Pharmacokinetics and metabolism of idebenone in healthy male subjects

Purpose: Idebenone is a synthetic analogue of ubiquinone that may be beneficial in the treatment of Friedreich's ataxia. Since in previous pharmacokinetic trials only lower doses were studied, it was the aim of this study to evaluate the pharmacokinetics of idebenone in higher doses of up to 2,250mg/day. Methods: In this open, randomized trial, 25 healthy male subjects received first either a single oral dose of 150mg or 750mg of idebenone, then the same dose given at 8-h intervals for 14days. Results: Idebenone and its metabolites appeared in the plasma quickly. Over 99% of parent idebenone was metabolized, indicating a high first-pass effect. Cmax and AUC0−t values for parent idebenone and its metabolites increased in a dose-proportional manner. There was virtually no accumulation of parent drug or metabolites following multiple dosing. Conclusions: Idebenone exhibited dose-dependent pharmacokinetics in daily doses up to 2,250mg. In 6/14 subjects, adverse events of mild to moderate severity were observe

Bipolar spectrum disorders in a clinical sample of patients with Internet addiction: Hidden comorbidity or differential diagnosis?

Background and aims Behavioral addictions and bipolar disorders have a certain probability of co-occurrence. While the presence of a manic episode has been defined as an exclusion criterion for gambling disorder, no such exclusion has been formulated for Internet addiction. Methods A clinical sample of 368 treatment seekers presenting with excessive to addictive Internet use was screened for bipolar spectrum disorders using the Mood Disorder Questionnaire. Psychopathology was assessed by the Symptom Checklist 90R and a clinical interview was administered to screen for comorbid disorders. Results Comorbid bipolar disorders were more frequent in patients meeting criteria for Internet addiction (30.9%) than among the excessive users (5.6%). This subgroup showed heightened psychopathological symptoms, including substance use disorders, affective disorders and personality disorders. Further differences were found regarding frequency of Internet use regarding social networking sites and online-pornography. Discussion Patients with Internet addiction have a heightened probability for meeting criteria of bipolar disorders. It is not possible to draw conclusions regarding the direction of this association but it is recommended to implement screening for bipolar disorders in patients presenting with Internet addiction. Conclusion Similar to gambling disorder, it might prove necessary to subsume bipolar disorders as an exclusion criterion for the future criteria of Internet addiction

Systematic reviews and meta-analyses of treatment interventions for Internet use disorders: Critical analysis of the methodical quality according to the PRISMA guidelines

Rationale As a result of concerns about predominantly online behavioral addictions, an increasing number of systematic reviews and meta-analyses (SRMA) of treatment interventions for internet use disorders (IUD) are being recorded. This review was designed to (a) systematically identify the evidence base of SRMA and to (b) critically appraise the quality of reporting according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methods Four databases were searched until August 2022 to systematically identify SRMA. PRISMA indicators were evaluated on a three-level response format to obtain an overall score operationalizing the quality of reporting (score range: 0–84). Additionally, the percentage of adherence to the PRISMA indicators was calculated. Results Reporting quality of 23 SRMA, comprising 12 systematic reviews and 11 meta-analyses was evaluated. Quality scores ranged from 25 to 77 (M: 52.91; SD: 17.46). Results of the critical appraisal revealed deviations from the PRISMA indicators, including missing information on (a) registration of a study protocol, (b) statistical synthesis methods (c) evaluation of certainty of evidence, and (d) risk of bias assessment. Eleven (47.83%) of the SRMAs partially adhered, and twelve (52.17%) completely adhered to the PRISMA indicators. Conclusion This first critical appraisal on the reporting quality of SRMA on treatment interventions for IUD highlights limitations of the evidence base. Inadequate reporting compromises the practical utility and validity of SRMA and may complicate ongoing efforts of consensus on evidence-based interventions for IUD. Future research should focus on sufficient and transparent reporting of the methodological approach

How parents of young children manage digital devices at home: the role of income, education and parental style

The main focus of this report is on the role of parental education and household income. Together, these factors capture a major source of difference and inequality across households: hence we ask, how do they shape parental mediation of digital media? For policy-makers and practitioners, it is important to learn whether a generic approach to parental advice and awareness-raising is sufficient, or whether tailored guidance would be more effective for the different target groups of parents being addressed

Unfair play? Video games as exploitative monetized services: An examination of game patents from a consumer protection perspective

Video games as a consumer product have changed significantly with the advent of in-game purchasing systems (e.g., microtransactions, ‘loot boxes’). This review examines consumer protections related to in-game purchasing by anticipating some of the potential design strategies that might contribute to higher risk consumer behavior. Attention was directed towards the analysis of patents for potential in-game purchasing systems, with 13 identified on Google Patents. The design features were analysed in relation to the consumer rights and guarantees described in the terms of use agreements of the patent assignees. The analysis revealed that some in-game purchasing systems could be characterized as unfair or exploitative. These systems describe tactics that capitalize on informational advantages (e.g., behavioral tracking) and data manipulation (e.g., price manipulation) to optimize offers to incentivize continuous spending, while offering limited or no guarantees or protections (e.g., refund entitlement), with the potential to exploit vulnerable players (e.g., adolescents, problematic gamers). These findings are critically discussed in relation to behavioral economics, addiction psychology, and the clinical conceptualization of gaming disorder. Appropriate policy and consumer protection measures, psychologically informed interventions, and ethical game design guidelines are needed in order to protect the interests and wellbeing of consumers

Perfusion‐Dependent Cerebral Autoregulation Impairment in Hemispheric Stroke

Objective: Loss of cerebral autoregulation (CA) plays a key role in secondary neurologic injury. However, the regional distribution of CA impairment after acute cerebral injury remains unclear because, in clinical practice, CA is only assessed within a limited compartment. Here, we performed large-scale regional mapping of cortical perfusion and CA in patients undergoing decompressive surgery for malignant hemispheric stroke. Methods: In 24 patients, autoregulation over the affected hemisphere was calculated based on direct, 15 to 20-minute cortical perfusion measurement with intraoperative laser speckle imaging and mean arterial blood pressure (MAP) recording. Cortical perfusion was normalized against noninfarcted tissue and 6 perfusion categories from 0% to >100% were defined. The interaction between cortical perfusion and MAP was estimated using a linear random slope model and Pearson correlation. Results: Cortical perfusion and CA impairment were heterogeneously distributed across the entire hemisphere. The degree of CA impairment was significantly greater in areas with critical hypoperfusion (40-60%: 0.42% per mmHg and 60-80%: 0.46% per mmHg) than in noninfarcted (> 100%: 0.22% per mmHg) or infarcted (0-20%: 0.29% per mmHg) areas (*p 100% (r = 0.36; *p < 0.05). Tissue integrity had no impact on the degree of CA impairment. Interpretation: In hemispheric stroke, CA is impaired across the entire hemisphere to a variable extent. Autoregulation impairment was greatest in hypoperfused and potentially viable tissue, suggesting that precise localization of such regions is essential for effective tailoring of perfusion pressure-based treatment strategies. ANN NEUROL 202

A clinical evaluation of the DSM-5 criteria for Internet Gaming Disorder and a pilot study on their applicability to further Internet-related disorders

Background and aims: Internet Gaming Disorder (IGD) and other Internet-related disorders (IRDs) have become growing health concerns in our today’s lives. Based on defined diagnostic criteria, IGD has been recognized as a condition for further research in the DSM-5; however, other IRDs have been excluded. Since the release of the DSM-5, representativeness and appropriateness of the nine diagnostic criteria have been debated. Although some first evidence has been published to evaluate these criteria, our knowledge is still limited. Thus, the purpose of this study was to provide data on the clinical validity of the DSM-5 criteria for IGD and other types of IRD. We were also interested in examining the additional diagnostic validity of craving that is currently not being considered in the DSM-5. Methods: Analyses on a sample of n = 166 treatment seekers for IRDs were performed. The clinician’s diagnosis was used as a main reference for determining the DSM criteria’s diagnostic performance. Secondary criteria (depression and anxiety) were defined as indicators for the construct validity. Results: The overall diagnostic accuracy ranged between 76.6% for deceiving and 92% for loss of control and craving. Considerable differences occurred in the degree of sensitivity and specificity between the single criteria. No particular differences were found for the applicability of the criteria to other forms of IRDs. Discussion and conclusions: Our results confirm the validity of the DSM criteria. However, the diagnostic utility of the criterion escaping aversive moods is critically discussed. Considering craving as an additional diagnostic indicator might be recommendable

A case report of delayed cortical infarction adjacent to sulcal clots after traumatic subarachnoid hemorrhage in the absence of proximal vasospasm

Background Cortical ischemic lesions represent the predominant pathomorphological pattern of focal lesions after aneurysmal subarachnoid hemorrhage (aSAH). Autopsy studies suggest that they occur adjacent to subarachnoid blood and are related to spasm of small cortical rather than proximal arteries. Recent clinical monitoring studies showed that cortical spreading depolarizations, which induce cortical arterial spasms, are involved in lesion development. If subarachnoid blood induces adjacent cortical lesions, it would be expected that (i) they also develop after traumatic subarachnoid hemorrhage (tSAH), and (ii) lesions after tSAH can occur in absence of angiographic vasospasm, as was found for aSAH. Case presentation An 86-year-old woman was admitted to our hospital with fluctuating consciousness after hitting her head during a fall. The initial computed tomography (CT) was significant for tSAH in cortical sulci. On day 8, the patient experienced a secondary neurological deterioration with reduced consciousness and global aphasia. Whereas the CT scan on day 9 was still unremarkable, magnetic resonance imaging (MRI) on day 10 revealed new cortical laminar infarcts adjacent to sulcal blood clots. Proximal vasospasm was ruled out using MR and CT angiography and Doppler sonography. CT on day 14 confirmed the delayed infarcts. Conclusions We describe a case of delayed cortical infarcts around sulcal blood clots after tSAH in the absence of proximal vasospasm, similar to results found previously for aSAH. As for aSAH, this case suggests that assessment of angiographic vasospasm is not sufficient to screen for risk of delayed infarcts after tSAH. Electrocorticography is suggested as a complementary method to monitor the hypothesized mechanism of spreading depolarizations

Prevalence, risk factors, and psychosocial adjustment of problematic gambling in adolescents: Results from two representative German samples

Background and aims Gambling disorder is a significant public health concern. Especially, male minors have been shown to gamble in a problematic way, despite legal prohibitions. Methods We examined representative samples of students aged from 12 to 18 years (N = 9,309) in two German federal states to provide prevalence data and clinical description of risk factors for problematic gambling. Results We found that about 40% of the adolescents reported engaging in gambling activities within the past 12 months and found prevalence rates of 1.7% and 2.2% for problematic gambling. Especially, use of online gambling and slot machines was found to be related to problematic gambling. Male adolescents with a migration background were of higher risk for problematic gambling and psychopathological symptoms were significantly elevated among that group. Discussion The results indicate that participation in gambling activities is common among underaged adolescents and that prevalence of problematic gambling exceeds rates of adults. Similarly, problematic gambling is associated with increased psychopathological strain. Conclusion Given that a high proportion of adult gamblers report having started gambling in adolescents, our data emphasize the need for prevention and early intervention strategies for problematic gambling