KaryoCreate: A CRISPR-based technology to study chromosome-specific aneuploidy by targeting human centromeres.

Aneuploidy, the presence of chromosome gains or losses, is a hallmark of cancer. Here, we describe KaryoCreate (karyotype CRISPR-engineered aneuploidy technology), a system that enables the generation of chromosome-specific aneuploidies by co-expression of an sgRNA targeting chromosome-specific CENPA-binding ɑ-satellite repeats together with dCas9 fused to mutant KNL1. We design unique and highly specific sgRNAs for 19 of the 24 chromosomes. Expression of these constructs leads to missegregation and induction of gains or losses of the targeted chromosome in cellular progeny, with an average efficiency of 8% for gains and 12% for losses (up to 20%) validated across 10 chromosomes. Using KaryoCreate in colon epithelial cells, we show that chromosome 18q loss, frequent in gastrointestinal cancers, promotes resistance to TGF-ß, likely due to synergistic hemizygous deletion of multiple genes. Altogether, we describe an innovative technology to create and study chromosome missegregation and aneuploidy in the context of cancer and beyond.

Warming-induced tree growth may help offset increasing disturbance across the Canadian boreal forest.

Large projected increases in forest disturbance pose a major threat to future wood fiber supply and carbon sequestration in the cold-limited, Canadian boreal forest ecosystem. Given the large sensitivity of tree growth to temperature, warming-induced increases in forest productivity have the potential to reduce these threats, but research efforts to date have yielded contradictory results attributed to limited data availability, methodological biases, and regional variability in forest dynamics. Here, we apply a machine learning algorithm to an unprecedented network of over 1 million tree growth records (1958 to 2018) from 20,089 permanent sample plots distributed across both Canada and the United States, spanning a 16.5 °C climatic gradient. Fitted models were then used to project the near-term (2050 s time period) growth of the six most abundant tree species in the Canadian boreal forest. Our results reveal a large, positive effect of increasing thermal energy on tree growth for most of the target species, leading to 20.5 to 22.7% projected gains in growth with climate change under RCP 4.5 and 8.5. The magnitude of these gains, which peak in the colder and wetter regions of the boreal forest, suggests that warming-induced growth increases should no longer be considered marginal but may in fact significantly offset some of the negative impacts of projected increases in drought and wildfire on wood supply and carbon sequestration and have major implications on ecological forecasts and the global economy.

Maintenance of Procedural Motor Memory across Brief Rest Periods Requires the Hippocampus.

Research on the role of the hippocampus in memory acquisition has generally focused on active learning. But to understand memory, it is at least as important to understand processes that happen offline, during both wake and sleep. In a study of patients with amnesia, we previously demonstrated that although a functional hippocampus is not necessary for the acquisition of procedural motor memory during training session, it is required for its offline consolidation during sleep. Here, we investigated whether an intact hippocampus is also required for the offline consolidation of procedural motor memory while awake. Patients with amnesia due to hippocampal damage (n = 4, all male) and demographically matched controls (n = 10, 8 males) trained on the finger tapping motor sequence task. Learning was measured as gains in typing speed and was divided into online (during task execution) and offline (during interleaved 30 s breaks) components. Amnesic patients and controls showed comparable total learning, but differed in the pattern of performance improvement. Unlike younger adults, who gain speed across breaks, both groups gained speed only while typing. Only controls retained these gains over the breaks; amnesic patients slowed down and compensated for these losses during subsequent typing. In summary, unlike their peers, whose motor performance remained stable across brief breaks in typing, amnesic patients showed evidence of impaired access to motor procedural memory. We conclude that in addition to being necessary for the offline consolidation of motor memories during sleep, the hippocampus maintains access to motor memory across brief offline periods during wake.

Autorecoding A-to-I RNA editing sites in the Adar gene underwent compensatory gains and losses in major insect clades.

As one of the most prevalent RNA modifications in animals, adenosine-to-inosine (A-to-I) RNA editing facilitates the environmental adaptation of organisms by diversifying the proteome in a temporal-spatial manner. In flies and bees, the editing enzyme Adar has independently gained two different autorecoding sites that form an autofeedback loop, stabilizing the overall editing efficiency. This ensures cellular homeostasis by keeping the normal function of target genes. However, in a broader range of insects, the evolutionary dynamics and significance of this Adar autoregulatory mechanism are unclear. We retrieved the genomes of 377 arthropod species covering the five major insect orders (Hemiptera, Hymenoptera, Coleoptera, Diptera, and Lepidoptera) and aligned the Adar autorecoding sites across all genomes. We found that the two autorecoding sites underwent compensatory gains and losses during the evolution of two orders with the most sequenced species (Diptera and Hymenoptera), and that the two editing sites were mutually exclusive among them: One editable site is significantly linked to another uneditable site. This autorecoding mechanism of Adar could flexibly diversify the proteome and stabilize global editing activity. Many insects independently selected different autorecoding sites to achieve a feedback loop and regulate the global RNA editome, revealing an interesting phenomenon during evolution. Our study reveals the evolutionary force acting on accurate regulation of RNA editing activity in insects and thus deepens our understanding of the functional importance of RNA editing in environmental adaptation and evolution.

Variation in body weight, glucose/insulin tolerances, blood lipids and liver enzymes in mice in response to a high-fat-diet from lard.

It raises questions about the impact of lard on the health and the differences in individual responses. Therefore, we developed a model of mice fed with high fat (HF) from lard in 130 days. The weight of the mice was measured every two days. Glucose tolerance test and insulin tolerance tests were performed at 70 days and 130 days of experiment. At the end of the study, the fat tissue was collected to check the weight, and a blood sample was collected to check the blood lipids and liver enzymes. Surprisingly, mice responded variously to the HF by being classified into two groups, one group had significantly high gained weight (HG_HF) versus the mice fed a standard diet (STD) (p < 0.001), and another group (LG_HF) has not difference in body weight compared to the STD groups. This phenomenon in body weight is directly reflected by the white fat accumulation, but not by brown fat. Eating HF from lard for a long time can disrupt glucose tolerance and cause dyslipidemia in mice, even in the LG_HF group, but can not disrupt insulin tolerance and cause liver enzyme disorders. In summary, our findings are a wake-up call for many cases where eating HF from lard does not gain weight and not increase the white fat storage, but still has the potential to cause adverse health effects. Further studies are encouraged to understand the molecular mechanisms that causes the body to regulate its weight and responses when eating HF from lard, especially in the LG_HF group.

Multi-trait index: selection and recommendation of superior black bean genotypes as new improved varieties.

Common bean provides diet rich in vitamins, fiber, minerals, and protein, which could contribute into food security of needy populations in many countries. Developing genotypes that associate favorable agronomic and grain quality traits in the common bean crop could increase the chances of adopting new cultivars black bean. In this context, the present study aimed at selection of superior black bean lines using multi-variate indexes, Smith-Hazel-index, and genotype by yield*trait biplot analysis. These trials were conducted in Campos dos Goytacazes - RJ, in 2020 and 2021. The experimental design used was randomized blocks, with 28 treatments and three replications. The experimental unit consisted of four rows 4.0 m long, spaced at 0.50 m apart, with a sowing density of 15 seeds per meter. The two central rows were used for the evaluations. The selection of superior genotypes was conducted using the multiple trait stability index (MTSI), multi-trait genotype-ideotype distance index (MGIDI), multi-trait index based on factor analysis and genotype-ideotype distance (FAI-BLUP), Smith-Hazel index, and Genotype by Yield*Trait Biplot (GYT). The multivariate indexes efficiently selected the best black bean genotypes, presenting desirable selection gains for most traits. The use of multivariate indexes and GYT enable the selection of early genotypes with higher grain yields. These lines G9, G13, G17, G23, and G27 were selected based on their performance for multiple traits closest to the ideotype and could be recommended as new varieties.

Post-transfer adaptation of HGT-acquired genes and contribution to guanine metabolic diversification in land plants.

Horizontal gene transfer (HGT) is a major driving force in the evolution of prokaryotic and eukaryotic genomes. Despite recent advances in distribution and ecological importance, the extensive pattern, especially in seed plants, and post-transfer adaptation of HGT-acquired genes in land plants remain elusive. We systematically identified 1150 foreign genes in 522 land plant genomes that were likely acquired via at least 322 distinct transfers from nonplant donors and confirmed that recent HGT events were unevenly distributed between seedless and seed plants. HGT-acquired genes evolved to be more similar to native genes in terms of average intron length due to intron gains, and HGT-acquired genes containing introns exhibited higher expression levels than those lacking introns, suggesting that intron gains may be involved in the post-transfer adaptation of HGT in land plants. Functional validation of bacteria-derived gene GuaD in mosses and gymnosperms revealed that the invasion of foreign genes introduced a novel bypass of guanine degradation and resulted in the loss of native pathway genes in some gymnosperms, eventually shaping three major types of guanine metabolism in land plants. We conclude that HGT has played a critical role in land plant evolution.

Efficiency and productivity gains of robotic surgery: The case of the English National Health Service.

This paper examines the effect of new medical technology (robotic surgery) on efficiency gains and productivity changes for surgical treatment in patients with prostate cancer from the perspective of a public health sector organization. In particular, we consider three interrelated surgical technologies within the English National Health System: robotic, laparoscopic and open radical prostatectomy. Robotic and laparoscopic techniques are minimally invasive procedures with similar clinical benefits. While the clinical benefits in adopting robotic surgery over laparoscopic intervention are unproven, it requires a high initial investment cost and carries high on-going maintenance costs. Using data from Hospital Episode Statistics for the period 2000-2018, we observe growing volumes of prostatectomies over time, mostly driven by an increase in robotic-assisted surgeries, and further analyze whether hospital providers that adopted a robot see improved measures of throughput. We then quantify changes in total factor and labor productivity arising from the use of this technology. We examine the impact of robotic adoption on efficiency gains employing a staggered difference-in-difference estimator and find evidence of a 50% reduction in length of stay (LoS), 49% decrease in post-LoS and 44% and 46% decrease in postoperative visits after 1 year and 2 years, respectively. Productivity analysis shows the growth in radical prostatectomy volume is sustained with a relatively stable number of urology surgeons. The robotic technique increases total production at the hospital level between 21% and 26%, coupled with a 29% improvement in labor productivity. These benefits lend some, but not overwhelming support for the large-scale hospital investments in such costly technology.

Brain plasticity underlying sleep-dependent motor consolidation after motor imagery.

Motor imagery can, similarly to physical practice, improve motor performance through experience-based plasticity. Using magnetoencephalography, we investigated changes in brain activity associated with offline consolidation of motor sequence learning through physical practice or motor imagery. After an initial training session with either physical practice or motor imagery, participants underwent overnight consolidation. As control condition, participants underwent wake-related consolidation after training with motor imagery. Behavioral analyses revealed that overnight consolidation of motor learning through motor imagery outperformed wake-related consolidation (95% CI [0.02, 0.07], P < 0.001, RP2 = 0.05). As regions of interest, we selected the generators of event-related synchronization/desynchronization of alpha (8-12 Hz) and beta (15-30 Hz) oscillations, which predicted the level of performance on the motor sequence. This yielded a primary sensorimotor-premotor network for alpha oscillations and a cortico-cerebellar network for beta oscillations. The alpha network exhibited increased neural desynchronization after overnight consolidation compared to wake-related consolidation. By contrast, the beta network exhibited an increase in neural synchronization after wake-related consolidation compared to overnight consolidation. We provide the first evidence of parallel brain plasticity underlying behavioral changes associated with sleep-dependent consolidation of motor skill learning through motor imagery and physical practice.

Blessing or curse: the role of authoritarian filial piety and self-efficacy in caregiver gains among Chinese family caregivers caring for physically impaired older adults.

BACKGROUND: This study investigated the effects of authoritarian filial piety (AFP) and caregiver self-efficacy on the caregiving experience of adult children of physically impaired older adults. Socio-cultural stress and coping model was applied to test the influence of AFP on caregiver gains. METHODS: A total of 601 Chinese adult children caregivers and care-recipient dyads participated in this cross-sectional study in 2021. Four instruments were used to collect data: the 4-item Zarit Burden Interview, Positive Aspects of Caregiving Scale, Caregiver Task Inventory Scale, and Authoritarian Filial Piety Scale. All mediation and moderated mediation effects were estimated using SPSS 26.0. RESULTS: Caregiver self-efficacy was found to not only mediate but also help family caregivers convert their burden into positive gains. AFP moderates the association between caregiver burden and self-efficacy, as well as between caregiver burden and caregiver gains. CONCLUSIONS: This study provides valuable insights into filial piety, elucidating AFP's comprehensive impact on cognitive appraisals of caregiving. Culturally sensitive psychoeducational therapy, addressing AFP expectations and boosting caregiver self-efficacy, is recommended to enhance positive caregiving outcomes.

Efficacy of health literacy interventions aimed to improve health gains of higher education students-a systematic review.

BACKGROUND: Health literacy (HL) among higher education students is low, making them vulnerable about their health. To reverse this trend, higher education institutions promote HL interventions with various topics and methods. A comprehensive understanding of HL interventions is essential to determine whether these interventions meet the health information needs to improve health outcomes (health gains). The aim of this review was to identify and synthesise evidence on the efficacy of HL interventions implemented in academic settings to improve health outcomes. METHODS: A systematic review was performed followed the PRISMA guidelines, protocol was registered in PROSPERO (CRD42022369869). A search strategy was performed in the EBSCO Host Web platform, the time limit placed was: 01/01/2017 to 30/09/2022. Eligible studies were those published in peer-reviewed journals and involved higher education students over the age of 18 as the subject of the intervention. Eligible interventions included any interventions evaluated in a study with comparison group that included a pre-post measure of health outcomes, were conducted in an academic setting. To methodology quality of included studies, it was used the Joanna Briggs Institute critical appraisal tool. To synthesise results narrative and thematic synthesis was conducted. RESULTS: A total of 9 articles were included in this review, identified health literacy interventions with an impact on health outcomes. The total studies involved 2902 higher education students. All 9 studies were randomised controlled trials. The synthesised evidence supports the efficacy of interventions that contributed to positive changes in mental health, attitudes, norms, and self-efficacy of condom use, emotional, social, and psychological well being, subjective sleep quality, sleep latency, and habitual sleep efficiency, physical activity, and self-reported servings fried foods. HL interventions were educational or motivational and related to health promotion, disease prevention or healthcare. CONCLUSIONS: HL interventions in higher education students can significantly improve health outcomes protecting them from the negative effects of threats for their health. The interventions designed with different strategies are more effective. HL interventions are associated with health benefits on health promotion, disease prevention and healthcare. For the attendance of higher education to be a successful experience, continuity of HL interventions developed in academic settings is necessary.

Defining desired genetic gains for Pacific white shrimp (Litopenaeus vannamei) breeding objective using participatory approaches.

The objective of this study was to define desired genetic gains from economically important traits of Pacific white shrimp (Litopenaeus vannamei) using participatory approaches. Two questionnaires were sent out to 100 Pacific white shrimp farmers in all five Iranian shrimp farming provinces. Questionnaire A (Q-A) includes management factors and farming environments. Moreover, in this questionnaire, farmers were asked to rank the fourth most important traits in shrimp among 10 economic traits in the list for genetic improvement. In questionnaire B (Q-B), priorities of the four traits with the highest value were obtained using pairwise comparison. The results showed that the four most important traits were white spot syndrome virus resistance (WSSV), growth rate before 4 months (GR), acute hepatopancreatic necrosis disease resistance (AHPND), and female total weight at ablation (FTW). Medians of the best individual preference values were WSSV (0.222), GR (0.173), AHPND (0.157), and FTW (0.053). Most disagreements were found between the social group preference values in the commercial products and water salinity categories. Desired genetic gains were 1.71%, 1.57%, 0.53% and 0.31% for GR, AHPND, WSSV and FTW, respectively. This study highlighted that despite environmental and management differences, participatory approaches can achieve desired genetic results for Pacific white shrimp breeding programme.

Facilitating active learning of sectional anatomy with technology-enhanced small-group tasks: Assessment of knowledge gains, technology usability, and students' perceptions.

Learning 2D sectional anatomy facilitates the comprehension of 3D anatomical structures, anatomical relationships, and radiological anatomy. However, the efficacy of technology-enhanced collaborative instructional activities in sectional anatomy remains unclear, especially if theoretical frameworks, namely the Cognitive Theory of Multimedia Learning (CTML), are applied in instructional design. Thus, this study compared the educational impact of distinct 45-min-long technology-enhanced collaborative learning tasks in sectional anatomy. A sample of 115 first-year medical students was randomly divided into three experimental groups that used different supporting technologies to learn the sectional anatomy of the chest: IMAIOS e-learning platform and Microsoft Surface Hub (n = 37); anatomage table (n = 38); anatomage table with CTML-based presets (n = 40). Prelearning and postlearning tests revealed that significant knowledge gains in sectional anatomy were obtained by all groups even though no inter-group differences were found. Moreover, a five-point Likert scale questionnaire showed that the learning session was highly valued by all participants and that users of the anatomage with CTML-based presets reported higher enjoyment than users of the IMAIOS system (mean difference = 0.400; p = 0.037). In addition, students using the IMAIOS system and the anatomage with CTML-based presets provided System Usability Scale (SUS) scores of 67.64 and 67.69, respectively, reaching the benchmark of usability. By contrast, students using the anatomage table without presets awarded a SUS score of 64.14. These results suggest that the integration of multimedia technologies in anatomy teaching and learning should be grounded on CTML principles of instructional design. Otherwise, students' perceptions of ed-tech usability are potentially hindered.

Study on regional carbon quota allocation at provincial level in China from the perspective of carbon peak.

This paper constructs a carbon quota allocation index that takes into account equity, efficiency and ecological construction, and calculates carbon emissions and energy consumption data in important periods based on the expected carbon emission targets and economic and social development indicators of the Chinese government. Based on the calculated carbon emissions, the zero-sum game data Envelopment model (ZSG-DEA) is used to discuss the initial allocation of regional quotas and the optimal carbon quota scheme. The results show that:(1) there is a large gap between the optimal carbon quota and the initial carbon quota allocation in Shandong, Guangdong, Jiangsu and other provinces in 2025, and the implementation of emission reduction measures should be accelerated. (2) By 2030, the final allocation of Beijing, Tianjin, Inner Mongolia, Qinghai, Shanghai, Ningxia, Liaoning and Xinjiang will be positive. The provinces with negative final allocation should carry out the work of carbon peak as soon as possible to avoid increasing the pressure of emission reduction in the future. (3) The central region faces greater pressure of emission reduction, while the western region can accept the transfer of carbon emissions from other regions over time. The research conclusions have important policy implications for establishing a fair and effective carbon quota allocation mechanism, achieving the national total carbon emission control target, stimulating the vitality of the unified carbon market, and promoting regional coordinated emission reduction.

Adaptive and maladaptive pathways of COVID-19 worry on well-being: A cross-national study.

OBJECTIVE: In a preregistered study, we examined whether worries about COVID-19 are simultaneously linked with enhanced well-being through social interaction and with reduced well-being through depression symptoms. METHOD: In August 2020, census-matched participants from high- and low-prevalence regions in the United States and Italy (N = 857) completed assessments of COVID-19 worry, social interaction, depression symptoms, and well-being. RESULTS: Worries about COVID-19 predicted both more social interaction and more depression (ps < 0.001). In multiple mediational analyses, an adaptive pathway of COVID-19 worry through social interaction was associated with higher well-being, whereas a maladaptive pathway through depression symptoms was associated with lower well-being. Further, a comparison of high and low COVID-19 prevalence regions replicated the mediational findings for social interaction, providing evidence against reverse causation and common method variance. CONCLUSION: Findings suggest that normative worries about acute stressors may both benefit and undermine well-being, depending on their impact on social behavior or depression symptoms.

Genetic parameters, genetic trends and correlated responses of growth traits considering maternal ability in Nelore cattle.

The growth of Nelore cattle was analysed considering the following performance parameters; the effect of the calving order of cows on the phenotypic expression of birth weight (BW), average daily gain from birth to weaning (BWG), and weaning weight (WW), the estimated genetic parameters for the traits, including the covariance components between direct and maternal genetic effects. Genetic trends and correlated responses were also obtained for the studied traits. The calving order of cows, as well as other fixed effects used to obtain the adjusted phenotypic means, were statistically significant (p < 0.001) for studied traits. Direct heritability was estimated at 0.24 ± 0.01 (BW), 0.15 ± 0.01 (BWG), and 0.18 ± 0.01 (WW), while maternal heritability was 0.06 ± 0.01 (BW), 0.12 ± 0.01 (BWG), and 0.11 ± 0.01 (WW). The correlations between direct and maternal effects within the same trait were negligible. Moderate to higher direct genetic correlations (ranging from 0.54 ± 0.04 to 0.98 ± 0.01) and maternal genetic correlations (ranging from 0.34 ± 0.09 to 0.99 ± 0.002) were estimated between the studied traits. Unlike direct genetic effects, there was no significant change in maternal genetic effects over time (p > 0.05). These results indicated the need for revising selection indexes for enhancing maternal ability. Correlated responses were generally lower compared to direct responses, except for BWG. The selection for BWG, considering the maternal genetic effect, would be more efficient to improve maternal ability of the cows for pre-weaning growth in relation to selection for WW. Our results found that direct genetic merit improves pre-weaning weight and this trait can be incorporated into the breeding goal as reflected in the WW.

Disentangling spatiotemporal dynamics in metacommunities through a species-patch network approach.

Colonization and extinction at local and regional scales, and gains and losses of patches are important processes in the spatiotemporal dynamics of metacommunities. However, analytical challenges remain in quantifying such spatiotemporal dynamics when species extinction-colonization and patch gain and loss processes act simultaneously. Recent advances in network analysis show great potential in disentangling the roles of colonization, extinction, and patch dynamics in metacommunities. Here, we developed a species-patch network approach to quantify metacommunity dynamics including (i) temporal changes in network structure, and (ii) temporal beta diversity of species-patch links and its components that reflect species extinction-colonization and patch gain and loss. Application of the methods to simulated datasets demonstrated that the approach was informative about metacommunity assembly processes. Based on three empirical datasets, our species-patch network approach provided additional information about metacommunity dynamics through distinguishing the effects of species colonization and extinction at different scales from patch gains and losses and how specific environmental factors related to species-patch network structure. In conclusion, our species-patch network framework provides effective methods for monitoring and revealing long-term metacommunity dynamics by quantifying gains and losses of both species and patches under local and global environmental change.

A Decade of Health Innovation: The Impact of New Medicines on Patient Health and the Implications for NICE's Size of Benefit Multiplier.

OBJECTIVES: This study aimed to estimate the incremental health benefits of pharmaceutical innovations approved between 2011 and 2021 and the share that would surpass the National Institute for Health and Care Excellence (NICE) "size of benefit" decision weight thresholds. METHODS: We identified all US-approved drugs between 2011 and 2021. Health benefits, in terms of quality-adjusted life-years (QALYs) for each treatment, were extracted from published cost-effectiveness analyses. Summary statistics by therapeutic area and cell/gene therapy status identified the treatments with the largest QALY gains. RESULTS: The Food and Drug Administration approved 483 new therapies between 2011 and 2021 and of these 252 had a published cost-effectiveness analysis meeting our inclusion criteria. The average incremental health benefits produced by these treatments were 1.04 QALYs (SD = 2.00) relative to standard of care, with wide variation by therapeutic area. Pulmonary and ophthalmologic therapies produced the highest health benefits with 1.47 (SD = 2.17, n = 13) and 1.41 QALYs gained (SD = 3.53, n = 7), respectively; anesthesiology and urology had the lowest gains (< 0.1 QALYs). Cell and gene therapies produced an average health benefit that was 4 times greater than noncell and gene therapies (4.13 vs 0.96). Among the top treatments in terms of incremental QALYs gained, half (10 of 20) were oncology therapies. Three of 252 treatments (1.2%) met NICE's threshold for a "size of benefit" multiplier. CONCLUSIONS: Treatments for rare disease, oncology, and cell and gene therapies produced some of the highest level of health innovation relative to previous standard of care, but few therapies would have qualified for NICE's "size of benefit" multiplier as currently constructed.

Real-world evidence on the economic implications of CGRP-mAbs as preventive treatment of migraine.

BACKGROUND: Calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) are approved in Europe as preventive treatment of migraine in patients with at least four monthly migraine days. Migraine gives rise to direct healthcare expenditures, but most of the economic burden of migraine is socioeconomic. Evidence on the socioeconomic implications of CGRP-mAbs is, however, limited. There is an increasing interest in supplementing evidence from randomised controlled trials (RCTs) with real-world evidence (RWE) to aid clinical decision making and inform decision making for migraine management. The objective of this study was to generate RWE on the health economic and socioeconomic implications of administering CGRP-mAbs to patients with chronic migraine (CM) and episodic migraine (high-frequency episodic migraine (HFEM), and low-frequency episodic migraine (LFEM)). METHODS: Real-world data (RWD) on Danish patients with CM, HFEM, and LFEM were collected via two Danish patient organisations and two informal patient networks and used in a tailored economic model. Treatment effects of CGRP-mAbs on health economic and socioeconomic outcomes were estimated using a sub-sample of patients with CM who receive CGRP-mAb treatment. RESULTS: A total of 362 patients (CM: 199 [55.0%], HFEM: 80 [22.1%], LFEM: 83 [22.9%]) were included in the health economic model (mean age 44.1 ± 11.5, 97.5% female, 16.3% received treatment with CGRP-mAbs), and 303 patients were included in the socioeconomic model (15.2% received treatment with CGRP-mAbs). Health economic savings from initiating CGRP-mAb treatment totalled €1,179 per patient with CM per year on average (HFEM: €264, LFEM: €175). Socioeconomic gains from initiating CGRP-mAb treatment totalled an average gross domestic product (GDP) gain of €13,329 per patient with CM per year (HFEM: €10,449, LFEM: €9,947). CONCLUSION: Our results indicate that CGRP-mAbs have the potential to reduce both health economic expenditures and the socioeconomic burden of migraine. Health economic savings are used as a basis for health technology assessments (HTAs) of the cost-effectiveness of new treatments, which implies that important socioeconomic gains may not be given enough importance in decision making for migraine management.

Factors affecting the success of pulmonary rehabilitation in asthma.

OBJECTIVE: The majority of patients with asthma limit their physical activity due to the fear of exercise dyspnea. Regular exercise, on the other hand, is currently suggested as one of the non-pharmaceutical treatment alternatives for patients with asthma since it improves their quality of life and symptom control. This study aimed to investigate the indicators of success in patients with asthma receiving pulmonary rehabilitation (PR). METHODS: A total of 131 patients with the diagnosis of asthma were included in the study. All patients attended an 8-week comprehensive, multidisciplinary, outpatient and individualized PR program. RESULTS: The factors related to the gains in dyspnea perception, exercise capacity, peripheral muscle strength, respiratory muscle strength and quality of life were evaluated. In the multivariate linear regression analysis, the gain in dyspnea perception is related to baseline dyspnea. The gain in exercise capacity is related to baseline exercise capacity and the amount of smoking. The gain in peripheral muscle strength is related to gender. The gain in respiratory muscle strength is related to age, and finally the gain in quality of life is related to baseline dyspnea and anxiety levels. CONCLUSIONS: Especially men, young people, heavy smokers, and those with low initial exercise capacity, high perception of dyspnea, and high anxiety are more likely to benefit from PR.