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OBJECTIVE: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. METHOD: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. RESULTS: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. CONCLUSION: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.

Abstract Exposure to pollutants is a potentially crucial but overlooked driver of population declines in shorebirds along the East Asian-Australasian Flyway. We combined knowledge of moult strategy and life history with a standardised sampling protocol to assess mercury (Hg) contamination in 984 individuals across 33 migratory shorebird species on an intercontinental scale. Over one-third of the samples exceeded toxicity benchmarks. Feather Hg was best explained by moulting region, while habitat preference (coastal obligate vs. non-coastal obligate), the proportion of invertebrates in the diet and foraging stratum (foraging mostly on the surface vs. at depth) also contributed, but were less pronounced. Feather Hg was substantially higher in South China (Mai Po and Leizhou), Australia and the Yellow Sea than in temperate and Arctic breeding ranges. Non-coastal obligate species (Tringa genus) frequently encountered in freshwater habitats were at the highest risk. It is important to continue and expand biomonitoring research to assess how other pollutants might impact shorebirds.

Abstract Background Work-related violence committed by clients, patients, and customers represents a major occupational health risk for employees that needs to be reduced. Methods We tested a comprehensive violence prevention intervention involving active participation of both employees and managers in the Prison and Probation Service (PPS) and on psychiatric wards in Denmark. We used a stepped wedge cluster randomised controlled trial design. We measured the degree of implementation of the intervention by registration of fidelity, reach, and dose and used a mixed-effects regression analysis to estimate the effects of the intervention. Results We recruited 16 work units for the intervention, but three work units dropped out. The average implementation rate was 73%. In the psychiatric wards, the intervention led to statistically significant improvements in the primary outcome (an increase in the degree to which managers and employees continuously work on violence prevention practices based on their registration and experiences), but none statistically significant improvements in any of the secondary outcomes. In the PPS units, the intervention did not lead to a statistically significant improvement in the primary outcome, but to statistically significant improvements in three secondary outcomes. Conclusion Most work units were able to carry out the intervention as planned. The intervention showed mixed results regarding the primary outcome. Nevertheless, the results indicate improvements also in the sector where a change in the primary outcome was not achieved. The results point at that a participatory and comprehensive approach could be a viable way of working with violence prevention in high-risk workplaces. Trial registration ISRCTN86993466: 20/12/2017

Czech translation of Karl Jaspers’ Über meine Philosophie.

Background: Inhalation of biomass smoke is associated with adverse respiratory effects in those with chronic pulmonary conditions. There are few published data regarding the effects of anti-inflammatory interventions on these outcomes. Objective: Our aim was to assess the effects of postexposure prednisone on woodsmoke (WS)-induced sputum neutrophilia. Methods: We carried out a randomized, placebo-controlled, crossover pilot study assessing the effect of a postexposure dose of 60 mg prednisone on induced sputum inflammation after controlled exposure to WS (500 μg/m3 for 2 hours) in healthy adults who had been identified in a separate screening protocol as being “PMN responsive” to WS. Secondary end points were sputum cytokine level and mucociliary clearance as measured by γ-scintigraphy. Results: A total of 11 subjects yielded complete data for the primary analysis. At 24 hours after WS exposure, there was a significant increase in sputum percentage of PMNs (%PMN) versus at baseline after placebo (median = 42% [IQR = 31%-53%]) (P = .02) but not after prednisone (median = 32% [IQR = 18%-40%]) (P = .09). Prednisone reduced Δ%PMN at 24 hours, but this difference did not reach statistical significance. However, for the 8 of 11 subjects who were PMN responsive after placebo, prednisone reduced Δ%PMN significantly (P = .05). Prednisone had no significant effects on sputum levels of IL-1β, IL-6, IL-8, or TNF-α. WS exposure tended to reduce mucociliary clearance in the placebo arm but not in the prednisone arm. Conclusions: Prednisone taken immediately after exposure to WS mitigated short-term increase in sputum %PMN among healthy volunteers selected for their underlying inflammatory responsiveness to WS. Our data support future studies assessing anti-inflammatory interventions and the role of mucus clearance in WS-induced respiratory health effects.

E-cigarette or vaping product use-associated lung injury (EVALI) is a severe pulmonary illness associated with the use of e-cigarettes or vaping products that was officially identified and named in 2019. This American Thoracic Society workshop was convened in 2021 to identify and prioritize research and regulatory needs to adequately respond to the EVALI outbreak and to prevent similar instances of disease associated with e-cigarette or vaping product use. An interdisciplinary group of 26 experts in adult and pediatric clinical care, public health, regulatory oversight, and toxicology were convened for the workshop. Four major topics were examined: 1) the public health and regulatory response to EVALI; 2) EVALI clinical care; 3) mechanisms contributing to EVALI; and 4) needed actions to address the health effects of EVALI. Oral presentations and group discussion were the primary modes used to identify top priorities for addressing EVALI. Initiatives including a national EVALI case registry and biorepository, integrated electronic medical record coding system, U.S. Food and Drug Administration regulation and enforcement of nicotine e-cigarette standards, regulatory authority over nontobacco-derived e-cigarettes, training in evaluating exogenous exposures, prospective clinical studies, standardized clinical follow-up assessments, ability to more readily study effects of cannabinoid e-cigarettes, and research to identify biomarkers of exposure and disease were identified as critical needs. These initiatives will require substantial federal investment as well as changes to regulatory policy. Overall, the workshop identified the need to address the root causes of EVALI to prevent future outbreaks. An integrated approach from multiple perspectives is required, including public health; clinical, basic, and translational research; regulators; and users of e-cigarettes. Improving the public health response to reduce the risk of another substantial disease-inducing event depends on coordinated actions to better understand the inhalational toxicity of these products, informing the public of the risks, and developing and enforcing regulatory standards for all e-cigarettes.

Cardiovascular diseases (CVDs) are a global burden that requires attention. For the detection and diagnosis of CVDs, the 12-lead ECG is a key tool. With technological advancements, ECG devices are becoming smaller and available for home use. Most of these devices contain a limited number of leads and are aimed to detect atrial fibrillation (AF). To investigate whether a four-electrode arrangement could provide enough information to diagnose other CVDs, further research is necessary. At the University Medical Center Utrecht in a multidisciplinary team, we developed the miniECG, a four-electrode ECG handheld system for scientific research in clinical environments (TRL6). This paper describes the process followed during the development of the miniECG. From assembling a multidisciplinary team, which includes engineers, cardiologists, and clinical physicians to the contribution of team members in the design input, design, and testing for safety and functionality of the device. Finally, we detail how the development process was composed by iterative design steps based on user input and intended use evolution. The miniECG is a device compliant for scientific research with patients within Dutch Medical Centers. We believe that hospital-based development led to a streamlined process, which could be applied for the design and development of other technologies used for scientific research in clinical environments.

BackgroundDementia-related impairments can cause complex barriers to access, use, and adopt digital health technologies (DHTs). These barriers can contribute to digital health inequities. Therefore, literature-based design principles called DEMIGNED have been developed to support the design and evaluation of DHTs for this rapidly increasing population. ObjectiveThis study aims to apply the DEMIGNED principles in usability evaluation methods to (1) capture usability problems on a mobile website providing information resources for people visiting a memory clinic, including those living with subjective cognitive decline (SCD), mild cognitive impairment (MCI), or dementia, and (2) investigate the realness of usability problems captured by the DEMIGNED principles in expert testing, specifically for mobile websites that act as a means of providing DHTs. MethodsFirst, a heuristic evaluation was conducted, with the DEMIGNED principles serving as domain-specific guidelines, with 3 double experts (experienced in both usability and dementia) and 2 usability engineering experts. Second, think-aloud sessions were conducted with patients visiting a memory clinic who were living with SCD, MCI, or dementia. ResultsThe heuristic evaluation resulted in 36 unique usability problems. A representative sample of 7 people visiting a memory clinic participated in a think-aloud session, including 4 (57%) with SCD, 1 (14%) with MCI, and 2 (29%) with dementia. The analysis of the think-aloud sessions revealed 181 encounters with usability problems. Of these encounters, 144 (79.6%) could be mapped to 18 usability problems identified in the heuristic evaluation. The remaining 37 (20.4%) encounters from the user testing revealed another 10 unique usability problems. Usability problems frequently described in the think-aloud sessions encompassed difficulties with using the search function, discrepancies between the user’s expectations and the content organization, the need for scrolling, information overload, and unclear system feedback. ConclusionsBy applying the DEMIGNED principles in expert testing, evaluators were able to capture 79.6% (144/181) of all usability problem encounters in the user testing of a mobile website for people visiting a memory clinic, including people living with dementia. Regarding unique usability problems, 50% (18/36) of the unique usability problems identified during the heuristic evaluation were captured by the user-testing sessions. Future research should look into the applicability of the DEMIGNED principles to other digital health functionalities to increase the accessibility of digital health and decrease digital health inequity for this complex and rapidly increasing population.

BackgroundDespite the global upscale of teledermatology during the COVID-19 pandemic, persistent barriers, such as the poor anamnesis and photo quality, hinder its effective use in practice. Understanding Dutch dermatologists’ experiences and satisfaction with using the teledermatology system in the Dutch health care system is needed. A holistic evaluation may provide valuable insight to understand how barriers interrelate which is deemed necessary for the innovation of teledermatology in practice. ObjectiveGuided by a complex adaptive system perspective, this study aims to understand Dutch dermatologists’ experience and satisfaction with their training, support communication, interaction, and usage of a teledermatology platform of a Dutch digital hospital during the COVID-19 pandemic, uncovering insights to improve teledermatology services for the future. MethodsA web-based questionnaire was sent in December 2021 to Dutch dermatologists who (1) had an active teledermatology platform account, and (2) responded to a teledermatology consultation between October 1, 2019, and September 30, 2021. The questionnaire consisted of the validated Store-and-Forward Telemedicine Service User-satisfaction Questionnaire (SAF-TSUQ) questionnaire, and new questions regarding; demographics of teledermatologists, the use of teledermatology during the COVID-19 pandemic, the performance of teledermatology by general practitioners (GP), and the role of dermatologists in the teledermatology process. The open-ended questions were analyzed by a grounded theory approach guided by a sociotechnical model and complemented by a complex adaptive system perspective. A panel discussion with 3 dermatologists was performed to provide additional insight into the responses to the questionnaire. ResultsWe obtained responses from 25 out of the 249 (10%) invited dermatologists. Overall, dermatologists had a positive experience with teledermatology. Interestingly, teledermatology use frequency remained unaffected by the COVID-19 pandemic. However, the insufficient quality and incompleteness of the clinical content (photos and anamneses information) of the teledermatology consultation impacted the efficiency of the teledermatology workflow. Dermatologists expressed the need for improvement to avoid time-consuming processes or physical referrals. The panel discussion enriched and confirmed the responses, suggesting solutions like mandatory fields for the GPs for a complete anamnesis. ConclusionsDutch Dermatologists view teledermatology as a valuable tool to provide access to dermatology care. However, improvements regarding the quality and completeness of the provided clinical content are necessary for the effectiveness and efficiency of the complex teledermatology system in Dutch health care. This could increase both the dermatologists’ satisfaction and the quality of teledermatology services. Managing trade-offs, such as time investments versus image quality, is crucial for teledermatology implementation and should be assessed from a complexity perspective to understand trade-offs and prevent unintended consequences.

Lipids play pivotal roles in an extensive range of metabolic and physiological processes. In recent years, the convergence of trapped ion mobility spectrometry and MS has enabled 4D-lipidomics, a highly promising technology for comprehensive lipid analysis. 4D-lipidomics assesses lipid annotations across four distinct dimensions—retention time, collisional cross section, m/z (mass-to-charge ratio), and MS/MS spectra—providing a heightened level of confidence in lipid annotation. These advantages prove particularly valuable when investigating complex disorders involving lipid metabolism, such as adrenoleukodystrophy (ALD). ALD is characterized by the accumulation of very-long-chain fatty acids (VLCFAs) due to pathogenic variants in the ABCD1 gene. A comprehensive 4D-lipidomics strategy of ALD fibroblasts demonstrated significant elevations of various lipids from multiple classes. This indicates that the changes observed in ALD are not confined to a single lipid class and likely impacts a broad spectrum of lipid-mediated physiological processes. Our findings highlight the incorporation of mainly saturated and monounsaturated VLCFA variants into a range of lipid classes, encompassing phosphatidylcholines, triacylglycerols, and cholesterol esters. These include ultra-long-chain fatty acids with a length of up to thirty carbon atoms. Lipid species containing C26:0 and C26:1 were the most frequently detected VLCFA lipids in our study. Furthermore, we report a panel of 121 new candidate biomarkers in fibroblasts, exhibiting significant differentiation between controls and individuals with ALD. In summary, this study demonstrates the capabilities of a 4D-lipid profiling workflow in unraveling novel insights into the intricate lipid modifications associated with metabolic disorders like ALD.

Summary: This retrospective study examined bone flap displacement during radiotherapy in 25 post-operative brain tumour patients. Though never exceeding 2.5 mm, the sheer frequency of displacement highlights the need for future research on larger populations to validate its presence and assess the potential clinical impact on planning tumour volume margins.

Background: Resilience is an increasingly used term in medicine and subject to various definitions, often not easy to grasp. There are established core concepts for patients receiving palliative care, for example, meaning in life, that have already been researched a lot. Resilience, relative to these concepts, is a new object of research in palliative care, where it has so far been used predominantly with regard to the well-being of teams. Aim: To explore how experts in palliative care define the concept of resilience and its suitability for patients, significant others, and professionals. Design: Qualitative study using summarizing content analysis according to Mayring. Setting/participants: Twenty-one health and social care professionals with expertise caring for persons with life-threatening/limiting illnesses and their relatives were interviewed in three individual interviews and four focus groups. All conversations were recorded, transcribed, coded via MAXQDA, and validated by another researcher. Results: Resilience has been described as something procedural, dynamic, individual, and flexible. In connection with well-known concepts such as posttraumatic growth or terms from the field of mindfulness, social environment or personal factors have also been linked to resilience. Resources such as spirituality can contribute to resilience, and resilience itself can function as a resource, for example, by contributing to quality of life. An active use of the term in practical work with patients or relatives is rare, but it is used in education or team measures. Limited lifespan can pose a challenge to an active use of the concept of resilience. Conclusion: Resilience as a very individual approach provides added value to other core concepts of palliative care. Within the palliative context, the normative dimension of resilience must be well reflected. A broader definition of resilience is recommended, leaving room for everyone to find their own form of resilience. The concept of resilience in palliative care includes opportunities as well as risks and should, therefore, be implemented carefully, requiring specific training.