Now showing items 1-20 of 92

    • Hyoscine butylbromide mode of action on bowel motility: From pharmacology to clinical practice

      Corsetti, Maura (2023)
      BACKGROUND: Hyoscine butylbromide (HBB) has been available for use as an antispasmodic since 1951 and is indicated for the treatment of abdominal pain associated with cramps. A previous review in 2007 summarized the evidence on the mode of action of HBB in vitro and in vivo in both animal and human studies. However, since then, novel publications have appeared within the literature and also our knowledge of what represents normal motility in humans has evolved. PURPOSE: This review is the result of the collaboration between a basic scientist and clinicians with the aim of providing an updated overview of the mechanisms of action of HBB and its clinical efficacy to guide not only use in clinical practice, but also future research. Copyright © 2022 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.
    • Bronchopulmonary dysplasia prediction models: A systematic review and meta-analysis with validation

      Kwok, T'ng Chang; Batey, Natalie; Luu, Ka Ling; Prayle, Andrew; Sharkey, Don (2023)
      Prediction models could identify infants at the greatest risk of bronchopulmonary dysplasia (BPD) and allow targeted preventative strategies. We performed a systematic review and meta-analysis with external validation of identified models. Studies using predictors available before day 14 of life to predict BPD in very preterm infants were included. Two reviewers assessed 7628 studies for eligibility. Meta-analysis of externally validated models was followed by validation using 62,864 very preterm infants in England and Wales. A total of 64 studies using 53 prediction models were included totalling 274,407 infants (range 32-156,587/study). In all, 35 (55%) studies predated 2010; 39 (61%) were single-centre studies. A total of 97% of studies had a high risk of bias, especially in the analysis domain. Following meta-analysis of 22 BPD and 11 BPD/death composite externally validated models, Laughon's day one model was the most promising in predicting BPD and death (C-statistic 0.76 (95% CI 0.70-0.81) and good calibration). Six models were externally validated in our cohort with C-statistics between 0.70 and 0.90 but with poor calibration. Few BPD prediction models were developed with contemporary populations, underwent external validation, or had calibration and impact analyses. Contemporary, validated, and dynamic prediction models are needed for targeted preventative strategies. IMPACT: This review aims to provide a comprehensive assessment of all BPD prediction models developed to address the uncertainty of which model is sufficiently valid and generalisable for use in clinical practice and research. Published BPD prediction models are mostly outdated, single centre and lack external validation. Laughon's 2011 model is the most promising but more robust models, using contemporary data with external validation are needed to support better treatments. Copyright © 2023. The Author(s).
    • MRI and molecular characterization of pediatric high-grade midline thalamic gliomas: The HERBY phase II trial

      Dineen, Robert A.; Morgan, Paul S.; Jaspan, Timothy (2022)
      Background Diffuse midline gliomas (DMG) are characterized by a high incidence of H3 K27 mutations and poorer outcome. The HERBY trial has provided one of the largest cohorts of pediatric DMGs with available radiologic, histologic-genotypic, and survival data. Purpose To define MRI and molecular characteristics of DMG. Materials and Methods This study is a secondary analysis of a prospective trial (HERBY; identifier, NCT01390948) undertaken between October 2011 and February 2016. Among 121 HERBY participants, 50 had midline nonpontine-based tumors. Midline high-grade gliomas were reclassified into DMG H3 K27 mutant, H3 wild type with enhancer of zest homologs inhibitory protein overexpression, epidermal growth factor receptormutant, or not otherwise stated. The epicenter of each tumor and other radiologic characteristics were ascertained from MRI and correlated with the new subtype classification, histopathologic characteristics, surgical extent, and outcome parameters. Kaplan-Meier curves and log-rank tests were applied to determine and describe survival differences between groups. Results There were 42 participants (mean age, 12 years +/- 4 [SD]; 23 girls) with radiologically evaluable thalamic-based DMG. Eighteen had partial thalamic involvement (12 thalamopulvinar, six anteromedial), 10 involved a whole thalamus, nine had unithalamic tumors with diffuse contiguous extension, and five had bithalamic tumors (two symmetric, three partial). Twenty-eight participants had DMG H3 K27 mutant tumors; there were no differences in outcome compared with other DMGs (n = 4). Participants who underwent major debulking or total or near-total resection had longer overall survival (OS): 18.5 months vs 11.4 months (P = .02). Enrolled participants who developed leptomeningeal metastatic dissemination before starting treatment had worse outcomes (event-free survival, 2.9 months vs 8.0 months [P = .02]; OS, 11.4 months vs 18.5 months [P = .004]). Conclusion Thalamic involvement of diffuse midline gliomas ranged from localized partial thalamic to holo- or bithalamic with diffuse contiguous spread and had poor outcomes, irrespective of H3 K27 subtype alterations. Leptomeningeal dissemination and less than 50% surgical resection were adverse risk factors for survival. Clinical trial registration no. NCT01390948 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Widjaja in this issue.
    • Towards development of a non-toxigenic clostridioides difficile oral spore vaccine against toxigenic C. difficile

      Griffin, Ruth (2022)
      Clostridioides difficile is an opportunistic gut pathogen which causes severe colitis, leading to significant morbidity and mortality due to its toxins, TcdA and TcdB. Two intra-muscular toxoid vaccines entered Phase III trials and strongly induced toxin-neutralising antibodies systemically but failed to provide local protection in the colon from primary C. difficile infection (CDI). Alternatively, by immunising orally, the ileum (main immune inductive site) can be directly targeted to confer protection in the large intestine. The gut commensal, non-toxigenic C. difficile (NTCD) was previously tested in animal models as an oral vaccine for natural delivery of an engineered toxin chimera to the small intestine and successfully induced toxin-neutralising antibodies. We investigated whether NTCD could be further exploited to induce antibodies that block the adherence of C. difficile to epithelial cells to target the first stage of pathogenesis. In NTCD strain T7, the colonisation factor, CD0873, and a domain of TcdB were overexpressed. Following oral immunisation of hamsters with spores of recombinant strain, T7-0873 or T7-TcdB, intestinal and systemic responses were investigated. Vaccination with T7-0873 successfully induced intestinal antibodies that significantly reduced adhesion of toxigenic C. difficile to Caco-2 cells, and these responses were mirrored in sera. Additional engineering of NTCD is now warranted to further develop this vaccine.
    • Economic evaluation of using daily prednisolone versus placebo at the time of an upper respiratory tract infection for the management of children with steroid-sensitive nephrotic syndrome: A model-based analysis

      Christian, Martin T. (2022)
      Background: Childhood steroid-sensitive nephrotic syndrome is a frequently relapsing disease with significant short- and long-term complications, leading to high healthcare costs and reduced quality of life for patients. The majority of relapses are triggered by upper respiratory tract infections (URTIs) and evidence shows that daily low-dose prednisolone at the time of infection may reduce the risk of relapse. Objective(s): The aim of this study was to assess the cost effectiveness of a 6-day course of low-dose prednisolone at the start of a URTI when compared with placebo. Method(s): A state-transition Markov model was developed to conduct a cost-utility analysis with the outcome measured in quality-adjusted life-years (QALYs). Resource use and outcome data were derived from the PREDNOS2 trial. The analysis was performed from a UK National Health Service perspective and the results were extrapolated to adulthood. Model parameter and structural uncertainty were assessed using sensitivity analyses. Result(s): The base-case results showed that administering low-dose prednisolone at the time of a URTI generated more QALYs and a lower mean cost at 1 year compared with placebo. In the long-term, low-dose prednisolone was associated with a cost saving (176) and increased effectiveness (0.01 QALYs) compared with placebo and thus remained the dominant treatment option. These findings were robust to all sensitivity analyses. Conclusion(s): A 6-day course of low-dose prednisolone at the time of a URTI in children with steroid-sensitive nephrotic syndrome has the potential to reduce healthcare costs and improve quality of life compared with placebo.Copyright © 2022, The Author(s).
    • Utilising electronic PROMs to measure a change in health following elective laparoscopic cholecystectomy: A feasibility study

      Daliya, Prita; Lobo, Dileep N.; Parsons, Simon L. (2022)
      BACKGROUND: The collection of patient-reported outcome measures (PROMs) has many benefits for clinical practice. However, there are many barriers that prevent them from becoming a part of routine clinical care. The aim of this feasibility study was to pilot the use of a digital platform to facilitate the routine collection of pre- and post-operative electronic PROMs (ePROMs) in participants undergoing elective laparoscopic cholecystectomy and to validate the use of existing patient-reported outcomes for our population. METHOD(S): Participants scheduled for elective laparoscopic cholecystectomy were asked to complete digital versions of the Otago gallstones Condition-Specific Questionnaire (CSQ), and the RAND 36-item health survey (SF36). An assessment of methodological quality of ePROM questionnaires was also performed. RESULT(S): Preoperative ePROMs were completed by 200 participants undergoing laparoscopic cholecystectomy. Post-operatively attrition was high (completion at 30 days, 3 months, and 6months: n = 61, 54, and 38, respectively) due to difficulties accessing our ePROMs portal. Of those able to complete, a significant improvement in quality of life was seen across all health domains post-operatively when compared with baseline preoperative values for both disease-specific and generic PROMs. Methodological quality was assessed as good to excellent in both digital questionnaires. CONCLUSION(S): The collection of ePROMs is possible with current technological advances. Although it may be an acceptable, and convenient process for patients, and a useful measure of quality-of-life trends for clinicians, further developmental work is necessary to improve accessibility for patients, improve compliance, and reduce reporting bias from high attrition rates.Copyright © 2022. The Author(s).
    • Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: Results from a genome-wide case-control study

      Innes, Hamish; Guha, Neil (2023)
      Objective Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. Design Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). Results Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41x10 -9, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94x10 -5, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12x10 -44). Conclusion This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.Copyright © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.
    • Laparoscopic colorectal surgery outcomes improved after national training program (LAPCO) for specialists in England

      Aulin, Paul; Acheson, Austin; Maxwell-Armstrong, Charles (2022)
      OBJECTIVE: To examine the impact of The National Training Program for Lapco on the rate of laparoscopic surgery and clinical outcomes of cases performed by Lapco surgeons after completion of training. SUMMARY OF BACKGROUND DATA: Lapco provided competency-based supervised clinical training for specialist colorectal surgeons in England. METHODS: We compared the rate of laparoscopic surgery, mortality, and morbidity for colorectal cancer resections by Lapco delegates and non-Lapco surgeons in 3-year periods preceding and following Lapco using difference in differences analysis. The changes in the rate of post-Lapco laparoscopic surgery with the Lapco sign-off competency assessment and in-training global assessment scores were examined using risk-adjusted cumulative sum to determine their predictive clinical validity with predefined competent scores of 3 and 5 respectively. RESULTS: One hundred eight Lapco delegates performed 4586 elective colo-rectal resections pre-Lapco and 5115 post-Lapco while non-Lapco surgeons performed 72,930 matched cases. Lapco delegates had a 37.8% increase in laparoscopic surgery which was greater than non-Lapco surgeons by 20.9% [95% confidence interval (CI), 18.5-23.3, P Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
    • Whole-body and muscle responses to aerobic exercise training and withdrawal in ageing and COPD

      Constantin, Despina; Bolton, Charlotte E.; Greenhaff, Paul L. (2022)
      BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients exhibit lower peak oxygen uptake (V'O2peak), altered muscle metabolism and impaired exercise tolerance compared with age-matched controls. Whether these traits reflect muscle-level deconditioning (impacted by ventilatory constraints) and/or dysfunction in mitochondrial ATP production capacity is debated. By studying aerobic exercise training (AET) at a matched relative intensity and subsequent exercise withdrawal period we aimed to elucidate the whole-body and muscle mitochondrial responsiveness of healthy young (HY), healthy older (HO) and COPD volunteers to whole-body exercise. METHOD(S): HY (n=10), HO (n=10) and COPD (n=20) volunteers were studied before and after 8 weeks of AET (65% V'O2peak) and after 4 weeks of exercise withdrawal. V'O2peak, muscle maximal mitochondrial ATP production rate (MAPR), mitochondrial content, mitochondrial DNA (mtDNA) copy number and abundance of 59 targeted fuel metabolism mRNAs were determined at all time-points. RESULT(S): Muscle MAPR (normalised for mitochondrial content) was not different for any substrate combination in HO, HY and COPD at baseline, but mtDNA copy number relative to a nuclear-encoded housekeeping gene (mean+/-sd) was greater in HY (804+/-67) than in HO (631+/-69; p=0.041). AET increased V'O2peak in HO (17%; p=0.002) and HY (21%; pRESULT(S): Muscle MAPR (normalised for mitochondrial content) was not different for any substrate combination in HO, HY and COPD at baseline, but mtDNA copy number relative to a nuclear-encoded housekeeping gene (mean+/-sd) was greater in HY (804+/-67) than in HO (631+/-69; p=0.041). AET increased V'O2peak in HO (17%; p=0.002) and HY (21%; pCONCLUSION(S): Intrinsic mitochondrial function was not impaired by ageing or COPD in the untrained state. Whole-body and muscle mitochondrial responses to AET were robust in HY, evident in HO, but deficient in COPD. All groups showed robust muscle mRNA responses. Higher relative exercise intensities during whole-body training may be needed to maximise whole-body and muscle mitochondrial adaptation in COPD.Copyright ©The authors 2022.
    • Reconstructing the puzzle of the role of therapeutic endoscopy in the management of post-bariatric surgery complications

      Parra-Blanco, Adolfo (2022)
      We have recently read with interest the mini-review article "Therapeutic endoscopy for the treatment of post-bariatric surgery complications". The abovementioned article is a brief overview of the different endoscopic modalities employed in the management of bariatric surgery complications and represents an important decision support tool for clinicians to improve their current practice. Although we appreciate the endeavor of Larsen and Kozarek, based on our in-depth analysis, we came across several minor issues in this article; thus, we present our comments in this letter. In case the authors contemplate these comments in their relevant research, we believe that their contribution would be considerable for future studies. Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
    • Human parainfluenza 2 & 4: Clinical and genetic epidemiology in the UK, 2013-2017, reveals distinct disease features and co-circulating genomic subtypes

      Clark, Gemma; Howson-Wells, Hannah C.; Berry, Louise; Irving, William L. (2022)
      Background: Human Parainfluenza viruses (HPIV) comprise of four members of the genetically distinct genera of Respirovirus (HPIV1&3) and Orthorubulavirus (HPIV2&4), causing significant upper and lower respiratory tract infections worldwide, particularly in children. However, despite frequent molecular diagnosis, they are frequently considered collectively or with HPIV4 overlooked entirely. We therefore investigated clinical and viral epidemiological distinctions of the relatively less prevalent Orthorubulaviruses HPIV2&4 at a regional UK hospital across four autumn/winter epidemic seasons. Method(s): A retrospective audit of clinical features of all HPIV2 or HPIV4 RT-PCR-positive patients, diagnosed between 1st September 2013 and 12th April 2017 was undertaken, alongside sequencing of viral genome fragments in a representative subset of samples. Result(s): Infection was observed across all age groups, but predominantly in children under nine and adults over 40, with almost twice as many HPIV4 as HPIV2 cases. Fever, abnormal haematology, elevated C-reactive protein and hospital admission were more frequently seen in HPIV2 than HPIV4 infection. Each of the four seasonal peaks of either HPIV2, HPIV4 or both, closely matched that of RSV, occurring in November and December and preceding that of Influenza A. A subset of viruses were partially sequenced, indicating co-circulation of multiple subtypes of both HPIV2&4, but with little variation between each epidemic season or from limited global reference sequences. Conclusion(s): Despite being closest known genetic relatives, our data indicates a potential difference in associated disease between HPIV2 and HPIV4, with more hospitalisation seen in HPIV2 mono-infected individuals, but a greater overall number of HPIV4 cases.Copyright © 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.
    • Integrating distribution-based and anchor-based techniques to identify minimal important change for the tinnitus functional index (TFI) questionnaire

      Barry, Joanna (2022)
      The Tinnitus Functional Index (TFI) was developed to be responsive to small treatment-related changes in the impact of tinnitus. Yet, no studies have integrated anchor-based and distribution-based techniques to produce a single Minimal Important Change (MIC) score. Here, we evaluated the responsiveness and interpretability of the TFI, determining for the first time a robust MIC score in a UK clinical population. Two-hundred and fifty-five patients with tinnitus participated in this prospective longitudinal validation study. Distribution-based estimates (Standard Error of Measurement, Smallest Detectable Change and Effect size) and anchor-based estimates of important change (minimal clinically important difference and Receiver Operator Curve optimal value) were calculated and then integrated using a visual anchor-based MIC distribution plot. A reduction in score of -14 was determined as the MIC estimate that exceeds the measurement error, most of the variability and reliably identifies patients demonstrating true improvement. It is therefore recommended that a reduction of 14 points should be used as a minimum change required when calculating statistical power and sample size in tinnitus intervention studies and assessing patients in clinical practice.
    • Longitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis: A genome-wide association study

      Hubbard, Richard B.; Navaratnam, Vidya; Braybrooke, Rebecca; Saini, Gauri (2023)
      BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an incurable lung disease characterised by progressive scarring leading to alveolar stiffness, reduced lung capacity, and impeded gas transfer. We aimed to identify genetic variants associated with declining lung capacity or declining gas transfer after diagnosis of IPF. METHODS: We did a genome-wide meta-analysis of longitudinal measures of forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) in individuals diagnosed with IPF. Individuals were recruited to three studies between June, 1996, and August, 2017, from across centres in the US, UK, and Spain. Suggestively significant variants were investigated further in an additional independent study (CleanUP-IPF). All four studies diagnosed cases following American Thoracic Society/European Respiratory Society guidelines. Variants were defined as significantly associated if they had a meta-analysis p-8 when meta-analysing across all discovery and follow-up studies, had consistent direction of effects across all four studies, and were nominally significant (p when meta-analysing across all discovery and follow-up studies, had consistent direction of effects across all four studies, and were nominally significant (p-12). INTERPRETATION: Our analysis identifies a genetic variant associated with disease progression, which might highlight a new biological mechanism for IPF. We found that PKN2, a Rho and Rac effector protein, is the most likely gene of interest from this analysis. PKN2 inhibitors are currently in development and signify a potential novel therapeutic approach for IPF. FUNDING: Action for Pulmonary Fibrosis, Medical Research Council, Wellcome Trust, and National Institutes of Health National Heart, Lung, and Blood Institute. Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
    • Imaging in inflammatory bowel disease: Current and future perspectives

      Shaban, Nader; Hoad, Caroline L.; Naim, Iyad; Alshammari, Meshari; Radford, Shellie J.; Clarke, Christopher; Marciani, Luca; Moran, Gordon (2022)
      The use of cross-sectional imaging and ultrasonography has long complemented endoscopic assessment of inflammatory bowel disease (IBD). Clinical symptoms alone are often not enough to assess disease activity, so a reliance on non-invasive techniques is essential. In this paper, we aim to examine the current use of radiological modalities in aiding the management of patients with IBD. We focus on the various sections of the gastrointestinal tract and how different modalities can aid in assessing current disease state and response to treatments. We also have a look at how newer sequences in cross-sectional imaging and ultrasonography can allow for better differentiation of disease activity (ie, fibrotic vs inflammatory) as well improve evaluation of small bowel, colonic and perianal disease. Furthermore, we examine how advanced image processing has the potential to allow radiology to be a surrogate for biomarkers. An example of this is explored when reviewing the ability of MR sequences to quantify visceral fat, which potentially plays a role in determining disease activity in Crohn's disease. Lastly, we look into the expected role for artificial intelligence to be used as an adjunct to radiology to better improve IBD evaluation.Copyright © 2022 BMJ Publishing Group. All rights reserved.
    • LiverScreen project: Study protocol for screening for liver fibrosis in the general population in European countries

      Guha, Neil (2022)
      Background: The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. Method(s): This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged >= 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is >= 8 kPa and/or if ALT levels are >=1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM >= 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. Discussion(s): This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country. Trial registration: This study is registered on (NCT03789825). Copyright © 2022, The Author(s).
    • Digital follow-up after elective laparoscopic cholecystectomy: A feasibility study

      Daliya, Prita; Carvell, Jody; Rozentals, Judith; Lobo, Dileep N.; Parsons, Simon L. (2022)
      BACKGROUND: Although recommendations exist for patients to be offered a post-operative helpline or telephone follow-up appointment at discharge after cholecystectomy, implementation of these is resource-intensive. Whilst the benefits of telephone follow-up are well documented, the use of digital modalities is less so. We aimed to identify if digital follow-up (DFU) was equivalent to routine care with telephone follow-up (TFU), for patients undergoing elective laparoscopic cholecystectomy. METHOD(S): All patients listed for elective laparoscopic cholecystectomy between August 2016 and March 2018 were offered routine post-operative care (TFU or no follow-up) or DFU at a tertiary referral centre in Nottingham. RESULT(S): Of 597 patients undergoing laparoscopic cholecystectomy, 199 (33.3%) opted for TFU, and 98 (16.4%) for DFU. DFU was completed for 85 (86.7%) participants and TFU for 125 (62.8%), pRESULT(S): Of 597 patients undergoing laparoscopic cholecystectomy, 199 (33.3%) opted for TFU, and 98 (16.4%) for DFU. DFU was completed for 85 (86.7%) participants and TFU for 125 (62.8%), pRESULT(S): Of 597 patients undergoing laparoscopic cholecystectomy, 199 (33.3%) opted for TFU, and 98 (16.4%) for DFU. DFU was completed for 85 (86.7%) participants and TFU for 125 (62.8%), pCONCLUSION(S): This feasibility study has demonstrated that digital follow-up is an acceptable alternative to telephone follow-up after elective laparoscopic cholecystectomy.Copyright © 2022. The Author(s).
    • Image-enhanced endoscopy and molecular biomarkers vs Seattle protocol to diagnose dysplasia in Barrett's esophagus

      Kaye, Philip (2022)
      Background & Aims: Dysplasia in Barrett's esophagus often is invisible on high-resolution white-light endoscopy (HRWLE). We compared the diagnostic accuracy for inconspicuous dysplasia of the combination of autofluorescence imaging (AFI)-guided probe-based confocal laser endomicroscopy (pCLE) and molecular biomarkers vs HRWLE with Seattle protocol biopsies. Method(s): Barrett's esophagus patients with no dysplastic lesions were block-randomized to standard endoscopy (HRWLE with the Seattle protocol) or AFI-guided pCLE with targeted biopsies for molecular biomarkers (p53 and cyclin A by immunohistochemistry; aneuploidy by image cytometry), with crossover to the other arm after 6 to 12 weeks. The primary end point was the histologic diagnosis from all study biopsies (trial histology). A sensitivity analysis was performed for overall histology, which included diagnoses within 12 months from the first study endoscopy. Endoscopists were blinded to the referral endoscopy and histology results. The primary outcome was diagnostic accuracy for dysplasia by real-time pCLE vs HRWLE biopsies. Result(s): Of 154 patients recruited, 134 completed both arms. In the primary outcome analysis (trial histology analysis), AFI-guided pCLE had similar sensitivity for dysplasia compared with standard endoscopy (74.3%; 95% CI, 56.7-87.5 vs 80.0%; 95% CI, 63.1-91.6; P = .48). Multivariate logistic regression showed pCLE optical dysplasia, aberrant p53, and aneuploidy had the strongest correlation with dysplasia (secondary outcome). This 3-biomarker panel had higher sensitivity for any grade of dysplasia than the Seattle protocol (81.5% vs 51.9%; P Result(s): Of 154 patients recruited, 134 completed both arms. In the primary outcome analysis (trial histology analysis), AFI-guided pCLE had similar sensitivity for dysplasia compared with standard endoscopy (74.3%; 95% CI, 56.7-87.5 vs 80.0%; 95% CI, 63.1-91.6; P = .48). Multivariate logistic regression showed pCLE optical dysplasia, aberrant p53, and aneuploidy had the strongest correlation with dysplasia (secondary outcome). This 3-biomarker panel had higher sensitivity for any grade of dysplasia than the Seattle protocol (81.5% vs 51.9%; P Conclusion(s): Seattle protocol biopsies miss dysplasia in approximately half of patients with inconspicuous neoplasia. AFI-guided pCLE has similar accuracy to the current gold standard. The addition of molecular biomarkers could improve diagnostic accuracy.Copyright © 2022 The Authors
    • Quality standards for the management of non-alcoholic fatty liver disease (NAFLD): Consensus recommendations from the British Association for the Study of the Liver and British Society of Gastroenterology NAFLD Special Interest Group

      Jack, Kathryn; Thiagarajan, Prarthana (2022)
      Non-alcoholic fatty liver disease (NAFLD) is common, affecting approximately 25% of the general population. The evidence base for the investigation and management of NAFLD is large and growing, but there is currently little practical guidance to support development of services and delivery of care. To address this, we produced a series of evidence-based quality standard recommendations for the management of NAFLD, with the aim of improving patient care. A multidisciplinary group of experts from the British Association for the Study of the Liver and British Society of Gastroenterology NAFLD Special Interest Group produced the recommendations, which cover: management of people with, or at risk of, NAFLD before the gastroenterology or liver clinic; assessment and investigations in secondary care; and management in secondary care. The quality of evidence for each recommendation was evaluated by the Grading of Recommendation Assessment, Development and Evaluation tool. An anonymous modified Delphi voting process was conducted individually by each member of the group to assess the level of agreement with each statement. Statements were included when agreement was 80% or greater. From the final list of statements, a smaller number of auditable key performance indicators were selected to allow services to benchmark their practice. It is hoped that services will review their practice against our recommendations and key performance indicators and institute service development where needed to improve the care of patients with NAFLD.Copyright © 2022 Elsevier Ltd
    • The Clinical Research Bias Index (CRBI): A novel journal ranking method applied to child health respiratory studies

      Prayle, Andrew; Davies, Patrick (2022)
      Background and Aims: Journal impact factor has historically been taken as a proxy for quality. However, this is open to significant manipulation and bias. There is currently not widely adopted, robust journal and paper ranking metric which is focused solely on risk of bias. Method(s): Risk of bias data was extracted from all Cochrane database systematic reviews in Child Health, Lungs, and Airways for the years 2017-2019. A novel paper quality score, the Clinical Research Bias Index (CRBI), was applied. Individual paper data were pooled for each journal. A comparison was made to journal impact factors, individual paper citations, reads, and altmetric scores. Result(s): 927 papers were analyzed for risk of bias. 119 (12.8%) scored a CRBI of 100%, with a mean score of 70%. A journal's overall CRBI risk of bias score was poorly correlated with impact factor (r 0.25). Citations (r 0.02), and reads (r 0.01) of individual papers showed very little association with the paper's risk of bias. Likewise, reads were not correlated with citations (r 0.03). H-index and Altmetric scores were similarly poorly correlated with CRBI. Conclusion(s): The novel research quality tool CRBI demonstrates the poor correlation between journal impact factor, citations, and risk of bias. Journal and paper ranking metrics should ensure that they are fit for purpose, and enable the dissemination of high-quality research for the benefit of patients. We propose the CRBI as a potential solution which is resistant to manipulation and will reward the creation and publication of bias-free research.Copyright © 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.