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Background: Identifying risk factors contributing the most to mortality of childhood cancer survivors is essential to guide harm reduction efforts in childhood cancer treatments, and long-term follow-up of childhood cancer survivors., Methods: We assessed Life Years Lost from childhood cancer treatments and their health-related late effects among the French Childhood Cancer Survivors Study, a cohort of 7670 5-year childhood cancer survivors. Using a landmark strategy, we also assessed time-varying effects of risk factors, and how the multi-morbidity affects life years lost., Results: We found subsequent malignant neoplasm (9.0 years [95 %CI: 4.3-13.7]), severe cardiac disease (8.0 years [95 %CI: 1.2-14.9]), and the use of radiotherapy (6.0 years [95 %CI: 4.7-7.3]) to be the highest contributors to Life Years Lost among childhood cancer survivors. We found no interaction impact on life years lost between health related late effects considered., Conclusions: Those findings suggest that radiotherapy is the root cause of early mortality among childhood cancer survivors. Moreover patients experiencing a subsequent malignant neoplasm or a cardiac disease should be monitored closely after the event, as comorbidity is common and causes premature deaths., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In controlled organ donation after circulatory determination of death (cDCDD), accurate and timely death determination is critical, yet knowledge gaps persist. Further research to improve the science of defining and determining death by circulatory criteria is therefore warranted. In a workshop sponsored by the National Heart, Lung, and Blood Institute, experts identified research opportunities pertaining to scientific, conceptual, and ethical understandings of DCDD and associated technologies. This article identifies a research strategy to inform the biomedical definition of death, the criteria for its determination, and circulatory death determination in cDCDD. Highlighting knowledge gaps, we propose that further research is needed to inform the observation period following cessation of circulation in pediatric and neonatal populations, the temporal relationship between the cessation of brain and circulatory function after the withdrawal of life-sustaining measures in all patient populations, and the minimal pulse pressures that sustain brain blood flow, perfusion, activity, and function. Additionally, accurate predictive tools to estimate time to asystole following the withdrawal of treatment and alternative monitoring modalities to establish the cessation of circulatory, brainstem, and brain function are needed. The physiologic and conceptual implications of postmortem interventions that resume circulation in cDCDD donors likewise demand attention to inform organ recovery practices. Finally, because jurisdictionally variable definitions of death and the criteria for its determination may impede collaborative research efforts, further work is required to achieve consensus on the physiologic and conceptual rationale for defining and determining death after circulatory arrest., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Web-based interventions can be effective in treating depressive symptoms. Patients with risk not responding to treatment have been identified by early change patterns. This study aims to examine whether early changes are superior to baseline parameters in predicting long-term outcome. In a randomized clinical trial with 409 individuals experiencing mild to moderate depressive symptoms using the web-based intervention deprexis, three latent classes were identified (early response after registration, early response after screening and early deterioration) based on early change in the first four weeks of the intervention. Baseline variables and these classes were included in a Stepwise Cox Proportional Hazard Multiple Regression to identify predictors associated with the onset of remission over 36-months. Early change class was a significant predictor of remission over 36 months. Compared to early deterioration after screening, both early response after registration and after screening were associated with a higher likelihood of remission. In sensitivity and secondary analyses, only change class consistently emerged as a predictor of long-term outcome. Early improvement in depression symptoms predicted long-term outcome and those showing early improvement had a higher likelihood of long-term remission. These findings suggest that early changes might be a robust predictor for long-term outcome beyond baseline parameters.

Measurement-based care, that is, incorporating data-informed decision support for therapists into psychological therapy, has undergone significant advancements over the past 2 decades. Technological innovations such as computerized data assessment and feedback tools have facilitated its widespread adoption across various settings. For instance, clinicians can utilize psychometric data to personalize therapeutic approaches, strategies, or modules and track a patient's response to therapy in real time (e.g., Lutz, Schwartz, & Delgadillo, 2022). Furthermore, new algorithm-based clinical support tools used within measurement-based care can optimize treatment for such patients at risk for treatment failure. Consequently, measurement-based care is evolving into a data-informed and precision psychological therapy concept that can be viewed as a low-intensity transtheoretical adjunct to evidence-based treatments. It can be integrated at multiple care points into clinical practice regardless of the clinical modality, manual, or program used in a given health care system. Therefore, it emerges as an important component of clinical competence, practice, and training, akin to continuous monitoring of physical health indicators (e.g., insulin, fever, or blood pressure). In this viewpoint article, we summarize the core concepts of data-informed psychological therapy that customizes individual psychological interventions to meet specific patient needs. We also explore implications and future steps to integrate this approach into clinical practice and further advance precision mental health care . (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Giant cell tumor (GCT) of bone is an uncommon indolent tumor, typically occurring in the meta-epiphysis of long bones in young adults. GCT arising in the clivus is exceedingly rare, and even more uncommon in the pediatric population. We present a case of a 13-year-old patient diagnosed with a large GCT in the clivus. Initial clinical and radiographic findings were suspicious for a GCT, although other more common skull base tumors were also considered in the differential diagnosis. Certain key radiographic features suggested the diagnosis of a GCT, including the low T2 signal within the mass on MRI and the T2 hypointense rim corresponding with a cortical shell present on CT. An endoscopic biopsy confirmed the diagnosis. This report highlights the unique diagnostic challenges and broad differential in this case while underscoring the role of imaging in detection and precise anatomic delineation that helps guide therapeutic decisions and improve patient prognosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shah et al.)

Purpose: Childhood cancer survivors (CCS) have an increased risk of developing late chronic diseases, which can be influenced by the cancer type and its treatment. These chronic diseases can be severe and disabling, typically emerging years to decades after treatment. These deficits negatively impact quality of life, intelligence quotient, and memory. This study investigated how much the cancer type and treatment could affect the neurological hospitalisations in the French Childhood Cancer Survivors Study (FCCSS)., Methods: We included 5579 childhood cancer survivors (CCS), diagnosed with solid tumours or lymphoma between 1945 and 2000, treated before 2001 and below the age of 21 years at initial treatment. The follow-up period was from 2006 to 2018. Hospitalisation data were obtained by linkage with the National Health Data System. We calculated the relative hospitalisation rate (RHRs) and absolute excess rate (AERs). Multivariable analyses were conducted using a Generalized Linear Model (GLM) with a Poisson distribution to estimate the association between neurological hospitalisation and patient characteristics. The expected number of hospitalisations served as an offset to compare the risk for FCCSS survivors with that of the reference population. Risk estimates were reported as relative risk (RR) with 95% confidence intervals., Results: The hospitalisation rate for CCS was 114.2 per 10,000 person-years (PY), compared to 48.4 in the reference population. The highest hospitalisation rates were observed for epilepsy (AER = 27.1 per 10000 PY, 95%CI: 23.5-31.2 and RHR = 5.1, 95%CI 4.4-5.7). In multivariable analyses, central nervous system (CNS) tumours survivors had the highest relative risk (RR) of hospitalisation (RR = 9.4, 95%CI: 6.7-13.1) followed by neuroblastoma survivors (RR = 2.5, 95%CI: 1.7-3.7). In the whole population, survivors who received radiation to the head and neck had a significantly higher risk of hospitalisation (RR = 3.9, 95%CI: 3.3-4.7) compared to those who did not receive radiotherapy., Conclusions: Head and neck irradiation was identified as a strong risk factor for hospitalisation. This underlines the importance of implementing specific neurologic surveillance programs for at-risk individuals., (© 2024. The Author(s).)

Competing Interests: Competing interests: None declared.

Outcome measurement including data-informed decision support for therapists in psychological therapy has developed impressively over the past two decades. New technological developments such as computerized data assessment, and feedback tools have facilitated advanced implementation in several seetings. Recent developments try to improve the clinical decision-making process by connecting clinical practice better with empirical data. For example, psychometric data can be used by clinicians to personalize the selection of therapeutic programs, strategies or modules and to monitor a patient's response to therapy in real time. Furthermore, clinical support tools can be used to improve the treatment for patients at risk for a negative outcome. Therefore, measurement-based care can be seen as an important and integral part of clinical competence, practice, and training. This is comparable to many other areas in the healthcare system, where continuous monitoring of health indicators is common in day-to-day clinical practice (e.g., fever, blood pressure). In this paper, we present the basic concepts of a data-informed decision support system for tailoring individual psychological interventions to specific patient needs, and discuss the implications for implementing this form of precision mental health in clinical practice., (© 2023. The Author(s).)

Background: Previous data on the prevalence of unruptured intracranial aneurysms (UIAs) vary widely, and studies based on these data are plagued with unintentional bias. Accurate prevalence data are paramount for any physician who counsels patients with intracranial aneurysms on rupture risk and treatment. We therefore sought to determine a more accurate number for the true prevalence of UIAs., Methods: A retrospective chart review was conducted at a level 1 trauma center and tertiary care hospital in an urban setting between 2019 and 2020. Inclusion criteria included patients admitted with blunt trauma. Exclusion criteria included not having a head and neck CTA performed and read by an attending radiologist. All head and neck CTA radiology reads were reviewed for incidentally discovered UIAs. Subgroup analysis was performed by age group, race, and gender., Results: A total of 5978 out of 8999 patients met the inclusion criteria, and 54 patients with 58 total aneurysms were identified giving an overall prevalence of 0.9%. Subgroup analysis was performed for all age groups, genders, and racial groups., Conclusion: The overall aneurysm prevalence was found to be 0.9% in this sample. This rate is lower than rates previously cited in the literature and those quoted in local practice. This finding has significant implications when attempting to understand average rupture risk. Further studies are needed to power more subgroup analyses to use a more personalized approach to understanding an individual's risk of rupture., Competing Interests: Competing interests: VI-A is a consultant for Siemens and Penumbra and received research support from Medtronic. DH is a consultant for Covidien/Medtronic and Microvention and is a shareholder of Cerebrotech, Marblehead Medical, and Silver Bullett. LE is a consultant for Balt, Cerenovus, Medtronic, MicroVention, Penumbra, and Stryker. ASA is a consultant for Johnson and Johnson, Medtronic, Microvention, Penumbra, Scientia, Siemens, and Stryker; received research support from Balt, Cerenovus, Medtronic, Microvention, Penumbra, Siemens, and Stryker; and is a shareholder in Bendit, Cerebrotech, Endostream, Magneto, Marble-head, Neurogami, Serenity, Synchron, TriadMedical, and VascularSimulations. CN is a consultant for Leica and received research support from Microvention., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumors, and WRN inhibitors are in development. In this study, we used CRISPR-Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target. Fragment-based screening led to the development of potent and highly selective WRN helicase covalent inhibitors. These compounds selectively suppressed MSI model growth in vitro and in vivo by mimicking WRN loss, inducing DNA double-strand breaks at expanded TA repeats and DNA damage. Assessment of biomarkers in preclinical models linked TA-repeat expansions and mismatch repair alterations to compound activity. Efficacy was confirmed in immunotherapy-resistant organoids and patient-derived xenograft models. The discovery of potent, selective covalent WRN inhibitors provides proof of concept for synthetic lethal targeting of WRN in MSI cancer and tools to dissect WRN biology. Significance: We report the discovery and characterization of potent, selective WRN helicase inhibitors for MSI cancer treatment, with biomarker analysis and evaluation of efficacy in vivo and in immunotherapy-refractory preclinical models. These findings pave the way to translate WRN inhibition into MSI cancer therapies and provide tools to investigate WRN biology. See related commentary by Wainberg, p. 1369., (©2024 American Association for Cancer Research.)

Objective: To date, many prediction studies in psychotherapy research have used cross-sectional data to predict treatment outcome. The present study used intensive longitudinal assessments and continuous time dynamic modeling (CTDM) to investigate the temporal dynamics of affective states and emotion regulation in the early phase of therapy and their ability to predict treatment outcome., Method: Ninety-one patients undergoing psychological treatment at a university outpatient clinic took part in a 2-week ecological momentary assessment (EMA) period. Participants answered self-report measures on positive affect (PA), negative affect, and emotion regulation (ER) four times a day. Hierarchical Bayesian CTDM was conducted to identify temporal effects within (autoregressive) and between (cross-regressive) PA, negative affect, and ER. The resulting CTDM parameters, simple EMA parameters (e.g., mean), and cross-sectional predictors were entered into a LASSO model to be examined as predictors of treatment outcome at Session 15., Results: Two significant predictors were identified: initial impairment and the continuous time cross-effect of PA on ER. The final model explained 40% of variance in treatment outcome, with the cross-effect (PA-ER) accounting for 4% of variance beyond initial impairment., Conclusions: The results demonstrate that temporal patterns of affective EMA data are valuable for the mapping of individual differences and the prediction of treatment outcome. This information can be used to provide therapists with feedback to personalize treatments. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Isolated fallopian tube torsion (IFTT) is a rare form of adnexal torsion that is more difficult to diagnose, which may lead to delays in treatment. Our objectives were to identify clinical and radiologic factors associated with surgically-confirmed IFTT and compare them with those of patients without torsion and with adnexal torsion (AT) in a large pediatric population., Methods: We conducted a retrospective chart review of all patients who underwent surgery for suspected adnexal torsion from 2016 to 2019. Torsion was determined intraoperatively, with IFFT defined as those with only tubal but no ovarian torsion and AT defined as those with ovarian torsion, with or without involvement of the ipsilateral fallopian tube. Clinical and radiologic variables were compared between patients with IFTT and those without torsion and with AT using descriptive statistics. A previously-described composite score to predict torsion based on the presence of vomiting and adnexal volume (VVCS) was calculated for each patient., Results: Of 291 patients who underwent surgery for suspected torsion, 168 had confirmed torsion: 33 (19.6%) IFTT and 135 (80.4%) AT. Patients with IFTT were more likely to be younger (12.8 vs. 14.2 years, P = 0.02), premenarchal (29.0% vs. 10.7%, P = 0.009), experience nausea (90.6% vs. 70.9%, P = 0.02) and vomiting (81.3% vs. 32.8%, P < 0.001), have a paratubal cyst on imaging (18.8% vs. 2.5%, P = 0.003), and have larger adnexal volume (143.3 vs. 64.9 ml, P < 0.001) than those without torsion. Higher BMI (26.6 vs. 22.9 kg/m2, P = 0.03), a paratubal cyst on imaging (18.8% vs. 1.5%, P < 0.001), presence of arterial (65.5% vs. 44.1%, P = 0.04) and venous Doppler flow (79.3% vs. 55.9%, P = 0.02), and radiologic impression indicating lack of torsion (37.9% vs. 16.8%, P = 0.04) were more common in IFTT than AT. The accuracy of the VVCS in predicting torsion for the IFFT group was 83.9%., Conclusions: IFTT has a similar clinical presentation to AT but with a higher likelihood of a paratubal cyst and preserved Doppler flow on imaging. IFTT should be strongly considered in patients who present with pain, nausea, and vomiting and have an adnexal mass separate from the ovary on imaging, regardless of Doppler flow., Level of Evidence: Level II., Type of Study: Prognosis study., Competing Interests: Conflicts of interest All authors report no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Complications after abdominoplasty remain an unsolved issue in body contouring surgery. The antifibrinolytic drug tranexamic acid (TXA) has gained increasing recognition as a valuable pharmacologic agent within plastic surgery. The aim of this study was to investigate the influence of intravenously administered TXA on complications and patient safety after abdominoplasty., Methods: Within this retrospective single-center study, patients who underwent abdominoplasty and received intravenous TXA were selected and compared to randomly selected patients who underwent abdominoplasty without administration of TXA. The patient population was divided into two study groups (TXA vs no TXA). Demographic and surgical data as well as complications were evaluated and compared. Appropriate statistical analysis was performed., Results: Fifty-seven female and 3 male patients with a median age of 38 years and a mean BMI of 25.6 ± 3.3 kg/m 2 were included in the study. Except smoking history, demographic data showed no statistically significant differences between both groups. The most common complication was seroma formation (n = 16; 23.9%), and its occurrence was statistically significantly lower in the TXA group (p = 0.023). Furthermore, postoperative seroma aspiration was performed in statistically significant lower numbers in the TXA group (p < 0.05). No thromboembolic events or seizures were observed., Discussion: The outcomes of this study showed that the intravenous administration of TXA leads to a significant reduction of seroma formation and postoperative seroma aspiration after abdominoplasty. Simultaneously, no adverse thromboembolic events were detected. Hence we would recommend administration of TXA in body contouring surgery to decrease the incidence of seroma formation., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

The intricate relationship between the gastrointestinal (GI) microbiome and the progression of chronic non-communicable diseases underscores the significance of developing strategies to modulate the GI microbiota for promoting human health. The administration of probiotics and prebiotics represents a good strategy that enhances the population of beneficial bacteria in the intestinal lumen post-consumption, which has a positive impact on human health. In addition, dietary fibers serve as a significant energy source for bacteria inhabiting the cecum and colon. Research articles and reviews sourced from various global databases were systematically analyzed using specific phrases and keywords to investigate these relationships. There is a clear association between dietary fiber intake and improved colon function, gut motility, and reduced colorectal cancer (CRC) risk. Moreover, the state of health is reflected in the reciprocal and bidirectional relationships among food, dietary antioxidants, inflammation, and body composition. They are known for their antioxidant properties and their ability to inhibit angiogenesis, metastasis, and cell proliferation. Additionally, they promote cell survival, modulate immune and inflammatory responses, and inactivate pro-carcinogens. These actions collectively contribute to their role in cancer prevention. In different investigations, antioxidant supplements containing vitamins have been shown to lower the risk of specific cancer types. In contrast, some evidence suggests that taking antioxidant supplements can increase the risk of developing cancer. Ultimately, collaborative efforts among immunologists, clinicians, nutritionists, and dietitians are imperative for designing well-structured nutritional trials to corroborate the clinical efficacy of dietary therapy in managing inflammation and preventing carcinogenesis. This review seeks to explore the interrelationships among dietary antioxidants, dietary fiber, and the gut microbiome, with a particular focus on their potential implications in inflammation and cancer.

Purpose: The purpose of this analysis is to: 1) describe the most common mental health diagnoses in the emergency department (ED) and inpatient hospital settings among transgender and gender diverse (TGD) youth vs. matched controls and 2) evaluate if a gender-affirming hormone therapy (GAHT) or gonadotropin-releasing hormone agonist (GnRHa) prescription decreased the risk of suicidality within these settings. Methods: Using the PEDSnet dataset (years 2009-2019), TGD youth aged 8-18 ( n = 3414, with a median age at last visit of 16.2 [14.4, 17.7] years, were propensity-score matched to controls ( n = 13,628, age 16.6 [14.2, 18.3] years). Relative risks of the most common mental health diagnoses within ED and inpatient settings were calculated for TGD youth compared with controls. Recurrent time-to-event analysis was used to examine whether GAHT or GnRHa attenuated the risk of suicidality among subsamples of TGD youth. Results: TGD youth had a higher relative risk (95% confidence interval [CI]) of mental health diagnoses and suicidality in the ED (5.46 [4.71-6.33]) and inpatient settings (6.61 [5.28-8.28]) than matched controls. TGD youth prescribed GAHT had a 43.6% lower risk of suicidality (hazard ratio [HR] = 0.564 [95% CI 0.36-0.89]) compared with those never prescribed GAHT during our study period or before GAHT initiation. TGD youth who were prescribed GnRHa therapy had a nonstatistically significant reduction in ED or inpatient suicidality diagnoses compared with those never prescribed GnRHa (HR = 0.79 [0.47-1.31]). Conclusion: Although risk of mental health diagnoses and suicidality in ED and inpatient settings was high among TGD youth, a GAHT prescription was associated with a significant reduction in suicidality risk.

We aim to use topic modeling, an approach for discovering clusters of related words ("topics"), to predict symptom severity and therapeutic alliance in psychotherapy transcripts, while also identifying the most important topics and overarching themes for prediction. We analyzed 552 psychotherapy transcripts from 124 patients. Using BERTopic (Grootendorst, 2022), we extracted 250 topics each for patient and therapist speech. These topics were used to predict symptom severity and alliance with various competing machine-learning methods. Sensitivity analyses were calculated for a model based on 50 topics, LDA-based topic modeling, and a bigram model. Additionally, we grouped topics into themes using qualitative analysis and identified key topics and themes with eXplainable Artificial Intelligence (XAI). Symptom severity could be predicted with highest accuracy by patient topics ( r =0.45, 95%-CI 0.40, 0.51), whereas alliance was better predicted by therapist topics ( r =0.20, 95%-CI 0.16, 0.24). Drivers for symptom severity were themes related to health and negative experiences. Lower alliance was correlated with various themes, especially psychotherapy framework, income, and everyday life. This analysis shows the potential of using topic modeling in psychotherapy research allowing to predict several treatment-relevant metrics with reasonable accuracy. Further, the use of XAI allows for an analysis of the individual predictive value of topics and themes. Limitations entail heterogeneity across different topic modeling hyperparameters and a relatively small sample size., (© 2024. The Author(s).)

Objective and Aim: This study aimed to assess the impact of switching from face-to-face (f2f) psychotherapy to video therapy (VT) due to the COVID-19 pandemic on in-session processes, i.e., the therapeutic alliance, coping skills, and emotional involvement, as rated by both patients and therapists., Methods: A total of N = 454 patients with mood or anxiety disorders were examined. The intervention group (IG) consisted of n = 227 patient-therapist dyads, who switched from f2f to VT, while the control group (CG) consisted of n = 227 patient-therapist dyads, who were treated f2f before the pandemic. To evaluate the effects of switching to VT on in-session processes, three longitudinal piecewise multilevel models, one per process variable, were fitted. Each process variable was regressed on the session number with a slope for the three sessions before switching to VT and a second slope for up to six VT sessions afterwards., Results: The therapeutic alliance significantly increased after switching from f2f to VT across the two groups (IG and CG) and raters (patients and therapists) with no differences between IG and CG. On average, patients rated the therapeutic alliance better than therapists. Coping skills significantly increased after switching from f2f to VT across the two groups and raters, but the CG rated coping skills higher than the IG after the switch. Overall, therapists rated coping skills higher than patients. Emotional involvement did not significantly increase after switching to VT across the two groups and raters and there was no significant difference between patient and therapist ratings., Discussion: In conclusion, the switch to VT had no negative impact on the therapeutic alliance and emotional involvement. However, more coping skills were reported in the CG than in the IG after the switch to VT, which was mainly due to a stagnation in patient-rated coping skills in the IG., (© 2024. The Author(s).)

Pericarditis and pericardial effusion related to COVID-19 can lead to cardiac tamponade. Most case reports describe these complications in middle-aged or elderly patients. This case highlights a 29-year-old healthy patient who developed cardiac tamponade requiring an emergent pericardial window within one week of COVID-19 infection. This case also highlights the utility of point-of-care ultrasound in diagnosing serious COVID-19 complications., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Schwartz et al.)

Research algorithms are seldom externally validated or integrated into clinical practice, leaving unknown challenges in deployment. In such efforts, one needs to address challenges related to data harmonization, the performance of an algorithm in unforeseen missingness, automation and monitoring of predictions, and legal frameworks. We here describe the deployment of a high-dimensional data-driven decision support model into an EHR and derive practical guidelines informed by this deployment that includes the necessary processes, stakeholders and design requirements for a successful deployment. For this, we describe our deployment of the chronic lymphocytic leukemia (CLL) treatment infection model (CLL-TIM) as a stand-alone platform adjoined to an EPIC-based Danish Electronic Health Record (EHR), with the presentation of personalized predictions in a clinical context. CLL-TIM is an 84-variable data-driven prognostic model utilizing 7-year medical patient records and predicts the 2-year risk composite outcome of infection and/or treatment post-CLL diagnosis. As an independent validation cohort for this deployment, we used a retrospective population-based cohort of patients diagnosed with CLL from 2018 onwards (n = 1480). Unexpectedly high levels of missingness for key CLL-TIM variables were exhibited upon deployment. High dimensionality, with the handling of missingness, and predictive confidence were critical design elements that enabled trustworthy predictions and thus serves as a priority for prognostic models seeking deployment in new EHRs. Our setup for deployment, including automation and monitoring into EHR that meets Medical Device Regulations, may be used as step-by-step guidelines for others aiming at designing and deploying research algorithms into clinical practice., (© 2024. The Author(s).)

Objective: Research suggests that some therapists achieve better outcomes than others. However, an overlooked area of study is how institution differences impact patient outcomes independent of therapist variance. This study aimed to examine the role of institution and therapist differences in adult outpatient psychotherapy., Method: The study included 1428 patients who were treated by 196 therapists at 10 clinics. Two- and three-level hierarchical linear regression models were employed to investigate the effects of therapists and institutions on three dependent patient variables: (1) symptom change, (2) treatment duration, and (3) dropout. Level three explanatory variables were tested., Results: The results showed that therapist effects (TE) were significant for all three types of treatment outcome (7.8%-18.2%). When a third level (institution) was added to the model, the differences between therapists decreased, and significant institution effects (IE) were found: 6.3% for symptom change, 10.6% for treatment duration, and 6.5% for dropout. The exploratory analyses found no predictors able to explain the systematic variation at the institution level., Discussion: TE on psychotherapy outcomes remain a relevant factor but may have been overestimated in previous studies due to not properly distinguishing them from differences at the institution level.

Carbon sorbent materials have shown great promise for solid-state hydrogen (H 2 ) storage. Modification of these materials with nitrogen (N) dopants has been undertaken to develop materials that can store H 2 at ambient temperatures. In this work density functional theory (DFT) calculations are used to systematically probe the influence of curvature on the stability and activity of undoped and N-doped carbon materials toward H binding. Specifically, four models of carbon materials are used: graphene, [5,5] carbon nanotube, [5,5] D 5d -C 120, and C 60 , to extract and correlate the thermodynamic properties of active sites with varying degrees of sp 2 hybridization (curvature). From the calculations and analysis, it is found that graphitic N-doping is thermodynamically favored on more pyramidal sites with increased curvature. In contrast, it is found that the hydrogen binding energy is weakly affected by curvature and is dominated by electronic effects induced by N-doping. These findings highlight the importance of modulating the heteroatom doping configuration and the lattice topology when developing materials for H 2 storage., (© 2024 Wiley‐VCH GmbH.)

In a workshop sponsored by the U.S. National Heart, Lung, and Blood Institute, experts identified current knowledge gaps and research opportunities in the scientific, conceptual, and ethical understanding of organ donation after the circulatory determination of death and its technologies. To minimize organ injury from warm ischemia and produce better recipient outcomes, innovative techniques to perfuse and oxygenate organs postmortem in situ, such as thoracoabdominal normothermic regional perfusion, are being implemented in several medical centers in the US and elsewhere. These technologies have improved organ outcomes but have raised ethical and legal questions. Re-establishing donor circulation postmortem can be viewed as invalidating the condition of permanent cessation of circulation on which the earlier death determination was made and clamping arch vessels to exclude brain circulation can be viewed as inducing brain death. Alternatively, TA-NRP can be viewed as localized in-situ organ perfusion, not whole-body resuscitation, that does not invalidate death determination. Further scientific, conceptual, and ethical studies, such as those identified in this workshop, can inform and help resolve controversies raised by this practice., Competing Interests: Conflict of interest statement James L. Bernat has no conflicts of interest to disclose. All authors have submitted completed JHLT conflict of interest disclosure forms., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: Clinical factors related to development of amenorrhea in adolescents with the etonogestrel contraceptive implant are not well-understood. The purpose of this study is to describe what baseline clinical characteristics are associated with amenorrhea in adolescents with a contraceptive implant 12 months after placement., Study Design: This retrospective cohort study included 252 post-menarchal individuals aged 12-22 years with a contraceptive implant placed between 2016-2020. Data abstracted at insertion, three months post-insertion, and 12 months post-insertion included demographics, baseline bleeding pattern, prior contraception use, post-insertion bleeding pattern, and method discontinuation. We assessed possible predictive characteristics of our outcomes using bivariate and multivariable logistic regression analyses., Results: Twenty nine percent of patients were amenorrheic 12 months after placement. Patients who were amenorrheic at 12 months were more likely to be obese (41.1% vs 24.6%, p = 0.01), to have been amenorrheic prior to implant insertion (16.9% vs 5.4%, p < 0.01, to have used hormonal contraception immediately prior to insertion (42.5% vs 26.3%, p = 0.01), to have had the most recent contraceptive method being another implant (12.3% vs 3.6%, p = 0.02), and to have developed amenorrhea within three months after placement (22.2% vs 12.6%, p < 0.01). After multivariable regression analysis, only obesity (adjusted odds ratio [aOR] 2.2 95% CI 1.1-4.2) and amenorrhea at three months (aOR 3.6, CI 1.1-11.5) were associated with amenorrhea at 12 months., Conclusion: Obesity and early amenorrhea were associated with 12-month amenorrhea in adolescents using the etonogestrel subdermal implant. Understanding this can help with contraceptive method selection and counseling for patients and providers., Implications: Obesity and early amenorrhea with the etonogestrel contraceptive implant are associated with longer-term amenorrhea in adolescents using this method. These findings can aid providers with method selection and pre-insertion decision-making for adolescents considering contraceptive implant use, as well as continued counseling after placement., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) is a critical public health concern with profound consequences for affected individuals. This comprehensive literature review delves into TBI intricacies, encompassing primary injury biomechanics and the molecular pathophysiology of the secondary injury cascade. Primary TBI involves a complex interplay of forces, including impact loading, blast overpressure, and impulsive loading, leading to diverse injury patterns. These forces can be categorized into inertial (e.g., rotational acceleration causing focal and diffuse injuries) and contact forces (primarily causing focal injuries like skull fractures). Understanding their interactions is crucial for effective injury management. The secondary injury cascade in TBI comprises multifaceted molecular and cellular responses, including altered ion concentrations, dysfunctional neurotransmitter networks, oxidative stress, and cellular energy disturbances. These disruptions impair synaptic function, neurotransmission, and neuroplasticity, resulting in cognitive and behavioral deficits. Moreover, neuroinflammatory responses play a pivotal role in exacerbating damage. As we endeavor to bridge the knowledge gap between biomechanics and molecular pathophysiology, further research is imperative to unravel the nuanced interplay between mechanical forces and their consequences at the molecular and cellular levels, ultimately guiding the development of targeted therapeutic strategies to mitigate the debilitating effects of TBI. In this study, we aim to provide a concise review of the bridge between biomechanical processes causing primary injury and the ensuing molecular pathophysiology of secondary injury, while detailing the subsequent clinical course for this patient population. This knowledge is crucial for advancing our understanding of TBI and developing effective interventions to improve outcomes for those affected., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In this paper, we present the conceptual background and clinical implications of a research-based transtheoretical treatment and training model (4TM)., Method: The model implements findings from psychotherapy outcome, process, and feedback research into a clinical and training framework that is open to future research., Results: The framework is based on interventions targeting patient processes on a behavioral, cognitive, emotional, motivational, interpersonal, and systemic/socio-cultural level. The 4TM also includes a data-based decision support and feedback system called the Trier Treatment Navigator (TTN)., Conclusion: We discuss important problems associated with clinical orientations solely based on one school of thought. We then contrast these concerns with a clinical and training framework that embraces ongoing research, serving as a guiding structure for process-based transtheoretical interventions. Such research-based psychological therapy can take both traditional and novel clinical developments as well as findings from psychotherapy research into account and be adaptively disseminated to a variety of patient populations., Competing Interests: The authors have declared that no competing interests exist.

Objective: This study aimed to provide evidence for treatment credibility (TC) as a potential mechanism of change in cognitive behavioral therapy (CBT). Therefore, it focused on within-person effects that are free of the influence of stable characteristics and thus allow to exclude certain alternative explanations for the association under study., Method: The sample included 1,423 patients receiving outpatient CBT, who presented a wide variety of psychiatric diagnoses (mostly affective and anxiety disorders). TC, depression, and anxiety were measured every fifth session from Session 5 to 25 using the Credibility Expectancy Questionnaire (CEQ), the Patient Health Questionnaire-9 (PHQ-9), and the General Anxiety Disorder-7 (GAD-7), respectively. Symptom severity was assessed every session using the Hopkins Symptom Checklist-11. Within- and between-person effects of TC, depression, and anxiety were analyzed using the latent curve model with structured residuals (LCM-SRs). In exploratory analyses, within-person effects of TC on next-session symptom severity were assessed using a modification of the LCM-SR., Results: LCM-SRs exhibited excellent fit in main analyses. There were significant negative correlations of both intercepts and slopes (between-person level) of CEQ and PHQ-9 as well GAD-7. No significant cross-lagged effects (within-person level) were found over the five-session interval. However, session-wise analyses revealed significant cross-lagged effects of CEQ on Hopkins Symptom Checklist-11., Conclusions: This study is the first to find significant within-person effects of TC in session-wise analyses. This lends preliminary support to the notion of TC as a mechanism of change. The lack of significant findings at the five-session interval is discussed considering the specific design used in this study. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objective: We investigated the presence of latent transition profiles in a sample of users of a cognitive-behavioral mental health app for the general population. Users' baseline characteristics were used as predictors of the profiles. The role of engagement with the app in the transition profiles was examined., Method: A total of 541 users completed the Patient Health Questionnaire-9 and the General Anxiety Disorder-7 when started using the app and 30 days after. Random-Intercept Latent Transition Analysis was implemented to identify users' profiles and transition patterns as classes. The age of the users and the Emotional Self-Awareness Scale-Revised (ESAS-R) were used as predictors of class membership at baseline. The Homework Rating Scale-Mobile Application (HRS-MA; as a measure of engagement) was used as a predictor of class membership at 30 days of app use., Results: A 3-class solution was obtained according to the severity of symptoms (from mild to moderately severe). Age and ESAS-R predicted class membership initially; the higher the age and ESAS-R, the higher the probability of starting using the app with lower distress levels. The HRS-MA predicted class membership at 30 days of app use; the higher the engagement for more symptomatic and younger users, the higher the probability of improvement. However, older users tended to engage less., Conclusion: Our findings underpin the relevance of easily accessible digital interventions for young adults with mild to moderate mental health problems. Further studies and developments are required to enhance these apps for older cohorts., (Copyright © 2023 Association for Behavioral and Cognitive Therapies. Published by Elsevier Ltd. All rights reserved.)

The National Institutes of Health (NIH) has a long-standing history of support for research in Down syndrome (DS). In response to a 2018 congressional directive for a trans-NIH initiative to address medical issues in DS, NIH launched the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Reflecting the three INCLUDE components of basic science research, cohort development, and clinical trials, the Project has published funding opportunities to address conditions such as immune disorders and Alzheimer's disease. Due to a steady expansion in dedicated funding over its first 5 years, INCLUDE has invested $258 M in over 250 new research projects. INCLUDE also supports training initiatives to expand the number and diversity of investigators studying DS. NIH has funded an INCLUDE Data Coordinating Center that is collecting de-identified clinical information and multi-omics data from research participants for broad data sharing and secondary analyses. Through the DS-Connect® registry, INCLUDE investigators can access recruitment support. The INCLUDE Research Plan articulates research goals for the program, with an emphasis on diversity of research participants and investigators. Finally, a new Cohort Development Program is poised to increase the impact of the INCLUDE Project by recruiting a large DS cohort across the lifespan., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)