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Background Muscular dystrophies (MDs) are inherited diseases in which a dysregulation of the immune response exacerbates disease severity and are characterized by infiltration of various immune cell types leading to muscle inflammation, fiber necrosis and fibrosis. Immunosuppressive properties have been attributed to mesenchymal stem cells (MSCs) that regulate the phenotype and function of different immune cells. However, such properties were poorly considered until now for adult stem cells with myogenic potential and advanced as possible therapeutic candidates for MDs. In the present study, we investigated the immunoregulatory potential of human MuStem (hMuStem) cells, for which we previously demonstrated that they can survive in injured muscle and robustly counteract adverse tissue remodeling. Methods The impact of hMuStem cells or their secretome on the proliferative and phenotypic properties of T-cells was explored by co-culture experiments with either peripheral blood mononucleated cells or CD3-sorted T-cells. A comparative study was produced with the bone marrow (BM)-MSCs. The expression profile of immune cell-related markers on hMuStem cells was determined by flow cytometry while their secretory profile was examined by ELISA assays. Finally, the paracrine and cell contact-dependent effects of hMuStem cells on the T-cell-mediated cytotoxic response were analyzed through IFN-γ expression and lysis activity. Results Here, we show that hMuStem cells have an immunosuppressive phenotype and can inhibit the proliferation and the cytotoxic response of T-cells as well as promote the generation of regulatory T-cells through direct contact and via soluble factors. These effects are associated, in part, with the production of mediators including heme-oxygenase-1, leukemia inhibitory factor and intracellular cell adhesion molecule-1, all of which are produced at significantly higher levels by hMuStem cells than BM-MSCs. While the production of prostaglandin E2 is involved in the suppression of T-cell proliferation by both hMuStem cells and BM-MSCs, the participation of inducible nitric oxide synthase activity appears to be specific to hMuStem cell-mediated one. Conclusions Together, our findings demonstrate that hMuStem cells are potent immunoregulatory cells. Combined with their myogenic potential, the attribution of these properties reinforces the positioning of hMuStem cells as candidate therapeutic agents for the treatment of MDs.

Inflammatory bowel disease (IBD) is a chronic condition that significantly affects the quality of life of its patients. Biologic drugs have been the mainstay treatment in the management of IBD patients but despite their significant contribution, there remains a proportion of patients that do not respond or lose response to treatment. Therapeutic drug monitoring (TDM) involves measuring levels of serum drug concentrations and anti-drug antibodies. TDM of biologic drugs initially emerged to understand treatment failure in other immune mediated inflammatory diseases. This was then introduced in IBD to rationalize primary non-response or secondary loss of response, given that low serum drug concentrations or the formation of anti-drug antibodies are variably associated with treatment failure. The aim of this narrative review is to provide an overview regarding the current use of TDM in clinical practice and to present the evidence available regarding its use in both proactive and reactive clinical settings in preventing and managing treatment failure. This review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations, in everyday practice. A narrative review of published articles and conference abstracts regarding the use of TDM in IBD management, through an electronic search using PubMed and ScienceDirect. TDM has proven to be superior and more cost effective in guiding management of patients with treatment failure compared to empiric dose escalation or change in treatment. Despite a trend towards an association between clinical outcomes and drug concentrations, proactive TDM based strategies have not been shown to achieve clear benefit in long-term outcomes. In the clinical setting, TDM has proven to be useful in managing IBD patients, and its use in the reactive setting, as an additional tool to help manage patients with treatment failure, is being promoted as newer guidelines and consensus groups implement TDM as part of the management plan.

Background and Aims: Acute non-variceal upper gastrointestinal bleeding (UGIB) is associated with significant morbidity and mortality. Our aim was to evaluate the incidence, management, risk factors and outcomes of acute non-variceal UGIB in a population-based study from Hungary. Methods: The present prospective one–year study involved six major community hospitals in Western Hungary covering a population of 1,263,365 persons between January 1 and December 31, 2016. Data collection included demographics, comorbidities endoscopic management, Glasgow-Blatchford score (GBS), Rockall score (RS) transfusion requirements, length of hospital stay and mortality. Results: 688 cases of acute non-variceal UGIB were included with an incidence rate of 54.4 (95%CI: 50.5-58.6) per 100,000 per year. Endoscopy was performed within 12 hours in 71.8%. 5.3% of the patients required surgical treatment and the overall mortality was 13.5%. Weekend presentation was associated with increased transfusion requirements (p=0.047), surgery (p=0.016) and mortality (p=0.021). Presentation with hemodynamic instability or presence of comorbidities was associated with transfusion (p7points), while mortality was best predicted by the post-endoscopic RS (AUC:0.75; cut-off: RS >5points). Conclusions: Incidence rates of acute non-variceal UGIB in Western Hungary are in line with international trends. Longer pre-hospital time, comorbidities, hemodynamic instability, weekend presentation, treatment with anticoagulants or non-steroidal anti-inflammatory drugs was associated with worse outcomes.

Background Caregivers in healthcare settings are exposed to a risk of antineoplastic drug contamination which can lead to adverse health effects. Biological monitoring is necessary to estimate the actual level of exposure of these workers. This study was conducted with the aim of assessing blood contamination levels by irinotecan and its metabolites of pharmaceutical staff operating inside and outside a compounding unit. Methods The study took place within the pharmaceutical unit of a French comprehensive cancer centre. Blood samples were collected from the pharmacy workers operating inside and outside the compounding unit, and analysed by UHPLC-MS/MS. Plasma and red blood cell irinotecan and its metabolites (SN-38; APC) were determined with a validated analytical method detection test. Results A total of 17/78 (21.8%) plasma and red blood cell-based assays were found to be contaminated among staff. Overall, the total number of positive assays was significantly higher for staff members working outside the compounding unit than for workers working inside it ( P = 0.022), with respectively 5/42 (11.9%) and 12/36 (33.3%) positive assays. For plasma dosages, the “outside” group had a significantly higher number of positive assays ( P = 0.014). For red blood cell-based assays, no significant difference was found ( P = 0.309). Conclusions This study reveals that pharmaceutical staff serving in health care settings are exposed to a risk of antineoplastic drug contamination, not only inside the compounding room but also in adjacent rooms. The results would help to raise awareness and potentially establish protective measures for caregivers working in areas close to the compounding room as well.

New data suggest that incidence and prevalence of inflammatory bowel diseases [IBD] are still increasing worldwide, and approximately 0.2% of the European population suffer from IBD at the present time. Medical therapy and disease management have evolved significantly in recent decades, with an emphasis on tight objective monitoring of disease progression and a treat-to-target approach in Europe and also worldwide, aiming to prevent early bowel damage and disability. Surgery rate declined over time in Europe, with 10–30% of CD and 5–10% of UC patients requiring a surgery within 5 years. The health economic burden associated with IBD is high in Europe. Direct health care costs [approximately €3500 in CD and €2000 in UC per patient per year] have shifted from hospitalisation and surgery towards drug-related expenditures with the increasing use of biologic therapy and other novel agents, and substantial indirect costs arise from work productivity loss [approximately €1900 per patient yearly]. The aim of this paper is to provide an updated review of the burden of IBD in Europe by discussing current data on epidemiology, disease course, risk for surgery, hospitalisation, and mortality and cancer risks, as well as the economic aspects, patient disability, and work impairment, by discussing the latest population-based studies from the region.

Angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma with T follicular helper phenotype (PTCL-TFH) are a group of complex clinicopathological entities that originate from T follicular helper cells and share a similar mutation profile. Their diagnosis is often a challenge, particularly at an early stage, because of a lack of specific histological and immunophenotypic features, paucity of neoplastic T cells and prominent polymorphous infiltrate. We investigated whether the lymphoma-associated RHOA Gly17Val (c.50G>T) mutation, occurring in 60% of cases, is present in the early “reactive” lesions, and whether mutation analysis could help to advance the early diagnosis of lymphoma. The RHOA mutation was detected by quantitative polymerase chain reaction with a locked nucleic acid probe specific to the mutation, and a further peptide nucleic acid clamp oligonucleotide to suppress the amplification of the wild-type allele. The quantitative polymerase chain reaction assay was highly sensitive and specific, detecting RHOA Gly17Val at an allele frequency of 0.03%, but not other changes in Gly17, nor in 61 controls. Among the 37 cases of AITL and PTCL-TFH investigated, RHOA Gly17Val was detected in 62.2% (23/37) of which 19 had multiple biopsies including preceding biopsies in ten and follow-up biopsies in 11 cases. RHOA Gly17Val was present in each of these preceding or follow-up biopsies including 18 specimens that showed no evidence of lymphoma by combined histological, immunophenotypic and clonality analyses. The mutation was seen in biopsies 0-26.5 months (mean 7.87 months) prior to the lymphoma diagnosis. Our results show that RHOA Gly17Val mutation analysis is valuable in the early detection of AITL and PTCL-TFH.

Background Studies on adolescent secondhand smoke exposure within the family often dichotomously operationalize migration background without paying attention to social and cultural diversity within migrant populations. As a result, little is known about variation within migrant groups in smoke-free family environments (SFFEs). This study analyses the association between SFFEs and parental migration from different world regions. Methods Data from 14- to 16-year-old adolescents (N = 17 144) on SFFEs and parental migration were obtained from cross-sectional repeated SILNE-R surveys. A multivariable multinomial regression was applied, presenting relative risks (RRs) with 95% confidence intervals (CIs) for maternal or paternal tobacco smoking and home smoking bans. Variation in migration background was measured according to parental sex and place of birth. Results Approximately 18% of adolescents are exposed to maternal smoking, and 25% are exposed to paternal smoking. Almost half of the respondents do not live in SFFEs but are subject to permissive (5%) or partial (39%) smoking bans at home. We found that adolescents of Eastern European descent are at a higher risk of being exposed to both paternal and maternal smoking. A sex difference in parental smoking was found among Arabic/Islamic migrants, where mothers are less likely to be smokers. Maternal and paternal African origins are associated with prohibitive smoking bans at home. Eastern European mothers show higher odds of permissiveness and freely allowing smoking at home. Conclusion Notable within-differences according to parental sex and place of birth were found for SFFEs and should be taken into account when implementing equity-sensitive tobacco prevention programs.

Background and Aims: Anemia is a common complication of inflammatory bowel diseases (IBD), as well as a predictor of poor outcomes. The aim of this study was to determine the prevalence of anemia over time and the management of moderate to severe anemia at a tertiary referral IBD center. Methods: We retrospectively reviewed the occurrence of anemia at the time of referral or diagnosis and during follow-up at the McGill University Health Centre IBD center. Consecutive patients presenting with an outpatient visit between July and December 2016 and between December 2018 and March 2019 were included. Disease characteristics, biochemistry and medical management, including the need for intravenous iron therapy were recorded. Results: 1,356 Crohn’s disease (CD) and 1,293 ulcerative colitis (UC) patients [disease duration: 12 (IQR: 6-22) and 10 (IQR: 5-19) years respectively] were included. The prevalence of moderate to severe anemia at referral/diagnosis (15.4% and 8.5%) and during follow-up (11.1% and 8.1%) were higher in CD than in UC patients. In CD, previous resective surgery, perianal disease and elevated C-reactive protein (CRP) at assessment, while in UC steroid therapy, an elevated CRP and fecal calprotectin at assessment were associated with anemia in a multivariate analysis. Anemia improved by >2g/dL in 56.5% after 4-6 weeks (intravenous iron dose >1000 mg in 87% of patients). Conclusion: Anemia occurred frequently in this IBD cohort, at referral to the center and during follow-up, and contributes to the burden of IBD in referral populations. Most patients were assessed for anemia regularly and with accurate anemia workup; however, the targeted management of moderate to severe anemia was suboptimal.

IntroductionMany European schools implement smoke-free school policies (SFSPs). SFSPs may decrease adolescent smoking by causing adolescents to perceive stronger antismoking norms, yet there exists no quantitative evidence that indicates for which norms and for whom such effects may occur. This study therefore assessed to what extent adolescents’ perceived antismoking norms among best friends, teachers, and society at large were associated with SFSPs, and whether these associations were moderated by adolescents’ level of school connectedness.Aims and MethodsSurvey data were collected in 2016/2017 on 10,653 adolescents aged 14–16 years old and 315 staff members in 55 schools from seven European cities. Associations of adolescent-perceived SFSPs and staff-reported SFSPs with best friend, teacher, and societal antismoking norms were estimated in multilevel logistic regression models, adjusted for demographics and school-level smoking prevalence. We tested for interaction between school connectedness and SFSPs.ResultsAdolescent-perceived SFSPs were positively associated with antismoking norms by teachers (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 1.15–1.85), were negatively associated with antismoking norms by best friends (OR: 0.81, 95% CI: 0.67–0.99), but were not significantly associated with antismoking norms by society at large (OR: 0.87, 95% CI: 0.74–1.02). All interaction tests between adolescent-perceived SFSPs and school connectedness were nonsignificant. Staff-reported SFSPs were not associated with any norm and showed no significant interaction with school connectedness.ConclusionsWe found that SFSPs are associated with adolescents’ perception of more antismoking norms by teachers, but less antismoking norms by best friends, irrespective of adolescents’ level of school connectedness.ImplicationsSmoke-free school policies, just as many other tobacco control policies, are assumed to foster adolescents’ perception of antismoking norms. Still, current evidence does not demonstrate which antismoking norms may be influenced by SFSPs and whether this influence is equal for adolescents with different levels of school connectedness. This study suggests that SFSPs foster adolescents’ perception of antismoking norms by teachers, but may concurrently lead to the perception of less antismoking norms by best friends, irrespective of adolescents’ school connectedness. SFSPs may therefore need to be complemented with interventions that target antismoking norms in adolescent peer groups.

Skin moles and lesions can be the first signs of severe skin diseases such as cancer. This paper presents the development of an end-user device capable of capturing images, segmentation and diagnosis of moles by using the ABCD rule, which stands for analyzing moles’ parameters as: asymmetry, border, color, and diameter. These are the main mole characteristics that doctors look at, each of them having a different factor of importance, and depending on these an accurate diagnosis can be given. For the hardware, we developed a small and compact device that can be manipulated easily by anyone without knowledge of medicine, in which we considered a custom-designed 3D enclosure with two white LEDs to control the light. The device has the role of facilitating analysis of the suspicious moles regularly at home, even if only from an indicative and not from a medical point of view. The developed PC software permits the storage of the images in a local database for easy tracking and analysis in time. The image processing developed for the ABCD rule is incorporated into the PC software and tested extensively on the international PH2 database with skin melanoma images to validate our segmentation and criteria evaluation. Using the developed device, we captured mole images for patients, who also took a medical examination by a specialist using the standard dermatoscope. Therefore, we obtained our own database containing 26 images for which we have also the specialists’ diagnosis. The performance evaluation measures obtained using our device are—Accuracy: 0.92, Precision: 1.0, Recall: 0.92, F1-score: 0.96.

Background Malignancies in the urinary tract and the kidney graft are quite common after kidney transplantation. In some selected cases tumours develop from donor-derived tissue. Objectives We hypothesised that there is a clinical value to investigate donor/recipient origin in urologic malignancies in renal transplant recipients. Methods In this retrospective study, including patients transplanted between the years 1969 and 2014 at Uppsala University Hospital, Sweden, 11 patients with malignancies in urinary tract and 4 patients with malignancies in kidney transplants were investigated. Donor/recipient origin of tumour tissue was analysed by polymerase chain reaction (PCR) of human leucocyte antigen (HLA) genotypes or by fluorescence in situ hybridization (FISH analysis) of sex chromosomes. HLA genotype and sex chromosomes of the tumour were compared to the known HLA genotype and sex chromosomes of recipient and donor. Results Three of ten cancers in the urinary tract and three of four cancers in the kidney transplants were donor-derived. Conclusions We suggest that urologic malignancies in renal transplant recipients can be investigated for transplant origin. In addition to conventional therapy the allograft immune response against these tumours can be valuable to treat donor-derived cancers.

Background General Practitioners (GPs) are the first point of contact for people from ethnic and migrant groups who have health problems. Discrimination can occur in this health care sector. Few studies, however, have investigated implicit and explicit biases in general practice against ethnic and migrant groups. This study, therefore, investigated the extent of implicit ethnic biases and willingness to adapt care to migrant patients among trainee GPs, and the factors involved therein, in order to measure explicit bias and explore a dimension of cultural competence. Methods In 2021, data were collected from 207 trainee GPs in the French-speaking part of Belgium. The respondents passed an Implicit Association Test (IAT), a validated tool used to measure implicit biases against ethnic groups. An explicit attitude of willingness to adapt care to diversity, one of the dimensions of cultural competence, was measured using the Hudelson scale. Results The overwhelming majority of trainee GPs (82.6%, 95% CI: 0.77 – 0.88) had implicit preferences for their ingroup to the detriment of ethnic and migrant groups. Overall, the majority of respondents considered it the responsibility of GPs to adapt their attitudes and practices to migrants’ needs. More than 50% of trainee GPs, however, considered it the responsibility of migrant patients to adapt to the values and habits of the host country. Conclusions This study found that the trainee GPs had high to very high levels of implicit ethnic bias and that they were not always willing to adapt care to the values of migrants. We therefore recommend that they are made aware of this bias and we recommend using the IAT and Hudelson scales as educational tools to address ethnic biases in primary care.

Background. Imlifidase is an immunoglobulin G (IgG)-specific protease conditionally approved in the EU for desensitization in highly sensitized crossmatch positive kidney transplant patients. Imlifidase efficiently cleaves both heavy chains of IgG in a 2-step process. However, low levels of the intermediate cleavage product, single-cleaved IgG (scIgG), may persist in the circulation. The study objective was to investigate Fc-mediated effector functions of scIgG and its potential impact on common clinical immunologic assays used to assess transplant eligibility. Methods. Imlifidase-generated scIgG, obtained by in vitro cleavage of HLA-sensitized patient serum or selected antibodies, was investigated in different complement- and Fc gamma R-dependent assays and models, including clinical tests used to evaluate HLA-specific antibodies. Results. ScIgG had significantly reduced Fc-mediated effector function compared with intact IgG, although some degree of activity in complement- and Fc gamma R-dependent models was still detectable. A preparation of concentrated scIgG generated from a highly HLA-sensitized individual gave rise to a positive signal in the anti-HLA IgG LABScreen, which uses anti-Fc detection, but was entirely negative in the C1qScreen. The same high-concentration HLA-binding scIgG preparation also generated positive complement-dependent cytotoxicity responses against 80%-100% of donor T and B cells, although follow-up titrations demonstrated a much lower intrinsic activity than for intact anti-HLA IgG. Conclusions. ScIgG has a significantly reduced capacity to mediate Fc-dependent effector functions. However, remaining HLA-reactive scIgG in plasma after imlifidase treatment can cause positive assay results equivalent to intact IgG in clinical assays. Therefore, complete IgG cleavage after imlifidase treatment is essential to allow correct decision-making in relation to transplant eligibility.

Kinase activity is frequently altered in renal cell carcinoma (RCC), and tyrosine kinase inhibitors (TKIs) are part of the standard treatment strategy in patients with metastatic disease. However, there are still no established biomarkers to predict clinical benefits of a specific TKI. Here, we performed protein tyrosine kinase (PTK) profiling using PamChip® technology. The aim of this study was to identify differences in PTK activity between normal and malignant kidney tissue obtained from the same patient, and to investigate the inhibitory effects of TKIs frequently used in the clinics: sunitinib, pazopanib, cabozantinib and tivozanib. Briefly, our results showed that 36 kinase substrates differs (FDR < 0.05) between normal and cancer kidney tissue, where members of the Src family kinases and the phosphoinositide-3-kinase (PI3K) pathway exhibit high activity in renal cancer. Furthermore, ex vivo treatment of clear cell RCC with TKIs revealed that pathways such as Rap1, Ras and PI3K pathways were strongly inhibited, whereas the neurotrophin pathway had increased activity upon TKI addition. In our assay, tivozanib and cabozantinib exhibited greater inhibitory effects on PTK activity compared to sunitinib and pazopanib, implying they might be better suitable as TKIs for selected RCC patients.

To assess the level and factors of compliance of carbapenem prescriptions with guidelines and to determine the impact of an antibiotic stewardship team in a university hospital.Five-month prospective study in the intensive care, surgery, and medicine units to measure the compliance of carbapenem prescriptions with guidelines from French scientific societies; compliance was assessed by an infectious disease specialist warned by the pharmacy, and the prescribers' compliance with the infectious disease specialist's advice was then assessed.One hundred and four treatment initiations for 94 patients were included. Prescriptions were mostly empirical (64%), for pulmonary (35%), urinary tract (23%), and intra-abdominal (17%) infections. Prescriptions were mostly made in an intensive care unit (50%), by a junior physician (66%), with the use of imipenem (74%), and were followed by an objective reassessment (80%). Compliance with guidelines (82%) was significantly higher for empirical than documented prescriptions (91% vs 65%, P0.001). Compliance was higher in intensive care units than medicine units (87% vs 61%, P=0.037). No change in the compliance rate was observed during the study. Compliance with the infectious disease specialist's advice (68%) improved, although not significantly (P=0.066).Because of a higher than expected compliance of carbapenem prescriptions with guidelines and a lower than expected inclusions in the study, we did not show any impact. The diffusion of guidelines and long-term control of carbapenem prescriptions seem to be possible and necessary in hospitals to limit their ecological impact.

Purpose Long lengths of stay (LoS) in psychiatric hospitals or repeated admission may affect the social integration of patients with psychiatric disorders. So far, however, studies have been inconclusive. This study aimed to analyse whether long LoS or repeated admissions in psychiatric wards were associated in different ways with changes in the social integration of patients. Methods Within a prospective cohort study, data were collected on 2181 patients with a main ICD-10 diagnosis of psychotic, affective, or anxiety disorder, hospitalised in the UK, Italy, Germany, Poland, and Belgium in 2015. Social integration was measured at baseline and 1 year after admission using the SIX index, which includes four dimensions: employment, housing, family situation, and friendship. Regression models were performed to test the association between LoS, the number of admissions, and the change in social integration over the study period, controlling for patients’ characteristics (trial registration ISRCTN40256812). Results A longer LoS was significantly associated with a decrease in social integration (β = − 0.23, 95%CI − 0.32 to − 0.14, p = 0.03), particularly regarding employment (OR = 2.21, 95%CI 1.18–3.24, p = 0.02), housing (OR = 3.45, 95%CI 1.74–5.16, p p = 0.04). In contrast, repeated admissions were only associated with a decrease in friendship contacts (OR = 1.15, 95CI% 1.08–1.22, p = 0.03). Conclusions Results suggest that a longer hospital LoS is more strongly associated with a decrease in patients’ social integration than repeated admissions. Special attention should be paid to helping patients to find and retain housing and employment while hospitalised for long periods.

An important amount of cytotoxic drug may accumulate in the workplace following the breakage of a vial containing an anticancer drug. Thanks to the monthly monitoring of the surface contamination in our compounding unit, a strong increase of cyclophosphamide contamination was highlighted in the storage area following the breakage of the vial, despite application of the emergency procedure. This study presents an analysis of chemical decontamination in the context of massive contamination. Samples were taken on the floor and on the caster of a storage shelf where the vial broke. The residual contamination was measured with a liquid chromatography–mass spectrometry/mass spectrometry method. An admixture of 10−2 M sodium dodecyl sulfate and 70% isopropanol (SDS/IPA 8:2) was selected as the decontamination solution. High amounts of cyclophosphamide were retrieved. The initial contamination on the floor was over 20 ng/cm2. Three decontaminations with SDS/IPA were carried out at Day 61, Day 68, and Day 71. The amount of cyclophosphamide decreased to 0.45 ng/cm2 at D134. However, high values were still measured on the caster despite successive decontaminations, with a maximal value of 19.78 ng/cm2 observed at Day 106. Continuous monitoring in our unit led us to highlight the inefficiency of our emergency procedure to eliminate high cyclophosphamide contamination. The procedure involving the SDS/IPA admixture was more efficient on the floor compared to the caster, which is a different surface type and porosity. This work highlights the importance of improving the procedures of incident management using contamination monitoring and repeated decontamination procedures adapted to different contaminants and surfaces.

BACKGROUND Emergency situations in inflammatory bowel diseases (IBD) put significant burden on both the patient and the healthcare system. AIM To prospectively measure Quality-of-Care indicators and resource utilization after the implementation of the new rapid access clinic service (RAC) at a tertiary IBD center. METHODS Patient access, resource utilization and outcome parameters were collected from consecutive patients contacting the RAC between July 2017 and March 2019 in this observational study. For comparing resource utilization and healthcare costs, emergency department (ED) visits of IBD patients with no access to RAC services were evaluated between January 2018 and January 2019. Time to appointment, diagnostic methods, change in medical therapy, unplanned ED visits, hospitalizations and surgical admissions were calculated and compared. RESULTS 488 patients (Crohn’s disease: 68.4%/ulcerative colitis: 31.6%) contacted the RAC with a valid medical reason. Median time to visit with an IBD specialist following the index contact was 2 d. Patients had objective clinical and laboratory assessment (C-reactive protein and fecal calprotectin in 91% and 73%). Fast-track colonoscopy/sigmoidoscopy was performed in 24.6% of the patients, while computed tomography/magnetic resonance imaging in only 8.1%. Medical therapy was changed in 54.4%. ED visits within 30 d following the RAC visit occurred in 8.8% (unplanned ED visit rate: 5.9%). Diagnostic procedures and resource utilization at the ED (n = 135 patients) were substantially different compared to RAC users: Abdominal computed tomography was more frequent (65.7%, P < 0.001), coupled with multiple specialist consults, more frequent hospital admission (P < 0.001), higher steroid initiation (P < 0.001). Average medical cost estimates of diagnostic procedures and services per patient was $403 CAD vs $1885 CAD comparing all RAC and ED visits. CONCLUSION Implementation of a RAC improved patient care by facilitating easier access to IBD specific medical care, optimized resource utilization and helped avoiding ED visits and subsequent hospitalizations.

Angioimmunoblastic T‐cell lymphoma (AITL) is a neoplastic proliferation of T follicular helper cells with clinical and histological presentations suggesting a role of antigenic drive in its development. Genetically, it is characterized by a stepwise acquisition of somatic mutations, with early mutations involving epigenetic regulators (TET2, DNMT3A) and occurring in haematopoietic stem cells, with subsequent changes involving signaling molecules (RHOA, VAV1, PLCG1, CD28) critical for T‐cell biology. To search for evidence of potential oncogenic cooperation between genetic changes and intrinsic T cell receptor (TCR) signaling, we investigated somatic mutations and T‐cell receptor β (TRB) rearrangement in 119 AITL, 11 peripheral T‐cell lymphomas with T follicular helper phenotype (PTCL‐TFH), and 25 PTCL‐NOS using Fluidigm polymerase chain reaction (PCR) and Illumina MiSeq sequencing. We confirmed frequent TET2, DNMT3A, and RHOA mutations in AITL (72%, 34%, 61%) and PTCL‐TFH (73%, 36%, 45%) and showed multiple TET2 mutations (2 or 3) in 57% of the involved AITL and PTCL‐TFH. Clonal TRB rearrangement was seen in 76 cases with multiple functional rearrangements (2–4) in 18 cases (24%). In selected cases, we confirmed bi‐clonal T‐cell populations and further demonstrated that these independent T‐cell populations harboured identical TET2 mutations by using BaseScope in situ hybridization, suggesting their derivation from a common TET2 mutant progenitor cell population. Furthermore, both T‐cell populations expressed CD4. Finally, in comparison with tonsillar TFH cells, both AITL and PTCL‐TFH showed a significant overrepresentation of several TRB variable family members, particularly TRBV19*01. Our findings suggest the presence of parallel neoplastic evolutions from a common TET2 mutant haematopoietic progenitor pool in AITL and PTCL‐TFH, albeit to be confirmed in a large series of cases. The biased TRBV usage in these lymphomas suggests that antigenic stimulation may play an important role in predilection of T cells to clonal expansion and malignant transformation. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

The skin is the first protective barrier of our body. Wound healing is therefore an essential mechanism. However, this phenomenon can be impaired when wounds are too large or chronic, for example, in diabetes. Interestingly, adult skin heals with scars, whereas foetuses present scarless regeneration. The objective of this review is to highlight the difference in healing pathways between foetal and adult skin and to present the recent therapeutic strategies envisaged using foetal properties in the clinic. The main features that distinguish foetal wound healing from adult wound healing are less tissue inflammation, faster reepithelialisation, and less contraction of the neodermis, allowing foetal tissues to regenerate. Recently, new therapies in regenerative medicine have been introduced using these foetal properties. For the first time, our team has developed CICAFAST, an innovative dressing composed of foetal keratinocytes and fibroblasts, which has been tested on a skin graft donor site in a clinical Phase 1/2 trial.

In recent years, there has been a critical change in treatment paradigms in inflammatory bowel diseases (IBD) triggered by the arrival of new effective treatments aiming to prevent disease progression, bowel damage and disability. The insufficiency of symptomatic disease control and the well-known discordance between symptoms and objective measures of disease activity lead to the need of reviewing conventional treatment algorithms and developing new concepts of optimal therapeutic strategy. The treat-to-target strategies, defined by the selecting therapeutic targets in inflammatory bowel disease consensus recommendation, move away from only symptomatic disease control and support targeting composite therapeutic endpoints (clinical and endoscopical remission) and timely assessment. Emerging data suggest that early therapy using a treat-to-target approach and an algorithmic therapy escalation using regular disease monitoring by clinical and biochemical markers (fecal calprotectin and C-reactive protein) leads to improved outcomes. This review aims to present the emerging strategies and supporting evidence in the current therapeutic paradigm of IBD including the concepts of “early intervention”, “treat-to-target” and “tight control” strategies. We also discuss the real-word experience and applicability of these new strategies and give an overview on the future perspectives and areas in need of further research and potential improvement regarding treatment targets and (“tight”) disease monitoring strategies.

BackgroundWound repair is one of the most complex biological processes of human life. Allogeneic cell-based engineered skin substitutes provide off-the-shelf temporary wound coverage and act as biologically active dressings, releasing growth factors, cytokines and extracellular matrix components essential for proper wound healing. However, they are susceptible to immune rejection and this is their major weakness.Thanks to their low immunogenicity and high effectiveness in regeneration, fetal skin cells represent an attractive alternative to the commonly used autologous and allogeneic skin grafts.Methods/designWe developed a new dressing comprising a collagen matrix seeded with a specific ratio of active fetal fibroblasts and keratinocytes. These produce a variety of healing growth factors and cytokines which will increase the speed of wound healing and induce an immunotolerant state, with a slight inflammatory reaction and a reduction in pain.The objective of this study is to demonstrate that the use of this biological dressing for wound healing at the split-thickness skin graft (STSG) donor site, reduces the time to healing, decreases other co-morbidities, such as pain, and improves the appearance of the scar.This investigation will be conducted as part of a randomized study comparing our new biological dressing with a conventional treatment in a single patient, thus avoiding the factors that may influence the healing of a graft donor site.DiscussionThis clinical trial should enable the development of a new strategy for STSG donor-wound healing based on a regenerative dressing. The pain experienced in the first few days of STSG healing is well known due to the exposure of sensory nerve endings. Reducing this pain will also reduce analgesic drug intake and the duration of sick leave.Our biological dressing will meet the essential need of surgeons to “re-crop” from existing donor sites, e.g., for thermal-burn patients. By accelerating healing, improving the appearance of the scar and reducing pain, we hope to improve the conditions of treatment for skin grafts.Trial registrationClinicalTrials.gov, ID:NCT03334656. Registered on 7 November 2017.

BACKGROUND BK virus (BKV) infection after kidney transplantation leads to BKV-associated nephropathy (BKVAN) in up to 10% of recipients, and is associated with an increased risk of allograft dysfunction or loss. The objective of this study was to estimate the incidence of BKVAN and to analyze whether enhanced induction is associated with an increased risk of BKVAN, possibly justifying more intensive surveillance. MATERIAL AND METHODS This was a single-center retrospective cohort study. All patients who underwent kidney transplantation or simultaneous pancreas and kidney transplantation at the Uppsala University Hospital in Sweden between 2005 and 2014 were included, a period when BKV screening was not yet implemented. The effect of enhanced induction, defined as treatment with thymoglobulin, rituximab, and/or eculizumab, often in combination with IVIg and glycosorb, immunoadsorption and/or plasmapheresis/apheresis, was analyzed in a multivariable Cox proportional hazards model together with sex, age, cytomegalovirus mismatch (donor+/recipient-) and rejection treatment as co-predictors. Further, the effects of BKVAN on graft survival was analyzed in a univariable Cox proportional hazards model. RESULTS In total 44 of 928 (4.7%) patients developed a biopsy-verified BKVAN 4.8 (1.5-34.2) months after transplantation. Male sex was identified as a risk factor (HR 2.02, P=0.04) but not enhanced induction. Patients with BKVAN experienced a significantly higher risk of graft loss (HR 4.37, P

Background: Social support is a key dimension of personal recovery for patients with severe mental disorders. Although clinicians and health professionals should monitor the social support resources of patients in order to provide effective treatment, no specific tool or intervention exist for that purpose. Egonet is a computer-assisted intervention for health and social services that enables the mapping, assessment and fostering of patients’ social support networks. Aims: This paper describes the intervention and evaluates the appropriateness and acceptability of its implementation in a clinical setting. Method: We described the computer-assisted intervention. We used a questionnaire to assess how appropriate and acceptable clinicians found a preliminary version to be. We also collected patients’ level of satisfaction with their social support networks before and after the intervention and carried out qualitative interviews. Results: Egonet is made up of four components: (1) a computer-assisted interview for mapping social networks, (2) a remote data server, (3) a data-mining module and (4) a customisable reporting tool. Egonet was implemented for 232 patients by 91 clinicians from five services. The intervention was perceived by clinicians as appropriate and useful for clinical practice, although it was noted that considerable effort was required to obtain its benefits. Patients were slightly more satisfied with their social support after the intervention than before, and expressed the opinion that more attention should be paid to the social support network. Conclusions: EGONET is appropriate and acceptable for use in work related to the social support networks of patients with psychiatric disorders.

Purpose Providing effective treatment for immigrants is an increasing challenge for mental health services across Europe. Yet, little is known as to whether current practice is associated with different outcomes in migrant and non-migrant patients. We compared outcomes of inpatient psychiatric treatment for migrants and non-migrants in a sample from five European countries. Methods Patients with psychotic disorders, affective disorders or anxiety/somatisation disorders admitted to routine psychiatric inpatient treatment were assessed in hospitals in Belgium, Germany, Italy, Poland and the United Kingdom. Treatment outcomes were satisfaction with care during hospitalisation, length of stay, readmission to hospital (any and, specifically, involuntary re-hospitalisation), as well as untoward incidents in a 1-year follow-up period. Outcomes were compared between patients born inside (non-migrants) and outside (migrants) the country of treatment, through mixed regression models. Results Across all sites, 985 migrant patients and 6298 non-migrant patients were included. After accounting for the influence of confounding patient characteristics, migrants reported significantly lower treatment satisfaction, but there were no significant differences for length of stay and re-hospitalisations, in general and involuntary ones. Migrants had a lower rate of suicide attempts, but there was no significant difference in other types of untoward incidents in the year following the index admission. Conclusion The study suggests that migrants are less satisfied with their hospital treatment, there is no evidence that routine inpatient care as currently provided results overall in poorer objective outcomes for migrants than in non-migrant populations.

Currently, no single best primary endpoint exists for measuring the efficacy of treatments in seriously ill patients with respiratory infections, such as influenza, who require hospitalization. The Hospital Recovery Scale is an ordinal endpoint used to evaluate treatment outcomes in clinical studies of hospitalized patients infected with influenza.To determine whether Hospital Recovery Scale outcomes correspond to those for other clinical endpoints in patients hospitalized due to influenza, data from the phase 3 randomized, double-blind ZORO clinical trial (NCT01231620) were analyzed. Randomized influenza-infected patients were divided into subgroups of interest based on prespecified baseline and infection-related characteristics, as well as randomized treatment arms (intravenous zanamivir 300 mg or 600 mg, or oral oseltamivir 75 mg). Clinical endpoints relevant to this population were included to analyze differences in outcomes between the subgroups, and correspondence of these endpoints and hospital recovery endpoint was evaluated.Data from 488 patients were analyzed. There were strong correlations (ρThe Hospital Recovery Scale is applicable as a primary endpoint in trials to evaluate new therapies for severely ill patients hospitalized due to influenza, and may have utility in other severe respiratory illnesses such as COVID-19.

Background and Objectives: In recent years, the rate of caesarean section (CS) has increased constantly. Although vaginal breech delivery has a long history, breech presentation has become the third most common indication for CS. This study aims to identify factors associated with the success of external cephalic version (ECV), underline the success rate of ECV for breech presentation and highlight the high rate of vaginal delivery after successful ECV. Material and Methods: This retrospective observational study included 113 patients with singleton fetuses in breech presentation, who underwent ECV from January 2016 to March 2021 in the Clinic of Obstetrics and Gynecology, Diakonieklinikum Schwäbisch Hall, Germany. Maternal and fetal parameters and data related to procedure and delivery were collected. Possible predictors of successful ECV were evaluated. Results: The success rate of ECV was 54.9%. The overall rate of vaginal birth was 44.2%, regardless of ECV outcome. The vaginal birth rate after successful ECV was 80.6%. Overall, 79.0% of women with successful ECV delivered spontaneously without complications, 19.4% delivered through CS performed during labor by medical necessity, and 1.6% delivered through vacuum extraction. ECV was performed successfully in three of the four women with history of CS. Gravidity, parity, maternal age, gestational age, fetal weight, and amniotic fluid index (AFI) were significantly correlated with the outcome of ECV. Conclusions: ECV for breech presentation is a safe procedure with a good success rate, thus increasing the proportion of vaginal births. Maternal and fetal parameters can be used to estimate the chances of successful ECV.

Background For psychiatric service users suffering from severe mental disorders, the social support provided by personal social networks is essential for living a meaningful life within the community. However, the importance of the support received depend on the relations between the providers of social support. Yet this hasn’t been addressed in the literature so far for people with severe mental disorders. This article seeks to investigate how characteristics of service users with severe mental disorders, their social contacts, and the pattern of relationships between those contacts influence the distribution and provision of social support to people with severe mental disorders. Methods We collected personal network data relating to 380 psychiatric service users from a random sample of health care providers in Belgium. We computed various measures of the structure of those networks and of the position of support persons within those networks. We conducted a multilevel analysis of the importance of the support provided by each support persons. Results The results show that the more central a support person was in the network of a service user, the more important his or her support was considered to be by the service user. Also, the denser the network in which a support person was embedded, the less important was the support he or she offers, but only for hospitalised service users. Conclusion These finding highlight the collective dimension of social support. We discuss the implications for the organisation of mental health care.

Background: Patients with severe mental illnesses (SMI) have low levels of social integration, which could be improved if they used social services. To our knowledge, however, the extent to which they use generic social services remains unknown. Aims: We assessed the extent to which patients with SMI use generic social services and the factors that may drive that usage. Method: In 2014, we carried out a multi-setting clustered survey of patients with severe mental disorders ( n = 1,019, participation rate = 71%) and of services ( n = 517, participation rate = 53%) in 19 networks of services, covering most of Belgium. On the one hand, we asked patients, amongst other, about their health condition, their social integration in the community, and their use of social services of different types. On the other hand, we asked each service to report on its relationships with other services in the services networks. Results: On average, patients’ use of generic social services within the previous 6 months was low (6%–16%), with the exception of administrative services. There were few differences in usage according to the severity of patients’ symptoms, but some differences according to gender and age were observed. Social integration was improved when generic social services were more central in the networks. Conclusions: We suggest that generic social services should be more central in mental health services networks.

International audience; Purpose: The purpose of this study was to evaluate the safety and oncologic efficacy of percutaneous magnetic resonance imaging (MRI)-guided cryoablation of intraparenchymal renal cancer. Materials and methods: Between February 2009 and August 2019, 31 consecutives patients with 31 entirely intraparenchymal biopsy-proven renal cancers were treated with cryoablation under MRI-guidance in our institution, and were retrospectively included. There were 20 men and 11 women with a mean age of 68.5±12.5 (SD) (range: 40-91years). Patient, tumor- and procedure-related, and follow-up data were retrospectively collected and analyzed. Local recurrence free (LRFS), metastasis free (MFS), disease free (DFS), cancer specific (CSS), and overall survivals (OS) were calculated. Results: Primary and secondary technical efficacy rates were 94% and 100%, respectively. Median follow-up was 27months. Seven (7/31; 23%) minor complications were noted in 7 patients. Patients showed a significant decline of the estimated glomerular filtration rate (eGFR) between baseline and nadir (mean basal eGFR 65.9±22.4 [SD] mL/min/1.73m2vs. mean nadir eGFR 52.8±26.0 [SD] mL/min/1.73m2; P

Optimal management of patients with ulcerative colitis (UC) requires the accurate, objective assessment of disease activity.We aimed to determine how strong patient-reported outcomes, clinical scores and symptoms correlate with endoscopy and biomarkers for assessment of disease activity in patients with UC.Consecutive patients with UC followed at the McGill University IBD Center and referred for endoscopy (surveillance or flare) were included prospectively between September 2018 and August 2020. Patient-reported outcome (PRO2), partial Mayo, Simple Clinical Colitis Activity Index (SCCAI), Mayo endoscopic subscore (MES) and Baron and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores were calculated. C-reactive protein (CRP) and fecal calprotectin (FCAL) were collected.A total of 171 patients with UC [age: 49(IQR:38-61) years, female: 46.2%, 57.3% extensive disease, 42.7% on biologicals] were included prospectively. Rectal bleeding (RBS), stool frequency (SF) subscore of 0, or total PRO2 remission (RBS0 and SF ≤ 1), partial Mayo (≤ 2) and SCCAI (≤ 2.5) remission were similarly associated with mucosal healing defined by MES (0 or ≤ 1), Baron (0 or ≤ 1) or UCEIS (≤ 3) scores in ROC analysis (AUC:0.93-0.72). There was a moderate-to-strong agreement between MES Baron and UCEIS (K = 0.91-0.41). A UCEIS of ≤ 3 was identified as the best cutoff to clinical or endoscopic remission. Agreement between CRP and clinical remission or endoscopic healing (MES/Baron) was poor (K ~ 0.2), while agreement between FCAL and RBS-PRO2 or MES/Baron/UCEIS was moderate to strong (K = 0.44-0.70).Agreement between RBS, SF, PRO2, partial Mayo and SCCAI in predicting endoscopic healing was moderate to strong, while no clinically meaningful difference was found in accuracy across the scores and definitions. FCAL, but not CRP, was associated to clinical and endoscopic remission.

Although efficacy of ustekinumab (UST) has been demonstrated through randomized trials, data from real-life prospective cohorts are still limited. Our aim was to evaluate clinical efficacy, drug sustainability, dose intensification and results from therapeutic drug monitoring in UST treated patients with Crohn's disease (CD) using a prospective, nationwide, multicenter cohort.Patients from 10 Inflammatory Bowel Disease centers were enrolled between 2019 January and 2020 May. Patient demographics, disease phenotype, treatment history, clinical disease activity (Crohn's Disease Activity Index(CDAI), Harvey Bradshaw Index(HBI)), biomarkers, and serum drug levels were obtained. Evaluations were performed at week8 (post-induction), w16-20, w32-36, and w52-56 follow-up visits.A total of 142 patients were included [57.4% female; complex disease behavior (B2/B3):48%, previous anti-TNF exposition:97%]. Clinical response and remission rates after induction(w8) were 78.1% and 57.7% using CDAI, and 82.5% and 51.8% based on HBI scores. The one-year clinical remission rate was 58%/57.3%(CDAI/HBI). Composite clinical and biomarker remission (CDAI150 and C-reactive protein10 mg/L) rates were 35.4%; 33.3%; 38.6% and 36.6% at w8/w16-20/w32-36 and w52-56. Drug sustainability was 81.9%(standard deviation(SD): 3.4) at 1 year(1y). Probability of dose intensification was high and introduced early, 42.2%(SD:4.2) at ~w32 and 51.9%(SD:4.4%) at 1y.Ustekinumab showed favorable drug sustainability and clinical efficacy in a patient population with severe disease phenotype and previous anti-tumor necrosis factor (anti-TNF) failure, however frequent dose intensification was required.

Reports of acute pulmonary embolism associated with coronavirus disease 2019 (COVID-19) have emerged in the literature. For example, Chen et al (1) described 25 pulmonary CT angiographic examinations from 1008 patients with COVID-19; 10 were positive for pulmonary embolism, mostly as segmental or subsegmental acute pulmonary embolism. In addition, d-dimer levels have been reported as elevated in patients with COVID-19 (2,3), with the suggestion of an independent association between the severity of the disease and the level of d-dimer (4). The purpose of this report is to describe the rate of pulmonary embolus in patients classified as having COVID-19 infection who underwent chest CT at a tertiary referral center.

Background Nicotine dependence during adolescence increases the risk of continuing smoking into adulthood. The magnitude of nicotine dependence among adolescents in the European Union (EU) has not been established. We aimed to estimate the number of nicotine dependent 15-year-old adolescents in the EU, and identify high-risk groups. Methods The number of nicotine dependent 15-year-olds in the EU was derived combining: (i) total number of 15-year-olds in the EU (2013 Eurostat), (ii) smoking prevalence among 15-year-olds (2013/2014 HBSC survey) and (iii) proportion of nicotine dependent 15-year-olds in six EU countries (2013 SILNE survey). Logistic regression analyses identified high-risk groups in the SILNE dataset. Results We estimated 172 636 15-year-olds were moderately to highly nicotine dependent (3.2% of all 15 years old; 35.3% of daily smokers). In the total population, risk of nicotine dependence was higher in males, adolescents with poor academic achievement, and those with smoking parents or friends. Among daily smokers, only lower academic achievement and younger age of smoking onset were associated with nicotine dependence. Conclusion According to our conservative estimates, more than 172 000 15-year-old EU adolescents were nicotine dependent in 2013. Prevention of smoking initiation, especially among adolescents with poor academic performance, is necessary to prevent a similar number of adolescents getting addicted to nicotine each consecutive year.

BackgroundAlthough there is evidence for socioeconomic inequalities in health and health behaviour in adolescents, different indicators of socioeconomic status (SES) have rarely been compared within one data sample. We examined associations of five SES indicators with self-rated health (SRH) and smoking (ie, a leading cause of health inequalities) in Europe.MethodsData of adolescents aged 14–17 years old were obtained from the 2013 SILNE survey (smoking inequalities: learning from natural experiments), carried out in 50 schools in 6 European cities (N=10 900). Capturing subjective perceptions of relative SES and objective measures of education and wealth, we measured adolescents’ own SES (academic performance, pocket money), parental SES (parental educational level) and family SES (Family Affluence Scale, subjective social status (SSS)). Logistic regression models with SRH and smoking as dependent variables included all SES indicators, age and gender.ResultsCorrelations between SES indicators were weak to moderate. Low academic performance (OR=1.96, 95% CI 1.53 to 2.51) and low SSS (OR=2.75, 95% CI 2.12 to 3.55) were the strongest indicators of poor SRH after adjusting for other SES-indicators. Results for SSS were consistent across countries, while associations with academic performance varied. Low academic performance (OR=5.71, 95% CI 4.63 to 7.06) and more pocket money (OR=0.21, 95% CI 0.18 to 0.26) were most strongly associated with smoking in all countries.ConclusionsSocioeconomic inequalities in adolescent health were largest according to SES indicators more closely related to the adolescent’s education as well as the adolescent’s perception of relative family SES, rather than objective indicators of parental education and material family affluence. For future studies on adolescent health inequalities, consideration of adolescent-related SES indicators was recommended.

Background The American Board of Pediatrics requires that pediatricians be able to initiate stabilization of a newborn. After residency, 45% of general pediatricians routinely attend deliveries. However, there is no standard approach or tool to measure resident proficiency in newborn resuscitation across training programs. In a national survey, we found a large variability in faculty assessment of the amount of supervision trainees need for various resuscitation scenarios. Objective documentation of trainee performance would permit competency-based decisions on the level of supervision required and facilitate feedback on trainee performance. Methods A simplified tool was created following the Neonatal Resuscitation Program (NRP) algorithm, with emphasis on communication, leadership, knowledge of equipment, and initial stabilization. To achieve content validity, the tool was evaluated by the NRP steering committee. To assess internal structure of the tool, we filmed 10 simulated resuscitation scenarios, 9 of which contained errors. Experienced resuscitation team members used the tool to assess performance of the team leader in the videos. To evaluate the response process, the tool was used to assess experienced resuscitators in real time at academic and non-academic sites. Results The NRP steering committee approved the tool, providing evidence of content validity. Performance of the team leader in the simulated videos was assessed by 16 evaluators using the tool. There was an intraclass coefficient of 0.86, showing excellent agreement. There was no statistical difference in scores between 102 resuscitations led by experienced resuscitators at academic and nonacademic hospitals (P = .98), which demonstrates generalizability. Conclusions The tool we have developed to assess performance in initiating newborn resuscitation shows evidence of construct validity based on assessment of content and internal structure (interobserver agreement, response processes, and generalizability).

Background Patients with Crohn’s disease [CD] and ulcerative colitis [UC] are at increased risk for colorectal dysplasia [CRD] and colorectal cancer [CRC]. Adherence to CRC surveillance guidelines is reportedly low internationally. Aim To evaluate surveillance practices at the tertiary IBD Center of the McGill University Health Center [MUHC] and to determine CRD/CRC incidence. Methods A representative inflammatory bowel disease cohort with at least 8 years of disease duration [or with primary sclerosing cholangitis] who visited the MUHC between July 1 and December 31, 2016 were included. Adherence to surveillance guidelines was compared to modified 2010 British Society of Gastroenterology guidelines. Incidence rates of CRC, high-grade dysplasia [HGD], low-grade dysplasia [LGD] and colorectal adenomas [CRA] were calculated based on pathology. Results In total, 1356 CD and UC patients (disease duration: 12 [interquartile range: 6–22) and 10 [interquartile range: 5–19] years) were identified. The surveillance cohort consisted of 680 patients [296 UC and 384 CD]. Adherence to surveillance guidelines was 76/82% in UC/colonic CD. An adequate number of biopsies were taken in 54/54% of UC/colonic CD patients. The incidence of CRC/HGD in UC and CD with colonic involvement was 19.5/58.5 and 25.1/37.6 per 100,000 patient-years, respectively. The incidence of dysplasia before 8 years of disease duration was low in both UC/CD [19.5 and 12.5/100,000 patient-years] with no CRC detected. The CRA rate was 30/38% in UC/colonic CD. Conclusion High adherence to surveillance guidelines and low CRC and dysplasia, but not CRA rates were found, suggesting that adhering to updated, stratified, surveillance recommendations may result in low advanced neoplasia rates. The incidence of dysplasia before the start of surveillance was low.

Background:In Europe, at discharge from a psychiatric hospital, patients with severe mental illness may be exposed to one of two main care approaches: personal continuity, where one clinician is responsible for in- and outpatient care, and specialisation, where various clinicians are. Such exposure is decided through patient-clinician agreement or at the organisational level, depending on the country’s health system. Since personal continuity would be more suitable for patients with complex psychosocial needs, the aim of this study was to identify predictors of patients’ exposure to care approaches in different European countries.Methods:Data were collected on 7302 psychiatric hospitalised patients in 2015 in Germany, Poland, and Belgium (patient-level exposure); and in the UK and Italy (organisational-level exposure). At discharge, patients were exposed to one of the care approaches according to usual practice. Putative predictors of exposure at patients’ discharge were assessed in both groups of countries.Results:Socially disadvantaged patients were significantly more exposed to personal continuity. In all countries, the main predictor of exposure was the admission hospital, except in Germany, where having a diagnosis of psychosis and a higher education status were predictors of exposure to personal continuity. In the UK, hospitals practising personal continuity had a more socially disadvantaged patient population.Conclusion:Even in countries where exposure is decided through patient-clinician agreement, it was the admission hospital, not patient characteristics, that predicted exposure to care approaches. Nevertheless, organisational decisions in hospitals tend to expose socially disadvantaged patients to personal continuity.

BackgroundManaging older people in the emergency department remains a challenge. We aimed to identify the factors influencing the care quality of older patients in the emergency department, to fine-tune future interventions for older people, considering the naturalistic context of the ED.MethodsThis is a qualitative study of some 450 h of observations performed in three emergency departments selected for their diverse contexts. We performed seventy observations of older patient trajectories admitted to the emergency department. Themes were extracted from the material using an inductive reasoning approach, to highlight factors positively or negatively influencing management of patient’s trajectories, in particular those presenting with typically geriatric syndromes.ResultsFour themes were developed: no geriatric flow routine; risk of discontinuity of care; unmet basic needs and patient-centered care; complex older patients are unwelcome in EDs.ConclusionsThe overall process of care was based on an organ- and flow-centered paradigm, which ignored older people’s specific needs and exposed them to discontinuity of care. Their basic needs were neglected and, when their management slowed the emergency department flow, older people were perceived as unwelcome. Findings of our study can inform the development of interventions about the influence of context and organizational factors.

Background In this systematic review, our objective was to assess inflammatory bowel disease (IBD) patient preferences and perspectives relating to their disease diagnosis, treatment, knowledge needs and telemedicine. Methods This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four databases and conference proceedings were searched between January 1, 1980, and May 1, 2020. The methodological quality of the included studies was assessed using the Standards for reporting qualitative research checklist. Results Our search identified 240 citations and 52 studies met the inclusion criteria. The major expectations of the patients are symptomatic and pain control, quality of life and normal endoscopy. Patients main concerns are access to information and healthcare, and shared decision making. At the time of diagnosis, patients expressed a greater need for knowledge about their IBD, preferentially by their treating gastroenterologist. The main treatment expectations in active disease are efficacy, safety and convenience. Patients are willing to accept relatively high risks of complications from medical therapy to avoid a permanent ostomy and to achieve durable remission. Patients are more interested in disease monitoring, research and development during the time of remission. Telemedicine and self-management with supervised e-health tools are feasible and acceptable amongst patients with IBD. Conclusion This systematic review demonstrates that patients with IBD expect more information about their disease process, shared decision making and symptom control. Further research is needed to help align patient and physician expectations in order to improve the quality of care provided to patients with IBD. Supplementary Information The online version contains supplementary material available at 10.1007/s10620-021-07025-y.

Background The COVID-19 pandemic and subsequent suppression measures have had health and social implications for billions of individuals. The aim of this paper is to investigate the risk of psychological distress associated with the COVID-19 pandemic and suppression measures during the early days of the lockdown. We compared the level of psychological distress at the beginning of that period with a pre-pandemic health survey and assessed the psychological effects of exposure to the COVID-19 pandemic and changes in social activity and support. Methods An online survey was distributed to the general population in Belgium 3 days after the beginning of the lockdown. 20,792 respondents participated. The psychological distress of the population was measured using the GHQ-12 scale. Social activities and support were assessed using the Social Participation Measure, the Short Loneliness Scale, and the Oslo Social Support Scale. An index of subjective exposure to the COVID-19 pandemic was constructed, as well as a measure of change in occupational status. Measurements were compared to a representative sample of individuals extracted from the Belgian Health Interview Survey of 2018. Bootstrapping was performed and analyses were reweighted to match the Belgian population in order to control for survey selection bias. Results Half of the respondents reported psychological distress in the early days of the lockdown. A longer period of confinement was associated with higher risk of distress. Women and younger age groups were more at risk than men and older age groups, as were respondents who had been exposed to COVID-19. Changes in occupational status and a decrease in social activity and support also increased the risk of psychological distress. Comparing the results with those of the 2018 Belgian Health Interview shows that the early period of the lockdown corresponded to a 2.3-fold increase in psychological distress (95% CI: 2.16–2.45). Conclusions Psychological distress is associated with the consequences of the COVID-19 pandemic and suppression measures. The association is measurable from the very earliest days of confinement and it affected specific at-risk groups. Authorities should consider ways of limiting the effect of confinement on the mental and social health of the population and developing strategies to mitigate the adverse consequences of suppression measures.

To retrospectively report on safety, pain relief and local tumor control achieved with percutaneous ablation of sacral bone metastases.From February 2009 to June 2020, 23 consecutive patients (12 women and 11 men; mean age, 60±8 [SD] years; median, 60; range: 48-80 years) with 23 sacral metastases underwent radiofrequency (RFA) or cryo-ablation (CA), with palliative or curative intent at our institution. Patients' demographics and data pertaining to treated metastases, procedure-related variables, safety, and clinical evolution following ablation were collected and analyzed. Pain was assessed with numerical pain rating scale (NPRS).Sixteen (70%) patients were treated with palliative and 7 (30%) with curative intent. Mean tumor diameter was 38±19 (SD) mm (median, 36; range: 11-76). External radiation therapy had been performed on five metastases (5/23; 22%) prior to ablation. RFA was used in 9 (39%) metastases and CA in the remaining 14 (61%). Thermo-protective measures and adjuvant bone consolidation were used whilst treating 20 (87%) and 8 (35%) metastases, respectively. Five (22%) minor complications were recorded. At mean 31±21 (SD) (median, 32; range: 2-70) months follow-up mean NPRS was 2±2 (SD) (median, 1; range: 0-6) vs. 5±1 (median, 5; range: 4-8; P0.001) at the baseline. Three metastases out of 7 (43%) undergoing curative ablation showed local progression at mean 4±4 (SD) (median, 2; range: 1-8) months follow-up.Percutaneous ablation of sacral metastases is safe and results in significant long-lasting pain relief. Local tumor control seems sub-optimal; however, further investigations are needed to confirm these findings due to paucity of data.

Carry out a national inventory of the current situation regarding the quality management of the investigational health products circuit, to develop adapted standardised tools.A survey of 76 questions, developed by a regional working group, was conducted among clinical research pharmacists in French facilities. Tools were developed to meet the identified needs and validated by participating pharmacists, using the Delphi method. The consensus was defined by achieving a score above 80% on relevance, clarity and evaluability.Among 94 pharmacists participating in the survey, 88 were interested in standardised tools. The score for the implementation of a quality approach depended on the type of health facility (P0.0005) and increased with the number of active trials (P0.0005). All nine proposed tools were useful for over two thirds of pharmacists, but the self-assessment and audit grids have been prioritised. Indeed, only 26% of pharmacies carried out a prior risk assessment and 14% carried out internal audits. The review of both grids led to a consensus on 89% and 97% of the criteria respectively. The validated grids include 62 and 72 criteria respectively.The quality approach of the investigational health products circuit is heterogeneous in the participating centres, with a strong need for standardised tools. The two grids are relevant tools developed by and for professionals.The tools developed will enable to optimise the quality approach by identifying the non-conformities of the investigational health products circuit.

Imlifidase is a cysteine proteinase which specifically cleaves IgG, inhibiting Fc-mediated effector function within hours of administration. Imlifidase converts a positive crossmatch to a potential donor (T cell, B cell, or both), to negative, enabling transplantation to occur between previously HLA incompatible donor-recipient pairs. To date, 39 crossmatch positive patients received imlifidase prior to a kidney transplant in four single-arm, open-label, phase 2 studies. At 3 years, for patients who were AMR+ compared to AMR-, death-censored allograft survival was 93% vs 77%, patient survival was 85% vs 94%, and mean eGFR was 49 ml/min/1.73 m2 vs 61 ml/min/1.73 m2 , respectively. The incidence of AMR was 38% with most episodes occurring within the first month post-transplantation. Sub-analysis of patients deemed highly sensitized with cPRA ≥ 99.9%, and unlikely to be transplanted who received crossmatch-positive, deceased donor transplants had similar rates of patient survival, graft survival, and eGFR but a higher rate of AMR. These data demonstrate that outcomes and safety up to 3 years in recipients of imlifidase-enabled allografts is comparable to outcomes in other highly sensitized patients undergoing HLA-incompatible transplantation. Thus, imlifidase is a potent option to facilitate transplantation among patients who have a significant immunologic barrier to successful kidney transplantation. Clinical Trial: ClinicalTrials.gov (NCT02790437), EudraCT Number: 2016-002064-13.

Background The relationship between socioeconomic position (SEP) and adolescent physical activity is uncertain, as most evidence is limited to specific settings and a restricted number of SEP indicators. This study aimed to assess the magnitude of socioeconomic differences in adolescent vigorous physical activity (VPA) across various European countries using a wide range of SEP indicators, including family-based (education, family affluence, perceived social standing, parents’ employment, housing tenure) and adolescent-based (academic performance and pocket money) ones. Methods We used data from a survey among 10,510 students aged 14–17 from 50 schools in six European cities: Namur (BE), Tampere (FI), Hannover (DE), Latina (IT), Amersfoort (NL), Coimbra (PT). The questionnaire included socio-demographic characteristics and the amount of time spent in VPA. Results The mean time spent practicing VPA was 60.4 min per day, with lower values for Namur (BE) and Latina (IT), and higher values for Amersfoort (NL). In the multivariable analysis, both categories of SEP indicators (family-based and adolescent based indicators) were independently associated with VPA. For each SEP indicator, lower levels of VPA were recorded in lower socioeconomic groups. In the total sample, each additional category of low SEP was associated with a decrease in mean VPA of about 4 min per day. Conclusions This study showed that across European cities adolescent VPA is positively related to both family-based SEP and adolescents’ own SEP. When analysing socioeconomic differences in adolescent VPA, one should consider the use of multiple indicators of SEP.

The difficulty of implementing mental healthcare reforms owes much to the influence of stakeholders. So far, the endorsement of mental health policy reforms by stakeholder coalitions has received little attention. This study describes stakeholder coalitions formed around common mental health policy goals and highlights their central goals and oppositions. Data were collected on the policy priorities of 469 stakeholders (policymakers, service managers, clinicians, and user representatives) involved in the Belgian mental healthcare reform. Four coalitions of stakeholders endorsing different mental health policy goals were identified using a hierarchical cluster analysis on stakeholders’ policy priorities. A belief network analysis was performed to identify the central and peripheral policy goals within coalitions. Coalitions brought together stakeholders with similar professional functions. Disagreements were observed between service managers and policymakers around policy goals. The two coalitions composed of policymakers supported a comprehensive approach that combines the different goals and also supported the shortening of hospital stays, whereas the two coalitions composed of service managers emphasised the personal recovery of users and continuity of care. Regardless of the coalitions’ differing policy priorities, strengthening community care was a central goal while patient-centred goals were peripheral. The competing policy positions of the coalitions identified may explain the slow and inconsistent pace of the Belgian mental healthcare reform. Strengthening community care may be an essential part of reaching consensus across coalitions. Finally, special care must be taken to ensure that patient-centred policy goals, such as social integration, are not set aside in favour of other goals.

Appropriate care delivery for patients with severe mental illness (SMI) requires a high level of collaboration quality between primary, mental health, and social care services. Few studies have addressed the interpersonal and inter-organizational components of collaboration within one unique study setting and it is unclear how these components contribute to overall collaboration quality. Using a comprehensive model that includes ten key indicators of collaboration in relation to both components, we evaluated how interpersonal and inter-organizational collaboration quality were associated in 19 networks that included 994 services across Belgium. Interpersonal collaboration was significantly higher than inter-organizational collaboration. Despite the internal consistency of the model, analysis showed that respondents perceived a conflict between client-centered care and leadership in the network. Our results reveal two approaches to collaborative service networks, one relying on interpersonal interactions and driven by client needs and another based on formalization and driven by governance procedures. The results reflect a lack of strategy on the part of network leaders for supporting client-centered care and hence, the persistence of the high level of fragmentation that networks were expected to address. Policy-makers should pay more attention to network formalization and governance. mechanisms with a view to achieving effective client-centered outcomes.

Background Most research on mental illness stigma has involved people with psychosis; less information is available for people with affective and anxiety disorders. We aimed to compare experienced and anticipated discrimination among people with schizophrenia, and affective and anxiety disorders. Methods People with schizophrenia (n=773), affective (n=1010) and anxiety disorders (n=372) were recruited during psychiatric admission across 5 EU countries. The Discrimination and Stigma Scale (DISC-12) was used. Multivariate mixed effect logistic regression models with a random effect for hospital and country were performed to explore patient characteristics associated with experienced and anticipated discrimination. Results With anxiety disorders, there were more reports of experiences of discrimination in social life (35%), intimate relationships (23.5%), and physical healthcare (19%); in schizophrenia, in relations with neighbours (23.6%) and mental health staff (21.7%); and in affective disorders, in parental role (22.8%). In multivariate analyses, anxiety was associated with increased likelihood of experiencing discrimination in police interactions (OR=1.675; p=0.038) and physical healthcare (OR=1.816; p=0.003), and reduced likelihood when starting a family (OR=0.474; p=0.01) as compared with schizophrenia. Affective (OR=1.367; p=0.004) and anxiety disorders (OR=1.354; p=0.034) were associated with increased likelihood of concealing a diagnosis compared with schizophrenia. Limitations As patients with affective and anxiety disorders were recruited from hospital inpatient units, their experiences may not be representative of all people with these disorders. Conclusions In a sample of people receiving inpatient treatment, experienced and anticipated discrimination are perceived, at least in some life domains, as more of a burden for people with affective and anxiety disorders than those with schizophrenia.

Background Studies comparing adolescent e-cigarette use in different countries are scarce. We study students’ e-cigarette and conventional cigarette ever-use, their social correlates and e-liquid use in seven EU countries. Methods SILNE-R data (N=12 167, response rate 79.4%) of 14–17-year-olds from Amersfoort (NL), Coimbra (PT), Dublin (IR), Hanover (GE), Latina (IT), Namur (BE) and Tampere (FI) were used. E-cigarette and conventional cigarette ever-use, dual-use, type of e-liquid and social correlates were measured with a school survey and analyzed with cross-tabulations and multinomial logistic regression. Results About 34% had tried e-cigarettes, but the variation was large between the cities (Latina 50%; Hanover 23%). Of e-cigarette ever-users, 37% had used nicotine e-liquid, 43% exclusively non-nicotine liquid and 20% did not know the content. Nicotine e-liquid was more prevalent among monthly e-cigarette users and weekly smoking e-cigarette users. The social correlates were mainly the same for exclusive e-cigarette ever-use, exclusive conventional cigarette ever-use and dual-use. Boys had greater odds for exclusive e-cigarette and dual-use compared to girls. Of social correlates, low academic achievement and parental smoking were positively associated with all categories of use, but parental education and immigrant background were not. The strongest association was found between peer smoking (most/all best friends smoke) and dual-use (OR 34.29). Conclusions Students’ e-cigarette ever-use varies greatly between EU countries. E-cigarettes seem not to be a substitute for conventional cigarettes but more a complementary product. Tobacco control policies might also prevent e-cigarette use but specific regulations on e-cigarettes are needed to prevent nicotine addiction originating from them.