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Background The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial enrolled patients with estimated glomerular filtration rate 25–75 mL/min/1.73 m2 and urine albumin-to-creatinine ratio >200 mg/g. The Dapagliflozin Effect on CardiovascuLAR Events-Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial enrolled patients with type 2 diabetes, a higher range of kidney function and no albuminuria criterion. The study objective was to estimate the cost-effectiveness of dapagliflozin in a broad chronic kidney disease population based on these two trials in the UK, Spain, Italy and Japan. Methods We adapted a published Markov model based on the DAPA-CKD trial but to a broader population, irrespective of urine albumin-to-creatinine ratio, using patient-level data from the DAPA-CKD and DECLARE-TIMI 58 trials. We sourced cost and utility inputs from literature and the DAPA-CKD trial. The analysis considered healthcare system perspectives over a lifetime horizon. Results Treatment with dapagliflozin was predicted to attenuate disease progression and extend projected life expectancy by 0.64 years (12.5 versus 11.9 years, undiscounted) in the UK, with similar estimates in other settings. Clinical benefits translated to mean quality-adjusted life year (QALY; discounted) gains between 0.45 and 0.68 years across countries. Incremental cost-effectiveness ratios in the UK, Spain, Italy and Japan ($10 676/QALY, $14 479/QALY, $7771/QALY and $13 723/QALY, respectively) were cost-effective at country-specific willingness-to-pay thresholds. Subgroup analyses suggest dapagliflozin is cost-effective irrespective of urinary albumin-to-creatine ratio and type 2 diabetes status. Conclusion Treatment with dapagliflozin may be cost-effective for patients across a wider spectrum of estimated glomerular filtration rates and albuminuria than previously demonstrated, with or without type 2 diabetes, in the UK, Spanish, Italian and Japanese healthcare systems. [ABSTRACT FROM AUTHOR]

Background Studies confirm the positive effect of sugar-sweetened beverage (SSB) taxation on public health. However, only a few countries in Europe adopt SSB taxes. From a public policy perspective, we investigate the conditions under which countries do or do not follow this evidence. Methods Crisp-set Qualitative Comparative Analysis (QCA) of 26 European Organization of Economic Cooperation and Development countries with and without an SSB tax. We test which configurations of conditions (problem pressure, governmental composition, strategic planning, health care system, public health policies, inclusion of expert advice in policymaking) emerge as relevant in determining adoption and non-adoption between the years 1981 and 2021. Pathways that lead to the presence and absence of SSB taxes are identified separately. Results At least one of the following configurations of conditions is present in countries that introduced taxation: (i) high financial problem pressure, low regulatory impact assessment activity; (ii) high public health problem pressure, a contribution-financed health care system, no holistic strategy for combatting non-communicable diseases (NCDs); (iii) a tax-financed health care system, a holistic NCD strategy, high strategic and executive planning capacity. In countries that did not adopt SSB taxes, we find (i) high regulatory impact assessment activity, high levels of sugar export; (ii) no holistic NCD strategy, high spending on preventive care; (iii and iv) a lack of strategic planning capacity and either a high share of spending on preventive care or inclusion of expert advice. Discussion Evidence inclusion requires clear policy priorities in terms of strategy and resources to promote public health. [ABSTRACT FROM AUTHOR]

Background Palliative sedation is a commonly accepted medical practice. This study aims to clarify how palliative sedation is regulated in various countries and whether this may impact its practice. Methods An online survey requesting regulations on palliative sedation was conducted in Belgium, Germany, Hungary, Italy, The Netherlands, Spain, Romania and the UK. Purposive sampling strategy was used to identify clinicians from different medical fields and legal experts for each country. Regulations were analyzed using the principles of the European Association for Palliative Care Framework on palliative sedation. Country reports describing how palliative sedation is regulated were elaborated. Results One hundred and thirty-nine out of 223 (62%) participants identified 31 laws and other regulations affecting palliative sedation. In Spain, 12 regional laws recognize palliative sedation as a right of the patient at the end of life when there are refractory symptoms. In Italy, the law of informed consent and advance directives specifically recognizes the doctor can use deep sedation when there are refractory symptoms. There are also general medical laws that, while not explicitly referring to palliative sedation, regulate sedation-related principles: the obligation of doctors to honour advance directives, informed consent, the decision-making process and the obligation to document the whole process. In Germany, the Netherlands and the UK, palliative sedation is also regulated through professional guidelines that are binding as good practice with legal significance. Conclusions Palliative sedation is considered in the general law of medical practice, in laws regarding the patient's autonomy, and through professional guidelines. [ABSTRACT FROM AUTHOR]

Background In responding to Covid-19, governments have tried to balance protecting health while minimizing gross domestic product (GDP) losses. We compare health-related net benefit (HRNB) and GDP losses associated with government responses of the UK, Ireland, Germany, Spain and Sweden from UK healthcare payer perspective. Methods We compared observed cases, hospitalizations and deaths under 'mitigation' to modelled events under 'no mitigation' to 20 July 2020. We thus calculated healthcare costs, quality adjusted life years (QALYs), and HRNB at £20,000/QALY saved by each country. On per population (i.e. per capita) basis, we compared HRNB with forecast reductions in 2020 GDP growth (overall or compared with Sweden as minimal mitigation country) and qualitatively and quantitatively described government responses. Results The UK saved 3.17 (0.32–3.65) million QALYs, £33 (8–38) billion healthcare costs and £1416 (220–1637) HRNB per capita at £20,000/QALY. Per capita, this is comparable to £1455 GDP loss using Sweden as comparator and offsets 46.1 (7.1–53.2)% of total £3075 GDP loss. Germany, Spain, and Sweden had greater HRNB per capita. These also offset a greater percentage of total GDP losses per capita. Ireland fared worst on both measures. Countries with more mask wearing, testing, and population susceptibility had better outcomes. Highest stringency responses did not appear to have best outcomes. Conclusions Our exploratory analysis indicates the benefit of government Covid-19 responses may outweigh their economic costs. The extent that HRNB offset economic losses appears to relate to population characteristics, testing levels, and mask wearing, rather than response stringency. [ABSTRACT FROM AUTHOR]

Background To stop the spread of the new coronavirus disease in 2019 (COVID-19), many countries had completely locked down. This lockdown restricted the everyday life of the affected residents and changed their mobility pattern, but its effects on sleep pattern were largely unknown. Methods Here, utilizing one of the largest crowdsourced database (Sleep as Android), we analyzed the sleep pattern of 25 217 users with 1 352 513 sleep records between 1 January and 29 April 2020 in the US and 16 European countries (Germany, UK, Spain, France, Italy, The Netherlands, Belgium, Hungary, Denmark, Finland, Norway, Czech, Sweden, Austria, Poland and Switzerland) with more than 100 records in all days of 2020. Results During the COVID-19 pandemic, the sleeping pattern before and after the country-level lockdown largely differed. The subjects increased their sleep duration by an average of 11.3 to 18.6 min on weekday nights, except Denmark (4.9 min) and Finland (7.1 min). In addition, subjects form all 16 European countries delayed their sleep onset from 10.7 min (Sweden) to 29.6 min (Austria). Conclusion During the COVID-19 pandemic, residents in the US and 16 European countries delayed their bedtime and slept longer than usual. [ABSTRACT FROM AUTHOR]

Objectives Smoking is a major risk factor for the development of both cardiovascular disease (CVD) and RA and may cause attenuated responses to anti-rheumatic treatments. Our aim was to compare disease activity, CVD risk factors and CVD event rates across smoking status in RA patients. Methods Disease characteristics, CVD risk factors and relevant medications were recorded in RA patients without prior CVD from 10 countries (Norway, UK, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico). Information on CVD events was collected. Adjusted analysis of variance, logistic regression and Cox models were applied to compare RA disease activity (DAS28), CVD risk factors and event rates across categories of smoking status. Results Of the 3311 RA patients (1012 former, 887 current and 1412 never smokers), 235 experienced CVD events during a median follow-up of 3.5 years (interquartile range 2.5–6.1). At enrolment, current smokers were more likely to have moderate or high disease activity compared with former and never smokers (P  < 0.001 for both). There was a gradient of worsening CVD risk factor profiles (lipoproteins and blood pressure) from never to former to current smokers. Furthermore, former and never smokers had significantly lower CVD event rates compared with current smokers [hazard ratio 0.70 (95% CI 0.51, 0.95), P  = 0.02 and 0.48 (0.34, 0.69), P  < 0.001, respectively]. The CVD event rates for former and never smokers were comparable. Conclusion Smoking cessation in patients with RA was associated with lower disease activity and improved lipid profiles and was a predictor of reduced rates of CVD events. [ABSTRACT FROM AUTHOR]

Background Studies on the association between frailty and health-related quality of life (HRQoL) are scarce and show contradictory results. This study aimed to evaluate the association between physical, psychological and social frailty and HRQoL among community-dwelling older people. Methods A cross-sectional study was performed with baseline data collected in 2015 from the Urban Health Centers Europe (UHCE) project in five European countries, the United Kingdom, Greece, Croatia, The Netherlands and Spain. A total of 2325 participants were included in the baseline measurements of the Urban Health Centers Europe project; 2167 participants (mean age = 79.7; SD=5.6) were included in the analyses after excluding participants with missing data. The Tilburg Frailty Indicator measured overall frailty as well as physical, psychological and social frailty. The 12-Item Short-Form Health Survey was used to measured physical and mental HRQoL. Results Regarding physical HRQoL, a large difference (d =1.29) between physically and not physically frail participants was observed. Regarding mental HRQoL, a large difference (d =1.20) between psychologically and not psychologically frail participants was observed. In the full model with all three domains of frailty and the covariates to explain physical HRQoL, physical (P <0.001) and social frailty (P <0.001) remained significant. In the full model to explain mental HRQoL, all three domains of frailty remained significant (P <0.001). Conclusion Physical frailty had the strongest association with physical HRQoL, and psychological frailty had the strongest association with mental HRQoL. The associations between social frailty and both physical and mental HRQoL remain significant when controlling for physical and psychological frailty. [ABSTRACT FROM AUTHOR]

Posterior cortical atrophy is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer's disease and recent evidence for genetic risk factors specifically related to posterior cortical atrophy, the syndrome can provide important insights into selective vulnerability and phenotypic diversity. The present study describes the first major longitudinal investigation of posterior cortical atrophy disease progression. Three hundred and sixty-one individuals (117 posterior cortical atrophy, 106 typical Alzheimer's disease, 138 controls) fulfilling consensus criteria for posterior cortical atrophy-pure and typical Alzheimer's disease were recruited from three centres in the UK, Spain and USA. Participants underwent up to six annual assessments involving MRI scans and neuropsychological testing. We constructed longitudinal trajectories of regional brain volumes within posterior cortical atrophy and typical Alzheimer's disease using differential equation models. We compared and contrasted the order in which regional brain volumes become abnormal within posterior cortical atrophy and typical Alzheimer's disease using event-based models. We also examined trajectories of cognitive decline and the order in which different cognitive tests show abnormality using the same models. Temporally aligned trajectories for eight regions of interest revealed distinct (P < 0.002) patterns of progression in posterior cortical atrophy and typical Alzheimer's disease. Patients with posterior cortical atrophy showed early occipital and parietal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion leading to tissue loss of comparable extent later. Hippocampal, entorhinal and frontal regions underwent a lower rate of change and never approached the extent of posterior cortical involvement. Patients with typical Alzheimer's disease showed early hippocampal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion. Cognitive models showed tests sensitive to visuospatial dysfunction declined earlier in posterior cortical atrophy than typical Alzheimer's disease whilst tests sensitive to working memory impairment declined earlier in typical Alzheimer's disease than posterior cortical atrophy. These findings indicate that posterior cortical atrophy and typical Alzheimer's disease have distinct sites of onset and different profiles of spatial and temporal progression. The ordering of disease events both motivates investigation of biological factors underpinning phenotypic heterogeneity, and informs the selection of measures for clinical trials in posterior cortical atrophy. [ABSTRACT FROM AUTHOR]

Objective. To gain insight into clinical practice regarding referral, early diagnosis and other aspects of the management of patients with dcSSc in Europe and the USA. Methods. Semi-structured interviews were conducted with 84 rheumatologists (or internal medicine physicians) and 40 dermatologists in different countries (the UK, France, Germany, Italy, Spain and the USA). Physicians were asked to identify key steps in the patient pathway relating to patient presentation, diagnosis and referral, in addition to other treatment and follow-up processes. Results. The interviewed physicians reported that late presentation with dcSSc was common, with some patients presenting to primary care physicians after symptoms had persisted for up to 1 year. Awareness of dcSSc is reported to vary widely among primary care physicians. Final diagnosis, generally following guideline-based recommendations, was by rheumatologists in most cases (or internal medicine physicians in France) and they remained responsible for global patient management, with lesser involvement in diagnosis and management by dermatologists. Specialist centres were not well defined and did not exist in all countries. Conclusion. Patients and primary healthcare providers can be unaware of the symptoms of dcSSc, therefore presentation and referral to specialist care are often late. Thus, improved awareness among patients and primary care physicians is necessary to facilitate earlier referral and diagnosis. Once referred, more consistent use of the modified Rodnan skin score at diagnosis and follow-up may help to monitor disease progression. Furthermore, establishing specialist centres may help to promote such changes and improve patient care. [ABSTRACT FROM AUTHOR]

Background: Effective linkage to specialist care following screening is crucial for secondary prevention of chronic viral hepatitis-related consequences. Methods: To explore the frequency of referral of patients to secondary care from the health services involved in screening and to gather information on the services responsible for the provision of post-test counselling and contact tracing, four online surveys were conducted among general practitioners (GP), and experts working in sexual health services (SHS), antenatal care (ANC) and specialist secondary care in Germany, Hungary, Italy, The Netherlands, Spain and the UK. Results: Overall, 60% of GPs report referring all patients to specialist care. Although 67% of specialists commonly receive patients referred by GPs, specialists in Germany rarely or never receive patients from ANC or from centres testing injecting drug users; and specialists in the Netherlands, Hungary and Germany rarely receive patients from SHS. Gastroenterologists/hepatologists are the professionals mainly responsible for the provision of counselling following a positive diagnosis of viral hepatitis according to two-thirds of specialists, 14% of SHS providers and 11% of ANC providers. Almost half of ANC providers (45%) stated that gynaecologists are the professionals responsible for the provision of counselling to positive pregnant women; among SHS providers, only 14% identified SHS as the services responsible. Conclusion: Our findings suggest the existence of complex/ineffective referral practices or that opportunities to screen risk groups are missed. Recommendations clarifying the services responsible at each step of the referral pathway are needed in order to increase the success of screening programmes. [ABSTRACT FROM AUTHOR]

The article discusses research which examined link between tumor necrosis factor ligand superfamily member 4 gene (TNFSF4) rs844648 polymorphism and systemic sclerosis (SS)-related calcinosis. Topics explored include the prevalence of calcinosis in patients with SS, the observed increase in OX40L serum levels in early-onset SS patients, and brief details about the genotyping and meta-analysis of data performed.

Background: The Seven Countries Study in the 1960s showed very low mortality from coronary heart disease (CHD) in Japan, which was attributed to very low levels of total cholesterol. Studies of migrant Japanese to the USA in the 1970s documented increase in CHD rates, thus CHD mortality in Japan was expected to increase as their lifestyle became Westernized, yet CHD mortality has continued to decline since 1970. This study describes trends in CHD mortality and its risk factors since 1980 in Japan, contrasting those in other selected developed countries.Methods: We selected Australia, Canada, France, Japan, Spain, Sweden, the UK and the USA. CHD mortality between 1980 and 2007 was obtained from WHO Statistical Information System. National data on traditional risk factors during the same period were obtained from literature and national surveys.Results: Age-adjusted CHD mortality continuously declined between 1980 and 2007 in all these countries. The decline was accompanied by a constant fall in total cholesterol except Japan where total cholesterol continuously rose. In the birth cohort of individuals currently aged 50-69 years, levels of total cholesterol have been higher in Japan than in the USA, yet CHD mortality in Japan remained the lowest: >67% lower in men and > 75% lower in women compared with the USA. The direction and magnitude of changes in other risk factors were generally similar between Japan and the other countries.Conclusions: Decline in CHD mortality despite a continuous rise in total cholesterol is unique. The observation may suggest some protective factors unique to Japanese. [ABSTRACT FROM AUTHOR]