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1.
J Neurol ; 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561543

RESUMEN

BACKGROUND: The Big Multiple Sclerosis Data (BMSD) network ( https://bigmsdata.org ) was initiated in 2014 and includes the national multiple sclerosis (MS) registries of the Czech Republic, Denmark, France, Italy, and Sweden as well as the international MSBase registry. BMSD has addressed the ethical, legal, technical, and governance-related challenges for data sharing and so far, published three scientific papers on pooled datasets as proof of concept for its collaborative design. DATA COLLECTION: Although BMSD registries operate independently on different platforms, similarities in variables, definitions and data structure allow joint analysis of data. Certain coordinated modifications in how the registries collect adverse event data have been implemented after BMSD consensus decisions, showing the ability to develop together. DATA MANAGEMENT: Scientific projects can be proposed by external sponsors via the coordinating centre and each registry decides independently on participation, respecting its governance structure. Research datasets are established in a project-to-project fashion and a project-specific data model is developed, based on a unifying core data model. To overcome challenges in data sharing, BMSD has developed procedures for federated data analysis. FUTURE PERSPECTIVES: Presently, BMSD is seeking a qualification opinion from the European Medicines Agency (EMA) to conduct post-authorization safety studies (PASS) and aims to pursue a qualification opinion also for post-authorization effectiveness studies (PAES). BMSD aspires to promote the advancement of real-world evidence research in the MS field.

2.
BMC Genomics ; 25(1): 243, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443832

RESUMEN

BACKGROUND: Mosaic loss of chromosome Y (LOY) in leukocytes is the most prevalent somatic aneuploidy in aging humans. Men with LOY have increased risks of all-cause mortality and the major causes of death, including many forms of cancer. It has been suggested that the association between LOY and disease risk depends on what type of leukocyte is affected with Y loss, with prostate cancer patients showing higher levels of LOY in CD4 + T lymphocytes. In previous studies, Y loss has however been observed at relatively low levels in this cell type. This motivated us to investigate whether specific subsets of CD4 + T lymphocytes are particularly affected by LOY. Publicly available, T lymphocyte enriched, single-cell RNA sequencing datasets from patients with liver, lung or colorectal cancer were used to study how LOY affects different subtypes of T lymphocyte. To validate the observations from the public data, we also generated a single-cell RNA sequencing dataset comprised of 23 PBMC samples and 32 CD4 + T lymphocytes enriched samples. RESULTS: Regulatory T cells had significantly more LOY than any other studied T lymphocytes subtype. Furthermore, LOY in regulatory T cells increased the ratio of regulatory T cells compared with other T lymphocyte subtypes, indicating an effect of Y loss on lymphocyte differentiation. This was supported by developmental trajectory analysis of CD4 + T lymphocytes culminating in the regulatory T cells cluster most heavily affected by LOY. Finally, we identify dysregulation of 465 genes in regulatory T cells with Y loss, many involved in the immunosuppressive functions and development of regulatory T cells. CONCLUSIONS: Here, we show that regulatory T cells are particularly affected by Y loss, resulting in an increased fraction of regulatory T cells and dysregulated immune functions. Considering that regulatory T cells plays a critical role in the process of immunosuppression; this enrichment for regulatory T cells with LOY might contribute to the increased risk for cancer observed among men with Y loss in leukocytes.


Asunto(s)
Cromosomas Humanos Y , Neoplasias , Humanos , Masculino , Cromosomas Humanos Y/genética , Linfocitos T Reguladores , Leucocitos Mononucleares , Mosaicismo
3.
PeerJ ; 11: e14634, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37810783

RESUMEN

Background: Accurate and reliable assessment of clinician integrity in the delivery of empirically supported treatments is critical to effective research and training interventions. Assessment of clinician integrity can be performed through recording simulated (SI) or real-life (RL) consultations, yet research examining the equivalence of these data is in its infancy. To explore the strength of integrity assessment between SI and RL samples in Motivational Interviewing (MI) consultations, this article examines whether Motivational Interviewing Treatment Integrity (MITI) assessments differ between SI and RL consultations and reviews the predictive validity of SI and RL MI skills categorisations for RL client response language. Methods: This study first compared MITI coding obtained in SI and RL consultations for 36 veterinary clinicians. Multilevel models of 10 MITI behaviour counts and four MITI global scores were run using MLwiN 3.02 to assess if a significant difference existed between SI and RL MITI data, with consultation within clinician within cohort (A and B) as nested random effects. Second, we investigated the effect of SI and RL MI skills groupings on rate of RL client response talk using three multivariable regression models. Two Poisson regression models, with random intercepts for farm and veterinarian and offset for number of minutes of the recordings, were estimated in the statistical software R using the package glmmTMB for the two response variables Change Talk and Sustain Talk. A logistic regression model, with the same random intercepts, with the response variable Proportion Change Talk was also estimated using the same package. Results: Veterinary clinicians were less MI consistent in RL consultations, evidenced through significantly lower global MITI Cultivating Change Talk (p < 0.001), Partnership (p < 0.001) and Empathy (p = 0.003) measures. Despite lower objective MI skills groupings in RL consultations, ranking order of veterinary clinicians by MI skills was similar between contexts. The predictive validity of SI and RL MI skills groupings for RL client Change Talk was therefore similar, with significantly more RL client Change Talk associated with veterinarians categorised in the highest grouping ('moderate') in both SI (p = 0.01) and RL (p = 0.02) compared to untrained veterinarians in each respective context. Conclusions: Findings suggest SI and RL data may not be interchangeable. Whilst both data offer useful insights for specific research and training purposes, differing contextual MI skills thresholds may offer a more equitable assessment of clinician RL client-facing MI integrity. Further research is needed to explore the applicability of these findings across health contexts.


Asunto(s)
Entrevista Motivacional , Veterinarios , Humanos , Lenguaje , Granjas , Derivación y Consulta
4.
Ther Adv Neurol Disord ; 16: 17562864231198963, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37771841

RESUMEN

Introduction: Prescribing guidance for disease-modifying treatment (DMT) in multiple sclerosis (MS) is centred on a clinical diagnosis of relapsing-remitting MS (RRMS). DMT prescription guidelines and monitoring vary across countries. Standardising the approach to diagnosis of disease course, for example, assigning RRMS or secondary progressive MS (SPMS) diagnoses, allows examination of the impact of health system characteristics on the stated clinical diagnosis and treatment access. Methods: We analysed registry data from six cohorts in five countries (Czech Republic, Denmark, Germany, Sweden and United Kingdom) on patients with an initial diagnosis of RRMS. We standardised our approach utilising a pre-existing algorithm (DecisionTree, DT) to determine patient diagnoses of RRMS or secondary progressive MS (SPMS). We identified five global drivers of DMT prescribing: Provision, Availability, Funding, Monitoring and Audit, data were analysed against these concepts using meta-analysis and univariate meta-regression. Results: In 64,235 patients, we found variations in DMT use between countries, with higher usage in RRMS and lower usage in SPMS, with correspondingly lower usage in the UK compared to other registers. Factors such as female gender (p = 0.041), increasing disability via Expanded Disability Status Scale (EDSS) score (p = 0.004), and the presence of monitoring (p = 0.029) in SPMS influenced the likelihood of receiving DMTs. Standardising the diagnosis revealed differences in reclassification rates from clinical RRMS to DT-SPMS, with Sweden having the lowest rate Sweden (Sweden 0.009, range: Denmark 0.103 - UK portal 0.311). Those with higher EDSS at index (p < 0.03) and female gender (p < 0.049) were more likely to be reclassified from RRMS to DT-SPMS. The study also explored the impact of diagnosis on DMT usage in clinical SPMS, finding that the prescribing environment and auditing practices affected access to treatment. Discussion: This highlights the importance of a healthcare system's approach to verifying the clinical label of MS course in facilitating appropriate prescribing, with some flexibility allowed in uncertain cases to ensure continued access to treatment.

5.
Mult Scler J Exp Transl Clin ; 9(1): 20552173231153557, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36816812

RESUMEN

Background: To assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing-remitting MS (RRMS) and SPMS and may identify situations where SPMS is under reported. Materials and methods: Data were obtained for 61,900 MS patients from MS registries in the Czech Republic, Denmark, Germany, Sweden, and the United Kingdom (UK), including date of birth, sex, SP conversion year, visits with an Expanded Disability Status Scale (EDSS) score, MS onset and diagnosis date, relapses, and disease-modifying treatment (DMT) use. We included RRMS or SPMS patients with at least one visit between January 2017 and December 2019 if ≥ 18 years of age. We applied three objective methods: A set of SPMS clinical trial inclusion criteria ("EXPAND criteria") modified for a real-world evidence setting, a modified version of the MSBase algorithm, and a decision tree-based algorithm recently published. Results: The clinically assigned proportion of SPMS varied from 8.7% (Czechia) to 34.3% (UK). Objective classifiers estimated the proportion of SPMS from 15.1% (Germany by the EXPAND criteria) to 58.0% (UK by the decision tree method). Due to different requirements of number of EDSS scores, classifiers varied in the proportion they were able to classify; from 18% (UK by the MSBase algorithm) to 100% (the decision tree algorithm for all registries). Objectively classified SPMS patients were older, converted to SPMS later, had higher EDSS at index date and higher EDSS at conversion. More objectively classified SPMS were on DMTs compared to the clinically assigned. Conclusion: SPMS appears to be systematically underdiagnosed in MS registries. Reclassified patients were more commonly on DMTs.

6.
Waste Manag Res ; 41(8): 1342-1348, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36843382

RESUMEN

This field experiment investigates the effect of first-time inspections of restaurants' waste sorting and explores whether motivational interviewing (MI) training of inspectors in this specific setting enhances the propensity of restaurants to be compliant with regulations. Our results show strong positive effects of first inspections with an average improvement of 55%. Also, the MI training of inspectors seems to affect compliance. However, this may also be a combined effect of the first inspection, MI training and more days between inspections. Further research is needed.


Asunto(s)
Entrevista Motivacional , Eliminación de Residuos , Humanos , Entrevista Motivacional/métodos , Eliminación de Residuos/normas
7.
Front Neurol ; 14: 1274194, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38187157

RESUMEN

Background: Treatment switching is a common challenge and opportunity in real-world clinical practice. Increasing diversity in disease-modifying treatments (DMTs) has generated interest in the identification of reliable and robust predictors of treatment switching across different countries, DMTs, and time periods. Objective: The objective of this retrospective, observational study was to identify independent predictors of treatment switching in a population of relapsing-remitting MS (RRMS) patients in the Big Multiple Sclerosis Data Network of national clinical registries, including the Italian MS registry, the OFSEP of France, the Danish MS registry, the Swedish national MS registry, and the international MSBase Registry. Methods: In this cohort study, we merged information on 269,822 treatment episodes in 110,326 patients from 1997 to 2018 from five clinical registries. Patients were included in the final pooled analysis set if they had initiated at least one DMT during the relapsing-remitting MS (RRMS) stage. Patients not diagnosed with RRMS or RRMS patients not initiating DMT therapy during the RRMS phase were excluded from the analysis. The primary study outcome was treatment switching. A multilevel mixed-effects shared frailty time-to-event model was used to identify independent predictors of treatment switching. The contributing MS registry was included in the pooled analysis as a random effect. Results: Every one-point increase in the Expanded Disability Status Scale (EDSS) score at treatment start was associated with 1.08 times the rate of subsequent switching, adjusting for age, sex, and calendar year (adjusted hazard ratio [aHR] 1.08; 95% CI 1.07-1.08). Women were associated with 1.11 times the rate of switching relative to men (95% CI 1.08-1.14), whilst older age was also associated with an increased rate of treatment switching. DMTs started between 2007 and 2012 were associated with 2.48 times the rate of switching relative to DMTs that began between 1996 and 2006 (aHR 2.48; 95% CI 2.48-2.56). DMTs started from 2013 onwards were more likely to switch relative to the earlier treatment epoch (aHR 8.09; 95% CI 7.79-8.41; reference = 1996-2006). Conclusion: Switching between DMTs is associated with female sex, age, and disability at baseline and has increased in frequency considerably in recent years as more treatment options have become available. Consideration of a patient's individual risk and tolerance profile needs to be taken into account when selecting the most appropriate switch therapy from an expanding array of treatment choices.

8.
Front Psychol ; 13: 890579, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35959019

RESUMEN

As evaluation of practitioners' competence is largely based on self-report, accuracy in practitioners' self-assessment is essential for ensuring high quality treatment-delivery. The aim of this study was to assess the relationship between independent observers' ratings and practitioners' self-reported treatment integrity ratings of Motivational interviewing (MI). Practitioners (N = 134) were randomized to two types of supervision [i.e., regular institutional group supervision, or individual telephone supervision based on the MI Treatment Integrity (MITI) code]. The mean age was 43.2 years (SD = 10.2), and 62.7 percent were females. All sessions were recorded and evaluated with the MITI, and the MI skills were self-assessed with a questionnaire over a period of 12 months. The associations between self-reported and objectively assessed MI skills were overall weak, but increased slightly from baseline to the 12-months assessment. However, the self-ratings from the group that received monthly objective feedback were not more accurate than those participating in regular group supervision. These results expand findings from previous studies and have important implications for assessment of practitioners' treatment fidelity: Practitioners may learn to improve the accuracy of self-assessment of competence, but to ensure that patients receive intended care, adherence and competence should be assessed objectively.

9.
Science ; 377(6603): 292-297, 2022 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-35857592

RESUMEN

Hematopoietic mosaic loss of Y chromosome (mLOY) is associated with increased risk of mortality and age-related diseases in men, but the causal and mechanistic relationships have yet to be established. Here, we show that male mice reconstituted with bone marrow cells lacking the Y chromosome display increased mortality and age-related profibrotic pathologies including reduced cardiac function. Cardiac macrophages lacking the Y chromosome exhibited polarization toward a more fibrotic phenotype, and treatment with a transforming growth factor ß1-neutralizing antibody ameliorated cardiac dysfunction in mLOY mice. A prospective study revealed that mLOY in blood is associated with an increased risk for cardiovascular disease and heart failure-associated mortality. Together, these results indicate that hematopoietic mLOY causally contributes to fibrosis, cardiac dysfunction, and mortality in men.


Asunto(s)
Envejecimiento , Deleción Cromosómica , Insuficiencia Cardíaca , Células Madre Hematopoyéticas , Miocardio , Cromosoma Y , Envejecimiento/genética , Animales , Anticuerpos Neutralizantes/farmacología , Anticuerpos Neutralizantes/uso terapéutico , Fibrosis , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/terapia , Macrófagos , Masculino , Ratones , Mosaicismo , Miocardio/patología , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Cromosoma Y/genética
10.
Prev Vet Med ; 204: 105679, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35636232

RESUMEN

Communication has been identified as one constraint for cattle veterinarians to act as proactive health consultants. Motivational Interviewing (MI), an evidence-based client-centered communication methodology, may therefore be a useful tool in veterinary herd health management (VHHM). The aim of this exploratory study was to investigate associations between training in MI and different measures of performance in VHHM. MI skills of 36 Swedish cattle veterinarians randomly assigned to two groups - MI veterinarians (n = 18) who had received six-months training in MI and control veterinarians (n = 18) who were not trained - were assessed using the MI Treatment Integrity coding system. Skills were categorized as untrained, trained_poor, trained_near moderate and trained_moderate. Veterinarians each visited two to six cattle farms for VHHM consultations and revisited the same farms three to six months later to document implementation of recommendations. A gamma model and logistic or ordered logistic regression models were used to evaluate associations between MI training and performance measured as: a) proportion of consultations resulting in written herd health plans, b) proportion of recommended measures fully or partially implemented, c) Likert scores of different estimates of client satisfaction and d) total time during 6 months allocated to VHHM visits on cattle farms. We found no evidence of any significant effects of MI training on the eight performance variables analyzed. However, a pattern of numerically higher values (better performance) in trained veterinarians with poor or moderate MI skills than in untrained veterinarians was observed in most variables. Clients were highly satisfied with veterinarians' attitude, competence and time efficiency. Farms implemented a median of 66.7% (interquartile range: 50-100) of the measures partially or fully. Veterinarians allocated little time to VHHM visits (median: 2.2; interquartile range: 0.65-4.1 h per week of full-time work within cattle). Veterinarians with moderate skills spent 2.14 times more time on VHHM visits than untrained veterinarians, but the confidence interval was wide (0.88-5.21). The pattern of numerically higher values in trained veterinarians supported findings from other studies in the same project indicating a positive effect of MI training on VHHM. Our observations suggest a considerable potential to increase veterinarians' engagement in VHHM.


Asunto(s)
Entrevista Motivacional , Veterinarios , Animales , Bovinos , Humanos , Industria Lechera/métodos , Agricultores , Granjas
12.
Mult Scler ; 28(7): 1051-1059, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34212816

RESUMEN

BACKGROUND: The primary objective of this study was to analyse the association between multiple sclerosis (MS) disease-modifying therapy (DMT) exposure and hospitalisation in patients infected with COVID-19. METHODS: Associations between MS DMT exposure and COVID-19 hospitalisation were analysed using univariable and multi-variable-clustered propensity score weighted logistic regression, where the models were clustered on the individual patients to control for patients contributing multiple COVID-19 episodes. FINDINGS: As of 18 January 2021, a total of 476 reported COVID-19 cases had been recorded in MS patients in the Swedish MS registry. Of these, 292 (61.3%) had confirmed COVID-19. The mean value (standard deviation (SD)) age at infection was 44.0 years (11.6). Of the 292 confirmed infections, 68 (23.2%) required hospitalisation. A total of 49 of the 164 confirmed COVID-19 patients on rituximab at baseline (29.9%) required hospitalisation, compared to a rate of 12.7% for all other DMTs combined. Rituximab in confirmed COVID-19 patients was associated with 2.95 times the odds of hospitalisation relative to any other DMT combined (odds ratio = 2.95; 95% confidence interval (CI) = 1.48-5.87). INTERPRETATION: Rituximab treatment, known to increase the risk of severe infections in general, also confers such a risk for MS patients with COVID-19, in comparison with other MS DMTs.


Asunto(s)
COVID-19 , Esclerosis Múltiple , Hospitalización , Humanos , Esclerosis Múltiple/inducido químicamente , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/epidemiología , Sistema de Registros , Rituximab/efectos adversos , Suecia/epidemiología
14.
Cell Biosci ; 11(1): 205, 2021 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-34895331

RESUMEN

BACKGROUND: Mosaic loss of Y chromosome (LOY) is the most common somatic change that occurs in circulating white blood cells of older men. LOY in leukocytes is associated with increased risk for all-cause mortality and a range of common disease such as hematological and non-hematological cancer, Alzheimer's disease, and cardiovascular events. Recent genome-wide association studies identified up to 156 germline variants associated with risk of LOY. The objective of this study was to use these variants to calculate a novel polygenic risk score (PRS) for LOY, and to assess the predictive performance of this score in a large independent population of older men. RESULTS: We calculated a PRS for LOY in 5131 men aged 70 years and older. Levels of LOY were estimated using microarrays and validated by whole genome sequencing. After adjusting for covariates, the PRS was a significant predictor of LOY (odds ratio [OR] = 1.74 per standard deviation of the PRS, 95% confidence intervals [CI] 1.62-1.86, p < 0.001). Men in the highest quintile of the PRS distribution had > fivefold higher risk of LOY than the lowest (OR = 5.05, 95% CI 4.05-6.32, p < 0.001). Adding the PRS to a LOY prediction model comprised of age, smoking and alcohol consumption significantly improved prediction (AUC = 0.628 [CI 0.61-0.64] to 0.695 [CI 0.67-0.71], p < 0.001). CONCLUSIONS: Our results suggest that a PRS for LOY could become a useful tool for risk prediction and targeted intervention for common disease in men.

15.
Neurology ; 97(19): e1870-e1885, 2021 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-34610987

RESUMEN

BACKGROUND AND OBJECTIVES: People with multiple sclerosis (MS) are a vulnerable group for severe coronavirus disease 2019 (COVID-19), particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. METHODS: Data from 12 data sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs) covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit (ICU) admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale (EDSS) score. RESULTS: Six hundred fifty-seven (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.01-2.41; aOR 2.43, 95% CI 1.48-4.02) and ICU admission (aOR 2.30, 95% CI 0.98-5.39; aOR 3.93, 95% CI 1.56-9.89), although only rituximab was associated with higher risk of artificial ventilation (aOR 4.00, 95% CI 1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization (aOR 1.75, 95% CI 1.29-2.38; aOR 2.76, 95% CI 1.87-4.07) and ICU admission (aOR 2.55, 95% CI 1.49-4.36; aOR 4.32, 95% CI 2.27-8.23), but only rituximab was associated with artificial ventilation (aOR 6.15, 95% CI 3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization (aOR 1.86, 95% CI 1.13-3.07; aOR 2.88, 95% CI 1.68-4.92) and ICU admission (aOR 2.13, 95% CI 0.85-5.35; aOR 3.23, 95% CI 1.17-8.91), but only rituximab was associated with ventilation (aOR 5.52, 95% CI 1.71-17.84). Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity. DISCUSSION: Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19.


Asunto(s)
COVID-19/complicaciones , Hospitalización/estadística & datos numéricos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , COVID-19/patología , COVID-19/fisiopatología , Estudios Transversales , Dimetilfumarato/efectos adversos , Dimetilfumarato/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Natalizumab/efectos adversos , Natalizumab/uso terapéutico , Respiración Artificial/estadística & datos numéricos , Rituximab/efectos adversos , Rituximab/uso terapéutico , SARS-CoV-2 , Adulto Joven
16.
Sci Rep ; 11(1): 15160, 2021 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-34312421

RESUMEN

Mosaic loss of chromosome Y (LOY) in immune cells is a male-specific mutation associated with increased risk for morbidity and mortality. The CD99 gene, positioned in the pseudoautosomal regions of chromosomes X and Y, encodes a cell surface protein essential for several key properties of leukocytes and immune system functions. Here we used CITE-seq for simultaneous quantification of CD99 derived mRNA and cell surface CD99 protein abundance in relation to LOY in single cells. The abundance of CD99 molecules was lower on the surfaces of LOY cells compared with cells without this aneuploidy in all six types of leukocytes studied, while the abundance of CD proteins encoded by genes located on autosomal chromosomes were independent from LOY. These results connect LOY in single cells with immune related cellular properties at the protein level, providing mechanistic insight regarding disease vulnerability in men affected with mosaic chromosome Y loss in blood leukocytes.


Asunto(s)
Antígeno 12E7/sangre , Cromosomas Humanos Y/genética , Leucocitos/inmunología , Mosaicismo , Antígeno 12E7/deficiencia , Antígeno 12E7/genética , Anciano , Anciano de 80 o más Años , Envejecimiento/sangre , Envejecimiento/genética , Envejecimiento/inmunología , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/inmunología , Cromosomas Humanos Y/inmunología , Cromosomas Humanos Y/metabolismo , Humanos , Leucocitos/metabolismo , Masculino , Mutación , ARN Mensajero/sangre , ARN Mensajero/genética , Análisis de la Célula Individual
17.
Cell Mol Life Sci ; 78(8): 4019-4033, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33837451

RESUMEN

Epidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation and is associated with aberrant clonal expansion of cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA and RNA from leukocytes in sorted- and single-cells in vivo and in vitro. DNA analyses of sorted cells showed that men diagnosed with Alzheimer's disease was primarily affected with LOY in NK cells whereas prostate cancer patients more frequently displayed LOY in CD4 + T cells and granulocytes. Moreover, bulk and single-cell RNA sequencing in leukocytes allowed scoring of LOY from mRNA data and confirmed considerable variation in the rate of LOY across individuals and cell types. LOY-associated transcriptional effect (LATE) was observed in ~ 500 autosomal genes showing dysregulation in leukocytes with LOY. The fraction of LATE genes within specific cell types was substantially larger than the fraction of LATE genes shared between different subsets of leukocytes, suggesting that LOY might have pleiotropic effects. LATE genes are involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y, challenging the view of it as a "genetic wasteland", and support the hypothesis that altered immune function in leukocytes could be a mechanism linking LOY to increased risk for disease.


Asunto(s)
Enfermedad de Alzheimer/genética , Cromosomas Humanos Y , Mosaicismo , Neoplasias de la Próstata/genética , Linfocitos T CD4-Positivos/metabolismo , Regulación de la Expresión Génica , Humanos , Células Asesinas Naturales/metabolismo , Leucocitos/metabolismo , Masculino
18.
Surg Obes Relat Dis ; 17(6): 1108-1114, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33753006

RESUMEN

BACKGROUND: Despite an association between obesity and multiple sclerosis (MS), very little is known regarding the safety and efficacy outcomes for patients with MS and severe obesity undergoing metabolic surgery. OBJECTIVES: The aim of the present study was to evaluate early complications and efficacy outcomes of metabolic surgery in patients with severe obesity and MS. SETTING: Nationwide, Sweden. METHODS: In this, matched cohort study, 196 patients with an MS diagnosis in the Swedish MS register who were undergoing metabolic surgery (gastric bypass or sleeve gastrectomy) with a registration in the Scandinavian Obesity Surgery Registry (SOReg) were matched 1:10 with a control group without MS diagnosis from the SOReg. A 2-stage matching procedure was used (exact match by surgical method, followed by propensity Score matching, including age, sex, preoperative BMI, surgical center, surgical access, year of surgery, hypertension, diabetes, sleep apnea, and dyslipidemia). RESULTS: Weight loss at 2 years after surgery was similar for patients with MS and controls (total weight loss 31.6 ± 9.1 versus 31.8 ± 9.2, P = .735). No significant differences were seen in either the overall postoperative complication rate (7.9% versus 7.2%, P = .778), or serious postoperative complications (3.7% versus 2.8%, P = .430). All aspects of health-related quality of life (HRQoL) improved in both groups but less so for the physical aspects of HRQoL in patients with MS. CONCLUSION: Metabolic surgery is a safe and efficient treatment for severe obesity in patients with MS, and it leads to subsequent improvements in HRQoL. Further studies addressing the effects of metabolic surgery on MS-related symptoms are needed.


Asunto(s)
Cirugía Bariátrica , Derivación Gástrica , Esclerosis Múltiple , Obesidad Mórbida , Estudios de Cohortes , Gastrectomía , Humanos , Esclerosis Múltiple/complicaciones , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Calidad de Vida , Estudios Retrospectivos , Suecia/epidemiología , Resultado del Tratamiento
20.
Patient Educ Couns ; 104(8): 2037-2044, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33541759

RESUMEN

OBJECTIVE: To assess skills in Motivational interviewing (MI) at the Swedish National Board of Institutional Care (SiS), and to evaluate different ways to provide MI supervision. METHODS: SiS practitioners (n = 134) were randomized to regular group supervision, or individual telephone supervision based on only the behavioral component of a feedback protocol, or the full protocol. Participant's mean age was 43.2 (SD =10.2), and the majority (62.7%) were females. RESULTS: Many participants showed beginning proficiency already at baseline, indicating a successful implementation. Still, results varied widely. The regular supervision and the supervision based on objective feedback were equally effective, and the group receiving feedback based on fewer variables of the protocol performed better on only one of the seven skill measures. The objective feedback did not provoke supervisee discomfort/distress, or negatively affect the supervisory relationship. CONCLUSIONS: Extensive MI implementation can increase practitioners' skills in MI, but the question of the best mode of ongoing supervision needs further attention. PRACTICE IMPLICATIONS: Objective feedback does not seem to negatively affect the supervisee's skill acquisition or the supervisor-supervisee working alliance, but the question of how to most efficiently provide feedback from multifaceted feedback tools remains unanswered.


Asunto(s)
Entrevista Motivacional , Adulto , Femenino , Objetivos , Humanos , Estudios Longitudinales , Proyectos de Investigación , Suecia
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