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The mediating role of reflective functioning and general psychopathology in the relationship between childhood conduct disorder and adult aggression among offenders
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is properly cited.BACKGROUND: The nature of the pathway from conduct disorder (CD) in adolescence to antisocial behavior in adulthood has been debated and the role of certain mediators remains unclear. One perspective is that CD forms part of a general psychopathology dimension, playing a central role in the developmental trajectory. Impairment in reflective functioning (RF), i.e., the capacity to understand one's own and others' mental states, may relate to CD, psychopathology, and aggression. Here, we characterized the structure of psychopathology in adult male-offenders and its role, along with RF, in mediating the relationship between CD in their adolescence and current aggression. METHODS: A secondary analysis of pre-treatment data from 313 probation-supervised offenders was conducted, and measures of CD symptoms, general and specific psychopathology factors, RF, and aggression were evaluated through clinical interviews and questionnaires. RESULTS: Confirmatory factor analyses indicated that a bifactor model best fitted the sample's psychopathology structure, including a general psychopathology factor (p factor) and five specific factors: internalizing, disinhibition, detachment, antagonism, and psychoticism. The structure of RF was fitted to the data using a one-factor model. According to our mediation model, CD significantly predicted the p factor, which was positively linked to RF impairments, resulting in increased aggression. CONCLUSIONS: These findings highlight the critical role of a transdiagnostic approach provided by RF and general psychopathology in explaining the link between CD and aggression. Furthermore, they underscore the potential utility of treatments focusing on RF, such as mentalization-based treatment, in mitigating aggression in offenders with diverse psychopathologies.https://www.cambridge.org/core/journals/psychological-medicine/article/mediating-role-of-reflective-functioning-and-general-psychopathology-in-the-relationship-between-childhood-conduct-disorder-and-adult-aggression-among-offenders/15FD2888DE64D91DCA403AC197011C1
Safety and feasibility of early discharge after transcatheter aortic valve implantation with ACURATE Neo-the POLESTAR trial
No full textBackground: Transcatheter aortic valve implantation (TAVI) serves a growing range of patients with severe aortic stenosis (AS). TAVI has evolved to a streamlined procedure minimizing length of hospital stay. Aims: To evaluate the safety and efficacy of an early discharge (ED) strategy after TAVI. Methods: We performed an international, multi-center, prospective observational single-arm study in AS patients undergoing TAVI with the ACURATE valve platform. Eligibility for ED was assessed prior to TAVI and based on prespecified selection criteria. Discharge ≤ 48 h was defined as ED. Primary Valve Academic Research Consortium (VARC)-3-defined 30-day safety and efficacy composite endpoints were landmarked at 48 h and compared between ED and non-ED groups. Results: A total of 252 patients were included. The median age was 82 [25th-75th percentile, 78-85] years and the median Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 2.2% [25th-75th percentile, 1.6-3.3]. ED and non-ED were achieved in 173 (69%) and 79 (31%) patients respectively. Monitoring for conduction disturbances was the principal reason for non-ED (33%). Overall, at 30 days, all-cause mortality was 1%, new permanent pacemaker rate was 4%, and valve- or procedure-related rehospitalization was 4%. There was no difference in the primary safety and efficacy endpoint between the ED and non-ED cohorts (OR 0.84 [25th-75th percentile, 0.31-2.26], p = 0.73, and OR 0.97 [25th-75th percentile, 0.46-2.06], p = 0.94). The need for rehospitalization was similarly low for ED and non-ED groups. Conclusion: Early discharge after TAVI with the ACURATE valve is safe and feasible in selected patients. Rhythm monitoring and extended clinical observation protracted hospital stay.https://link.springer.com/article/10.1007/s00392-024-02436-
The 1000 Mitoses Project: a consensus-based international collaborative study on mitotic figures classification
No full textIntroduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.https://journals.sagepub.com/doi/10.1177/10668969241234321?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubme
Daylight photodynamic therapy as a treatment for actinic field change in patients diagnosed with oculocutaneous albinism in sub-Saharan Africa
No full textBackground: Oculocutaneous albinism (OCA) is a genetically inherited condition, whereby melanin is reduced or absent in the skin. A lack of melanin predisposes people to actinic damage and skin malignancies. In Tanzania, a resource-limited country, the treatment of choice for precancerous skin lesions is cryotherapy. Objectives: To investigate whether daylight photodynamic therapy (dPDT) is a safe and well-tolerated treatment for actinic field change in the OCA population in Tanzania. Methods: Twelve participants with actinic damage were recruited from a Standing Voice skin surveillance clinic and treated with dPDT. Study participants completed tolerability and acceptability questionnaires at day 5 and 3 months after treatment. A dermatologist assessed their clinical response to dPDT at 3 months. Results: dPDT was well-tolerated and acceptable to the majority of patients. Actinic damage was reduced by 25-90%. No skin cancers developed during the treatment. Conclusions: This pilot study suggests that dPDT is a safe and tolerable treatment for actinic damage in people with OCA in Tanzania. Further work is required to compare the efficacy of dPDT against other topical therapies for actinic field change.https://academic.oup.com/ced/article-abstract/49/5/484/7442645?redirectedFrom=fulltext&login=fals
Ibrutinib as part of risk-stratified treatment for post-transplant lymphoproliferative disorder: The phase 2 TIDaL trial
No full textPost-transplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation, and cytotoxic chemotherapy is associated with treatment-related morbidity and mortality. Current treatment takes a sequential, risk-stratified approach, patients with low-risk disease following initial immunotherapy can avoid escalation to immunochemotherapy. TIDaL is a prospective, single-arm phase 2 trial investigating the activity and tolerability of ibrutinib combined with risk-stratified therapy for first-line treatment of PTLD. Eligible patients were adults with newly-diagnosed CD20-positive B-cell PTLD after solid organ transplant and performance status 0 to 2. Initial treatment comprised 49 days of ibrutinib 560mg once daily, with 4 doses of weekly rituximab. Treatment response on interim scan and baseline international prognostic index were used to allocate patients to either a low-risk arm (who continued ibrutinib, alongside 4 further doses of 3-weekly rituximab) or high-risk (escalation to R-CHOP immunochemotherapy, ibrutinib continuing in patients aged <65 years). The primary outcome was complete response on interim scan, achieved by 11/38 patients (29%, 95% confidence interval (CI) 15% - 46%). This did not reach the pre-specified threshold for clinically significant activity. Secondary outcomes included allocation to the low-risk arm (41% of patients), 2-year progression-free survival (58%, 95% CI 44% - 76%), and 2-year overall survival (76%, 95% CI 63% - 91%). Adverse events were mostly haematological, gastrointestinal and infective. Whilst TIDaL does not support adding ibrutinib into first-line treatment of PTLD, increasing the proportion of patients who can be treated without cytotoxic chemotherapy remains an important aim of future research. This trial was registered as ISRCTN32667607.https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2024023847/515797/Ibrutinib-as-part-of-risk-stratified-treatment-for?redirectedFrom=fulltex
Regular follow-up with cervical cytology is of questionable value following surgical treatment of microinvasive cervical cancer.
No full textOBJECTIVES: To assess the follow-up smears and their outcomes of patients with conservatively managed early-stage cervical cancer as per UK guidelines within our service. To evaluate whether intensive follow-up can detect pre-cancer early compared to the standard 3 yearly follow-up. STUDY DESIGN: Retrospective review. METHODS: All patients treated for early stage (stage 1A1 and 1A2) with cervical cancer from 01/2002 to 01/2020 at University Hospitals of Derby and Burton were included. Patients who had initial hysterectomy were excluded from our analysis. Review conducted using electronic patient records for treatment, histology, and follow-up smears. Number of abnormal follow-up smears and number of recurrent cervical cancers were considered the main outcome measures. RESULTS: 98 cases were identified. 81 (82.65 %) were stage 1A1 and 17 (17.35 %) were stage 1A2. 74 (75.51 %) patients had squamous histology and 24 (24.49 %) had adenocarcinomas. Median follow-up was 11.08 years (4043 days). 510 follow-up smears were performed, of which 33 (6.47 %) were abnormal. 5 of these abnormal smears showed low grade dyskaryosis (0.98 %) and 2 smears showed high grade dyskaryosis (0.39 %). The positive predictive value of follow-up smears to detect pre-cancerous changes was 5.71 %. There were no recurrent cancers detected. CONCLUSIONS: Microinvasive cervical cancer is effectively managed with conservative surgery. There were no recurrent cancers detected in our cohort during follow-up and there were only 2 high grade dyskaryoses detected (n = 2/510, 0.39 %). We therefore believe that reducing the intensity of follow up of these patients should be considered
A systematic review and meta-analysis of diagnostic performance of fluorescein-guided sentinel lymph node biopsy in early breast cancer
No full textBACKGROUND: Evaluation of axillary lymph nodes status in cN0 axilla is performed by sentinel lymph node biopsy (SLNB) utilizing a combination of radioactive isotope and blue dye or alternative to isotope like Indocyanine green (ICG). Both are very resource-intensive; which has prompted development of low-cost technique of Fluorescein Sodium (FS)-guided SLNB. This systematic review and meta-analysis evaluate the diagnostic performance of FS-guided SLNB in early breast cancer. OBJECTIVES: The objective was to evaluate the diagnostic performance of FS for sentinel lymph node biopsy. METHODS: Eligibility criteria: Studies where SLNB was performed using FS. INFORMATION SOURCES: PubMed, EMBASE, Cochrane library and online clinical trial registers. Risk of bias: Articles were assessed for risk of bias using the QUADAS-2 tool. SYNTHESIS OF RESULTS: The main summary measures were pooled Sentinel Lymph Node Identification Rate (SLN-IR) and pooled False Negative Rate (FNR) using random-effects model. RESULTS: A total of 45 articles were retrieved by the initial systematic search. 7 out of the 45 studies comprising a total of 332 patients were included in the meta-analysis. The pooled SLN-IR was 93.2% (95% confidence interval [CI], 0.87-0.97; 87% to 97%). Five validation studies were included for pooling the false negative rate and included a total of 211 patients. The pooled FNR was 5.6% (95% confidence interval [CI], 2.9-9.07). CONCLUSION: Fluorescein-guided SLNB is a viable option for detection of lymph node metastases in clinically node negative patients with early breast cancer. It achieves a high pooled Sentinel Lymph Node Identification Rate (SLN-IR) of 93% with a false negative rate of 5.6% for the detection of axillary lymph node metastasis
Internet-delivered exposure and response prevention for pediatric tourette syndrome: 12-month follow-up of a randomized clinical trial
Get PDFThis is an open access article distributed under the terms of the CC-BY License. © 2024 Andrén P
et al.JAMA Network OpenIMPORTANCE: Behavior therapy is a recommended intervention for Tourette syndrome (TS) and chronic tic disorder (CTD), but availability is limited and long-term effects are uncertain. OBJECTIVE: To investigate the long-term efficacy and cost-effectiveness of therapist-supported, internet-delivered exposure and response prevention (ERP) vs psychoeducation for youths with TS or CTD. DESIGN, SETTING, AND PARTICIPANTS: This 12-month controlled follow-up of a parallel group, superiority randomized clinical trial was conducted at a research clinic in Stockholm, Sweden, with nationwide recruitment. In total, 221 participants aged 9 to 17 years with TS or CTD were enrolled between April 26, 2019, and April 9, 2021, of whom 208 (94%) provided 12-month follow-up data. Final follow-up data were collected on June 29, 2022. Outcome assessors were masked to treatment allocation throughout the study. INTERVENTIONS: A total of 111 participants were originally randomly allocated to 10 weeks of therapist-supported, internet-delivered ERP and 110 participants to therapist-supported, internet-delivered psychoeducation. MAIN OUTCOMES AND MEASURES: The primary outcome was within-group change in tic severity, measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS), from the 3-month follow-up to the 12-month follow-up. Treatment response was defined as 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement scale. Analyses were intention-to-treat and followed the plan prespecified in the published study protocol. A health economic evaluation was performed from 3 perspectives: health care organization (including direct costs for treatment provided in the study), health care sector (additionally including health care resource use outside of the study), and societal (additionally including costs beyond health care [eg, parent's absenteeism from work]). RESULTS: In total, 221 participants were recruited (mean [SD] age, 12.1 [2.3] years; 152 [69%] male). According to the YGTSS-TTSS, there were no statistically significant changes in tic severity from the 3-month to the 12-month follow-up in either group (ERP coefficient, -0.52 [95% CI, -1.26 to 0.21]; P = .16; psychoeducation coefficient, 0.00 [95% CI, -0.78 to 0.78]; P > .99). A secondary analysis including all assessment points (baseline to 12-month follow-up) showed no statistically significant between-group difference in tic severity from baseline to the 12-month follow-up (coefficient, -0.38 [95% CI, -1.11 to 0.35]; P = .30). Treatment response rates were similar in both groups (55% in ERP and 50% in psychoeducation; odds ratio, 1.25 [95% CI, 0.73-2.16]; P = .42) at the 12-month follow-up. The health economic evaluation showed that, from a health care sector perspective, ERP produced more quality-adjusted life years (0.01 [95% CI, -0.01 to 0.03]) and lower costs (adjusted mean difference -440.20 to 79 000. CONCLUSIONS AND RELEVANCE: There were no statistically significant changes in tic severity from the 3-month through to the 12-month follow-up in either group. The ERP intervention was not superior to psychoeducation at any time point. While ERP was not superior to psychoeducation alone in reducing tic severity at the end of the follow-up period, ERP is recommended for clinical implementation due to its likely cost-effectiveness and support from previous literature.https://jamanetwork.com/journals/jamanetworkopen/fullarticle/281824
Nature of neurological complications and outcome after surgery for type A aortic dissection
No full textSurgery for type A aortic dissection (TAAD) is frequently complicated by neurologic complications. The prognostic impact of neurologic complications of different nature has been investigated in this study. The subjects of this analysis were 3,902 patients who underwent surgery for acute TAAD from the multicenter European Registry of Type A Aortic Dissection (ERTAAD). During the index hospitalization, 722 patients (18.5%) experienced stroke/global brain ischemia. Ischemic stroke was detected in 539 patients (13.8%), hemorrhagic stroke in 76 patients (1.9%) and global brain ischemia in 177 patients (4.5%), with a few patients having had findings of more than 1 of these conditions. In-hospital mortality was increased significantly in patients with postoperative ischemic stroke (25.6%, adjusted odds ratio [OR] 2.422, 95% confidence interval [CI] 1.825 to 3.216), hemorrhagic stroke (48.7%, adjusted OR 4.641, 95% CI 2.524 to 8.533), and global brain ischemia (74.0%, adjusted OR 22.275, 95% CI 14.537 to 35.524) compared with patients without neurologic complications (13.5%). Similarly, patients who experienced ischemic stroke (46.3%, adjusted hazard ratio [HR] 1.719, 95% CI 1.434 to 2.059), hemorrhagic stroke (62.8%, adjusted HR 3.236, 95% CI 2.314 to 4.525), and global brain ischemia (83.9%, adjusted HR 12.777, 95% CI 10.325 to 15.810) had significantly higher 5-year mortality than patients without postoperative neurologic complications (27.5%). The negative prognostic effect of neurologic complications on survival vanished about 1 year after surgery. In conclusion, postoperative ischemic stroke, hemorrhagic stroke, and global cerebral ischemia increased early and midterm mortality after surgery for acute TAAD. The magnitude of risk of mortality increased with the severity of the neurologic complications, with postoperative hemorrhagic stroke and global brain ischemia being highly lethal complications.https://www.ajconline.org/article/S0002-9149(24)00167-X/abstrac
Developing a process for assessing the safety of a digital mental health intervention and gaining regulatory approval: A case study and academic's guide
Get PDF© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the
original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or
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regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this
licence, visit http://creativecommons.org/licenses/by/4.0/.BACKGROUND: The field of digital mental health has followed an exponential growth trajectory in recent years. While the evidence base has increased significantly, its adoption within health and care services has been slowed by several challenges, including a lack of knowledge from researchers regarding how to navigate the pathway for mandatory regulatory approval. This paper details the steps that a team must take to achieve the required approvals to carry out a research study using a novel digital mental health intervention. We used a randomised controlled trial of a digital mental health intervention called STOP (Successful Treatment of Paranoia) as a worked example. METHODS: The methods section explains the two main objectives that are required to achieve regulatory approval (MHRA Notification of No Objection) and the detailed steps involved within each, as carried out for the STOP trial. First, the existing safety of digital mental health interventions must be demonstrated. This can refer to literature reviews, any feasibility/pilot safety data, and requires a risk management plan. Second, a detailed plan to further evaluate the safety of the digital mental health intervention is needed. As part of this we describe the STOP study's development of a framework for categorising adverse events and based on this framework, a tool to collect adverse event data. RESULTS: We present literature review results, safety-related feasibility study findings and the full risk management plan for STOP, which addressed 26 possible hazards, and included the 6-point scales developed to quantify the probability and severity of typical risks involved when a psychiatric population receives a digital intervention without the direct support of a therapist. We also present an Adverse Event Category Framework for Digital Therapeutic Devices and the Adverse Events Checklist-which assesses 15 different categories of adverse events-that was constructed from this and used in the STOP trial. CONCLUSIONS: The example shared in this paper serves as a guide for academics and professionals working in the field of digital mental health. It provides insights into the safety assessment requirements of regulatory bodies when a clinical investigation of a digital mental health intervention is proposed. Methods, scales and tools that could easily be adapted for use in other similar research are presented, with the expectation that these will assist other researchers in the field seeking regulatory approval for digital mental health products.https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-024-08421-