Non-academic Centres Research Articles

Sub-optimal therapy of patients with primary biliary cholangitis (PBC) in the real-life stetting of the German PBC cohort.

Real-world data on the management of patients with primary biliary cholangitis (PBC) are so far scarce in Germany. Therefore, we aimed to establish a nationwide registry and describe the clinical characteristics and therapy of PBC patients.Three different cohorts defined as ursodeoxycholic acid (UDCA) responders, as inadequate responders according to Paris II criteria, and as newly diagnosed patients were prospectively recruited.This manuscript includes the baseline data of the project.In total, 33/77 (43%) contacted centres (58% of university hospitals, 38% of non-university hospitals, and 24% of private practices) recruited 515 patients including 204 UDCA responders, 221 inadequate responders to UDCA, and 90 newly diagnosed patients.All patients were treated with UDCA; however, a UDCA dosage below the recommended dosage of 13 mg/kg/d was observed in 38.5% of individuals after 12 months of treatment. UDCA dosages were lower in nonacademic compared to academic centres.Only 75/219 (38.5%) of inadequate responders to UDCA received a second-line therapy with obeticholic acid (OCA) and/or bezafibrate (BZF). OCA (13% vs. 4.5%) and BZF (14% vs. 6.5%) were significantly more often prescribed by academic vs. nonacademic centres.Pruritus (27% vs. 15.5%), fatigue (23% vs. 4.5%), and sicca syndrome (14% vs. 1%) were significantly more often reported by academic centres.The German PBC registry could be established, which indicates suboptimal therapy in a relevant proportion of patients and shows significant differences between academic and nonacademic centres. Results are fundamental to improving clinical management at different levels of care.

Efficacy of a real-time intelligent quality-control system for the detection of early upper gastrointestinal neoplasms: a multicentre, single-blinded, randomised controlled trial

Oesophagogastroduodenoscopy (OGD) quality and identification of the early upper gastrointestinal (UGI) neoplasm play an important role in detecting the UGI neoplasm. However, the optimal method for quality control in daily OGD procedures is currently lacking. We aimed to evaluate the efficacy of a real-time intelligent quality-control system (IQCS), which combines OGD quality control with lesion detection of early UGI neoplasms. We performed a multicentre, single-blinded, randomised controlled trial at 6 hospitals in China. Patients aged 40-80 years old who underwent painless OGD were screened for enrolment in this study. Patients with a history of advanced UGI cancer, stenosis, or obstruction in UGI tract were excluded. Eligible subjects were randomly assigned (1:1) to either the routine or IQCS group to undergo standard OGD examination and OGD examination aided by IQCS, respectively. Patients were masked to the randomisation status. The primary outcome was the detection of early UGI neoplasms. All analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, NCT04720924. Between January 16, 2021 and December 23, 2022, 1840 patients were randomised (IQCS group: 919, routine group: 921). The full analysis set consisted of 914 in the IQCS group and 915 in the routine group. The early UGI neoplasms detection rate in the IQCS group (6.1%, 56/914) was significantly higher than in the routine group (2.3%, 21/915; P=0.0001). The IQCS group had fewer blind spots (2.3 vs. 6.2, P<0.0001). The IQCS group had higher stomach cleanliness on cardia or fundus (99.5% vs. 87.9%, P<0.0001), body (98.9% vs. 88.0%, P<0.0001), angulus (99.8% vs. 88.4%, P<0.0001) and antrum or pylorus (100.0% vs. 87.4%, P<0.0001). The inspection time (576.2 vs. 574.5s, P=0.91) and biopsy rate (57.2% vs. 56.6%, P=0.83) were not different between the groups. The early UGI neoplasms detection rate in the IQCS group increased in both non-academic centres (RR=3.319, 95% CI 1.277-9.176; P=0.0094) and academic centres (RR=2.416, 95% CI 1.301-4.568; P=0.0034). The same improvements were observed for both less-experienced endoscopists (RR=2.650, 95% CI 1.330-5.410; P=0.0034) and experienced endoscopists (RR=2.710, 95% CI 1.226-6.205; P=0.010). No adverse events or serious adverse events were reported in the two groups. The IQCS improved the OGD quality and increased early UGI neoplasm detection in different hospital types and endoscopist experiences. IQCS could play an important role in primary basic hospitals and non-expert endoscopists to improve the diagnostic accuracy of early UGI neoplasms. The effectiveness of IQCS in real-world clinical settings needs a larger population validation. Key R&D Program of Shandong Province, China (Major Scientific and Technological Innovation Project), National Natural Science Foundation of China, the Taishan Scholars Program of Shandong Province, the National Key Research and Development Program of China, and the Shandong Provincial Natural Science Foundation.

Highly specialised functions in non-academic medical centres

Introduction: Highly specialised functions in non-academic medical centres in the Netherlands are currently not funded. Highly specialised functions are the overarching term of the combination of complex care, applied (clinical) scientific research, and related education. While academic medical centres receive a service provision contribution for their top specialist position, non-academic medical centres do not receive the desired structural funding. 10 projects in the Netherlands have received a subsidy of 4 years to fund their highly specialised function(s). For this qualitative study the project and other relevant stakeholders have been interviewed. The aim of the study is to explore the sustainable governance of highly specialised functions.&#x0D; Methods: 45 semi-structured interviews have been conducted with various stakeholder groups. These participants have, among other things, been questioned about the definition of highly specialised functions, terms and conditions of this functions, current bottlenecks of funding this functions, desirable future funding of this functions, relevant stakeholders for defining, and funding and assessing these functions. Each participant has signed the informed consent form and all interviews have been transcribed anonymously. During a conference with the participants some results of the qualitative research have been presented to validate the outcomes.&#x0D; Key findings: It is an understatement that the viewpoints differ. While most interviewees acknowledge that funding is currently lacking, and that sustainable funding is required others also stated that highly specialised functions in non-academic medical centres are undesirable for the concentration of healthcare. However, based on these interviews and a previous literature review a definition of the highly specialised function is suggested. Namely, care for a specifically defined complex patient group / intervention in non-academic medical centres, combined with applied (clinical) scientific research and education. In addition, a set of terms and conditions to be fulfilled to receive funding for the highly specialised function is proposed. These terms and conditions are concrete scientific evidence, complex care, coordination, capacity, culture, knowledge dissemination, and collaboration with patient organisations, applying to the non-academic centre or the intervention provided.&#x0D; Conclusions: Although most stakeholders acknowledge the need for sustainable governance of highly specialised functions in non-academic medical centres it is hard to reach a consensus. Especially terms and conditions of funding highly specialised functions are hard to define and to realise in practice. &#x0D; Implications: With this research governance of highly specialised functions has been explored. A definition and a set of terms and conditions have been proposed and reviewed by various stakeholders to be used for the funding of highly specialised functions in non-academic medical centres. Policymakers may be able to use the results for embedding sustainable governance of highly specialised functions in non-academic medical centres.

Analysis of active surveillance uptake for localized prostate cancer in Quebec in 2016: A Canadian bicentric study and comparison with 2010 data

IntroductionActive surveillance (AS) has emerged as a primary management strategy for low-risk prostate cancer (PC) patients. We aimed to assess AS uptake over a 1-year snapshot throughout Quebec and to compare it to 2010 multicentric Canadian data. MethodsA retrospective chart review and data collection was performed in 1 academic and 2 non-academic community centres from Quebec, among men identified in 2016 with localized T1c-T2c PC on biopsy, fulfilling NCCN criteria of low-risk (LR)-PC, including very-low-risk (VLR) and non-VLR-PC, and favourable-intermediate risk (FIR)-PC. AS adherence was defined when chosen as initial strategy, without any radical treatment within 6 months. ResultsOverall, 259 patients fulfilled the inclusion criteria with 50.2% of VLR-PC patients. At 6 months, 81% patients in the LR group and 65% in the FIR group were considered as adherent to AS, in both centres, but with an increased use of AS in the community centres compared to 2010 data. The rates of AS maintenance decreased at 12 months to respectively 69% and 58%. Among the VLR group, the rate of initiation was 98% and decreased to 85% at 12 months. ConclusionOur data suggest that the majority of low-risk PC patients indeed initiated an AS in 2016, with even a greater proportion of VLR-PC patients compared to 2010. This ideal strategy should be encouraged and improved at 12 months, and assessed with recent data and longer follow-up. Level of evidence4

First proficiency testing for NGS-based and combined NGS- and FISH-based detection of FGFR2 fusions in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma harbours druggable genetic lesions including FGFR2 gene fusions. Reliable and accurate detection of these fusions is becoming a critical component of the molecular work-up, but real-world data on the performance of fluorescence in situ hybridisation (FISH) and targeted RNA-based next-generation sequencing (NGS) are very limited. Bridging this gap, we report results of the first round robin test for FGFR2 fusions in cholangiocarcinoma and contextualise test data with genomic architecture. A cohort of 10 cholangiocarcinoma (4 fusion positive and 6 fusion negative) was tested by the Institute of Pathology, University Hospital Heidelberg, Germany. Data were validated by four academic pathology departments in Germany. Fusion-positive cases comprised FGFR2::BICC1, FGFR2::DBP, FGFR2::TRIM8, and FGFR2::ATE1 fusions. In a second step, a round robin test involving 21 academic and non-academic centres testing with RNA-based NGS approaches was carried out; five participants performed FISH testing in addition. Thirteen of 16 (81%) centres successfully passed the NGS only and 3 of 5 (60%) centres passed the combined NGS + FISH round robin test. Identified obstacles were bioinformatic pipelines not optimised for the detection of FGFR2 fusions and assays not capable of detecting unknown fusion partners. This study shows the benefit of targeted RNA-NGS for the detection of FGFR2 gene fusions. Due to the marked heterogeneity of the genomic architecture of these fusions, fusion partner agnostic (i.e. open) methodological approaches that are capable of identifying yet unknown fusion partners are superior. Furthermore, we highlight pitfalls in subsequent bioinformatic analysis and limitations of FISH-based tests.

Assisted peritoneal dialysis across Europe: Practice variation and factors associated with availability.

In Europe, the number of elderly end-stage kidney disease patients is increasing. Few of those patients receive peritoneal dialysis (PD), as many cannot perform PD autonomously. Assisted PD programmes are available in most European countries, but the percentage of patients receiving assisted PD varies considerably. Hence, we assessed which factors are associated with the availability of an assisted PD programme at a centre level and whether the availability of this programme is associated with proportion of home dialysis patients. An online survey was sent to healthcare professionals of European nephrology units. After selecting one respondent per centre, the associations were explored by χ2 tests and (ordinal) logistic regression. In total, 609 respondents completed the survey. Subsequently, 288 respondents from individual centres were identified; 58% worked in a centre with an assisted PD programme. Factors associated with availability of an assisted PD programme were Western European and Scandinavian countries (OR: 5.73; 95% CI: 3.07-10.68), non-academic centres (OR: 2.01; 95% CI: 1.09-3.72) and centres with a dedicated team for education (OR: 2.87; 95% CI: 1.35-6.11). Most Eastern & Central European respondents reported that the proportion of incident and prevalent home dialysis patients was <10% (72% and 63%), while 27% of Scandinavian respondents reported a proportion of >30% for both incident and prevalent home dialysis patients. Availability of an assisted PD programme was associated with a higher incidence (cumulative OR: 1.91; 95% CI: 1.21-3.01) and prevalence (cumulative OR: 2.81; 95% CI: 1.76-4.47) of patients on home dialysis. Assisted PD was more commonly offered among non-academic centres with a dedicated team for education across Europe, especially among Western European and Scandinavian countries where higher incidence and prevalence of home dialysis patients was reported.

Patterns of first-line systemic therapy delivery and adoption of bevacizumab in advanced ovarian cancer in Ontario, Canada.

292 Background: Initial treatment of epithelial ovarian cancer (EOC) consists of combination of cytoreductive surgery (CSR) and/or chemotherapy. Targeted therapies such as bevacizumab have shown to improve outcomes in a subset population with high-risk features. Real-world patterns of systemic therapy delivery in EOC in the modern era are not well understood. Our objective is to evaluate the patterns of first-line systemic treatment of advanced EOC in Ontario, focusing on adoption of bevacizumab, which was approved for use in 2016. Methods: We conducted a retrospective, population cohort study using administrative databases held at the ICES in Ontario, Canada. Patients diagnosed with non-mucinous EOC between 2014 and 2018 were identified from the Ontario Cancer Registry; early-stage disease was excluded. Information on systemic therapy was obtained from Activity Level Reporting and New Drug Funding Program databases. Provider of care (gynecologic oncologist vs medical oncologist) information was obtained from billing codes. Academic cancer centers were identified using validated systemic facility codes from Cancer Care Ontario. Statistical analyses include descriptive statistics, t-tests, and multivariable logistic regression using SAS. Results: Out of 4,680 cases diagnosed with EOC during the study period, 3,632 (77.6%) were considered advanced stage. Median age of cohort was between 65-70, and the majority had Charlson score of 1-2 (97%) and are urban (91.8%). A total of 3,181 (87.6%) patients underwent CRS and 2,722(74.9%) patients underwent chemotherapy. Of those who received chemotherapy, 1,259 (46.2%) received neoadjuvant chemotherapy, 1,012 (37.2%) received upfront CRS, and 451(16.5%) received chemotherapy only. The majority of chemotherapy was delivered by gynecologic oncologists (60.6%) and in academic cancer centres (61.7%). There was no significant difference in use of neoadjuvant chemotherapy between medical oncologists and gynecologic oncologists (p = 0.67). Only 53 chemotherapy patients (1.9%) received bevacizumab containing-regimen in the first-line setting. Medical oncologists were 4 times more likely to administer bevacizumab-containing regimen compared to gynecologic oncologists (OR 4.03, 95% CI.29 – 7.36) after adjusting for age, stage, Charlson score and rurality score on logistic regression. Delivery of bevacizumab is relatively higher in non-academic cancer centres (OR 2.61, 95% CI 2.32- 2.94) while 83% of intraperitoneal chemotherapy is delivered in academic cancer centres. Conclusions: Patterns of care of EOC in Ontario remain heterogenous between care providers and institutions, while uptake of bevacizumab for first-line treatment of EOC remains low. Factors leading to low uptake and real-world outcomes should be explored.

Practice patterns of vasal reconstruction in a large United States cohort.

We aimed to characterise diverse practice patterns for vasal reconstruction and to determine whether surgeon volume is associated with vasoepididymostomy performance at the time of reconstruction. We identified adult men who underwent vasal reconstruction from 2000 to 2020 in Premier Healthcare Database and determined patient, surgeon, cost and hospital characteristics for each procedure. We identified 3,494 men who underwent either vasovasostomy-alone (N=2,595, 74.3%) or any-vasoepididymostomy (N=899, 25.7%). The majority of providers (N=487, 88.1%) performed only-vasovasostomy, 10 (1.8%) providers performed only-vasoepididymostomy and 56 (10.1%) providers performed both. Median total hospital charge of vasoepididymostomy was significantly higher than vasovasostomy ($39,163, interquartile range [IQR]$11,854-53,614 and $17,201, IQR$10,904-29,986, respectively). On multivariable regression, men who underwent procedures at nonacademic centres (OR 2.71, 95% CI 2.12-3.49) with higher volume surgeons (OR 11.60, 95% CI 8.65-16.00) were more likely to undergo vasoepididymostomy. Furthermore, men who underwent vasoepididymostomy were more likely to self-pay (OR 2.35, 95% CI 1.83-3.04, p<.001) and more likely had procedures in the Midwest or West region (OR 2.22, 95% CI 1.66-2.96 and OR 2.11, 95% CI 1.61-2.76, respectively; p<.001). High-volume providers have increased odds of performing vasoepididymostomy at the time of reconstruction but at a significantly higher cost. These data suggest possibly centralising reconstructive procedures among high-volume providers.

Role of the halo sign in the assessment of giant cell arteritis: a systematic review and meta-analysis.

ObjectivesThis systematic review and meta-analysis aimed to evaluate the diagnostic value of the halo sign in the assessment of GCA.MethodsA systematic literature review was performed using MEDLINE, EMBASE and Cochrane central register databases up to August 2020. Studies informing on the sensitivity and specificity of the US halo sign for GCA (index test) were selected. Studies with a minimum of five participants were included. Study articles using clinical criteria, imaging such as PET-CT and/or temporal artery biopsy (TAB) as the reference standards were selected. Meta-analysis was conducted with a bivariate model.ResultsThe initial search yielded 4023 studies. Twenty-three studies (patients n = 2711) met the inclusion criteria. Prospective (11 studies) and retrospective (12 studies) studies in academic and non-academic centres were included. Using clinical diagnosis as the standard (18 studies) yielded a pooled sensitivity of 67% (95% CI: 51, 80) and a specificity of 95% (95% CI: 89, 98%). This gave a positive and negative likelihood ratio for the diagnosis of GCA of 14.2 (95% CI: 5.7, 35.5) and 0.375 (95% CI: 0.22, 0.54), respectively. Using TAB as the standard (15 studies) yielded a pooled sensitivity of 63% (95% CI: 50, 75) and a specificity of 90% (95% CI: 81, 95).ConclusionThe US halo sign is a sensitive and specific approach for GCA assessment and plays a pivotal role in diagnosis of GCA in routine clinical practice.RegistrationPROSPERO 2020 CRD42020202179.

Perception of Cancer Risk and Management Practice for Colitis-associated Dysplasia Is Influenced by Colonoscopy Experience and Workplace Affiliation: Results of an International Clinician Survey.

Background and AimsA successful colitis cancer surveillance programme requires effective action to be taken when dysplasia is detected. This is the first international cross-sectional study to evaluate clinician understanding of dysplasia-cancer risk and management practice since the most recent international guidelines were introduced in 2015.MethodsA 15-item international online survey was disseminated to gastroenterologists and colorectal surgeons.ResultsA total of 294 clinicians [93.5% gastroenterologists] from 60 countries responded; 23% did not have access to high-definition chromoendoscopy. University hospitals were more likely than non-academic workplaces to provide second expert histopathologist review [67% vs 46%; p = 0.002] and formal multidisciplinary team meeting discussion [73% vs 52%; p = 0.001] of dysplasia cases. Perceptions of 5-year cancer risk associated with endoscopically unresectable low-grade dysplasia varied between 0% and 100%. Non-academic hospital affiliation was predictive of lower perceived cancer risks. Although most [98.4%] respondents advised a colectomy for endoscopically unresectable visible high-grade dysplasia, only 34.4% advised a colectomy for unresectable visible low-grade dysplasia. Respondents from university hospitals were more likely to consider colectomy for multifocal low-grade dysplasia (odds ratio [OR] 2.17). If invisible unifocal low-grade dysplasia was detected, continued surveillance over colectomy was the preferred management among clinicians working mainly in private clinics [OR 9.4] and least preferred in those who had performed more than 50 surveillance colonoscopies [OR 0.41].ConclusionsClinicians with less surveillance colonoscopy experience and from non-academic centres appear to have lower cancer risk perceptions and are less likely to advocate colectomy for higher-risk low-grade dysplasia. Further education may align current management practice with clinical guidelines.

Patients with an increased time to treatment initiation have a poorer overall survival after definitive surgery for localized high-grade soft-tissue sarcoma in the extremity or trunk

Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI. Patients in whom the time to treatment initiation was prolonged had poorer overall survival than those with a TTI of 0 to 30 days. These were: 31 to 60 days (hazard ratio (HR) 1.08, p = 0.011); 61 to 90 days (HR 1.11, p = 0.044); and 91 days (HR 1.22; p = 0.003). The restricted cubic spline showed that the hazard ratio increased substantially with a TTI longer than 50 days. Non-academic centres (vs academic centres; IRR ranging from 0.64 to 0.86; p < 0.001) had a shorter TTI. Those insured by Medicaid (vs private insurance; IRR 1.34), were uninsured (vs private insurance; IRR 1.17), or underwent a transition in care (IRR 1.62) had a longer TTI. A time to treatment initiation of more than 30 days after diagnosis was independently associated with poorer survival. The hazard ratio showed linear increase, especially if the TTI was more than 50 days. We recommend starting treatment within 30 days of diagnosis to achieve the highest likelihood of cure for localized high-grade soft-tissue sarcomas in the limbs and trunk, even when a patient needs to be referred to a specialist centre. Cite this article: Bone Joint J2021;103-B(6):1142-1149.

P348 Perception of cancer risk in inflammatory bowel disease-associated dysplasia and management practice is influenced by colonoscopy experience and workplace affiliation: results of an international clinician survey

Abstract Background A successful inflammatory bowel disease (IBD) surveillance cancer preventative programme requires effective action to be taken when dysplasia is detected. This is the first international cross-sectional study to evaluate current clinician understanding of IBD dysplasia risk, their management practice and adherence to the most recent international guidelines introduced since 2015. Methods A 15-item online survey was disseminated to IBD gastroenterologist and colorectal surgeon members of the British Society of Gastroenterology in June 2019 and the European Crohn’s and Colitis Organisation in February 2020. Results 294 clinicians (93.5% gastroenterologists) from 60 countries responded. A significant proportion indicated not having access to high definition chromoendoscopy IBD surveillance (23%) in their endoscopy units. University hospitals were more likely than non-academic workplaces to provide second expert histopathologist review (67% vs. 46%; p=0.002) and formal multidisciplinary team meeting discussion (73% vs. 52%; p=0.001) of dysplasia cases. Most respondents would advocate endoscopic resection of all visible dysplasia and would refer to a regional specialist therapeutic endoscopist if needed (70%). However, perceptions of 5-year cancer risk associated with endoscopically unresectable low-grade dysplasia (LGD) varied between 0 – 100% (median 20% for visible LGD and median 25% for invisible LGD). Although most (98.4%) would advise a colectomy for endoscopically unresectable visible high-grade dysplasia (HGD), only 34.4% would also advise a colectomy for unresectable visible LGD. Working at a non-academic hospital was predictive of a lower perceived cancer risk with HGD [OR 0.4 (95% CI 0.23-0.95)] and unresectable LGD. Working in a private clinic predicted surveillance preference over colectomy to manage invisible LGD [OR 9.4 (95% CI 1.19-74.1)] and multifocal LGD. Greater surveillance colonoscopy experience predicted a lower preference for continued surveillance over colectomy for invisible LGD [OR 0.41 (95% CI 0.20-0.84)]. Conclusion This study of mainly European gastroenterologists with a sub-specialist interest in IBD has revealed wide variations in colorectal cancer risk perceptions and dysplasia management practices. Clinicians with less IBD surveillance colonoscopy experience and from non-academic centres appeared to have lower cancer risk perceptions and were less likely to advocate colectomy over continued surveillance for high-risk LGD. This study suggests that further education is required to align current management practice with clinical guidelines.

Non-compliance to practice guidelines still exist in the early management of acute pancreatitis: Time for reappraisal?

IntroductionEarlier national surveys on the management of acute pancreatitis (AP) had reported non-compliance to practice guidelines. In the past decade, several guidelines were revised based on new evidence. In this multicenter international survey, we aimed to evaluate the practice patterns of early management of AP and compliance to the revised treatment guidelines across different disciplines and practice environments. MethodsA structured questionnaire was sent via email to a target population of 654 that constituted of medical and surgical gastroenterologists, physicians and general surgeons, paediatricians from academic and non-academic centres across 30 countries. Other than demographic variables, the questionnaire contained items pertaining to early management of AP, such as, assessment at admissions and within first 72 h s, details regarding analgesics, IV hydration, oral/enteral feeding and antibiotic use. ResultsThe response rate was 46.2% and after exclusions, a total of 297 participant's responses were analysed. Majority of the participants were from Asia, followed by Europe and the Americas. 181 (60.9%) claimed to follow practice guidelines, out of which 59 (32.6%) followed more than one. On further probing, only 41.9% were actually compliant to feeding and 59.7% to antibiotic guidelines. Even though participants opted for aggressive hydration, early feeding and avoidance of prophylactic antibiotics, there were non-compliance and discrepancies in titration of fluid therapy, indications of feeding and antibiotic use. DiscussionDiscrepancies and non-compliance still appear to exist in the early management of AP due to lack of strong evidence. We discuss ways that could improve compliance to the existing guidelines until stronger evidence comes to the fore.

Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trial

In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV. STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183. Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment. In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality. National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.

The burden of psoriatic arthritis in the biologics era: data from the Belgian Epidemiological Psoriatic Arthritis Study.

To characterize the frequency of PsA subtypes, estimate the severity based on damage and inflammation and estimate the impact of PsA on patients' health-related quality of life. We conducted a longitudinal observational study in 17 academic and non-academic centres in Belgium. Patients with PsA fulfilling Classification Criteria for Psoriatic Arthritis were recruited. Three visits were scheduled: at baseline (T0), at 1 year (±1 month; T1) and at 2 years (±1 month; T2) of follow-up. Demographics, clinical data and patient-reported outcome measures were collected at T0, T1 and T2. X-rays of the hands and feet were collected yearly (T0, T1 and T2). X-rays of the spine were collected at T0 and T2. Here we report on the burden of disease based on the clinical data and patient-reported outcomes. A total of 461 patients were recruited; 73.5% had combined peripheral and axial involvement and 13.7% had hip involvement. Plaque psoriasis was predominant (83.9%). At inclusion, 42.7% and 58.8% had no tender or swollen joints, respectively. Dactylitis and enthesitis were still present in 13.7% and 24.1% of the patients, respectively. Patients was treated with DMARDs (68%) and/or anti-TNF (44.2%). Forty-three per cent of the patients had a state of minimal disease activity and 62% considered the actual state as satisfactory. The mean HAQ score was 0.7%, with 32.5% of patients having a normal score (<0.3). Despite the availability of different treatment options, including biologics (anti-TNF), a substantial number of patients have active disease and have a high disease burden.

Multicentric Italian survey on daily practice for autoimmune pancreatitis: Clinical data, diagnosis, treatment, and evolution toward pancreatic insufficiency.

Autoimmune pancreatitis (AIP) is a rare, and relatively new, form of chronic pancreatitis. The management of AIP can vary considerably among different centres in daily clinical practice. The aim of this study is to present a picture of epidemiological, clinical characteristics, outcomes, and the real-life practice in terms of management in several academic and non-academic centres in Italy. Data on the clinical presentation, diagnostic work-up, treatments, frequency of relapses, and long-term outcomes were retrospectively collected in a cohort of AIP patients diagnosed at 14 centres in Italy. One hundred and six patients were classified as type 1 AIP, 48 as type 2 AIP, and 19 as not otherwise specified. Epidemiological, clinical, radiological, and serological characteristics, and relapses were similar to those previously reported for different types of AIP. Endoscopic cytohistology was available in 46.2% of cases, and diagnostic for AIP in only 35.2%. Steroid trial to aid diagnosis was administered in 43.3% cases, and effective in 93.3%. Steroid therapy was used in 70.5% of cases, and effective in 92.6% of patients. Maintenance therapy with low dose of steroid (MST) was prescribed in 25.4% of cases at a mean dose of 5 (±1.4) mg/die, and median time of MST was 60 days. Immunosuppressive drugs were rarely used (10.9%), and rituximab in 1.7%. Faecal elastase-1 was evaluated in only 31.2% of patients, and was pathological in 59.2%. In this cohort of AIP patients, diagnosis and classification for subtype was frequently possible, confirming the different characteristics of AIP1 and AIP2 previously reported. Nevertheless, we observed a low use of histology and steroid trial for a diagnosis of AIP. Steroid treatment was the most used therapy in our cohort. Immunosuppressants and rituximab were rarely used. The evaluation of exocrine pancreatic insufficiency is underemployed considering its high prevalence.

National Multidisciplinary Survey of Regional Anesthesia Preferences in Breast Reconstruction.

The purpose of this work was to determine the regional anesthesia preferences of plastic surgeons (PS) and anesthesiologists (A) involved in breast reconstruction in Canada. Online surveys were sent to members of the Canadian Society of Plastic Surgeons (CSPS) and the Canadian Anesthesiologists Society (CAS). The primary outcome was regional anesthesia preferences in breast reconstruction (delayed, immediate, alloplastic, autologous). Secondary outcomes included the availability and the influence of specialty and academic status on preferences. Statistical analysis used descriptive statistics and Pearson χ2 test. Responses from CSPS and CAS totaled 141 (response rate = 30%) and 217 (response rate = 14%), respectively. Compared with non-academic centres (NAC), academic centres (AC) had significantly greater access to (AC = 60%, NAC = 39%, P = .001) and preferred to use regional anesthesia more often (AC = 36%, NAC = 10%, P < .001). The following proportions of physicians preferred to use regional anesthesia: 40% (PS = 32%, A = 44%, P = .081) for immediate alloplastic reconstruction, 23% (PS = 24%, A = 22%, P = .821) for delayed alloplastic reconstruction, 34% (PS = 18%, A = 41%, P < .001) for immediate autologous reconstruction, and 19% (PS = 13%, A = 21%, P = .195) for delayed autologous reconstruction. Regional anesthesia preferences were significantly different between plastic surgeons and anesthesiologists (P < .001)-anesthesiologists favoured paravertebral blocks for all reconstructions, while plastic surgeons favoured pectoral nerve blocks for immediate alloplastic reconstruction and intercostal nerve blocks for all other reconstructions. Plastic surgeons and anesthesiologists prefer not to use regional anesthesia in the majority breast reconstructions. Among those who deploy regional anesthesia, plastic surgeons and anesthesiologist have divergent preferences with respect to modality. There is a need for a prospective study comparing paravertebral blocks and intercostal nerve blocks.

Imperfect by design: the problematic ethics of surgical training

There exists in academic medicine a core ethical issue that is seldom pursued: trainees are frequently not the best person in the operating room at a given intervention being performed,...

Accessible laparoscopic liver resection performed in low volume centers: Is it time for democratization?

Laparoscopic liver resection (LLR) has been developed and is daily practiced by many expert teams. However, very few data are available on the experience of low volume centres. The aim of our study was to report and discuss the operative results of LLR performed in three low volume centres. Records of patients who underwent a LLR in three low volume centres in France between May 2014 and November 2017 were collected. Endpoints studied were indications, intra and postoperative outcomes as well as short-term outcomes. A total of 46 patients (57 specimen resected) underwent a LLR during this period, representing 29.6% of total liver resections. Indications of LLR were benign lesions in 26%, primitive malignant lesions in 32.6% and metastatic tumours in 41.3%. Median size of lesions was 22mm (range 11-100). Most liver resections were non-anatomic (64.7%), while left lateral sectionectomies represented 19.2%. Five patients required conversion and there were at the end 3 specimen with margins inferior to 1mm resected laparoscopically. Postoperative mortality was nil and morbidity rate was 17.3%. Median hospital stay was 6 days (3-15). Although LLR have gained acceptance in surgeons' arsenal, it remains concentrated in referral centres. Our results suggest the feasibility of LLR in non-academic centres when it comes to small accessible lesions. Further studies would provide data about the long-term safety of this procedure in those centres.

The characterisation of interstitial lungdisease multidisciplinary team meetings:aglobal study.

Multidisciplinary team (MDT) diagnosis of interstitial lung disease (ILD) has been proposed as a gold standard, but there are no formal recommendations for MDT process or composition and limited knowledge regarding prevalence in routine practice.We performed a systematic evaluation of ILD diagnostic practice across a range of healthcare settings around the world. Electronic questionnaires were distributed across all global regions via society and collaborators networks.Responses from 457 unique centres across 64 countries were included in the analysis. Of the 350 (76.6%) centres holding formal meetings, the majority held face-to-face MDT meetings (80%), for a minimum of 30 min (93%), and discussed diagnosis (96.9%) and patient management (94.9%) at the meetings. Compared with non-academic and academic non-ILD centres, ILD academic centres reported a higher ILD caseload, held more formal MDT meetings, and were more likely to include histopathology and rheumatology specialists in their diagnostic team. Of the centres holding MDT meetings, 5.5% routinely discussed all new cases at such meetings.An MDT approach to ILD diagnosis is consistently interpreted and widely implemented across a range of routine care settings around the world. This observation will inform future ILD diagnostic agreement studies and diagnostic pathway recommendations.