Waterhouse Friderichsen Syndrome: Medico-legal issues

The Waterhouse-Friderichsen Syndrome (WFS) is a pediatric emergency characterized by high mortality due to the combination of bilateral adrenal haemorrhage, meningococcal infection and cutaneous purpura. WFS often raises medico-legal problems related to missed or delayed diagnosis mainly related to the short clinical course, the sudden onset of symptoms and unexpected death. We report the death of a 2-year-old child who had no other pathologies. Death occurred quickly about 20 h after the first care visit. The forensic autopsy was ordered following the parental complaint for diagnostic delay in primary care. Clinical data, autopsy and histological findings were consistent for WFS by Neisseria meningitidis (NM) serotype B. Medical malpractice was excluded. WFS has a rapid clinical course. By the time fever and purpura are reported, it may be too late as thrombotic and bleeding complications may already be present

Depressive symptoms and depression in individuals with internet gaming disorder: A systematic review and meta-analysis

Background: Although depression has frequently been associated with Internet Gaming Disorder (IGD), its epidemiological impact on this emerging condition has not been systematically assessed. In this study, we aimed to synthesize the available evidence focusing on depression and depressive symptoms in individuals with IGD. Methods: We searched PubMed, Embase, PsycINFO, GreyLit, OpenGrey, and ProQuest up to March 2020 for observational studies focusing on depression-related outcomes in IGD. We conducted random-effects meta-analyses on 1) rate of comorbid depression in IGD; 2) severity of depressive symptoms in IGD participants without depression. Results: We identified 92 studies from 25 different countries including 15,148 participants. 21 studies (n = 5025 participants) provided data for the first analysis, resulting in a pooled event rate of depression of 0.32 (95% Confidence Interval 0.21–0.43). The pooled Beck Depression Inventory scores in individuals without depression were suggestive of mild severity (13 studies, n = 508; 10.3, 95% Confidence Interval 8.3–12.4). Limitations: The considerable inconsistency of methods employed across studies limits the transferability of these findings to clinical practice. Conclusions: The prevalence of depression in individuals with IGD varied considerably across studies, affecting approximately one out of three participants overall. Furthermore, a globally major severity of depressive symptoms was found in those without a clinical diagnosis of depression, compared to the general population. These findings confirm a relevant impact of mood disturbances in IGD. Registration detail: PROSPERO (CRD42018100823)

Digital mental health in schizophrenia and other severe mental illness: an international consensus on current challenges and potential solutions

Background: Digital approaches may be helpful in augmenting care to address unmet mental health needs, particularly in schizophrenia and severe mental illness (SMI). Objectives: An international multidisciplinary group was convened to reach consensus on the challenges and potential solutions in collecting data, delivering treatment and the ethical challenges in digital mental health approaches in schizophrenia and SMI. Methods: The consensus development panel method was used, with an in-person meeting of two groups: the expert group and the panel. Membership was multidisciplinary, including those with lived experience with equal participation at all stages, and co-production of the consensus outputs and summary. Relevant literature was shared in advance of the meeting and a systematic search of the recent literature on digital mental health interventions in schizophrenia and psychosis was completed to ensure the panel was informed before the meeting with the expert group. Results: Four broad areas of challenge and proposed solutions were identified: (i) user involvement for real coproduction, (ii) new approaches to methodology in digital mental health, including agreed standards, data sharing, measuring harms, prevention strategies and mechanistic research (iii) regulation and funding issues (iv) implementation in real-world settings (including multidisciplinary collaboration, training, augmenting existing service provision, social and population-focussed approaches). Examples are provided with more detail on human-centred research design, lived experience perspectives and biomedical ethics in digital mental health approaches in SMI. Conclusions: The consensus agreed on a number of recommendations: (i) a new and improved approach to digital mental health research (with agreed reporting standards, data sharing, and shared protocols) (ii) equal emphasis on social and population research as well as biological and psychological approaches (iii) meaningful collaborations across varied disciplines that have previously not worked closely together (iv) increased focus on the business model and product with planning and new funding structures across the whole development pathway (v) increased focus and reporting on ethical issues and potential harms (vi) organisational changes to allow true communication and coproduction with those with lived experience of SMI. This approach, combining an international expert meeting with PPIE (patient and public involvement and engagement) throughout the process, consensus methodology, discussion, and publication, is a helpful way to identify directions for future research and clinical implementation in rapidly evolving areas, and can be combined with measurements of real-world clinical impact over time. Similar initiatives will be helpful in other areas of digital mental health and similarly fast-evolving fields, to focus research and organisational change and effect improved real-world clinical implementation

Pramipexole augmentation for the acute phase of treatment-resistant, unipolar depression: a placebo-controlled, double-blind, randomised trial in the UK

\ua9 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: About 30% of patients with depression treated with antidepressant medication do not respond sufficiently to the first agents used. Pramipexole might usefully augment antidepressant medication in such cases of treatment-resistant depression, but data on its effects and tolerability are scarce. We aimed to assess the efficacy and tolerability of pramipexole augmentation of ongoing antidepressant treatment, over 48 weeks, in patients with treatment-resistant depression. Methods: We did a multicentre, double-blind, placebo-controlled randomised trial in which adults with resistant major depressive disorder were randomly assigned (1:1; using an online randomisation system) to 48 weeks of pramipexole (titrated to 2\ub75 mg) or placebo added to their ongoing antidepressant medication. The study was conducted in nine National Health Service Trusts in England. Participants, investigators, and researchers involved in recruitment and assessment were masked to group allocation, and the central pharmacy team dispensing the medication was not masked. The primary outcome was change from baseline to week 12 in the total score of the 16-item Quick Inventory of Depressive Symptomology self-report version (QIDS-SR16). The primary analysis was performed on the intention-to-treat population that included all eligible, randomly assigned participants. People with lived experience were involved in the design, oversight, and interpretation of the study. The trial was registered with ISCTRN (ISRCTN84666271) and EudraCT (2019-001023-13) and is complete. Findings: Between Feb 16 and May 29, 2024, 217 participants attended a screening visit, of whom 66 were excluded due to ineligibility. 151 participants were randomly assigned (75 to the pramipexole group and 75 to the placebo group, after one participant was found to be ineligible after randomisation). 84 (56%) participants were female and 66 (44%) were male and the mean age of participants was 44\ub79 years (SD 14\ub70). Ethnicity data were not available. The mean QIDS-SR16 total score at baseline was 16\ub74 (SD 3\ub74) in the pramipexole group and 16\ub72 (3\ub75) in the placebo group. The mean dose of pramipexole received at week 12 was 2\ub73 mg (SD 0\ub745). Adjusted mean decrease from baseline to week 12 of the QIDS-SR16 total score was 6\ub74 (SD 4\ub79) for the pramipexole group and 2\ub74 (4\ub70) for the placebo group; the mean difference between groups was −3\ub791 (95% CI −5\ub737 to −2\ub745; p<0\ub70001). Termination of trial treatment due to adverse events was more frequent in the pramipexole group (15 participants [20%]) than in the placebo group (four participants [5%]), with reported adverse events consistent with known side-effects of pramipexole, in particular nausea, headache, and sleep disturbance or somnolence. Interpretation: In this trial involving participants with treatment-resistant depression, pramipexole augmentation of antidepressant treatment, at a target dose of 2\ub75 mg, demonstrated a reduction in symptoms relative to placebo at 12 weeks but was associated with some adverse effects. These results suggest that pramipexole is a clinically effective option for reducing symptoms in patients with treatment-resistant depression. Future trials directly comparing pramipexole with existing treatments for this disorder are needed. Funding: National Institute of Health and Care Research, Efficacy and Mechanism Evaluation Programme

Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs

Epidemiological studies have shown not only a relationship between the intake of dietary lipids and an increased risk of developing metastatic prostate cancer, but also the type of lipid intake that influences the risk of metastatic prostate cancer. The Omega-6 poly-unsaturated fatty acid, Arachidonic acid, has been shown to enhance the proliferation of malignant prostate epithelial cells and increase the risk of advanced prostate cancer. However, its role in potentiating the migration of cancer cells is unknown. Here we show that arachidonic acid at concentrations ⩽5 μM is a potent stimulator of malignant epithelial cellular invasion, which is able to restore invasion toward hydrocortisone-deprived adipocyte-free human bone marrow stroma completely. This observed invasion is mediated by the arachidonic acid metabolite prostaglandin E2 and is inhibited by the Omega-3 poly-unsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid at a ratio of 1 : 2 Omega-3 : Omega-6, and by the COX-2 inhibitor NS-398. These results identify a mechanism by which arachidonic acid may potentiate the risk of metastatic migration and secondary implantation in vivo, a risk which can be reduced with the uptake of Omega-3 poly-unsaturated fatty acids

Off–label long acting injectable antipsychotics in real–world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction: Information on the off–label use of Long–Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on– vs off–label LAIs and predictors of off–label First– or Second–Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method: In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off– or on–label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off–label group. Results: SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on– and off–label use. Approximately 1 in 4 patients received an off–label prescription. In the off–label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion: Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off–label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co–morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

Modelling of z-Core composite sandwich panels

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