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BackgroundCurrent clinical guidelines recommend treating chronic hepatitis B virus (HBV) infection in a minority of cases, but there are relatively scarce data on evolution or progression of liver inflammation and fibrosis in cases of chronic HBV (CHB) that do not meet treatment criteria. We aimed to assess the impact of TDF on liver disease, and the risk of renal impairment in treated CHB patients in comparison to untreated patients.MethodsWe studied a longitudinal ethnically diverse CHB cohort in the UK attending out-patient clinics between 2005 and 2018. We examined TDF treatment (vs. untreated) as the main exposure, with HBV DNA viral load (VL), ALT, elastography scores and eGFR as the main outcomes, using paired tests and mixed effects model for longitudinal measurements. Additionally, decline of eGFR during follow-up was quantified within individuals by thresholds based on clinical guidelines. Baseline was defined as treatment initiation for TDF group and the beginning of clinical follow-up for untreated group respectively.ResultsWe included 206 adults (60 on TDF, 146 untreated), with a median ± IQR follow-up duration of 3.3 ± 2.8 years. The TDF group was significantly older (median age 39 vs. 35 years,p = 0.004) and more likely to be male (63% vs. 47%,p = 0.04) compared to the untreated group. Baseline difference between TDF and untreated groups reflected treatment eligibility criteria. As expected, VL and ALT declined significantly over time in TDF-treated patients. Elastography scores normalised during treatment in the TDF group reflecting regression of inflammation and/or fibrosis. However, 6/81 (7.4%) of untreated patients had a progression of fibrosis stage from F0-F1 to F2 or F3. There was no evidence of difference in rates or incidence of renal impairment during follow-up in the TDF vs. untreated group.ConclusionsRisk of liver inflammation and fibrosis may be raised in untreated patients compared to those receiving TDF, and TDF may benefit a larger percentage of the CHB population.

We report a unique case of a 34-year-old man with ulcerative colitis, previously in complete remission with intravenous vedolizumab monotherapy, who developed an urticarial injection-site reaction on switching to a subcutaneous preparation and thereafter experienced a new hypersensitivity reaction on switch back to intravenous vedolizumab, necessitating complete discontinuation from this drug. This case highlights the need for vigilance on switching back to intravenous preparations of vedolizumab, in response to injection-site reactions with a subcutaneous preparation, even if the intravenous preparation had been previously well tolerated by the patient.

The study investigated student understanding of development of their clinical skills learning, focusing on personal experiences of the learning strategies they employ and their experiences of judging their own competency, integrating skills and transferring skill knowledge.Twenty-nine veterinary students from two veterinary schools took part in semi-structured interviews investigating their perceptions of clinical skills importance and development. Thematic analysis of transcribed interviews was used for data analysis.Themes that were developed were: (1) Students understand clinical skills to be individual technical practical skills but also understand how skills are combined to achieve complex tasks. (2) Students understand the concept of competency development and learn skills, review their progress and self-audit their skill competency in similar ways throughout the course. (3) Personal confidence, success and positive communication with peers and supervisors are critical to learn clinical skills.Students understand clinical skills learning and use reflective skills widely to track developing skills competency. Prioritising individual feedback within practical sessions and training on integration of skills and communicating with supervisors ahead of clinical placements would be beneficial. Training in clinical skills study techniques, reflection and resilience will enable students to be proactive and to manage their feelings around uncertainty.

Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available via www.palliativedrugs.com. The series editors welcome feedback on the articles.

Introduction Tofacitinib is an oral partially selective Janus kinase inhibitor approved for the treatment of refractory moderate to severe ulcerative colitis (UC). Real-world experience of patients with UC treated with tofacitinib is however limited, and safety concerns over the risk of venous thromboembolism (VTE) have recently emerged. Further, factors linked to primary non-response remain poorly defined. We therefore sought to define the effectiveness and safety of tofacitinib in a real-world cohort. Methods We conducted a retrospective observational cohort study of 134 patients with UC (64% male; median age 37 years [range 16–81]; 83% patients had previously received at least one biologic) treated with tofacitinib from October 2018 to October 2019 in four UK centres. Disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI) or Partial Mayo Score (PMS) depending on study site. Response and remission were defined as a reduction in SCCAI or PMS of ≥3, and SCCAI ≤2 or PMS ≤1, respectively. Results Overall, 74% (88/119; 95% CI 65–81%) patients responded to tofacitinib at week 8 and steroid free remission was observed in 44% (47/108; 95% CI 34%-53%) patients at week 26 (figure 1). Endoscopy was undertaken in 90 patients (67%) at baseline with routine follow-up endoscopy in 11 patients at week 8 and 34 patients at week 14. Median baseline UCEIS was 5 (IQR 4–6) falling to 2 (1–6) at week 8 and 2 (1–4) at week 14. Primary non-response was independently associated with younger age (p=0.014) and higher baseline CRP (p=0.004). Prior biologic exposure did not influence response or remission rates. Continuing tofacitinib in the setting of primary non-response was rarely helpful. Dose escalation recaptured response in 9/19 patients who lost response. Dyslipidaemia was observed in 20% (27/134; 95% CI 14%-28%) of patients but no major adverse cardiovascular events occurred. Seven patients had serious infections, with herpes zoster in 3 patients. Overall, adverse events that curtailed treatment were uncommon and no VTE occurred. Conclusions In this multi-centre real-world cohort, tofacitinib was well tolerated and clinically effective in a treatment refractory UC population.

Introduction Acute severe ulcerative colitis (ASUC) is a common medical emergency, with up to 25% of patients with ulcerative colitis experiencing at least one severe attack in their life-time. Since first Randomized control of efficacy of intravenous steroids published in 1954, many drugs have been discovered and used in management of acute severe colitis either as rescue therapy(Ciclosporin/Infliximab) or maintenance agents( 5-ASA, Immunomodulator (Azathioprine/6-Mercaptopurine), Biologic( Infliximab/Adalimumab/Vedolizumab) and small molecules( Tofacitinib).What is not known if these drugs have materialized into better outcomes in acute severe colitis. Methods We analysed outcomes from different papers from Oxford representing different cohorts of different era i.e Dinesen et al(1953–2007), Travis et al( 1996) and Corte et al( 2015).We compared the outcomes with most recent cohort from 2015–2019. Results Consecutive 131 admissions (117 patients) between 2015–9 were analysed. All satisfied modified TW definition of ASUC. Sixty-eight patients (58%) were female, index presentation 38 (29%),median age at presentation 40 years (16–76),median disease duration 1 year (1–43), median follow up 23 months (1–49).Seventy-one (54%) received rescue therapy (ciclosporin 35/71 and anti-TNF 36/71).Colectomy rates were 15% (19/131) during same admission and 26% (30/117) within 1 year of follow up. We compared the outcomes in different cohorts. We observed that colectomy rates have been decreasing significantly with better treatment (Image 1). We also observed that readmissions with acute severe colitis have also reduced (better maintenance) with only 12% patients requiring readmission in first year. Seventy percent of patients in current cohort have been maintained on biologic or Tofacitinib leading to colectomy free survival for median follow up of 2 years. Conclusion Availability of multiple drug options and improvement in healthcare have led to improved outcomes in acute severe colitis justifying the cost associated with these drugs.

AimCurrent clinical recommendations suggest treating chronic hepatitis B virus (HBV) infection in a minority of cases, but more data are needed to determine the benefits and risks of Tenofovir disoproxil fumarate (TDF) therapy. We aimed to assess the impact of TDF on liver disease, and the risk of nephrotoxicity.MethodWe studied a longitudinal UK chronic HBV (CHB) cohort attending out-patient clinics between 2005 and 2018, analysing data for 206 ethnically diverse adults (60 on TDF, 146 untreated), with median follow-up 3.3±2.8 years.ResultsPatients prescribed TDF were older (39 vs. 35 years, p=0.004) with a male excess (63% vs. 47%, p=0.04) compared to untreated patients. Reflecting treatment eligibility criteria, at baseline, treated patients were more likely to have elevated ALT (pConclusionTDF may have long-term benefits for a wider pool of the CHB population.

Background Tofacitinib is a partially selective Janus kinase inhibitor approved for the treatment of refractory moderate to severe ulcerative colitis [UC]. We sought to define the effectiveness and adverse effects of tofacitinib in a real-world cohort. Methods We conducted a retrospective observational cohort study of 134 patients with UC [64% male; median age 37 years [range 16–81]; 83% of patients had previously received at least one biologic] treated with tofacitinib from October 2018 to October 2019 in four UK centres. Disease activity was assessed using the Simple Clinical Colitis Activity Index [SCCAI] or partial Mayo score [PMS], depending on study site. Response and remission were defined as a reduction in SCCAI or PMS of ≥3and SCCAI ≤2 or a PMS ≤1, respectively. Results Overall, 74% (88/119; 95 confidence interval [CI] 65–81%] patients responded to tofacitinib at Week 8 and steroid-free remission was observed in 44% [47/108; 95% CI 3453%] patients at Week 26. Primary non-response was independently associated with younger age [p = 0.014] and higher C-reactive protein [CRP] levels at baseline [p = 0.004]. Only 23% [3/13] of patients who continued tofacitinib in the setting of primary non-response were in steroid-free remission at Week 26. Prior biologic exposure did not influence response or remission rates. Dose escalation, however, recaptured response in approximately half of patients who had lost response. Dyslipidaemia was observed in 20% [27/134; 95% CI 1428%] of patients, but adverse events necessitating drug withdrawal were uncommon and no venous thromboembolic events occurred. Conclusions In this multicentre real-world cohort, tofacitinib was well tolerated and clinically effective in a treatment-refractory UC population.

Advances in the diagnosis, monitoring, and treatment of hepatitis B virus (HBV) infection are urgently required if we are to meet international targets for elimination by the year 2030. Here we demonstrate how routine clinical data can be harnessed through an unbiased electronic pipeline, showcasing the significant potential for amassing large clinical data sets that can help to inform advances in patient care and provide insights that may help to inform new cure strategies. Our cohort from a large UK hospital includes adults from diverse ethnic groups that have previously been underrepresented in the literature. By tracking two protein biomarkers that are used to monitor chronic HBV infection, we provide new insights into the timelines of HBV clearance, both on and off treatment. These results contribute to improvements in individualized clinical care and may provide important clues into the immune events that underpin disease control., HBsAg and HBeAg have gained traction as biomarkers of control and clearance during chronic hepatitis B virus infection (CHB). Improved understanding of the clearance correlates of these proteins could help inform improvements in patient-stratified care and advance insights into the underlying mechanisms of disease control, thus underpinning new cure strategies. We collected electronic clinical data via an electronic pipeline supported by the National Institute for Health Research Health Informatics Collaborative (NIHR HIC), adopting an unbiased approach to the generation of a robust longitudinal data set for adults testing HBsAg positive from a large UK teaching hospital over a 6-year period (2011 to 2016 inclusive). Of 553 individuals with CHB, longitudinal data were available for 319, representing >107,000 weeks of clinical follow-up. Among these 319 individuals, 13 (4%) cleared HBsAg completely. Among these 13, the HBsAg clearance rate in individuals on nucleos(t)ide analogue (NA) therapy (n = 4 [31%]; median clearance time,150 weeks) was similar to that in individuals not on NA therapy (n = 9 [69%]; median clearance time, 157 weeks). Those who cleared HBsAg were significantly older and less likely to be on NA therapy than nonclearers (P = 0.003 and P = 0.001, respectively). Chinese ethnicity was associated with HBeAg positivity (P = 0.025). HBeAg clearance occurred in individuals both on NA therapy (n = 24; median time, 49 weeks) and off NA therapy (n = 19; median time, 52 weeks). Improved insights into the dynamics of these biomarkers can underpin better prognostication and patient-stratified care. Our systematized approach to data collection paves the way for scaling up efforts to harness clinical data to address research questions and support improvements in clinical care.

Background Tofacitinib is a partially selective Janus kinase inhibitor that was approved for the treatment of refractory moderate to severe ulcerative colitis (UC) in 2018. We report the real-world clinical effectiveness and adverse effects of tofacitinib in UC. Methods We conducted a retrospective observational cohort study of tofacitinib-treated patients with UC between October 2018 to October 2019 from 4 UK centres. Disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI) or Partial Mayo Score (PMS) depending on the study site. Response and remission were defined at week 8 and 26 as a reduction in SCCAI or PMS of ≥3, and SCCAI Results We included 140 patients (65% M; median age 37y [range 16–81]) with a median disease duration of 5.5y (IQR 2.2–11.8). Forty-six per cent (65/140) were receiving corticosteroids at baseline and 83% (116/140) had previously received at least one biologic (62 anti-TNF, 4 vedolizumab, 50 both). Median (IQR) serum CRP and faecal calprotectin levels at baseline were 4 mg/l (1.6–15) and 540 µg/g (316–1175). Response and remission rates were 73% (81/111) and 56% (62/111) respectively at week 8 (median ΔSCCAI of −3 [IQR -6 to -1], median ΔPMS −4 [−6 to −1]) and 48% (39/82) and 39% (32/82) respectively at week 26 (median ΔSCCAI −3 [IQR −7 to –1], median ΔPMS −4 [−6 to –1]). Steroid-free remission was seen in 47% (52/111) and 37% (30/82) patients at week 8 and 26. Patients with response or remission had a significantly lower CRP (p = 0.02) but not calprotectin (p = 0.38) levels at baseline. Response and remission rates were no different stratified by prior biologic use (p = 0.56). Treatment was discontinued after a median of 3 months (IQR 2–4) in 43 patients: 32 with primary non-response, 9 loss of response and in 1 each because of an adverse drug reaction (headache) and patient choice. 7/17 patients had a clinical response to dose re-escalation following a loss of response on dose reduction. The median time to dose de-escalation was 67 (IQR 25–240) days. Seven patients were hospitalised and 5 underwent colectomy. Six serious infections were noted including 2 herpes zoster infections but there were no venous thromboembolic events. Median total cholesterol, low-density lipoprotein and high-density lipoprotein increased from 4.4 mmol/l (IQR 3.7–5.2), 2.47 (1.9–2.9) and 1.5 (1.1–1.9) to 4.8 mmol/l (4.1–6.0), 2.8 (2.13.5) and 1.7 (1.4–1.9) respectively after 8 weeks of tofacitinib. Conclusion Clinical effectiveness and side-effect profile of tofacitinib in UC in this multi-centre real-world cohort were similar to that reported in the pivotal OCTAVE clinical trials.

HBsAg and HBeAg have gained traction as biomarkers of control and clearance during monitoring of chronic hepatitis B virus infection (CHB). An improved understanding of the correlates of clearance of these proteins could help inform improvements in patient-stratified care and advance insights into the underlying mechanisms of disease control, thus underpinning new cure strategies. We collected electronic clinical data via an electronic pipeline supported by the National Institute for Health Research Health Informatics Collaborative (NIHR-HIC), adopting an unbiased approach to generating a robust longitudinal dataset for adults testing HBsAg-positive from a large UK teaching hospital over a six year period (2011-2016 inclusive). From 553 individuals with CHB, longitudinal data were available for 319, representing >107,000 weeks of clinical follow-up. Among these 319 individuals, 13 (4%) cleared HBsAg completely. HBsAg clearance rate was similar in individuals on NA therapy (n=4, median clearance time 150 weeks) vs those not on NA therapy (n=9, median clearance time 157 weeks). Those who cleared HBsAg were significantly older, and less likely to be on NA therapy compared to non-clearers (p=0.003 and p=0.001, respectively). Chinese ethnicity was associated with HBeAg positivity (p=0.025). HBeAg clearance occurred both on NA therapy (n=24, median time 49 weeks) and off NA therapy (n=19, median time 52 weeks). Improved insights into the dynamics of these biomarkers can underpin better prognostication and patient-stratified care. Our systematised approach to data collection paves the way for scaling up efforts to harness clinical data to address research questions and underpin improvements in clinical care provision.IMPORTANCEAdvances in the diagnosis, monitoring and treatment of hepatitis B virus (HBV) infection are urgently required if we are to meet international targets for elimination by the year 2030. Here we demonstrate how routine clinical data can be harnessed through an unbiased electronic pipeline, showcasing the significant potential for amassing large clinical datasets that can help to inform advances in patient care, and provide clues that inform new cure strategies. Our cohort from a large UK hospital includes adults from diverse ethnic groups that have previously been under-represented in the literature. Tracking two protein biomarkers that are used to monitor chronic HBV infection, we provide new insights into the timelines of HBV clearance, both on and off treatment. These results contribute to improvements in individualised clinical care and may provide important clues into the immune events that underpin disease control.

Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract. Individuals with CD present with acute inflammatory exacerbations as well as acute and chronic complications. Management requires specialist input from gastroenterologists, colorectal surgeons, nurse specialists and pharmacists as well as general and primary care physicians to allow appropriate selection of treatment options including surgery and rapid assessment and treatment of those with acute exacerbations. Monitoring of the individual and their medication is crucial in preventing and recognising complications including those associated with treatment. This concise guideline focuses on recommendations from National Institute for Health and Care Excellence (NICE) -Clinical -Guideline 152 (CG152) considered of key importance for implementation.

Well-designed studies that help guide physicians to apply the optimal therapeutic strategy for the management of pyoderma gangrenosum are lacking in the literature. A multidisciplinary approach is paramount for the effective management of this condition, with close involvement of a wound-care specialist and a microbiologist. Treatment should be stepwise in nature. Local wound care, avoidance of trauma and the application of local steroid or tacrolimus ointment are the first-line treatments. Steroid therapy is the most widely published effective therapy for achieving resolution of pyoderma gangrenosum, although there is growing evidence for the efficacy of infliximab in refractory cases. Other therapies such as dapsone and clofazamine should be left as third-line agents for refractory pyoderma gangrenosum, while novel treatments such as granulocyte apheresis should only be used under trial conditions, to gain an objective evaluation of their efficacy. This article reviews the published treatment strategies in current use, and aims to guide the effective management of pyoderma gangrenosum.