Correlates of chronic pain onset and recovery in the CoLaus cohort.

BACKGROUND: Only few previous cohort studies examined simultaneously predictors of chronic pain (CP) onset and recovery. Furthermore, these studies used various sociodemographic and pain-related characteristics, without standardized measures of sleep and depression. The present study aimed at expanding and strengthening these findings in a large Swiss population. METHODS: We analysed data from a longitudinal cohort (n = 4602) collected at two time points separated by 5 years in Lausanne, Switzerland. We studied through two independent multivariable logistic regression models, the predictors of CP onset and recovery, including socio-demographic data as well as standardized measures of sleep and mood. RESULTS: Chronic pain was reported by 43.1% and 44.4% of participants, with 11.6% at the second follow-up reporting moderate or intense pain. Neuropathic pain, regardless of intensity, had a more negative impact on quality of life. An inferential model (n = 1331) identified the male sex as predictive for recovering from CP. Older age, being overweight or obese (compared to normal weight), higher depression scores and pain medication intake were predictive for sustained pain at the second follow-up. A second model (n = 1886) identified being overweight or obese (compared to normal weight), low quality of sleep and being a former smoker (compared to a non-smoker) as predictive for developing CP, while the male sex was lowering the risk. CONCLUSIONS: While sex and weight are associated with both recovery and new CP onset, separate variables also need to be considered in these processes, underlining specific factors to be addressed, depending on the context, whether preventive or therapeutic. SIGNIFICANCE STATEMENT: Multivariable models in a Swiss cohort (N = 4602) associate male sex, not taking pain medication, normal weight, lower depression scores and younger age with recovery from chronic pain, while females, obese or overweight, having worse sleep and former smokers are associated with onset of new chronic pain. These common and separate factors need to be considered in treatment and prevention efforts.

Cohort Profile Update: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS).

Introduction: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS) is a national cohort that was established in 2015 with the aim of improving quality of care of affected adults with eosinophilic esophagitis (EoE). Between 2020 and 2022, paper questionnaires were gradually replaced by fully electronic data capture using Research Electronic Data Capture (REDCap®) software. We aim to provide an update of the SEECS 8 years after its launch. Methods: The SEECS prospectively includes adults (≥18 years of age) with EoE as well as patients with gastroesophageal reflux disease (GERD) and healthy control subjects (HC). Upon inclusion and follow-up (typically once every 12-18 months), patients and physicians complete REDCap® questionnaires, which are available in German, French, and English. Patient-reported outcomes (PROs) and biologic findings are assessed on the same day using validated instruments (EEsAI PRO for symptoms; EoE-QoL-A for QoL; EREFS for endoscopic activity; modified EoE-HSS for histologic activity). The SEECS biobank includes biosamples from patients with EoE, GERD, and HC. Results: As of July 2023, the SEECS included 778 patients (716 [92%] with EoE, 29 [3.8%] with GERD, and 33 [4.2%] HC; 559/778 [71.9%] were male). Mean age ± SD (years) at enrollment according to diagnosis was as follows: EoE 41.9 ± 12.9, GERD 53.6 ± 16.4, HC 51.7 ± 17.2. Concomitant GERD was found in 200 patients (27.9%) of the EoE cohort. Concomitant allergic disorders (asthma, rhinoconjunctivitis, eczema) were present in 500 EoE patients (74.4%). At inclusion, 686 (95.8%) of EoE patients were on ongoing treatment (orodispersible budesonide tablet [Jorveza®] in 281 patients [41%]; budesonide or fluticasone syrup or swallowed powder in 290 patients [42.3%]; proton-pump inhibitors in 162 patients [23.6%]; elimination diets in 103 patients [15%]; and esophageal dilation at last visit in 166 patients [24.2%]). A total of 8,698 biosamples were collected, of which 1,395 (16%) were used in the framework of translational research projects. Conclusion: SEECS continuously grows and is operational using fully electronic data capture. SEECS offers up-to-date epidemiologic and real-world clinical efficacy data on EoE and promotes clinical and translational research.

Non-pulmonary complications of intrathecal morphine administration: a systematic review and meta-analysis with meta-regression.

BACKGROUND: Intrathecal morphine provides effective analgesia for a range of operations. However, widespread implementation into clinical practice is hampered by concerns for potential side-effects. We undertook a systematic review, meta-analysis, and meta-regression with the primary objective of determining whether a threshold dose for non-pulmonary complications could be defined and whether an association could be established between dose and complication rates when intrathecal morphine is administered for perioperative or obstetric analgesia. METHODS: We systematically searched the literature for randomised controlled trials comparing intrathecal morphine vs control in patients undergoing any type of surgery under general or spinal anaesthesia, or women in labour. Primary outcomes were rates of postoperative nausea and vomiting, pruritus, and urinary retention within the first 24 postoperative hours, analysed according to doses (1-100 µg; 101-200 µg; 201-500 µg; >500 µg), type of surgery, and anaesthetic strategy. Trials were excluded if doses were not specified. RESULTS: Our analysis included 168 trials with 9917 patients. The rates of postoperative nausea and vomiting, pruritus, and urinary retention were significantly increased in the intrathecal morphine group, with an odds ratio (95% confidence interval) of 1.52 (1.29-1.79), P<0.0001; 6.11 (5.25-7.10), P<0.0001; and 1.73 (1.17-2.56), P=0.005, respectively. Meta-regression could not establish an association between dose and rates of non-pulmonary complications. There was no subgroup difference according to surgery for any outcome. The quality of evidence was low (Grading of Recommendations Assessment, Development, and Evaluation [GRADE] system). CONCLUSIONS: Intrathecal morphine significantly increased postoperative nausea and vomiting, pruritus, and urinary retention after surgery or labour in a dose-independent manner. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023387838).

Odynophagia and Retrosternal Pain Are Common in Eosinophilic Esophagitis and Associated with an Increased Overall Symptom Severity.

BACKGROUND AND AIMS: Dysphagia is the hallmark symptom in eosinophilic esophagitis (EoE). However, data are limited regarding the overall prevalence and potential implications of atypical symptoms like odynophagia and retrosternal pain. METHODS: Patients enrolled into the Swiss EoE cohort study (SEECS) were analyzed regarding the presence of odynophagia and retrosternal pain. Demographics, other EoE-related symptoms, histologic and endoscopic activity were compared between EoE-patients with vs. without odynophagia and/or retrosternal pain. RESULTS: 474 patients (75.2% male) were analyzed. In their individual course of disease 110 (23.2%) patients stated to have ever experienced odynophagia and 64 (13.5%) retrosternal pain independent of food intake, 24 (5%) patients complained about both symptoms. Patients with odynophagia consistently scored higher in symptom severity (p < 0.001), EREFS score (median 3.0 vs. 2.0, p = 0.006), histologic activity and a lower quality of life (p = 0.001) compared to patients without odynophagia. Sex, age at diagnosis, EoE-specific treatment, complications such as candida or viral esophagitis and disease duration were similar in patients with vs. without odynophagia. Also patients with retrosternal pain scored higher in symptom severity (2.0 vs. 1.0, p = 0.001 and 2.0 vs. 1.0, p < 0.001 in physician and patient questionnaire assessment, respectively). However, there was neither a difference in endoscopic/histologic disease activity nor in quality of life according to presence or absence of retrosternal pain. Due to logistic reasons, a stratification regarding the presence of concomitant dysphagia was not possible. CONCLUSION: Odynophagia and swallowing-independent retrosternal pain are common symptoms in patients with EoE, associate with an overall higher EoE-related symptom severity and for the case of odynophagia lower quality of life. However, the influence of concomitant dysphagia and its severity remains unclear and needs to be included in future analyses.

Long-Term Outcome of Surgery for Perianal Crohn's Fistula.

Background and Objectives: Patients with perianal Crohn's (CD) fistula often need repetitive surgeries and none of the established techniques was shown to be superior or preferable. Furthermore, the long-term outcome of fistula Seton drainage is not well described. The aims of this study were to analyze the long-term healing and recurrence rate of CD perianal fistulas in a large patient cohort. Materials and Methods: Database analysis of the Swiss IBD (Inflammatory Bowel Disease) cohort study. Results: 365 perianal fistula patients with 576 surgical interventions and a median follow-up of 7.5 years (0-12.6) were analyzed. 39.7% of patients required more than one procedure. The first surgical interventions were fistulectomies ± mucosal sliding flap (59.2%), Seton drainage (29.6%), fistula plugs or fibrin glue installations (2.5%) and combined procedures (8.8%). Fistulectomy patients required no more surgery in 69%, one additional surgery in 25% and more than one additional surgery in 6%, with closure rates at 7.5 years follow-up of 77.1%, 74.1% and 66.7%, respectively. In patients with Seton drainage as index surgery, 52% required no more surgery, and over 75% achieved fistula closure after 10 years. Conclusions: First-line fistulectomies, when feasible, achieved the highest healing rates, but one-third of patients required additional surgeries, and one-fourth of patients will remain with a fistula at 10 years. Initial Seton drainage and concurrent medical therapy can achieve fistula closure in 75%. However, in 50% of patients, more surgeries are needed, and fistula closure is achieved in only two-thirds of patients.

Impact of spinal versus general anaesthesia on perioperative obstructive sleep apnoea severity in patients undergoing hip arthroplasty: a post hoc analysis of two randomised controlled trials.

BACKGROUND: Recommendations suggest favouring regional over general anaesthesia to reduce impact on postoperative sleep apnoea severity, but there is currently no evidence to support this. We compared the impact of general vs spinal anaesthesia on postoperative sleep apnoea severity and assessed the evolution of sleep apnoea severity up to the third postoperative night. METHODS: This post hoc analysis used pooled data from two previous randomised controlled trials in patients undergoing total hip arthroplasty under general or spinal anaesthesia (n=96), without performing a preliminary power analysis. All participants underwent respiratory polygraphy before surgery and on the first and third postoperative nights. The primary outcomes were the supine apnoea-hypopnea index on the first postoperative night and the evolution of the supine apnoea-hypopnea index up to the third postoperative night. Secondary outcomes included the oxygen desaturation index on the first and third postoperative nights. RESULTS: In the general and spinal anaesthesia groups, mean (95% confidence interval) values for the supine apnoea-hypopnoea index on the first postoperative night were 20 (16-25) and 21 (16-26) events h-1 (P=0.82), respectively; corresponding values on the third postoperative night were 34 (22-45) and 35 (20-49) events h-1 (P=0.91). The generalised estimating equations model showed a significant time effect. Secondary outcomes were similar in the two groups. CONCLUSIONS: Use of spinal anaesthesia compared with general anaesthesia was not associated with a reduction in postoperative sleep apnoea severity, which was worse on the third postoperative night. CLINICAL TRIAL REGISTRATION: NCT02717780 and NCT02566226.

Risk Assessment Models for Venous Thromboembolism in Medical Inpatients.

Importance: Thromboprophylaxis is recommended for medical inpatients at risk of venous thromboembolism (VTE). Risk assessment models (RAMs) have been developed to stratify VTE risk, but a prospective head-to-head comparison of validated RAMs is lacking. Objectives: To prospectively validate an easy-to-use RAM, the simplified Geneva score, and compare its prognostic performance with previously validated RAMs. Design, Setting, and Participants: This prospective cohort study was conducted from June 18, 2020, to January 4, 2022, with a 90-day follow-up. A total of 4205 consecutive adults admitted to the general internal medicine departments of 3 Swiss university hospitals for hospitalization for more than 24 hours due to acute illness were screened for eligibility; 1352 without therapeutic anticoagulation were included. Exposures: At admission, items of 4 RAMs (ie, the simplified and original Geneva score, the Padua score, and the IMPROVE [International Medical Prevention Registry on Venous Thromboembolism] score) were collected. Patients were stratified into high and low VTE risk groups according to each RAM. Main Outcomes and Measures: Symptomatic VTE within 90 days. Results: Of 1352 medical inpatients (median age, 67 years [IQR, 54-77 years]; 762 men [55.4%]), 28 (2.1%) experienced VTE. Based on the simplified Geneva score, 854 patients (63.2%) were classified as high risk, with a 90-day VTE risk of 2.6% (n = 22; 95% CI, 1.7%-3.9%), and 498 patients (36.8%) were classified as low risk, with a 90-day VTE risk of 1.2% (n = 6; 95% CI, 0.6%-2.6%). Sensitivity of the simplified Geneva score was 78.6% (95% CI, 60.5%-89.8%) and specificity was 37.2% (95% CI, 34.6%-39.8%); the positive likelihood ratio of the simplified Geneva score was 1.25 (95% CI, 1.03-1.52) and the negative likelihood ratio was 0.58 (95% CI, 0.28-1.18). In head-to-head comparisons, sensitivity was highest for the original Geneva score (82.1%; 95% CI, 64.4%-92.1%), while specificity was highest for the IMPROVE score (70.4%; 95% CI, 67.9%-72.8%). After adjusting the VTE risk for thromboprophylaxis use and site, there was no significant difference between the high-risk and low-risk groups based on the simplified Geneva score (subhazard ratio, 2.04 [95% CI, 0.83-5.05]; P = .12) and other RAMs. Discriminative performance was poor for all RAMs, with an area under the receiver operating characteristic curve ranging from 53.8% (95% CI, 51.1%-56.5%) for the original Geneva score to 58.1% (95% CI, 55.4%-60.7%) for the simplified Geneva score. Conclusions and Relevance: This head-to-head comparison of validated RAMs found suboptimal accuracy and prognostic performance of the simplified Geneva score and other RAMs to predict hospital-acquired VTE in medical inpatients. Clinical usefulness of existing RAMs is questionable, highlighting the need for more accurate VTE prediction strategies.

Histological Phenotyping in Eosinophilic Esophagitis: Localized Proximal Disease Is Infrequent but Associated with Less Severe Disease and Better Disease Outcome.

INTRODUCTION: It is still unknown whether eosinophilic esophagitis (EoE) patients with localized disease are different from those with extended disease. METHODS: We evaluated prospectively included patients in the Swiss EoE cohort. Data on all patients with active disease at baseline, no concomitant gastroesophageal reflux disease, no strictures at baseline, and at least one follow-up visit were analyzed. We compared patients with histologically localized proximal versus distal versus extended (=proximal and distal) disease with regard to patient, disease characteristics, disease presentation, and development of complications. RESULTS: We included 124 patients with a median of 2.5 years of follow-up (73.4% males, median age 35.0 years). Ten patients had proximal (8.1%), 46 patients had distal (37.1%), and 68 patients had extended disease (54.8%). Patients with proximal disease were significantly more often females (80%) compared with patients with distal (26.1%, p = 0.002) or extended disease (19.1%, p < 0.001) and reported less severe symptoms (VAS 0 vs. VAS 1, p = 0.001). Endoscopic and histological disease was less pronounced in the proximal esophagus of proximal EoE compared to extended disease (EREFS 1.0 vs. 3.0, p = 0.001; 27.0 eos/hpf vs. 52.5 eos/hpf, p = 0.008). Patients with proximal disease were less likely to undergo dilation compared to patients with distal disease in the follow-up (3.3% vs. 23.3%, p = 0.010). In a multivariate Cox regression model, proximal eosinophilia was less likely to be associated with treatment failure compared to distal eosinophilia. CONCLUSION: Although isolated proximal EoE is infrequent, it is associated with less severe disease and better disease outcome. Proximal disease appears to present a unique EoE phenotype.

Association of pharmacologic thromboprophylaxis with clinically relevant bleeding and hospital-acquired anemia in medical inpatients: the risk stratification for hospital-acquired venous thromboembolism in medical patients study.

BACKGROUND: Pharmacologic thromboprophylaxis (pTPX) might exacerbate the risk of clinically relevant bleeding (CRB) and hospital-acquired anemia (HAA) in older multimorbid inpatients. OBJECTIVES: We aimed to evaluate the association of pTPX use with CRB and HAA. METHODS: We used data from a prospective cohort study conducted in 3 Swiss university hospitals. Adult patients admitted to internal medicine wards with no therapeutic anticoagulation were included. pTPX use was ascertained during hospitalization. Outcomes were in-hospital CRB and HAA. We calculated incidence rates by status of pTPX. We assessed the association of pTPX with CRB using survival analysis and with HAA using logistic regression, adjusted for infection, length of stay, and the International Medical Prevention Registry on Venous Thromboembolism bleeding risk score. RESULTS: Among 1305 patients (mean age, 63.7 years; 44% women, 90% at low risk of bleeding), 809 (62%) received pTPX. The incidence of CRB was 2.4 per 1000 patient-days and was not significantly higher in patients with pTPX than in those without. We found no significant association between pTPX and CRB. HAA was frequent (20.2%) and higher in patients with pTPX than in those without (23.2% vs 15.3%). The incidence of HAA was 21.2 per 1000 patient-days and did not significantly differ between patients with pTPX and those without. We found an association between pTPX and HAA (adjusted odds ratio, 1.4; 95% CI, 1.0-2.1). CONCLUSION: Our study confirmed the safety of pTPX in medical inpatients at low risk of bleeding but identified an association between pTPX and HAA. Adherence to guidelines that recommend administering pTPX to medical inpatients at increased venous thromboembolism risk and low bleeding risk is necessary.

Femoral vs sciatic nerve block to provide analgesia after medial open wedge high tibial osteotomy in the setting of multimodal analgesia: A randomized, controlled, single-blinded trial.

STUDY OBJECTIVE: Medial open wedge high tibial osteotomy (MOW HTO) is associated with moderate to severe postoperative pain. The proximal part of the tibia is innervated by branches from the femoral nerve anteriorly and the sciatic nerve posteriorly. There is a paucity of information regarding the optimal peripheral nerve block for postoperative analgesia with minimal impact on motor function. This study tested the hypothesis that a femoral nerve block provides superior analgesia to a sciatic nerve block after MOW HTO in the setting of multimodal analgesia. DESIGN: Randomized controlled single-blind trial. SETTING: Operating room, postoperative recovery area and ward, up to 6 postoperative months. PATIENTS: Fifty patients undergoing MOW HTO. INTERVENTIONS: Interventions were femoral or sciatic nerve block under ultrasound guidance. For each intervention, a total of 100 mg of ropivacaine was injected. Postoperative pain treatment followed a pre-defined protocol with intravenous patient-controlled analgesia of morphine, paracetamol, and ibuprofen. MEASUREMENTS: The primary outcome was intravenous morphine consumption at 24 h postoperatively. Secondary outcomes included rest and dynamic pain scores (on a numeric rating scale out of 10) at 2, 24 and 48 h postoperatively. Functional outcomes included the Short Form-12, Knee injury and Osteoarthritis Outcome Score, and International Knee Documentation Committee (IKDC) scores measured at 6 months postoperatively. MAIN RESULTS: Mean [95% confidence interval] i.v. morphine consumption at 24 postoperative hours were 24 mg [15 mg,33 mg] in the femoral nerve block group and 24 mg [16 mg,32 mg] in the sciatic nerve block group (p = 0.98). There were no significant differences in the secondary outcomes between groups. CONCLUSIONS: This trial failed to demonstrate that a femoral nerve block provides superior analgesia to a sciatic nerve block after MOW HTO under general anesthesia in the setting of multimodal analgesia. There was no significant difference in quality of life and functional outcomes at 6 months postoperatively between groups. Trial registry number:Clinicaltrials.com - NCT05728294; Kofam.ch - SNCTP000003048 | BASEC2018-01774.

Duration of analgesia after forefoot surgery compared between an ankle and a sciatic nerve block at the popliteal crease: A randomised controlled single-blinded trial.

BACKGROUND: Forefoot surgery is associated with severe postoperative pain. Ankle and sciatic nerve blocks provide satisfactory postoperative analgesia after forefoot surgery, but little is known on their respective duration of analgesia. OBJECTIVE: This randomised controlled, single-blinded trial tested the hypothesis that after forefoot surgery in the setting of multimodal analgesia, an ankle block provides analgesia superior to that of a sciatic nerve block at the popliteal crease. DESIGN: A randomised controlled study. SETTING: A single centre study in a university hospital in Switzerland, from September 2018 to November 2022. PATIENTS: From 91 patients scheduled for forefoot surgery, 60 met the inclusion criteria of which 56 completed the protocol and their data were available for analysis. Exclusion criteria were existing sciatic nerve deficit, pre-existing peripheral neuropathy, chronic pain diagnosis, pregnancy, or identified contraindications to peripheral nerve block. INTERVENTION: Patients undergoing forefoot surgery were randomly allocated to either a multi-injection ankle block (partly under ultrasound guidance) or a sciatic nerve block at the popliteal crease (under ultrasound guidance) combined with a saphenous nerve block at the ankle. Patients in each group received a total of 30 ml of ropivacaine 0.5% and a multimodal analgesic regimen inclusive of dexamethasone, paracetamol, ketorolac then ibuprofen. MAIN OUTCOME MEASURE: The primary outcome was duration of analgesia, defined as time to first morphine request. RESULTS: Mean ±â€ŠSD duration of analgesia was 15.4 ±â€Š8.0 h in the ankle block group and 20.0 ±â€Š10.3 h in the sciatic nerve block group ( P  = 0.32). Of note, 15 of 26 (58%) and 24 of 30 (80%) patients of the ankle and sciatic nerve block groups did not request any morphine ( P  = 0.09). Other secondary outcomes were similar between groups. CONCLUSION: Compared with the ankle block, the sciatic nerve block at the popliteal crease does not provide a longer duration of analgesia in patients undergoing forefoot surgery in the setting of multimodal analgesia. TRIAL REGISTRATION: Clinicaltrials.com identifier: NCT03683342.

Concomitant 5-aminosalicylic acid treatment does not affect 6-thioguanine nucleotide levels in patients with inflammatory bowel disease on thiopurines.

Background: There are conflicting data as to whether co-treatment with 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) under azathioprine (AZA) or 6-mercaptopurine (6-MP) therapy may influence 6-thioguanine nucleotide (6-TGN) concentrations, and whether this combination puts patients at risk of side-effects. The aim of the study was to determine 6-TGN levels in patients treated with AZA/6-MP, either alone or in combination with 5-ASA. Methods: Available blood samples from patients treated with AZA or 6-MP were retrieved from the Swiss IBD Cohort Study (SIBDCS). The eligible individuals were divided into 2 groups: those with vs. without 5-ASA co-medication. Levels of 6-TGN and 6-methylmercaptopurine ribonucleotides (6-MMPR) were determined and compared. Potential confounders were compared between the groups, and also evaluated as potential predictors for a multivariate regression model. Results: Of the 110 patients enrolled in this analysis, 40 received concomitant 5-ASA at the time of blood sampling. The median 6-TGN levels in patients with vs. those without 5-ASA co-treatment were 261 and 257 pmol/8×108 erythrocytes, respectively (P=0.97). Likewise, there were no significant differences in 6-MMPR levels (P=0.79). Through multivariate analysis, 6-TGN levels were found to be significantly higher in non-smokers, patients without prior surgery, and those without signs of stress-hyperarousal. Conclusions: Blood concentrations of 6-TGN and 6-MMPR did not differ between patients with vs. those without 5-ASA co-treatment. Our data warrant neither more frequent lab monitoring nor dose adaptation of AZA in patients receiving concomitant 5-ASA treatment.

Single-bolus injection of local anesthetic, with or without continuous infusion, for interscalene brachial plexus block in the setting of multimodal analgesia: a randomized controlled unblinded trial.

INTRODUCTION: Previous trials favored a continuous interscalene brachial plexus block over a single injection for major shoulder surgery. However, these trials did not administer a multimodal analgesic regimen. This randomized, controlled unblinded trial tested the hypothesis that a continuous infusion of local anesthetic for an interscalene brachial plexus block still provides superior analgesia after major shoulder surgery when compared with a single injection in the setting of multimodal analgesia, inclusive of intravenous dexamethasone, magnesium, acetaminophen and ketorolac. METHODS: Sixty patients undergoing shoulder arthroplasty or arthroscopic rotator cuff repair were randomized to receive a bolus of ropivacaine 0.5%, 20 mL, with or without a continuous infusion of ropivacaine 0.2% 4-8 mL/hour, for an interscalene brachial plexus block. Patients were provided with intravenous morphine patient-controlled analgesia. The primary outcome was cumulative intravenous morphine consumption at 24 hours postoperatively. Secondary outcomes included pain scores at rest and on movement, and functional outcomes, measured over 48 hours after surgery. RESULTS: Median (IQR) cumulative intravenous morphine consumption at 24 hours postoperatively was 10 mg (4-24) in the continuous infusion group and 14 mg (8-26) in the single injection group (p=0.74). No significant between-group differences were found for any of the secondary outcomes. CONCLUSIONS: A continuous infusion of local anesthetic for an interscalene brachial plexus block does not provide superior analgesia after major shoulder surgery when compared with a single injection in the setting of multimodal analgesia, inclusive of intravenous dexamethasone, magnesium, acetaminophen and ketorolac. The findings of this study are limited by performance and detection biases. TRIAL REGISTRATION NUMBER: NCT04394130.

Prediction of in-hospital bleeding in acutely ill medical patients: External validation of the IMPROVE bleeding risk score.

INTRODUCTION: Pharmacological thromboprophylaxis slightly increases bleeding risk. The only risk assessment model to predict bleeding in medical inpatients, the IMPROVE bleeding risk score, has never been validated using prospectively collected outcome data. METHODS: We validated the IMPROVE bleeding risk score in a prospective multicenter cohort of medical inpatients. Primary outcome was in-hospital clinically relevant bleeding (CRB) within 14 days of admission, a secondary outcome was major bleeding (MB). We classified patients according to the score in high or low bleeding risk. We assessed the score's predictive performance by calculating subhazard ratios (sHRs) adjusted for thromboprophylaxis use, positive and negative predictive values (PPV, NPV), and the area under the receiver operating characteristic curves (AUC). RESULTS: Of 1155 patients, 8 % were classified as high bleeding risk. CRB and MB within 14 days occurred in 0.94 % and 0.47 % of low-risk and in 5.6 % and 3.4 % of high-risk patients, respectively. Adjusted for thromboprophylaxis, classification in the high-risk group was associated with an increased risk of 14-day CRB (sHR 4.7, 95 % confidence interval [CI] 1.5-14.5) and MB (sHR 4.9, 95%CI 1.0-23.4). PPV was 5.6 % and 3.4 %, while NPV was 99.1 % and 99.5 % for CRB and MB, respectively. The AUC was 0.68 (95%CI 0.66-0.71) for CRB and 0.73 (95%CI 0.71-0.76) for MB. CONCLUSION: The IMPROVE bleeding risk score showed moderate to good discriminatory power to predict bleeding in medical inpatients. The score may help identify patients at high risk of in-hospital bleeding, in whom careful assessment of the risk-benefit ratio of pharmacological thromboprophylaxis is warranted.

Effectiveness of a real-life program (DIAfit) to promote physical activity in patients with type 2 diabetes: a pragmatic cluster randomized clinical trial.

Introduction: The aim of this study was to evaluate the effectiveness of a real-life clinical physical activity program (DIAfit) on improving physical fitness, body composition, and cardiometabolic health in an unselected population with type 2 diabetes mellitus, and to compare the effects of two variants a different exercise frequencies on the same outcomes. Research design and methods: This was a cluster randomized-controlled assessor-blind trial conducted in 11 clinical centres in Switzerland. All participants in the clinical program with type 2 diabetes were eligible and were randomized to either standard (3 sessions/week for 12 weeks) or alternative (1 session/week for the first four weeks, then 2 sessions/week for the rest of 16 weeks) physical activity program each consisting of 36 sessions of combined aerobic and resistance exercise. Allocation was concealed by a central office unrelated to the study. The primary outcome was aerobic fitness. Secondary outcome measures included: body composition, BMI, HbA1c, muscle strength, walking speed, balance, flexibility, blood pressure, lipid profile. Results: All 185 patients with type 2 diabetes (mean age 59.7 +-10.2 years, 48% women) agreed to participate and were randomized in two groups: a standard group (n=88) and an alternative group (n=97)). There was an 11% increase in aerobic fitness after the program (12.5 Watts; 95% CI 6.76 to 18.25; p<0.001). Significant improvements in physical fitness, body composition, and cardiometabolic parameters were observed at the end of the DIAfit program (improvements between 2-29%) except for lean body mass, triglycerides and cholesterol. No differences were observed between both programs, except for a larger weight reduction of -0.97kg (95% CI -0.04 to -1.91; p=0.04) in the standard program. Conclusions: Both frequency variants of the nation-wide DIAfit program had beneficial effects on physical fitness, HbA1c, body composition, and blood pressure in type 2 diabetes patients and differences were negligible. Clinical trial registration: clinicaltrials.gov, identifier NCT01289587.

The Inlet and Outlet Ratio: Retrospective and Prospective Study on an Improved Diagnostic Ultrasound Tool for Carpal Tunnel Syndrome.

Purpose: This study hypothesized that ratios of sonographic cross-sectional areas (CSAs) throughout the median nerve provide a more reliable tool for diagnosing carpal tunnel syndrome (CTS) than a single CSA value. We first tested this hypothesis in a retrospective cohort and subsequently confirmed it in a prospective blinded case-control series. Methods: Seventy patients were included in the retrospective study, and 50 patients and matched controls were included for the prospective study. We evaluated 4 CSAs, at the forearm, inlet, tunnel, outlet, and their ratios (Rforearm, Rinlet, Routlet, Routlet forearm) to evaluate compression of the median nerve. All patients underwent nerve conduction studies. For the prospective cohort, Disabilities of the Arm, Shoulder, and Hand scores and Boston Carpal Tunnel Questionnaire scores were evaluated, and ultrasound was performed by 2 examiners for each participant. Results: The Boston and Disabilities of the Arm, Shoulder, and Hand scores showed worse subjective function in patients with CTS than in controls. Three ultrasonography parameters (CSAs at the inlet, Rinlet, and Routlet) correlated significantly with subjective function. Age and Rinlet were significantly correlated with severity of CTS in the nerve conduction studies. In both the retrospective and prospective patient groups, the numbers of CSAs at the inlet and outlet were significantly higher than that of CSAs at the tunnel, whereas in the control group, no such compression was found. Of the single measurements, CSAs at the inlet had the best diagnostic performance with an optimized cutoff of 11.75 mm2. The Rinlet and Routlet ratios performed even better and showed the highest adjusted odds ratios for predicting CTS of all parameters (cutoff Rinlet, 1.25; Routlet, 1.45). Inter-observer correlation was generally high, with better values for single CSAs than for ratios. Conclusions: The 3 CSA measurements of the median nerve and the associated ratios improved diagnostic power for ultrasonography in CTS in our study. Type of study/level of evidence: Diagnostic I.

Identification of High Platelet Reactivity Despite ADP P2Y 12 Inhibitor Treatment: Two Populations in the Vasodilator-Stimulated Phosphoprotein Assay and Variable PFA-P2Y Shapes of Curve.

Introduction Response to ADP P2Y 12 receptor inhibition by clopidogrel can be evaluated by various techniques. Here, we compared a functional rapid point-of-care technique (PFA-P2Y) with the degree of biochemical inhibition assessed by the VASP/P2Y 12 assay. Methods Platelet response to clopidogrel was investigated in 173 patients undergoing elective intracerebral stenting (derivation cohort n = 117; validation cohort n = 56). High platelet reactivity (HPR) was defined as PFA-P2Y occlusion time <106 seconds or VASP/P2Y 12 platelet reactivity index (PRI) >50%. Results In the derivation cohort, receiver operator characteristics analysis for the ability of PFA-P2Y to detect biochemical HPR showed high specificity (98.4%) but poor sensitivity (20.0%) and a very low area under the curve (0.59). The VASP/P2Y 12 assay revealed two coexisting platelet populations with different levels of vasodilator-stimulated phosphoprotein (VASP) phosphorylation: a fraction of highly phosphorylated, inhibited platelets and another of poorly phosphorylated, reactive platelets. Analysis of the PFA-P2Y curve shape revealed different types, categorized by time of occlusion (<106 seconds, 106 to 300 seconds, >300 seconds), and pattern (regular, irregular, and atypical). Noteworthy, curves with late occlusion and permeable curves with an irregular or atypical pattern correlated with VASP-PRI >50% and smaller sizes of the inhibited platelet subpopulation. Considering the PFA-P2Y shape of the curve for the detection of HPR improved sensitivity (72.7%) and preserved specificity (91.9%), with a rather high AUC (0.823). The validation cohort confirmed the VASP/P2Y 12 assay data and the usefulness of considering the PFA-P2Y curve shape. Conclusion In patients treated with acetylsalicylic acid and clopidogrel for 7-10 days, the VASP/P2Y 12 assay reveals two coexisting subpopulations of differentially inhibited platelets, whose relative sizes predict global PRI and distinct PFA-P2Y curve patterns, indicating incomplete clopidogrel efficacy. The detailed analysis of both VASP/P2Y 12 and PFA-P2Y is necessary for optimal detection of HPR.

Barrett's Esophagus in Eosinophilic Esophagitis in Swiss Eosinophilic Esophagitis Cohort Study (SEECS).

INTRODUCTION: There is a complex interrelationship between gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) potentially promoting the occurrence and modulating severity of each other reciprocally. Presence of Barrett's esophagus (BE) is a defining factor for the diagnosis of GERD. While several studies investigated the potential impact of concomitant GERD on the presentation and course of EoE, little was known with regards to BE in EoE patients. METHODS: We analyzed prospectively collected clinical, endoscopic, and histological data from patients enrolled in the Swiss Eosinophilic Esophagitis Cohort Study (SEECS) regarding differences between EoE patients with (EoE/BE+) versus without BE (EoE/BE-) and determined the prevalence of BE in EoE patients. RESULTS: Among a total of 509 EoE patients included in our analysis, 24 (4.7%) had concomitant BE with a high male preponderance (EoE/BE+ 83.3% vs. EoE/BE- 74.4%). While there were no differences in dysphagia, odynophagia was significantly (12.5 vs. 3.1%, p = 0.047) more common in EoE/BE+ versus EoE/BE-. General well-being at last follow-up was significantly lower in EoE/BE+. Endoscopically, we observed an increased incidence of fixed rings in the proximal esophagus in EoE/BE+ (70.8 vs. 46.3% in EoE/BE-, p = 0.019) and a higher fraction of patients with a severe fibrosis in the proximal histological specimen (8.7 vs. 1.6% in EoE/BE, p = 0.017). CONCLUSION: Our study reveals that BE is twice as frequent in EoE patients compared to general population. Despite many similarities between EoE patients with and without BE, the finding of a more pronounced remodeling in EoE patients with Barrett is noteworthy.

Sensory block duration after spinal anaesthesia supplemented with intravenous dexamethasone: a randomised controlled double-blinded trial.

BACKGROUND: Intravenous dexamethasone prolongs duration of analgesia or sensory block after injection of local anaesthetics close to peripheral nerves by an average of 8 h. Uncertainty remains on the potential increase in the duration of sensory block after spinal anaesthesia. The objective of this randomised controlled double-blinded trial was to investigate whether dexamethasone i.v. prolongs the sensory block of spinal anaesthesia with bupivacaine when compared with a control group. METHODS: Of 50 patients undergoing lower limb osteoarticular surgery under spinal anaesthesia with isobaric bupivacaine 15 mg i.t. with morphine 100 µg i.t. were randomised to receive either dexamethasone 0.15 mg kg-1 i.v. or normal saline 3 ml i.v. The primary outcome was duration of sensory block defined as the time elapsed between injection of the local anaesthetic in the intrathecal space and the regression of sensory block by two dermatomes compared with the highest dermatome blocked. Secondary outcomes included intravenous morphine consumption, pain scores at rest and on movement, postoperative nausea and vomiting, and blood glucose at 2, 24, and 48 h. RESULTS: Median duration of sensory block was 135 (105-225) min in the dexamethasone group and 158 (135-240 min) in the control group (P=0.19). Patients in the dexamethasone group received less morphine at 24 h, had significantly less postoperative nausea and vomiting at 2 h and 24 h, and had increased blood glucose at 24 h. Other secondary outcomes were similar between groups. CONCLUSION: Intravenous dexamethasone did not prolong the sensory block of spinal anaesthesia with isobaric bupivacaine. However, it reduced morphine consumption and rate of postoperative nausea and vomiting at 24 h, at the expense of an increased blood glucose. CLINICAL TRIAL REGISTRATION: NCT03527576 (Clinicaltrials.gov).

Effect of closed and permanent stoma on disease course, psychological well-being and working capacity in Swiss IBD cohort study patients.

BACKGROUND: Little is known about the impact of ostomy formation in inflammatory bowel disease patients on course of disease, psychological well-being, quality of life and working capacity. METHODS: We analyzed patients over a follow-up of up to 16 years in the Swiss inflammatory bowel disease cohort study (SIBDCS) with prospective data collection. We compared Ulcerative colitis and Crohn's disease patients with and without ostomy as well as permanent and closed stoma formation before and after surgery, investigating disease activity, psychological wellbeing and working capacity in a case-control design. RESULTS: Of 3825 SIBDCS patients, 176 with ostomy were included in the study and matched with 176 patients without ostomy using propensity score, equaling 352 patients for the analysis. As expected, we observed a lower mean and maximal disease activity in patients after stoma surgery compared with control patients without stoma. Overall, psychological wellbeing in patients with stomas vs. controls as well as patients with permanent vs. closed stoma was similar in terms of disease-specific quality of life (total score of the Inflammatory Bowel Disease Quality of Life questionnaire), psychological distress (total score of the Hospital Anxiety and Depression Scale), and stress at work (effort-reward-imbalance ratio), with the exception of a higher Posttraumatic Diagnostic Scale total score in patient with vs. without stoma. Compared to IBD patients without stoma, the adverse impact on working capacity in overall stoma IBD patients appeared to be modest. However we observe a significantly higher reduction in working capacity in permanent vs. closed stoma in CD but not UC patients. CONCLUSION: As to be expected, IBD patients may benefit from closed and permanent stoma application. Stoma surgery appears to only modestly impact working capacity. Importantly, stoma surgery was not associated with adverse psychological outcomes, with comparable psychological well-being regardless of presence and type of stoma.