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.

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.

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.

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.

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.

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.

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.

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.

OBJECTIVE: To determine the feasibility of designing and conducting a definitive trial to evaluate the effectiveness of sacral fracture fixation compared with non-surgical management among older people admitted with a lateral compression pelvic fragility fracture (PFF). DESIGN: Single-site, parallel, two-arm randomised controlled feasibility trial. SETTING: A UK tertiary centre hospital. PARTICIPANTS: Patients aged >=70 years who were ambulating pre-injury requiring hospital admission (within 28 days of injury) with a type 1 lateral compression PFF. INTERVENTIONS: The intervention group received sacral fracture fixation (cement augmentation+/-screw fixation) within 7 days of randomisation. Routine preoperative and postoperative care followed each surgical intervention. The control group received usual care consisting of analgesia, and regular input from the medical and therapy team. PRIMARY AND SECONDARY OUTCOME MEASURES: The feasibility outcomes were the number of eligible patients, willingness to be randomised, adherence to allocated treatment, retention, data on the completeness and variability of the proposed definitive trial outcome measures, and reported adverse events. RESULTS: 241 patients were screened. 13 (5.4%) were deemed eligible to participate. Among the eligible participants, nine (69.2%) were willing to participate. Five participants were randomised to the intervention group and four to the control group. The clinicians involved were willing to allow their patients to be randomised and adhere to the allocated treatment. One participant in the intervention group and two participants in the control group received their allocated treatment. All participants were followed up until 12 weeks post-randomisation, and had an additional safety follow-up assessment at 12 months. Overall, the proportion of completeness of outcome measures was at least 75%. No adverse events were directly related to the trial. CONCLUSIONS: There were significant challenges in recruiting sufficient participants which will need to be addressed prior to a definitive trial. TRIAL REGISTRATION NUMBER: ISRCTN16719542. Copyright © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

Background: There are a limited number of treatment options for people with corticosteroid-refractory ulcerative colitis. Animal models of inflammatory bowel disease and uncontrolled studies in humans suggest that tacrolimus may be an effective treatment for ulcerative colitis. Objective(s): To evaluate the efficacy and safety of tacrolimus for induction of remission in people with corticosteroid-refractory ulcerative colitis. Search Method(s): We searched the Cochrane Gut group specialised register, CENTRAL, MEDLINE (PubMed), Embase, Clinicaltrials.gov and WHO ICTRP from inception to October 2021 to identify relevant randomised controlled trials (RCT). Selection Criteria: Two review authors independently selected potentially relevant studies to determine eligibility based on the prespecified criteria. Data Collection and Analysis: Two review authors independently extracted data and analysed them using Review Manager Web. The primary outcomes were induction of remission and clinical improvement, as defined by the studies and expressed as a percentage of the participants randomised (intention-to-treat analysis). Main Result(s): This review included five RCTs with 347 participants who had active ulcerative colitis or ulcerative proctitis. The duration of intervention varied between two weeks and eight weeks. Tacrolimus versus placebo. Tacrolimus (oral and rectal) may be superior in achieving clinical remission compared to placebo (oral and rectal) (14/87 participants with tacrolimus versus 1/61 participants with placebo; risk ratio (RR) 3.76, 95% confidence interval (CI) 1.03 to 13.73; 3 studies). These results are of low certainty due to imprecision and risk of bias. Tacrolimus (oral and rectal) may be superior for clinical improvement compared to placebo (oral and rectal) (45/87 participants with tacrolimus versus 7/61 participants with placebo; RR 4.47, 95% CI 2.15 to 9.29; 3 studies). These results are of low certainty due to imprecision and risk of bias. The evidence is very uncertain about the effects of tacrolimus (oral and rectal) on serious adverse events compared to placebo (oral and rectal) (2/87 participants with tacrolimus versus 0/61 participants with placebo; RR 2.44, 95% CI 0.12 to 48.77; 3 studies). These results are of very low certainty due to high imprecision and risk of bias. Tacrolimus versus ciclosporin. One study compared oral tacrolimus to intravenous ciclosporin, with an intervention lasting two weeks and 113 randomised participants. The evidence is very uncertain about the effect of tacrolimus on achievement of clinical remission compared to ciclosporin (15/33 participants with tacrolimus versus 24/80 participants with ciclosporin; RR 1.52, 95% CI 0.92 to 2.50). The results are of very low certainty due to risk of bias and high imprecision. The evidence is very uncertain about the effect of tacrolimus on clinical improvement compared to intravenous ciclosporin (23/33 participants with tacrolimus versus 62/80 participants with ciclosporin; RR 0.90, 95% CI 0.70 to 1.16). The results are of very low certainty due to risk of bias and imprecision. Tacrolimus versus beclometasone. One study compared tacrolimus suppositories with beclometasone suppositories in an intervention lasting four weeks with 88 randomised participants. There may be little to no difference in achievement of clinical remission (16/44 participants with tacrolimus versus 15/44 participants with beclometasone; RR 1.07, 95% CI 0.60 to 1.88). The results are of low certainty due to high imprecision. There may be little to no difference in clinical improvement when comparing tacrolimus suppositories to beclometasone suppositories (22/44 participants with tacrolimus versus 22/44 with beclometasone; RR 1.00, 95% CI 0.66 to 1.52). The results are of low certainty due to high imprecision. There may be little to no difference in serious adverse events when comparing tacrolimus suppositories to beclometasone suppositories (1/44 participants with tacrolimus versus 0/44 with beclometasone; RR 3.00, 95% CI 0.13 to 71.70). These results are of low certainty due to high imprecision. There may be little to no difference in total adverse events when comparing tacrolimus suppositories to beclometasone suppositories (21/44 participants with tacrolimus versus 14/44 participants with beclometasone; RR 1.50, 95% CI 0.88 to 2.55). These results are of low certainty due to high imprecision. No secondary outcomes were reported for people requiring rescue medication or to undergo surgery. Authors' conclusions: There is low-certainty evidence that tacrolimus may be superior to placebo for achievement of clinical remission and clinical improvement in corticosteroid-refractory colitis or corticosteroid-refractory proctitis. The evidence is very uncertain about the effect of tacrolimus compared to ciclosporin for achievement of clinical remission or clinical improvement. There may be no difference between tacrolimus and beclometasone for inducing clinical remission or clinical improvement. The cohorts studied to date were small, with missing data sets, offered short follow-up and the clinical endpoints used were not in line with those suggested by regulatory bodies. Therefore, no clinical practice conclusions can be made. This review highlights the need for further research that targets the relevant clinical questions, uses appropriate trial methodology and reports key findings in a systematic manner that facilitates future integration of findings with current evidence to better inform clinicians and patients. Future studies need to be adequately powered and of pertinent duration so as to capture the efficacy and effectiveness of tacrolimus in the medium to long term. Well-structured efficacy studies need to be followed up by long-term phase 4 extensions to provide key outputs and inform in a real-world setting.Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.