Angers Hospital Research Articles

How to optimise the use of psychotropic drugs in the elderly? Focus groups in a geriatric unit

The elderly person (EP) treated with psychotropics is at risk of iatropathology. The guidelines for the proper use of these treatments are difficult to apply and the difficulties met by hospital teams are little described in the literature. Our objective was to investigate the problem of psychotropic management in EP among the medical and care teams. Three focus groups were run consecutively in 2021 with the geriatric team at Angers Hospital, France, to highlight the difficulties met daily and to bring innovative solutions. Following a thematic analysis of the content, 10 themes were described, including 4 emerging. These 4 themes are a greater precision of the conditional prescriptions of psychotropics, the choice of the moment of administration, the route of administration in case of agitation, and the revaluation during and after hospitalization management. Among the solutions mentioned, some will be gradually implemented according to a prioritization matrix as an awareness of teams to behavioral disorders and their management, or the development of teleconsultation to check the re-evaluation of prescriptions.

R-DHA-oxaliplatin (R-DHAOx) versus R-DHA-cisplatin (R-DHAP) regimen in B-cell lymphoma treatment: A eight-year trajectory study.

The R-DHAP regimen (rituximab, cisplatin, dexamethasone, and high-dose cytarabine) is standardly used to treat relapsed Non-Hodgkin lymphoma (NHL). Despite scarce data, cisplatin is frequently substituted with oxaliplatin (R-DHAOx) to avoid nephrotoxicity. We compared nephrotoxicity of cisplatin and oxaliplatin based on creatinine-based trajectory modeling. All patients with NHL treated by R-DHAP or R-DHAOx in Angers hospital between January 01, 2007, and December 31, 2014, were included. Patients received cisplatin 100mg/m2 or oxaliplatin 130mg/m2 (d1) with cytarabine (2000mg/m2 , two doses, d2), dexamethasone (40mg, d1-4), and rituximab (375mg/m2 , d1). Creatinine levels were recorded before each cycle. Individual profiles of trajectories were clustered to detect homogeneous patterns of evolution. Twenty-two patients received R-DHAP, 35 R-DHAOx, 6 switched from R-DHAP to R-DHAOx due to nephrotoxicity. Characteristics of patients were similar between two groups. Patients receiving R-DHAP experienced more severe renal injury than patients receiving R-DHAOx (68% vs. 7.7%, P<.001). Two homogeneous clusters appeared: cluster A, with a majority of R-DHAOx (32, 91.4%), was less nephrotoxic than B, with a majority of R-DHAP (19, 86.4%), with a decreased average serum creatinine level (P<.0001). There were no other differences between clusters. Our study confirms that R-DHAOx regimen causes less nephrotoxicity than R-DHAP regimen.

L’immunohistochimie (clone VE1) est une méthode économique, spécifique et sensible pour détecter la présence d’une mutation BRAFV600E dans le mélanome

Determination of BRAF mutation status is mandatory in the management of patients with inoperable stage IIIC or stage IV melanoma. Currently, molecular biology (MB) has been validated for detecting the presence of BRAF mutations. To compare the sensitivity, specificity and cost of immunohistochemistry (IHC) (clone VE1) versus BM methods (qPCR and Sanger sequencing). All the samples for which BRAF mutation status was requested between March 2013 and February 2015 at the cellular and molecular analysis laboratory of the Angers Hospital were included retrospectively and consecutively. The IHC (clone VE1) and BM analyses were performed with the same formalin-fixed paraffin embedded tumour samples. The cost of these two methods was determined on the basis of the cost for the French Health Insurance. Two hundred and seven samples were subjected to a determination of BRAF mutational status in IHC and BM. Only one sample was discordant between these two methods (positive in IHC, negative in BM). The sensitivity and specificity of the IHC was 100% and 99.25% respectively. The ratio of the cost of IHC/BM testing was 1:2.1. IHC (clone VE1) is a specific, sensitive and economic method for determining BRAFV600E mutation status. Nevertheless, this method must be validated in order to be integrated into a decisional algorithm, alongside BM methods, to determine whether targeted BRAF-inhibitor therapy is indicated.

Relationship Between the Expression of O6-Methylguanine-DNA Methyltransferase (MGMT) and p53, and the Clinical Response in Metastatic Pancreatic Adenocarcinoma Treated with FOLFIRINOX.

To date, no predictive biomarker for the efficacy of FOLFIRINOX in metastatic pancreatic adenocarcinoma has been demonstrated. Deficiency in O6-methylguanine-DNA methyltransferase (MGMT) has been associated with a therapeutic response in endocrine tumors of the pancreas and the lack of expression of protein 53 (p53) could interfere with the action of MGMT. The aim of our study was to assess the prevalence of MGMT and p53 in patients with metastatic pancreatic adenocarcinoma treated with FOLFIRINOX as a first-line treatment and to investigate their association with therapeutic response and survival. The immunohistochemical expression of MGMT was recorded as present or absent and the expression of p53 was semi-quantitatively scored in 30 patients with metastatic pancreatic adenocarcinoma, at Angers Hospital in France between September 2011 and June 2015. Clinical and radiologic data were collected retrospectively. The presence or absence of MGMT expression entailed no significant differences in response rate. Median values of progression-free survival (PFS) and overall survival (OS) were lower in patients with MGMT expression, but sample size is too small to conclude that there is a statistically significant difference. No significant relationship for response rate and PFS was observed in relation with p53 expression. By contrast, patients with a strong tumor expression of p53 had a significantly lower OS compared to patients with no or weak expression of the protein (p=0.027). There was a positive correlation between the expression of p53 and MGMT (p=0.08). These preliminary findings suggest that for patients treated with FOLFIRINOX as a first-line treatment for metastatic pancreatic adenocarcinoma, the immunohistochemical evaluation of MGMT could not predict the clinical outcome; however, the survival was not significant probably because of the under-powered study (due to small sample size). A strong tumor expression of p53 is associated with a poor prognosis of OS.

0077 : Long-term clinical outcomes of patients having a chest pain negative evaluation in a dedicated Chest Pain Unit (CPU): Angers Hospital 3 year-experience

Chest pain is still one of the most frequent symptom in emergency department today. Chest pain units (CPU) have been developed to provide standardized care and rapid diagnosis, but few data exist in France about such structures. To assess the prognosis of patients having chest pain without final diagnosis at the term of CPU evaluation. Between January 2010 and December 2012, 1374 patients were admitted for non-traumatic chest pain in Angers Hospital CPU and analysed retrospectively. Clinical characteristics, final diagnosis and functional tests performed were noted. Primary outcome was major cardiac events (cardiovascular death or STEMI) occurring during the first year of follow-up. MACCEs, chest pain recurrence and rehospitalizations during long-term follow-up were analysed as secondary endpoints. 250 patients (18.2%) displayed an acute coronary syndrome and 678 (49.3%) had chest pain without final established diagnosis. Among them, only 1 patient displays a major cardiac event (cardiovascular death) < 1 year after CPU discharge. 11 cardiovascular deaths (1.8%) and 37 MACCEs (5.9%) were numbered during follow-up (median time=3.6 years [2.79; 4.25]). Recurrent chest pain was frequent (34.3%) but was not predictive of MACCEs. CPU evaluation is safe to rule out correctly acute coronary syndrome and patients presenting a negative evaluation display a low rate of major cardiac events. Further prospective studies are needed to support these preliminary results. The author hereby declares no conflict of interest

Staff accreditation in parenteral nutrition production in hospital pharmacy

This work aims to provide staff accreditation methodology to harmonize and secure practices for parenteral nutrition bags preparation. The methodology used in the present study is inspired from project management and quality approach. Existing training supports were used to produce accreditation procedure and evaluation supports. We first defined abilities levels, from level 1, corresponding to accredited learning agent to level 3, corresponding to expert accredited agent. Elements assessed for accreditation are: clothing assessment either by practices audit or by microbiologic test, test bags preparation and handling assessment, bag production to assess aseptic filling for both manual or automatized method, practices audit, number of days of production, and non-conformity following. At Angers Hospital, in 2014, production staff is composed of 12 agents. Staff accreditation reveals that 2 agents achieve level 3, 8 agents achieve level 2 and 2 agents are level 1. We noted that non-conformity decreased as accreditation took place from 81 in 2009 to 0 in 2014. To date, there is no incident due to parenteral bag produced by Angers hospital for neonatal resuscitation children. Such a consistent study is essential to insure a secured nutrition parenteral production. This also provides a satisfying quality care for patients.

R-DHA-Oxaliplatin Versus R-DHA-Cisplatin Regimen in B-Cell Nhl's Treatment: A Eight Years Retrospective Study

Background: R-DHAP regimen (rituximab, cisplatin, dexamethasone, high dose cytarabine) based on the 1988 Velasquez's study is a standard scheme used to treat relapsed Non-Hodgkin lymphomas (NHL). Cisplatin is frequently substituted with oxaliplatin to avoid nephrotoxicity, resulting in R-DHAX that is currently prescribed in first or second line treatment for aggressive NHL. However data are scarce. We compared the nephrotoxicity of cisplatine to oxaliplatine in R-DHA-platinum in this setting.Methods: All consecutive patients with NHL treated by R-DHAP or R-DHAX in Angers hospital between the 1st January 2007 and the 31th December 2014 were included. Either cisplatin 100 mg/m2 during 24 hours (R-DHAP) or oxaliplatin 130 mg/m2 during 2 hours (R-DHAX) were associated at d1 with cytarabine (2000 mg/m2 during 3 hours, two doses, d 2), dexamethasone (40 mg, d 1-4) and rituximab (375mg/m2, d 1) (Details on table 1). Cisplatin dosage were reduced from 25% to 50% according to individual renal tolerance. Up to 6 courses were delivered. Serum creatinine was recorded before each course of chemotherapy and was checked between d3 and d15 after administration, allowing to trace individual profiles of trajectories for their levels. These trajectories were clusterized in order to detect the existence of homogeneous patterns of evolution. This is a classical, semiparametric group-based statistical approach (Ref 1). Concomitant nephrotoxic drugs and events (sepsis…) were recorded to identify potential bias.Results: 21 patients received R-DHAP and 32 received R-DHAX. 6 patients switched from R-DHAP to R-DHAX due to nephrotoxicity. 2 different homogeneous clusters appeared. Cluster A included a majority of R-DHAX: 31 R-DHAX (88.6%), 3 R-DHAP (8.6%), 1 R-DHAP who changed to R-DHAX (2.9%). Cluster B contained a majority of R-DHAP: 11 R-DHAP (64.7%), 1 R-DHAX (5.9%), 5 R-DHAP to R-DHAX (29.4%) (p = 7.5.10-9). Cluster A graphic profile appeared less toxic than cluster B according to average serum creatinine level (mean cluster A: 70.2 µmol/L; mean cluster B: 99.5 µmol/L (p = 2.2.10-16)). Patients treated with R-DHAP experienced more severe renal failure than patients treated with R-DHAX (Chi-square test: p = 2.9.10-8, table 2). Nephrotoxic concomitant treatments have no significant discriminant effect. No differences were observed between either R-DHAP versus R-DHAX or cluster A versus B patients, as regards to age, sex, malnutrition status, histology, stage of the lymphoma, performans status, comorbidities including renal comorbidities and the history of nephrotoxic therapy. No significant difference was shown in OS and EFS (respectively, p = 0.463 and p = 0.290).Conclusions: Although R-DHAX is now widely used in NHL treatment, our study is one of the first to evaluate efficacy and renal tolerance of this treatment. R-DHAX nephrotoxicity is not significant whereas most patients receiving R-DHAP had significant acute renal impairment. We found no difference as regards to survival. A prospective study should compare these schedules in NHL to adapt future practices and improve morbidity.Table 1Patients characteristicsCaractéristicsDHAPDHAXTotalSexM14 (66.7%)23 (71.9%)37 (69.8%)F7 (33.3%)9 (28.1%)16 (30.2%)Age (years)Median (min-max)61 (34-80)61 (39-77)61 (34-80)BMI< 1800018 to 259 (42.9%)17 (53.1%)26 (49.1%)> 2512 (57.1%)15 (46.9%)27 (50.9%)Performans Status (N=49)PS > = 23 (17.6%)2 (6.3%)5 (10.2%)PS < 214 (82.4%)30 (93.8%)44 (89.8%)ComorbiditiesRenal1 (4.8%)3 (9.4%)4 (7.5%)Cardiovascular8 (38.1%)13 (40.6%)21 (39.6%)Other12 (57.1%)16 (50%)28 (52.8%)More than 2 comorbidities6 (28.6%)9 (28.1%)15 (28.3%)HistologieNHL low grade5 (23.8%)5 (15.6%)10 (18.9%)NHL High grade15 (71.4%)25 (78.1%)40 (75.5%)CLL1 (4.8%)2 (6.3%)3 (5.6%)Ann Arbor StageI000II2 (9.5%)2 (6.3%)4 (7.5%)III2 (9.5%)2 (6.3%)4 (7.5%)IV16 (76.2%)26 (81.3%)42 (79.2%)Previous chemotherapyNephrotoxic2 (9.5%)3 (9.3%)5 (9.4%)Non nephrotoxic17 (80.9%)21 (65.6%)38 (71.7%)Albumine blood level< = 305 (23.8%)5 (15.6%)10 (18.9%)LDH> N11 (52.4%)12 (37.5%)23 (43.4%)Total213253Table 2Renal Failures gradeR-DHAPR-DHAXNo renal failure13 (27.7%)100 (74.6%)Renal Failure34 (72.3%)34 (25.4%)(Reference 1: Group-based trajectory modeling in clinical research, Nagin et al. Annu Rev Clin Psychol. 2010) DisclosuresNo relevant conflicts of interest to declare.

Home-based urinary HPV DNA testing in women who do not attend cervical cancer screening clinics

In France, cervical cancer screening is currently based on cytological examination of a Pap smear for women aged 25 to 65, but screening coverage is unsatisfactory. Previous studies have shown that self-sampling for human papillomavirus (HPV) testing increases rates of compliance. With this purpose in mind, we performed the CapU study to evaluate the acceptance of a urinary HPV test. Letters proposing a new cervical cancer screening method using at-home urine self-sampling were sent to 5000 women aged 40-65 years who had not had a Pap smear over the past three years. The participating patients had to send their urine samples to the Angers Hospital Virology Laboratory for analysis using real-time PCR. Of the 771 samples received, 687 were analyzed. High-risk HPV were detected in 29 women. In follow-up, 28 women with positive urinary HPV results had a Pap smear or colposcopy done. The cytological results showed nine abnormal Pap smears, among which histology studies confirmed three cases of cervical intraepithelial neoplasia grade III lesions. Our study shows that urinary HPV testing may be pertinent to women who do not have cervical Pap smears done and lead to the diagnosis of high-grade cervical lesions.

O42: Two case-reports of intoxication with T61®, a mixture used in veterinary medecine

T61® is a mixture of three compounds (embutramide 200 mg/ml, mebezonium iodide 50 mg/ml and tetracaine 5 mg/ml) solubilised in N, N-dimethylformamide and commonly used for euthanasia of animals because of its narcotic and curariform-like activities. Unfortunately, T61® has been also involved in suicide or suicide attempts. A mother, veterinary assistant, injected T61® by intravenous route to her 7-year old child, together with ketamine (Clorketam®). She also explained that then she administered by herself T61® by oral and/or intramuscular route(s). A neighbour found the mother into status of epilepticus and the child presenting a cardiac-respiratory arrest. They were admitted to the emergency department of Angers's hospital 6-hours later and blood samples were collected. Chromatographic analyses (LC-UV/DAD and GC-MS) were performed on blood samples and a liquid contained in the bottle found near the bodies. Plasma embutramide concentrations were 2,5 mg/L for the mother and 5,0 mg/L for the child. Ketamine and norketamine were also found, in the blood of the child at 0.55 and 0,9 mg/L, respectively. The liquid contained embutramide (160 mg/L) and tetracaine, which is consistent with the hypothesis of using T61®, even if mebezonium was not visible with our method. On the admission, the child presented a cerebral oedema, bilateral papillary mydriasis fixed to light, lactic acidosis, then she was brain dead 10h later. The mother waked out from the coma and the administration of N-acetylcysteine was continued to counteract the hepatic side effects of N, N-dimethylformamide as she presented cytolytic hepatits (PT of 29%) 3 days after her admission. Eight fatal case-reports were described, mainly after intravenous injection of T61® (or Tanax®) and the postmortem blood concentrations of embutramide were ranging from 3 to 90 mg/L. Our case-report was the first described for a child, with a concentration of 5 mg/L. The simultaneous presence of ketamine and embutramide associated with mebezonium could have contributed to her death. The mother survived probably because she would have administered T61® by extravascular route, hence lowering the drug exposition.

Effectiveness of three treatment strategies on occupational limitations and quality of life for patients with non-specific chronic low back pain: Is a multidisciplinary approach the key feature to success: study protocol for a randomized controlled trial.

BackgroundChronic low back pain (cLBP) is a significant public health problem, being the primary cause of work absenteeism, as well as affecting sufferers’ quality of life, in industrialized society. International guidelines recommend intensive multidisciplinary approaches for patients with cLBP. However, these costly and time-consuming programs can only be offered to a minority of the most heavily affected patients and therefore do not seem likely to respond to public health requirements. Lighter programs may be an alternative to full time hospital-based programs with valuable results in terms of disability and occupational activity for cLBP patients. It is therefore important to define both what the determining components of management to improve activity restriction are and how to treat a larger number of patients more effectively at a lower cost. The aim of this study is to compare three programs with various levels of intensity and multidisciplinary.Methods/DesignThis paper describes the protocol for a prospective, randomized, controlled, clinical trial in working aged patients with cLBP. Three treatment strategies are compared: (1) intensive and multidisciplinary program conducted in a rehabilitation center; (2) less intensive outpatient program conducted by a private physiotherapist; (3) mixed strategy combining the same out program with a multidisciplinary intervention. The primary outcome of the trial is the impact of the mixed strategy on being able to work compared to hospital centered-program and out program. The secondary outcome is the impact of the mixed strategy on quality of life and social ability compared to the two others programs. The intervention part of the trial programs will take 5 weeks and observational follow-up will take 12 months. The sample size will be 180 participants (60 for each arm). The project has been approved by the Ethical Committee of Angers Hospital, France.DiscussionOn the hypothesis that a multidisciplinary approach is the key feature to programs success in reducing social and occupational impairment in cLBP patients, we suggest that it is possible to achieve the same results with less intensive strategies if a multidisciplinary approach is maintained.Trial registrationCurrent Controlled Trials NCT02030171.

Beyond to pattern of risk factors in elderly subjects

Most falls in the elderly result from an interaction between several risk factors in. Interventions targeting risk factors for a fall have been effective in the prevention of falls. The aim of this prospective study was to identify pattern of risk factors in hospitalized elderly subjects for fall in a geriatric acute care unit. over a 5-year period, 471 patients hospitalized in the geriatric unit of Angers Hospital following a fall were randomly assigned to 471 patients without any fall history. The prevalence of risk factors for a fall, and the existence of predisposing and precipitating factors were compared between the two groups. risk factors for fall, namely gait unsteadiness, hip disorders, peripheral neuropathy, convulsions and syncope, were significantly more prevalent in the group of fallers compared to the controls. Two faller patterns were proposed: (1) patients with depression and receiving benzodiazepine and neuroleptic, and (2) patients with poor vision and osteoarticular disorders. Two further factors, namely parkinsonism and foot disorders, seemed to be sufficient to explain a fall. this study for the first time has identified risk factors patterns of fall in elderly patients hospitalized in a geriatric acute care unit, which can be used to implement diagnosis and treatment strategies.

Mastering the allergen risk in chidren nutrition, the Manoe project

Regulatory agencies have enforced allergen labelling rules for food ingredients on pre-packed food. HACCP procedures driven on by food manufacturers reveals that possible cross-contaminations of their products cannot be absolutely discarded or checked. As a result and because allergen absence cannot be accurately warranted in most food industry, numerous warning mentions on pre-packed foods appeared to inform allergic consumers of potential cross contaminations even if levels are very low. For Allergic consumers, accessibility to food is clearly restricted. In a practical view, the Unit of Allergology in Angers Hospital (France) has developed an oral reintroduction protocol of low doses of allergens to evaluate the sensitivity of allergic patients. It appeared that most of the patients tolerate low amount (few mg) of allergen and would support the consumption of product contaminated by traces of allergen. Based on these facts, the French competitiveness cluster Pole Enfant gathered four food manufacturers (pastry, meat, milk products: BRIOCHE PASQUIER, CHARAL, LACTALIS, SADAC), ATLANGENE®-SILLIKER specialized in food analysis, ten university hospitals and hospitals, 3 academic laboratories (INRA, CNRS, and AUDENCIA), and an association of French allergic consumers (AFPRAL) to construct the MANOE project. This project funded by the regional council of Pays de la Loire aims to develop food products designed for the general population which would be tolerated by children allergic to peanut, egg, milk or wheat. In a large multicentric clinical trial, 400 allergic children will be submitted to the standardized reintroduction protocol. The acceptance and the usefulness of these new products by allergic children and their parents will be evaluated. In the context where thresholds values for allergen labelling rules are in discussion all around the world, this integrated project will provide a practical insight on how food companies will deal with thresholds, if the analytical methods are good enough to guaranty these levels, and how the patient will use this new information.

Information prénatale sur l’allaitement maternel : enquête en Pays de Loire

The main aim of this study was to evaluate how well expectant mothers were informed on breastfeeding by healthcare professionals. The secondary objective was to determine the factors associated with the initiation of breastfeeding. The survey was conducted in a group of 500 women who had delivered at the Angers Hospital (France), based on a questionnaire filled out by the postpartum women during their hospital stay. The rate of breastfeeding was 61.2%. More than a quarter (26.9%) of the women did not receive any prenatal breastfeeding information. The survey showed that 77.8% of the women had been informed of breastfeeding advantages for infants and 51.5% of breastfeeding advantages for themselves. Only 27.5% had received the advice of exclusive breastfeeding for 6months. Only 5.2% had been informed of the uselessness of breast preparation during pregnancy and a minority had been informed of correct and incorrect breastfeeding contraindications. Only 15.4% of fathers had been involved in a discussion on infant feeding practices during prenatal consultations. Only 4.8% of the women had come to prenatal classes on breastfeeding with a relative. The maternal factors positively associated with breastfeeding initiation were age between 25 and 34 years, non-French origin, a high socioeconomic status, being married, having been breastfed, and having previous experience with breastfeeding. Breastfeeding initiation was negatively associated with maternal smoking. All the factors concerning prenatal breastfeeding information in women were associated with the choice of breastfeeding. This study pointed out the populations at risk of not breastfeeding. Breastfeeding information given to pregnant women by healthcare professionals may influence them on whether or not they choose to breastfeed their newborn. However, this survey showed that women are insufficiently informed on prenatal breastfeeding. Therefore, prenatal breastfeeding information should be improved.

Evalutaion de l'interet de la recherche des papillomavirus humains (HPV) dans le depistage des lesions precancereuses et cancereuses du col de l'uterus

In France, cervical cancer screening is currently based on cytological examination of a Pap smear for women aged 25 to 65, but screening coverage is unsatisfactory. Previous studies have shown that self-sampling for human papillomavirus (HPV) testing increases rates of compliance. With this purpose in mind, we performed the CapU study to evaluate the acceptance of a urinary HPV test. Letters proposing a new cervical cancer screening method using at-home urine self-sampling were sent to 5000 women aged 40–65 years who had not had a Pap smear over the past three years. The participating patients had to send their urine samples to the Angers Hospital Virology Laboratory for analysis using real-time PCR. Of the 771 samples received, 687 were analyzed. High-risk HPV were detected in 29 women. In follow-up, 28 women with positive urinary HPV results had a Pap smear or colposcopy done. The cytological results showed nine abnormal Pap smears, among which histology studies confirmed three cases of cervical intraepithelial neoplasia grade III lesions. Our study shows that urinary HPV testing may be pertinent to women who do not have cervical Pap smears done and lead to the diagnosis of high-grade cervical lesions.