RIP140 regulates transcription factor HES1 oscillatory expression and mitogenic activity in colon cancer cells.

The transcription factor receptor-interacting protein 140 (RIP140) regulates intestinal homeostasis and tumorigenesis through Wnt signaling. In this study, we investigated its effect on the Notch/HES1 signaling pathway. In colorectal cancer (CRC) cell lines, RIP140 positively regulated HES1 gene expression at the transcriptional level via a recombining binding protein suppressor of hairless (RBPJ)/neurogenic locus notch homolog protein 1 (NICD)-mediated mechanism. In support of these in vitro data, RIP140 and HES1 expression significantly correlated in mouse intestine and in a cohort of CRC samples, thus supporting the positive regulation of HES1 gene expression by RIP140. Interestingly, when the Notch pathway is fully activated, RIP140 exerted a strong inhibition of HES1 gene transcription controlled by the level of HES1 itself. Moreover, RIP140 directly interacts with HES1 and reversed its mitogenic activity in human CRC cells. In line with this observation, HES1 levels were associated with a better patient survival only when tumors expressed high levels of RIP140. Our data identify RIP140 as a key regulator of the Notch/HES1 signaling pathway, with a dual effect on HES1 gene expression at the transcriptional level and a strong impact on colon cancer cell proliferation.

Endoscopic management of esophageal mucosal bridges in children with esophageal atresia.

BACKGROUND AND STUDY AIMS: Esophageal mucosal bridge (EMB) may be diagnosed at the anastomotic site in children operated on for esophageal atresia (EA) but so far only a few cases (n = 4) have been reported. This study aimed to characterize EMB in children with EA, risk factors, and treatment. PATIENTS AND METHODS: This retrospective multicenter study recorded patient's characteristics, EMB diagnosis circumstances, endoscopic management, follow-up, and EMB recurrence in children with EA aged less than 18 years, compared with paired EA patients without EMB. RESULTS: Thirty patients were included (60% male, 90% EA/tracheoesophageal fistula, 43% associated malformations). Compared to 44 paired controls, EMB was associated with a history of nasogastric tube feeding (31% vs. 9.1%, p = 0.02) and severe gastroesophageal reflux disease (history of fundoplication: 41.4% vs. 13.6%, p < 0.01). 77% had symptoms (food impaction and/or dysphagia). Endoscopic management was performed in 53% of patients (83% electrocoagulation) with no technical difficulties or complications. 80% of the symptomatic patients with EMB improved after endoscopic treatment, independently of anastomotic stricture dilatation or not. CONCLUSION: EMB endoscopic management by electrocoagulation is safe and often leads to symptom improvement.

Evaluation of vaccination coverage in heart failure patients in a tertiary center.

Background: Despite current recommendation, vaccination coverage (VC) for patients with heart failure (HF) remains far too limited. Aims: To evaluate the VC of HF patients followed in our hospital center and investigate the barriers to vaccination and the ways to address them. Methods: This was a cross-sectional monocentric descriptive study conducted between December 2019 and January 2021 at the University Hospital of Montpellier, France. Patients with HF history hospitalized in cardiology unit (CU) and patients in a HF telemonitoring program (TP) were included. An interview was conducted by a pharmacist to find out the patient's vaccination status against influenza and pneumococcus. For non-vaccinated patients, opinion and willingness to be vaccinated were also obtained. Results: Data from 335 patients were collected (185 in CU, 150 in TP). The mean age was 69.3 years and the proportion of males was 72%. About 65% were vaccinated against influenza in the last year (60% in CU, 72% in TP, p = 0.022) and 22% were up to date with pneumococcal vaccination (11% in CU, 35% in TP, p < 0.001). Among patients not vaccinated, 17% refused vaccination. Among unvaccinated patients who consider vaccination, 69% wanted to be vaccinated by their general practitioner (GP). Conclusions: The VC of HF patients remains insufficient. Patients in TP are more vaccinated than patients in CU, which could involve better management. The low rate of vaccinated patients is mainly explained by a lack of awareness. The medical team, including the clinical pharmacist by his dedicated time during medication reconciliation may play a major role in the management of hospitalized patients as well as GP's as local actors.

Nutritional status at age 1 year in patients born with esophageal atresia: A population-based, prospective cohort study.

Objective: Despite recent progress in caring for patients born with esophageal atresia (EA), undernutrition and stunting remain common. Our study objective was to assess nutritional status in the first year after birth with EA and to identify factors associated with growth failure. Study design: We conducted a population-based study of all infants born in France with EA between 2010 and 2016. Through the national EA register, we collected prenatal to 1 year follow-up data. We used body mass index and length-for-age ratio Z scores to define patients who were undernourished and stunted, respectively. Factors with P < 0.20 in univariate analyses were retained in a logistic regression model. Results: Among 1,154 patients born with EA, body mass index and length-for-age ratio Z scores at 1 year were available for about 61%. Among these, 15.2% were undernourished and 19% were stunted at the age of 1 year. There was no significant catch-up between ages 6 months and 1 year. Patients born preterm (41%), small for gestational age (17%), or with associated abnormalities (55%) were at higher risk of undernutrition and stunting at age 1 year (P < 0.05). Neither EA type nor surgical treatment was associated with growth failure. Conclusion: Undernutrition and stunting are common during the first year after birth in patients born with EA. These outcomes are significantly influenced by early factors, regardless of EA type or surgical management. Identifying high-risk patient groups with EA (i.e., those born preterm, small for gestational age, and/or with associated abnormalities) may guide early nutritional support strategies.

RIP140 regulates POLK gene expression and the response to alkylating drugs in colon cancer cells.

Aim: The transcription factor RIP140 (receptor interacting protein of 140 kDa) is involved in intestinal tumorigenesis. It plays a role in the control of microsatellite instability (MSI), through the regulation of MSH2 and MSH6 gene expression. The aim of this study was to explore its effect on the expression of POLK, the gene encoding the specialized translesion synthesis (TLS) DNA polymerase κ known to perform accurate DNA synthesis at microsatellites. Methods: Different mouse models and engineered human colorectal cancer (CRC) cell lines were used to analyze by RT-qPCR, while Western blotting and luciferase assays were used to elucidate the role of RIP140 on POLK gene expression. Published DNA microarray datasets were reanalyzed. The in vitro sensitivity of CRC cells to methyl methane sulfonate and cisplatin was determined. Results: RIP140 positively regulates, at the transcriptional level, the expression of the POLK gene, and this effect involves, at least partly, the p53 tumor suppressor. In different cohorts of CRC biopsies (with or without MSI), a strong positive correlation was observed between RIP140 and POLK gene expression. In connection with its effect on POLK levels and the TLS function of this polymerase, the cellular response to methyl methane sulfonate was increased in cells lacking the Rip140 gene. Finally, the association of RIP140 expression with better overall survival of CRC patients was observed only when the corresponding tumors exhibited low levels of POLK, thus strengthening the functional link between the two genes in human CRC. Conclusion: The regulation of POLK gene expression by RIP140 could thus contribute to the maintenance of microsatellite stability, and more generally to the control of genome integrity.

Comparison of Endoscopic Dilatation and Heller's Myotomy for Treating Esophageal Achalasia in Children: A Multicenter Study.

OBJECTIVE: To compare the efficacy of, and complications from, the 2 main treatments for achalasia: endoscopic dilatation and surgical cardiomyotomy (Heller's myotomy). STUDY DESIGN: We retrospectively collected data on children treated for achalasia over an 11-year period from 8 tertiary pediatric centers. A line of treatment was defined as performing either Heller's myotomy or 1-3 sessions of endoscopy dilatation over 3 months. Treatment success was a priori defined as clinical improvement and no need for new treatment. RESULTS: Ninety-seven children (median age, 12 years; 57% boys) were included. The median time to diagnosis was 10.5 months, and the median follow-up period was 27 months. Thirty-seven children were treated by Heller's myotomy and 60 by endoscopy dilatation as the first-line treatment. After adjustment for potentially confounding factors, Heller's myotomy was significantly more successful than endoscopy dilatation (hazard ratio, 3.93 [1.74; 8.88]; P = .001), with a median survival without failure of 49 and 7 months, respectively, and with no significant difference in the occurrence of complications (35.2% for Heller's myotomy, 29.7% for endoscopy dilatation, P = .56). Hydrostatic dilatation was as successful as pneumatic dilatation (hazard ratio, 1.35 [0.56; 3.23]; P = .50). CONCLUSIONS: Heller's myotomy is more successful than endoscopy dilatation, with no significant difference in the occurrence of serious complications. This raises the potential role of peroral endoscopic myotomy as an alternative treatment to Heller's myotomy.

Endoscopic Gastrojejunostomy in Infants and Children.

OBJECTIVE: To evaluate the feasibility of endoscopic gastrojejunal tube (GJT) placement in infants and children. STUDY DESIGN: All children undergoing endoscopic GJT placement between January 2010 and December 2019 were included in this single-center retrospective study. Difficulties with and failure of GJT placement, complication rates, and device longevity, efficacy, and duration were assessed. RESULTS: A total of 107 children, median age 10 months (IQR, 5.0-23.0 months) and median weight 6.6 kg (IQR, 5.3-9.5 kg), underwent endoscopic GJT placement using the gastric stoma to introduce the endoscope (one step: n = 36 of 107; 33.6%). Endoscopic placement was successful in 99%. Eight periprocedure complications occurred, including 1 pneumoperitoneum requiring exsufflation, 2 acute pulmonary hypertension episodes leading to death in 1 case, and 5 episodes of bronchospasm. Minor complications were frequent and mostly mechanical (79%), whereas major complications were rare (5.6%): intussusception (n = 4), intestinal perforation (n = 1), and pneumoperitoneum (n = 1). Ten patients died. Of the 97 patients who lived, 85 (87%) were weaned from jejunal feeding at a median of 179 days (IQR, 69-295 days) after initiation. Among them, 30 (35.2%) required fundoplication. Weight for age z-score was significantly higher at weaning. CONCLUSIONS: GJT placement is feasible in children, even low-weight infants. Complications are frequent but are mostly minor.

Feeding disorders in children with oesophageal atresia: a cross-sectional study.

INTRODUCTION: With advances in surgical and neonatal care, the survival of patients with oesophageal atresia (OA) has improved over time. Whereas a number of OA-related conditions (delayed primary anastomosis, anastomotic stricture and oesophageal dysmotility) may have an impact on feeding development and although children with OA experience several oral aversive events, paediatric feeding disorders (PFD) remain poorly described in this population. The primary aim of our study was to describe PFD in children born with OA, using a standardised scale. The secondary aim was to determine conditions associated with PFD. METHODS: The Feeding Disorders in Children with Oesophageal Atresia Study is a national cohort study based on the OA registry from the French National Network. Parents of children born with OA between 2013 and 2016 in one of the 22 participating centres were asked to complete the French version of the Montreal Children's Hospital Feeding Scale. RESULTS: Of the 248 eligible children, 145 children, with a median age of 2.3 years (Q1-Q3 1.8-2.9, min-max 1.1-4.0 years), were included. Sixty-one children (42%) developed PFD; 13% were tube-fed (n=19). Almost 40% of children with PFD failed to thrive (n=23). The presence of chronic respiratory symptoms was associated with the development of PFD. Ten children with PFD (16%) had no other condition or OA-related complication. CONCLUSION: PFD are common in children with OA, and there is no typical profile of patients at risk of PFD. Therefore, all children with OA require a systematic screening for PFD that could improve the care and outcomes of patients, especially in terms of growth.

Prevalence of acid gastroesophageal reflux disease in infants with esophageal atresia/tracheoesophageal fistula.

BACKGROUND: Given the high prevalence and complication risks of acid gastroesophageal reflux (GERD) in the first months of life in infants with esophageal atresia, the ESPGHAN/NASPGHAN consensus statement recommends systematic treatment with proton pump inhibitors (PPIs) until the age of 1 year and checking for acid GERD thereafter. However, these recommendations have not been evaluated. METHODS: This prospective study was conducted from 2007 to 2016. We evaluated the prevalence of acid GERD in 100 consecutive infants presenting with esophageal atresia/tracheoesophageal fistula after the age of 18 months when PPI treatment was stopped. The diagnosis of acid GERD was based on positive pH-metry and/or evidence of complications (e.g., peptic esophagitis, need for jejunal nutrition, or antireflux surgery). Those with acid GERD at a median age of 18 months received a control examination every year or adapted to their clinical situation. RESULTS: The prevalence rates of acid GERD were 64.3% at 18 months and 22.8% at the last follow-up (median age 65 months).There is no risk factor for acid GERD identified. CONCLUSIONS: This study shows a high prevalence of acid GERD in late infancy and supports the recommendation of systematic checking for acid GERD when treatment with PPI is stopped. IMPACT: Acid gastroesophageal reflux disease (GERD) is a frequent complication of esophageal atresia in infants. The ESPGHAN/NASPGHAN consensus, which is based on expert opinion, recommends systematic treatment of children with PPI until the age of 1 year. The prevalence rates of acid GERD were 64.3% at 18 months and 22.8% at the last follow-up. This study shows a high prevalence of acid GERD in late infancy and supports the recommendation of systematic checking for acid GERD when treatment with PPI is stopped.

Weaning children from prolonged enteral nutrition: A survey of practice on behalf of the French Society of Paediatric Gastroenterology, Hepatology, and Nutrition.

BACKGROUND: No consensus currently exists on tube-weaning practice worldwide. The aim of this study was to describe tube-weaning practice (indications and modalities) of a panel of pediatric gastroenterologists involved in the management of prolonged enteral nutrition (EN). METHODS: A cross-sectional survey of pediatric gastroenterologists involved in the management of children receiving prolonged (>3 months) EN who were likely to be weaned was conducted. A questionnaire containing 24 questions was disseminated to the French Speaking Group of Paediatric Gastroenterology, Hepatology, and Nutrition members. The association between weaning practice and the experience of respondents was investigated. RESULTS: In total, 311 professionals were approached, and 64 questionnaires were completed (response rate 21%). Nearly all respondents (n = 61, 95%) reported using individualized weaning programs. Weaning attempts were performed more frequently at home, and follow-up was performed in the outpatient clinic (97%) by progressive EN volume reduction (83%). Inpatient weaning was performed by only 28% of participants. The choice of the setting was predominantly (59%) based on parental request. Management and follow-up involved mainly the referring pediatric gastroenterologist and the dietitian. Fifty-one (80%) of the respondents experienced ≥1 weaning failure. CONCLUSIONS: This is one of only a few studies examining real-life pediatric tube-weaning practices. Considerable practice variation between centers was observed; some of the common practices included the setting of weaning (outpatient vs inpatient) and the eligibility criteria. Increasing knowledge about weaning modalities is the starting point for the design of consensual standardized programs.

Prevalence of and Risk Factors for Sagittal Posture Abnormalities in Children Born With Esophageal Atresia: A Prospective Cohort Study.

Introduction: Scoliosis is a well-described complication of esophageal atresia (EA) caused by the associated spine malformations and/or thoracotomy. However, the sagittal posture abnormalities in patients with EA have not been described. The aim of this study was to evaluate the prevalence of and risk factors for sagittal posture abnormalities at the age of 6 years in patients operated on for EA. Methods: A prospective cohort of 123 patients with EA was examined by the same rehabilitation doctor at the time of a multidisciplinary visit scheduled at the age of 6 years. Children presenting with scoliosis (n = 4) or who missed the consultation (n = 33) were excluded. Univariate and multivariate logistic regression models with Firth's penalized-likelihood approach were used to identify risk factors associated with sagittal posture anomalies. Candidate risk factors included neonatal characteristics, associated malformations, atresia type, postoperative complications, psychomotor development retardation, orthopedic abnormalities, and neurological hypotonia. Results: The prevalence rates of sagittal posture abnormalities were 25.6% (n = 22; 95% CI, 16.7-36.1%). Multivariate analysis showed that minor orthopedic abnormalities (OR: 4.02, 95% CI: 1.29-13.43, P = 0.021), and VACTERL (OR: 3.35, 95% CI: 1.09-10.71, P = 0.042) were significant risk factors for sagittal posture abnormalities. Conclusion: This study shows that sagittal posture anomalies occur frequently in children operated on at birth for EA and are not directly linked to the surgical repair. These children should be screened and treated using postural physiotherapy, especially those with VACTERL and minor orthopedic abnormalities.

Compliance with Prescription Guidelines for Glucose-Lowering Therapies According to Renal Function: Real-Life Study in Inpatients of Internal Medicine, Endocrinology and Cardiology Units.

Background and objectives: Renal failure is a contraindication for some glucose-lowering drugs and requires dosage adjustment for others, particularly biguanides, sulfonylureas, and inhibitors of dipeptidyl peptidase 4. In this study, we assessed adherence to prescription recommendations for glucose-lowering drugs according to renal function in hospitalized diabetic subjects. Materials and Methods: This prospective cohort study was carried out over a 2-year period in a university hospital. Glomerular filtration rate (GFR) was determined by averaging all measurements performed during hospitalization. Glucose-lowering drug dosages were analyzed according to the recommendations of the relevant medical societies. Results: In total, 2071 diabetic patients (53% hospitalized in cardiology units) were examined. GFR was <30 mL/min/1.73 m2 in 13.4% of these patients, 30-44 in 15.1%, 45-60 in 18.3%, and >60 in 53.3%. Inappropriate oral glucose-lowering treatments were administered to 273 (13.2%) patients, including 53 (2.6%) with a contraindication. In cardiology units, 53.1% and 14.3% of patients had GFRs of <60 and <30 mL/min/1.73 m2, respectively, and 179 (15.4%) patients had a contraindication or were prescribed an excessive dose of glucose-lowering drugs. Conclusions: We showed that the burden of inappropriate prescriptions is high in diabetic patients. Given the high number of patients receiving these medications, particularly in cardiology units, a search for potential adverse effects related to these drugs should be performed.

Use of Hypnosis in Paediatric Gastrointestinal Endoscopy: A Pilot Study.

Objectives: Experience of hypnosis in gastrointestinal (GI) endoscopy is scarce in children. Our aims were to assess the rate of successful GI endoscopy performed using hypnosis alone or in combination with midazolam, with or without additional equimolar mixture of oxygen and nitrous oxide (EMONO), and to identify predictive factors of successful endoscopy in children. Methods: This prospective single-centre study included children older than 6 years requiring a diagnostic esophagogastroduodenoscopy (EGD) or rectosigmoidoscopy. Ericksonian hypnosis was performed alone or in combination with midazolam, with or without additional EMONO. Successful endoscopy was defined by a complete and well-tolerated procedure. Levels of satisfaction of the endoscopist, nurse, and patient were assessed. Results: One hundred forty children [70 boys, median age: 12 years (Q1-Q3: 9-14)] were included over a 14-month period. They underwent EGD in 51.4% (n = 72) and rectosigmoidoscopy in 48.6% (n = 68) of cases. EMONO and midazolam were combined with hypnosis in 136 cases (97.1%). Successful endoscopy rate reached 82.9%. The procedure was interrupted due to poor tolerance and was rescheduled under general anaesthesia in 11 patients (7.9%). Predictive factors for successful endoscopy were older age (13 vs. 8 years, OR: 1.34, CI 95% [1.10-1.62], p = 0.003) and type of endoscopy (EGD vs. rectosigmoidoscopy, OR: 16.34 [2.14-124.68], p = 0.007). A good cooperation of the patient was reported by the endoscopist and the nurse in 88.4 and 86.9% of cases, respectively. Ninety-two per cent of patients mentioned that the procedure went well. Conclusions: Our study suggests that hypnosis combined with EMONO and/or midazolam is of additional value to perform diagnostic EGD or rectosigmoidoscopy in children older than 6 years without systematic need for general anaesthesia.

A Truncated NRIP1 Mutant Amplifies Microsatellite Instability of Colorectal Cancer by Regulating MSH2/MSH6 Expression, and Is a Prognostic Marker of Stage III Tumors.

Microsatellite instability (MSI) is related to the alteration of mismatch repair (MMR) genes and plays a key role in colorectal cancer (CRC) pathogenesis. We previously reported that the transcription factor Nuclear Receptor Interacting Protein 1 (NRIP1) is involved in sporadic intestinal tumorigenesis. The aim of this study was to decipher its role in MSI CRC. By using different mouse models and engineered cell lines, we demonstrated that NRIP1 increased MSH2 and MSH6 MMR gene transcription and mRNA/protein levels. In human CRC cells, NRIP1 expression was associated with decreased MSI and the hypermutator phenotype, and with resistance to chemotherapy drugs. Using a cohort of 194 CRC patients, we detected in 22% of the cases a MSI-induced frameshift mutation in the NRIP1 coding sequence. This genetic alteration generates a truncated protein with a dominant negative activity that increased human CRC cell proliferation and impaired the regulation of MSH2 and MSH6 gene expression. Moreover, the NRIP1 mutant correlated with a decreased overall survival of patients with advanced CRC, especially when MLH1-deficient. By decreasing the expression of MSH2 and MSH6 gene expression, the NRIP1 variant may amplify MLH1-dependent CRC progression and behave as a new prognostic marker of advanced MSI CRC.

Impact of medication characteristics and adverse drug events on hospital admission after an emergency department visit: Prospective cohort study.

OBJECTIVES: Emergency department (ED) overcrowding is a problem for the delivery of adequate and timely emergency care. To improve patient flow and the admission process, the quick prediction of a patient's need for admission is crucial. We aimed to investigate the variables associated with hospitalisation after an ED visit, with a particular focus on the variables related to medication. METHODS: This prospective study was conducted from 2011 to 2018 in subacute medical ED of a French University Hospital. Specialised EDs (paediatric, gynaecologic, head and neck and psychiatric) and the outpatient unit of the ED were not included. Participation in this study was proposed to all adult patients who underwent a medication history interview with a pharmacist. Pharmacists conducted structured interviews for the completion of the medication history and the detection of adverse drug events (ADE). Relations between patient characteristics and hospitalisation were analysed using logistic regression. RESULTS: Among the 14 511 included patients, 5972 (41.2%) were hospitalised including 69 deaths. In total, 7458 patients (51.4%) took more than 5 medications and 2846 patients (19.6%) had an ADE detected during the ED visit. In hospitalised patients, bleeding (32.2%) and metabolic disorders (16.8%) were the most observed ADE symptoms. Variables associated with increased hospital admission included 2 demographic variables (age, male gender), 4 clinical variables (renal and hepatic failures, alcohol addiction, ED visit for respiratory reason) and 6 medication-related variables (medications >5, use of blood, systemic anti-infective, metabolism and antineoplastic/immunomodulating medications and ADE). CONCLUSION: We identified variables associated with hospitalisation including drug-related variables. These results point out the importance and the relevance of collecting medication data in a subacute medical ED (study registered on ClinicalTrials.gov, NCT03442010).

Medication Errors at Hospital Admission and Discharge: Risk Factors and Impact of Medication Reconciliation Process to Improve Healthcare.

OBJECTIVE: First, the aim of the study was to assess the prevalence, characteristics, and severity of unintended medication discrepancies (UMDs) and medication errors (MEs) at admission and discharge of hospitalization. Second, the aim of the study was to identify clinical and hospitalization factors associated with risk of UMDs as well as characteristics of the medication reconciliation process associated with UMDs detection. METHODS: This prospective observational study included all adult patients admitted from 2013 to 2015 in the Endocrinology-Diabetology-Nutrition Department of Montpellier Hospital, France. Clinical pharmacists conducted medication reconciliation by collecting the best possible medication history from different sources and comparing it with admission and discharge prescriptions to identify discrepancies. Unintended medication discrepancies corrected by the physician were considered as MEs. Risk factors of UMDs were identified with logistic regression. RESULTS: Of 904 patients included, 266 (29.4%) had at least one UMD, at admission or at discharge. In total, 378 (98.2%) of 385 UMDs were considered to be MEs. Most MEs were omissions (59.3%). Medication errors were serious or very serious in 36% of patients and had potentially moderate severity in almost 40% of patients. The risk of UMDs increased constantly with the number of treatments (P < 0.001). Thyroid (adjusted odds ratio [OR] = 1.79, 95% CI = 1.12-2.86) and infectious diseases (adjusted OR = 1.80, 95% CI = 1.17-2.78) were associated with UMDs risk at admission. The best type of source for the detection of UMDs was the general practitioner or nurse (OR = 2.64, 95% CI = 1.51-4.63). CONCLUSIONS: Unintended medication discrepancies are frequent at hospital and depend on intrinsic clinical parameters but also on practice of medication reconciliation process, such as number and type of sources used.

Clinical, Economic, and Organizational Impact of the Clinical Pharmacist in an Orthopedic and Trauma Surgery Department.

AIM: The aim of this study was to evaluate the clinical, economic, and organizational impact of clinical pharmacist services added to an adult orthopedic and trauma surgery unit in a university hospital. METHODS: This was a prospective, observational study performed from January to February 2017. All pharmacists' interventions were documented, and their clinical, economic, and organizational impact and the probability of adverse drug events (ADEs) were assessed using the clinical, economic and organizational scale three-dimensional scale. An expert panel composed of three clinical pharmacists, one surgeon and one anesthetist classified the pharmacist intervention. The potential clinical impact was determined through a consensus by the expert panel. Cost avoidance was calculated for serious ADEs with a major impact by avoiding an additional cost of €4912 per event and taking into account the probability of ADE occurrence. RESULTS: The pharmacists performed 1014 interventions for 28 days with a 95.3% acceptance rate by prescribers. Thirty-nine interventions were rated to have a major clinical impact (3.8%). The organizational impact was estimated favorable for 856 (84.4%) pharmacist interventions. Cost avoidance was estimated at €24,364, and the indirect costs benefit was estimated at €11,864 during the study. The cost-benefit ratio of the clinical pharmacist intervention was €1.94 in savings for every €1 invested. CONCLUSIONS: Clinical pharmacist services in an orthopedic and trauma surgery department have the potential to improve patient outcomes and avoid healthcare costs. Furthermore, the presence of a pharmacist in surgical units allows for communication between the unit and the pharmacy, which produces better fluidity and improves the quality of care.

Development and validation of a score to assess risk of medication errors detected during medication reconciliation process at admission in internal medicine unit: SCOREM study.

BACKGROUND: Medication errors (ME) can be reduced through preventive strategies such as medication reconciliation. Such strategies are often limited by human resources and need targeting high risk patients. AIMS: To develop a score to identify patients at risk of ME detected during medication reconciliation in a specific population from internal medicine unit. METHODS: Prospective observational study conducted in an internal medicine unit of a French University Hospital from 2012 to 2016. Adult hospitalised patients were eligible for inclusion. Medication reconciliation was conducted by a pharmacist and consisted in comparing medication history with admission prescription to identify MEs. Risk factors of MEs were analysed using multivariate stepwise logistic regression model. A risk score was constructed using the split-sample approach. The split was done at random (using a fixed seed) to define a development data set (N = 1256) and a validation sample (N = 628). A regression coefficient-base scoring system was used adopting the beta-Sullivan approach (Sullivan's scoring). RESULTS: Pharmacists detected 740 MEs in 368/1884 (19.5%) patients related to medication reconciliation. Female gender, number of treatments >7, admission from emergency department and during night or weekend were significantly associated with a higher risk of MEs. Risk score was constructed by attributing 1 or 2 points to these variables. Patients with a score ≥3 (OR [95% CI] 3.10 [1.15-8.37]) out of 5 (OR [95% CI] 8.11 [2.89-22.78]) were considered at high risk of MEs. CONCLUSIONS: Risk factors identified in our study may help prioritising patients admitted in internal medicine units who may benefit the most from medication reconciliation (ClinicalTrials.gov number NCT03422484).

Hypoglycemia While Driving in Insulin-Treated Patients: Incidence and Risk Factors.

OBJECTIVES: This study aimed to investigate a potential daily-life concern for patients with diabetes hypoglycemia while driving by (1) estimating their incidence in insulin-treated drivers, (2) determining factors associated with their occurrence, and (3) analyzing patients' behavior regarding prevention of hypoglycemia. METHODS: We conducted an observational study from November 2013 to May 2018 in the endocrinology-diabetology-nutrition department of our university hospital. All patients treated for diabetes older than 18 years admitted in the department were eligible. A specific questionnaire assessing attitudes, knowledge, and consequences of hypoglycemia was provided. In this study, only insulin-treated patients who regularly drive were analyzed. RESULTS: On the 233 insulin-treated drivers included, 45 (19%) self-reported at least 1 hypoglycemia while driving in the preceding year. Two factors were significantly associated with their occurrence: type 1 diabetes (odds ratio [OR] = 3.19; 95% confidence interval [CI] = 1.55-6.57) and experiences of asymptomatic hypoglycemia (OR = 2.20; 95% CI = 1.05-4.63). Awareness of the treatment hypoglycemia risk because of information provided by a medical specialist was also but nonsignificantly associated with hypoglycemia while driving (OR = 2.61; 95% CI = 0.86-7.92). Forty-one patients (18%) combined those 3 variables, 20 (49%) of them self-reported hypoglycemia while driving. Thirty-four percent of the patients never carried carbohydrates for hypoglycemia correction. Seventy-six percent do not monitor blood glucose level before driving. CONCLUSIONS: Our questionnaire allowed us to highlight that 19% our cohort of insulin-treated drivers declared experiencing hypoglycemia while driving. Risk factors identified and prevention data collected should help us better target patient education.

Adverse Drug Events Detected by Clinical Pharmacists in an Emergency Department: A Prospective Monocentric Observational Study.

OBJECTIVES: Adverse drug events (ADEs) are a major public health issue in hospitals. They are difficult to detect because of incomplete or unavailable medication history. In this study, we aimed to assess the rate and characteristics of ADEs identified by pharmacists in an emergency department (ED) to identify factors associated with ADEs. METHODS: In this prospective observational study, we included consecutive adult patients presenting to the ED of a French 2600-bed tertiary care university hospital from November 2011 to April 2015. Clinical pharmacists conducted structured interviews and collected the medication history to detect ADEs (i.e., injuries resulting directly or indirectly from adverse drug reactions and noncompliance to medication prescriptions). Unsure ADE cases were reviewed by an expert committee. Relations between patient characteristics, type of ED visit, and ADE risk were analyzed using logistic regression. RESULTS: Among the 8275 included patients, 1299 (15.7%) presented to the ED with an ADE. The major ADE symptoms were bleeding, endocrine problems, and neurologic disorders. Moreover, ADEs led to the ED visit, hospitalization, and death in 87%, 49.3%, and 2.2% of cases, respectively. Adverse drug event risk was independently associated with male sex, ED visit for neurological symptoms, visit to the ED critical care unit, or ED short stay hospitalization unit, use of blood, anti-infective, antineoplastic, and immunomodulating drugs. CONCLUSIONS: This study improves the knowledge about ADE characteristics and on the patients at risk of ADE. This could help ED teams to better identify and manage ADEs and to improve treatment quality and safety.