Standardized one-day evaluation before urinary reconstructive surgery for neurogenic lower urinary tract dysfunction: Feasibility and impact on surgical strategy and care pathway.

OBJECTIVES: To describe a concept of standardized preoperative one-day evaluation before urinary reconstructive or diversion surgery for the treatment of neurogenic lower urinary tract (LUT) dysfunction, and to evaluate its feasibility and its impact on the care pathway. MATERIALS AND METHODS: All patients who underwent a one-day standardized evaluation before a urinary reconstructive or derivation surgery for the treatment of neurogenic LUT dysfunction between January 2017 and December 2021 in our institution were included. Data were collected retrospectively from standardized reports. The main outcome was the rate of completion of the tests and consultations planned during this evaluation. Secondary outcomes included the findings from the one-day evaluation and changes in the urological surgical strategy at different time points within one year. RESULTS: One hundred and thirty-one patients benefited from this one-day standardized evaluation. The overall completeness rate of the data collected was 77.5%, increasing from 62.3% in 2017 to 89.3% in 2021. The urological surgical plan was modified for 19.1% of patients following this preoperative evaluation. The indication was then confirmed for 114 patients (87.0%) by the multidisciplinary meeting and was carried out unchanged during the following year for 89 patients (67.9%). An associated colostomy procedure was proposed for 18.3% of patients and was finally performed in 11.5%. CONCLUSION: A standardized multidisciplinary preoperative one-day evaluation before performing reconstructive or diversion surgery for the treatment of neurogenic LUT dysfunction seems feasible and makes it possible to optimize the surgical plan and adapt the course of care.

High genetic diversity and zoonotic potential of Staphylococcus aureus strains recovered from bovine intramammary infections in Colombians dairy herds.

Genotyping of Staphylococcus aureus isolated from mastitis has become a fundamental tool to understand its complex epidemiology and to evaluate spillover events. The aim of this study was to describe the frequency of genotypes of the S. aureus strains isolated from intramammary infections by spa typing technique, and to evaluate the association between genotypes and the ability to form biofilm under in vitro conditions. Sixty-six strains of S. aureus recovered from bovines intramammary infections on 56 dairy herds located in 14 municipalities of the department of Antioquia were characterized. The majority of strains (65/66) were isolated from milk samples collected from dairy cows with subclinical intramammary infections. Nineteen different spa types were found in this study, t521 (19.70%), t267 (15.15%), and t605 (12.12%) being the most frequent. The strains from the t605 spa type showed the highest biofilm production. The high frequency of spa types with zoonotic potential found in this study, identified cattle as an important reservoir of theses clones for people in close proximity, such as milkers and consumers of unpasteurized dairy products.

Delayed response to environmental conditions and infra-seasonal dynamics of the short-beaked common dolphin distribution.

Cetaceans adjust their distribution and abundance to encountered conditions across years and seasons, but we poorly understand such small-scale changes for many species, especially in winter. Crucial challenges confront some populations during this season, such as the high levels of fisheries-induced mortality faced by the common dolphin (Delphinus delphis) in the Northeast Atlantic shelves. For such species, understanding the winter fine-scale dynamics is crucial. We aimed to identify the dolphin distribution drivers during the winters of 2020 and 2021, with a focus on determining the lag between changes in oceanographic conditions and dolphin distribution. The changes were related to temporal delays specific to the nature and cascading effects that oceanographic processes had on the trophic chain. By determining the most important conditions and lags to dolphin distributions, we shed light on the poorly understood intrusions of dolphins within coastal waters during winter: they displayed a strong preference for the coastal-shelf waters front and extensively followed its spatial variations, with their overall densities increasing over the period and peaking in March-April. The results presented here provide invaluable information on the winter distribution dynamics and should inform management decisions to help reduce the unsustainable mortalities of this species in the by-catch of fisheries.

Safety of Inulin and Sinistrin: Combining Several Sources for Pharmacovigilance Purposes.

Introduction: Inulin and its analog sinistrin are fructose polymers used in the food and pharmaceutical industries. In 2018, The French National Agency for the Safety of Medicines and Health Products (ANSM) decided to withdraw products containing sinistrin and inulin due to several reports of serious hypersensitivity reactions, including a fatal outcome. Objective: To assess the safety of inulin and sinistrin use in France. Methods: We searched multiple sources to identify adverse reactions (ARs) to inulin or sinistrin: first, classical pharmacovigilance databases including the French Pharmacovigilance (FPVD) and the WHO Database (VigiBase); second, data from a clinical trial, MultiGFR; third, data regarding current use in an hospital. All potential ARs to inulin or sinistrin were analyzed with a focus on hypersensitivity reactions and relationships to batches of sinistrin. Results: From 1991 to 2018, 134 ARs to inulin or sinistrin were registered in the FPVD or VigiBase. Sixty-three cases (47%) were classified as serious, and 129 cases (96%) were hypersensitivity reactions. We found an association between a batch of sinistrin and the occurrence of hypersensitivity reactions. During the MultiGFR clinical trial, 7 patients (7/163 participants) had an Adverse reaction; of these, 4 were hypersensitivity reactions including one case of grade 4 anaphylactic shock. In the hospital, no ARs were observed. In the literature, ARs to inulin and sinistrin are very rarely reported and mostly benign. Conclusion: Most ARs to inulin and sinistrin are hypersensitivity reactions that appear to be associated with sinistrin batches.

The effect of selenium source on the oxidative status and performance of broilers reared at standard and high ambient temperatures.

1. This study investigated the oxidative status of broilers fed diets containing selenium (Se) from 14 to 35 d of age and reared at two different constant temperatures. Measurements of oxidative status included blood glutathione peroxidase (GSH-Px) and plasma total antioxidant status (TAS). Other variables included feed intake (FI), weight gain (WG), feed conversion ratio (FCR), Se levels in breast and liver tissue, jejunal villus morphometry, percentage weight of organs in relation to body weight; apparent metabolisable energy adjusted for nitrogen (AMEn); dry matter retention (DMR); fat retention (FR) and nitrogen retention (NR).2. The experiment started at 14 d of age, when 240 birds were randomly allocated to 48 pens (12 pens in four rooms). Treatments included a control diet 1 (SFC; 209.4 g/kg CP and 12.98 MJ/kg ME and no added Se containing saturated fat); diet 2 (SFSe) the control plus 12.605 mg/kg Se additive; diet 3 (USFC) was a second control diet (208.2 g/kg CP and 13.10 MJ/kg ME with no added Se containing unsaturated fat as rapeseed oil); diet 4 (USFSe) was the latter control plus 12.605 mg/kg Se additive. Two rooms were kept at a standard temperature of 20°C (ST) and two rooms were kept at high temperature of 35°C (HT).3. A temperature x Se interaction existed for GSH-Px in birds reared at ST (P < 0.05), and these birds had the highest levels of Se in liver tissue (P < 0.05). Fat x Se interactions were evident in breast tissue with highest levels in USFSe (P < 0.05). Adding Se improved jejunal VH: CD in USFSe fed birds (P < 0.001).4. Birds reared at ST had higher FI and WG than those reared at HT (P < 0.001), and had lower FCR than those reared at HT (P < 0.05). AMEn (MJ/kg DM) and FR were higher in birds fed USF diets, and lowest in birds fed SF (P < 0.50 and P < 0.001 respectively). NR was highest in birds raised at ST (P < 0.50).5. Broiler growth performance was reduced by HT. Oxidative status and Se in liver tissue was improved by adding Se in both diets.

The effect of feeding different sources and levels of selenium on growth performance and antioxidant status of broilers raised at two different temperatures.

1. This study examined the effects of different dietary sources and levels of selenium (Se) on growth performance, hepatic and breast meat Se content, glutathione peroxidase (GSH-Px) activity and total antioxidant status (TAS) in blood, when fed to broilers from 14 to 35 d of age and reared at two different temperatures (20°C and 35°C). 2. Five hundred and sixty male Ross 308 broilers were reared in a single floor pen and fed the same proprietary starter diet from 0 to 14 d age (229.9 g/kg CP and 12.67 MJ/kg ME, without Se supplementation). 3. The experiment started at 14 d age, and the birds randomly assigned to 112 raised-floor pens (0.36 m2 area, 5 birds/pen). Each of the seven experimental diets were offered to birds in 16 pens within four rooms. Two rooms were at 20°C and two rooms were maintained at 35°C. The experimental diets were fed from 14 to 35 d age and contained 214.9 g/kg CP and 13.11 MJ/kg ME. The experimental diets were as follows; control diet containing background Se only (0.189 mg/kg; C); low level sodium selenite (0.376 mg/kg; LSS): high level sodium selenite (0.558 mg/kg; HSS); low level commercial B Traxim® Se (0.244 mg/kg) (LBT); high level B Traxim® Se (0.448 mg/kg; HBT); low level selenised yeast (0.290 mg/kg; LSY); high level selenised yeast (0.487 mg/kg; HSY). 4. Birds consumed more when raised at 20°C compared to birds reared at 35°C (P ≤ 0.05). Birds fed lower Se level reared at 35°C had higher weight gain versus those fed higher Se level (P < 0.05). Birds fed SY had the lowest feed intake, weight gain and FCE (P < 0.05). The greatest GSH-Px activity was observed in birds fed SS diets (P < 0.001). There were interactions between diet x level for TAS, which were highest in birds fed LBT compared to birds fed HBT (P < 0.05). Breast Se content was higher in birds fed HSY compared to LSY (P < 0.001). The highest hepatic Se was seen in birds fed SY and lowest in C (P < 0.001). 5. Birds fed BT diets showed similar levels of Se to those birds fed inorganic Se, and similar levels of GSH-Px to birds fed SY. Further comparative work with broilers fed BT and other Se supplemented diets may elucidate the findings from this report.

Genomic heterogeneity of Dichelobacter nodosus within and between UK sheep flocks and between age groups within a flock.

BACKGROUND: Footrot and interdigital dermatitis are endemic infectious diseases in all sheep farming regions, impairing welfare and production. The development of efficacious vaccines against the primary causative pathogen has been hampered by the extensive antigenic diversity of Dichelobacter nodosus. Understanding the heterogeneity of the pathogen within and between flocks is essential if the feasibility of bespoke vaccine production is to be assessed for use in the U.K. RESULTS: In this study 56 ewe and lamb isolates from 9 flocks were compared by D. nodosus serogroup and Multi Locus Sequence Type which provides significantly enhanced discriminatory power for molecular epidemiology. Serogroup heterogeneity between flocks ranged from two to five unique serogroups per flock. Three flocks contained isolates of two serogroups, two flocks contained isolates of three serogroups and one flock included isolates of five serogroups. Analysis of 25 isolates from one flock with high prevalence of lameness, identified that serogroup and sequence type was significantly correlated with age. Significantly higher proportion of lambs were infected with serogroup B (principally ST85) as opposed to serogroup H (principally ST86), which predominated amongst adult sheep. CONCLUSIONS: Genomic heterogeneity of the pathogen was significantly lower within flock compared to heterogenicity observed between flocks. Furthermore, this study indicates that within a flock, the host-pathogen dynamics and susceptibility to particular D. nodosus strains may be age dependent.

[Predictors of asthenia in breast and prostate cancer patients undergoing curative radiotherapy]. / Facteurs de risque d'asthénie en cours de la radiothérapie des cancers du sein et de la prostate.

PURPOSE: Patients frequently report asthenia during radiation. The present study aimed at identifying the correlation between numerous clinical and tumoral factors and asthenia in breast and prostate cancer patients treated by curative radiotherapy. MATERIALS AND METHODS: A retrospective study was conducted at the Lucien Neuwirth Cancer Institute (France). All breast and prostate cancer patients undergoing curative radiotherapy during 2015 were screened (n=806). Patient's self-evaluation of asthenia and radiotherapy tolerance was assessed through verbal analogic scale (0/10 to 10/10). Data about toxicities, travel distance and travel time, tumor's characteristics, radiotherapy treatment planning, previous cancer therapies, were collected from medical records. RESULTS: 500 patients were included (350 in the breast cancer group and 150 in the prostate cancer group). In all, 86% of patients in the breast cancer group reported asthenia, with a 5/10 median score. In all, 54% of patients in the prostate cancer group reported asthenia, with a 2/10 median score. Univariate analysis showed correlation between asthenia and radiotherapy tolerance as well as tumor staging, in the prostate cancer group. No other correlation was evidenced. CONCLUSION: Radiotherapy-related fatigue is a common side effect. This study showed that most of the factors related to patients or disease that are commonly used to explain fatigue during curative treatments, seem finally to be not correlated with asthenia.

Effect of feeding different sources of selenium on growth performance and antioxidant status of broilers.

1. This study was conducted to determine the effect of different sources of selenium (Se) on breast and liver tissue deposition, apparent metabolisable energy (AME), growth performance and antioxidant status of broilers, measured as Se content in liver and breast tissues and glutathione peroxidase (GSH-Px) in blood, when used in 0-35 d broiler chicken diets. 2. A total of 200 male Ross 308 broilers were used in the feeding trial, which comprised two dietary phases, a starter from 0 to 21 d and finisher from 21 to 35 d of age. Four treatments with 10 replications each were used. A control diet (C) was formulated that was sufficient in protein and energy (230 and 215 g/kg of crude protein and 12.67 and 13.11 MJ/kg of metabolisable energy, respectively), for both phases, but contained background Se only from the feed ingredients. Diet 2 (IS) was supplemented with 10.35 g/t inorganic, elemental source of Se. Diet 3 (SY) was supplemented with 136.36 g/t selenised yeast, an organic source derived from Saccharomyces cerevisiae. Diet 4 (SS) was supplemented with 0.666 g/t sodium selenite, an inorganic source. 3. Birds fed the SY diet consumed less and weighed less than those fed IS or C (P < 0.05; 0-35 d of age), but there was no difference compared to birds fed SS diets. There were no differences in FCR or dietary AME between broilers fed different Se sources. All diets containing supplementary Se increased concentrations in the liver and breast muscle, and for GSH-Px levels in blood compared to birds fed the C diet (P < 0.001). Birds fed SY diets had greater Se levels in liver and breast tissues compared to birds fed any of the other diets (P < 0.001). 4. Diets supplemented with Se had variable effects on broiler growth performances and antioxidant status. Feeding Se from a yeast source has higher transfer into breast tissues. Feeding different sources and levels of Se to birds in a more challenging situation to induce oxidative stress may bring more conclusive results.

[Non continent urinary diversion and other bladder managements in patients with multiple sclerosis]. / Dérivation urinaire non continente et modes mictionnels alternatifs chez les patients atteints de sclérose en plaques.

INTRODUCTION: To compare non-continent urinary diversion (NCUD) and other bladder managements in patients with multiple sclerosis (MS), in terms of satisfaction and burden of care. MATERIAL AND METHODS: All patients with MS that were proposed a NCUD in our center for refractory lower urinary tract disorders between January 2005 and March 2018 were eligible. Patients were attributed to two distinct groups: "NCUD" and "Other bladder management". The primary endpoint was the satisfaction related to the bladder management quoted by a numerical rating scale (NRS) from 0 to 10. The secondary endpoints included, among other things, the evaluation of the burden of care associated with the bladder management. RESULTS: Twenty-three patients were included in the "NCUD" group and 11 in the "Other bladder management" group, with 4 patients pursuing with spontaneous voiding, 3 with intermittent catheterization, 2 that have undergone a sphincterotomy, 1 still performing self-intermittent catheterization and 1 with a supra-pubic catheter. The "NCUD" group had a significant higher NRS than the "Other bladder management" group (8.22±1.78 vs. 6.27±2.45; P=0.0056). The daily average duration of care was 16.42minutes in the "NCUD" group and 35.6minutes in the "Other bladder management" group (P=0.1111) CONCLUSION: This exploratory study, even if not conclusive, brings to light the preliminary results needed to elaborate a high level of evidence protocol regarding the satisfaction and the burden of care associated with NCUD in MS patients. LEVEL OF EVIDENCE: 4.

Pembrolizumab-induced obstructive bronchiolitis in a patient with stage IV non-small-cell lung cancer.

Objective: Immune checkpoint inhibitors are now a standard of care for the management of many metastatic cancers, including non-small-cell lung cancer. Pembrolizumab, a selective anti-PD-1 monoclonal antibody, augments the host antitumoural response. This hyperactivation of the immune system has side effects, the so-called immune-related adverse effects. The objective of this case report was to review and point out a new pattern of immune checkpoint inhibitor-associated pneumonitis. Case Description: A 69-year-old woman with stage iv non-small-cell lung cancer receiving pembrolizumab presented for increased dyspnea. Pembrolizumab-related obstructive bronchiolitis was diagnosed based on a new severe obstructive disorder, without bronchodilator reversibility, and mosaic attenuation on angiography, without other identifiable causes. Summary: To our knowledge, this is the first description of a case of pembrolizumab-induced obstructive bronchiolitis. Various patterns of immune checkpoint inhibitor-associated lung disease have been described, and bronchiolitis should be included in the differential diagnosis.

Use of 4D-CT for radiotherapy planning and reality in France: Data from a national survey.

PURPOSE: Lung and some digestive tumours move during a respiratory cycle. Four-dimensional scanography (4D-CT) is commonly used in treatment planning to account for respiratory motion. Although many French radiotherapy centres are now equipped, there are no guidelines on this subject to date. We wanted to draw up a description of the use of the 4D-CT for the treatment planning in France. METHODS AND MATERIAL: We conducted a survey in all French radiotherapy centres between March and April 2017. RESULTS: One hundred and seventy-two were contacted. The participation rate was 88.37%. The use of the 4D-CT seems to be common and concerned planning for 15.28% of kidney and adrenal cancers, 19.72% of pancreatic cancers, 27.78% of oesophageal cancers and 73.24% of lung cancers in case of normofractionated treatments. The use of the 4D-CT was also widespread in the case of stereotactic body radiation therapy: with 61.11% in the case of pulmonary irradiation and 34.72% in the case of hepatic irradiation. Many centres declared they carried out several 4D-CT for treatment planning (29, 55% in case of stereotactic body radiation therapy for lung tumours and 20% for liver tumours). Private centres tend to repeat 4D-CT more. CONCLUSION: Although the use of the 4D-CT appears to be developing, it remains very heterogeneous. To date, the repetition of the 4D-CT has been very poorly studied and could be the subject of clinical studies, allowing to define in which indications and for which populations there is a real benefit.

[Physiopathology and pharmacological perspectives in the treatment of radiation enteritis]. / Physiopathologie et modulation pharmacologique de l'entérite radique.

The small intestine is an organ frequently exposed in abdominal and pelvic irradiations. Acute and late toxicity can sometimes be difficult to manage and can significantly affect the quality of life of patients. Currently there is no guideline on the management of acute and late side effects induced by therapeutic irradiation. The aim of this review is to summarize available data on the pathophysiology of radiation enteritis, and to highlight potential preventive strategies and principles of treatment of radiation enteritis.

[Use of 4D-CT: Main technical aspects and clinical benefits]. / Utilisation de la scanographie quadridimensionnelle : principaux aspects techniques et intérêts cliniques.

The four-dimensional scannography, also called 4D-CT, was created in the early 2000s. This method enables the aquistion of CT-scans synchronised with the patient's breathing. It allows an anatomical observation depending on the time. Different systems have been marketed. They are commonly used in treatment planning. It allows to take into account respiratory motion, considering the changes of shape and position of the tumor and organs. In the age of new techniques and stereotactic irradiations, 4D-CT is a valuable tool for estimating the uncertainties associated with respiratory movements, This technique also presents some limitations, including artifacts. The quality of the examination can be degraded in some patients with irregular respiration. Here we propose a summary of this technique detailing its principle of operation, its advantages and its main limits.

[Medical prevention and treatment of radiation-induced urological and nephrological complications]. / Prévention médicale et traitement des complications urologiques et néphrologiques secondaires à la radiothérapie.

Abdominal and pelvic irradiations play a major place in the management of patients with cancer and present a risk of acute and late side effects. Radiation-induced lesions can affect kidney or urological structures. These side effects can have an impact in the quality of life of patients. The aim of this article is to describe the physiopathology, the symptomatology, and the principles of management of radiation-induced nephropathy, uretheritis, cystitis, and urethritis.

Harnessing drug/radiation interaction through daily routine practice: Leverage medical and methodological point of view (MORSE 02-17 study).

BACKGROUND: Safety profile of the interaction between anticancer drugs and radiation is a recurrent question. However, there are little data regarding the non-anticancer treatment (NACT)/radiation combinations. The aim of the present study was to investigate concomitant NACTs in patients undergoing radiotherapy in a French comprehensive cancer center. METHODS: A prospective cross-sectional study was conducted. All cancer patients undergoing a palliative or curative radiotherapy were consecutively screened for six weeks in 2016. Data on NACTs were collected. RESULTS: Out of 214 included patients, a NACT was concomitantly prescribed to 155 patients (72%), with a median number of 5 NACTs per patient (range: 1-12). The most prescribed drugs were anti-hypertensive drugs (101 patients, 47.2%), psychotropic drugs (n = 74, 34.6%), analgesics (n = 78, 36.4%), hypolipidemic drugs (n = 57, 26.6%), proton pump inhibitors (n = 46, 21.5%) and antiplatelet drugs (n = 38, 17.8%). Although 833 different molecules were reported, only 20 possible modifiers of cancer biological pathways (prescribed to 74 patients (34.5%)) were identified. Eight out of the 833 molecules (0.9%), belonging to six drug families, have been investigated in 28 ongoing or published clinical trials in combo with radiotherapy. They were prescribed to 63 patients (29.4%). CONCLUSION: Drug-radiation interaction remains a subject of major interest, not only for conventional anticancer drugs, but also for NACTs. New trial designs are thus required.

Diepoxybutane-induced apoptosis is mediated through the ERK1/2 pathway.

Diepoxybutane (DEB) is the most potent active metabolite of butadiene, a regulated air pollutant. We previously reported the occurrence of DEB-induced, p53-dependent, mitochondrial-mediated apoptosis in human lymphoblasts. The present study investigated the role of the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathway in DEB-induced apoptotic signaling in exposed human lymphoblasts. Activated ERK1/2 and mitogen-activated protein (MAP) kinase/ERK1/2 kinase (MEK) levels were significantly upregulated in DEB-exposed human lymphoblasts. The MEK inhibitor PD98059 and ERK1/2 siRNA significantly inhibited apoptosis, ERK1/2 activation, as well as p53 and phospho-p53 (serine-15) levels in human lymphoblasts undergoing DEB-induced apoptosis. Collectively, these results demonstrate that DEB induces apoptotic signaling through the MEK-ERK1/2-p53 pathway in human lymphoblasts. This is the first report implicating the activation of the ERK1/2 pathway and its subsequent role in mediating DEB-induced apoptotic signaling in human lymphoblasts. These findings contribute towards the understanding of DEB toxicity, as well as the signaling pathways mediating DEB-induced apoptosis in human lymphoblasts.

[Infants living with their mothers in the Rennes, France, prison for women between 1998 and 2013. Facts and perspectives]. / Les nourrissons vivant auprès de leur mère incarcérée au centre pénitentiaire des femmes de Rennes entre 1998 et 2013. Constats et perspectives.

Every year in France, nearly 50 infants live in a prison nursery with their mother. According to French law, infants can live with their mother in the prison nursery until they reach 18 months of age. The international community is concerned about the lack of validated social, medical and legal data on these infants living in prison. This was a retrospective and descriptive study. Medical and paramedical files of the General Council of Île-et-Vilaine, France, were studied. Every infant born between 1998 and 2013 while their mother was in prison were included. Fifty-four files were collected. The average length of stay was 6.2 months (n=54). The type of the mother's prison sentence was property damage in 40 % of cases, personal injury in 51.1 % of cases and both in 8.9 % of cases (n=45). The length of the mother's imprisonment was on average 45 months, ranging from 3 to 216 months (n=34). After prison, 42.9 % of the infants were placed in foster care and 57.1 % resided with their family (n=42). This child-mother incarceration could be an opportunity for positive intergenerational paramedical, medical and social services. The lack of data and problems collecting data restrict our knowledge of these families. This should motivate a national follow-up for these children.

Risk factor analysis of equine strongyle resistance to anthelmintics.

Intestinal strongyles are the most problematic endoparasites of equids as a result of their wide distribution and the spread of resistant isolates throughout the world. While abundant literature can be found on the extent of anthelmintic resistance across continents, empirical knowledge about associated risk factors is missing. This study brought together results from anthelmintic efficacy testing and risk factor analysis to provide evidence-based guidelines in the field. It involved 688 horses from 39 French horse farms and riding schools to both estimate Faecal Egg Count Reduction (FECR) after anthelmintic treatment and to interview farm and riding school managers about their practices. Risk factors associated with reduced anthelmintic efficacy in equine strongyles were estimated across drugs using a marginal modelling approach. Results demonstrated ivermectin efficacy (96.3% ± 14.5% FECR), the inefficacy of fenbendazole (42.8% ± 33.4% FECR) and an intermediate profile for pyrantel (90.3% ± 19.6% FECR). Risk factor analysis provided support to advocate for FEC-based treatment regimens combined with individual anthelmintic dosage and the enforcement of tighter biosecurity around horse introduction. The combination of these measures resulted in a decreased risk of drug resistance (relative risk of 0.57, p = 0.02). Premises falling under this typology also relied more on their veterinarians suggesting practitionners play an important role in the sustainability of anthelmintic usage. Similarly, drug resistance risk was halved in premises with frequent pasture rotation and with stocking rate below five horses/ha (relative risk of 0.53, p < 0.01). This is the first empirical risk factor analysis for anthelmintic resistance in equids. Our findings should guide the implementation of more sustained strongyle management in the field.

Navigating the highlights of phase III trials: a watchful eye on evidence-based radiotherapy.

BACKGROUND: Phase III randomized controlled trials (RCTs) are the cornerstone of evidence-based oncology. However, there is no exhaustive review describing the radiotherapy RTCs characteristics. The objective of the present study was to describe features of all phase III RCTs including at least a radiation therapy. METHODS AND MATERIALS: Requests were performed in the Medline database (via PubMed). The latest update was performed in April 2016, using the following MESH terms: 'clinical trials: phase III as topic', 'radiotherapy', 'brachytherapy', as keywords. RESULTS: A total of 454 phase III RCTs were identified. Studies were mainly based on open (92.1%) multicenter (77.5%) designs, analyzed in intend to treat (67.6%), aiming at proving superiority (91.6%) through overall survival assessment (46.5%). Most frequently studied malignancies were head and neck (21.8%), lung (14.3%) and prostate cancers (9.9%). Patients were mainly recruited with a locally advanced disease (73.7%). Median age was 59 years old. Out of 977 treatment arms, 889 arms experienced radiotherapy, mainly using 3D-conformal radiotherapy (288 arms, 32.4%). Intensity-modulated techniques were tested in 12 arms (1.3%). The intervention was a non-cytotoxic agent addition in 89 studies (19.6%), a radiation dose/fractionation modification in 74 studies (16.3%), a modification of chemotherapy regimen in 63 studies (13.9%), a chemotherapy addition in 63 studies (13.9%) and a radiotherapy addition in 53 trials (11.7%). With a median follow-up of 50 months, acute all-grade and grade 3-5 toxicities were reported in 49.6% and 69.4% of studies, respectively. Radiotherapy technique, follow-up and late toxicities were reported in 60.1%, 74%, and 31.1% of studies, respectively. CONCLUSION: Phase III randomized controlled trials featured severe limitations, since a third did not report radiotherapy technique, follow-up or late toxicities. The fast-paced technological evolution creates a discrepancy between literature and radiotherapy techniques performed in daily-routine, suggesting that phase III methodology needs to be reinvented.