Challenges and lessons learned from a long-term postauthorisation safety study programme of rivaroxaban in Europe.

OBJECTIVES: To describe opportunities and challenges experienced from the four pharmacoepidemiological database studies included in the rivaroxaban post authorisation safety study (PASS) programme and propose ways to maximise the value of population-based observational research when addressing regulatory requirements. DESIGN: PASS programme of rivaroxaban carried out as part of the regulatory postapproval commitment to the European Medicines Agency. SETTING: Clinical practice in Germany, the Netherlands, Sweden and the UK (electronic health records)-undertaken by pharmacoepidemiology research teams using country-specific databases with different coding structures. PARTICIPANTS: 355 152 patients prescribed rivaroxaban and 338 199 patients prescribed vitamin K antagonists. RESULTS: Two major challenges that were encountered throughout the lengthy PASS programme were related to: (1) finalising country-tailored study designs before the extent of rivaroxaban uptake was known, and (2) new research questions that arose during the programme (eg, those relating to an evolving prescribing landscape). RECOMMENDATIONS: We advocate the following strategies to help address these major challenges (should they arise in any future PASS): conducting studies based on a common data model that enable the same analytical tools to be applied when using different databases; maintaining early, clear, continuous communication with the regulator (including discussing the potential benefit of studying drug use as a precursor to planning a safety study); consideration of adaptive designs whenever uncertainty exists and following an initial period of data collection; and setting milestones for the review of study objectives.

Safety profile of rivaroxaban in first-time users treated for venous thromboembolism in four European countries.

BACKGROUND: The European rivaroxaban post-authorization safety study evaluated bleeding risk among patients initiated on rivaroxaban or vitamin K antagonists for the treatment and secondary prevention of venous thromboembolism in routine clinical practice. METHODS: Cohorts were created using electronic healthcare databases from the UK, the Netherlands, Germany and Sweden. Patients with a first prescription of rivaroxaban or vitamin K antagonist during the period from December 2011 (in the UK, January 2012) to December 2017 (in Germany, December 2016) for venous thromboembolism indication, with no record of atrial fibrillation or recent cancer history, were observed until the occurrence of each safety outcome (hospitalization for intracranial, gastrointestinal, urogenital or other bleeding), death or study end (December 2018; in Germany, December 2017). Crude incidence rates of each outcome per 100 person-years were computed. RESULTS: Overall, 44 737 rivaroxaban and 45 842 vitamin K antagonist patients were enrolled, mean age, 59.9-63.8 years. Incidence rates were similar between rivaroxaban and vitamin K antagonist users with some exceptions, including higher incidence rates for gastrointestinal bleeding in rivaroxaban users than in vitamin K antagonist users. Among rivaroxaban users, mortality and bleeding risk generally increased with age, renal impairment and diabetes. CONCLUSIONS: This study provides further data from routine clinical practice that broadly support safety profile of rivaroxaban for VTE indication and complement findings from previous randomized clinical trials.

Association of Statin Use With Risk of Stroke Recurrence After Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: Survivors of spontaneous intracerebral hemorrhage (ICH) may have indications for statin therapy. The effect of statins on the risk of subsequent hemorrhagic and ischemic stroke (IS) in this setting is uncertain. We sought to determine the risk of any stroke (ischemic stroke, IS or recurrent ICH), IS, and recurrent ICH associated with statin use among ICH survivors. METHODS: Using the Danish Stroke Registry, we identified all patients admitted to a hospital in Denmark (population 5.8 million) with a first-ever ICH between January 2003 and December 2021 who were aged 50 years or older and survived >30 days. Patients were followed up until August 2022. Within this cohort, we conducted 3 nested case-control analyses for any stroke, IS, and recurrent ICH. We matched controls for age, sex, time since first-ever ICH, and history of prior IS. The primary exposure was statin use before or on the date of subsequent stroke or the equivalent date in matched controls. Using conditional logistic regression, we calculated adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CIs) for any stroke, IS, and recurrent ICH associated with statin exposure. RESULTS: We identified 1,959 patients with any stroke (women 45.3%; mean [SD] age, 72.6 [9.7] years) who were matched to 7,400 controls; 1,073 patients with IS (women 42.0%; mean [SD] age, 72.4 [10.0] years) who were matched to 4,035 controls and 984 patients with recurrent ICH (women 48.7%; mean [SD] age, 72.7 [9.2] years) who were matched to 3,755 controls. Statin exposure was associated with a lower risk of both any stroke (cases 38.6%, controls 41.1%; aOR 0.88; 95% CI 0.78-0.99) and IS (cases 39.8%, controls 41.8%, aOR 0.79; 95% CI 0.67-0.92), but was not associated with recurrent ICH risk (cases 39.1%, controls 40.8%, aOR 1.05; 95% CI 0.88-1.24). DISCUSSION: Exposure to statins was not associated with an increased risk of recurrent ICH but was associated with a lower risk of any stroke, largely due to a lower risk of IS. Confirmation of these findings in randomized trials is needed. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that statin use in patients with ICH is associated with a lower risk of any stroke and IS and not with increased risk of recurrent ICH.

Major Cardiovascular Events After Spontaneous Intracerebral Hemorrhage by Hematoma Location.

Importance: Survivors of spontaneous (ie, nontraumatic and with no known structural cause) intracerebral hemorrhage (ICH) have an increased risk of major cardiovascular events (MACEs), including recurrent ICH, ischemic stroke (IS), and myocardial infarction (MI). Only limited data are available from large, unselected population studies assessing the risk of MACEs according to index hematoma location. Objective: To examine the risk of MACEs (ie, the composite of ICH, IS, spontaneous intracranial extra-axial hemorrhage, MI, systemic embolism, or vascular death) after ICH based on ICH location (lobar vs nonlobar). Design, Setting, and Participants: This cohort study identified 2819 patients in southern Denmark (population of 1.2 million) 50 years or older hospitalized with first-ever spontaneous ICH from January 1, 2009, to December 31, 2018. Intracerebral hemorrhage was categorized as lobar or nonlobar, and the cohorts were linked to registry data until the end of 2018 to identify the occurrence of MACEs and separately recurrent ICH, IS, and MI. Outcome events were validated using medical records. Associations were adjusted for potential confounders using inverse probability weighting. Exposure: Location of ICH (lobar vs nonlobar). Main Outcomes and Measures: The main outcomes were MACEs and separately recurrent ICH, IS, and MI. Crude absolute event rates per 100 person-years and adjusted hazard ratios (aHRs) with 95% CIs were calculated. Data were analyzed from February to September 2022. Results: Compared with patients with nonlobar ICH (n = 1255; 680 [54.2%] men and 575 [45.8%] women; mean [SD] age, 73.5 [11.4] years), those with lobar ICH (n = 1034; 495 [47.9%] men and 539 [52.1%] women, mean [SD] age, 75.2 [10.7] years) had higher rates of MACEs per 100 person-years (10.84 [95% CI, 9.51-12.37] vs 7.91 [95% CI, 6.93-9.03]; aHR, 1.26; 95% CI, 1.10-1.44) and recurrent ICH (3.74 [95% CI, 3.01-4.66] vs 1.24 [95% CI, 0.89-1.73]; aHR, 2.63; 95% CI, 1.97-3.49) but not IS (1.45 [95% CI, 1.02-2.06] vs 1.77 [95% CI, 1.34-2.34]; aHR, 0.81; 95% CI, 0.60-1.10) or MI (0.42 [95% CI, 0.22-0.81] vs 0.64 [95% CI, 0.40-1.01]; aHR, 0.64; 95% CI, 0.38-1.09). Conclusions and Relevance: In this cohort study, spontaneous lobar ICH was associated with a higher rate of subsequent MACEs than nonlobar ICH, primarily due to a higher rate of recurrent ICH. This study highlights the importance of secondary ICH prevention strategies in patients with lobar ICH.

Association Between Statin Use and Intracerebral Hemorrhage Location: A Nested Case-Control Registry Study.

BACKGROUND AND OBJECTIVES: A causal relationship between statin use and intracerebral hemorrhage (ICH) is uncertain. We hypothesized that an association between long-term statin exposure and ICH risk might vary for different ICH locations. METHODS: We conducted this analysis using linked Danish nationwide registries. Within the Southern Denmark Region (population 1.2 million), we identified all first-ever cases of ICH between 2009 and 2018 in persons aged ≥55 years. Patients with medical record-verified diagnoses were classified as having a lobar or nonlobar ICH and matched for age, sex, and calendar year to general population controls. We used a nationwide prescription registry to ascertain prior statin and other medication use that we classified for recency, duration, and intensity. Using conditional logistic regression adjusted for potential confounders, we calculated adjusted ORs (aORs) and corresponding 95% CIs for the risk of lobar and nonlobar ICH. RESULTS: We identified 989 patients with lobar ICH (52.2% women, mean age 76.3 years) who we matched to 39,500 controls and 1,175 patients with nonlobar ICH (46.5% women, mean age 75.1 years) who we matched to 46,755 controls. Current statin use was associated with a lower risk of lobar (aOR 0.83; 95% CI, 0.70-0.98) and nonlobar ICH (aOR 0.84; 95% CI, 0.72-0.98). Longer duration of statin use was also associated with a lower risk of lobar (<1 year: aOR 0.89; 95% CI, 0.69-1.14; ≥1 year to <5 years aOR 0.89; 95% CI 0.73-1.09; ≥5 years aOR 0.67; 95% CI, 0.51-0.87; p for trend 0.040) and nonlobar ICH (<1 year: aOR 1.00; 95% CI, 0.80-1.25; ≥1 year to <5 years aOR 0.88; 95% CI 0.73-1.06; ≥5 years aOR 0.62; 95% CI, 0.48-0.80; p for trend <0.001). Estimates stratified by statin intensity were similar to the main estimates for low-medium intensity therapy (lobar aOR 0.82; nonlobar aOR 0.84); the association with high-intensity therapy was neutral. DISCUSSION: We found that statin use was associated with a lower risk of ICH, particularly with longer treatment duration. This association did not vary by hematoma location.

Safety and effectiveness of rivaroxaban for prevention of stroke in patients with nonvalvular atrial fibrillation: analysis of routine clinical data from four countries.

BACKGROUND: The safety and effectiveness of rivaroxaban versus vitamin K antagonists (standard of care [SOC]) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) was evaluated in Europe. RESEARCH DESIGN AND METHODS: Observational studies were conducted in the UK, the Netherlands, Germany, and Sweden. Primary safety outcomes were hospitalization for intracranial hemorrhage, gastrointestinal bleeding, or urogenital bleeding among new users of rivaroxaban and SOC with NVAF; outcomes were analyzed using cohort (rivaroxaban or SOC use) and nested case-control designs (current vs nonuse). Statistical analyses comparing rivaroxaban and SOC cohorts were not performed. RESULTS: Overall, 162,919 rivaroxaban users and 177,758 SOC users were identified. In the cohort analysis, incidence ranges for rivaroxaban users were 0.25-0.63 events per 100 person-years for intracranial bleeding, 0.49-1.72 for gastrointestinal bleeding, and 0.27-0.54 for urogenital bleeding. Corresponding ranges for SOC users were 0.30-0.80, 0.30-1.42, and 0.24-0.42, respectively. In the nested case-control analysis, current SOC use generally presented a greater risk of bleeding outcomes than nonuse. Rivaroxaban use (vs nonuse) was associated with a higher risk of gastrointestinal bleeding, but a similar risk of intracranial or urogenital bleeding, in most countries. Ischemic stroke incidence ranged from 0.31 to 1.52 events per 100 person-years for rivaroxaban users. CONCLUSIONS: Incidences of intracranial bleeding were generally lower with rivaroxaban than with SOC, whereas incidences of gastrointestinal and urogenital bleeding were generally higher. The safety profile of rivaroxaban for NVAF in routine practice is consistent with findings from randomized controlled trials and other studies.

Association of Prior Intracerebral Hemorrhage With Major Adverse Cardiovascular Events.

Importance: Patients with stroke due to nontraumatic (spontaneous) intracerebral hemorrhage (ICH) often harbor vascular risk factors and comorbidities, but it is unclear which major adverse cardiovascular events (MACEs) occur more frequently among patients with a prior ICH than the general population. Objective: To evaluate the risk of a MACE for patients with a prior ICH compared with the general population. Design, Setting, and Participants: This cohort study identified 8991 patients with a first ICH in the Danish Stroke Registry from January 1, 2005, to June 30, 2018, who were aged 45 years or older and survived more than 30 days after an ICH. Patients in this ICH cohort were matched 1:40 on age, sex, and ICH-onset date with a comparison cohort of 359 185 individuals from the general population without a prior ICH. Both cohorts were followed up for 6 months or more until December 31, 2018, for outcomes using registry data. Data were analyzed from October 1, 2021, to July 19, 2022. Exposures: Intracerebral hemorrhage identified by a nationwide clinical database. Main Outcomes and Measures: The main outcomes were ICH, ischemic stroke, myocardial infarction, and a composite of MACEs. For each outcome, a case-control study nested within the cohorts was also performed, adjusting for time-varying exposures and potential confounders. Crude absolute event rates per 100 person-years, adjusted hazard ratios (aHRs) and 95% CIs and, in the nested case-control analyses, crude and adjusted odds ratios and 95% CIs were calculated. Results: The ICH cohort (n = 8991; 4814 men [53.5%]; mean [SD] age, 70.7 [11.5] years) had higher event rates than the comparison cohort (n = 359 185; 192 256 men [53.5%]; mean [SD] age, 70.7 [11.5] years) for MACEs (4.16 [95% CI, 3.96-4.37] per 100 person-years vs 1.35 [95% CI, 1.33-1.36] per 100 person-years; aHR, 3.13 [95% CI, 2.97-3.30]), ischemic stroke (1.52 [95% CI, 1.40-1.65] per 100 person-years vs 0.56 [95% CI, 0.55-0.57] per 100 person-years; aHR, 2.64 [95% CI, 2.43-2.88]), and ICH (1.44 [95% CI, 1.32-1.56] per 100 person-years vs 0.06 [95% CI, 0.06-0.07] per 100 person-years; aHR, 23.49 [95% CI, 21.12-26.13]) but not myocardial infarction (0.52 [95% CI, 0.45-0.60] per 100 person-years vs 0.48 [95% CI, 0.47-0.49] per 100 person-years; aHR, 1.12 [95% CI, 0.97-1.29]). Nested case-control analyses returned risk estimates of similar magnitude as the cohort analyses. Conclusions and Relevance: The findings of this cohort study suggest that Danish patients with a prior ICH had statistically significantly higher rates of MACEs than the general population, indicating a need for attention to optimal secondary prevention with blood pressure lowering and antithrombotic and statin therapies after an ICH in clinical research and practice.

Secondary sclerosing cholangitis after critical COVID-19: Three case reports.

BACKGROUND: The global coronavirus disease 2019 (COVID-19) pandemic has caused more than 5 million deaths. Multiorganic involvement is well described, including liver disease. In patients with critical COVID-19, a new entity called "post-COVID-19 cholangiopathy" has been described. CASE SUMMARY: Here, we present three patients with severe COVID-19 that subsequently developed persistent cholestasis and chronic liver disease. All three patients required intensive care unit admission, mechanical ventilation, vasopressor support, and broad spectrum antibiotics due to secondary infections. Liver transplant protocol was started for two of the three patients. CONCLUSION: Severe COVID-19 infection should be considered a potential risk factor for chronic liver disease and liver transplantation.

Safety and effectiveness of appropriately and inappropriately dosed rivaroxaban or apixaban versus warfarin in patients with atrial fibrillation: a cohort study with nested case-control analyses from UK primary care.

OBJECTIVES: To investigate effects of appropriately and inappropriately dosed apixaban/rivaroxaban versus warfarin on effectiveness and safety outcomes in patients with non-valvular atrial fibrillation (NVAF). DESIGN: Cohort study with nested case-control analyses using primary care electronic health records (IQVIA Medical Research Data UK database). SETTING: UK primary care. PARTICIPANTS: Patients aged ≥18 years with NVAF newly prescribed apixaban (N=14 701), rivaroxaban (N=14 288) or warfarin (N=16 175) between 1 January 2012 and 30 June 2018, and followed up to 31 December 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident cases of ischaemic stroke/systemic embolism (IS/SE) and intracranial bleeding (ICB). Cases were matched to controls on age, sex and OAC naïve status. Using logistic regression, adjusted ORs with 95% CIs were calculated for the outcomes comparing apixaban/rivaroxaban use (appropriate or inappropriate dosing based on the product label criteria) and warfarin. RESULTS: For IS/SE, ORs (95% CIs) for apixaban versus warfarin were 1.19 (0.92-1.52) for appropriate dose and 1.01 (0.67-1.51) for inappropriate dose; for rivaroxaban versus warfarin, estimates were 1.07 (0.83-1.37) for appropriate dose and 1.21 (0.78-1.88) for inappropriate dose. For ICB, ORs (95% CIs) for apixaban versus warfarin were 0.67 (0.44-1.00) for appropriate dose and 0.45 (0.21-0.95) for inappropriate dose; for rivaroxaban versus warfarin, estimates were 0.81 (0.55-1.20) for appropriate dose and 1.14 (0.56-2.31) for inappropriate dose. CONCLUSIONS: Dosing appropriateness in NVAF was not associated with a significant difference in IS/SE risk or increase in ICB risk versus warfarin. These findings may reflect residual confounding and biases that were difficult to control, as also seen in other observational studies. They should, therefore, be interpreted with caution, and prescribers should adhere to the dosing instructions in the respective Summary of Product Characteristics. Further studies on this topic from real-world populations are needed.

Association of Long-term Statin Use With the Risk of Intracerebral Hemorrhage: A Danish Nationwide Case-Control Study.

BACKGROUND AND OBJECTIVES: A causal relationship between long-term statin use and the risk of intracerebral hemorrhage (ICH) remains uncertain. We investigated the association between statin use prior to hospital admission for ICH in a Danish population-based, nationwide case-control study. METHODS: We used the Danish Stroke Registry to identify all patients age ≥45-years with a first-ever ICH between 2005-2018. ICH cases were matched for age, sex, and calendar year to controls selected from the general population. A medication registry with information on all dispensed prescriptions at community pharmacies in Denmark since 1995 was used to ascertain prior statin exposure that was classified for recency, duration, and intensity. Using conditional regression and adjusting for potential confounders, we calculated adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CIs) for the risk of ICH. RESULTS: The study population consisted of 16,235 patients with ICH and 640,943 controls. Current statin use (cases 25.9% vs controls 24.5%; aOR 0.74, 95% CI, 0.71-0.78) and longer duration of current statin use (<1 year: aOR 0.86; 95%CI, 0.81-0.92; ≥1 to <5 years: aOR 0.72; 95%CI, 0.68-0.76; ≥5 to <10 years: aOR 0.65; 95%CI, 0.60-0.71; ≥10 years of use, 0.53; 95%CI 0.45-0.62; P for trend <0.001) were associated with lower risk of ICH. Similar treatment duration relationships were found in analyses stratified by statin use intensity (high intensity therapy: <1 year of use, aOR 0.78; 95%CI, 0.66-0.93; ≥10 years of use: 0.46; 95% CI 0.33-0.65; P for trend 0.001). DISCUSSION: We found that longer duration of statin use is associated with a lower risk of ICH. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that current statin use and longer duration of statin use are each associated with a lower risk of ICH.

Manifestaciones de la resiliencia psicológica en atletas de alto rendimiento

La presente investigación se fundamentó en las teorías que exploran la resiliencia en el ámbito de la Psicología del Deporte, se planteó como objetivo analizar la manifestación de la resiliencia psicológica en atletas cubanos de alto rendimiento, específicamente en la exdeportista corredora de 800 metros Ana Fidelia Quiroz Moret y en deportistas de la categoría Juvenil y Mayores del equipo nacional de tenis de Mesa de Cuba. Se utilizaron métodos de investigación con predominio de la metodología cualitativa analítica como estudios de caso individual y de grupo, análisis-síntesis, entrevista, análisis de documentos y videos, observación, el cuestionario de Afrontamiento de estrés de Sandín y Chorot y la escala de Resiliencia de Wagnild y Young. Se utilizó el porcentaje como método matemático. Los resultados principales permitieron constatar la presencia de nivel alto de resiliencia en la exdeportista estudiada y niveles medio-alto y alto en los tenimesistas estudiados, se identificaron los factores protectores que influyen en el afrontamiento de eventos vitales y situaciones estresantes. Las conclusiones principales destacaron la necesidad de valorar en los deportistas de alto rendimiento estudiados, las manifestaciones de la resiliencia psicológica de manera particular: los factores protectores de la personalidad, la influencia de las redes de apoyo social así como las estrategias y estilos de afrontamiento al estrés que afloran ante situaciones adversas que se presentan en la vida deportiva, dificultades propias del entrenamiento y la competencia a las que se enfrentan con regularidad, que pueden constituir modelos a tener en cuenta para otros deportistas que se inician.

O objetivo desta pesquisa foi analisar a manifestação da resiliência psicológica em atletas cubanos de alto rendimento, especificamente na ex-corredora Ana Fidelia Quiroz Moret, de 800m, e em atletas da seleção nacional cubana de tênis de mesa, nas categorias jovem e sênior. Foram utilizados métodos de pesquisa com predominância de metodologia analítica qualitativa, como estudos de casos individuais e de grupo, análise-síntese, entrevista, análise de documentos e vídeos, observação, o questionário de Cópia de Estresse de Sandin e Chorot e a escala de Resiliência de Wagnild e Young. A porcentagem foi utilizada como um método matemático. Os principais resultados mostraram a presença de um alto nível de resiliência na ex-esportista estudada e níveis médios-altos e altos nos tenistas estudados. Os fatores de proteção que influenciam o enfrentamento de eventos da vida e situações estressantes foram identificados. As principais conclusões destacaram a necessidade de avaliar nos atletas de alto rendimento estudados, as manifestações de resiliência psicológica em particular: os fatores protetores da personalidade, a influência das redes de apoio social, assim como as estratégias e estilos de lidar com o estresse que surgem em situações adversas que surgem na vida esportiva, as dificuldades de treinamento e competição que enfrentam regularmente, que podem constituir modelos a serem levados em conta para outros atletas que estão começando.

The present research was based on the theories that explore resilience in the field of Sport Psychology. The objective was to analyze the manifestation of psychological resilience in Cuban high-performance athletes, specifically in the former 800-meter runner Ana Fidelia Quiroz Moret and in athletes of the Cuban national Table Tennis team in the Juvenile and Senior categories. Research methods were used with a predominance of analytical qualitative methodology such as individual and group case studies, analysis-synthesis, interview, analysis of documents and videos, observation, the Stress Coping questionnaire of Sandin and Chorot and the Resilience scale of Wagnild and Young. The percentage was used as a mathematical method. The main results showed the presence of a high level of resilience in the ex-sportswoman studied and medium-high and high levels in the tennis players studied. The main conclusions highlighted the need to assess in the high performance athletes studied, the manifestations of psychological resilience in particular: the protective factors of the personality, the influence of social support networks as well as the strategies and styles of coping with stress that emerge in adverse situations that arise in sports life, difficulties of training and competition that they face regularly, which may constitute models to be taken into account for other athletes who are starting out.

Higher Risk of Ischemic Stroke After an Intracerebral Hemorrhage Than in General Population: A Cohort Study From the United Kingdom.

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Effectiveness of a Mindfulness and Self-Compassion Standard Training Program versus an Abbreviated Training Program on Stress in Tutors and Resident Intern Specialists of Family and Community Medicine and Nursing in Spain.

Stress is one of the most common problems among healthcare professionals, as they are exposed to potentially stressful and emotionally challenging situations in the workplace. Mindfulness-based stress reduction (MBSR) training programs have been shown to decrease stress. The objective of this study was to compare the effectiveness of an abbreviated 4-weeks MBSR training program in relation to a standard 8-weeks one on the stress levels. A controlled and randomized clinical trial was designed, in which 112 tutors and resident intern specialists in Family and Community Medicine and Nursing of six Spanish National Health System teaching units (TUs) participated. Participants included in the experimental groups (EGs) received a MBRS training program (standard or abbreviated), while control group (CG) participants did not receive any intervention. The stress levels were assessed by the Perceived Stress Questionnaire (PSQ) in three different moments during the study: before, immediately after, and 3 months after the intervention. Adjusted covariance analysis (ANCOVA), using pretest scores as the covariate, showed a significant reduction in stress (F(2,91) = 5.165; p = 0.008; η2 = 0.102) in the post-test visit, attributable to the implementation of the standard training program, but without the maintenance of its effects over time. No significant impact of the abbreviated training program on stress levels was observed in the intergroup comparison. A standard 8-weeks MBSR training program aimed at tutors and resident intern specialists in Family and Community Medicine and Nursing produces significant improvements in stress levels compared with the abbreviated intervention and no intervention. New studies about abbreviated training programs are needed to provide effective treatments which improve well-being of these professionals.

Public health impact of low-dose aspirin on colorectal cancer, cardiovascular disease and safety in the UK - Results from micro-simulation model.

BACKGROUND: Low-dose aspirin therapy reduces the risk of cardiovascular disease and may have a positive effect on the prevention of colorectal cancer. We evaluated the population-level expected effect of regular low-dose aspirin use on cardiovascular disease (CVD), colorectal cancer (CRC), gastrointestinal bleeding, symptomatic peptic ulcers, and intracranial hemorrhage, using a microsimulation study design. METHODS: We used individual-level state transition modeling to assess the impact of aspirin in populations aged 50-59 or 60-69 years old indicated for low-dose aspirin usage for primary or secondary CVD prevention. Model parameters were based on data from governmental agencies from the UK or recent publications. RESULTS: In the 50-59 years cohort, a decrease in incidence rates (IRs per 100 000 person years) of non-fatal CVD (-203 and -794) and fatal CVD (-97 and-381) was reported in the primary and secondary CVD prevention setting, respectively. The IR reduction of CRC (-96 and -93) was similar for primary and secondary CVD prevention. The IR increase of non-fatal (116 and 119) and fatal safety events (6 and 6) was similar for primary and secondary CVD prevention. Similar results were obtained for the 60-69 years cohort. CONCLUSIONS: The decrease in fatal CVD and CRC events was larger than the increase in fatal safety events and this difference was more pronounced when low-dose aspirin was used for secondary compared to primary CVD prevention. These results provide a comprehensive image of the expected effect of regular low-dose aspirin therapy in a UK population indicated to use aspirin for CVD prevention.

Trends in Incidence of Intracerebral Hemorrhage and Association With Antithrombotic Drug Use in Denmark, 2005-2018.

Importance: Spontaneous (nontraumatic) intracerebral hemorrhage (ICH) is the most severe complication of antithrombotic drug use. Objectives: To estimate the strength of association between use of antithrombotic drugs and risk of ICH and to examine major changes in the incidence of ICH in the general population. Design, Setting, and Participants: This case-control study of patients with a first-ever ICH from January 1, 2005, to December 31, 2018, matched by age, sex, and calendar year with general population controls (1:40 ratio), assessed case and control patients 20 to 99 years of age in population-based nationwide registries in Denmark (population of 5.8 million). Exposures: Use of low-dose aspirin, clopidogrel, a vitamin K antagonist (VKA), or a direct oral anticoagulant (DOAC). Main Outcomes and Measures: Association of ICH with antithrombotic drug use, annual age- and sex-standardized incidence rate of ICH, and prevalence of treatment with antithrombotic drugs. Conditional logistic regression models estimated adjusted odds ratios (aORs) (95% CIs) for the association of antithrombotic drugs with ICH. Results: Among 16 765 cases with ICH (mean [SD] age, 72.8 [13.1] years; 8761 [52.3%] male), 7473 (44.6%) were exposed to antithrombotic medications at the time of ICH onset. The association with ICH was weakest for current use of low-dose aspirin (cases: 28.7%, controls: 22.6%; aOR, 1.51; 95% CI, 1.44-1.59) and clopidogrel (cases: 6.2%, controls: 3.4%; aOR, 1.65; 95% CI, 1.47-1.84) and strongest with current use of a VKA (cases: 12.0%, controls: 5.0%; aOR, 2.76; 95% CI, 2.58-2.96). The association with ICH was weaker for DOACs (cases: 3.0%, controls: 1.8%; aOR, 1.83; 95% CI, 1.61-2.07) than for VKAs. Compared with 2005, the prevalence of use of oral anticoagulants among general population controls in 2018 was higher (3.8% vs 11.1%), predominantly because of increased use of DOACs (DOACs: 0% vs 7.0%; VKA: 3.8% vs 4.2%). Antiplatelet drugs were used less frequently (24.7% vs 21.4%) because of decreased use of low-dose aspirin (24.3% vs 15.3%), whereas clopidogrel use increased (1.0% vs 6.8%). The age- and sex-standardized incidence rate of ICH decreased from 33 per 100 000 person-years in 2005 to 24 per 100 000 person-years in 2018 (P < .001 for trend). Conclusions and Relevance: In Denmark from 2005 to 2018, use of antithrombotic drugs, especially VKAs, was associated with ICH. Although use of oral anticoagulation increased substantially during the study period, the incidence rate of ICH decreased.

Comparison of the Effectiveness of an Abbreviated Program versus a Standard Program in Mindfulness, Self-Compassion and Self-Perceived Empathy in Tutors and Resident Intern Specialists of Family and Community Medicine and Nursing in Spain.

Health professionals are among the most vulnerable to work stress and emotional exhaustion problems. These health professionals include tutors and resident intern specialists, due to the growing demand for the former and the high work overload of the latter. Mindfulness training programs can support these professionals during times of crisis, such as the current global pandemic caused by the coronavirus-19 disease. The objective of this study was to compare the effectiveness of an abbreviated Mindfulness-Based Stress Reduction (MBSR) and Mindful Self-Compassion (MSC) training program in relation to a standard training program on the levels of mindfulness, self-compassion, and self-perceived empathy in tutors and resident intern specialists of Family and Community Medicine and Nursing. A total of 112 professionals attached to six Spanish National Health System teaching units (TUs) participated in this randomized and controlled clinical trial. Experimental Group (GE) participants were included in the standard or abbreviated MBSR programs. The Five Facet Mindfulness Questionnaire (FFMQ), the Self-Compassion Scale short form (SCS-SF), and the Jefferson Scale of Physician Empathy (JSPE) were administered three times during the study: before, immediately after, and 3 months after the intervention. Adjusted covariance analysis (ANCOVA), using pretest scores as the covariate, showed a significant increase in mindfulness (F(2,91) = 3.271; p = 0.042; η2 = 0.067) and self-compassion (F(2,91) = 6.046; p = 0.003; η2 = 0.117) in the post-test visit, and in self-compassion (F(2,79) = 3.880; p = 0.025; η2 = 0.089) in the follow-up visit, attributable to the implementation of the standard training program. The standard MBSR and MSC training program improves levels of mindfulness and self-compassion, and promotes long-lasting effects in tutors and resident intern specialists. New studies are needed to demonstrate the effectiveness of abbreviated training programs.

Acciones metodológicas para la inclusión educativa de educandos con discapacidad intelectual mediante el parakarate / Ações metodológicas para a inclusão educacional de alunos com deficiências intelectuais através do parakarate / Methodological actions for the educational inclusion of students with intellectual disabilities through para-karate

RESUMEN La presente investigación responde a las necesidades del organismo Inder; está dirigida al proceso de inclusión educativa desde el contexto del deporte para todos, en educandos con discapacidad intelectual, del combinado deportivo Guanabo, municipio de la Habana del Este. El objetivo es establecer acciones metodológicas como herramienta de trabajo para los especialistas de kárate-do que tienen la responsabilidad de la atención físico educativo de esta población. A partir de un enfoque dialéctico materialista de interpretación de los fenómenos, se emplearon como principales métodos y técnicas la entrevista, encuesta, observación científica y los métodos estadísticos. Estos métodos y técnicas empleados permitieron revelar las relaciones causales entre el objeto y el campo de acción declarado. Se constató que es limitado el sistema de preparación de los profesionales de esta actividad para la enseñanza y atención a los educandos con discapacidad intelectual dentro de la clase de kárate-do, producto a insuficiencias en las indicaciones metodológicas que precisen dicha atención lo cual impide que se produzca un proceso inclusivo. Las acciones metodológicas beneficiarías a los profesionales que atienden estos educandos, al aplicarse con sistematicidad, permitirá la inclusión, diversidad en la participación y el aprendizaje de las prácticas de este; reduce además la exclusión dentro del proceso de entrenamiento como lo requiere la sociedad en todas sus esferas de actuación.

RESUMO A presente investigação responde às necessidades da organização Inder; é dirigida ao processo de inclusão educacional a partir do contexto do desporto para todos, em estudantes com deficiência intelectual, da equipa desportiva de Guanabo, município de Havana Leste. O objetivo é estabelecer ações metodológicas como um instrumento de trabalho para os especialistas em Karate-do que são responsáveis pelo cuidado educativo físico desta população. Com base numa abordagem materialista dialética da interpretação dos fenómenos, os principais métodos e técnicas utilizados foram a entrevista, o inquérito, a observação científica e os métodos estatísticos. Estes métodos e técnicas utilizados permitiram revelar as relações causais entre o objeto e o campo de ação declarado. Verificou-se que o sistema de preparação dos profissionais desta actividade para o ensino e cuidado dos estudantes com deficiência intelectual dentro da aula de karaté-do é limitado, devido a insuficiências nas indicações metodológicas que requerem tais cuidados, o que impede a realização de um processo inclusivo. As ações metodológicas beneficiarão os profissionais que frequentam estes estudantes, uma vez que são aplicadas sistematicamente, permitirão a inclusão, diversidade na participação e aprendizagem das práticas deste; reduz também a exclusão dentro do processo de formação tal como é exigido pela sociedade em todas as suas esferas de atuação.

ABSTRACT This research responds to the needs of the National Institute of Sport Physical education and Recreation staff (Inder in Spanish), it is aimed at the process of educational inclusion from the context of sport for all, in students with intellectual disabilities, in the Guanabo sports complex, Habana del Este municipality. The objective is to establish methodological actions as a work tool for Karate-do specialists, who are responsible for the educational physical care of this population. From a materialist dialectical approach to the interpretation of phenomena, the main methods and techniques used were: interview, survey, scientific observation and statistics, which allowed revealing the causal relationships between the object and the declared field of action. It was found that the system of preparation of the professionals of this activity for the teaching and care of students with intellectual disabilities within the Karate-do class is limited, due to inadequacies in the methodological indications that require such attention, which prevents them from an inclusive process occurs. The methodological actions would benefit the professionals who assist these students, as they are applied with systematicity, allowing inclusion, diversity in participation and learning of the practices of the student; it also reduces exclusion within the training process as required by society in all its spheres of performance.

Use of non-vitamin K antagonist oral anticoagulants in Colombia: A descriptive study using a national administrative healthcare database.

PURPOSE: We aimed to describe time-trends in the use of NOACs among a group of ambulatory patients with nonvalvular atrial fibrillation (NVAF) in Colombia and to describe treatment patterns and user characteristics. METHODS: Using the Audifarma S.A administrative healthcare database in Colombia, we identified 10 528 patients with NVAF aged at least 18 years between July 2009 and June 2017 with a first prescription (index date) for apixaban, dabigatran or rivaroxaban (index NOAC) and followed them for at least year (max, 8.0 years, mean 2.2 years). We described patient characteristics, NOAC use over time, and the dose of the first NOAC prescription. RESULTS: A total of 2153 (20.5%) patients started on apixaban, 3089 (29.3%) on dabigatran and 5286 (50.2%) on rivaroxaban. The incidence of new users of apixaban and rivaroxaban increased over study years while for dabigatran it decreased. Mean age at the index date was: 78.5 years (apixaban), 76.5 years (dabigatran), 76.0 years (rivaroxaban). The percentage of patients started NOAC therapy on the standard dose was: apixaban 38.0%, dabigatran 30.9%, rivaroxaban 56.9%. The percentage still prescribed their index NOAC at 6 months was apixaban 44.6%, dabigatran 51.4%, rivaroxaban 52.7%. Hypertension was the most common comorbidity (>80% in each NOAC cohort). CONCLUSION: During the last decade, the incidence of NOAC use in patients with NVAF affiliated with a private healthcare regime in Colombia has markedly increased. Future studies should evaluate whether the large number of patients with NVAF starting NOAC treatment on a reduced dose are done so appropriately.

The Validity of Intracerebral Hemorrhage Diagnoses in the Danish Patient Registry and the Danish Stroke Registry.

PURPOSE: To establish the validity of intracerebral hemorrhage (ICH) diagnoses in the Danish Stroke Registry (DSR) and the Danish National Patient Registry (DNPR). PATIENTS AND METHODS: Based on discharge summaries and brain imaging reports, we estimated the positive predictive value (PPV) of a first-ever diagnosis code for ICH (ICD-10, code I61) for all patients in the Region of Southern Denmark (1.2 million) during 2009-2017 according to either DNPR or DSR. We estimated PPVs for any non-traumatic ICH (a-ICH) and spontaneous ICH (s-ICH) alone (ie, without underlying structural cause). We also calculated the sensitivity of these diagnoses in each of the registers. Finally, we classified the location of verified s-ICH. RESULTS: A total of 3,956 patients with ICH diagnosis codes were studied (DSR only: 87; DNPR only: 1,513; both registries: 2,356). In the DSR, the PPVs were 86.5% (95% CI=85.1-87.8) for a-ICH and 81.8% (95% CI=80.2-83.3) for s-ICH. The PPVs in DNPR (discharge code, primary diagnostic position) were 76.2% (95% CI=74.7-77.6) for a-ICH and 70.2% (95% CI=68.6-71.8) for s-ICH. Sensitivity for a-ICH and s-ICH was 76.4% (95% CI=74.8-78.0) and 78.7% (95% CI=77.1-80.2) in DSR, and 87.3% (95% CI=86.0-88.5) and 87.7% (95% CI=86.3-88.9) in DNPR. The location of verified s-ICH was lobar (39%), deep (33.6%), infratentorial (13.2%), large unclassifiable (11%), isolated intraventricular (1.9%), or unclassifiable due to insufficient information (1.3%). CONCLUSION: The validity of a-ICH diagnoses is high in both registries. For s-ICH, PPV was higher in DSR, while sensitivity was higher in DNPR. The location of s-ICH was similar to distributions seen in other populations.

Discontinuation of oral anticoagulation in atrial fibrillation and risk of ischaemic stroke.

OBJECTIVE: To evaluate associations between oral anticoagulant (OAC) discontinuation and risk of ischaemic stroke (IS) among patients with atrial fibrillation (AF). METHODS: We undertook a population-based cohort study with nested case-control analysis using UK primary care electronic health records (IQVIA Medical Research Data-UK) and linked registries from the Region of Southern Denmark (RSD). Patients with AF (76 882 UK, 41 526 RSD) were followed to identify incident IS cases during 2016-2018. Incident IS cases were matched by age and sex to controls. Adjusted ORs for OAC discontinuation (vs current OAC use) were calculated using logistic regression. RESULTS: We identified 616 incident IS cases in the UK and 643 in the RSD. ORs for IS with any OAC discontinuation were 2.99 (95% CI 2.31 to 3.86, UK) and 2.30 (95% CI 1.79 to 2.95, RSD), for vitamin K antagonist discontinuation they were 2.38 (95% CI 1.72 to 3.30, UK) and 1.83 (95% CI 1.34 to 2.49, RSD), and for non-vitamin K antagonist oral anticoagulant discontinuation they were 4.59 (95% CI 2.97 to 7.08, UK) and 3.37 (95% CI 2.35 to 4.85, RSD). ORs were unaffected by time since discontinuation and duration of use. Annually, up to 987 IS cases in the UK and 132 in Denmark could be preventable if OAC therapy is not discontinued. CONCLUSIONS: Our results suggest that patients with AF who discontinue OAC therapy have a significant twofold to threefold higher risk of IS compared with those who continue therapy. Addressing OAC discontinuation could potentially result in a significant reduction in AF-attributed IS.