Health economic evaluations of interventions to increase physical activity and decrease sedentary behavior at the workplace : a systematic review

Objective The workplace is an ideal setting to implement public health strategies, but economic justification for such interventions is needed. Therefore, we performed a critical appraisal and synthesis of health economic evaluations (HEE) of workplace interventions aiming to increase physical activity (PA) and/or decrease sedentary behavior (SB). Methods A comprehensive search filter was developed using appropriate guidelines, such as the Peer Review of Electronic Search Strategies (PRESS) checklist, and published search algorithms. Six databases and hand searches were used to identify eligible studies. Full HEE of workplace interventions targeting PA/SB were included. Methodological quality was assessed using the Consensus Health Economic Criteria (CHEC) list. Two researchers independently performed all procedures. Hedges' g was calculated to compare intervention effects. Outcomes from HEE were recalculated in 2017 euros and benefit-standardized. Results Eighteen HEE were identified that fulfilled on average 68% of the CHEC list criteria. Most studies showed improvements in PA/SB, but effects were small and thus, their relevance is questionable. Interventions were heterogeneous, no particular intervention type was found to be more effective. HEE were heterogeneous regarding methodological approaches and the selection of cost categories was inconsistent. Indirect costs were the main cost driver. In all studies, effects on costs were subject to substantial uncertainty. Conclusions Due to small effects and uncertain impact on costs, the economic evidence of worksite PA/SB-interventions remains unclear. Future studies are needed to determine effective strategies. The HEE of such interventions should be developed using guidelines and validated measures for productivity costs. Additionally, studies should model the long-term costs and effects because of the long pay-back time of PA/SB interventions

Health economic evaluation of weight reduction interventions in individuals suffering from overweight or obesity and a musculoskeletal diagnosis—a systematic review

Background Most of the worldwide population is overweight and suffers from the resulting musculoskeletal comorbidities such as knee osteoarthritis or back pain. Practice guidelines recommend weight loss interventions for individuals suffering from these conditions. This systematic review investigated whether including a weight loss intervention in the musculoskeletal therapy of these individuals was cost-effective compared to administering the musculoskeletal therapy alone. Methods This study followed the PRISMA guidelines to systematically and independently search six databases and select full health economic evaluations published up to May 2024 from health care or societal perspectives according to predefined eligibility criteria. Cost data were standardised to 2023 Belgium Euros. The methodological quality was assessed using two health economic-specific checklists. Results The searches produced 5′305 references, of which 8 studies were selected for a total of 1′726 participants. The interventions consisted of different exercise plans and nutritional targets. Six values were in the north-eastern; leading to increased quality-adjusted life year (QALY) and higher costs; and two in the south-eastern quadrant of the cost-utility plane; leading to increased QALYs and lower costs. Two studies observed no differences in QALYs. Incremental cost utility ratios (ICUR) ranged from €13′580.10 to €34′412.40 per additional QALY from a healthcare perspective. From a societal perspective, the ICUR was €30′274.84. The included studies fulfilled 86 percent of the criteria in trial-based economic evaluations and 57 percent in model-based economic evaluations. The most common limitations of the studies were related to appropriate cost measures’ specifications, research questions, time horizon choices, and sensitivity analyses. Conclusions This systematic review showed weak but consistent evidence of cost-effectiveness for adding a weight loss intervention to musculoskeletal therapy for individuals with overweight, from either perspective. Further economic evaluations should evaluate the long-term cost-effectiveness of the intervention

What are the economic dimensions of occupational health and how should they be measured? A qualitative study.

BACKGROUND Decision makers want to know if there is a financial benefit in investing scarce resources in occupational health management (OHM). Economic evaluations (EEs) of OHM-strategies try to answer this question. However, EEs of OHM-strategies which are strongly marked by quantitative methods may be limited by contextual, qualitative residuals. Therefore, the objectives of this study were to (1) explore important economic dimensions of OHM and (2) to discuss the methods used in current EEs for measuring these dimensions. METHODS In this explorative qualitative study, OHM-specialists were recruited via the Swiss organisation for health promotion. Thirteen semi-structured interviews were performed from November 2020 until May 2021. Videotapes were transcribed verbatim and organised by using an open coding strategy. Codes were clustered and synthesised as themes (i.e. the dimensions of EEs of OHM) through a mix of inductive and deductive content analysis. Member check with eight participants was accomplished to validate the results. RESULTS The interviews had an average duration of 70.5 min and yielded 609 individual codes. These codes were merged into 28 subcategories which were finally categorised into five main themes: Understanding of OHM, costs, benefits, environmental aspects, and evaluation of OHM. Participants stated that the greater part of costs and benefits cannot be quantified or monetised and thus, considered in quantitative EEs. For example, they see a culture of health as key component for a successful OHM-strategy. However, the costs to establish such a culture as well as its benefits are hard to quantify. Participants were highly critical of the use of absenteeism as a linear measure of productivity. Furthermore, they explained that single, rare events, such as a change in leadership, can have significant impact on employee health. However, such external influence factors are difficult to control. CONCLUSIONS Participants perceived costs and benefits of OHM significantly different than how they are represented in current EEs. According to the OHM-specialists, most benefits cannot be quantified and thus, monetised. These intangible benefits as well as critical influencing factors during the process should be assessed qualitatively and considered in EEs when using them as a legitimation basis vis-à-vis decision makers

Stage Specific Glaucomatous Changes of the Macula recorded using Spectral Domain Optical Coherence Tomography.

BACKGROUND This study aimed to compare the thickness of different macular retinal layers in glaucomatous eyes and healthy controls, and evaluate the diagnostic performance of spectral domain optical coherence tomography (SD-OCT) parameters. METHODS In this cross-sectional comparative study, 48 glaucomatous eyes and 44 healthy controls were included. The thickness of the total retina and all retinal layers were obtained using the Early Treatment Diagnostic Retinopathy Study (ETDRS) grid. The minimal and average values of outer and inner ETDRS-rings were calculated. The diagnostic performance for detection of glaucoma was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS The thickness of the total retina, ganglion cell layer (GCL), and inner-plexiform layer (IPL) was significantly thinner in glaucomatous eyes in all sectors except the center (all p<0.05). The thickness of retinal nerve fiber layer (RNFL) was significantly thinner in the glaucoma group except in the center, nasal inner, and temporal outer sectors (all p<0.05). Layer thinning advanced with glaucoma severity. The minimal outer GCL thickness showed the highest AUC value for discrimination between glaucomatous eyes and healthy controls(0.955). The minimal outer IPL showed the highest AUC value for discriminating early-stage glaucomatous eyes from healthy controls (0.938). CONCLUSIONS Glaucomatous eyes were found to have significant thinning in the macular region. GCL and IPL showed high ability to discriminate glaucomatous and early-stage glaucomatous eyes from controls. Applying the minimal value to the ETDRS grid has the potential to provide good diagnostic abilities in glaucoma screening

Characterization of encapsulated graphene layers using extreme ultraviolet coherence tomography

Many applications of two-dimensional materials such as graphene require the encapsulation in bulk material. While a variety of methods exist for the structural and functional characterization of uncovered 2D materials, there is a need for methods that image encapsulated 2D materials as well as the surrounding matter. In this work, we use extreme ultraviolet coherence tomography to image graphene flakes buried beneath 200 nm of silicon. We show that we can identify mono-, bi-, and trilayers of graphene and quantify the thickness of the silicon bulk on top by measuring the depth-resolved reflectivity. Furthermore, we estimate the quality of the graphene interface by incorporating a model that includes the interface roughness. These results are verified by atomic force microscopy and prove that extreme ultraviolet coherence tomography is a suitable tool for imaging 2D materials embedded in bulk materials

A high resolution extreme ultraviolet spectrometer system optimized for harmonic spectroscopy and XUV beam analysis

We present a modular extreme ultraviolet (XUV) spectrometer system optimized for a broad spectral range of 12-41 nm (30-99 eV) with a high spectral resolution of λ/Δλ 784 ± 89. The spectrometer system has several operation modes for (1) XUV beam inspection, (2) angular spectral analysis, and (3) imaging spectroscopy. These options allow for a versatile use in high harmonic spectroscopy and XUV beam analysis. The high performance of the spectrometer is demonstrated using a novel cross-sectional imaging method called XUV coherence tomography. © 2019 Author(s)

Absolute EUV reflectivity measurements using a broadband high-harmonic source and an in situ single exposure reference scheme

We present a tabletop setup for extreme ultraviolet (EUV) reflection spectroscopy in the spectral range from 40 to 100 eV by using high-harmonic radiation. The simultaneous measurements of reference and sample spectra with high energy resolution provide precise and robust absolute reflectivity measurements, even when operating with spectrally fluctuating EUV sources. The stability and sensitivity of EUV reflectivity measurements are crucial factors for many applications in attosecond science, EUV spectroscopy, and nano-scale tomography. We show that the accuracy and stability of our in situ referencing scheme are almost one order of magnitude better in comparison to subsequent reference measurements. We demonstrate the performance of the setup by reflective near-edge x-ray absorption fine structure measurements of the aluminum L2/3 absorption edge in α-Al2O3 and compare the results to synchrotron measurements

Targeting macrophage Histone deacetylase 3 stabilizes atherosclerotic lesions

Macrophages are key immune cells found in atherosclerotic plaques and critically shape atherosclerotic disease development. Targeting the functional repertoire of macrophages may hold novel approaches for future atherosclerosis management. Here, we describe a previously unrecognized role of the epigenomic enzyme Histone deacetylase 3 (Hdac3) in regulating the atherosclerotic phenotype of macrophages. Using conditional knockout mice, we found that myeloid Hdac3 deficiency promotes collagen deposition in atherosclerotic lesions and thus induces a stable plaque phenotype. Also, macrophages presented a switch to anti-inflammatory wound healing characteristics and showed improved lipid handling. The pro-fibrotic phenotype was directly linked to epigenetic regulation of the Tgfb1 locus upon Hdac3 deletion, driving smooth muscle cells to increased collagen production. Moreover, in humans, HDAC3 was the sole Hdac upregulated in ruptured atherosclerotic lesions, Hdac3 associated with inflammatory macrophages, and HDAC3 expression inversely correlated with pro-fibrotic TGFB1 expression. Collectively, we show that targeting the macrophage epigenome can improve atherosclerosis outcome and we identify Hdac3 as a potential novel therapeutic target in cardiovascular disease

Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma

The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show that CYC065 (fadraciclib), a clinical inhibitor of CDK9 and CDK2, selectively targeted MYCN-amplified neuroblastoma via multiple mechanisms. CDK9 — a component of the transcription elongation complex P-TEFb — bound to the MYCN-amplicon superenhancer, and its inhibition resulted in selective loss of nascent MYCN transcription. MYCN loss led to growth arrest, sensitizing cells for apoptosis following CDK2 inhibition. In MYCN-amplified neuroblastoma, MYCN invaded active enhancers, driving a transcriptionally encoded adrenergic gene expression program that was selectively reversed by CYC065. MYCN overexpression in mesenchymal neuroblastoma was sufficient to induce adrenergic identity and sensitize cells to CYC065. CYC065, used together with temozolomide, a reference therapy for relapsed neuroblastoma, caused long-term suppression of neuroblastoma growth in vivo, highlighting the clinical potential of CDK9/2 inhibition in the treatment of MYCN-amplified neuroblastoma