Building a predictive model for assessing the risk of Salmonella shedding at slaughter in fattening pigs.

Salmonellosis continues to be a major cause of foodborne outbreaks worldwide, and pigs are one of the main sources of human infection. Salmonella pork contamination is a major concern for abattoirs and is related to the presence of Salmonella in pigs' feces at slaughter. Being able to predict the risk of Salmonella shedding in pigs arriving at the slaughterhouse could help mitigate abattoir and carcass contamination. For this purpose, 30 batches of 50 pigs each were selected from 30 different fattening units. The pigs were tagged and bled for the detection of antibodies against Salmonella approximately one month before slaughter. Pooled floor fecal samples were also collected from 10 pens per unit for Salmonella detection, and a questionnaire on biosecurity was administered to each farm. At the abattoir, colon content was collected from each tagged pig for the Salmonella shedding assessment. A predictive model for Salmonella shedding at slaughter was built with two-third of the pigs by employing random-effects logistic regression analysis, with Salmonella shedding as the dependent variable and pig serology and other farm/environmental characteristics as the independent variables. The model included farm as the grouping factor. Data from the remaining one-third of the pigs were used for model validation. Out of 1,500 pigs initially selected, 1,341 were identified at the abattoir and analyzed. Salmonella was detected in 13 (43.3%; 95%CI = 27.4-60.8) of the fattening units. The mean batch seroprevalence (cut-off OD% ≥40) among the fattening units was 31.7% (95%CI = 21.8-41.0), and a total of 316 pigs (23.6%; 95%CI = 21.4-25.9) shed Salmonella at slaughter. The model predicted reasonably well (Area under the curve = 0.76; P < 0.05) whether a pig would shed Salmonella at slaughter, with estimates of sensitivity and specificity at 71.6% and 73.6%, respectively. Serology, the percentage of Salmonella-positive pens on the farm, and the internal biosecurity score were significantly associated (P < 0.05) with Salmonella shedding at the abattoir, and several scenarios were observed by the model. The study highlighted that although serology may be helpful for identifying batches of pigs at risk of shedding Salmonella upon their arrival at the abattoir, it may not be necessary in some scenarios.

Salmonella Control in Fattening Pigs through the Use of Esterified Formic Acid in Drinking Water Shortly before Slaughter.

The presence of Salmonella in pig feces is a major source of abattoir and carcass contamination, and one of the main sources of human salmonellosis. This study assessed whether using a form of esterified formic acid (30% formic acid) in drinking water (10 kg/1000 L) 5 days before slaughter could be a helpful strategy to mitigate this public health issue. Thus, 240 pigs from three Salmonella-positive commercial fattening farms were selected. From each farm, 40 pigs were allocated to a control group (CG) and 40 to a treatment group (TG). At the abattoir, fecal samples from both groups were collected for Salmonella detection (ISO 6579-1:2017) and quantification (ISO/TS 6579-2:2012). Salmonella was present in 35% (95% IC = 29.24-41.23) of the samples collected. The prevalence was significantly higher in the CG than in the TG (50% vs. 20%; p < 0.001). In all farms, the TG showed a lower percentage of shedders than the CG. A random-effects logistic model showed that the odds of shedding Salmonella were 5.63 times higher (95% CI = 2.92-10.8) for the CG than for the TG. Thus, the proportion of pigs shedding Salmonella that was prevented in the TG due to the use of this form of organic acid was 82.2%. In addition, a Chi-squared analysis for trends showed that the higher the Salmonella count, the higher the odds of the sample belonging to the CG. These results suggest that adding this type of acid to drinking water 5 days before slaughter could reduce the proportion of Salmonella-shedding pigs and the Salmonella loads in the guts of shedder pigs.

Diagnóstico y tratamiento quirúrgico de una paciente con una neoplasia trofoblástica gestacional / Diagnosis and surgical treatment of a patient with gestational trophoblastic neoplasia

Resumen ANTECEDENTE: La neoplasia trofoblástica gestacional forma parte del grupo de afecciones derivadas de la proliferación anómala del trofoblasto con capacidad para invasión y metástasis. CASO CLÍNICO: Paciente de 42 años, asintomática, con sospecha ecográfica de mola hidatiforme. El legrado uterino y el estudio anatomopatológico confirmaron el diagnóstico de mola hidatiforme completa. Con la cuantificación consecutiva de tres elevaciones de la β-HCG se diagnosticó: neoplasia trofoblástica gestacional. Se estadificó en estadio I, bajo riesgo y ante el deseo genésico satisfecho la paciente aceptó la histerectomía más salpingectomía bilateral. En el seguimiento posterior la paciente se encontró asintomática, con determinaciones seriadas de b-HCG negativa y ecografías vaginales sin hallazgos. CONCLUSIÓN: La histerectomía con salpingectomía bilateral puede ser el tratamiento definitivo en casos seleccionados de neoplasia trofoblástica. La evidencia disponible es escasa, por lo que es necesario seguir investigando en este campo.

Abstract BACKGROUND: Gestational trophoblastic neoplasia is one of a group of conditions resulting from abnormal trophoblast proliferation with capacity for invasion and metastasis. CLINICAL CASE: 42-year-old asymptomatic patient with ultrasound suspicion of hydatidiform mole. Uterine curettage and anatomopathological study confirmed the diagnosis of complete hydatidiform mole. With the consecutive quantification of three elevations of β-HCG a diagnosis of gestational trophoblastic neoplasia was made. It was staged as stage I, low-risk, and the patient agreed to hysterectomy plus bilateral salpingectomy. At subsequent follow-up the patient was found to be asymptomatic, with negative serial determinations of β-HCG and vaginal ultrasound scans without findings. CONCLUSION: Hysterectomy with bilateral salpingectomy may be the definitive treatment in selected cases of trophoblastic neoplasia. The available evidence is scarce and further research is needed in this field.

Different Brain Phenotypes in Magnetic Resonance Imaging of Healthy Children after Prenatal Insults.

In this study, we used magnetic resonance imaging (MRI) to identify the different brain phenotypes within apparently healthy children and to evaluate whether these phenotypes had different prenatal characteristics. We included 65 healthy children (mean age, 10 years old) with normal neurological examinations and without structural abnormalities. We performed cluster analyses to identify the different brain phenotypes in the brain MRI images. We performed descriptive analyses, including demographic and perinatal characteristics, to assess the differences between the clusters. We identified two clusters: Cluster 1, or the "small brain phenotype" (n = 44), which was characterized by a global reduction in the brain volumes, with smaller total intracranial volumes (1044.53 ± 68.37 vs. 1200.87 ± 65.92 cm3 (p < 0.001)), total grey-matter volumes (644.65 ± 38.85 vs. 746.79 ± 39.37 cm3 (p < 0.001)), and total white-matter volumes (383.68 ± 40.17 vs. 443.55 ± 36.27 cm3 (p < 0.001)), compared with Cluster 2, or the "normal brain phenotype" (n = 21). Moreover, almost all the brain areas had decreased volumes, except for the ventricles, caudate nuclei, and pallidum areas. The risk of belonging to "the small phenotype" was 82% if the child was preterm, 76% if he/she was born small for his/her gestational age and up to 80% if the mother smoked during the pregnancy. However, preterm birth appears to be the only substantially significant risk factor associated with decreased brain volumes.

Salmonella Shedding in Slaughter Pigs and the Use of Esterified Formic Acid in the Drinking Water as a Potential Abattoir-Based Mitigation Measure.

Pigs shedding Salmonella at slaughter are considered a source of carcass contamination and human infection. To assess this potential risk, the proportion of Salmonella shedders that arrive for slaughter was evaluated in a population of 1068 pigs from 24 farms. Shedding was present in 27.3% of the pigs, and the monophasic variant of Salmonella Typhimurium, an emerging zoonotic serotype, was the most prevalent (46.9%). Antimicrobial resistance (AMR) in Salmonella isolates was common, but few isolates showed AMR to antimicrobials of critical importance for humans such as third-generation cephalosporins (5%), colistin (0%), or carbapenems (0%). However, AMR to tigecycline was moderately high (15%). The efficacy of an esterified formic acid in the lairage drinking water (3 kg formic acid/1000 L) was also assessed as a potential abattoir-based strategy to reduce Salmonella shedding. It was able to reduce the proportion of shedders (60.7% in the control group (CG) vs. 44.3% in the treatment group (TG); p < 0.01). After considering clustering and confounding factors, the odds of shedding Salmonella in the CG were 2.75 (95% CI = 1.80−4.21) times higher than those of the TG, suggesting a potential efficacy of reduction in shedding as high as 63.6%. This strategy may contribute to mitigating the burden of abattoir environmental contamination.

Visual Acuity and Contrast Sensitivity in Preterm and Full-Term Children Using a Novel Digital Test.

Visual assessment in preverbal children mostly relies on the preferential looking paradigm. It requires an experienced observer to interpret the child's responses to a stimulus. DIVE (Device for an Integral Visual Examination) is a digital tool with an integrated eye tracker (ET) that lifts this requirement and automatizes this process. The aim of our study was to assess the development of two visual functions, visual acuity (VA) and contrast sensitivity (CS), with DIVE, in a large sample of children from 6 months to 14 years (y) of age, and to compare the results of preterm and full-term children. Participants were recruited in clinical settings from five countries. There were 2208 children tested, 609 of them were born preterm. Both VA and CS improved throughout childhood, with the maximum increase during the first 5 years of age. Gestational age, refractive error and age had an impact on VA results, while CS values were only influenced by age. With this study we report normative reference outcomes for VA and CS throughout childhood and validate the DIVE tests as a useful tool to measure basic visual functions in children.

Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study.

PURPOSE: Primary or secondary mutations in KIT or platelet-derived growth factor receptor alpha (PDGFRA) underlie tyrosine kinase inhibitor resistance in most GI stromal tumors (GISTs). Avapritinib selectively and potently inhibits KIT- and PDGFRA-mutant kinases. In the phase I NAVIGATOR study (NCT02508532), avapritinib showed clinical activity against PDGFRA D842V-mutant and later-line KIT-mutant GIST. VOYAGER (NCT03465722), a phase III study, evaluated efficacy and safety of avapritinib versus regorafenib as third-line or later treatment in patients with unresectable or metastatic GIST. PATIENTS AND METHODS: VOYAGER randomly assigned patients 1:1 to avapritinib 300 mg once daily (4 weeks continuously) or regorafenib 160 mg once daily (3 weeks on and 1 week off). Primary end point was progression-free survival (PFS) by central radiology per RECIST version 1.1 modified for GIST. Secondary end points included objective response rate, overall survival, safety, disease control rate, and duration of response. Regorafenib to avapritinib crossover was permitted upon centrally confirmed disease progression. RESULTS: Four hundred seventy-six patients were randomly assigned (avapritinib, n = 240; regorafenib, n = 236). Median PFS was not statistically different between avapritinib and regorafenib (hazard ratio, 1.25; 95% CI, 0.99 to 1.57; 4.2 v 5.6 months; P = .055). Overall survival data were immature at cutoff. Objective response rates were 17.1% and 7.2%, with durations of responses of 7.6 and 9.4 months for avapritinib and regorafenib; disease control rates were 41.7% (95% CI, 35.4 to 48.2) and 46.2% (95% CI, 39.7 to 52.8). Treatment-related adverse events (any grade, grade ≥ 3) were similar for avapritinib (92.5% and 55.2%) and regorafenib (96.2% and 57.7%). CONCLUSION: Primary end point was not met. There was no significant difference in median PFS between avapritinib and regorafenib in patients with molecularly unselected, late-line GIST.

Effects of Dietary Supplementation with Protected Sodium Butyrate on Gut Microbiota in Growing-Finishing Pigs.

The study assessed changes in the gut microbiota of pigs after dietary supplementation with protected sodium butyrate (PSB) during the growing-fattening period (≈90 days). One gram of colon content from 18 pigs (9 from the treatment group -TG- and 9 from the control group -CG-) was collected. Bacterial DNA was extracted and 16S rRNA high-throughput amplicon sequencing used to assess microbiota changes between groups. The groups shared 75.4% of the 4697 operational taxonomic units identified. No differences in alpha diversity were found, but significant differences for some specific taxa were detected between groups. The low-represented phylum Deinococcus-Thermus, which is associated with the production of carotenoids with antioxidant, anti-apoptotic, and anti-inflammatory properties, was increased in the TG (p = 0.032). Prevotellaceae, Lachnospiraceae, Peptostreptococcaceae, Peptococcaceae, and Terrisporobacter were increased in the TG. Members of these families have the ability to ferment complex dietary polysaccharides and produce larger amounts of short chain fatty acids. Regarding species, only Clostridium butyricum was increased in the TG (p = 0.048). Clostridium butyricum is well-known as probiotic in humans, but it has also been associated with overall positive gut effects (increased villus height, improved body weight, reduction of diarrhea, etc.) in weanling pigs. Although the use of PSB did not modify the overall richness of microbiota composition of these slaughter pigs, it may have increased specific taxa associated with better gut health parameters.

Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial.

BACKGROUND: PDGFRA D842V mutations occur in 5-10% of gastrointestinal stromal tumours (GISTs), and previously approved tyrosine kinase inhibitors (TKIs) are inactive against this mutation. Consequently, patients have a poor prognosis. We present an updated analysis of avapritinib efficacy and long-term safety in this patient population. METHODS: NAVIGATOR (NCT02508532), a two-part, open-label, dose-escalation/dose-expansion phase I study, enrolled adult patients with unresectable GISTs. Patients with PDGFRA D842V-mutant GIST were a prespecified subgroup within the overall safety population, which included patients who received ≥1 avapritinib dose. Primary end-points were overall response rate (ORR) and avapritinib safety profile. Secondary end-points were clinical benefit rate (CBR), duration of response (DOR) and progression-free survival (PFS). Overall survival (OS) was an exploratory end-point. RESULTS: Between 7 October 2015 and 9 March 2020, 250 patients enrolled in the safety population; 56 patients were included in the PDGFRA D842V population, 11 were TKI-naïve. At data cut-off, median follow-up was 27.5 months. Safety profile was comparable between the overall safety and PDGFRA D842V populations. In the PDGFRA D842V population, the most frequent adverse events were nausea (38 [68%] patients) and diarrhoea (37 [66%]), and cognitive effects occurred in 32 (57%) patients. The ORR was 91% (51/56 patients). The CBR was 98% (55/56 patients). The median DOR was 27.6 months (95% confidence interval [CI]: 17.6-not reached [NR]); median PFS was 34.0 months (95% CI: 22.9-NR). Median OS was not reached. CONCLUSION: Targeting PDGFRA D842V-mutant GIST with avapritinib resulted in an unprecedented, durable clinical benefit, with a manageable safety profile. Avapritinib should be considered as first-line therapy for these patients.

Avapritinib in Patients With Advanced Gastrointestinal Stromal Tumors Following at Least Three Prior Lines of Therapy.

BACKGROUND: Most gastrointestinal stromal tumors (GIST) driven by KIT or platelet-derived growth factor receptor A (PDGFRA) mutations develop resistance to available tyrosine kinase inhibitor (TKI) treatments. NAVIGATOR is a two-part, single-arm, dose escalation and expansion study designed to evaluate safety and antineoplastic activity of avapritinib, a selective, potent inhibitor of KIT and PDGFRA, in patients with unresectable or metastatic GIST. MATERIALS AND METHODS: Eligible patients were 18 years or older with histologically or cytologically confirmed unresectable GIST and Eastern Cooperative Oncology Group performance status ≤2 and initiated avapritinib at 300 mg or 400 mg once daily. Primary endpoints were safety in patients who initiated avapritinib at 300 mg or 400 mg once daily and overall response rate (ORR) in patients in the safety population with three or more previous lines of TKI therapy. RESULTS: As of November 16, 2018, in the safety population (n = 204), the most common adverse events (AEs) were nausea (131 [64%]), fatigue (113 [55%]), anemia (102 [50%]), cognitive effects (84 [41%]), and periorbital edema (83 [41%]); 17 (8%) patients discontinued due to treatment-related AEs, most frequently confusion, encephalopathy, and fatigue. ORR in response-evaluable patients with GIST harboring KIT or non-D842V PDGFRA mutations and with at least three prior therapies (n = 103) was 17% (95% confidence interval [CI], 10-25). Median duration of response was 10.2 months (95% CI, 7.2-10.2), and median progression-free survival was 3.7 months (95% CI, 2.8-4.6). CONCLUSION: Avapritinib has manageable toxicity with meaningful clinical activity as fourth-line or later treatment in some patients with GIST with KIT or PDGFRA mutations. IMPLICATIONS FOR PRACTICE: In the NAVIGATOR trial, avapritinib, an inhibitor of KIT and platelet-derived growth factor receptor A tyrosine kinases, provided durable responses in a proportion of patients with advanced gastrointestinal stromal tumors (GIST) who had received three or more prior therapies. Avapritinib had a tolerable safety profile, with cognitive adverse events manageable with dose interruptions and modification in most cases. These findings indicate that avapritinib can elicit durable treatment responses in some patients with heavily pretreated GIST, for whom limited treatment options exist.

Salmonella Infection in Nursery Piglets and Its Role in the Spread of Salmonellosis to Further Production Periods.

Few studies have focused on assessing Salmonella infection in the nursery and its role in further pig production periods. Mesenteric lymph nodes, intestinal content, and meat juice from 389 6-week-old male piglets intended for human consumption from five breeding farms and 191 pooled floor fecal samples from gilt development units (GDU) from the same farms were analyzed to estimate and characterize (by pulsed-field gel electrophoresis and antimicrobial resistance analyses) Salmonella infection. The prevalence of infection and shedding among piglets was 36.5% and 37.3%, respectively, shedding being significantly associated with infection (Odds Ratio = 12.7; CI 7.3-22.0). Salmonella Rissen; S. 4,[5],12:i:-; and S. Derby were the most common serotypes. A low level of Salmonella-specific maternal antibodies at the beginning of the nursery period suggested it was a period of high risk of infection. Resistance to 3rd- and 4th-generation cephalosporins was detected in piglet isolates although the piglets never received antibiotics, indicating they could be vectors of antimicrobial resistance. The same Salmonella clones were detected in piglet and GDU isolates, suggesting that infected piglets play a significant role in the infection of gilts and consequently of finishing pigs in the case of production farms. The control of Salmonella infection in nursery piglets may decrease the risk of abattoir and carcass contamination.

Optimal Avapritinib Treatment Strategies for Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumors.

BACKGROUND: Avapritinib, a novel inhibitor of KIT/PDGFRA, is approved in the U.S. for the treatment of adults with PDGFRA exon 18-mutant unresectable or metastatic gastrointestinal stromal tumors (U/M GISTs). We assessed the safety of avapritinib and provide evidence-based guidance on management of avapritinib-associated adverse events (AEs), including cognitive effects and intracranial bleeding. MATERIALS AND METHODS: We performed a post hoc analysis of data from a two-part, single-arm dose escalation/expansion phase I study (NAVIGATOR; NCT02508532) in patients with U/M GISTs treated with oral avapritinib 30-600 mg once daily. The primary endpoints were safety and tolerability; the impact of dose modification (interruption and/or reduction) on progression-free survival (PFS) was a secondary endpoint. Efficacy analyses were limited to patients who started avapritinib at 300 mg (approved dose). RESULTS: Of 250 patients enrolled in the study, 74.0% presented with KIT mutation and 24.8% presented with PDGFRA exon 18-mutation; 66.8% started avapritinib at 300 mg. The most common treatment-related AEs (any grade) were nausea (59.2%), fatigue (50.0%), periorbital edema (42.0%), anemia (39.2%), diarrhea (36.0%), vomiting (36.0%), and increased lacrimation (30.8%). No treatment-related deaths occurred. Among 167 patients starting on 300 mg avapritinib, all-cause cognitive effects rate (grade 1-2) was 37.0% in all patients and 52.0% in patients ≥65 years. Cognitive effects improved to a lower grade more quickly with dose modification (1.3-3.1 weeks) than without (4.9-7.6 weeks). Median PFS was 11.4 months with dose modification and 7.2 months without. CONCLUSION: Tolerability-guided dose modification of avapritinib is an effective strategy for managing AEs in patients with GISTs. IMPLICATIONS FOR PRACTICE: Early recognition of adverse events and tailored dose modification appear to be effective approaches for managing treatment-related adverse events and maintaining patients on avapritinib. Dose reduction does not appear to result in reduced efficacy. Patients' cognitive function should be assessed at baseline and monitored carefully throughout treatment with avapritinib for the onset of cognitive adverse events. Dose interruption is recommended at the first sign of any cognitive effect, including grade 1 events.

Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial.

BACKGROUND: Targeting of KIT and PDGFRA with imatinib revolutionised treatment in gastrointestinal stromal tumour; however, PDGFRA Asp842Val (D842V)-mutated gastrointestinal stromal tumour is highly resistant to tyrosine kinase inhibitors. We aimed to assess the safety, tolerability, and antitumour activity of avapritinib, a novel KIT and PDGFRA inhibitor that potently inhibits PDGFRA D842V, in patients with advanced gastrointestinal stromal tumours, including patients with KIT and PDGFRA D842V-mutant gastrointestinal stromal tumours (NAVIGATOR). METHODS: NAVIGATOR is a two-part, open-label, dose-escalation and dose-expansion, phase 1 study done at 17 sites across nine countries (Belgium, France, Germany, Poland, Netherlands, South Korea, Spain, the UK, and the USA). Patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 2 or less, and with adequate end-organ function were eligible to participate. The dose-escalation part of the study included patients with unresectable gastrointestinal stromal tumours. The dose-expansion part of the study included patients with an unresectable PDGFRA D842V-mutant gastrointestinal stromal tumour regardless of previous therapy or gastrointestinal stromal tumour with other mutations that either progressed on imatinib and one or more tyrosine kinase inhibitor, or only received imatinib previously. On the basis of enrolment trends, ongoing review of study data, and evolving knowledge regarding the gastrointestinal stromal tumour treatment paradigm, it was decided by the sponsor's medical director together with the investigators that patients with PDGFRA D842V mutations would be analysed separately; the results from this group of patients is reported in this Article. Oral avapritinib was administered once daily in the dose-escalation part (starting dose of 30 mg, with increasing dose levels once daily in continuous 28-day cycles until the maximum tolerated dose or recommended phase 2 dose was determined; in the dose-expansion part, the starting dose was the maximum tolerated dose from the dose-escalation part). Primary endpoints were maximum tolerated dose, recommended phase 2 dose, and safety in the dose-escalation part, and overall response and safety in the dose-expansion part. Safety was assessed in all patients from the dose-escalation part and all patients with PDGFRA D842V-mutant gastrointestinal stromal tumour in the dose-expansion part, and activity was assessed in all patients with PDGFRA D842V-mutant gastrointestinal stromal tumour who received avapritinib and who had at least one target lesion and at least one post-baseline disease assessment by central radiology. This study is registered with ClinicalTrials.gov, NCT02508532. FINDINGS: Between Oct 26, 2015, and Nov 16, 2018 (data cutoff), 46 patients were enrolled in the dose-escalation part, including 20 patients with a PDGFRA D842V-mutant gastrointestinal stromal tumour, and 36 patients with a PDGFRA D842V-mutant gastrointestinal stromal tumour were enrolled in the dose-expansion part. At data cutoff (Nov 16, 2018), 38 (46%) of 82 patients in the safety population (median follow-up of 19·1 months [IQR 9·2-25·5]) and 37 (66%) of the 56 patients in the PDGFRA D842V population (median follow-up of 15·9 months [IQR 9·2-24·9]) remained on treatment. The maximum tolerated dose was 400 mg, and the recommended phase 2 dose was 300 mg. In the safety population (patients with PDGFRA D842V-mutant gastrointestinal stromal tumour from the dose-escalation and dose-expansion parts, all doses), treatment-related grade 3-4 events occurred in 47 (57%) of 82 patients, the most common being anaemia (14 [17%]); there were no treatment-related deaths. In the PDGFRA D842V-mutant population, 49 (88%; 95% CI 76-95) of 56 patients had an overall response, with five (9%) complete responses and 44 (79%) partial responses. No dose-limiting toxicities were observed at doses of 30-400 mg per day. At 600 mg, two patients had dose-limiting toxicities (grade 2 hypertension, dermatitis acneiform, and memory impairment in patient 1, and grade 2 hyperbilirubinaemia in patient 2). INTERPRETATION: Avapritinib has a manageable safety profile and has preliminary antitumour activity in patients with advanced PDGFRA D842V-mutant gastrointestinal stromal tumours. FUNDING: Blueprint Medicines.

[Rate of episiotomy in the University Clinical Hospital of Arrixaca and factors that influence in its practice.] / Tasa de episiotomía en el Hospital Clínico Universitario de La Arrixaca y factores que influyen en su práctica.

OBJECTIVE: The conduction of episiotomy is a questioned practice given the strong scientific evidence on its adverse effects. The study objectives were to know the episiotomy rate and its adaptation to the recommendations of the Ministry of Health, Consumption and Social Welfare and assess the associated factors. METHODS: It has been made a Observational, descriptive and transversal quantitative study, it was carried out in the university clinical hospital arrixaca. Data were collected from deliveries attended between January 1, 2016 and October 30, 2017, obtaining a sample of 10,630 women, registered in the SELENE computer program which is the clinical database of said hospital. To perform the data analysis, were used the SPSS statistical program and an Excel database. At the first level, it was carried out a descriptive analysis of the obstetric variables and, at a second level, the data were compared with the Ministry of Health indicators by means of a comparison of two proportions and the chi-square test. In order to estimate the Effect Size, the Cramer V was used for qualitative variables and the relative risk was calculated for each pair of qualitative variablesas a relative measure of the effect, to determine the strength of association between the variables. RESULTS: The episiotomy rate was 36.5%. When the birth started spontaneously, the percentage was 35.5%, when it was induced 47.2% and stimulated rate was 42.3%. The rate in eutocic deliveries was 20.6% and in instrumented was 95.25%. In primiparas, the episiotomy was 49.64% and in multiparas the conduction was 15.55%. Was observed a tendency of second-degree tears (43.40%), followed by first-degree (35.61%) and third-degree (19.81%) with episiotomy. CONCLUSIONS: The episiotomy rate in our study exceeds current recommendations. The variables associated with the performance of the episiotomy are induced or stimulated delivery, instrumentation and primiparity. There is a significant relationship between the practice of episiotomy and the greater degree of tear.

OBJETIVO: La realización de episiotomías es una práctica cuestionada dada la fuerte evidencia científica existente sobre sus efectos adversos. Los objetivos de este estudio fueron conocer la tasa de episiotomías y su adecuación a las recomendaciones del Ministerio de Sanidad, Consumo y Bienestar Social y valorar los factores asociados. METODOS: Se realizó un estudio cuantitativo observacional, descriptivo y transversal, que fue llevado a cabo en el Hospital Clinico Universitario Arrixaca. Se recogieron datos De los partos atendidos entre el 1 de enero de 2016 y el 30 de octubre de 2017, obteniendo una muestra de 10.630 mujeres, a través del programa informático SELENE, que es la base de datos clínicos de dicho hospital. Para realizar el análisis de datos se utilizó el programa estadístico SPSS y una base de datos Excel. En un primer nivel, se efectuó un análisis descriptivo de las variables obstétricas y, en un segundo nivel, se contrastaron los datos con los indicadores del Ministerio de Sanidad, Consumo y Bienestar Social mediante una comparación de dos proporciones y el test de la ji al cuadrado. Para poder estimar el Tamaño del Efecto se utilizó la V de Cramer para variables cualitativas, y se calculó el riesgo relativo para cada par de variables cualitativas como medida relativa del efecto, para determinar así la fuerza de asociación entre las variables. RESULTADOS: La tasa de episiotomías fue del 36,5%. Cuando el parto comenzó espontáneamente el porcentaje fue del 35,5%; cuando fue inducido, la tasa fue del 47,2% y cuando fue estimulado, el porcentaje fue del 42,3%. La tasa en partos eutócicos fue del 20,6% y en instrumentados fue del 95,25%. En primíparas, la realización de episiotomía fue del 49,64% y en multíparas la realización fue del 15,55%. Se observó una tendencia a desgarros de segundo grado (43,40%), seguidos de primer grado (35,61%) y de tercer grado (19,81%) con episiotomía. CONCLUSIONES: La tasa de episiotomía de nuestro estudio supera las actuales recomendaciones. Las variables asociadas a la realización de la episiotomía son el parto inducido o estimulado, la instrumentación y la primiparidad. Se evidencia una relación significativa entre la práctica de episiotomia y el mayor grado de desgarro.

Tasa de episiotomía en el Hospital Clínico Universitario de La Arrixaca y factores que influyen en su práctica / Rate of episiotomy in the University Clinical Hospital of Arrixaca and factors that influence in its practice

OBJETIVO: La realización de episiotomías es una práctica cuestionada dada la fuerte evidencia científica existente sobre sus efectos adversos. Los objetivos de este estudio fueron conocer la tasa de episiotomías y su adecuación a las recomendaciones del Ministerio de Sanidad, Consumo y Bienestar Social y valorar los factores asociados. MÉTODOS: Se realizó un estudio cuantitativo observacional, descriptivo y transversal, que fue llevado a cabo en el Hospital Clinico Universitario Arrixaca. Se recogieron datos De los partos atendidos entre el 1 de enero de 2016 y el 30 de octubre de 2017, obteniendo una muestra de 10.630 mujeres, a través del programa informático SELENE, que es la base de datos clínicos de dicho hospital. Para realizar el análisis de datos se utilizó el programa estadístico SPSS y una base de datos Excel. En un primer nivel, se efectuó un análisis descriptivo de las variables obstétricas y, en un segundo nivel, se contrastaron los datos con los indicadores del Ministerio de Sanidad, Consumo y Bienestar Social mediante una comparación de dos proporciones y el test de la ji al cuadrado. Para poder estimar el Tamaño del Efecto se utilizó la V de Cramer para variables cualitativas, y se calculó el riesgo relativo para cada par de variables cualitativas como medida relativa del efecto, para determinar así la fuerza de asociación entre las variables. RESULTADOS: La tasa de episiotomías fue del 36,5%. Cuando el parto comenzó espontáneamente el porcentaje fue del 35,5%; cuando fue inducido, la tasa fue del 47,2% y cuando fue estimulado, el porcentaje fue del 42,3%. La tasa en partos eutócicos fue del 20,6% y en instrumentados fue del 95,25%. En primíparas, la realización de episiotomía fue del 49,64% y en multíparas la realización fue del 15,55%. Se observó una tendencia a desgarros de segundo grado (43,40%), seguidos de primer grado (35,61%) y de tercer grado (19,81%) con episiotomía. CONCLUSIONES: La tasa de episiotomía de nuestro estudio supera las actuales recomendaciones. Las variables asociadas a la realización de la episiotomía son el parto inducido o estimulado, la instrumentación y la primiparidad. Se evidencia una relación significativa entre la práctica de episiotomia y el mayor grado de desgarro

OBJECTIVE: The conduction of episiotomy is a questioned practice given the strong scientific evidence on its adverse effects. The study objectives were to know the episiotomy rate and its adaptation to the recommendations of the Ministry of Health, Consumption and Social Welfare and assess the associated factors. METHODS: It has been made a Observational, descriptive and transversal quantitative study, it was carried out in the university clinical hospital arrixaca. Data were collected from deliveries attended between January 1, 2016 and October 30, 2017, obtaining a sample of 10,630 women, registered in the SELENE computer program which is the clinical database of said hospital. To perform the data analysis, were used the SPSS statistical program and an Excel database. At the first level, it was carried out a descriptive analysis of the obstetric variables and, at a second level, the data were compared with the Ministry of Health indicators by means of a comparison of two proportions and the chi-square test. In order to estimate the Effect Size, the Cramer V was used for qualitative variables and the relative risk was calculated for each pair of qualitative variablesas a relative measure of the effect, to determine the strength of association between the variables. RESULTS: The episiotomy rate was 36.5%. When the birth started spontaneously, the percentage was 35.5%, when it was induced 47.2% and stimulated rate was 42.3%. The rate in eutocic deliveries was 20.6% and in instrumented was 95.25%. In primiparas, the episiotomy was 49.64% and in multiparas the conduction was 15.55%. Was observed a tendency of second-degree tears (43.40%), followed by first-degree (35.61%) and third-degree (19.81%) with episiotomy. CONCLUSIONS: The episiotomy rate in our study exceeds current recommendations. The variables associated with the performance of the episiotomy are induced or stimulated delivery, instrumentation and primiparity. There is a significant relationship between the practice of episiotomy and the greater degree of tear

Factores de estrés laboral en el personal de enfermería hospitalario del equipo volante según el modelo de demanda-control-apoyo / Factors of work-related stress in hospital nursing bureau according to the demand-control-support model

Objetivos: Analizar la presencia de estrés laboral en el equipo volante de enfermería de un Hospital General Universitario tomando como referencia el modelo demandas-control-apoyo de Karasek. Método: Estudio observacional de corte transversal. La muestra estuvo constituida por 38 profesionales de enfermería del equipo volante de un Hospital General Universitario. Instrumentos de evaluación: para conocer la percepción de los profesionales de enfermería sobre el contenido de su trabajo y determinar los estresores laborales, se empleó el cuestionario Job Content Questionnaire (JCQ) traducido y validado para enfermería hospitalaria. Resultados: La tasa de participación fue del 90,47% (N=38). Se registró una media para la dimensión de apoyo social de 2,59±0,47, para la dimensión de demandas psicológicas en el trabajo de 3,26±0,47, y para la dimensión de control sobre el trabajo se obtuvo una media de 2,87±0,40. El análisis de datos puso de manifiesto un nivel moderado de estresores, destacando un déficit de apoyo social por parte de los superiores, que resultó ser más acusado en el grupo de profesionales adscritos a la dirección de enfermería (2,89 vs 2,49; p<0,05). Ninguna de las tres dimensiones se mostró asociada a las variables socio-laborales de sexo, edad, turno, adscripción y tipo de vinculación al hospital. Conclusiones: Existe una percepción moderada de estresores laborales, resaltando el escaso apoyo social por parte de los superiores, siendo este aspecto una área de mejora sobre la que intervenir

Objectives: To analyse the presence of work-related stress in the nursing bureau of a University General Hospital taking as reference Karasek's demand-control-support model. Methods: Cross-sectional observational study. The sample included 38 nursing professionals from the nursing bureau of a University General Hospital. Assessment tools: the Job Content Questionnaire (JQC), translated and validated for hospital nursing, was used to know the perception of nursing professionals concernins their work, and to determine the presence of any work-related stressors. Results: The participation rate was 90.47% (N=38). The average for the social support dimension was 2.59±0.47, for the psychological demands of 3.26±0.47, and for control over their own work of 2.87±0.40. Data analysis pointed to a moderate level of stress, reflecting a deficit in the social support provided by superiors, particulary in the group of professionals assigned to nursery management (2.89 vs 2.49; p<0.05). None of the three dimensions showed a link of any kind with socio-occupational variables of gender, age, shift, assignment or type of connection to the hospital. Conclusion: Improvement is needed in this area on the part of human resources management in order to lessen the effect of work-related stress, psychological demands and lack of control over these

El contexto del nacimiento en los años cuarenta en una zona rural del sur de España / Birth context in the forties in a rural area of southern Spain / Contexto do nascimento em quarenta anos em uma área rural do sul da Espanha

En este estudio nos planteamos como objetivos conocer el contexto del nacimiento en un pueblo rural de España en un período de posguerra, 1945-1950; determinar cómo influyeron los roles de género en la vivencia de estos acontecimientos; identificar qué valores y creencias influyeron en el proceso del nacimiento de sus hijos y descubrir qué actitudes promovieron cambios. Desde el enfoque cualitativo hemos escogido el método etnográfico. La información se obtuvo a través de historias de vida y entrevistas semiestructuradas durante 2009. El estudio se llevó a cabo en un pueblo rural del sureste de España (Abarán-Murcia). Se realizaron 11 historias de vida a mujeres que fueron madres entre 1945 y 1950 y 5 entrevistas semiestructuradas para la triangulación y ampliación de la información. Tras la trascripción y fragmentación de las entrevistas y mediante análisis temático del contenido surgieron tres categorías: trabajo/economía doméstica, matrimonio/familia y nacimiento. Los roles de género se han impuesto en la vida de los hombres y las mujeres. El modelo social relaciona a la mujer con las actividades dentro del hogar, sin embargo, la mujer trabajaba duro fuera de casa en labores agrícolas. Las creencias transmitidas provocaban que las mujeres no conocieran su propio cuerpo incluso en el momento del parto, la matrona es el personal de referencia para este acontecimiento

In this study we set objectives to define the birth context of a rural town in Spain in the post-war period 1945-1950; to define what influence gender roles had on experience of these events; to identify what values and beliefs had influence on the childbirth process and to investigate which attitudes promoted change. Taking a qualitative approach, we chose an ethnographic method. The information was obtained through life story reports and semi-structured interviews during 2009. The study was carried out in a rural town in southern Spain: Abarán, in the Region of Murcia. Eleven life stories were collected from women who became mothers between 1945 and 1950 and five semi-structured interviews were also carried out to enable triangulation and information expansion.After transcription of the interviews, the information was fragmented and, after thematic analysis of the content, three categories were defined: household work/ economy, marriage/family and childbirth. Despite the way that gender roles defined the lives of men and women. Even though the social model of the time links women to activities at home, these women also worked hard at agricultural labour outside the home. The prevailing beliefs meant that many of the women were ignorant of their own bodies, even up until the moment of giving birth. Midwives were the reference professionals for this event

Este estudo tem como objectivos conhecer o contexto do nascimento numa vila rural de Espanha no período de pós-guerra, 1945- 1950; determinar como o papel de género influiu na vivência desses eventos; identificar quais valores e crenças influíram no processo do nascimento dos filhos e descobrir quais actitudes promoveram as mudanças. A partir da abordagem qualitativa foi escolhido o método etnográfico. As informações foram obtidas através das histórias de vida e entrevistas semi-estruturadas ao longo de 2009. O estudo desenvolveu-se numa vila rural no sudeste da Espanha (Abarán, Murcia). Foram realizadas onze histórias de vida a mulheres que foram mães entre 1945 e 1950, e cinco entrevistas semi-estruturadas para a triangulação e ampliação da informação. Após a transcrição e fragmentação das entrevistas e da análise temática do conteúdo, surgiram três categorias: trabalho/economia doméstica, casamento/ família e nascimento. O papel do género tem-se imposto na vida dos homens e das mulheres. O modelo social relaciona à mulher com as actividades dentro de casa, no entanto, a mulher trabalhava duramente fora de casa na agricultura. As crenças transmitidas fizeram com que as mulheres não conhecessem o seu próprio corpo, mesmo no momento do parto, sendo a parteira a pessoa de referência para este acontecimento

Impact of support networks for breastfeeding: A multicentre study.

BACKGROUND: The rates of breastfeeding worldwide are slowly improving since 1996. Europe is still trailing behind the global breastfeeding incidence and prevalence rates. Thus, breastfeeding promotion, protection, prolongation and support have become an important challenge as breastfeeding sharply decreases in the first six months of life. OBJECTIVES: The aim of this project is to determine, assess and identify the real impact of breastfeeding support networks in Murcia (Spain). METHODS: After searching unsuccessfully for a validated questionnaire, a specific one was developed and validated for measuring the impact of formal and informal support networks through five dimensions: satisfaction, consultation, experience, problems and support. The questionnaire was provided to 500 mothers with experience in breastfeeding, who brought their children to baby paediatricians between 2 June and 27 November 2014. Upon completion of the survey and fieldwork, a detailed statistical analysis was conducted. RESULTS: The degree of satisfaction perceived by the users of the services of support breastfeeding networks is remarkable. In addition, mothers who clarified their doubts and discussed their problems with health professionals and/or breastfeeding support networks were more likely to breastfeed for a longer duration compared to those who did not (p=0.005). Furthermore, mothers who sought support in breastfeeding are more likely to breastfeed for more than 6 months (p<0.0005). CONCLUSION: Based on this information, we conclude that breastfeeding support networks have a positive influence in the duration of a women's decision to breastfeed.

Selective Killing of SMARCA2- and SMARCA4-deficient Small Cell Carcinoma of the Ovary, Hypercalcemic Type Cells by Inhibition of EZH2: In Vitro and In Vivo Preclinical Models.

The SWI/SNF complex is a major regulator of gene expression and is increasingly thought to play an important role in human cancer, as evidenced by the high frequency of subunit mutations across virtually all cancer types. We previously reported that in preclinical models, malignant rhabdoid tumors, which are deficient in the SWI/SNF core component INI1 (SMARCB1), are selectively killed by inhibitors of the H3K27 histone methyltransferase EZH2. Given the demonstrated antagonistic activities of the SWI/SNF complex and the EZH2-containing PRC2 complex, we investigated whether additional cancers with SWI/SNF mutations are sensitive to selective EZH2 inhibition. It has been recently reported that ovarian cancers with dual loss of the redundant SWI/SNF components SMARCA4 and SMARCA2 are characteristic of a rare rhabdoid-like subtype known as small-cell carcinoma of the ovary hypercalcemic type (SCCOHT). Here, we provide evidence that a subset of commonly used ovarian carcinoma cell lines were misdiagnosed and instead were derived from a SCCOHT tumor. We also demonstrate that tazemetostat, a potent and selective EZH2 inhibitor currently in phase II clinical trials, induces potent antiproliferative and antitumor effects in SCCOHT cell lines and xenografts deficient in both SMARCA2 and SMARCA4. These results exemplify an additional class of rhabdoid-like tumors that are dependent on EZH2 activity for survival. Mol Cancer Ther; 16(5); 850-60. ©2017 AACR.

An exploratory study of the relationship between resilience, academic burnout and psychological health in nursing students.

OBJECTIVES: The purpose of this study was to examine the relationship between resilience, academic burnout and psychological health in a sample of nursing students. METHOD/DESIGN: A descriptive and cross-sectional design was applied, with questionnaires as tools. PARTICIPANTS: The convenience sample consisted of 113 nursing students in their final academic year, who voluntarily participated in the study. RESULTS: The results indicated a statistically significant relationship between resilience and both emotional exhaustion (r = -.55; p < .01) and psychological health (r = -.62; p < .01), as well as between all three dimensions of burnout and psychological health. Hierarchical multiple regression analysis indicated that high scores for resilience and low scores for emotional exhaustion predict better perceived psychological health [F(2.96) = 17.75; p < .001]. CONCLUSIONS: Resilience was associated with lower levels of psychological discomfort and academic burnout. These findings highlight the importance of developing resilience and integrating it as an element in the nursing educational programme.