGROUND: Single-sided deafness (SSD) has functional, psychological, and social consequences. Interventions for adults with SSD include hearing aids and auditory implants. Benefits and harms (outcome domains) of these interventions are until now reported inconsistently in clinical trials. Inconsistency in reporting outcome measures prevents meaningful comparisons or syntheses of trial results. The Core Rehabilitation Outcome Set for Single-Sided Deafness (CROSSSD) international initiative used structured communication techniques to achieve consensus among healthcare users and professionals working in the field of SSD. The novel contribution is a set of core outcome domains that experts agree are critically important to assess in all clinical trials of SSD interventions. METHODS: A long list of candidate outcome domains compiled from a systematic review and published qualitative data, informed the content of a two-round online Delphi survey. Overall, 308 participants from 29 countries were enrolled. Of those, 233 participants completed both rounds of the survey and scored each outcome domain on a 9-point scale. The set of core outcome domains was finalised via a web-based consensus meeting with 12 participants. Votes involved all stakeholder groups, with an approximate 2:1 ratio of professionals to healthcare users participating in the Delphi survey, and a 1:1 ratio participating in the consensus meeting. RESULTS: The first round of the survey listed 44 potential outcome domains, organised thematically. A further five outcome domains were included in Round 2 based on participant feedback. The structured voting at round 2 identified 17 candidate outcome domains which were voted on at the consensus meeting. Consensus was reached for a core outcome domain set including three outcome domains: spatial orientation, group conversations in noisy social situations, and impact on social situations. Seventy-seven percent of the remaining Delphi participants agreed with this core outcome domain set. CONCLUSIONS: Adoption of the internationally agreed core outcome domain set would promote consistent assessment and reporting of outcomes that are meaningful and important to all relevant stakeholders. This consistency will in turn enable comparison of outcomes reported across clinical trials comparing SSD interventions in adults and reduce research waste. Further research will determine how those outcome domains should best be measured. Copyright © 2022. The Author(s).

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