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Low serum levels of 25-hydroxyvitamin D [25(OH)D] and low sunlight exposure are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown. We aimed to test the hypothesis that oral vitamin D3 supplementation in high-risk clinically isolated syndrome (abnormal MRI, at least three T2 brain and/or spinal cord lesions), delays time to conversion to definite multiple sclerosis, that the therapeutic effect is dose-dependent, and that all doses are safe and well tolerated. We conducted a double-blind trial in Australia and New Zealand. Eligible participants were randomized 1:1:1:1 to placebo, 1000, 5000 or 10 000 international units (IU) of oral vitamin D3 daily within each study centre (n = 23) and followed for up to 48 weeks. Between 2013 and 2021, we enrolled 204 participants. Brain MRI scans were performed at baseline, 24 and 48 weeks. The main study outcome was conversion to clinically definite multiple sclerosis based on the 2010 McDonald criteria defined as either a clinical relapse or new brain MRI T2 lesion development. We included 199 cases in the intention-to-treat analysis based on assigned dose. Of these, 116 converted to multiple sclerosis by 48 weeks (58%). Compared to placebo, the hazard ratios (95% confidence interval) for conversion were 1000 IU 0.87 (0.50, 1.50); 5000 IU 1.37 (0.82, 2.29); and 10 000 IU 1.28 (0.76, 2.14). In an adjusted model including age, sex, latitude, study centre and baseline symptom number, clinically isolated syndrome onset site, presence of infratentorial lesions and use of steroids, the hazard ratios (versus placebo) were 1000 IU 0.80 (0.45, 1.44); 5000 IU 1.36 (0.78, 2.38); and 10 000 IU 1.07 (0.62, 1.85). Vitamin D3 supplementation was safe and well tolerated. We did not demonstrate reduction in multiple sclerosis disease activity by vitamin D3 supplementation after a high-risk clinically isolated syndrome. [ABSTRACT FROM AUTHOR]

Objective: Stability and developmental effects of electroencephalography (EEG) and event related potential (ERP) correlates of ADHD are understudied. This pilot study examined stability and developmental changes in ERP and EEG metrics of interest. Methods: Thirty-seven 7 to 11-year-old children with ADHD and 15 typically developing (TD) children completed EEG twice, 11 to 36 months apart. A series of mixed effects linear models were run to examine stability and developmental effects of EEG and ERP metrics. Results: Stability and developmental effects of EEG and ERP correlates of ADHD varied considerably across metrics. P3 amplitude was stable over time and showed diverging developmental trajectories across groups. Developmental differences were apparent in error related ERPs and resting aperiodic exponent. Theta-beta ratio was stable over time among all children. Conclusions: Developmental trajectories of EEG and ERP correlates of ADHD are candidate diagnostic markers. Replication with larger samples is needed. [ABSTRACT FROM AUTHOR]

Pioneering longitudinal studies of boys with hyperactivity by Satterfield et al. 1 indicated that one of the most deleterious outcomes associated with attention-deficit/hyperactivity disorder (ADHD) is later antisocial behaviors. This risk grows when ADHD is accompanied by severe behavior problems.2 Though most children with ADHD will not go on to engage in criminal behavior, dimensional measures of externalizing behavior problems as well as categorical diagnoses of oppositional defiant disorder and conduct disorder have strong associations with ADHD. Moreover, cross-sectional studies of incarcerated adults indicate that 20% to 30% meet diagnostic criteria for ADHD.3 These associations between childhood ADHD, oppositional defiant disorder, and conduct disorder and later criminal behavior beg the question of whether treatment of ADHD can reduce the severity of, or in some cases prevent, criminal behavior. [ABSTRACT FROM AUTHOR]

Objective: ADHD is associated with suboptimal health behaviors including physical activity (PA). LEAP is a parent BMT group program enhanced to focus on health behaviors, integrated with mHealth technology. Little is known about implementing BMT via telemedicine "telegroups." Methods: Children ages 5 to 10 with ADHD and their caregiver wore activity trackers and participated in an 8 to 9 week parent BMT and social media group emphasizing PA, sleep, and screen use. A 7-day child accelerometer-wear and parent and teacher measures were completed pre- and post-group. Groups were in-person prior to the COVID-19 pandemic and in telegroup format during the pandemic. Results: Thirty-three families participated in person and 23 participated via virtual telegroup. Group attendance was superior for telegroup with equivalent satisfaction and skill use. Changes in health behavior and clinical outcomes were equivalent. Conclusions: LEAP is a feasible and novel BMT intervention that can be delivered in an accessible telegroup format with high participation and acceptability. [ABSTRACT FROM AUTHOR]

Background ADXS31-142 is an attenuated Listeria monocytogenes -based immunotherapy targeting prostate-specific antigen (PSA), being evaluated as monotherapy and combined with pembrolizumab for metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods The 2-part phase I/II KEYNOTE-046 study enrolled men with mCRPC who have progressed after 2 or fewer prior systemic treatment regimens in the metastatic setting. In Part A, intravenous ADXS31-142 monotherapy was given every 3 weeks (q3w) to 3 dose-escalation cohorts. In Part B, ADXS31-142 (1 × 109 colony-forming units) plus pembrolizumab (200 mg) was administered intravenously q3w for 3 doses with a fourth pembrolizumab dose 3 weeks later (12-week cycles) for up to 24 months or until progression/toxicity. Endpoints included safety, overall response rate, progression-free survival (PFS), overall survival (OS), and immunogenicity. Results Fifty patients received ADXS31-142 alone (n = 13) or with pembrolizumab (n = 37). Among the 37 RECIST-evaluable patients (n = 8 Part A; n = 29 Part B), there were no objective responses. Median PFS was 2.2 months (95% CI: 0.8-7.4) with monotherapy and 5.4 months (95% CI: 2.3-7.9) with the combination; median OS was 7.8 months (95% CI: 4.4-18.5) and 33.7 months (95% CI: 15.4–not evaluable), respectively. Promising OS benefit was observed in combination-treated patients who had received prior docetaxel (16.0 months, 95% CI: 6.4-34.6; n = 20) and those with visceral metastasis (16.4 months, 95% CI 4.0-not evaluable; n = 11). All patients had ≥1 treatment-related adverse event, mostly grade 1/2 manageable events. No additive toxicity was observed with combination treatment. Conclusions Combining ADXS31-142 with pembrolizumab was safe and well tolerated. The observed OS in mCRPC warrants further testing of this combination. Clinical Trial registration NCT02325557. [ABSTRACT FROM AUTHOR]

Background: Despite widespread use of stimulants to treat ADHD, individual responses vary considerably and few predictors of response have been identified. The identification of reliable and clinically feasible biomarkers would facilitate a precision medicine approach to pharmacological treatment of ADHD. We test the hypothesis that two electroencephalography (EEG) based neural signatures of ADHD, resting aperiodic slope exponent and novelty P3 amplitude, are markers of methylphenidate response in children. We hypothesize that positive response to methylphenidate treatment will be associated with greater abnormality of both neural markers. Methods: Twenty-nine 7-11 year-old children with ADHD and a history of methylphenidate treatment, and 30 controls completed resting EEG and visual oddball event related potential (ERP) paradigms. ADHD participants were characterized as methylphenidate responders (n = 16) or non-responders (n = 13) using the clinical global improvement (CGI-I) scale during blinded retrospective interview. All participants abstained from prescribed medications for at least 48 hours prior to the EEG. Results: As expected, methylphenidate responders (CGI-I rating < 3) demonstrated attenuated P3 amplitude relative to controls. Unexpectedly, methylphenidate non-responders showed atypically flat aperiodic spectral slope relative to controls, while responders did not differ on this measure. Conclusion: ADHD symptoms associated with atypical patterns of intrinsic neural activity may be less responsive to methylphenidate. In contrast, ADHD symptoms associated with abnormal frontal-striatal neural network excitation may be correctable with methylphenidate. Altogether, EEG is a feasible and promising candidate methodology for identifying biomarkers of stimulant response. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that impairs the control of attention and behavioral inhibition in affected individuals. Recent genome-wide association findings have revealed an association between glutamate and GABA gene sets and ADHD symptoms. Consistently, people with ADHD show altered glutamate and GABA content in the brain circuitry that is important for attention control function. Yet, it remains unknown how glutamate and GABA content in the attention control circuitry change when people are controlling their attention, and whether these changes can predict impaired attention control in people with ADHD. To study these questions, we recruited 18 adults with ADHD (31–51 years) and 16 adults without ADHD (28–54 years). We studied glutamate + glutamine (Glx) and GABA content in the fronto-striatal circuitry while participants performed attention control tasks. We found that Glx and GABA concentrations at rest did not differ between participants with ADHD or without ADHD. However, while participants were performing the attention control tasks, participants with ADHD showed smaller Glx and GABA increases than participants without ADHD. Notably, smaller GABA increases in participants with ADHD significantly predicted their poor task performance. Together, these findings provide the first demonstration showing that attention control deficits in people with ADHD may be related to insufficient responses of the GABAergic system in the fronto-striatal circuitry. [ABSTRACT FROM AUTHOR]

To reduce damage to surrounding normal tissue from radiotherapy, it is important to minimize respiratory movement during the radiotherapy planning and treatment of patients with thoracic cancer. Procedure-related anxiety, pain and other psychological factors may affect respiratory parameters in a time-dependant manner, resulting in suboptimal planning and radiotherapy. Thirty-one patients with lung cancer, oesophagea[ cancer or breast cancer were randomized to the experimental intervention (HYPRE -- relaxation, autohypnotherapy and exposure in vivo) or to standard self-initiated support (SIS) (control). The primary outcome, respiratory amplitude during radiotherapy planning, was assessed objectively and repeatedly using the Varian RPM system. In addition, other respiratory parameters were assessed repeatedly during the course of radiotherapy, and quality-of-life was assessed on six occasions during the study using standardized psychometric measures. As hypothesized, patients randomized to HYPREL had a lower mean amplitude of respiration during radiotherapy planning (p=0.029). There were no significant differences in amplitude variability, respiration frequency, or frequency variability. The two groups did not differ on any of the respiratory or quality-of-life parameters during the course of radiotherapy. Levels of anxiety and depression were very low in both groups throughout the study. In conclusion, a feasible psychological intervention and protocol have been developed for use in patients undergoing thoracic radiotherapy. Initial evaluation has found the intervention to be widely acceptable and free from adverse effects. Preliminary evaluation found that the intervention reduced respiratory amplitude during radiotherapy planning, thereby optimizing planning and minimizing harm to normal tissue surrounding the tumour. These results are encouraging and provide the basis for a phase 3 randomized controlled trial. [ABSTRACT FROM AUTHOR]

The article focuses on the transformation of the Turkish Studies Association (TSA) into the Ottoman and Turkish Studies Association (OTSA). Topics include the challenges faced by TSA, efforts to revive the organization through publication, finding a new editor, redefining the association's identity, and its subsequent growth under the new name, reflecting a broader academic scope beyond nationalist confines.

Poor school readiness and high rates of expulsion from preschool or day care are common in very young children with attention-deficit/hyperactivity disorder (ADHD), while in cases of severe impulsivity and inadequate monitoring there is real danger of injury to the child and others. Compared to older children, preschool-age children with ADHD have more frequent and often severe ADHD symptoms and high rates of psychiatric and developmental comorbidity.1 As pediatricians are now routinely screening for ADHD in children as young as 4 years of age,2 identification will likely increase. However, once identified, far less is known about treating ADHD.3. [ABSTRACT FROM AUTHOR]

Delivery of mental health treatment in the home can close gaps in care. Telehealth also provides access to healthcare that has been disrupted due to the COVID-19 pandemic. In 2016, a home direct-to-consumer telehealth program was initiated. Mental health encounters made up a significant portion of all telehealth encounters and COVID-19 had a significant impact on accelerating the utilization of telehealth. Telemental health has been more successful at meeting targeted volumes than the overall health system. Of all the mental health diagnoses before and during COVID-19, attention deficit hyperactivity disorder, Autism Spectrum Disorder, and Anxiety Disorder were most common. The direct-to-consumer telehealth program saved patients a significant amount of travel miles and associated time, based on data from the period before COVID-19. Payment reimbursement for direct-to-consumer telehealth professional services was similar to reimbursement for in-person visits. This program demonstrates direct-to-consumer telehealth is a feasible and acceptable care modality for a variety of youth mental health disorders. [ABSTRACT FROM AUTHOR]

Since 2004, multiple blockbuster drugs have been approved for men with metastatic prostate cancer. Nevertheless, it has been reported that no improvement in survival was observed between 2004 and 2009. Herein, we have analyzed the SEER database to assess the survival outcome of metastatic prostate cancer patients since 2000. The results demonstrated that there was an improvement in both overall and prostate cancer‐specific survival for 4 months among men diagnosed with metastatic prostate cancer from 2010 to 2016 when compared to those in the pre‐2010 period. Interestingly, this survival benefit was limited to patients with bone and visceral metastasis (M1b and M1c stages). Collectively, our observation suggests that despite the new treatment agents such as second‐line antiandrogen therapies introduced in the modern era, the improvement in survival of metastatic prostate cancer patients has been surprisingly small. [ABSTRACT FROM AUTHOR]