Training for the future

Aim The aim of this prospective study was to examine the association between behavioural problems and medical and psychological outcomes in clinically treated children and adolescents with asthma. Methods Patients (n=134) were recruited from two high-altitude asthma clinics in Switzerland and one asthma clinic in the Netherlands. Outcome measures were Asthma Control Test (ACT), Paediatric Asthma Quality of Life Questionnaire (PAQLQ(S)), forced expiratory volume in 1sec (FEV1) and fractional concentration of exhaled nitric oxide (FeNO). Parents completed the Child Behaviour Checklist (CBCL) (predictor variable). Data were collected at the start and end of treatment. Multiple regression analysis was used while adjusting for demographic variables, clinic and length of stay. Results More severe internalizing behavioural problems were associated with less improvement of total quality of life (t=2.26, p=0.03) and the domains symptoms (t=2.04, p=0.04) and emotions (t=2.3, p=0.02) after clinical treatment. Behavioural problems were not associated with a change of lung function measurements (FEV1 and FeNO) and asthma control (ACT) during treatment. Conclusion A focus of healthcare professionals on the treatment of internalizing behavioural problems may optimize the quality of life in clinically treated youth with asthma

Recurrent acute biliary pancreatitis: The protective role of cholecystectomy and endoscopic sphincterotomy

Background: Recurrent attacks of acute biliary pancreatitis (RABP) are prevented by (laparoscopic) cholecystectomy. Since the introduction of endoscopic retrograde cholangiopancreaticography (ERCP), several series have described a similar reduction of RABP after endoscopic sphincterotomy (ES). This report discusses the different treatment options for preventing RABP including conservative treatment, cholecystectomy, ES, and combinations of these options as well as their respective timing. Methods: A search in PubMed for observational studies and clinical (comparative) trials published in the English language was performed on the subject of recurrent acute biliary pancreatitis and other galls

Crying Without Tears:Dimensions of Crying and Relations With Ocular Dryness and Mental Well-Being in Patients With Sjogren's Syndrome

This study examined dimensions of crying and its relations with ocular dryness and mental well-being in patients with Sjogren's syndrome, a systemic autoimmune disease with dryness as primary symptom. Three-hundred patients with Sjogren's syndrome completed questionnaires on crying, dryness, and well-being. The crying questionnaire revealed four dimensions: "Cryability" (comprising both crying sensibility and ability to cry), Somatic consequences, Frustration, and Suppression. Compared to 100 demographically-matched control participants from the general population, patients scored low on Cryability and high on Somatic consequences and Frustration. The crying dimensions generally showed significant but weak associations with ocular dryness and mental well-being in patients. This is the first quantitative study indicating that crying problems are more common in patients with Sjogren's syndrome than in the general population. Perhaps, patients who experience problems with crying could be helped to rely on other ways of expressing emotions than crying in tear-inducing situations.</p

Nationwide practice and outcomes of endoscopic biliary drainage in resectable pancreatic head and periampullary cancer

BACKGROUND: Guidelines advise self-expanding metal stents (SEMS) over plastic stents in preoperative endoscopic biliary drainage (EBD) for malignant extrahepatic biliary obstruction. This study aims to assess nationwide practice and outcomes. METHODS: Patients with pancreatic head and periampullary cancer who underwent EBD before pancreatoduodenectomy were included from the Dutch Pancreatic Cancer Audit (2017-2018). Multivariable logistic and linear regression models were performed. RESULTS: In total, 575/1056 patients (62.0%) underwent preoperative EBD: 246 SEMS (42.8%) and 329 plastic stents (57.2%). EBD-related complications were comparable between the groups (44/246 (17.9%) vs. 64/329 (19.5%), p = 0.607), including pancreatitis (22/246 (8.9%) vs. 25/329 (7.6%), p = 0.387). EBD-related cholangitis was reduced after SEMS placement (10/246 (4.1%) vs. 32/329 (9.7%), p = 0.043), which was confirmed in multivariable analysis (OR 0.36 95%CI 0.15-0.87, p = 0.023). Major postoperative complications did not differ (58/246 (23.6%) vs. 90/329 (27.4%), p = 0.316), whereas postoperative pancreatic fistula (24/246 (9.8%) vs. 61/329 (18.5%), p = 0.004; OR 0.50 95%CI 0.27-0.94, p = 0.031) and hospital stay (14.0 days vs. 17.4 days, p = 0.005; B 2.86 95%CI -5.16 to -0.57, p = 0.014) were less after SEMS placement. CONCLUSION: This study found that preoperative EBD frequently involved plastic stents. SEMS seemed associated with lower risks of cholangitis and less postoperative pancreatic fistula, but without an increased pancreatitis risk

Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study

Background: Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate comprised of trastuzumab covalently bound to a linker drug containing duocarmycin. Preclinical studies showed promising antitumour activity in various models. In this first-in-human study, we assessed the safety and activity of trastuzumab duocarmazine in patients with advanced solid tumours. Methods: We did a phase 1 dose-escalation and dose-expansion study. The dose-escalation cohort comprised patients aged 18 years or older enrolled from three academic hospitals in Belgium, the Netherlands, and the UK with locally advanced or metastatic solid tumours with variable HER2 status who were refractory to standard cancer treatment. A separate cohort of patients were enrolled to the dose-expansion phase from 15 hospitals in Belgium, the Netherlands, Spain, and the UK. Dose-expansion cohorts included patients aged 18 years or older with breast, gastric, urothelial, or endometrial cancer with at least HER2 immunohistochemistry 1+ expression and measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST). Trastuzumab duocarmazine was administered intravenously on day 1 of each 3-week cycle. In the dose-escalation phase, trastuzumab duocarmazine was given at doses of 0.3 mg/kg to 2.4 mg/kg (3 + 3 design) until disease progression or unacceptable toxicity. The primary endpoint of the dose-escalation phase was to assess safety and ascertain the recommended phase 2 dose, which would be the dose used in the dose-expansion phase. The primary endpoint of the dose-expansion phase was the proportion of patients achieving an objective response (complete response or partial response), as assessed by the investigator using RECIST version 1.1. This ongoing study is registered with ClinicalTrials.gov, number NCT02277717, and is fully recruited. Findings: Between Oct 30, 2014, and April 2, 2018, 39 patients were enrolled and treated in the dose-escalation phase and 146 patients were enrolled and treated in the dose-expansion phase. One dose-limiting toxic effect (death from pneumonitis) occurred at the highest administered dose (2.4 mg/kg) in the dose-escalation phase. One further death occurred in the dose-escalation phase (1.5 mg/kg cohort) due to disease progression, which was attributed to general physical health decline. Grade 3-4 treatment-related adverse events reported more than once in the dose-escalation phase were keratitis (n=3) and fatigue (n=2). Based on all available data, the recommended phase 2 dose was set at 1.2 mg/kg. In the dose-expansion phase, treatment-related serious adverse events were reported in 16 (11%) of 146 patients, most commonly infusion-related reactions (two [1%]) and dyspnoea (two [1%]). The most common treatment-related adverse events (grades 1-4) were fatigue (48 [33%] of 146 patients), conjunctivitis (45 [31%]), and dry eye (45 [31%]). Most patients (104 [71%] of 146) had at least one ocular adverse event, with grade 3 events reported in ten (7%) of 146 patients. No patients died from treatment-related adverse events and four patients died due to disease progression, which were attributed to hepatic failure (n=1), upper gastrointestinal haemorrhage (n=1), neurological decompensation (n=1), and renal failure (n=1). In the breast cancer dose-expansion cohorts, 16 (33%, 95% CI 20.4-48.4) of 48 assessable patients with HER2-positive breast cancer achieved an objective response (all partial responses) according to RECIST. Nine (28%, 95% CI 13.8-46.8) of 32 patients with HER2-low, hormone receptor-positive breast cancer and six (40%, 16.3-67.6) of 15 patients with HER2-low, hormone receptor-negative breast cancer achieved an objective response (all partial responses). Partial responses were also observed in one (6%, 95% CI 0.2-30.2) of 16 patients with gastric cancer, four (25%, 7.3-52.4) of 16 patients with urothelial cancer, and five (39%, 13.9-68.4) of 13 patients with endometrial cancer. Interpretation: Trastuzumab duocarmazine shows notable clinical activity in heavily pretreated patients with HER2-expressing metastatic cancer, including HER2-positive trastuzumab emtansine-resistant and HER2-low breast cancer, with a manageable safety profile. Further investigation of trastuzumab duocarmazine for HER2-positive breast cancer is ongoing and trials for HER2-low breast cancer and other HER2-expressing cancers are in preparation. Copyright (C) 2019 Elsevier Ltd. All rights reserved

Tune in to your emotions: a robust personalized affective music player

The emotional power of music is exploited in a personalized affective music player (AMP) that selects music for mood enhancement. A biosignal approach is used to measure listeners’ personal emotional reactions to their own music as input for affective user models. Regression and kernel density estimation are applied to model the physiological changes the music elicits. Using these models, personalized music selections based on an affective goal state can be made. The AMP was validated in real-world trials over the course of several weeks. Results show that our models can cope with noisy situations and handle large inter-individual differences in the music domain. The AMP augments music listening where its techniques enable automated affect guidance. Our approach provides valuable insights for affective computing and user modeling, for which the AMP is a suitable carrier application

Family doctor-driven follow-up for adult childhood cancer survivors supported by a web-based survivor care plan

To facilitate family doctor-driven follow-up for adult childhood cancer survivors, we developed a survivor care plan (SCP) for adult survivors and their family doctors. The SCP was accessible for survivors and their family doctors on a secure website and as a printed booklet. It included data on diagnosis, treatment and potential risks as well as recommendations for follow-up. Childhood cancer survivors who were off-treatment >= 5 years, aged >= 18 years and not involved in a long-term follow-up program were eligible. They were advised to visit their family doctor. The endpoints were numbers of participants, adherence of family doctors to the guidelines and satisfaction ratings. The eligibility criteria were fulfilled by 108 survivors. Three family doctors and 15 survivors refused, 10 survivors were non-responders. Of the remaining 80 survivors, 73 survivors visited 72 family doctors. Sixty-nine (96%) family doctors returned data of whom 60 (83%) fully adhered to the recommended tests. The majority of survivors and family doctors were satisfied about the SCP. A (web-based) SCP for survivors and family doctors can serve as an effective communication vehicle to provide adequate shared care by the long-term follow-up clinic and family doctors