Efficacy and safety of atomoxetine as add-on to psychoeducation in the treatment of attention deficit/ hyperactivity disorder

Objective: The primary objective of this study was to assess the impact of atomoxetine in combination with psychoeducation, compared with placebo and psychoeducation, on health-related quality of life (HRQL) in Swedish stimulant-naïve pediatric patients with attention deficit/ hyperactivity disorder (ADHD). HRQL results will be presented elsewhere. Here, psychoeducation as well as efficacy and safety of the treatment are described. Patients and methods: A total of 99 pediatric ADHD patients were randomized to a 10-week double-blind treatment with atomoxetine (49 patients) or placebo (50 patients). Parents of all patients received four sessions of psychoeducation. Atomoxetine was dosed up to approximately 1.2 mg/kg day (≤70 kg) or 80 mg/day (>70 kg). Improvement of ADHD symptoms was evaluated using the ADHD rating scale (ADHD-RS) and clinical global impression (CGI) rating scales. Safety was assessed based on adverse events (AEs). Results: The study population was predominantly male (80.8%) and diagnosed with the combined ADHD subtype (77.8%). The least square mean (lsmean) change from baseline to endpoint in total ADHD-RS score was −19.0 for atomoxetine patients and −6.3 for placebo patients, resulting in an effect size (ES) of 1.3 at endpoint. Treatment response (reduction in ADHD-RS score of ≥25 or ≥40%) was achieved in 71.4 or 63.3% of atomoxetine patients and 28.6 or 14.3% of placebo patients. The lsmean change from baseline to endpoint in CGI-Severity was −1.8 in the atomoxetine group compared with −0.3 in the placebo group. The difference between treatments in CGI-Improvement at endpoint was −1.4 in favor of atomoxetine. No serious AEs occurred. The safety profile of atomoxetine was in line with the current label. Conclusions: Atomoxetine combined with psychoeducation was superior to placebo and psychoeducation in ADHD core symptoms improvement. The large ES might be a result of including stimulant-naïve patients only, but also may indicate a positive interaction between atomoxetine treatment and psychoeducation, possibly by increased compliance

Virtual patients in a behavioral medicine massive open online course (MOOC) : a qualitative and quantitative analysis of participants' perceptions

Objective The purpose of this article is to explore learners' perceptions of using virtual patients in a behavioral medicine Massive Open Online Course (MOOCs) and thereby describe innovative ways of disseminating knowledge in health-related areas.Methods A 5-week MOOC on behavioral medicine was hosted on the edX platform. The authors developed two branched virtual patients consisting of video recordings of a live standardized patient, with multiple clinical decision points and narration unfolding depending on learners' choices. Students interacted with the virtual patients to treat stress and sleep problems. Answers to the exit survey and participant comments from the discussion forum were analyzed qualitatively and quantitatively.Results In total, 19,236 participants enrolled in the MOOC, out of which 740 received the final certificate. The virtual patients were completed by 2317 and 1640 participants respectively. Among survey respondents (n = 442), 83.1% agreed that the virtual patient exercise was helpful. The qualitative analysis resulted in themes covering what it was like to work with the virtual patient, with subthemes on learner-centered education, emotions/eustress, game comparisons, what the participants learned, what surprised them, how confident participants felt about applying interventions in practice, suggestions for improvement, and previous experiences of virtual patients.Conclusions Students were enthusiastic about interacting with the virtual patients as a means to apply new knowledge about behavioral medicine interventions. The most common suggestion was to incorporate more interactive cases with various levels of complexity. Further research should include patient outcomes and focus on interprofessional aspects of learning with virtual patients in a MOOC.</p

The interaction of Wnt-11 and signalling cascades in prostate cancer

Prostate cancer (PCa) is the second most common cancer among the male population. Conventional therapies target androgen signalling, which drives tumour growth; however, they provide limited survival benefits for patients. It is essential, therefore, to develop a more specific biomarker than the current gold standard, PSA testing. The Wnt signalling pathway induces expression of target genes through cell surface receptors. A non-canonical member of this family, Wnt-11, is evolutionarily highly conserved and is normally expressed by various cells in the developing embryo, as well as in the heart, liver and skeletal muscle of adult humans. We comprehensively review several cell signalling pathways to explain how they interact with Wnt-11, demonstrating its use as a potential biomarker for PCa. Several studies have shown that the expression of Wnt-11 is associated with gastric, renal and colorectal adenocarcinomas and PCa. Moreover, Wnt-11 affects extracellular matrix composition and cytoskeletal rearrangement, and it is required for proliferation and/or survival during cell differentiation. It was found that PCa cell lines express high levels of Wnt-11, which allows differentiation of the epithelial prostate tumour cells to neuron-like (NE) cells. The NE cells produce additional factors that can cause regression after treatment. Accumulating evidence shows that Wnt-11 could be a potential biomarker in diagnosing PCa. Many studies have shown both non-canonical and canonical Wnts interact with several signalling cascades such as PKC, JNK, NF-κB, Rho, PKA and PI3K. In particular, evidence demonstrates Wnt-11 is involved in the progression of PCa, thus it could have the potential to become both a specific disease marker and an important therapeutic target

Fibroblasts—a key host cell type in tumor initiation, progression, and metastasis

Tumor initiation, growth, invasion, and metastasis occur as a consequence of a complex interplay between the host environment and cancer cells. Fibroblasts are now recognized as a key host cell type involved in host–cancer signaling. This review discusses some recent studies that highlight the roles of fibroblasts in tumor initiation, early progression, invasion, and metastasis. Some clinical studies describing the prognostic significance of fibroblast-derived markers and signatures are also discussed

STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer

Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant of cancerassociated fibroblasts (CAF). Elevated expression of PDGF receptors on stromal CAFs is associated with metastasis and poor prognosis, but mechanism(s) that underlie these connections are not understood. Here, we report the identification of the secreted glycoprotein stanniocalcin-1 (STC1) as a mediator of metastasis by PDGF receptor function in the setting of colorectal cancer. PDGF-stimulated fibroblasts increased migration and invasion of cocultured colorectal cancer cells in an STC1-dependent manner. Analyses of human colorectal cancers revealed significant associations between stromal PDGF receptor and STC1 expression. In an orthotopic mouse model of colorectal cancer, tumors formed in the presence of STC1-deficient fibroblasts displayed reduced intravasation of tumor cells along with fewer and smaller distant metastases formed. Our results reveal a mechanistic basis for understanding the contribution of PDGF-activated CAFs to cancer metastasis. Cancer Res; 73(4); 1287¿97. 2012 AACR

Practical consensus guidelines for the management of enuresis

Despite the high prevalence of enuresis, the professional training of doctors in the evaluation and management of this condition is often minimal and/or inconsistent. Therefore, patient care is neither optimal nor efficient, which can have a profound impact on affected children and their families. Once comprehensive history taking and evaluation has eliminated daytime symptoms or comorbidities, monosymptomatic enuresis can be managed efficaciously in the majority of patients. Non-monosymptomatic enuresis is often a more complex condition; these patients may benefit from referral to specialty care centers. We outline two alternative strategies to determine the most appropriate course of care. The first is a basic assessment covering only the essential components of diagnostic investigation which can be carried out in one office visit. The second strategy includes several additional evaluations including completion of a voiding diary, which requires extra time during the initial consultation and two office visits before treatment or specialty referral is provided. This should yield greater success than first-line treatment. Conclusion: This guideline, endorsed by major international pediatric urology and nephrology societies, aims to equip a general pediatric practice in both primary and secondary care with simple yet comprehensive guidelines and practical tools (i.e., checklists, diary templates, and quick-reference flowcharts) for complete evaluation and successful treatment of enuresis

Feasibility study of intelligent autonomous determination of the bladder voiding need to treat bedwetting using ultrasound and smartphone ML techniques

Unsatisfactory cure rates for the treatment of nocturnal enuresis (NE), i.e. bed-wetting, have led to the need to explore alternative modalities. New treatment methods that focus on preventing enuretic episodes by means of a pre-void alerting system could improve outcomes for children with NE in many aspects. No such technology exists currently to monitor the bladder to alarm before bed-wetting. The aim of this study is to carry out the feasibility of building, refining and evaluating a new, safe, comfortable and non-invasive wearable autonomous intelligent electronic device to monitor the bladder using a single-element low-powered low-frequency ultrasound with the help of Machine Learning techniques and to treat NE by warning the patient at the pre-void stage, enhancing quality of life for these children starting from the first use. The sensitivity and specificity values are 0.89 and 0.93 respectively for determining imminent voiding need. The results indicate that customised imminent voiding need based on the expansion of the bladder can be determined by applying a single-element transducer on a bladder in intermittent manner. The acquired results can be improved further with a comfortable non-invasive device by adding several more features to the current features employed in this pilot study