An experience- and preference-based EQ-5D-3L value set derived using 18 months of longitudinal data in patients who sustained a fracture: results from the ICUROS.

INTRODUCTION: EQ-5D-3L preference-based value sets are predominately based on hypothetical health states and derived in cross-sectional settings. Therefore, we derived an experience-based value set from a prospective observational study. METHODS: The International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) was a multinational study on fragility fractures, prospectively collecting EQ-5D-3L and Time trade-off (TTO) within two weeks after fracture (including pre-fracture recall), and at 4, 12, and 18 months thereafter. We derived an EQ-5D-3L value set by regressing the TTO values on the ten impairment levels in the EQ-5D-3L. We explored the potential for response shift and whether preferences for domains vary systematically with prior impairment in that domain. Finally, we compared the value set to 25 other EQ-5D-3L preference-based value sets. RESULTS: TTO data were available for 12,954 EQ-5D-3L health states in 4683 patients. All coefficients in the value set had the expected sign, were statistically significant, and increased monotonically with severity of impairment. We found evidence for response shift in mobility, self-care, and usual activities. The value set had good agreement with the only other experience- and preference-based value set, but poor agreement with all hypothetical value sets. CONCLUSIONS: We present an experience- and preference-based value set with high face validity. The study indicates that response shift may be important to account for when deriving value sets. Furthermore, the study suggests that perspective (experienced versus hypothetical) is more important than country setting or demographics for valuation of EQ-5D-3L health states.

Effectiveness and feasibility of cardiovascular disease personalized prevention on high polygenic risk score subjects: a randomized controlled pilot study.

Aims: The aim of this study was to evaluate the effect of the intervention by proactively sharing a patient's high polygenic risk score (PRS) for coronary artery disease (CAD). Outcomes included: (i) reduction in cardiovascular disease (CVD) risk factors over 12 months; (ii) difference in purchased prescriptions of lipid-lowering and anti-hypertensive drugs between intervention group and control group subjects; and (iii) opinion of the participating physicians and subjects on PRS usefulness. Methods and results: This randomized controlled trial was conducted among middle-aged subjects with a top 20% CAD PRS in a family medicine setting. Participants were selected from 26 953 Estonian Biobank cohort participants. Subjects were informed and counselled about their PRS score and CAD risk using the visual tool at baseline (Visit I), counselling session (Visit II), and on the final Visit III at 12 months. The primary endpoint was not significantly different. However, the intervention group participants had a significantly higher probability of initiating statin treatment compared with the controls. Their levels of LDL-cholesterol (LDL-C) were significantly decreased compared with baseline on Visit III and significantly lower than in the control group. The vast majority of participating family physicians believe that finding out about genetic risks will affect the subject's lifestyle and medication compliance. Conclusion: Most of our outcome measures were in favour of this intervention. Participants achieved larger changes in cholesterol and blood pressure values. The vast majority (98.4%) of family physicians are interested in continuing to use genetic risk assessment in practice.

Physical-mental health comorbidity: A population-based cross-sectional study.

BACKGROUND: Multimorbidity is associated with physical-mental health comorbidity (PMHC). However, the scope of overlap between physical and mental conditions, associated factors, as well as types of mental illness involved are not well described in Eastern Europe. This study aims to assess the PMHC burden in the Estonian population. METHODS: In this population-based cross-sectional study we obtained health claims data for 55 chronic conditions from the Estonian Health Insurance Fund (EHIF) database, which captures data for all publicly insured individuals (n = 1 240 927 or 94.1% of the total population as of 31 December 2017). We assessed the period-prevalence (3 years) of chronic physical and mental health disorders, as well as associations between them, by age and sex. RESULTS: Half of the individuals (49.1% (95% CI 49.0-49.3)) had one or more chronic conditions. Mental health disorders (MHD) were present in 8.1% (8.1-8.2) of individuals, being higher among older age groups, women, and individuals with a higher number of physical conditions. PMHC was present in 6.2% (6.1-6.2) of the study population, and 13.1% (13.0-13.2) of the subjects with any chronic physical disorder also presented with at least one MHD. Dominating MHDs among PMHC patients were anxiety and depression. The prevalence of MHD was positively correlated with the number of physical disorders. We observed variation in the type of MHD as the number of physical comorbidities increased. The prevalence of anxiety, depression, and mental and behavioral disorders due to the misuse of alcohol and other psychoactive substances increased as physical comorbidities increased, but the prevalence of schizophrenia and dementia decreased with each additional physical disease. After adjusting for age and sex, this negative association changed the sign to a positive association in the case of dementia and mental and behavioral disorders due to psychoactive substance misuse. CONCLUSIONS: The burden of physical-mental comorbidity in the Estonian population is relatively high. Further research is required to identify clusters of overlapping physical and mental disorders as well as the interactions between these conditions. Public health interventions may include structural changes to health care delivery, such as an increased emphasis on integrated care models that reduce barriers to mental health care.

Prevalence of chronic conditions and multimorbidity in Estonia: a population-based cross-sectional study.

OBJECTIVES: Prevalence estimates for specific chronic conditions and multimorbidity (MM) in eastern Europe are scarce. This national study estimates the prevalence of MM by age group and sex in Estonia. DESIGN: A population-based cross-sectional study, using administrative data. SETTING: Data were collected on 55 chronic conditions from the Estonian Health Insurance Fund from 2015 to 2017. MM was defined as the coexistence of two or more conditions. PARTICIPANTS: The Estonian Health Insurance Fund includes data for approximately 95% of the Estonian population receiving public health insurance. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence and 95% CIs for MM stratified by age group and sex. RESULTS: Nearly half (49.1%) of the individuals (95% CI 49.0 to 49.3) had at least 1 chronic condition, and 30.1% (95% CI 30.0 to 30.2) had MM (2 or more chronic conditions). The number of conditions and the prevalence of MM increased with age, ranging from an MM prevalence of 3.5% (3.5%-3.6%) in the youngest (0-24 years) to as high as 80.4% (79.4%-81.3%) in the oldest (≥85 years) age group. Half of all individuals had MM by 60 years of age, and 75% of the population had MM by 75 years of age. Women had a higher prevalence of MM (34.9%, 95% CI 34.7 to 35.0) than men (24.4%, 95% CI 24.3 to 24.5). Hypertension was the most frequent chronic condition (24.5%), followed by chronic pain (12.4%) and arthritis (7.7%). CONCLUSIONS: Hypertension is an important chronic condition amenable to treatment with lifestyle and therapeutic interventions. Given the established correlation between uncontrolled hypertension and exacerbation of other cardiovascular conditions as well as acute illnesses, this most common condition within the context of MM may be suitable for targeted public health interventions.

COVID-19 Vaccines Safety Tracking (CoVaST): Protocol of a Multi-Center Prospective Cohort Study for Active Surveillance of COVID-19 Vaccines' Side Effects.

BACKGROUND: Coronavirus disease (COVID-19) vaccine-related side effects have a determinant role in the public decision regarding vaccination. Therefore, this study has been designed to actively monitor the safety and effectiveness of COVID-19 vaccines globally. METHODS: A multi-country, three-phase study including a cross-sectional survey to test for the short-term side effects of COVID-19 vaccines among target population groups. In the second phase, we will monitor the booster doses' side effects, while in the third phase, the long-term safety and effectiveness will be investigated. A validated, self-administered questionnaire will be used to collect data from the target population; Results: The study protocol has been registered at ClinicalTrials.gov, with the identifier NCT04834869. CONCLUSIONS: CoVaST is the first independent study aiming to monitor the side effects of COVID-19 vaccines following booster doses, and the long-term safety and effectiveness of said vaccines.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

The global burden of falls: global, regional and national estimates of morbidity and mortality from the Global Burden of Disease Study 2017.

BACKGROUND: Falls can lead to severe health loss including death. Past research has shown that falls are an important cause of death and disability worldwide. The Global Burden of Disease Study 2017 (GBD 2017) provides a comprehensive assessment of morbidity and mortality from falls. METHODS: Estimates for mortality, years of life lost (YLLs), incidence, prevalence, years lived with disability (YLDs) and disability-adjusted life years (DALYs) were produced for 195 countries and territories from 1990 to 2017 for all ages using the GBD 2017 framework. Distributions of the bodily injury (eg, hip fracture) were estimated using hospital records. RESULTS: Globally, the age-standardised incidence of falls was 2238 (1990-2532) per 100 000 in 2017, representing a decline of 3.7% (7.4 to 0.3) from 1990 to 2017. Age-standardised prevalence was 5186 (4622-5849) per 100 000 in 2017, representing a decline of 6.5% (7.6 to 5.4) from 1990 to 2017. Age-standardised mortality rate was 9.2 (8.5-9.8) per 100 000 which equated to 695 771 (644 927-741 720) deaths in 2017. Globally, falls resulted in 16 688 088 (15 101 897-17 636 830) YLLs, 19 252 699 (13 725 429-26 140 433) YLDs and 35 940 787 (30 185 695-42 903 289) DALYs across all ages. The most common injury sustained by fall victims is fracture of patella, tibia or fibula, or ankle. Globally, age-specific YLD rates increased with age. CONCLUSIONS: This study shows that the burden of falls is substantial. Investing in further research, fall prevention strategies and access to care is critical.

Quality of life after hip, vertebral, and distal forearm fragility fractures measured using the EQ-5D-3L, EQ-VAS, and time-trade-off: results from the ICUROS.

INTRODUCTION: The International Costs and Utilities Related to Osteoporotic fractures Study is a multinational observational study set up to describe the costs and quality of life (QoL) consequences of fragility fracture. This paper aims to estimate and compare QoL after hip, vertebral, and distal forearm fracture using time-trade-off (TTO), the EuroQol (EQ) Visual Analogue Scale (EQ-VAS), and the EQ-5D-3L valued using the hypothetical UK value set. METHODS: Data were collected at four time-points for five QoL point estimates: within 2 weeks after fracture (including pre-fracture recall), and at 4, 12, and 18 months after fracture. Health state utility values (HSUVs) were derived for each fracture type and time-point using the three approaches (TTO, EQ-VAS, EQ-5D-3L). HSUV were used to estimate accumulated QoL loss and QoL multipliers. RESULTS: In total, 1410 patients (505 with hip, 316 with vertebral, and 589 with distal forearm fracture) were eligible for analysis. Across all time-points for the three fracture types, TTO provided the highest HSUVs, whereas EQ-5D-3L consistently provided the lowest HSUVs directly after fracture. Except for 13-18 months after distal forearm fracture, EQ-5D-3L generated lower QoL multipliers than the other two methods, whereas no equally clear pattern was observed between EQ-VAS and TTO. On average, the most marked differences between the three approaches were observed immediately after the fracture. CONCLUSIONS: The approach to derive QoL markedly influences the estimated QoL impact of fracture. Therefore the choice of approach may be important for the outcome and interpretation of cost-effectiveness analysis of fracture prevention.

The impact of comorbidities on hip fracture mortality: a retrospective population-based cohort study.

The impact of comorbidities on hip fracture-related excess mortality was assessed in a population-based age- and sex-matched cohort over 10 years. On average, only 1 out of 12 excess deaths over 10 years was related to pre-fracture life-threatening comorbidities. The presence of life-threatening comorbidities increased the excess risk of death after hip fracture. PURPOSE: This work aimed to estimate the impact of pre-fracture comorbidities on the 10-year excess risk of all-cause death after hip fracture among Estonian men and women ≥ 50 years of age. METHODS: Retrospective, population-based 10-year study of people aged ≥ 50 in two cohorts: those with a hip fracture and an age- and sex-matched random sample from the national health insurance fund for comparison. RESULTS: We found that hip fracture was a strong independent risk factor for death. Upon adjustment for Charlson Comorbidities Index (CCI) score, the impact of life-threatening comorbidities on average hip fracture-related excess mortality was modest: only 8% of excess deaths over 10 years were related to comorbidities. Upon stratification by CCI groups, the excess risk of patients in CCI groups ≥ 3 and 1-2 exceeded that in the CCI 0 group over 5-7 years, indicating that in patients with life-threatening comorbidities, a hip fracture accelerates the chain of lethal events and brings deaths from other conditions forward. The impact of comorbidities was age- and time-dependent: in younger hip fracture patients, the comorbidities almost doubled the excess risk from a fracture in 10 years; in older patients, the effect was shorter and modest. CONCLUSIONS: The presence of pre-fracture comorbidities increases the risk of excess death in hip fracture patients, but the comorbidity impact on aggregated excess mortality is modest.

The impact of hip fracture on mortality in Estonia: a retrospective population-based cohort study.

BACKGROUND: Estimates of hip fracture mortality in Eastern Europe are scarce. We aimed to estimate the magnitude and duration of excess mortality after hip fracture in Estonia. METHODS: Retrospective, population-based 10-year study of persons aged ≥50 in two cohorts: with hip fracture and an age- and sex-matched (in a 1:4 ratio) random sample from the national health insurance fund database for comparison. Cumulative risks, excess risks and relative risks of death were estimated using Poisson regression with 95% bootstrap confidence intervals (CI). Risks were adjusted for age and Charlson comorbidity index. RESULTS: We identified 8298 (2383 men, 5915 women) incident hip fracture patients from 2005 to 2013 and 33,191 (9531 men, 23,660 women) individuals for the reference group. 5552 (1564 men, 3988 women) cases and 14,037 (3514 men, 10,523 women) reference individuals died during the 10-year follow-up period. Among hip fracture patients we observed a pronounced and durable excess risk of death that was highest within 3-6 months after fracture and persisted for the full 10-year follow-up period. After adjustment for age and Charlson index, hip fracture was associated with a 21.1% (95% CI 20.0-22.5%) 10-year cumulative excess risk of death (RR 1.37, 95% CI 1.35-1.40). We found a high immediate excess risk of death in older age groups (≥80 years) and gradually accumulating excess risk in younger age groups (50-79 years). The excess risk was more pronounced among men than women. CONCLUSIONS: By the end of the 10-year follow-up, 1 in 4 deaths in the hip fracture group was attributable to the hip fracture. The results indicate a high attributable impact of hip fracture as an independent risk factor for death.

The epidemiological and economic impact of a quadrivalent human papillomavirus (hpv) vaccine in Estonia.

BACKGROUND: This analysis assessed the epidemiological and economic impact of quadrivalent human papillomavirus (HPV4: 6/11/16/18) vaccination in Estonia. METHODS: A dynamic transmission model was used to assess the epidemiological and economic impact of the routine vaccination of 12-year-old girls with a HPV4 vaccine in preventing cervical cancer, cervical intraepithelial neoplasia (CIN) grades 1, 2 and 3 and genital warts. RESULTS: The model projected that at year 100, HPV4 vaccination would lead to a reduction of HPV 16/18 related cervical cancer incidence and deaths by over 97% and the incidence of HPV 6/11 related genital warts among Estonian women and men by over 94% and 81%, respectively. The incremental cost-effectiveness ratio of the HPV4 vaccination strategy was € 4,889 per QALY gained over a time horizon of 100 years. CONCLUSIONS: Routine vaccination of 12-year-old girls with HPV4 vaccine appears to be cost-effective in Estonia, in addition to providing both short term and long term health gains.

Incidence of cervical intraepithelial neoplasia in Estonia.

OBJECTIVE: This study aimed to assess the incidence of cervical intraepithelial neoplasia (CIN) by grade (CIN 1, CIN 2, CIN 3) and age in Estonia (a country with less developed cervical cancer screening program and high cervical cancer incidence). MATERIALS AND METHODS: This descriptive study uses data from a health insurance fund covering the whole country to estimate the incidence of CIN by grade. CIN case definition was based on specific diagnostic procedures (biopsy, pathological diagnosis, and colposcopy) and/or treatment procedures (excision, local destructive therapy, conization, and hysterectomy) with the CIN-specific diagnosis code (International Statistical Classification of Diseases, 10 Revision) reported on health care claims. Age-specific incidence rates were calculated together with the 95% CIs. Main outcome measure includes CIN grade-specific incidence rate per 1,000 women. RESULTS: The estimates for CIN incidence per 1,000 women range from 0.68 to 2.83 for CIN 1, 0.63 to 1.24 for CIN 2, and 0.13 to 0.53 for CIN 3 for narrow (biopsy/pathological diagnosis based) and broad (any CIN-specific diagnostic procedure/treatment based) case definition criteria, respectively. CONCLUSIONS: Our estimates for cervical dysplasia disease frequency and age distribution are in line with those from other developed countries. Administrative health care resources (such as health insurance fund data) are a valuable source for health research.