Search

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]

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]

Background: Attention-deficit/hyperactivity disorder (ADHD) treatment utilization among adolescents is highly variable. This article describes pharmacological and nonpharmacological treatment utilization in a community sample of primarily Latinx and/or Black adolescents with ADHD (N = 218), followed longitudinally for 4 years, from early adolescence until approximately age 17 (M = 16.80, standard deviation = 1.65). Methods: Electronic surveys administered between 2012 and 2019 queried parent and youth reports of medication initiation, persistence, diversion, and misuse, as well as reasons for desistence. Nonpharmacological treatment utilization (including complementary and alternative treatments) was also measured. Results: Results indicated that: (1) the majority of the sample sought treatment for ADHD in their community, (2) rates of psychosocial treatment utilization were higher than medication utilization, (3) approximately half of the medicated sample discontinued community-administered ADHD medication during the follow-up period, most frequently citing tolerability issues and concerns that they were "tired of taking" medication, and (4) medication misuse consisted of youth diversion and parent utilization of teen medication, but both were reported at low rates. Race/ethnicity did not predict treatment utilization patterns, but lower family adversity and psychiatric comorbidity predicted persistence of medication use over time. Conclusions: ADHD treatment engagement efforts for Latinx and/or Black adolescents might link treatment to goals valued by the youth, address concerns related to medication tolerability, and promote secure monitoring of medication. Nonpharmacological treatments for ADHD may be more palatable to Latinx and Black youth with ADHD, and efforts to engage youth with ADHD in treatment should consider offering medication and psychosocial treatment options. [ABSTRACT FROM AUTHOR]

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]

There is a robust literature of predominantly cross-sectional studies demonstrating an association between attention-deficit/hyperactivity disorder (ADHD) and sleep quality in childhood and adolescence, measured by subjective as well as objective measures, dimensional and categorical variables, and controlling for a wide range of confounders such as other disorders.1 Moreover, ADHD symptoms and sleep problems are independently associated with adverse functional outcome and quality of life.2 As a result, these are viewed as common and mutually exacerbating conditions, likely mediated by common neuropathways.3-5. [ABSTRACT FROM AUTHOR]

Objective: To identify patient- and treatment-level factors that predict intervention engagement and outcome for adolescents with attention-deficit/hyperactivity disorder (ADHD), guiding efforts to enhance care.Method: Integrative data analysis was used to pool data from 4 randomized controlled trials of adolescent ADHD treatment with participants (N = 854) receiving various evidence-based behavioral therapy packages in 5 treatment arms (standard [STANDARD], comprehensive [COMP], engagement-focused [ENGAGE]), community-based usual care (UC), or no treatment (NOTX). Participants also displayed varying medication use patterns (negligible, inconsistent, consistent) during the trial. Regression and latent growth curve analyses examined treatment- and patient-level predictors of engagement and outcome.Results: Compared with COMP, ENGAGE was associated with higher parent engagement in behavioral therapy (d = 1.35-1.73) when delivered in university, but not community, clinics. Under some conditions, ENGAGE also predicted youth engagement in behavioral therapy (d = 1.21) and lower likelihood of negligible medication use (odds ratio = 0.49 compared with NOTX). UC was associated with poorer parent engagement compared with COMP (d = -0.59) and negligible medication use (odds ratio = 2.29) compared with NOTX. Compared with COMP, ENGAGE (in university settings) was consistently associated with larger ADHD symptom improvements (d = 0.41-0.83) at 6-month follow-up and sometimes associated with larger grade point average (d = 0.68) and parent-teen conflict (d = 0.41) improvements. Consistent medication use during behavioral therapy was associated with larger improvements in ADHD symptoms (d = 0.28) and parent-teen conflict (d = 0.25-0.36). An ADHD+internalizing clinical profile predicted larger improvements in grade point average (d = 0.45). Family adversity predicted poorer parent and youth engagement (rate ratio = 0.90-0.95), negligible medication use (odds ratio = 1.22), and smaller improvements in grade point average (d = -0.23). African American race predicted smaller improvements in parent-teen conflict (d = -0.49).Conclusion: Engagement-focused behavioral therapy and consistent medication use most frequently predicted stronger clinical engagement and outcomes for adolescents with ADHD. Youths who are African American or who experience family adversity may demonstrate treatment-related disparities for certain outcomes; youths with ADHD+internalizing symptoms may demonstrate excellent academic outcomes following behavioral therapy.Data Sharing: The full ADHD TIDAL dataset is publicly available through the National Data Archive (https://nda.nih.gov), including a data dictionary. The study protocol is also publicly available: https://doi.org/10.1186/s12888-020-02734-6. [ABSTRACT FROM AUTHOR]

Formal Thought Disorder (FTD) is a defining feature of schizophrenia, which is often assessed through patients' speech. Meanwhile, the written language is less studied. The aim of the present study is to establish and validate a comprehensive clinical screening scale, capturing the full variety of empirical characteristics of writing in patients with schizophrenia. The 16-item Screening Instrument for Schizophrenic Features in Writing (SISFiW) is derived from detailed literature review and a "brainstorming" discussion on 30 samples written by patients with schizophrenia. One hundred and fifty-seven participants (114 patients with an ICD-10 diagnoses of schizophrenia; 43 healthy control subjects) were interviewed and symptoms assessed with the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Thought, Language, and Communication (TLC). Article samples written by each participant were rated with the SISFiW. Results demonstrated significant difference of the SISFiW-total between the patient group and healthy controls [(3.61 ± 1.72) vs. (0.49 ± 0.63), t = 16.64, p <0.001]. The inter-rater reliability (weighted kappa = 0.72) and the internal consistency (Cronbach's alpha coefficient = 0.613) were acceptable, but correlations with the criterion (PANSS and TLC) were unremarkable. The ROC analysis indicated a cutoff point at 2 with the maximal sensitivity (93.0 %)/specificity (93.0 %). Discriminant analysis of the SISFiW items yielded 8 classifiers that discriminated between the diagnostic groups at a perfect overall performance (with 90.4 % of original and 88.5 % cross-validated grouped cases classified correctly). This instrument appears to be practicable and reliable, with relatively robust discriminatory power, and may serve as a complementary tool to existing FTD rating scales. • Developed a screening instrument to assess features within the writing of subjects. • Items cover full variety of empirical characteristics of written language, as well as traits in graphology and writing trace. • The inter-rater reliability and the internal consistency of this scale are acceptable. • A minimum of 2 items can differentiate patient with schizophrenia from healthy people with accuracy higher than 90 %. • The properties measured in this screening instrument may not equate to Formal Thought Disorder (FTD) in written language. [ABSTRACT FROM AUTHOR]

Patients undergoing resection of renal cell carcinoma are at risk of disease relapse. We evaluated the effectiveness of the mammalian target of rapamycin inhibitor everolimus administered after surgery. In this randomised, double-blind, phase 3 trial, we enrolled adults with histologically confirmed renal cell carcinoma who had undergone a full surgical resection and were at intermediate-high or very high risk of recurrence at 398 academic and community institution centres in the USA. After nephrectomy, patients were randomly assigned (1:1) via a central web-based application using a dynamic balancing algorithm to receive 10 mg oral everolimus daily or placebo for 54 weeks. The primary endpoint was recurrence-free survival. Efficacy analyses included all eligible, randomly assigned patients; safety analysis included all patients who received treatment. This trial is registered with ClinicalTrials.gov , NCT01120249 and is closed to new participants. Between April 1, 2011, and Sept 15, 2016, a total of 1545 patients were randomly assigned to receive everolimus (n=775) or placebo (n=770), of whom 755 assigned to everolimus and 744 assigned to placebo were eligible for inclusion in the efficacy analysis. With a median follow-up of 76 months (IQR 61–92), recurrence-free survival was longer with everolimus than with placebo (5-year recurrence-free survival 67% [95% CI 63–70] vs 63% [60–67]; stratified log-rank p=0·050; stratified hazard ratio [HR] 0·85, 95% CI 0·72–1·00; p=0·051) but did not meet the prespecified p value for statistical significance of 0·044. Recurrence-free survival was longer with everolimus than with placebo in the very-high-risk group (HR 0·79, 95% CI 0·65–0·97; p=0·022) but not in the intermediate-high-risk group (0·99, 0·73–1·35; p=0·96). Grade 3 or higher adverse events occurred in 343 (46%) of 740 patients who received everolimus and 79 (11%) of 723 who received placebo. Postoperative everolimus did not improve recurrence-free survival compared with placebo among patients with renal cell carcinoma at high risk of recurrence after nephrectomy. These results do not support the adjuvant use of everolimus for renal cell carcinoma after surgery. US National Institutes of Health, National Cancer Institute, National Clinical Trials Network, Novartis Pharmaceuticals Corporation, and The Hope Foundation. [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]

Purpose: Veliparib (V), an oral poly(ADP-ribose) polymerase (PARP) inhibitor, potentiates effects of alkylating agents and topoisomerase inhibitors in preclinical tumor models. We conducted a phase I trial of V with iv cyclophosphamide (C) and V plus iv doxorubicin (A) and C. Methods: Objectives were to establish the maximum tolerated dose (MTD) of the combinations, characterize V pharmacokinetics (PK) in the presence and absence of C, measure PAR in peripheral blood mononuclear cells (PBMCs) and γH2AX in circulating tumor cells (CTCs). In Group 1, dose escalations of V from 10 to 50 mg every 12 h Days 1–4 plus C 450 to 750 mg/m2 Day 3 in 21-day cycles were evaluated. In Group 2, V doses ranged from 50 to 150 mg every 12 h Days 1–4 with AC (60/600 mg/m2) Day 3 in 21-day cycles. In Group 3, patients received AC Day 1 plus V Days 1–7, and in Group 4, AC Day 1 plus V Days 1–14 was given in 21-day cycles to evaluate effects on γH2AX foci. Results: Eighty patients were enrolled. MTD was not reached for V and C. MTD for V and AC was V 100 mg every 12 h Days 1–4 with AC (60/600 mg/m2) Day 3 every 21 days. V PK appears to be dose-dependent and has no effect on the PK of C. Overall, neutropenia and anemia were the most common adverse events. Objective response in V and AC treated groups was 22% (11/49). Overall clinical benefit rate was 31% (25/80). PAR decreased in PBMCs. Percentage of γH2AX-positive CTCs increased after treatment with V and AC. Conclusion: V and AC can be safely combined. Activity was observed in patients with metastatic breast cancer. [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]

• ADHD occurs in 5.9 % of youth and 2.5 % of adults. • Most cases of ADHD are caused by the combined effects of many genetic and environmental risks. • There are small differences in the brain between people with and without ADHD. • Untreated ADHD can lead to many adverse outcomes. • ADHD costs society hundreds of billions of dollars each year, worldwide. Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base. We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder. We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents. Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma. [ABSTRACT FROM AUTHOR]

Purpose: The rapid expansion of telemedicine has presented a challenge for the care of patients with genitourinary malignancies. We sought to assess patient and physician perspectives on the use of telemedicine for genitourinary cancer care.Methods: We conducted a prospective cross-sectional study of patients who had telemedicine visits with urology, medical oncology, or radiation oncology for management of genitourinary malignancies from July-August 2020. Patients and physicians each received a questionnaire regarding the telemedicine experience. Responses were scored on a 5-point Likert scale. The primary outcomes of the study were patient and physician satisfaction.Results: Of the 115 patients who enrolled, we received 96 patient responses and 46 physician responses. Overall, 77% of patients and 70% of physicians reported being "extremely satisfied" with the telemedicine encounter. Satisfaction was high among all components of the encounter including patient-physician communication, counseling, shared decision making, time spent, timeliness and efficiency, and convenience. Additionally, 78% of patients and 85% of physicians "strongly agreed" that they were able to discuss sensitive topics about cancer care as well as they could at an in-person visit. Nine telemedicine visits (9%) encountered technological barriers. Technological barriers were associated with lower overall satisfaction scores among both patients and physicians (p ≤ 0.01).Conclusion: We observed high levels of patient and physician satisfaction for telemedicine visits for management of genitourinary malignancies. Technological barriers were encountered by 9% of patients and were associated with decreased satisfaction. [ABSTRACT FROM AUTHOR]

When compared to other malignancies, the tumor microenvironment (TME) of primary and castration-resistant prostate cancer (CRPC) is relatively devoid of immune infiltrates. While androgen deprivation therapy (ADT) induces a complex immune infiltrate in localized prostate cancer, the composition of the TME in metastatic castration-sensitive prostate cancer (mCSPC), and the effects of ADT and other treatments in this context are poorly understood. Here, we perform a comprehensive single-cell RNA sequencing (scRNA-seq) profiling of metastatic sites from patients participating in a phase 2 clinical trial (NCT03951831) that evaluated standard-of-care chemo-hormonal therapy combined with anti-PD-1 immunotherapy. We perform a longitudinal, protein activity-based analysis of TME subpopulations, revealing immune subpopulations conserved across multiple metastatic sites. We also observe dynamic changes in these immune subpopulations in response to treatment and a correlation with clinical outcomes. Our study uncovers a therapy-resistant, transcriptionally distinct tumor subpopulation that expands in cell number in treatment-refractory patients. [Display omitted] • Protein-inferred activity clustering shows complex immune cells in CSPC metastases • ADT and aPD-1 treatment induces robust infiltrates of CD8+, CD4+ T cells, and Tregs • T cell infiltration determined by scRNA-seq correlated with T cells shown by qmIF • Baseline tumor and immune clusters associated with clinical outcomes TME composition of metastatic castration-sensitive prostate cancer (mCSPC) remains elusive. Hawley et al. perform scRNA-seq analysis of metastatic sites from mCSPC patients with ADT and anti-PD-1 treatment, identify tumor and immune subpopulations conserved across multiple metastatic sites, and reveal treatment-induced dynamic changes in these subpopulations and their correlation with clinical outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy has changed the landscape of treatment modalities available for many different types of malignancies. However, the factors that influence the success of immunotherapeutics have not been as clearly seen in advanced prostate cancer, likely due to immunosuppressive factors that exist within the prostate cancer tumor microenvironment. While there have been many immunotherapeutics used for prostate cancer, the majority have targeted a single immunosuppressive mechanism resulting in limited clinical efficacy. More recent research centered on elucidating the key mechanisms of immune resistance in the prostate tumor microenvironment has led to the discovery of a range of new treatment targets. With that in mind, many clinical trials have now set out to evaluate combination immunotherapeutic strategies in patients with advanced prostate cancer, in the hopes of circumventing the immunosuppressive mechanisms. The use of immunotherapy has become a critical treatment modality in many advanced cancers. However, immunotherapy in prostate cancer has not been met with similar success. Multiple interrelated mechanisms, such as low tumor mutational burden, immunosuppressive cells, and impaired cellular immunity, appear to subvert the immune system, creating an immunosuppressive tumor microenvironment and leading to lower treatment efficacy in advanced prostate cancer. The lethality of metastatic castrate-resistant prostate cancer is driven by the lack of therapeutic regimens capable of generating durable responses. Multiple strategies are currently being tested to overcome immune resistance including combining various classes of treatment modalities. Several completed and ongoing trials have shown that combining vaccines or checkpoint inhibitors with hormonal therapy, radiotherapy, antibody–drug conjugates, chimeric antigen receptor T cell therapy, or chemotherapy may enhance immune responses and induce long-lasting clinical responses without significant toxicity. Here, we review the current state of immunotherapy for prostate cancer, as well as tumor-specific mechanisms underlying therapeutic resistance, with a comprehensive look at the current preclinical and clinical immunotherapeutic strategies aimed at overcoming the immunosuppressive tumor microenvironment and impaired cellular immunity that have largely limited the utility of immunotherapy in advanced prostate cancer. [ABSTRACT FROM AUTHOR]