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Mindfulness witnessed a substantial popularity surge in the past decade, especially as digitally self-administered interventions became available at relatively low costs. Yet, it is uncertain whether they effectively help reduce stress. In a preregistered (OSF https://doi.org/10.17605/OSF.IO/UF4JZ ; retrospective registration at ClinicalTrials.gov NCT06308744 ) multi-site study (nsites = 37, nparticipants = 2,239, 70.4% women, Mage = 22.4, s.d.age = 10.1, all fluent English speakers), we experimentally tested whether four single, standalone mindfulness exercises effectively reduced stress, using Bayesian mixed-effects models. All exercises proved to be more efficacious than the active control. We observed a mean difference of 0.27 (d = -0.56; 95% confidence interval, -0.43 to -0.69) between the control condition (M = 1.95, s.d. = 0.50) and the condition with the largest stress reduction (body scan: M = 1.68, s.d. = 0.46). Our findings suggest that mindfulness may be beneficial for reducing self-reported short-term stress for English speakers from higher-income countries.

Despite the emerging evidence in recent years, successful implementation of clinical genomic sequencing (CGS) remains limited and is challenged by a range of barriers. These include a lack of standardized practices, limited economic assessments for specific indications, limited meaningful patient engagement in health policy decision-making, and the associated costs and resource demand for implementation. Although CGS is gradually becoming more available and accessible worldwide, large variations and disparities remain, and reflections on the lessons learned for successful implementation are sparse. In this commentary, members of the Global Economics and Evaluation of Clinical Genomics Sequencing Working Group (GEECS) describe the global landscape of CGS in the context of health economics and policy and propose evidence-based solutions to address existing and future barriers to CGS implementation. The topics discussed are reflected as two overarching themes: (1) system readiness for CGS and (2) evidence, assessments, and approval processes. These themes highlight the need for health economics, public health, and infrastructure and operational considerations; a robust patient- and family-centered evidence base on CGS outcomes; and a comprehensive, collaborative, interdisciplinary approach.

Abstract Background A better understanding of adverse health and underlying risk factors in the context of military and law enforcement is essential to developing future preventative strategies. We conducted an umbrella review to provide an overview of the current literature regarding risk factors for adverse health in military and law enforcement populations. Methods We systematically searched the literature for systematic reviews and meta-analyses regarding risk factors for adverse health in military or law enforcement populations. We critically appraised the studies that matched our inclusion criteria, extracted the adverse health outcomes and underlying risk factors, and narratively synthesised the findings. Results This umbrella review included 34 systematic reviews that covered data from 43 countries. We identified twenty-six adverse health outcomes and 220 underlying risk factors. The adverse health outcomes covered in the included systematic reviews were one infectious disease (Heliobacter pylori infection); two endocrine, nutritional, or metabolic diseases (metabolic syndrome and obesity); seven mental, behavioural, or neurodevelopmental disorders (adjustment disorder, alcohol misuse, anxiety, depression, poor mental health, PTSD, and stress); two diseases of the nervous system (insomnia and sleep-disordered breathing); one disease of the ear or mastoid process (noise-induced hearing loss); eight diseases of the musculoskeletal system and connective tissue (cervical spine injuries, injuries, lower extremity injuries, musculoskeletal injuries, neck pain, rhabdomyolysis, and stress fractures); one symptom, signs and abnormal clinical and laboratory findings, not elsewhere classified (suicidal ideation); three injuries, poisonings, or other consequences of external causes (concussion, heat illness, and suicide); and one factor influencing health status and contact with health services (burnout). Of the 220 identified risk factors, 136 were modifiable, and the most frequently reported were female sex, older age, lower functional movement screen scores, maladaptive coping, lack of social support, and neuroticism. Conclusion This umbrella review identified twenty-six adverse health outcomes and their underlying risk factors in military and law enforcement populations. Hereby, this study provides potential starting points for preventing adverse health in these populations. It also identifies a broad lack of systematic reviews investigating mental, behavioural, or neurodevelopmental disorders in military populations and diseases of the musculoskeletal system and connective tissue in law enforcement populations. Prospero Registration Number CRD42022378123.

Abstract Imaging systems are inherently prone to aberrations. We present an optimization method to design two-dimensional (2D) freeform reflectors that minimize aberrations for various parallel ray beams incident on the optical system. We iteratively design reflectors using inverse methods from non-imaging optics and optimize them to obtain a system that produces minimal aberrations. This is done by minimizing a merit function that quantifies aberrations and is dependent on the energy distributions at the source and target of an optical system, which are input parameters essential for inverse freeform design. The proposed method is tested for two configurations: a single-reflector system and a double-reflector system. Classical designs consisting of aspheric elements are well-known for their ability to minimize aberrations. We compare the performance of our freeform optical elements with classical designs. The optimized freeform designs outperform the classical designs in both configurations.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16178. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Abstract Concatenated backward ray mapping is an alternative for ray tracing in 2D. It is based on the phase-space description of an optical system. Phase space is the set of position and direction coordinates of light rays intersecting a surface. The original algorithm (Filosa, ten Thije Boonkkamp and IJzerman in J Math Ind 11(1):4, 2021) is limited to optical systems consisting of only straight surfaces; we generalize it to accommodate curved surfaces. The algorithm is applied to a standard optical system, the compound parabolic concentrator. We compare the accuracy and speed of the generalized algorithm, the original algorithm and Monte Carlo ray tracing. The results show that the generalized algorithm outperforms both other methods.

Background: Advances in targeted therapy development and tumor sequencing technology are reclassifying cancers into smaller biomarker-defined diseases. Randomized controlled trials (RCTs) are often impractical in rare diseases, leading to calls for single-arm studies to be sufficient to inform clinical practice based on a strong biological rationale. However, without RCTs, favorable outcomes are often attributed to therapy but may be due to a more indolent disease course or other biases. When the clinical benefit of targeted therapy in a common cancer is established in RCTs, this benefit may extend to rarer cancers sharing the same biomarker. However, careful consideration of the appropriateness of extending the existing trial evidence beyond specific cancer types is required. A framework for extrapolating evidence for biomarker-targeted therapies to rare cancers is needed to support transparent decision-making. Objectives: To construct a framework outlining the breadth of criteria essential for extrapolating evidence for a biomarker-targeted therapy generated from RCTs in common cancers to different rare cancers sharing the same biomarker. Design: A series of questions articulating essential criteria for extrapolation. Methods: The framework was developed from the core topics for extrapolation identified from a previous scoping review of methodological guidance. Principles for extrapolation outlined in guidance documents from the European Medicines Agency, the US Food and Drug Administration, and Australia’s Medical Services Advisory Committee were incorporated. Results: We propose a framework for assessing key assumptions of similarity of the disease and treatment outcomes between the common and rare cancer for five essential components: prognosis of the biomarker-defined cancer, biomarker test analytical validity, biomarker actionability, treatment efficacy, and safety. Knowledge gaps identified can be used to prioritize future studies. Conclusion: This framework will allow systematic assessment, standardize regulatory, reimbursement and clinical decision-making, and facilitate transparent discussions between key stakeholders in drug assessment for rare biomarker-defined cancers.

Introduction: ALK–rearranged advanced NSCLC (aNSCLC) represents 4% of all NSCLCs, and multiple ALK-targeted therapies (ALK-inhibitors) are now available for use. Little is known about changes in treatment patterns, or how prognostic factors and sequence of therapy may impact overall survival in the real-world setting. We aim to describe initial and subsequent treatments used, survival outcomes, prognostic factors, and the impact of treatment on overall survival in the largest (N = 739) real-world cohort of patients with ALK+ aNSCLC reported in the literature. Methods: Retrospective observational cohort study with data drawn from a U.S.-based electronic health record–derived, deidentified database. Eligible patients were diagnosed with ALK+ aNSCLC between 2011-2020 and were treated in multiple different cancer clinics and across multiple geographic regions throughout the United States. Results: From a cohort of 63,667 patients with aNSCLC, 739 patients with ALK+ NSCLC were eligible for analysis, median age was 63 years, 54% patients were female, and 85% were managed in community setting. More than 168 different treatment sequences were observed, and treatment utilization changed over time. Cohort median overall survival was 37 months (95% confidence interval: 33–45). Positive prognostic factors were as follows: never-smoking history, younger age, treatment in an academic setting, and initial early stage at diagnosis. Initial treatment with a second-generation ALK-inhibitor was associated with improved survival compared with chemotherapy. Conclusions: For people with ALK+ aNSCLC, this study has identified several important clinical prognostic factors and is practice affirming; first-line treatment with a second-generation ALK-inhibitor improves survival compared with chemotherapy.

With over 450 genes, solute carriers (SLCs) constitute the largest transporter superfamily responsible for the uptake and efflux of nutrients, metabolites, and xenobiotics in human cells. SLCs are associated with a wide variety of human diseases, including cancer, diabetes, and metabolic and neurological disorders. They represent an important therapeutic target class that remains only partly exploited as therapeutics that target SLCs are scarce. Additionally, many small molecules reported in the literature to target SLCs are poorly characterized. Both features may be due to the difficulty of developing SLC transport assays that fulfill the quality criteria for high-throughput screening. Here, we report one of the main limitations hampering assay development within the RESOLUTE consortium: the lack of a resource providing high-quality information on SLC tool compounds. To address this, we provide a systematic annotation of tool compounds targeting SLCs. We first provide an overview on RESOLUTE assays. Next, we present a list of SLC-targeting compounds collected from the literature and public databases; we found that most data sources lacked specificity data. Finally, we report on experimental tests of 19 selected compounds against a panel of 13 SLCs from seven different families. Except for a few inhibitors, which were active on unrelated SLCs, the tested inhibitors demonstrated high selectivity for their reported targets. To make this knowledge easily accessible to the scientific community, we created an interactive dashboard displaying the collected data in the RESOLUTE web portal (https://re-solute.eu). We anticipate that our open-access resources on assays and compounds will support the development of future drug discovery campaigns for SLCs.

Histoplasmosis is a frequent cause of infections in people living with HIV/AIDS (PLWHA). This study introduces the application of a Histoplasma capsulatum urine antigen lateral flow assay (LFA) for diagnosing disseminated histoplasmosis in PLWHA in Suriname. The LFA's diagnostic accuracy was compared with the current diagnostic approach, aiming to assess whether this test resulted in improved early detection and management. Additionally, the prevalence of histoplasmosis among advanced stage HIV patients without clinical suspicion of infection was evaluated using the same LFA. In total, 98 patients were included in the study, of which 58 were classified as "possible disseminated histoplasmosis (DH)" based on clinical criteria and 40 as "controls". Of these possible DH cases, only 19 (32.7%) had a positive LFA. During the study, decisions for treatment were made without the treating physician being aware of the LFA result. Only 55% of the patients who started treatment for histoplasmosis based on clinical criteria had a positive LFA, and 21% of untreated patients had a positive LFA. This study shows that combining clinical signs with LFA results enhances diagnostic accuracy and is cost effective, resulting in better treatment decisions.

Abstract Background The number of complex eHealth interventions has increased considerably. Despite available implementation theory outlining well-designed strategies, implementing complex interventions within practice proves challenging and often does not lead to sustainable use. To improve sustainability, theory and practice should be addressed during the development of an implementation strategy. By subsequently transparently reporting the executed theory-based steps and their corresponding practice findings, others can learn from these valuable lessons learned. This study outlines the iterative approach by which a multifaceted implementation strategy for a complex eHealth intervention in clinical practice was developed, tested and refined. Methods We implemented the BENEFIT program, an advanced eHealth platform with Personal Health Portal facilitating healthy living in cardiac patients. In six iterative phases alternating between theory and practice, the implementation strategy was developed, tested and refined. The initial implementation strategy (phase 1) was drawn up using the Implementation model and RE-AIM. Subsequently, this strategy was further updated in brainstorming sessions and group discussions with twenty key stakeholders from three cardiac care centres and then evaluated in a pilot (phases 2 and 3). Results The pilot of the program led to the identification of (context-specific) key challenges in practice (phase 4), which were subsequently connected back to broader theory (phase 5) using the Consolidated Framework of Implementation Research (CFIR). In the final phase, practice recommendations tackling the key challenges were formulated (phase 6) based on CFIR theory, the CFIR-ERIC Matching Tool, and stakeholders’ input and feedback. These recommendations were then added to the refined strategy. Thus, executing this approach led to the realisation and use of a multifaceted theory-informed practice-based implementation strategy. Conclusion This case study gives an in-depth description of an iterative approach to developing an evidence-based, practice-tailored strategy for implementing a complex eHealth intervention in cardiac care. As such, this study may serve as a blueprint for other researchers aspiring to implement complex eHealth interventions within clinical practice sustainably.

Abstract This study explored the acceptability of a novel pharmacist‐led pharmacogenetics (PGx) screening program among patients with cancer and healthcare professionals (HCPs) taking part in a multicenter clinical trial of PGx testing (PACIFIC‐PGx ANZCTR:12621000251820). Medical oncologists, oncology pharmacists, and patients with cancer from across four sites (metropolitan/regional), took part in an observational, cross‐sectional survey. Participants were recruited from the multicenter trial. Two study‐specific surveys were developed to inform implementation strategies for scaled and sustainable translation into routine clinical care: one consisting of 21 questions targeting HCPs and one consisting of 17 questions targeting patients. Responses were collected from 24 HCPs and 288 patients. The 5‐to‐7‐day PGx results turnaround time was acceptable to HCP (100%) and patients (69%). Most HCPs (92%) indicated that it was appropriate for the PGx clinical pharmacist to provide results to patients. Patients reported equal preference for receiving PGx results from a doctor/pharmacist. Patients and HCPs highly rated the pharmacist‐led PGx service. HCPs were overall accepting of the program, with the majority (96%) willing to offer PGx testing to their patients beyond the trial. HCPs identified that lack of financial reimbursements (62%) and lack of infrastructure (38%) were the main reasons likely to prevent/slow the implementation of PGx screening program into routine clinical care. Survey data have shown overall acceptability from patients and HCPs participating in the PGx Program. Barriers to implementation of PGx testing in routine care have been identified, providing opportunity to develop targeted implementation strategies for scaled translation into routine practice.