Search

Contains fulltext : 288219.pdf (Publisher’s version ) (Open Access)

Background Heterogeneity exists in reported outcomes and outcome measurement instruments [OMI] from observational studies. A core outcome set [COS] for observational and real-world evidence [RWE] in inflammatory bowel disease [IBD] will facilitate pooling large datasets. This systematic review describes and classifies clinical and patient-reported outcomes, for COS development. Methods The systematic review of MEDLINE, EMBASE, and CINAHL databases identified observational studies published between 2000 and 2021 using the population exposure outcome [PEO] framework. Studies meeting eligibility criteria were included. After titles and abstracts screening, full-text articles were extracted by two independent reviewers. Primary and secondary outcomes with corresponding OMI were extracted and categorised in accordance with OMERACT Filter 2.1 framework. The frequency of outcomes and OMIs are described. Results From 5854 studies, 315 were included: 129 [41%] Crohn’s disease [CD], 60 [19%] ulcerative colitis [UC], and 126 [40%] inflammatory bowel disease [IBD] studies with 600 552 participants. Totals of 1632 outcomes and 1929 OMI were extracted mainly from medical therapy [181; 72%], surgical [34; 11%], and endoscopic [6; 2%] studies. Clinical and medical therapy-related safety were frequent outcome domains recorded in 194 and 100 studies. Medical therapy-related adverse events [n = 74] and need for surgery [n = 71] were the commonest outcomes. The most frequently reported OMI were patient or event numbers [n = 914], Harvey-Bradshaw Index [n = 45], and Montreal classification [n = 42]. Conclusions There is substantial variability in outcomes reporting and OMI types. Categorised outcomes and OMI from this review will inform a Delphi consensus on a COS for future RWE in IBD. Data collection standardisation may enhance the quality of RWE applied to decision-making.

Objective To summarize factors that are associated with a better treatment outcome after post-operative physical therapy in patients with shoulder arthroplasty. Data sources PubMed, Cochrane, and Web of Science. Review methods Studies examining factors that are associated with a better outcome after post-operative physical therapy interventions in patients with shoulder arthroplasty were included. Two independent reviewers performed screening, extracted data, and assessed the risk of bias and level of evidence, using the Quality In Prognosis Studies tool and Evidence-Based Guideline Development checklist. PRISMA guidelines were followed. Results In total, 460 articles were found and 14 studies were included. Two of the included articles had a moderate risk of bias, 12 high. The overall number of patients in the included studies varied from 20 to 2053. Patients had either a reverse ( N = 1863), an anatomic total shoulder arthroplasty ( N = 1029) or, a hemiarthroplasty ( N = 133). Anatomic total shoulder arthroplasty patients with a neutral rotation sling position showed less night pain and greater range of motion, which was awarded moderate evidence. Other modifiable and non-modifiable factors such as telemedicine, immediate range of motion exercises, and pre-operative function were only awarded preliminary or conflicting evidence. Conclusion Mainly preliminary and conflicting evidence was found. The possible causes of the conflicting evidence were the different measurement methods, implant types, and follow-up times used. The methodological quality was low and physical therapy protocols differed greatly. More high-quality research with standardized protocols is needed to determine the association of various factors with treatment outcomes after post-operative physical therapy in patients with shoulder arthroplasty.

Retrospective interpretation of sequenced data in light of the current literature is a major concern of the field. Such reinterpretation is manual and both human resources and variable operating procedures are the main bottlenecks.Genome Alert! method automatically reports changes with potential clinical significance in variant classification between releases of the ClinVar database. Using ClinVar submissions across time, this method assigns validity category to gene-disease associations.Between July 2017 and December 2019, the retrospective analysis of ClinVar submissions revealed a monthly median of 1247 changes in variant classification with potential clinical significance and 23 new gene-disease associations. Re-examination of 4929 targeted sequencing files highlighted 45 changes in variant classification, and of these classifications, 89% were expert validated, leading to 4 additional diagnoses. Genome Alert! gene-disease association catalog provided 75 high-confidence associations not available in the OMIM morbid list; of which, 20% became available in OMIM morbid list For more than 356 negative exome sequencing data that were reannotated for variants in these 75 genes, this elective approach led to a new diagnosis.Genome Alert! (https://genomealert.univ-grenoble-alpes.fr/) enables systematic and reproducible reinterpretation of acquired sequencing data in a clinical routine with limited human resource effect.

Objectives To assess the immediate and three days postintervention effect of one dry needling session compared to one sham needling session on pain, central pain processing, muscle co-contraction and spatiotemporal parameters during gait in knee osteoarthritis patients. Methods A double-blind randomized controlled trial was conducted. Sixty-one knee osteoarthritis patients were randomly assigned to the dry needling or sham needling group. Primary outcomes were pain and central pain processing. Secondary outcomes included muscle co-contraction and spatiotemporal parameters during gait. Patients were assessed at baseline and 15 min after the intervention, and pain also three days after the intervention. Linear mixed models were used to examine between- and within-group differences. Results No significant between-group differences for pain were found, but within-group scores showed a significant decrease 15 min after sham needling and three days after dry needling. The mean conditioned pain modulation effect measured at the m. Trapezius worsened significantly 15 min after sham needling compared to after dry needling (between-group difference). However, individual conditioned pain modulation percentage scores remained stable over time. Various significant within-group differences were found 15 min after sham needling: a decrease of conditioned pain modulation measured at m. Quadriceps and m. Trapezius and stride- and step-time scores, and an increase in step length and widespread pain pressure threshold. A significant decrease in muscle co-contraction index of the m. Vastus Medialis and Semitendinosus was found as within-group difference 15 min after dry needling. Conclusions Dry needling has no larger effect on pain, central pain processing, muscle co-contraction and gait pattern 15 min and three days postintervention compared to sham needling. Mean conditioned pain modulation scores worsened after sham needling compared to after dry needling. Further research remains necessary.

Adrenal cortisol-producing tumors can express illicit membrane receptors such as luteinizing hormone (LH), glucose-dependent insulinotropic peptide (GIP) or type 4 and 7 serotonin (5-HT4/7) receptors. Abnormal expression of the LH receptor (LH-R) has been ascribed to the activation of the Wnt/β-catenin signaling pathway in adrenocortical cells. In the present study, we have investigated whether β-catenin activation may also trigger the illegitimate expression of GIP and 5-HT receptors. Three models of β-catenin activation in adrenocortical cells were used: an APC-mutated adrenocortical tumor, human-transfected adrenocortical cells and genetically modified mouse adrenal glands. The methods employed include quantitative reverse transcription PCR, immunohistochemistry and measurement of cortisol secretion by cultured tumor cells. Abnormal expression of the GIP, 5-HT7and LH receptors was observed in the APC-mutated adrenocortical tumor tissue. In addition, GIP, 5-HT and human chorionic gonadotropin stimulated cortisol production from tumor cells in primary culture. Conversely, only the LHCGR was upregulated in human and mouse adrenocortical cells harboring the activation of β-catenin. Moreover, LH-R immunoreactivity was detected in clusters of zona fasciculata cells in the β-catenin-activated mouse model. Our data indicate that activation of the β-catenin signaling pathway can promote the illicit expression of functional LH-Rs in adrenal zona fasciculata cells but does not favor the abnormal expression of GIP and 5-HT receptors.

Treatment approaches for relapsed ovarian cancer have evolved over the past decade from a calendar-based decision tree to a patient-oriented biologically driven algorithm. Nowadays, platinum-based chemotherapy should be offered to all patients with a reasonable chance of responding to this therapy. The treatment-free interval for platinum is only one of many factors affecting patients' eligibility for platinum re-treatment. Bevacizumab increases the response to chemotherapy irrespective of the cytotoxic regimen and can be valuable in patients with an urgent need for symptom relief (e.g. pleural effusion, ascites). For patients with recurrent high-grade ovarian cancer, which responds to platinum-based treatment, maintenance therapy with a poly(ADP-ribose) polymerase inhibitor can be offered, regardless of the BRCA mutation status. Here we review contemporary decision-making processes in the systemic treatment of relapsed ovarian cancer.

Recruitment rates for Crohn's disease and ulcerative colitis clinical trials continue to decrease annually. The inability to reach recruitment targets and complete trials has serious implications for stakeholders in the inflammatory bowel disease (IBD) community. Action is required to ensure patients with an unmet medical need have access to new therapies to improve the management of their IBD.Identify challenges contributing to recruitment decline in IBD clinical trials and propose potential solutions.PubMed and Google were used to identify literature, regulatory guidelines and conference proceedings related to IBD clinical trials and related concepts. Data on IBD clinical trials conducted between 1989 and 2020 were extracted from the Trialtrove database.Key aspects that may improve recruitment rates were identified. An increasingly patient-centric approach should be taken to study design including improvements to the readability of key trial documentation and inclusion of patient representatives in trial planning. Placebo is unappealing to patients; approaches including platform trials should be explored to minimise placebo exposure. Non-invasive imaging, biomarkers and novel digital endpoints should continue to be examined to reduce the burden on patients. Reducing the administrative burden associated with trials via the use of electronic signatures, for example, may benefit study sites and investigators. Changes implemented to IBD trials during the COVID-19 pandemic provided examples of how trial conduct can be rapidly and constructively adapted.To improve recruitment in Crohn's disease and ulcerative colitis trials, the IBD community should address a broad range of issues related to clinical trial conduct.

Background: The combination of infliximab and immunosuppressant therapy is a standard management strategy for patients with Crohn's disease. Concerns regarding the implications of long-term combination therapy provided the rationale for a formal clinical trial of treatment de-escalation. Our aim was to compare the relapse rate and the time spent in remission over 2 years between patients continuing combination therapy and those stopping infliximab or immunosuppressant therapy. Methods: This multicentre, open-label, randomised controlled trial was performed in 64 hospitals in seven countries in Europe and Australia. Adult patients with Crohn's disease in steroid-free clinical remission for more than 6 months, on combination therapy of infliximab and immunosuppressant therapy for at least 8 months were randomly assigned (1:1:1) to either continue combination therapy (combination group), discontinue infliximab (infliximab withdrawal group), or discontinue immunosuppressant therapy (immunosuppressant withdrawal group). Randomisation was stratified according to disease duration before start of first anti-TNF treatment (≤2 or >2 years), failure of immunosuppressant therapy before start of infliximab, and presence of ulcers at baseline endoscopy. The patient number and group of each stratum were assigned by a central online randomisation website. Treatment was optimised or resumed in case of relapse in all groups. Participants, those assessing outcomes, and those analysing the data were not masked to group assignment. The coprimary endpoints were the relapse rate (superiority analysis) and time in remission over 2 years (non-inferiority analysis, non-inferiority margin 35 days). Analyses were done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT02177071, and with EU Clinical Trials Register, EUDRACT 2014-002311-41. The trial was completed in April, 2021. Findings: Between Nov 2, 2015, and April 24, 2019, 254 patients were screened. Of these, 211 were randomised and 207 were included in the final analysis (n=67 in the combination group, n=71 in the infliximab withdrawal group, and n=69 in the immunosuppressant withdrawal group). 39 patients had a relapse (eight [12%] of 67 in the combination group, 25 [35%] of 71 in the infliximab withdrawal group, six [9%] of 69 in the immunosuppressant withdrawal group). 2-year relapse rates were 14% (95% CI 4–23) in the combination group, 36% (24–47) in the infliximab withdrawal group, and 10% (2–18) in the immunosuppressant withdrawal group (hazard ratio [HR] 3·45 [95% CI 1·56–7·69], p=0·003, for infliximab withdrawal vs combination, and 4·76 [1·92–11·11], p=0·0004, for infliximab withdrawal vs immunosuppressant withdrawal). Of 28 patients who had a relapse and were retreated or optimised according to protocol, remission was achieved in 25 patients (one of two in the combination group, 22 of 23 in the infliximab withdrawal group, and two of three in the immunosuppressant withdrawal group). The mean time spent in remission over 2 years was 698 days (95% CI 668–727) in the combination group, 684 days (651–717) in the infliximab withdrawal group, and 706 days (682–730) in the immunosuppressant withdrawal group. The difference in restricted mean survival time in remission was –14 days (95% CI –56 to 27) between the infliximab withdrawal group and the combination group and –22 days (–62 to 16) between the infliximab withdrawal group and the immunosuppressant withdrawal group. The 95% CIs contained the non-inferiority threshold (–35 days). We recorded 31 serious adverse events, in 20 patients, with no difference in frequency between groups. The most frequent serious adverse events were infections (four in the combination group, two in the infliximab withdrawal group, and one in the immunosuppressant withdrawal group) and Crohn's disease exacerbation (three in the combination group, four in the infliximab withdrawal group, and one in the immunosuppressant withdrawal group). No death nor malignancy was recorded. Interpretation: In patients with Crohn's disease in sustained steroid-free remission under combination therapy with infliximab and immunosuppressant therapy, withdrawal of infliximab should only be considered after careful assessment of risks and benefits for each patient, whereas withdrawal of immunosuppressant therapy could generally represent a preferable strategy when considering treatment de-escalation. Funding: European Union's Horizon 2020.

BACKGROUND AND AIMS: Few data are available regarding the combination of biologics or small molecules in inflammatory bowel disease (IBD) patients. We report safety and efficacy of such combinations through a retrospective multicentre series. METHODS: Combination therapy was defined as the concomitant use of two biologics or one biologic with a small molecule. Patient demographics, disease characteristics and types of combinations were recorded. Safety was evaluated according to the occurrence of serious infection, opportunistic infection, hospitalisation, life-threatening event, worsening of IBD or immune-mediated inflammatory diseases (IMID), cancer and death. Efficacy was evaluated as the physician global assessment of the combination and comparison of clinical/endoscopic scores of IBD/IMID activity prior and during combination. RESULTS: A total of 104 combinations were collected in 98 patients. Concomitant IMID were present in 41 patients. Reasons for starting combination therapy were active IBD (67%), active IMID or extra-intestinal manifestations (EIM) (22%), both (10%) and unclassified in 1. Median duration of combination was 8 months (interquartile range 5-16). During 122 patient-years of follow-up, 42 significant adverse events were observed, mostly related to uncontrolled IBD. There were 10 significant infections, 1 skin cancer and no death. IBD disease activity was clinically improved in 70% and IMID/EIM activity in 81% of the patients. Overall, combination was continued in 55% of the patients. CONCLUSIONS: Combination of biologics and small molecules in patients with IBD and IMID/EIM seems to be a promising therapeutic strategy but is also associated with a risk of opportunistic infections or infections leading to hospitalisation in 10%. ispartof: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL vol:9 issue:10 pages:1136-1147 ispartof: location:England status: published

Background and study aims: Prospective data are lacking on evolution of trough levels, effectiveness, acceptance rate and patient satisfaction after switch from the adalimumab originator to a biosimilar in patients with inflammatory bowel disease.Patients and methods: Patients in clinical remission or stable response and treated with adalimumab originator in 2 Belgian centers were offered to participate in this phase IV, prospective trial in which patients were switched to adalimumab biosimilar SB5. The primary outcome was the description of adalimumab trough levels over time. Secondary outcomes were secondary loss of response, disease activity, patient satisfaction score and drug persistence over 12 months.Results: The study included 110 patients. Mean baseline adalimumab trough level was 9.21 mu g/ml. Concentration remained within the therapeutic range over time. No changes were observed in disease activity scores nor in biochemical parameters over time. The acceptance rate of switch was 84.6%. By month 12, 74.5% was still treated with SB5. The most frequent reason for discontinuation was occurrence of adverse events. 50% of these adverse events were injection site pain. The local discomfort was only significant the first 30 minutes after injection. Satisfaction with the decision to switch to SB5 was high and remained stable over time.Conclusions: After being well informed the great majority of patients treated with the adalimumab originator is willing to switch to biosimilar SB5. In our study, there was a persistence rate of 75% over one year. The trough levels remained within the therapeutic range and no change in disease activity was seen over time. (Acta gastroenterol. belg., 2022, 85, 557-564).

Background: Cognitive–motor interference (CMI) has been well recognized in persons with multiple sclerosis (pwMS); however, there are limited data on effects of task difficulty. Objective: Examine (1) the effects of motor and cognitive tasks varying in difficulty on the magnitude of CMI and (2) the discriminative validity of CMI between pwMS and healthy controls (HC). Methods: Nine cognitive–motor dual-task (DT) conditions (combinations of three cognitive and three walking tasks) were examined. Outcome measures were DT-performance and dual-task cost (DTC) of gait parameters and correct answers. Task differences and overall group-effects were analysed by mixed model analysis, plus the Wilcoxon signed-rank tests or multivariate analysis of variances (MANOVAs), respectively. Results: Task effects were examined in 82 pwMS (Expanded Disability Status Scale (EDSS): 3.3 ± 1.0) and discriminative validity in a subsample (35 pwMS and 33 HC). Motor-DTC and DT-performance were affected by difficulty of both the cognitive task ( p Conclusion: CMI, and especially motor performance, is affected by difficulty of the DT. Although pwMS performed worse on the tasks than HC, none of the DT-conditions showed a discriminative DTC.

A comprehensive two-dimensional liquid chromatography-based biomimetic platform (LCxLC) has been developed and validated for drug diffusion studies. Human serum albumin (HSA) and immobilized artificial membrane (IAM) were thereby used in the first (1D) and second (2D) separation dimension, respectively. While the former was meant to emulate the blood, the latter was instead intended to mimic the intestinal mucosa epithelium. Therefore, the experimental conditions, i.e. pH, temperature and buffer composition, were modulated to reflect faithfully in vivo conditions. 30 compounds, whose effective intestinal permeability (Peff) assayed in situ on humans by a validated technique was known from the literature, were used as model drugs. A good and orthogonal separation was achieved for the whole dataset, although for a better distribution of the most polar compounds in the elution window a segmented gradient elution program had to be employed. Interestingly, the passively uptaken compounds having the most favourable Peff populated a specific area of the 2D plots, implying that the affinity for HSA and IAM has to lie in specific ranges in order for a compound to be satisfactorily absorbed from the intestinal lumen. Although these results should be regarded as preliminary, this work paves an entirely new and unprecedented way to profile pharmaceutically relevant compounds for their in vivo absorption and distribution potential.

Hereditary factor (F) XIII-deficiency is a known risk factor for postoperative complications, but data of acquired FXIII-deficiency in malignancies are limited. Therefore, we evaluated the role of acquired FXIII-deficiency in surgery for advanced epithelial ovarian cancer (EOC).We performed a retrospective analysis of patients with known serum FXIII status and treatment between 2011 and 2018 at our center. We defined cohorts according to FXIII with values 75% as normal (group A), 55-75% as reduced (group B) and 55% as low (group C). Complications were classified according to the Clavien-Dindo Classification, class III-V complications were defined as severe.347 patients with EOC were identified. 180 patients (51.2%) were in group A, 82 patients (23.6%) in group B, and 85 patients (24.4%) in group C. Lower levels of FXIII were associated with higher amount of ascites, FIGO IV, high grade serous histology, low albumin, and higher CA-125 levels. Regarding intraoperative variables, low FXIII was associated with longer duration of surgery, higher blood loss, higher surgical complexity score/number of bowel anastomosis and a higher probability for macroscopic residual disease. The risk of severe complications in group A was 12.2%, 24.4% in group B, and 31.8% in group C. In a multivariate model, low FXIII (OR 2.8), 1 bowel anastomosis (OR 2.7), age-adjusted Charlson comorbidity index ≥ 4 (OR 3.6) and a longer duration of surgery ( 285 min.) were significant predictive factors for severe complications.FXIII is associated with tumor and treatment burden. A low level of FXIII is associated with postoperative complications. The knowledge about the presurgical serum FXIII-level might be helpful to plan the treatment strategy.

Out-of-hospital cardiac arrest (OHCA) in children is associated with a low survival rate. Conclusions in the literature are conflicting regarding the best way to handle ventilation. The purpose of this study was to assess the impact of two airway management strategies, endotracheal intubation (ETI) vs. supraglottic procedure, during cardiopulmonary resuscitation (CPR) on 30-day survival in paediatric OHCA.This was a retrospective, observational, multicentre, registry-based study conducted from July 2011 to March 2018. All paediatric OHCA patients under 18 years of age and managed by a mobile intensive care unit were included. The primary endpoint was 30-day survival in a weighted population (based on propensity scores).Of 1579 children, 1355 (85.8%) received ETI and 224 (14.2%) received supraglottic ventilation during CPR. We observe a lower 30-day survival in the ETI group compared to the supraglottic group (7.7% vs. 14.3%, absolute difference, 6.6 percentage points; 95% confidence interval [CI], 2.3-12.0; propensity-adjusted odds ratio [paOR], 0.39; 95% CI, 0.25-0.62; p 0.001), and also a poorer neurological outcome (paOR, 0.32; 95% CI, 0.19-0.54; p 0.001). However, we did not identify any significant association between airway management strategy and return of spontaneous circulation (paOR, 1.15; 95% CI, 0.80-1.65; p = 0.46).The findings of this large cohort study suggest that ETI in paediatric OHCA, although performed by trained physicians, is associated with a worse outcome, regardless of traumatic or non-traumatic aetiology.

OBJECTIVES To describe and compare survival among patients with out-of-hospital cardiac arrest as a function of their status for coronavirus disease 2019. DESIGN We performed an observational study of out-of-hospital cardiac arrest patients between March 2020 and December 2020. Coronavirus disease 2019 status (confirmed, suspected, or negative) was defined according to the World Health Organization's criteria. SETTING Information on the patients and their care was extracted from the French national out-of-hospital cardiac arrest registry. The French prehospital emergency medical system has two tiers: the fire department intervenes rapidly to provide basic life support, and mobile ICUs provide advanced life support. The study data (including each patient's coronavirus disease 2019 status) were collected by 95 mobile ICUs throughout France. PATIENTS We included 6,624 out-of-hospital cardiac arrest patients: 127 cases with confirmed coronavirus disease 2019, 473 with suspected coronavirus disease 2019, and 6,024 negative for coronavirus disease 2019. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The "confirmed" and "suspected" groups of coronavirus disease 2019 patients had similar characteristics and were more likely to have suffered an out-of-hospital cardiac arrest with a respiratory cause (confirmed: 53.7%, suspected coronavirus disease 2019: 56.5%; p = 0.472) than noncoronavirus disease 2019 patients (14.0%; p < 0.001 vs confirmed coronavirus disease 2019 patients). Advanced life support was initiated for 57.5% of the confirmed coronavirus disease 2019 patients, compared with 64.5% of the suspected coronavirus disease 2019 patients (p = 0.149) and 70.6% of the noncoronavirus disease 2019 ones (p = 0.002). The survival rate at 30-day postout-of-hospital cardiac arrest was 0% in the confirmed coronavirus disease 2019 group, 0.9% in the suspected coronavirus disease 2019 group (p = 0.583 vs confirmed), and 3.5% (p = 0.023) in the noncoronavirus disease 2019 group. CONCLUSIONS Our results highlighted a zero survival rate in out-of-hospital cardiac arrest patients with confirmed coronavirus disease 2019. This finding raises important questions with regard to the futility of resuscitation for coronavirus disease 2019 patients and the management of the associated risks.

Ethnic discrimination on the housing market has been subject of research for years. While a field experimental approach is widespread, alternative attempts to objectively measure mechanisms of discrimination on the housing market are scarce. In line with labor market research, we stress that to reduce rental discrimination against ethnic minorities, we need understanding its underlying mechanisms. This is the first paper that introduces a vignette experiment to do so. We distinguish between four mechanisms put forward in the literature but hardly ever empirically tested: agent taste-based discrimination, owner taste-based discrimination, neighborhood taste-based discrimination and statistical discrimination, in a multifactorial vignette experiment among 576 pre graduate real estate student. In addition, our experimental design allows us to examine whether unequal treatment is heterogeneous by property owner and neighborhood characteristics.

Background & Aims: Crohn's disease (CD) patients included in the Tailored Treatment With Infliximab for Active Crohn's Disease (TAILORIX) trial started infliximab in combination with an immunosuppressant for 1 year. The aim of the present study was to determine the long-term disease course beyond the study period. Methods: We compared the outcomes of patients who did or did not reach the primary end point of the TAILORIX trial, defined as sustained corticosteroid-free clinical remission from weeks 22 through 54, with no ulcers on ileocolonoscopy at week 54. The primary outcome of this follow-up study was the progression-free survival of CD defined by anal or major abdominal surgery, CD-related hospitalization, or the need for a new systemic CD treatment. Results: The 95 patients (median disease duration, 4.5 mo; interquartile range, 1.0–56.6 mo) analyzed, including 45 (47%) who achieved the primary end point, were followed up for a median duration of 64.2 months (interquartile range, 57.6–69.9 mo) after the end of the study period. There was no significant difference in CD progression-free survival at 1, 3, and 5 years between patients who achieved the TAILORIX primary end point and patients who did not (P =.64). No difference was observed between both groups for each component of CD progression: anal surgery, major abdominal surgery, CD-related hospitalization, or the need for a new systemic CD treatment. Conclusions: Achieving a sustained clinical remission off steroids with complete endoscopic remission in this cohort of 95 patients with early CD was not associated with less disease progression. Prospective trials to define the therapeutic goals that change the natural history of CD and prevent complications are needed.

BackgroundSince 2005, the international guidelines for out-of-hospital cardiac arrest (OHCA) use puberty to differentiate paediatric and adult care. This threshold is mainly relied on the more frequent respiratory aetiologies in children. Hitherto, to the best of our knowledge, no study has compared the characteristics and outcomes of non-pubescent children, adolescents and adult patients with OHCA. In this study, we intended to describe the characteristics, outcome and factors associated with survival of patients who experienced OHCA in the three groups: children, adolescents (pubescentMethodsData from the French national cardiac arrest registry (2012–2017) were used in this nationwide observational study. Victims of OHCA who were ResultsWe included 934 children, 433 adolescents and 26 952 adults. Respiratory aetiology was more frequent and shockable rhythm less frequent in children compared with adolescents (25.5% vs 17.2%, p=0.025 and 2.4% vs 6.8%, pConclusionFrequency of respiratory aetiologies and shockable rhythm were common in adolescents and adults and different between children and adolescents. These results indicate that puberty as a threshold in international guidelines seems to be relevant.

Background and Aims Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn’s disease. This open-label extension investigated the long-term safety, pharmacokinetics, immunogenicity and efficacy of risankizumab in responders to risankizumab in the parent phase 2 study. Methods Enrolled patients had achieved clinical response [decrease in Crohn’s Disease Activity Index from baseline ≥100] without clinical remission [Crohn’s Disease Activity Index Results Sixty-five patients were enrolled, including four who had lost response in the parent study and were first reinduced with risankizumab 600 mg every 4 weeks [three infusions]. Patients received risankizumab for a median of 33 months [total: 167.0 patient-years]. The rate of serious adverse events was 24.6 events/100 patient-years; the majority were gastrointestinal in nature. Rates of serious infections, opportunistic infections and fungal infections were 4.2, 1.8, and 6.6 events/100 patient-years, respectively. No deaths, malignancies, adjudicated major adverse cardiovascular events, latent/active tuberculosis or herpes zoster were reported. Treatment-emergent anti-drug antibodies developed in eight patients [12.3%]; none were neutralizing. Efficacy outcomes were maintained during the study, including the proportions of patients [observed analysis] with clinical remission [>71%] and endoscopic remission [>42%]. Conclusions Long-term maintenance treatment with subcutaneous risankizumab 180 mg every 8 weeks was well tolerated by patients with Crohn’s disease, with no new safety signals. Clinical trial registration number: NCT02513459

To compare walking access times to automated external defibrillators (AEDs) between area-level quintiles of socioeconomic status (SES) in out-of-hospital cardiac arrest (OHCA) cases occurring in 2 major urban regions of Canada and France.This was an international, multicenter, retrospective cohort study of adult, non-traumatic OHCA cases in the metropolitan Vancouver (Canada) and Rhône County (France) regions that occurred between 2014 and 2018. We calculated area-level SES for each case, using quintiles of country-specific scores (Q5 = most deprived). We identified AED locations from local registries. The primary outcome was the simulated walking time from the OHCA location to the closest AED (continuous and dichotomized by a 3-minute 1-way threshold). We fit multivariate models to analyze the association between OHCA-to-AED walking time and outcomes (Q5 vs others).A total of 6,187 and 3,239 cases were included from the Metro Vancouver and Rhône County areas, respectively. In Metro Vancouver Q5 areas (vs Q1-Q4), areas, AEDs were farther from (79 % over 400 m from case vs 67 %, p 0.001) and required longer walking times to (97 % above 3 min vs 91 %, p 0.001) cases. In Rhône Q5 areas, AEDs were closer than in other areas (43 % over 400 m from case vs 50 %, p = 0.01), yet similarly poorly accessible (85 % above 3 min vs 86 %, p = 0.79). In multivariate models, AED access time ≥ 3 min was associated with decreased odds of survival at hospital discharge in Metro Vancouver (odds ratio 0.41, 95 % CI [0.23-0.74], p = 0.003).Accessibility of public AEDs was globally poor in Metro Vancouver and Rhône, and even poorer in Metro Vancouver's socioeconomically deprived areas.

BACKGROUND & AIMS: Dose-optimization strategies for biologic therapies in Crohn's disease (CD) are not well established. The SERENE CD (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Crohn's Disease) trial evaluated higher vs standard adalimumab induction dosing and clinically adjusted (CA) vs therapeutic drug monitoring (TDM) maintenance strategies in patients with moderately to severely active CD. METHODS: In this phase 3, randomized, double-blind, multicenter trial, eligible adults (Crohn's Disease Activity Index score of 220-450, endoscopic evidence of mucosal inflammation, and previous failure of standard therapies) were randomized to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3; n = 308) or standard induction regimen (adalimumab 160 mg at week 0 and 80 mg at week 2; n = 206) followed by 40 mg every other week from week 4 onward. Co-primary end points included clinical remission at week 4 and endoscopic response at week 12. At week 12, patients were re-randomized to maintenance therapy optimized by Crohn's Disease Activity Index and C-reactive protein (CA; n = 92) or serum adalimumab concentrations and/or clinical criteria (TDM; n = 92); exploratory end points were evaluated at week 56. RESULTS: Similar proportions of patients receiving higher induction regimen and standard induction regimen achieved clinical remission at week 4 (44% in both; P = .939) and endoscopic response at week 12 (43% vs 39%, respectively, P = .462). Week 56 efficacy was similar between CA and TDM. Safety profiles were comparable between dosing regimens. CONCLUSIONS: Higher induction regimen was not superior to standard induction regimen, and CA and TDM maintenance strategies were similarly efficacious. Adalimumab therapy was well tolerated, and no new safety concerns were identified. (ClinicalTrials.gov, Number: NCT02065570). ispartof: GASTROENTEROLOGY vol:162 issue:7 pages:1876-1890 ispartof: location:United States status: published

Objective To compare the outcomes of different treatments for spontaneous intra-abdominal abscesses (IAA) in active Crohn's disease (CD). Methods A retrospective analysis of patients with CD between January 2007 and December 2018 was performed in two Belgian inflammatory bowel disease centers. Successful conservative management was defined as complete resolution of abscesses without the need for bowel resection. The primary outcome was suboptimal evolution, defined as a composite outcome of recurrence of abscess, postoperative complications or the need for a non-elective resection. Results Forty CD patients presenting with 43 independent episodes of spontaneous IAA development were included. One underwent immediate bowel resection. In all other 42 cases a conservative approach was taken, which led to a complete abscess resolution rate of 28.6% (12/42). The remaining abscesses required bowel resection. Anti-tumor necrosis factor (TNF) agent use was associated with successful conservative management (odds ratio [OR] 13.36, 95% confidence interval [CI] 11.19-15.52, P = 0.006), while the opposite trend was found for corticosteroids (OR 0.14, 95% CI 0.02-1.26, P = 0.055). There was a trend towards suboptimal evolution in case of previous bowel resection (OR 4.77, 95% CI 0.77-29.66, P = 0.094) or in patients aged above 50 years (OR 5.17, 95% CI 0.86-30.91, P = 0.072). Conclusions Bowel resection appears to be inevitable in most CD patients presenting with IAA. An attempt at conservative treatment may be particularly successful with anti-TNF agents in younger patients who have not undergone previous bowel resection. Large-scale prospective studies are needed to confirm these findings.

The chemotherapy response score (CRS) is a histopathological tool to evaluate response to neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (OC). We critically evaluated the clinical value of CRS and compared its predictive power to standard serological (CA125) and radiological response. A retrospective analysis of 277 OC patients, who received primary chemotherapy, was performed. CRS, serological, and radiological findings were correlated with progression-free (PFS) and overall survival (OS). CRS could be determined in 172 of 277 patients (62.1%). In patients with CRS3, a longer median PFS and OS was observed compared with CRS1/2 patients (31.2 vs. 18.9, P

Dysphagia is a frequent symptom in Parkinson's disease (PD). Thickening liquids facilitates safe swallowing, however, low treatment compliance is a major issue, due to patients' dislike of thickened liquids. Some studies suggest a negative impact of gum-based thickeners, currently most used in clinical practice, on sensory properties compared to starch-based thickeners. This has not yet been investigated in PD. This study's aim was to compare taste, texture, and aroma of gum-based and starch-based thickened soups in participants with PD. Gum-based resource thicken up clear (RTUC) and starch-based kitchen products potato starch (PS) and quinoa flour (QF) were evaluated in broccoli soup. Texture, aroma, and taste were characterized by rheology, volatile, and sensory profiling. Thickened soups were evaluated in participants with PD and controls through a paired comparison test. Reduced release of 61.4%, 46.2%, and 38.5% of volatiles was observed after thickening with RTUC, PS, and QF, respectively. Overall taste intensity was reduced in RTUC- and PS-thickened soup, respectively. Taste and aroma of PS-thickened soup were considered more intense by 70.3% and 63.8% of all participants, respectively (n = 36 PD, n = 41 controls), 56.3% preferred the PS-thickened soup's texture . Taste and aroma of QF-thickened soup were considered more intense by 68.1% and 65.6% of all participants, respectively (n = 47 PD, n = 31 controls), 58.0% preferred the QF-thickened soup's texture. Starch-based thickeners demonstrated higher taste and aroma intensity. However, volatile and sensory profiling demonstrated reduced taste and aroma in all thickeners. Combining kitchen products with flavor enhancers may increase palatability of thickened beverages.

Granulovacuolar degeneration (GVD) is a common feature in Alzheimer’s disease (AD). The occurrence of GVD is closely associated with that of neurofibrillary tangles (NFTs) and GVD is even considered to be a pre-NFT stage in the disease process of AD. Currently, the composition of GVD bodies, the mechanisms associated with GVD and how GVD exactly relates to NFTs is not well understood. By combining immunohistochemistry (IHC) and laser microdissection (LMD) we isolated neurons with GVD and those bearing tangles separately from human post-mortem AD hippocampus (n = 12) using their typical markers casein kinase (CK)1δ and phosphorylated tau (AT8). Control neurons were isolated from cognitively healthy cases (n = 12). 3000 neurons per sample were used for proteome analysis by label free LC–MS/MS. In total 2596 proteins were quantified across samples and a significant change in abundance of 115 proteins in GVD and 197 in tangle bearing neurons was observed compared to control neurons. With IHC the presence of PPIA, TOMM34, HSP70, CHMP1A, TPPP and VXN was confirmed in GVD containing neurons. We found multiple proteins localizing specifically to the GVD bodies, with VXN and TOMM34 being the most prominent new protein markers for GVD bodies. In general, protein groups related to protein folding, proteasomal function, the endolysosomal pathway, microtubule and cytoskeletal related function, RNA processing and glycolysis were found to be changed in GVD neurons. In addition to these protein groups, tangle bearing neurons show a decrease in ribosomal proteins, as well as in various proteins related to protein folding. This study, for the first time, provides a comprehensive human based quantitative assessment of protein abundances in GVD and tangle bearing neurons. In line with previous functional data showing that tau pathology induces GVD, our data support the model that GVD is part of a pre-NFT stage representing a phase in which proteostasis and cellular homeostasis is disrupted. Elucidating the molecular mechanisms and cellular processes affected in GVD and its relation to the presence of tau pathology is highly relevant for the identification of new drug targets for therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s00401-020-02261-4.

Background: According to guidelines and bystander skill, two different methods of cardiopulmonary resuscitation (CPR) are feasible: standard CPR (S-CPR) with mouth-to-mouth ventilations and chest compression-only CPR (CO-CPR) without rescue breathing. CO-CPR appears to be most effective for cardiac causes, but there is a lack of evidence for asphyxial causes of out-of-hospital cardiac arrest (OHCA). Thus, the aim of our study was to compare CO-CPR versus S-CPR in adult OHCA from medical etiologies and assess neurologic outcome in asphyxial and non-asphyxial causes.Methods: Using the French National OHCA Registry (RéAC), we performed a multicenter retrospective study over a five-year period (2013 to 2017). All adult-witnessed OHCA who had benefited from either S-CPR or CO-CPR by bystanders were included. Non-medical causes as well as professional rescuers as witnesses were excluded. The primary end point was 30-day neurological outcome in a weighted population for all medical causes, and then for asphyxial, non-asphyxial and cardiac causes. Results: Of the 8 619 subjects included for all medical causes, 6 742 had a non-asphyxial etiology, including 5 904 of cardiac causes, and 1 710 had an asphyxial OHCA. 8.6%; 95% CI [8.1-9.3] of subjects had a good neurological outcome (i.e. cerebral performance category of 1 or 2). Bystanders who performed S-CPR began more often immediately (89.0%; 95% CI [87.3-90.5] versus 78.2%; 95% CI [77.2-79.2]) and in younger subjects (64.1 years versus 65.7; p < 0.001). In the weighted population, subjects receiving bystander-initiated CO-CPR had an adjusted relative risk (aRR) of 1.04; 95% CI [0.79-1.38] of having a good neurological outcome at 30 days for all medical causes, 1.28; 95% CI [0.92-1.77] for asphyxial etiologies, 1.08; 95% CI [0.80-1.46] for non-asphyxial etiologies and 1.09; 95% CI [0.93-1.28] for cardiac-related OHCA.Conclusions: We observed no significant difference in neurological outcome when lay bystanders of OHCA initiated CO-CPR or S-CPR, whether the cause was asphyxial or not. CO-CPR should probably be promoted in adults because it has many advantages (easier to learn and lower infection risk).

Background: Research among adult and paediatric samples suggests that pain-related injustice appraisals contribute to adverse pain-related functioning. However, a singular focus on pain-related injustice appraisals carries the risk of underestimating the role of broader concepts of justice. This study examined the unique roles of child pain-related injustice appraisals and just-world beliefs in understanding disability and physical, emotional, social and academic functioning, as well as the mediating role of injustice appraisals in the relationship between just-world beliefs and functioning. Methods: Participants comprised a school sample of 2,174 children (Study 1) and a clinical sample of 146 paediatric chronic pain patients (Study 2) who completed the Injustice Experience Questionnaire (IEQ), Personal and General Belief in a Just World scales (JWB-P/G), Functional Disability Inventory (FDI), Pain Catastrophizing Scale for Children (PCS-C) and Pediatric Quality of Life Inventory (PEDSQL). Results: For both samples, child pain-related injustice appraisals were associated with poorer functioning, after controlling for just-world beliefs, catastrophizing, pain intensity, age and sex. In the school sample, injustice appraisals mediated the associations of both personal and general just-world beliefs with functioning. In the clinical sample, injustice appraisals mediated the association of personal, but not general, just-world beliefs with all functioning scales. Conclusions: The current findings attest to the unique role of pain-related injustice appraisals in understanding child pain-related functioning and their explanatory value in understanding the relationship between fundamental just-world beliefs and child pain-related functioning. Significance: The present study adds to emerging literature on the adverse effects of child pain-related injustice appraisals in the context of pain, through showing that pain-related injustice appraisals are uniquely associated with pain-related functioning and mediate the relationship between just-world beliefs and pain-related functioning. These findings suggest that interventions may target pain-related injustice appraisals as a mechanism for change in children.

Objective To estimate the diagnostic value of tumor and immune related proteins in the discrimination between benign and malignant adnexal masses, and between different subgroups of tumors. Methods In this exploratory diagnostic study, 254 patients with an adnexal mass scheduled for surgery were consecutively enrolled at the University Hospitals Leuven (128 benign, 42 borderline, 22 stage I, 55 stage II-IV, and 7 secondary metastatic tumors). The quantification of 33 serum proteins was done preoperatively, using multiplex high throughput immunoassays (Luminex) and electrochemiluminescence immuno-assay (ECLIA). We calculated univariable areas under the Receiver Operating Characteristic Curves (AUCs). To discriminate malignant from benign tumors, multivariable ridge logistic regression with backward elimination was performed, using bootstrapping to validate the resulting AUCs. Results CA125 had the highest univariable AUC to discriminate malignant from benign tumors (0.85, 95% confidence interval 0.79-0.89). Combining CA125 with CA72.4 and HE4 increased the AUC to 0.87. For benign vs borderline tumors, CA125 had the highest univariable AUC (0.74). For borderline vs stage I malignancy, no proteins were promising. For stage I vs II-IV malignancy, CA125, HE4, CA72.4, CA15.3 and LAP had univariable AUCs ≥0.80. Conclusions The results confirm the dominant role of CA125 for identifying malignancy, and suggest that other markers (HE4, CA72.4, CA15.3 and LAP) may help to distinguish between stage I and stage II-IV malignancies. However, further research is needed, also to investigate the added value over clinical and ultrasound predictors of malignancy, focusing on the differentiation between subtypes of malignancy.

Background: There is a great unmet need for new therapeutics with novel mechanisms of action for patients with Crohn's disease. The ADVANCE and MOTIVATE studies showed that intravenous risankizumab, a selective p19 anti-interleukin (IL)-23 antibody, was efficacious and well tolerated as induction therapy. Here, we report the efficacy and safety of subcutaneous risankizumab as maintenance therapy. Methods: FORTIFY is a phase 3, multicentre, randomised, double-blind, placebo-controlled, maintenance withdrawal study across 273 clinical centres in 44 countries across North and South America, Europe, Oceania, Africa, and the Asia-Pacific region that enrolled participants with clinical response to risankizumab in the ADVANCE or MOTIVATE induction studies. Patients in ADVANCE or MOTIVATE were aged 16–80 years with moderately to severely active Crohn's disease. Patients in the FORTIFY substudy 1 were randomly assigned again (1:1:1) to receive either subcutaneous risankizumab 180 mg, subcutaneous risankizumab 360 mg, or withdrawal from risankizumab to receive subcutaneous placebo (herein referred to as withdrawal [subcutaneous placebo]). Treatment was given every 8 weeks. Patients were stratified by induction dose, post-induction endoscopic response, and clinical remission status. Patients, investigators, and study personnel were masked to treatment assignments. Week 52 co-primary endpoints were clinical remission (Crohn's disease activity index [CDAI] in the US protocol, or stool frequency and abdominal pain score in the non-US protocol) and endoscopic response in patients who received at least one dose of study drug during the 52-week maintenance period. Safety was assessed in patients receiving at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03105102. Findings: 712 patients were initially assessed and, between April 9, 2018, and April 24, 2020, 542 patients were randomly assigned to either the risankizumab 180 mg group (n=179), the risankizumab 360 mg group (n=179), or the placebo group (n=184). Greater clinical remission and endoscopic response rates were reached with 360 mg risankizumab versus placebo (CDAI clinical remission was reached in 74 (52%) of 141 patients vs 67 (41%) of 164 patients, adjusted difference 15% [95% CI 5–24]; stool frequency and abdominal pain score clinical remission was reached in 73 (52%) of 141 vs 65 (40%) of 164, adjusted difference 15% [5–25]; endoscopic response 66 (47%) of 141 patients vs 36 (22%) of 164 patients, adjusted difference 28% [19–37]). Higher rates of CDAI clinical remission and endoscopic response (but not stool frequency and abdominal pain score clinical remission [p=0·124]) were also reached with risankizumab 180 mg versus withdrawal (subcutaneous placebo; CDAI clinical remission reached in 87 [55%] of 157 patients, adjusted difference 15% [95% CI 5–24]; endoscopic response 74 [47%] of 157, adjusted difference 26% [17–35]). Results for more stringent endoscopic and composite endpoints and inflammatory biomarkers were consistent with a dose–response relationship. Maintenance treatment was well tolerated. Adverse event rates were similar among groups, and the most frequently reported adverse events in all treatment groups were worsening Crohn's disease, arthralgia, and headache. Interpretation: Subcutaneous risankizumab is a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active Crohn's disease and offers a new therapeutic option for a broad range of patients by meeting endpoints that might change the future course of disease. Funding: AbbVie.

In 2018, Trèbes, 6,000 inhabitants with nine general practitioners (GPs) in southern France, experienced two tragedies; a terrorist attack in March, in which four people were killed, and a catastrophic flood in October, in which six people died and thousands more were affected.We aimed to obtain a substantive theory for improving crisis management by understanding the personal and professional effects of the two successive disasters on GPs in the same village.This qualitative study conducted complete interviews with eight GPs individually, with subsequent analyses involving the conceptualisation of categories based on grounded theory.The analysis revealed that GPs underwent a double status transition. First, doctors who experienced the same emotional shock as the population became victims; their usual professional relationship changed from empathy to sympathy. The helplessness they felt was amplified by the lack of demand from the state to participate in the first emergency measures; consequently, they lost their professional status. In a second phase, GPs regained their values and skills and acquired new ones, thus regaining their status as competent professionals. In this context, the participants proposed integrating a coordinated crisis management system and the systematic development of peer support.We obtained valuable information on the stages of trauma experienced by GPs, allowing a better understanding of the effects on personal/professional status. Thus, the inclusion of GPs in adaptive crisis management plans would limit the effects of traumatic dissociation while increasing their professional effectiveness.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is mainly transmitted via droplets and aerosols. To evaluate the role of transmission by fomites, SARS-CoV-2-specific data on transfer rates from surfaces to hands and from hands to face are lacking. Here, we generated quantitatively controlled transfer rates for SARS-CoV-2 from food items (lettuce, ham, and vegetarian meat alternative [VMA]) and packaging materials (cardboard and plastic) to gloves using a wet, dry, and frozen viral inoculum and from glove to glove using a wet viral inoculum. For biosafety reasons, the transfer from surfaces to hands and hands to face was simulated by using gloves. The cumulative transfer rate was calculated by using the data from the first transfer experiment, food or packaging material to glove, and combined with the transfer rate obtained from the second transfer experiment from glove to glove. The cumulative transfer rates from lettuce (4.7%) and ham (3.4%) were not significantly different (

All studies that investigated personal factors influencing pressure pain threshold (PPT) in healthy people were synthesized. Data was summarized, and risk of bias (RoB) and level of evidence were determined. Results were pooled per influencing factor, grouped by body region and included in meta-analyses. Fifty-four studies were eligible. Five had low, nine moderate, and 40 high RoB. Following meta-analyses, a strong conclusion was found for the influence of scapular position, a moderate for the influence of gender, and a weak for the influence of age (shoulder/arm region) and blood pressure on PPT. In addition, body mass index, gender (leg region), alcohol consumption and pain vigilance may not influence PPT. Based on qualitative summary, depression and menopause may not influence PPT. For other variables there was only preliminary or conflicting evidence. However, caution is advised, since the majority of included studies showed a high RoB and several were not eligible to include in meta-analyses. Heterogeneity was high in the performed meta-analyses, and most conclusions were weak. More standardized research is necessary. ispartof: NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS vol:139 ispartof: location:United States status: published

No large randomised controlled trial has assessed the potential benefits on neurologic outcomes of prehospital sodium bicarbonate administration in patients with nontraumatic out-of-hospital cardiac arrest (OHCA).To obtain information of assistance in designing a randomised controlled trial of bicarbonate therapy after OHCA in specific patient subgroups.We conducted two, separate, simultaneous, retrospective studies of two distinct, unlinked datasets.One dataset was a French nationwide population-based registry (RéAC Registry, French dataset) and the other was a randomised controlled trial comparing continuous to interrupted chest compressions in North America (ROC-CCC trial, North-American dataset).We investigated whether prehospital bicarbonate administration was associated with better neurologic outcomes.The main outcome measure was the functional outcome at hospital discharge. To adjust for potential confounders, we conducted a nested propensity-score-matched analysis with inverse probability-of-treatment weighting.In the French dataset, of the 54 807 patients, 1234 (2.2%) received sodium bicarbonate and 450 were matched. After propensity-score matching, sodium bicarbonate was not associated with a higher likelihood of favourable functional outcomes on day 30 [adjusted odds ratio (aOR), 0.912; 95% confidence interval (95%CI), 0.501-1.655]. In the North-American dataset, of the 23 711 included patients, 4902 (20.6%) received sodium bicarbonate and 1238 were matched. After propensity-score matching, sodium bicarbonate was associated with a lower likelihood of favourable functional outcomes at hospital discharge (aOR, 0.45; 95% CI, 0.34-0.58).In patients with OHCA, prehospital sodium bicarbonate administration was not associated with neurologic outcomes in a French dataset and was associated with worse neurologic outcomes in a North-American dataset. Given the considerable variability in sodium bicarbonate use by different prehospital care systems and the potential resuscitation-time bias in the present study, a large randomised clinical trial targeting specific patient subgroups may be needed to determine whether sodium bicarbonate has a role in the prehospital management of prolonged OHCA.

Background. Simultaneous execution of motor and cognitive tasks can result in worsened performance on one or both tasks, indicating cognitive-motor interference (CMI). A growing amount of research on CMI in persons with multiple sclerosis (pwMS) is observed. However, psychometric properties of dual-task outcomes have been scarcely reported. Objective. To investigate the between-day test-retest reliability of the motor and cognitive dual-task costs (DTCs) during multiple CMI test conditions with various task complexities in pwMS and matched healthy controls (HCs). Methods. A total of 34 pwMS (Expanded Disability Status Scale score 3.0 ± 0.8) and 31 HCs were tested and retested on 3 single cognitive, 4 single motor, and 12 cognitive-motor dual tasks. Cognitive tasks included serial subtraction by 7, titrated digit span backward, and auditory vigilance. Motor tasks were walking at self-selected speed, over obstacles, crisscross, and while carrying a water-filled cup. Outcome measures were cognitive and motor DTC, calculated as percentage change of dual-task performance compared with single-task performance. Intraclass correlations (ICCs) and Spearman correlation coefficients were calculated as appropriate. Results. For DTCmotor of gait speed, ICCs ranged from 0.45 to 0.81 and Spearman correlations from 0.74 to 0.82. For DTCcognitive, ICCs ranged from −0.18 to 0.49 and Spearman correlations from −0.28 to 0.26. Reliability depended on the type of motor and cognitive task. Conclusion. Reliability of the DTCmotor was, overall, good, whereas that of the DTCcognitive was poor. The “walking” and “cup” dual-task conditions were the most reliable regardless of the integrated cognitive task. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported by RIMS by Novartis AG, MS Society Flanders, Swedish Promobilia Foundation, and SailingChallenge4MS.

INTRODUCTION: The impact of severity and location of Crohn's disease (CD) endoscopic ulcers on endoscopic remission in patients treated with antitumor necrosis factor is poorly known. We aimed to describe the endoscopic evolution of CD lesions in a prospective cohort of patients treated with infliximab (IFX) in combo therapy. METHODS: We conducted a post hoc analysis of the TAILORIX randomized controlled trial, which studied biologic-naïve patients with active CD and endoscopic ulcers receiving IFX combo therapy. Ileocolonoscopies were performed at week 0, 12, and 54. Endoscopic healing was defined as the absence of ulcers and complete endoscopic remission as CD Endoscopic Index of Severity (CDEIS)

Background Standard of care in patients with advanced ovarian cancer (AOC) is upfront surgery followed by chemotherapy. Neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) is an alternative in selected patients. Most data exist with IDS following 3–4 cycles chemotherapy, however, some patients experience a delay of IDS. So far, the impact of a “delayed” interval debulking surgery (DID) is poorly defined. Methods We analyzed data from eight international gynecology-oncology referral centers. Patients were included if they had newly diagnosed AOC and were prone to DID (minimum 5 cycles of NACT) between 2011 and 2017. Results 308 patients underwent DID. 89.6% had a high-grade serous ovarian cancer. The median number of pre-op NACT was 6 cycles (range 5–9) and 6.1% of patients received additionally bevacizumab. The majority of patients had stage-IV disease (51.3%). Median duration of surgery was 210 min (range 34–561), the median surgical complexity score was 4 (range 1–16). Complete resection was achieved in 60.1%. The median number of post-op chemotherapy cycles was 2 (range 0–5). The rate of severe complications (Clavien-Dindo£3°) was 9.7% and 30 days post-op mortality was 0.3%. The median PFS and OS in patients with complete resection was 19.5 and 49.2 months compared to 14.8 and 33.0 months in patients with incomplete resection (p = 0.001), respectively. We did not observe any survival benefit for patients with cytoreduction to small residuals (1–10 mm) compared to residual disease >1 cm. Conclusion Our data may suggest that offering surgery to patients with persistent disease after 5+ cycles could be associated with favorable outcome if a complete resection is achieved. Patients who had residual disease postoperatively may experience rather peri-operative treatment burden than any benefit from DID.

Background: The COVID‐19 pandemic requires massive and rapid behavior change. The Health Action Process Approach (HAPA) describes personal determinants that play a key role in behavior change. This study investigated whether these determinants are associated with adherence to physical distancing measures to prevent the spread of COVID‐19 (i.e. keeping 1.5 m physical distance and staying at home). Decreased psychosocial well‐being and lack of social support were explored as barriers to adherence.Methods: Two cross‐sectional surveys were conducted among adults in Belgium. The first survey (N = 2,379; March 2020) focused on adherence to physical distancing measures. The second survey (N = 805; April 2020) focused on difficulty with, and perseverance in, adhering to these measures. Linear regression models were fitted to examine associations with HAPA determinants, psychosocial well‐being, and social support.Results: Self‐efficacy, outcome expectancies, intention, action planning, and coping planning were related to adhering to, difficulty with, and perseverance in, adhering to physical distancing measures. Decreased psychosocial well‐being and lack of social support were related to more difficulties with adhering to physical distancing and lower perseverance.Conclusions: Health action process approach determinants are associated with adherence to physical distancing measures. Future work could design HAPA‐based interventions to support people in adhering to these measures

Background The interpretation of germline TP53 variants is critical to ensure appropriate medical management of patients with cancer and follow-up of variant carriers. This interpretation remains complex and is becoming a growing challenge considering the exponential increase in TP53 tests. We developed a functional assay directly performed on patients’ blood. Methods Peripheral blood mononuclear cells were cultured, activated, exposed to doxorubicin and the p53-mediated transcriptional response was quantified using reverse transcription–multiplex ligation probe amplification and RT-QMPSF assays, including 10 p53 targets selected from transcriptome analysis, and two amplicons to measure p53 mRNA levels. We applied this blood functional assay to 77 patients addressed for TP53 analysis. Results In 51 wild-type TP53 individuals, the mean p53 functionality score was 12.7 (range 7.5–22.8). Among eight individuals harbouring likely pathogenic or pathogenic variants, the scores were reduced (mean 4.8, range 3.1–7.1), and p53 mRNA levels were reduced in patients harbouring truncating variants. We tested 14 rare unclassified variants (p.(Pro72His), p.(Gly105Asp), p.(Arg110His), p.(Phe134Leu), p.(Arg158Cys), p.(Pro191Arg), p.(Pro278Arg), p.(Arg283Cys), p.(Leu348Ser), p.(Asp352Tyr), p.(Gly108_Phe109delinsVal), p.(Asn131del), p.(Leu265del), c.-117G>T) and 12 yielded functionally abnormal scores. Remarkably, the assay revealed that the c.*1175A>C polymorphic variant within TP53 poly-adenylation site can impact p53 function with the same magnitude as a null variant, when present on both alleles, and may act as a modifying factor in pathogenic variant carriers. Conclusion This blood p53 assay should therefore be a useful tool for the rapid clinical classification of germline TP53 variants and detection of non-coding functional variants.

ACL; OBJECTIVE:The aim of the study was to compare outcomes after out-of-hospital cardiac arrest (OHCA) between comparable female and male OHCA cohorts in a large nationwide registry. METHODS:This was a national multicentre retrospective, case-control propensity score-matched study based on French National Cardiac Arrest Registry data from 1 July 2011 to 21 September 2017. Female and male survival rates at D30 were compared. RESULTS:At baseline 66 395 OHCA victims were included, of which 34.3% were women. At hospital admission, survival was 18.2% for female patients and 20.2% for male patients [odds ratio (OR), 1.138 (1.092-1.185)]; at 30 days, survival was 4.3 and 5.9%, respectively [OR, 1.290 (1.191-1.500)]. After matching (14 051 patients within each group), female patients received less advanced life support by mobile medical team (MMT), they also had a longer no-flow duration and shorter resuscitation effort by MMT than male patients. However, 15.3% of female patients vs. 9.1% of male patients were alive at hospital admission [OR, 0.557 (0.517-0.599)] and 3.2 vs. 2.6% at D30 [OR, 0.801 (0.697-0.921)], with no statistically significant difference in neurological outcome [OR, 0.966 (0.664-1.407)]. CONCLUSIONS:In this large nationwide matched OHCA study, female patients had a better chance of survival with no significant difference in neurological outcome. We also noticed that female patients received delayed care with a shorter resuscitation effort compared to men; these complex issues warrant further specific investigation. Encouraging bystanders to act as quickly as possible and medical teams to care for female patients in the same way as male patients should increase survival rates.

International audience; Aims: There are large differences between emergency medical systems, which may account for variability in outcomes. We seek to compare prehospital organizations, response modes, patient characteristics and outcomes after out-of-hospital cardiac arrest, between France and Canada, and discuss the need for the first European-North American prehospital research network on out-of-hospital cardiac arrest.Methods: Preliminary comparative description of data drawn from two nation-wide, population-based, Utstein-style prospectively implemented registries for out-of-hospital cardiac arrest in France and Canada (France: RéAC, Canada: CanROC), covering approximately 80 million people, and soon to be participating in an international research network in 2020.Results: Since creation, 103,722 cases were included in France and approximately 99,317 in Canada. Data used in this work were drawn from 2011 to 2016, and comprised around 33,688 adult, non-traumatic, treated cases in Canada, and 55,358 in France, leading to estimated incidence rates of 75.3/100,000 inhabitants in France and 83/100,000 in Canada. In both countries, out-of-hospital cardiac arrest predominantly occurred in male patients, in their late sixties, at home, of presumed cardiac aetiology. Bystander cardiopulmonary resuscitation was provided in half of the cases. First assessed cardiac rhythm was shockable in 16% (France) vs. 22% (Canada). Professional resuscitation was attempted in 82% (France) and 60% (Canada). Prehospital organizations and response modes differed in the constitution of responding teams (France: physician-led advanced life support, Canada: trained paramedics), in response time intervals (call to first professional responders' arrival at scene 6.5 min (interquartile range IQR [5.2-8.3]) (Canada) vs. 10 min [7-15] (France)), in on-scene interventions, type of referral at hospital (France: systematic bypass of emergency department, tertiary hospital first, Canada: occasional bypass, mainly closest hospital first), and in outcomes (overall survival at hospital discharge in France: 5% vs. Canada: 11%).Conclusion: Despite similarities in some out-of-hospital cardiac arrest Utstein variables, several differences exist between French and Canadian prehospital systems, and ultimately, between outcomes. The creation of the ReACanROC research network will facilitate the conduction of further analyses to better understand predictors of this variability.

International audience; The detection of copy-number variations (CNVs) from NGS data is underexploited as chip-based or targeted techniques are still commonly used. We assessed the performances of a workflow centered on CANOES, a bioinformatics tool based on read depth information. We applied our workflow to gene panel (GP) and whole-exome sequencing (WES) data, and compared CNV calls to quantitative multiplex PCR of short fluorescent fragments (QMSPF) or array comparative genomic hybridization (aCGH) results. From GP data of 3776 samples, we reached an overall positive predictive value (PPV) of 87.8%. This dataset included a complete comprehensive QMPSF comparison of four genes (60 exons) on which we obtained 100% sensitivity and specificity. From WES data, we first compared 137 samples with aCGH and filtered comparable events (exonic CNVs encompassing enough aCGH probes) and obtained an 87.25% sensitivity. The overall PPV was 86.4% following the targeted confirmation of candidate CNVs from 1056 additional WES. In addition, our CANOES-centered workflow on WES data allowed the detection of CNVs with a resolution of single exons, allowing the detection of CNVs that were missed by aCGH. Overall, switching to an NGS-only approach should be cost-effective as it allows a reduction in overall costs together with likely stable diagnostic yields. Our bioinformatics pipeline is available at: https://gitlab.bioinfo-diag.fr/nc4gpm/canoes-centered-workflow.

Background Bartonella spp. are vector-borne pathogens transmitted to humans via blood-sucking arthropods. Rodents such as the black rat (Rattus rattus) and Norway rat (R. norvegicus) are thought to be the main reservoirs. An infection with rodent-associated Bartonella spp. may cause severe symptoms in humans such as endocarditis and neuroretinitis. The current knowledge of Bartonella prevalence in rats from western Europe is scarce. Methods Rats and a few other rodent by-catches were trapped in the context of a rodenticide resistance study at different sites in Flanders, Belgium. During dissection, biometric data were collected, and spleen tissues were taken. DNA was extracted from spleen samples and tested for Bartonella spp. by conventional generic polymerase chain reaction (PCR). To determine the Bartonella species, a selected number of amplicons were sequenced and compared with GenBank entries. Results In total, 1123 rodents were trapped. The predominate species was R. norvegicus (99.64%). Other rodents trapped included: two water voles (Arvicola amphibius, 0.18%); one colour rat (R. norvegicus forma domestica, 0.09%); and one muskrat (Ondatra zibethicus, 0.09%). PCR analysis of 1097 rodents resulted in 410 (37.37%, 95% CI: 34.50–40.31%) Bartonella spp. DNA-positive samples. Bartonella tribocorum (94.68%, 95% CI: 88.02–98.25%) was the most frequently detected Bartonella species, followed by B. grahamii (3.19%, 95% CI: 0.66–9.04%) and B. doshiae (1.06%, 95% CI: 0.03–5.79%). An uncultured Bartonella species occurred in one water vole (1.06%, 95% CI: 0.03–5.79%). There was a significantly higher Bartonella prevalence in older rats compared to juveniles and a significant difference in Bartonella prevalence concerning the localisation of trapping sites. In contrast, there was no statistically significant difference in Bartonella prevalence regarding sex, degree of urbanisation and season. Conclusions Based on the high prevalence found, we conclude that the Norway rat seems to be a key reservoir host for zoonotic B. tribocorum in Belgium.

RATIONALE, AIMS, AND OBJECTIVES The human body is regulated by intrinsic factors which follow a 24-hour biological clock. Implications of a circadian rhythm in the out-of-hospital cardiac arrest (OHCA) are studied but the literature is not consistent. The main objective of our study was to identify temporal cluster of high or low incidence of OHCA occurrence during a day. METHODS Multicentre comparative study based on the French national OHCA registry data between 2013 and 2017. After describing the population, the detection of significant temporal clusters of OHCA incidence was achieved using temporal scan statistics based on a Poisson model adjusted for age and gender. Then, comparisons between identified patients clusters and the rest of the population were performed. RESULTS During the study, 37 163 medical OHCA victims were included. The temporal scan revealed a significant 3-hour high incidence temporal cluster between 8:00 am and 10:59 am (Relative R = 1.76, P

To compare intraosseous access with peripheral venous access on adults out-of-hospital cardiac arrest (OHCA) patients’ clinical outcomes. A national retrospective multicentre study was conducted based on the French National Cardiac Arrest Registry. Comparison of patients (intraosseous vs. peripheral venous access) was conducted before and after a matching using a propensity score. The propensity score included confounding factors: age, time between the call (T0) to epinephrine (to take account of how quickly vascular access was achieved), the aetiology of OHCA, the shock and the patient initial rhythm at MMT arrival. A total of 1576 patients received intraosseous access, and 27,280 received peripheral intravenous access. Before matching, OHCA patients with intraosseous access were less likely to survive at all stages (return of spontaneous circulation (ROSC), 0-day survival and 30-day survival). No significant difference in neurological outcome was observed. After propensity score matching, no significant differences in 30-day survival rates (OR = 0.763 [0.473;1.231]) and neurological outcome (OR = 1.296 [0.973;1.726]) were observed. However, intraosseous patients still showed lower likelihood of short-term survival (ROSC and 0-day survival) even after propensity score matching was implemented. The populations we investigated were similar to those of other studies suggesting that intraosseous access is associated with reduced survival and poorer neurological outcome. Our findings suggest that intraosseous access is a comparably effective alternative to peripheral intravenous access for treating OHCA patients on matched populations.

Background. In the general population, trajectories of walking capacity is accelerated and nonlinear with advanced age. Whether this is more pronounced in persons with multiple sclerosis (pwMS), along with the prevalence of dismobility (ie, slow gait speed), are currently unknown. Our objective was to investigate trajectories of walking capacity and prevalence of dismobility across the adult life span in pwMS versus healthy controls (HC). Methods. Data on maximal timed 25-foot walk test (T25FWT), 2-minute walk test (2MWT), and 6-minute walk test (6MWT) along with prevalence of dismobility were assembled from 2 RIMS multicenter studies (n = 502 pwMS; age range 21-77 years, 6 age groups: 20-29, 30-39, 40-49, 50-59, 60-69, and 70-79 years). HC data were extracted from studies containing normative reference values (n = 1070-3780 HC). Results. Age trajectories of walking capacity was nonlinear and accelerated in pwMS versus HC. While measures of walking capacity in pwMS were suppressed already early in life, the gap between pwMS and HC significantly widened across the 6 age groups (pwMS performed 64%, 70%, 57%, 59%, 51%, and 37% of HC, respectively). This coincided with high prevalences of dismobility in pwMS across the 6 age groups when using usual gait speed cut-point values

SALIHOGLU, ZIYA/0000-0002-6905-2664 WOS:000521719800002 PubMed ID: 32207048 Purpose LSG surgery is used for surgical treatment of morbid obesity. Obesity, anesthesia, and pneumoperitoneum cause reduced pulmoner functions and a tendency for atelectasis. The alveolar "recruitment" maneuver (RM) keeps airway pressure high, opening alveoli, and increasing arterial oxygenation. The aim of our study is to research the effect on respiratory mechanics and arterial blood gases of performing the RM in LSG surgery. Materials and Methods Sixty patients undergoing LSG surgery were divided into two groups (n = 30) Patients in group R had the RM performed 5 min after desufflation with 100% oxygen, 40 cmH(2)O pressure for 40 s. Group C had standard mechanical ventilation. Assessments of respiratory mechanics and arterial blood gases were made in the 10th min after induction (T1), 10th min after insufflation (T2), 5th min after desufflation (T3), and 15th min after desufflation (T4). Arterial blood gases were assessed in the 30th min (T5) in the postoperative recovery unit. Results In group R, values at T5, PaO2 were significantly high, while PaCO2 were significantly low compared with group C. Compliance in both groups reduced with pneumoperitoneum. At T4, the compliance in the recruitment group was higher. In both groups, there was an increase in PIP with pneumoperitoneum and after desufflation this was identified to reduce to levels before pneumoperitoneum. Conclusion Adding the RM to PEEP administration for morbidly obese patients undergoing LSG surgery is considered to be effective in improving respiratory mechanics and arterial blood gas values and can be used safely.