Publications by authors named "Tiina Laatikainen"

296 Publications

Effect of a multi-domain lifestyle intervention on cardiovascular risk in older people: the FINGER trial.

Eur Heart J 2022 Jan 20. Epub 2022 Jan 20.

Department of Public Health and Welfare, Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.

Aims: Joint prevention of cardiovascular disease (CVD) and dementia could reduce the burden of both conditions. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) demonstrated a beneficial effect on cognition (primary outcome) and we assessed the effect of this lifestyle intervention on incident CVD (pre-specified secondary outcome).

Methods And Results: FINGER enrolled 1259 individuals aged 60-77 years (ClinicalTrials.gov NCT01041989). They were randomized (1:1) to a 2-year multi-domain intervention with diet, physical and cognitive activity, and vascular monitoring (n = 631), or general health advice (n = 628). National registries provided data on CVD including stroke, transient ischaemic attack (TIA), or coronary heart event. During an average of 7.4 years, 229 participants (18%) had at least one CVD diagnosis: 107 in the intervention group and 122 in the control group. The incidence of cerebrovascular events was lower in the intervention than the control group: hazard ratio (HR) for combined stroke/TIA was 0.71 [95% confidence interval (CI): 0.51-0.99] after adjusting for background characteristics. Hazard ratio for coronary events was 0.84 (CI: 0.56-1.26) and total CVD events 0.80 (95% CI: 0.61-1.04). Among those with history of CVD (n = 145), the incidence of both total CVD events (HR: 0.50, 95% CI: 0.28-0.90) and stroke/TIA (HR: 0.40, 95% CI: 0.20-0.81) was lower in the intervention than the control group.

Conclusion: A 2-year multi-domain lifestyle intervention among older adults was effective in preventing cerebrovascular events and also total CVD events among those who had history of CVD.

Key Question: Can a 2-year multi-domain lifestyle intervention, primarily designed for prevention of cognitive impairment, prevent new cardiovascular events among older adults over an extended follow-up?

Key Finding: Among the 1259 participants aged 60-77 years, the intervention resulted in 13-20% lower cardiovascular disease (CVD) event rates (unadjusted and adjusted analyses), but with large degree of uncertainty. Cerebrovascular event rates were lower but for total CVD only among those with earlier CVD events.

Take-home Message: A 2-year multi-domain lifestyle intervention among older adults was effective in preventing cerebrovascular events and also total CVD events among those with a history of CVD.
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http://dx.doi.org/10.1093/eurheartj/ehab922DOI Listing
January 2022

Early childhood family background predicts meal frequency behaviour in children: Five-year follow-up study.

Scand J Public Health 2021 Dec 14:14034948211058544. Epub 2021 Dec 14.

Finnish Institute for Health and Welfare, Department of Welfare, Finland.

Aims: Childhood nutrition patterns have an important role in later health. We studied the role of family type, other family background factors and their changes over a five-year follow-up with respect to meal frequency among children.

Methods: Longitudinal data were collected in 2007-2009 and 2013-2014. A nationally representative sample of Finnish children ( = 1822) aged 0.5-5 years at baseline and 5-10 years at follow-up and their families were used. The participation rate was 83% at baseline and 54% at follow-up. Meal frequency was defined as four to six meals per day. The associations of meal frequency with family background factors over a five-year follow-up period were examined by bivariate and multivariate regression analyses.

Results: Eighty-nine per cent of the 5-10-year-old boys and girls had the recommended meal frequency at follow-up. Living in a single-parent family at baseline increased the risk of not eating the recommended number of meals compared with those living in intact families. After adjustments, a mother's low level of education (OR 0.51, CI 0.29-0.93) and a decrease in income sufficiency (OR 0.54, CI 0.35-0.84) during the follow-up period were unfavourably associated with the recommended meal frequency. The difference between children in stable single-parent, reconstituted or joint physical custody families and those living in stable intact families remained significant when controlling for other variables.

Conclusions: .
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http://dx.doi.org/10.1177/14034948211058544DOI Listing
December 2021

Long-term trends in blood pressure and hypertension in Russia: an analysis of data from 14 health surveys conducted in 1975-2017.

BMC Public Health 2021 Dec 7;21(1):2226. Epub 2021 Dec 7.

National Research University Higher School of Economics, Bolshoy Trekhsvyatitelskiy pereulok 3, Moscow, Russian Federation, 109038.

Background: Hypertension is recognized as an important contributor to high cardiovascular mortality in Russia. A comprehensive analysis of data from Russian studies that measured blood pressure in population-based samples has not been previously undertaken. This study aims to identify trends and patterns in mean blood pressure and the prevalence of hypertension in Russia over the most recent 40 years.

Methods: We obtained anonymized individual records of blood pressure measurements from 14 surveys conducted in Russia in 1975-2017 relating to a total of 137,687 individuals. For comparative purposes we obtained equivalent data from 4 surveys in the USA and England for 23,864 individuals. A meta-regression on aggregated data adjusted for education was undertaken to estimate time trends in mean systolic and diastolic blood pressure, the prevalence of elevated blood pressure (> 140/90 mmHg), and hypertension (defined as elevated blood pressure and/or the use of blood pressure-lowering) medication. A meta-analysis of pooled individual-level data was used to assess male-female differences in blood pressure and hypertension.

Results: During the period 1975-2017 mean blood pressure, the prevalence of elevated blood pressure and hypertension remained stable among Russian men. Among Russian women, mean systolic blood pressure decreased at an annual rate of 0.25 mmHg (p < 0.1) at age 35-54 years and by 0.8 mmHg (p < 0.01) at ages 55 and over. The prevalence of elevated blood pressure also decreased by 0.8% per year (p < 0.01), but the prevalence of hypertension remained stable. Mean blood pressure and prevalence of hypertension were higher in Russia compared to the USA and England at all ages and for both sexes.

Conclusions: In contrast to the generally observed downward trend in elevated blood pressure in many other countries, levels in Russia have changed little over the past 40 years, although there are some positive trends among women. Improved strategies to bring down the high levels of mean blood pressure and hypertension in Russia compared to countries such as England and the USA are important to further reduce the high burden of CVD in Russia.
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http://dx.doi.org/10.1186/s12889-021-12320-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653591PMC
December 2021

Patient-specific and healthcare real-world costs of atrial fibrillation in individuals treated with direct oral anticoagulant agents or warfarin.

BMC Health Serv Res 2021 Dec 3;21(1):1299. Epub 2021 Dec 3.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland.

Background: Anticoagulant therapies are used to prevent atrial fibrillation-related strokes, with warfarin and direct oral anticoagulant (DOAC) the most common. In this study, we incorporate direct health care costs, drug costs, travel costs, and lost working and leisure time costs to estimate the total costs of the two therapies.

Methods: This retrospective study used individual-level patient data from 4000 atrial fibrillation (AF) patients from North Karelia, Finland. Real-world data on healthcare use was obtained from the regional patient information system and data on reimbursed travel costs from the database of the Social Insurance Institution of Finland. The costs of the therapies were estimated between June 2017 and May 2018. Using a Geographical Information System (GIS), we estimated travel time and costs for each journey related to anticoagulant therapies. We ultimately applied therapy and travel costs to a cost model to reflect real-world expenditures.

Results: The costs of anticoagulant therapies were calculated from the standpoint of patient and the healthcare service when considering all costs from AF-related healthcare visits, including major complications arising from atrial fibrillation. On average, the annual cost per patient for healthcare in the form of public expenditure was higher when using DOAC therapy than warfarin therapy (average cost = € 927 vs. € 805). Additionally, the average annual cost for patients was also higher with DOAC therapy (average cost = € 406.5 vs. € 296.7). In warfarin therapy, patients had considerable more travel and time costs due the different implementation practices of therapies.

Conclusion: The results indicated that DOAC therapy had higher costs over warfarin from the perspectives of the patient and healthcare service in the study area on average. Currently, the cost of the DOAC drug is the largest determinator of total therapy costs from both perspectives. Despite slightly higher costs, the patients on DOAC therapy experienced less AF-related complications during the study period.
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http://dx.doi.org/10.1186/s12913-021-07125-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641166PMC
December 2021

LDL-cholesterol trajectories and statin treatment in Finnish type 2 diabetes patients: a growth mixture model.

Sci Rep 2021 11 19;11(1):22603. Epub 2021 Nov 19.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Yliopistonranta 1, 70210, Kuopio, Finland.

We aimed to identify distinct longitudinal trends of LDL-cholesterol (LDL-C) levels and investigate these trajectories' association with statin treatment. This retrospective cohort study used electronic health records from 8592 type 2 diabetes patients in North Karelia, Finland, comprising all primary and specialised care visits 2011‒2017. We compared LDL-C trajectory groups assessing LDL-C treatment target achievement and changes in statin treatment intensity. Using a growth mixture model, we identified four LDL-C trajectory groups. The majority (85.9%) had "moderate-stable" LDL-C levels around 2.3 mmol/L. The second-largest group (7.7%) consisted of predominantly untreated patients with alarmingly "high-stable" LDL-C levels around 3.9 mmol/L. The "decreasing" group (3.8%) was characterised by large improvements in initially very high LDL-C levels, along with the highest statin treatment intensification rates, while among patients with "increasing" LDL-C (2.5%), statin treatment declined drastically. In all the trajectory groups, women had significantly higher average LDL-C levels and received less frequent any statin treatment and high-intensity treatment than men. Overall, 41.9% of patients had no statin prescribed at the end of follow-up. Efforts to control LDL-C should be increased-especially in patients with continuously elevated levels-by initiating and intensifying statin treatment earlier and re-initiating the treatment after discontinuation if possible.
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http://dx.doi.org/10.1038/s41598-021-02077-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604948PMC
November 2021

Type 2 Diabetes-Related Health Economic Impact Associated with Increased Whole Grains Consumption among Adults in Finland.

Nutrients 2021 Oct 13;13(10). Epub 2021 Oct 13.

Department of Public Health and Welfare, Finnish Institute for Health and Welfare, 00271 Helsinki, Finland.

The prevalence of type 2 diabetes (T2D) is increasing rapidly worldwide. A healthy diet supporting the control of energy intake and body weight has major importance in the prevention of T2D. For example, a high intake of whole grain foods (WGF) has been shown to be inversely associated with risk for T2D. The objective of the study was to estimate the expected health economic impacts of increased WGF consumption to decrease the incidence of T2D in the Finnish adult population. A health economic model utilizing data from multiple national databases and published scientific literature was constructed to estimate these population-level health economic consequences. Among the adult Finnish population, increased WGF consumption could reduce T2D-related costs between 286€ and 989€ million during the next 10-year time horizon depending on the applied scenario (i.e., a 10%-unit increase in a proportion of daily WGF users, an increased number (i.e., two or more) of WGF servings a day, or alternatively a combination of these scenarios). Over the next 20-30 years, a population-wide increase in WGF consumption could lead to much higher benefits. Furthermore, depending on the applied scenario, between 1323 and 154,094 quality-adjusted life years (QALYs) could be gained at the population level due to decreased T2D-related morbidity and mortality during the next 10 to 30 years. The results indicate that even when the current level of daily WGF consumption is already at a relatively high-level in a global context, increased WGF consumption could lead to important health gains and savings in the Finnish adult population.
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http://dx.doi.org/10.3390/nu13103583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541656PMC
October 2021

The effect of adherence on cognition in a multidomain lifestyle intervention (FINGER).

Alzheimers Dement 2021 Oct 20. Epub 2021 Oct 20.

Department of Public Health and Welfare, Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.

Introduction: Lifestyle interventions may prevent cognitive decline, but the sufficient dose of intervention activities and lifestyle changes is unknown. We investigated how intervention adherence affects cognition in the FINGER trial (pre-specified subgroup analyses).

Methods: FINGER is a multicenter randomized controlled trial examining the efficacy of multidomain lifestyle intervention (ClinicalTrials.gov NCT01041989). A total of 1260 participants aged 60 to 77 with increased dementia risk were randomized to a lifestyle intervention and control groups. Percentage of completed intervention sessions, and change in multidomain lifestyle score (self-reported diet; physical, cognitive, and social activity; vascular risk) were examined in relation to change in Neuropsychological Test Battery (NTB) scores.

Results: Active participation was associated with better trajectories in NTB total and all cognitive subdomains. Improvement in lifestyle was associated with improvement in NTB total and executive function.

Discussion: Multidomain lifestyle changes are beneficial for cognitive functioning, but future interventions should be intensive enough, and supporting adherence is essential.
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http://dx.doi.org/10.1002/alz.12492DOI Listing
October 2021

The association of body mass index with quality of life and working ability: a Finnish population-based study.

Qual Life Res 2021 Sep 17. Epub 2021 Sep 17.

Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Purpose: The impact of obesity on quality of life (QoL) and working ability vary in different dimensions. This study investigated the association of obesity with QoL and working ability in Finnish adults. Comorbidities as associative factors were also characterised.

Methods: This cross-sectional study included 4956 randomly selected adults. QoL (EUROHIS-QOL 8 total score and individual components), perceived physical and psychological working ability, and sick leave days were analysed in different body mass index (BMI) groups. Regression models were used to study the role of comorbidities as associative factors.

Results: EUROHIS-QOL 8 total score was significantly lower in BMI group 25.0-29.9 kg/m (4.01; 95% confidence interval 3.97-4.05), BMI 30.0-34.9 kg/m (3.85; 3.79-3.91), BMI 35.0-39.9 kg/m (3.75; 3.66-3.85), and BMI ≥ 40.0 kg/m (3.73; 3.46-4.00) compared to individuals with normal (18.5-24.9 kg/m) BMI (4.08; 4.04-4.12). Individuals with obesity (BMI ≥ 30.0 kg/m) rated their QoL lower than individuals with normal BMI in seven of the eight EUROHIS-QOL 8 components. A lesser proportion of individuals (53-73%) with obesity rated their physical working ability as very or fairly good compared to individuals with normal BMI (90%, p values < 0.001). The psychological working ability was rated as very or fairly good by 71-75% of individuals with obesity compared to 85% of individuals with normal BMI (p = 0.008 and p = 0.001 in individuals with BMI 30.0-34.9 and BMI 35.0-39.9 kg/m, respectively).

Conclusions: Obesity was negatively associated with both physical and psychological components of QoL, even after accounting for obesity-related comorbidities. Obesity treatment can benefit from a holistic approach that considers these multifaceted associations.
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http://dx.doi.org/10.1007/s11136-021-02993-0DOI Listing
September 2021

Pharmacy-based screening to detect persons at elevated risk of type 2 diabetes: a cost-utility analysis.

BMC Health Serv Res 2021 Sep 5;21(1):916. Epub 2021 Sep 5.

Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland.

Background: Early identification of people at elevated risk of type 2 diabetes (T2D) is an important step in preventing or delaying its onset. Pharmacies can serve as a significant channel to reach these people. This study aimed to assess the potential health economic impact of screening and recruitment services in pharmacies in referring people to preventive interventions.

Methods: A decision analytic model was constructed to perform a cost-utility analysis of the expected national health economic consequences (in terms of costs and quality-adjusted life years, QALYs) of a hypothetical pharmacy-based service where people screened and recruited through pharmacies would participate in a digital lifestyle program. Cost-effectiveness was considered in terms of net monetary benefit (NMB). In addition, social return on investment (SROI) was calculated as the ratio of the intervention and recruitment costs and the net present value of expected savings. Payback time was the time taken to reach the break-even point in savings. In the base scenario, a 20-year time horizon was applied. Probabilistic and deterministic sensitivity analyses were applied to study robustness of the results.

Results: In the base scenario, the expected savings from the pharmacy-based screening and recruitment among the reached target cohort were 255.3 m€ (95% CI - 185.2 m€ to 717.2 m€) in pharmacy visiting population meaning 1412€ (95% CI - 1024€ to 3967€) expected savings per person. Additionally, 7032 QALYs (95% CI - 1344 to 16,143) were gained on the population level. The intervention had an NMB of 3358€ (95% CI - 1397€ to 8431€) using a cost-effectiveness threshold of 50,000 €/QALY. The initial costs were 122.2 m€ with an SROI of 2.09€ (95% CI - 1.52€ to 5.88€). The expected payback time was 10 and 8 years for women and men, respectively. Results were most sensitive for changes in effectiveness of the intervention and selected discount rate.

Conclusions: T2D screening and recruitment to prevention programs conducted via pharmacies was a dominant option providing both cost savings and QALY gains. The highest savings can be potentially reached by targeting recruitment at men at elevated risk of T2D.
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http://dx.doi.org/10.1186/s12913-021-06948-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418722PMC
September 2021

Facilitators and barriers to implementing lifestyle intervention programme to prevent cognitive decline.

Eur J Public Health 2021 10;31(4):816-822

Department of Public Health and Welfare, Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.

Background: The Finnish Intervention Study to Prevent Cognitive Impairment and Disability is a randomized controlled trial that has tested the efficacy of a multidomain intervention targeting modifiable risk factors to prevent cognitive impairment/dementia. A combination of healthy diet, physical, social and cognitive activity, and management of cardiovascular risks was shown to be an effective model to promote brain health among older people. The aim of this qualitative study was to explore healthcare professionals' perceptions of facilitators and barriers to implementing this lifestyle programme into health care.

Methods: Four semi-structured focus group interviews were conducted among healthcare professionals working in primary care and in non-governmental organizations (N=27). Participants were asked to discuss their perceptions of facilitators and barriers for implementing the multidomain intervention into clinical practice. Interviews were analyzed using content analysis.

Results: Barriers and facilitators described by the healthcare professionals were related to infrastructure and resources, client's personal characteristics and the lifestyle intervention itself. These main categories included several sub-categories related to knowledge, motivation, resources, individualization and collaboration. The interviewees pointed out that more education on dementia prevention is needed, the work should be coordinated efficiently, resources to provide preventive health care should be adequate and multiprofessional collaboration is needed.

Conclusions: Transferring a lifestyle intervention from a trial-setting to real life requires knowledge about the factors that influence effective implementation. Identifying drivers and constraints of successful implementation helps to design and tailor future prevention programmes, increases motivation and adherence and supports system change.
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http://dx.doi.org/10.1093/eurpub/ckab087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505000PMC
October 2021

Effect of a Multidomain Lifestyle Intervention on Estimated Dementia Risk.

J Alzheimers Dis 2021 ;82(4):1461-1466

Karolinska Institutet, NVS, Division of Clinical Geriatrics, Solna, Stockholm, Sweden.

We investigated the effect of a multidomain lifestyle intervention on the risk of dementia estimated using the validated CAIDE risk score (post-hoc analysis). The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a 2-year randomized controlled trial among 1,260 at-risk older adults (60-77 years). Difference in the estimated mean change in CAIDE score at 2 years in the intervention compared to the control group was -0.16 (95 %CI -0.31 to 0.00) (p = 0.013), corresponding to a relative dementia risk reduction between 6.04-6.50%. This could be interpreted as a reflection of the prevention potential of the intervention.
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http://dx.doi.org/10.3233/JAD-210331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461663PMC
November 2021

Evaluation and pilot implementation of essential interventions for the management of hypertension and prevention of cardiovascular diseases in primary health care in the Republic of Tajikistan.

BMC Health Serv Res 2021 May 18;21(1):472. Epub 2021 May 18.

World Health Organization Regional Office for Europe, Copenhagen, Denmark.

Background: The aim of this study was to determine the feasibility of implementing and evaluating essential interventions for the management of hypertension and prevention of cardiovascular disease in primary healthcare in Tajikistan.

Methods: The study protocol was published a priori. A pragmatic, sequential, mixed methods explanatory design was piloted. The quantitative strand is reported here. All primary health care facilities that met inclusion criteria in Shahrinav district were included and computer randomized to either usual care or intervention. The intervention consisted of: adaptation of WHO PEN/HEARTS clinical algorithms for hypertension and diabetes, a two-day training of doctors and nurses, supportive supervision visits, clinical decision support tools, and quality improvement support. Data were collected from paper-based clinical records at baseline and 12 months follow-up. The primary outcome was blood pressure control among patients with hypertension, in addition to several secondary process indicators along the care pathway. Age and sex adjusted logistic regression models were used for intervention and control clinics to determine changes between baseline and follow-up and to assess interactions between allocation group and time. For continuous variables, multivariate linear regression models were used.

Results: 19 primary health care centres were included of which ten were randomized to intervention and nine to control. 120 clinicians received training. The records of all registered hypertensive patients were reviewed at baseline and follow-up for a total of 1,085 patient records. Blood pressure control significantly improved in the intervention clinics (OR 3.556, 95 % CI 2.219, 5.696) but not the control clinics (OR 0.644, 95 % CI 0.370, 1.121) (p < 0.001 for interaction). Smoking assessment, statin prescribing, triple therapy prescribing, and blood pressure measurement significantly improved in intervention clinics relative to control, whereas cholesterol and glucose testing, and aspirin prescribing did not.

Conclusions: It is feasible to use routine, paper-based, clinical records to evaluate essential CVD interventions in primary health care in Tajikistan. Adapted WHO PEN/HEARTS guidelines in the context of a complex intervention significantly improved blood pressure control after 12 months.
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http://dx.doi.org/10.1186/s12913-021-06490-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132349PMC
May 2021

Change in CAIDE Dementia Risk Score and Neuroimaging Biomarkers During a 2-Year Multidomain Lifestyle Randomized Controlled Trial: Results of a Post-Hoc Subgroup Analysis.

J Gerontol A Biol Sci Med Sci 2021 07;76(8):1407-1414

Institute of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, Finland.

The CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Risk Score is a validated tool estimating dementia risk. It was previously associated with imaging biomarkers. However, associations between dementia risk scores (including CAIDE) and dementia-related biomarkers have not been studied in the context of an intervention. This study investigated associations between change in CAIDE score and change in neuroimaging biomarkers (brain magnetic resonance imaging [MRI] and Pittsburgh Compound B-positron emission tomography [PiB-PET] measures) during the 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) (post-hoc analyses). FINGER targeted at-risk older adults, aged 60-77 years, from the general population. Participants were randomized to either multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice). Neuroimaging (MRI and PiB-PET) data from baseline and 2-year visits were used. A toal of 112 participants had repeated brain MRI measures (hippocampal, total gray matter, and white matter lesion volumes, and Alzheimer's disease signature cortical thickness). Repeated PiB-PET scans were available for 39 participants. Reduction in CAIDE score (indicating lower dementia risk) during the intervention was associated with less decline in hippocampus volume in the intervention group, but not the control group (Randomization group × CAIDE change interaction β coefficient = -0.40, p = .02). Associations for other neuroimaging measures were not significant. The intervention may have benefits on hippocampal volume in individuals who succeed in improving their overall risk level as indicated by a reduction in CAIDE score. This exploratory finding requires further testing and validation in larger studies.
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http://dx.doi.org/10.1093/gerona/glab130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277089PMC
July 2021

The Finnish Allergy Program 2008-2018: Society-wide proactive program for change of management to mitigate allergy burden.

J Allergy Clin Immunol 2021 08 5;148(2):319-326.e4. Epub 2021 May 5.

Skin and Allergy Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

A 10-year national program to improve prevention and management of allergic diseases and asthma was implemented in Finland (population 5.5. million) in 2008-2018. The main aim was to reduce the long-term burden of these conditions. The strategy was changed from traditional avoidance to tolerance and resilience of the population. Health was endorsed instead of medicalization of mild symptoms. Disease severity was reevaluated, and disabling clinical manifestations were given high priority. For health care, 5 quantitative goals and 1 qualitative goal were set. For each of the goals, specific tasks, tools, and outcome evaluation were stipulated. During the program, 376 educational sessions gathered 24,000 health care participants. An information campaign targeted the lay public, and social media was used to contact people. In the 10 years of the program, the prevalence of allergic diseases and asthma leveled off. Asthma caused fewer symptoms and less disability, and 50% fewer hospital days. Food allergy diets in day care and schools decreased by half. Occupational allergies were reduced by 45%. In 2018, the direct and indirect costs of allergic diseases and asthma ranged from €1.5 billion to €1.8 billion, with the 2018 figures being 30% less than in the respective figures in 2007. The Finnish proactive and real-world intervention markedly reduced the public health burden of allergic disorders. The allergy paradigm was revisited to improve management with systematic education.
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http://dx.doi.org/10.1016/j.jaci.2021.03.037DOI Listing
August 2021

27-Hydroxycholesterol, cognition, and brain imaging markers in the FINGER randomized controlled trial.

Alzheimers Res Ther 2021 03 6;13(1):56. Epub 2021 Mar 6.

Division of Clinical Geriatrics, Center for Alzheimer Research, NVS, Karolinska Institutet, Stockholm, Sweden.

Background: 27-Hydroxycholesterol (27-OH), the main circulating oxysterol in humans and the potential missing link between peripheral hypercholesterolemia and Alzheimer's disease (AD), has not been investigated previously in relation to cognition and neuroimaging markers in the context of preventive interventions.

Methods: The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) included older individuals (60-77 years) at increased risk for dementia but without dementia or substantial cognitive impairment from the general population. Participants were randomized to a multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice) in a 1:1 ratio. Outcome assessors were masked to group allocation. This FINGER exploratory sub-study included 47 participants with measures of 27-OH, cognition, brain MRI, brain FDG-PET, and PiB-PET. Linear regression models were used to assess the cross-sectional and longitudinal associations between 27-OH, cognition, and neuroimaging markers, considering several potential confounders/intervention effect modifiers.

Results: 27-OH reduction during the intervention was associated with improvement in cognition (especially memory). This was not observed in the control group. The intervention reduced 27-OH particularly in individuals with the highest 27-OH levels and younger age. No associations were found between changes in 27-OH levels and neuroimaging markers. However, at baseline, a higher 27-OH was associated with lower total gray matter and hippocampal volume, and lower cognitive scores. These associations were unaffected by total cholesterol levels. While sex seemed to influence associations at baseline, it did not affect longitudinal associations.

Conclusion: 27-OH appears to be a marker not only for dementia/AD risk, but also for monitoring the effects of preventive interventions on cholesterol metabolism.

Trial Registration: ClinicalTrials.gov , NCT01041989 . Registered on 4 January 2010.
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http://dx.doi.org/10.1186/s13195-021-00790-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937194PMC
March 2021

Capacity building of health care professionals to perform interprofessional management of non-communicable diseases in primary care - experiences from Ukraine.

BMC Health Serv Res 2021 Jan 27;21(1):91. Epub 2021 Jan 27.

World Health Organization Regional Office for Europe, Copenhagen, Denmark.

Background: Non-communicable diseases are leading causes of death and disability across the world. Countries with the highest non-communicable disease (NCD) burden in the WHO European Region are often those that have some of the greatest health system challenges for achieving good outcomes in prevention and care. The aim of this study was to evaluate the effect of an interprofessional capacity building intervention carried out in Ukraine to improve the management non-communicable diseases in primary health care.

Methods: A mixed-methods evaluation study was performed in 2018 to analyse the effect of a capacity building intervention carried out for over 10,000 primary care professionals in Ukraine in 2018. Quantitative data were collected from primary health care records of intervention and control areas preceding the intervention and 1.5 to 2 years after the intervention. Altogether 2798 patient records before and 2795 after the intervention were reviewed. In control areas, 1202 patient records were reviewed. Qualitative data were collected carrying out focus group interviews for health professionals, clinic managers and patients. Also, observations of clinical practice and patient pathways were performed.

Results: The capacity building intervention improved the capacity of professionals in detection and management of non-communicable disease risk factors. Significant improvement was seen in detection rates of both behavioural and biological risk factors and in medication prescription rates in the intervention areas. However, almost similar improvement in prescription rates was also observed in control clinics. Improvements in control of blood pressure, blood glucose and cholesterol were not seen during the evaluated implementation period. Qualitative analyses highlighted the improved knowledge and skills but challenges in changing the current practice.

Conclusions: A large scale capacity building intervention improved primary health care professionals' knowledge, skills and clinical practice on NCD risk detection and reduction. We were not able to detect improvements in treatment outcomes - at least within 1.5 to 2 years follow-up. Improvement of treatment outcomes would most likely need more comprehensive systems change.
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http://dx.doi.org/10.1186/s12913-021-06068-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839221PMC
January 2021

The effect of the integration of health services on health care usage among patients with type 2 diabetes in North Karelia, Finland.

BMC Health Serv Res 2021 Jan 13;21(1):65. Epub 2021 Jan 13.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, PO Box 1627, 70211, Kuopio, Finland.

Background: The need to improve the care of people with complex care requirements has been driving the reforms integrating care processes. This study examines the effect of the integration of health services on health care usage and the processes and outcomes of care among type 2 diabetes patients.

Methods: Data include all type 2 diabetes patients who lived in North Karelia, Finland, between 2014 and 2018. Health care contacts and glycated haemoglobin (HbA1c) measurements were obtained from the electronic health records. Logistic, Poisson and linear models with generalised estimating equations and the Friedman test were used to study the differences between years.

Results: The health care usage was highest in 2017, the first year of a new organisation, and smallest in the following year. Before the new organisation, the health care usage was lowest in 2014, being slightly higher compared with 2018. Between the last two years, the mean number of contacts per person declined from 3.25 to 2.88 (-0.37, p < 0.001). The decreasing pattern seen in total health care usage was most obvious among contacts with primary health care nurses. The number of contacts increased only among specialised care nurses between the last two years. The number of HbA1c measurements was also in its lowest in 2018 but in its highest in 2015. Between the years 2014 and 2018, the difference in the mean number of contacts was - 0.05 (p = 0.011) for those not measured, -0.02 (p = 0.225) for those measured and within the target level of HbA1c, and 0.12 (p = 0.001) for those measured and not at the target level of HbA1c.

Conclusions: Health care integration first increased the health care usage but then brought it to a slightly lower level than before. The changes were most obvious in primary health care nurses' appointments, and no decline was observed in secondary-level care. Even though the numbers of HbA1c measurements and the proportion measured declined, measurements increased among those with poor glycaemic control. The observed changes might reflect the better targeting and more concordant services in different service units.
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http://dx.doi.org/10.1186/s12913-021-06059-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805148PMC
January 2021

Joint effects of alcohol use, smoking and body mass index as an explanation for the alcohol harm paradox: causal mediation analysis of eight cohort studies.

Addiction 2021 08 28;116(8):2220-2230. Epub 2021 Jan 28.

Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland.

Background And Aims: Lower socio-economic status (SES) is associated with higher alcohol-related harm despite lower levels of alcohol use. Differential vulnerability due to joint effects of behavioural risk factors is one potential explanation for this 'alcohol harm paradox'. We analysed to what extent socio-economic inequalities in alcohol-mortality are mediated by alcohol, smoking and body mass index (BMI), and their joint effects with each other and with SES.

Design: Cohort study of eight health examination surveys (1978-2007) linked to mortality data.

Setting: Finland.

Participants: A total of 53 632 Finnish residents aged 25+ years.

Measurements: The primary outcome was alcohol-attributable mortality. We used income as an indicator of SES. We assessed the joint effects between income and mediators (alcohol use, smoking and BMI) and between the mediators, adjusting for socio-demographic indicators. We used causal mediation analysis to calculate the total, direct, indirect and mediated interactive effects using Aalen's additive hazards models.

Findings: During 1 085 839 person-years of follow-up, we identified 865 alcohol-attributable deaths. We found joint effects for income and alcohol use and income and smoking, resulting in 46.8 and 11.4 extra deaths due to the interaction per 10 000 person-years. No interactions were observed for income and BMI or between alcohol and other mediators. The lowest compared with the highest income quintile was associated with 5.5 additional alcohol deaths per 10 000 person-years (95% confidence interval = 3.7, 7.3) after adjusting for confounders. The proportion mediated by alcohol use was negative (-69.3%), consistent with the alcohol harm paradox. The proportion mediated by smoking and BMI and their additive interactions with income explained 18.1% of the total effect of income on alcohol-attributable mortality.

Conclusions: People of lower socio-economic status appear to be more vulnerable to the effects of alcohol use and smoking on alcohol-attributable mortality. Behavioural risk factors and their joint effects with income may explain part of the alcohol harm paradox.
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http://dx.doi.org/10.1111/add.15395DOI Listing
August 2021

Quantifying dementia prevention potential in the FINGER randomized controlled trial using the LIBRA prevention index.

Alzheimers Dement 2021 07 6;17(7):1205-1212. Epub 2021 Jan 6.

Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden.

Introduction: Individuals in early dementia prevention trials may differ in how much they benefit from interventions depending on their initial risk level. Additionally, modifiable dementia risk scores might be used as surrogate/intermediate outcomes.

Methods: In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), we investigated in post hoc analyses (N = 1207) whether the cognitive benefits of the 2-year multi-domain lifestyle intervention differed by baseline dementia risk measured with the "LIfestyle for BRAin Health" (LIBRA) score. We also investigated intervention effects on change in LIBRA score over time.

Results: Overall, higher baseline LIBRA was related to less cognitive improvement over time. This association did not differ between the intervention and control groups. The intervention was effective in decreasing LIBRA scores over time, regardless of baseline demographics or cognition.

Discussion: The cognitive benefit of the FINGER intervention was similar across individuals with different LIBRA scores at baseline. Furthermore, LIBRA may be useful as a surrogate/intermediate endpoint and surveillance tool to monitor intervention success during trial execution.
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http://dx.doi.org/10.1002/alz.12281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359273PMC
July 2021

Shared DNA methylation signatures in childhood allergy: The MeDALL study.

J Allergy Clin Immunol 2021 03 15;147(3):1031-1040. Epub 2020 Dec 15.

Centre for Individualized Infection Medicine, CiiM, a joint venture between Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema.

Objective: We sought to identify DNA methylation profiles associated with childhood allergy.

Methods: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discovery study included 219 case patients and 417 controls at age 4 years and 228 case patients and 593 controls at age 8 years from 3 birth cohorts, with replication analyses in 325 case patients and 1111 controls. We performed additional analyses on 21 replicated sites in 785 case patients and 2124 controls by allergic symptoms only from 8 cohorts, 3 of which were not previously included in analyses.

Results: We identified 80 differentially methylated CpG sites that showed a 1% to 3% methylation difference in the discovery phase, of which 21 (including 5 novel CpG sites) passed genome-wide significance after meta-analysis. All 21 CpG sites were also significantly differentially methylated with allergic symptoms and shared between asthma, rhinitis, and eczema. The 21 CpG sites mapped to relevant genes, including ACOT7, LMAN3, and CLDN23. All 21 CpG sties were differently methylated in asthma in isolated eosinophils, and 10 were replicated in respiratory epithelium.

Conclusion: Reduced whole blood DNA methylation at 21 CpG sites was significantly associated with childhood allergy. The findings provide novel insights into the shared molecular mechanisms underlying asthma, rhinitis, and eczema.
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http://dx.doi.org/10.1016/j.jaci.2020.11.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238013PMC
March 2021

Cardiovascular health metrics from mid- to late-life and risk of dementia: A population-based cohort study in Finland.

PLoS Med 2020 12 15;17(12):e1003474. Epub 2020 Dec 15.

Aging Research Center & Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Stockholm University, Stockholm, Sweden.

Background: Very few studies have explored the patterns of cardiovascular health (CVH) metrics in midlife and late life in relation to risk of dementia. We examined the associations of composite CVH metrics from midlife to late life with risk of incident dementia.

Methods And Findings: This cohort study included 1,449 participants from the Finnish Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, who were followed from midlife (baseline from1972 to 1987; mean age 50.4 years; 62.1% female) to late life (1998), and then 744 dementia-free survivors were followed further into late life (2005 to 2008). We defined and scored global CVH metrics based on 6 of the 7 components (i.e., smoking, physical activity, and body mass index [BMI] as behavioral CVH metrics; fasting plasma glucose, total cholesterol, and blood pressure as biological CVH metrics) following the modified American Heart Association (AHA)'s recommendations. Then, the composite global, behavioral, and biological CVH metrics were categorized into poor, intermediate, and ideal levels. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Data were analyzed with Cox proportional hazards and the Fine and Gray competing risk regression models. During the follow-up examinations, dementia was diagnosed in 61 persons in 1998 and additional 47 persons in 2005 to 2008. The fully adjusted hazard ratio (HR) of dementia was 0.71 (95% confidence interval [CI]: 0.43, 1.16; p = 0.174) and 0.52 (0.29, 0.93; p = 0.027) for midlife intermediate and ideal levels (versus poor level) of global CVH metrics, respectively; the corresponding figures for late-life global CVH metrics were 0.60 (0.22, 1.69; p = 0.338) and 0.91 (0.34, 2.41; p = 0.850). Compared with poor global CVH metrics in both midlife and late life, the fully adjusted HR of dementia was 0.25 (95% CI: 0.08, 0.86; p = 0.028) for people with intermediate global CVH metrics in both midlife and late life and 0.14 (0.02, 0.76; p = 0.024) for those with midlife ideal and late-life intermediate global CVH metrics. Having an intermediate or ideal level of behavioral CVH in both midlife and late life (versus poor level in both midlife and late life) was significantly associated with a lower dementia risk (HR range: 0.03 to 0.26; p < 0.05), whereas people with midlife intermediate and late-life ideal biological CVH metrics had a significantly increased risk of dementia (p = 0.031). Major limitations of this study include the lack of data on diet and midlife plasma glucose, high rate of attrition, as well as the limited power for certain subgroup analyses.

Conclusions: In this study, we observed that having the ideal CVH metrics, and ideal behavioral CVH metrics in particular, from midlife onwards is associated with a reduced risk of dementia as compared with people having poor CVH metrics. Maintaining life-long health behaviors may be crucial to reduce late-life risk of dementia.
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http://dx.doi.org/10.1371/journal.pmed.1003474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737898PMC
December 2020

Simultaneous allergic traits in dogs and their owners are associated with living environment, lifestyle and microbial exposures.

Sci Rep 2020 12 15;10(1):21954. Epub 2020 Dec 15.

Research Programs Unit, Molecular Neurology, University of Helsinki, 00014, Helsinki, Finland.

Both humans and pet dogs are more prone to develop allergies in urban than in rural environments, which has been associated with the differing microbial exposures between areas. However, potential similarities in the microbiota, that associate with environmental exposures, in allergic dogs and owners has not been investigated. We evaluated skin and gut microbiota, living environment, and lifestyle in 168 dog-owner pairs. Due to partly different manifestations of allergies between species, we focused on aeroallergen sensitized humans and dogs with owner-reported allergic symptoms. Our results agree with previous studies: dog-owner pairs suffered simultaneously from these allergic traits, higher risk associated with an urban environment, and the skin, but not gut, microbiota was partly shared by dog-owner pairs. We further discovered that urban environment homogenized both dog and human skin microbiota. Notably, certain bacterial taxa, which were associated with living environment and lifestyle, were also related with allergic traits, but these taxa differed between dogs and humans. Thus, we conclude that dogs and humans can be predisposed to allergy in response to same risk factors. However, as shared predisposing or protective bacterial taxa were not discovered, other factors than environmental microbial exposures can mediate the effect or furry dog and furless human skin select different taxa.
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http://dx.doi.org/10.1038/s41598-020-79055-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738549PMC
December 2020

Weight transitions and psychosocial factors: A longitudinal cohort study of Finnish primary school children with overweight.

Prev Med Rep 2020 Dec 5;20:101239. Epub 2020 Nov 5.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.

For targeted prevention and treatment of childhood obesity, primary health care needs methods to identify children potentially developing obesity. The objectives of this study were to examine transitions across weight categories and their association with psychosocial family- and school-related factors, data on which were retrieved from health records. This longitudinal cohort study comprised 507 Finnish children with overweight, identified from a random sample of 2000 sixth graders in Helsinki in 2013. We applied Markov multistate models to analyze the transition rates over six primary school years between BMI SDS categories of normal weight, overweight and obesity, as assessed by Finnish BMI-for-age reference, and to examine relations between transition rates and family- and school-related factors. Among 3116 pairs of consecutive growth measurements from 225 girls and 282 boys aged 6-14, 719 transitions from weight category to another occurred. The highest 1-year probabilities were 0.76 for girls to stay in overweight and 0.80 for boys to stay in obesity. Transitions from normal weight to overweight and from obesity to overweight were more probable than vice versa. Transitions from overweight into obesity were among girls associated with older age (HR 2.63) and divorced or single parents (HR 2.29), as well as among boys with experiences of crises (HR 2.40) and being bullied (HR 1.66). Factors identifiable in school health care and associated with the probability of transition towards obesity should be considered when planning individual support and intervention programs.
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http://dx.doi.org/10.1016/j.pmedr.2020.101239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710645PMC
December 2020

Trends in the process and outcome indicators of type 2 diabetes care: a cohort study from Eastern Finland, 2012-2017.

BMC Fam Pract 2020 12 4;21(1):253. Epub 2020 Dec 4.

Institute of Public Health and Clinical Nutrition, University of Eastern Finland, PO Box 1627, FI-70211, Kuopio, Finland.

Background: Evidence-based guidelines include concrete treatment targets that can be used as process and outcome indicators in the evaluation of the quality of healthcare services and diabetes care. Quality improvement can be evaluated by monitoring longitudinal trends in the care indicators on the system level. The aim of this study is to describe trends in the processes and outcomes of care among people with type 2 diabetes in North Karelia, Finland.

Methods: The data consist of all adults with type 2 diabetes (identified from the EHRs using ICD-10 codes) who used primary or specialized care services in North Karelia during 2012-2017. The diabetes care was evaluated using the measurement activity, treatment levels, and the achievement of the treatment targets for HbA1c and LDL as care indicators. Logistic and linear models with generalized estimating equations were used to assess the differences between years, sexes, and age groups.

Results: The proportion of patients with annual measurement varied between 75.8 and 78.1% for HbA1c and between 67.4 and 69.1% for LDL during a five-year follow-up. The changes in average levels were moderate: a 0.2% (2 mmol/mol) increase for HbA1c and a 0.1 mmol/l decrease for LDL. Anyway, the proportion of patients meeting the treatment target for HbA1c decreased from 72.7 to 67.3% (age-adjusted decrease: 5.7%p, 95% CI: 4.5-6.9) and for LDL it increased from 53.4 to 59.5% (age-adjusted increase: 5.6%p, 95% CI: 4.2-7.0). Women were measured and met the HbA1c target level more often compared with men. Conversely, men met the LDL target level more often than women, and the age-adjusted difference between sexes increased smoothly from 7.9%p to 11.7%p.

Conclusions: The achievements in relation to type 2 diabetes care in North Karelia are very good, but no major improvement was observed during follow-up. HbA1c levels had a rising tendency and LDL levels declining tendency indicating quality improvement in LDL management, but challenges in further improvement in glucose control.
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http://dx.doi.org/10.1186/s12875-020-01324-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718663PMC
December 2020

Impact of co-payment level increase of antidiabetic medications on glycaemic control: an interrupted time-series study among Finnish patients with type 2 diabetes.

BMC Health Serv Res 2020 Nov 27;20(1):1095. Epub 2020 Nov 27.

Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, P.O.Box. 1627, FI-70211, Kuopio, Finland.

Background: A new special reimbursement scheme (SRS) for non-insulin medications used for treatment of hyperglycaemia in type 2 diabetes (T2D) was implemented in Finland on January 1, 2017. The new SRS affected all community-dwelling Finnish T2D patients as all community-dwelling residents are eligible for reimbursement for prescription medications. The aim of the study was to evaluate the impact of this co-payment increase on glycaemic control among Finnish T2D patients.

Methods: Data on glycaemic control were collected with HbA1c measures from electronic health records from primary health care and specialized care in the North Karelia region, Finland, from patients with a confirmed T2D diagnosis in 2012 who were alive on January 1, 2017 (n = 8436). Average HbA1c levels were measured monthly 36 months before and 33 months after the policy change. Consumption of diabetes medications was measured with defined daily doses (DDDs) based on reimbursed medication purchases. Interrupted time series design analysed with segmented regression model was applied to examine the effect of the policy change on average HbA1c levels.

Results: Eight thousand one hundred forty-three T2D patients had at least one HbA1c measurement within 01/2014-9/2019. Mean age of the patients was 68.1 (SD 11.3) years and 53.0% were women. Average time since T2D diagnosis was 11.5 (SD 6.1) years. An estimated increase of 0.81 (95% confidence interval, CI, 0.04-1.58) mmol/mol in average HbA1c levels was detected at the time of the policy change. In subgroup analyses, strongest effects were detected among patients who used only other diabetes medications than insulin or metformin in 2016 (3.56 mmol/mol, 95% CI 2.50-4.62). Meanwhile, yearly consumption of diabetes medications decreased slightly from 618.9 (SD 487.8) DDDs/patient in 2016 to 602.9 (SD 475.6) DDDs/patient in 2017 (p = 0.048).

Conclusions: Simultaneously with the increase of the co-payment level, the average HbA1c level increased among T2D patients from the North Karelia region, Finland. This may be explained by the decreased consumption of diabetes medications between 2016 and 2017. Special attention should be allocated to glycaemic control of patients utilizing only other antidiabetic medications than metformin or insulin.
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http://dx.doi.org/10.1186/s12913-020-05952-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694920PMC
November 2020

Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Nat Genet 2020 12 23;52(12):1314-1332. Epub 2020 Nov 23.

Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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http://dx.doi.org/10.1038/s41588-020-00713-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610439PMC
December 2020

Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline: A Randomized Clinical Trial.

J Gerontol A Biol Sci Med Sci 2021 02;76(3):491-498

Division of Clinical Geriatrics, Centre for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.

Background: Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs).

Methods: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60-77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989).

Results: This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was -0.016 (0.19) in the intervention group and -0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI -0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: -0.005 (95% CI -0.010 to -0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI -0.011 to 0.264).

Conclusions: This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits.

Clinical Trials Registration Number: NCT01041989.
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http://dx.doi.org/10.1093/gerona/glaa279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907495PMC
February 2021

Measurement error as an explanation for the alcohol harm paradox: analysis of eight cohort studies.

Int J Epidemiol 2021 01;49(6):1836-1846

Department of Public Health Solutions, Finnish Institute for Health and Welfare, 00271 Helsinki, Finland.

Background: Despite reporting lower levels of alcohol consumption, people with lower socio-economic status (SES) experience greater alcohol-related harm. Whether differential biases in the measurement of alcohol use could explain this apparent paradox is unknown. Using alcohol biomarkers to account for measurement error, we examined whether differential exposure to alcohol could explain the socio-economic differences in alcohol mortality.

Methods: Participants from eight representative health surveys (n = 52 164, mean age 47.7 years) were linked to mortality data and followed up until December 2016. The primary outcome was alcohol-attributable mortality. We used income and education as proxies for SES. Exposures include self-reported alcohol use and four alcohol biomarkers [serum gamma-glutamyl transferase (available in all surveys), carbohydrate-deficient transferrin, alanine aminotransferase and aspartate aminotransferase (available in subsamples)]. We used shared frailty Cox proportional hazards to account for survey heterogeneity.

Results: During a mean follow-up of 20.3 years, totalling 1 056 844 person-years, there were 828 alcohol-attributable deaths. Lower SES was associated with higher alcohol mortality despite reporting lower alcohol use. Alcohol biomarkers were associated with alcohol mortality and improved the predictive ability when used in conjunction with self-reported alcohol use. Alcohol biomarkers explained a very small fraction of the socio-economic differences in alcohol mortality, since hazard ratios either slightly attenuated (percent attenuation range 1.0-12.1%) or increased.

Conclusions: Using alcohol biomarkers in addition to self-reported alcohol use did not explain the socio-economic differences in alcohol mortality. Differential bias in the measurement of alcohol use is not a likely explanation for the alcohol-harm paradox.
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http://dx.doi.org/10.1093/ije/dyaa113DOI Listing
January 2021
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