Smartphone-RCCT: an online repository of randomized controlled clinical trials of smartphone applications for chronic conditions.

BACKGROUND: Chronic health conditions have a big impact on disability, morbidity, and mortality worldwide. Smartphone health applications (apps) can improve the health of patients with chronic conditions and enhance the quality and efficiency of healthcare. The number of randomized controlled trials (RCTs) of smartphone health apps is increasing, but a collection of the available evidence into a single database is still missing. The purpose of this study is to describe Smartphone-RCCT, which is an in-progress database of RCTs of smartphone apps for chronic conditions. METHODS: For a study to be included in the database, the following criteria had to be met: (a) RCT published in a peer-reviewed journal; (b) population: adult study participants with one or several chronic conditions that represent the main health problem addressed by the study intervention; (c) intervention: smartphone health app used by the patient; (d) comparator: any control condition; (e) outcomes: any patient-reported health outcome (studies exclusively measuring the patients' knowledge about the chronic conditions or their satisfaction with the smartphone app were excluded); (f) sample size: at least 15 participants per study arm. We searched in electronic databases and other resources to identify relevant studies. Two reviewers selected the studies and extracted data independently. Annual updates are planned. RESULTS: The proposed database is called Smartphone-RCCT, an open-access repository collecting bibliographic references and important characteristics of RCTs of smartphone apps for chronic conditions. The database is available for free in Open Science Framework (OSF): https://osf.io/nxerf/ . To date, it includes 70 trials. Their references can be exported to standard reference management software and the extracted data is available in a Microsoft Excel file. CONCLUSIONS: Smartphone-RCCT is the first systematic open-access database collecting peer-reviewed publications of RCTs of smartphone apps for patients with chronic conditions. The database accelerates the delivery of evidence-based information in a dynamic research field. It represents an essential resource for different stakeholders, such as professionals working in evidence synthesis, meta-epidemiological studies, or planning an RCT.

The influence of personality traits on the placebo/nocebo response: A systematic review.

OBJECTIVE: Some people might be more prone to placebo and nocebo responses than others depending on their personality traits. We aimed to provide a systematic review on the influence of personality traits on placebo and nocebo responses in controlled and uncontrolled studies. METHODS: We conducted a systematic literature search in the databases CINAHL, AMED, PsycINFO and EMBASE for relevant publications published between January 1997 and March 2018. For all included papers, we conducted an additional forward search. RESULTS: After screening 407 references, we identified 24 studies. The Big Five (i.e., neuroticism, extraversion, openness to experience, agreeableness and conscientiousness) and optimism were the most frequently investigated personality traits. Several studies found a positive association between optimism and the placebo response. Furthermore, we found that higher anxiety was associated with increased nocebo responses. CONCLUSION: Evidence points to a possible association between optimism and the placebo response. Therefore, further emphasising the investigation of the influence of optimism on the placebo/nocebo response seems warranted. For clinical practice, the impact of anxiety on the nocebo response might be important to identify patients who might be more prone to experiencing side effects of medical treatments.

Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.

Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.

Pediatric neuro-oncology in small centers--quality control of network support: the HIT-GBM experience.

BACKGROUND: The quality of care for children with brain tumors might be higher in large medical centers; however, it may be possible to improve the quality of care received in smaller centers if they join an effective network. AIM: This study used the HIT-GBM® database to compare the quality of care provided to pediatric high-grade glioma and diffuse intrinsic pontine glioma patients among various medical centers of differing sizes. PATIENTS AND METHODS: Overall survival was used as a defining parameter. Indirect measures were the time intervals between the first clinical signs of cancer, initial diagnostic imaging, surgery, or chemotherapy and radiation. RESULTS: From 1995 to 2003, 310 children (137 girls and 173 boys, aged 3 to 18 years old) were registered from 72 medical centers in Europe. Center sizes differed from 1 to 17 registered patients. Center size did not affect survival, nor any of the time intervals studied. CONCLUSION: There was no evidence that the quality of care differed between smaller and larger centers.

High dose methotrexate for pediatric high grade glioma: results of the HIT-GBM-D pilot study.

We conducted a phase II study to test methotrexate (5 g/m(2)), as a single agent prior to radiochemotherapy for pediatric high-grade glioma and diffuse intrinsic pontine glioma. Thirty patients (19 male, median age 10.8) were enrolled. Tumors were located as follows: cortex 10, pons 7, other 13. Tumor resection was classified as gross total in 6, subtotal in 6, partial in 4, biopsy in 11 and not performed in 3. WHO grading of the histology was: IV: 11, III: 12 and II: 3. Patients received methotrexate 5 g/m(2) in 24-hour infusions on days 1 and 15. Subsequently 54 Gy radiation was administered with simultaneous chemotherapy including cisplatin, etoposide, vincristine and ifosfamide as previously described. Eight 6-weeks cycles of maintenance chemotherapy consisted of vincristine 1.5 mg/m(2) on days 1, 8 and 15; lomustine 100 mg/m(2) on day 2 and prednisone 40 mg/kg on days 1-17. Event-free survival rates in the whole group of 30 patients were: 43, 20, and 13% after 1, 2 and 5 years, respectively. The response evaluation after methotrexate was available in 19 of the 24 patients who started treatment with measurable disease: CR: 0, PR: 1, SD 18, PD: 0. After radiochemotherapy the response of 24 patients with measurable disease was CR: 1, PR 10, SD 12, PD 1. Both response and event-free survival were superior to the control group of 330 patients treated in various protocols of the same cooperative group. In subgroup analyses the use of dexamethasone during early treatment was linked to poor event free survival. Giving two cycles of high-dose methotrexate prior to radiochemotherapy was feasible, and the approach was taken forward to a randomized phase III trial.