Long-Term Health Economic Evaluation of Intermittently Scanned Glucose Monitoring Compared with Self-Monitoring Blood Glucose in a Real-World Setting in Finnish Adult Individuals with Type 1 Diabetes.

Background and Aims: There has been an evolving trend in the use of intermittently scanned continuous glucose monitoring (isCGM) among individuals with type 1 diabetes. Although isCGM is proven to be beneficial in the treatment of individuals with type 1 diabetes, its use leads to increasing device costs. This study aimed to investigate the long-term cost-effectiveness of isCGM. Methods: Long-term clinical outcomes and costs were projected using the IQVIA Core Diabetes Model (v10.0) based on the observed real-world outcomes of isCGM. The clinical input data for the analysis were sourced from a real-world patient cohort from Eastern Finland, including 877 adult individuals with type 1 diabetes with isCGM (i.e., Freestyle Libre 1 and 2). At the baseline, the patients' mean age was 48 years, and the mean duration of diabetes was 25.8 years. The mean baseline HbA1c was 8.6%, and the mean 12-month change from baseline in HbA1c was -0.37% after the initiation of isCGM. The cost-effectiveness analysis was performed over a lifetime time horizon. A discount rate of 3% was used for the future costs and health outcomes. Results: The projected use of isCGM was associated with improved quality-adjusted life year (QALY) expectancy of 0.84 QALYs after the start of isCGM. The direct lifetime costs were 7861 EUR higher with the use of isCGM, which resulted in an incremental cost-effectiveness ratio of 9396 EUR per QALY gained. Conclusions: According to the present analysis, the use of isCGM is considered cost-effective in adult individuals with type 1 diabetes in a real-world setting in Finland.

Trajectories of Body Mass Index and Risk for Diabetes Complications and All-Cause Mortality in Finnish Type 2 Diabetes Patients.

Objective: We aimed to assess how longitudinal body mass index (BMI) trajectories are associated with diabetes complications and all-cause mortality in Finnish patients with type 2 diabetes (T2D). Methods: In this cohort study, electronic health records from public primary and specialized healthcare services in all 13 municipalities of North Karelia, Finland, were utilized. This study included a total of 889 adults with newly diagnosed T2D in 2011 or 2012 (mean age at baseline 62.0 years). Individual BMI trajectories from the T2D diagnosis until 2014 were estimated and grouped by growth mixture modeling (GMM). Hazard ratios (HRs) with 95% confidence intervals (CIs) for microvascular complications, macrovascular complications, any diabetes complications, and all-cause mortality from 2015 to 2022 across BMI trajectory groups were estimated using Cox regression models. Results: Three distinct BMI trajectory groups were identified using GMM and labeled as follows: "stable" (n = 774, 87.1%), "decreasing" (n = 87, 9.8%), and "increasing" (n = 28, 3.1%). During a median follow-up of 8 years, there were 119 (13.3%) patients with microvascular complications, 187 (21.0%) with macrovascular complications, 258 (29.0%) with any diabetes complications, and 180 (20.2%) deaths. Compared with the "stable" BMI, the "increasing" BMI was associated with an increased risk of microvascular complications (HR = 2.88, 95% CI: 1.32 to 6.28), macrovascular complications (HR = 2.52, 95% CI: 1.17 to 5.43), and any diabetes complications (HR = 2.21, 95% CI: 1.16 to 4.20). The "decreasing" BMI was associated with an increased risk of all-cause mortality (HR = 1.90, 95% CI: 1.14 to 3.15), compared to the "stable" BMI. Conclusion: Our findings underscore the significance of continuous BMI monitoring and weight management in patients with T2D. Tailored treatments are crucial for efficiently preventing weight gain and reducing the risk of diabetes complications.

A study on the quantity, type, economic value and reasons for pharmaceutical waste returned to pharmacies in Finland.

INTRODUCTION: Some medicines purchased are not used, resulting in pharmaceutical waste. Finland, among many other countries, is seeking to reduce the amount of pharmaceutical waste, but little information on this is currently available. This study aimed to evaluate the quantity, type, economic value, and reasons for returning pharmaceutical waste from households to community pharmacies in Finland. METHODS: Community pharmacies (n = 82) quantified and qualified the amount of pharmaceutical waste returned to them over three days in May 2022. The data was collected using an electronic form. The reasons for returning medicines were asked from customers who returned medicines using a paper questionnaire. The data was analyzed for frequencies and percentages. To estimate the economic value, we used the Finnish medicines prices at the end of June 2022. The annual economic value was calculated by means of a pharmacy size-weighted average. The confidence intervals were estimated using the non-parametric bootstrap method. Sensitivity analyses were conducted to examine the reliability of the results. RESULTS: In total, 5173 medicines were returned to pharmacies, of which 66 % were prescription medicines. The most common medicines group returned were medicines for nervous system (18 %), respiratory system (16 %), and alimentary tract and metabolism (12 %). The estimated annual economic value of the medicines returned was 81 million euros (CI 95 % M€61-M€103), of which the cost to society was 43 million euros (CI 95 % M€30-M€60). 799 customers responded to the questionnaire (Response rate 81.9 %). The limited shelf life of the medicine after opening (36 %), improvement of the medical condition or symptom (25 %), and the unnecessarily large pack size (22 %) were common reasons for returning. CONCLUSION: A considerable amount of pharmaceutical waste is returned to pharmacies, causing unnecessary costs to both individuals and society, indicating the need to reduce waste. The limited shelf life and large pack sizes of medicines account for a large proportion of causes for household pharmaceutical waste. Reducing pharmaceutical waste requires action from all actors in the pharmaceutical chain.

Effectiveness of the Coordinated Return to Work model after orthopaedic surgery for lumbar discectomy and hip and knee arthroplasty: a register-based study.

OBJECTIVES: This study examined the effectiveness of an individualised Coordinated Return to Work (CRtW) model on the length of the return to work (RTW) period compared with a standard prescription of 2-3 months RTW during recovery after lumbar discectomy and hip and knee arthroplasty among Finnish working-age population. METHODS: Cohorts on patients aged 18-65 years old with lumbar discectomy or hip or knee arthroplasty were extracted from the electronic health records of eight Finnish hospital districts in 2015-2021 and compiled with retirement and sickness benefits. The overall effect of the CRtW model on the average RTW period was calculated as a weighted average of area-specific mean differences in RTW periods between 1 year before and 1 year after the implementation. Longer-term effects of the model were examined with an interrupted time series design estimated with a segmented regression model. RESULTS: During the first year of the CRtW model, the average RTW period shortened by 9.1 days (95% CI 4.1 to 14.1) for hip arthroplasty and 14.4 days (95% CI 7.5 to 21.3) for knee arthroplasty. The observed differences were sustained over longer follow-up times. For lumbar discectomy, the first-year decrease was not statistically significant, but the average RTW had shortened by 36.2 days (95% CI 33.8 to 38.5) after 4.5 years. CONCLUSIONS: The CRtW model shortened average RTW periods among working-age people during the recovery period. Further research with larger samples and longer follow-up times is needed to ensure the effectiveness of the model as a part of the Finnish healthcare system.

Agreement between physician- and patient-reported Canadian cardiovascular society scores among patients undergoing elective coronary angiography-The CATS study.

The primary aim of revascularization in stable coronary artery disease (CAD) is symptom relief. The severity of symptoms is usually evaluated by the physician, not by the patient. We examined the agreement between physician- and patient-reported Canadian Cardiovascular Society (CCS) scores among patients scheduled for elective coronary angiography in a cross-sectional study. Patients (n = 650) and cardiologists evaluated the severity of angina symptoms by filling the CCS questionnaire before coronary angiography. Patients were divided into those without CAD (stenosis diameter <50%, n = 445) and those with CAD (stenosis diameter >50%, n = 205). CAD patients were further divided into three groups according to disease severity (single-, double- or triple-vessel disease). The mean age of the patients was 67.6 (9.9) years and 50.6% were women. In 51.8% (95% CI 44.5%-59.0%) of patients with CAD and 51.9% (95% CI 47.0%-56.8%) of those without, physician- and patient reported CCS scores agreed. The physician reported better CCS scores in 33.9% (95% CI 27.6%-40.7%) of patients with CAD and 36.2% (95% CI 31.8%-41.0%) of patients without CAD. The proportions of full or partial agreement between physician- and patient reported CCS scores were similar across the CAD severity groups. To summarize, we observed a significant discrepancy between the physician- and patient-reported symptom severity in patients with or without CAD scheduled for angiography. The physician underestimated the symptoms in third of the cases. Thus, patient-reported symptom severity, rather than physician's evaluation, should be the cornerstone of treatment decisions.

The use of isCGM leads to marked reduction in severe hypoglycemia requiring emergency medical service or hospital admission and diabetic ketoacidosis in adult type 1 diabetes patients.

AIMS: To determine the effect of the use of intermittently scanned continuous glucose monitoring (isCGM) on acute diabetes-related complications in adult type 1 diabetes patients. METHODS: Six hundred and forty-two adult type 1 diabetes patients with isCGM were identified from electronic health records in Siun sote region in Eastern Finland. A retrospective real-world analysis was conducted combining hospital admission and prehospital emergency service data to compare incidences of hypoglycemia requiring emergency medical support (EMS) involvement or hospital admission and diabetic ketoacidosis (DKA) before and after the start of isCGM. Data were collected from January 2015 to April 2020. Primary outcome was the rate of hypoglycemia requiring EMS involvement or hospital admission and DKA events. HbA1c was recorded at the start of isCGM and was compared with the last known HbA1c during the use of isCGM. The isCGM used in the study did not contain alarm functions. RESULTS: Altogether 220 hypoglycemic events were identified during the study period. Incidence rate of hypoglycemic events decreased after the start of isCGM (72 events, incidence rate 50 events/1000 person-years) compared with the time before the start (148 events, incidence rate 76 events/1000 person-years) (p = 0.043). The incidence rate of DKA decreased after the start of isCGM compared with time before isCGM use (4 and 15 events/1000 person-years, respectively; p = 0.002). The change in mean HbA1c was - 0.28% (- 3.1 mmol/mol) between baseline and the last HbA1c measurement (p < 0.001). CONCLUSIONS: In addition to lowering HbA1c in type 1 diabetes patients, isCGM is also effective in preventing acute diabetes-related complications such as hypoglycemia requiring EMS involvement or hospital admission and DKA.

Data-Driven Identification of Long-Term Glycemia Clusters and Their Individualized Predictors in Finnish Patients with Type 2 Diabetes.

Purpose: To gain an understanding of the heterogeneous group of type 2 diabetes (T2D) patients, we aimed to identify patients with the homogenous long-term HbA1c trajectories and to predict the trajectory membership for each patient using explainable machine learning methods and different clinical-, treatment-, and socio-economic-related predictors. Patients and Methods: Electronic health records data covering primary and specialized healthcare on 9631 patients having T2D diagnosis were extracted from the North Karelia region, Finland. Six-year HbA1c trajectories were examined with growth mixture models. Linear discriminant analysis and neural networks were applied to predict the trajectory membership individually. Results: Three HbA1c trajectories were distinguished over six years: "stable, adequate" (86.5%), "improving, but inadequate" (7.3%), and "fluctuating, inadequate" (6.2%) glycemic control. Prior glucose levels, duration of T2D, use of insulin only, use of insulin together with some oral antidiabetic medications, and use of only metformin were the most important predictors for the long-term treatment balance. The prediction model had a balanced accuracy of 85% and a receiving operating characteristic area under the curve of 91%, indicating high performance. Moreover, the results based on SHAP (Shapley additive explanations) values show that it is possible to explain the outcomes of machine learning methods at the population and individual levels. Conclusion: Heterogeneity in long-term glycemic control can be predicted with confidence by utilizing information from previous HbA1c levels, fasting plasma glucose, duration of T2D, and use of antidiabetic medications. In future, the expected development of HbA1c could be predicted based on the patient's unique risk factors offering a practical tool for clinicians to support treatment planning.

Medicine use in children aged under 12 years-Population survey in Finland.

PURPOSE: To study the prevalence of prescribed and over-the-counter (OTC) medicine use in children under 12 years of age in Finland and to examine factors associated with the medicine use. METHODS: A nationwide population survey was carried out in Finland in spring 2018 with a random sample of children under 12 years (n = 8000). A response rate of 24% (n = 1921) was attained. The questionnaire was sent to the child's primary guardian. Current use of prescribed medicines and the use of OTC medicines in the preceding 2 days were the main outcome measures. RESULTS: Of all the children 19% had used prescribed medicines, 15% OTC medicines, and 31% either prescription or OTC medicines during the preceding 22 days. Children's health related factors were positively associated with prescribed medicine use including fairly good to poor health status, symptoms experienced, and illnesses diagnosed by a physician. The guardian's healthcare education and use of prescribed medicines were also associated with children's prescribed medicine use. Symptoms of illnesses and fairly good health status were found to be associated with childrens' use of OTC medicines. CONCLUSIONS: The use of medicines in children under 12 years of age is quite common in Finland. As expected, children's health-related factors were associated with medicine use. Also, guardians' healthcare education and the use of prescribed medicines were associated with children's prescription medicine use. Children's medicine use should be continuously monitored and investigated further to identify the reasons leading to appropriate and inappropriate medicine use in children.

Marked Improvement in A1C Levels After Initiation of Intermittently Scanned Continuous Glucose Monitoring Is Maintained Over 4 Years in Patients With Type 1 Diabetes.

Objective: This study aimed to demonstrate the effectiveness of long-term use of intermittently scanned continuous glucose monitoring (isCGM) in adult patients with type 1 diabetes. Design and methods: In this retrospective real-world study, 689 patients with type 1 diabetes who were >18 years of age and using isCGM were identified from the electronic patient records in North Karelia, Finland. A1C data were collected before and after the initiation of isCGM. The primary outcome was a change in the mean A1C over time after isCGM started. Results: The greatest reductions in the mean A1C levels were observed 6 months (-0.54% [-5.9 mmol/mol], P <0.001) and 12 months (-0.42% [-4.6 mmol/mol], P <0.001) after the initiation of isCGM. Reduction in A1C remained significant for 4 years, although the mean reduction in A1C was -0.18% (-2.05 mmol/mol) (P = 0.009) at 48 months compared with baseline. In a subgroup analysis, patients with a baseline A1C >9% (75 mmol/mol) benefited the most from initiation of isCGM (reduction -0.97% [-10.6 mmol/mol], P <0.001, at 12 months and -0.92% [-10.1 mmol/mol], P <0.001, at 48 months). Neither sex nor age at the start of isCGM were correlated with A1C reduction. Conclusion: Use of isCGM improves A1C levels significantly in adult patients with type 1 diabetes. Significant reduction in A1C persisted over 4 years of use, although the effect diminished over time.

Effects of COVID-19 Pandemic and Lockdown on Monitoring and Treatment Balance of Finnish Coronary Heart Disease and Type 2 Diabetes Patients.

Purpose: We aimed to examine the effect of the COVID-19 pandemic and lockdown on monitoring and treatment balance of Finnish coronary heart disease (CHD) and type 2 diabetes (T2D) patients. Patients and Methods: We used data from the electronic health records on 1604 CHD and 10,136 T2D patients aged 18‒85 years in Eastern Finland. Measurement and levels of low-density lipoprotein cholesterol (LDL) of CHD patients and glycated haemoglobin (HbA1c) of T2D patients were assessed monthly during January 2019-June 2021. Interrupted time-series analysis design was utilized to examine the effect of the lockdown on proportion of patients monitored and treatment balance. Results: Reductions in frequencies of LDL testing of CHD and HbA1c testing of T2D patients were observed during the national lockdown. Downward trend in average LDL was observed from January 2019 until June 2021. Average HbA1c values increased from January 2019 to March 2020 with an additional increase by 2.04 mmol/mol (0.80 to 3.29) in April 2020. However, there was a downward trend in monthly average HbA1c during the lockdown until June 2021 with an additional change in level by 0.61 mmol/mol (95% CI 0.06 to 1.16) in July 2020. Conclusion: The lockdown decreased the frequency of monitoring among both CHD and T2D patients. Meanwhile, monthly average LDL had a steadily improving pattern in CHD patients during the follow-up while temporary worsening in HbA1c in patients with T2D was observed at the time of the lockdown. The lockdown may have introduced selection in patients who had their treatment outcomes monitored. Better self-management of risk factors among patients is also possible.

Economic evaluation of using polygenic risk score to guide risk screening and interventions for the prevention of type 2 diabetes in individuals with high overall baseline risk.

Type 2 diabetes (T2D) with increasing prevalence is a significant global public health challenge. Obesity, unhealthy diet, and low physical activity are one of the major determinants of the rise in T2D prevalence. In addition, family history and genetic risk of diabetes also play a role in the process of developing T2D. Therefore, solutions for the early identification of individuals at high risk for T2D for early targeted detection of T2D, prevention, and intervention are highly preferred. Recently, novel genomic-based polygenic risk scores (PRSs) have been suggested to improve the accuracy of risk prediction supporting the targeting of preventive interventions to those at highest risk for T2D. Therefore, the aim of the present study was to assess the cost-utility of an additional PRS testing information (as a part of overall risk assessment) followed by a lifestyle intervention and an additional medical therapy when estimated 10-year overall risk for T2D exceeded 20% among Finnish individuals screened as at the high-risk category (i.e., 10%-20% 10-year overall risk of T2D) based on traditional risk factors only. For a cost-utility analysis, an individual-level state-transition model with probabilistic sensitivity analysis was constructed. A 1-year cycle length and a lifetime time horizon were applied in the base-case. A 3% discount rate was used for costs and QALYs. Cost-effectiveness acceptability curve (CEAC) and estimates for the expected value of perfect information (EVPI) were calculated to assist decision makers. The use of the targeted PRS strategy reclassified 12.4 percentage points of individuals to be very high-risk individuals who would have been originally classified as high risk using the usual strategy only. Over a lifetime horizon, the targeted PRS was a dominant strategy (i.e., less costly, more effective). One-way and scenario sensitivity analyses showed that results remained dominant in almost all simulations. However, there is uncertainty, since the probability (EVPI) of cost-effectiveness at a WTP of 0€/QALY was 63.0% (243€) indicating the probability that the PRS strategy is a dominant option. In conclusion, the results demonstrated that the PRS provides moderate additional value in Finnish population in risk screening leading to potential cost savings and better quality of life when compared with the current screening methods for T2D risk.

Data-driven long-term glycaemic control trajectories and their associated health and economic outcomes in Finnish patients with incident type 2 diabetes.

BACKGROUND: Treatments should be customized to patients to improve patients' health outcomes and maximize the treatment benefits. We aimed to identify meaningful data-driven trajectories of incident type 2 diabetes patients with similarities in glycated haemoglobin (HbA1c) patterns since diagnosis and to examine their clinical and economic relevance. MATERIALS AND METHODS: A cohort of 1540 patients diagnosed in 2011-2012 was retrieved from electronic health records covering primary and specialized healthcare in the North Karelia region, Finland. EHRs data were compiled with medication purchase data. Average HbA1c levels, use of medications, and incidence of micro- and macrovascular complications and deaths were measured annually for seven years since T2D diagnosis. Trajectories were identified applying latent class growth models. Differences in 4-year cumulative healthcare costs with 95% confidence intervals (CIs) were estimated with non-parametric bootstrapping. RESULTS: Four distinct trajectories of HbA1c development during 7 years after T2D diagnosis were extracted: patients with "Stable, adequate" (66.1%), "Slowly deteriorating" (24.3%), and "Rapidly deteriorating" glycaemic control (6.2%) as well as "Late diagnosed" patients (3.4%). During the same period, 2.2 (95% CI 1.9-2.6) deaths per 100 person-years occurred in the "Stable, adequate" trajectory increasing to 3.2 (2.4-4.0) in the "Slowly deteriorating", 4.7 (3.1-6.9) in the "Rapidly deteriorating" and 5.2 (2.9-8.7) in the "Late diagnosed" trajectory. Similarly, 3.5 (95% CI 3.0-4.0) micro- and macrovascular complications per 100 person-years occurred in the "Stable, adequate" trajectory increasing to 5.1 (4.1-6.2) in the "Slowly deteriorating", 5.5 (3.6-8.1) in the "Rapidly deteriorating" and 7.3 (4.3-11.8) in the "Late diagnosed" trajectory. Patients in the "Stable, adequate" trajectory had lower accumulated 4-year medication costs than other patients. CONCLUSIONS: Data-driven patient trajectories have clinical and economic relevance and could be utilized as a step towards personalized medicine instead of the common "one-fits-for-all" treatment practices.

Correlation of the disease-specific Canadian Cardiovascular Society (CCS) classification and health-related quality of life (15D) in coronary artery disease patients.

BACKGROUND: Generic health-related quality of life (HRQoL) and disease-specific instruments measure HRQoL from different aspects, although generic instruments often contain dimensions that reflect common symptoms. We evaluated how the change in 15D HRQoL and Canadian Cardiovascular Society (CCS) grading of angina severity correlate among coronary artery disease patients during 12-month follow-up. METHODS: Altogether 1 271 patients scheduled for coronary angiography between June 2015 and February 2017 returned the 15D HRQoL and CCS questionnaires before angiography and after one-year follow-up as a part of routine clinical practice. Spearman correlations between one-year changes in the CCS and the 15D and its dimensions were evaluated. Changes in 15D were classified into 5 categories based on the reported minimal important difference (MID) for the instrument. RESULTS: Change in the CCS grade correlated moderately with the MID-based change in the 15D (r = 0.33, 95% confidence interval 0.27-0.39). Correlations between these instruments were similar in different age groups, between sexes and treatment modalities. Of the individual 15D dimensions, changes in breathing (r = 0.40) and vitality (r = 0.30) had the strongest correlations with CCS change. CONCLUSION: The symptom-based evaluation of the change in the CCS grade may not catch the full benefit or harm of the treatment and vice versa, a generic instrument, such as 15D, likely does not fully capture change in disease-specific symptoms. Thus, generic and disease-specific instruments are complementary and should be used in conjunction.

Digitally Supported Lifestyle Intervention to Prevent Type 2 Diabetes Through Healthy Habits: Secondary Analysis of Long-Term User Engagement Trajectories in a Randomized Controlled Trial.

BACKGROUND: Digital health interventions may offer a scalable way to prevent type 2 diabetes (T2D) with minimal burden on health care systems by providing early support for healthy behaviors among adults at increased risk for T2D. However, ensuring continued engagement with digital solutions is a challenge impacting the expected effectiveness. OBJECTIVE: We aimed to investigate the longitudinal usage patterns of a digital healthy habit formation intervention, BitHabit, and the associations with changes in T2D risk factors. METHODS: This is a secondary analysis of the StopDia (Stop Diabetes) study, an unblinded parallel 1-year randomized controlled trial evaluating the effectiveness of the BitHabit app alone or together with face-to-face group coaching in comparison with routine care in Finland in 2017-2019 among community-dwelling adults (aged 18 to 74 years) at an increased risk of T2D. We used longitudinal data on usage from 1926 participants randomized to the digital intervention arms. Latent class growth models were applied to identify user engagement trajectories with the app during the study. Predictors for trajectory membership were examined with multinomial logistic regression models. Analysis of covariance was used to investigate the association between trajectories and 12-month changes in T2D risk factors. RESULTS: More than half (1022/1926, 53.1%) of the participants continued to use the app throughout the 12-month intervention. The following 4 user engagement trajectories were identified: terminated usage (904/1926, 46.9%), weekly usage (731/1926, 38.0%), twice weekly usage (208/1926, 10.8%), and daily usage (83/1926, 4.3%). Active app use during the first month, higher net promoter score after the first 1 to 2 months of use, older age, and better quality of diet at baseline increased the odds of belonging to the continued usage trajectories. Compared with other trajectories, daily usage was associated with a higher increase in diet quality and a more pronounced decrease in BMI and waist circumference at 12 months. CONCLUSIONS: Distinct long-term usage trajectories of the BitHabit app were identified, and individual predictors for belonging to different trajectory groups were found. These findings highlight the need for being able to identify individuals likely to disengage from interventions early on, and could be used to inform the development of future adaptive interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03156478; https://clinicaltrials.gov/ct2/show/NCT03156478. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-019-6574-y.

Antipsychotic Use and Risk of Stroke Among Community-Dwelling People With Alzheimer's Disease.

OBJECTIVES: Antipsychotic use for neuropsychiatric symptoms in Alzheimer's disease (AD) is common despite the increased risk of cardiovascular events and mortality. There is limited and inconsistent evidence on the possible risk of stroke. We assessed whether antipsychotic initiation increases the risk of stroke in people with a verified diagnosis of AD and whether there is a difference in stroke risk between the 2 most commonly used antipsychotics, risperidone and quetiapine. DESIGN: Register-based exposure-matched cohort study. SETTING AND PARTICIPANTS: The Medication Use and Alzheimer's Disease (MEDALZ) cohort included 70,718 community-dwelling people with AD in Finland during 2005-2011. People with previous strokes were excluded. METHODS: For each incident antipsychotic user (n = 20,467), 1 nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with inverse probability of treatment-weighted (IPTW) Cox proportional hazards models. RESULTS: Compared with nonuse, antipsychotic use was associated with an increased risk of stroke within 60 days of antipsychotic initiation [IPTW hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.32-2.28]. However, there was no significant overall association between antipsychotic use and the risk of stroke (IPTW HR 1.09, 95% CI 0.98-1.22). There was no difference in stroke risk between risperidone and quetiapine (IPTW HR 1.12, 95% CI 0.91-1.37). CONCLUSIONS AND IMPLICATIONS: Stroke risk is increased shortly after antipsychotic initiation in people with AD, suggesting that even short-term use of antipsychotics should be avoided if possible. If antipsychotics are prescribed, effectiveness and safety should be assessed soon after initiation and treatment limited to the shortest possible duration.

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

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.

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

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

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.

Patient-reported outcomes in coronary artery disease: the relationship between the standard, disease-specific set by the International Consortium for Health Outcomes Measurement (ICHOM) and the generic health-related quality of life instrument 15D.

BACKGROUND: Patient-reported outcome (PRO) instruments measure health gains, including changes in health-related quality of life (HRQoL). Previous studies have assessed the reliability and relationship of multiple HRQoL instruments in search of the optimal instrument for feasible measurement of PROs. Although the 15D instrument was shown to have the best sensitivity and construct validity among cardiac patients, it is unknown how well it captures relevant disease-specific information scores compared to instruments included in the International Consortium for Health Outcomes Measurement (ICHOM) standard set. The aim of this study was to investigate whether the disease-specific PRO instruments and a generic HRQoL instrument capture disease related symptoms in coronary artery disease (CAD) patients. METHODS: Health status and HRQoL were assessed with the instruments included in the ICHOM standard set: Seattle Angina Questionnaire short-form (SAQ-7), Rose Dyspnea Scale (RDS), two-item Patient Health Questionnaire (PHQ-2), and with the 15D HRQoL instrument at baseline and 1 year from the treatment in a university hospital setting. Spearman correlation and explanatory factor analysis were used to assess the relationship of baseline scores and 1-year change in scores of 297 patients. RESULTS: At baseline, the overall 15D score and SAQ-physical limitation (SAQ-PL), 15D "breathing" and SAQ-PL, as well as "breathing" and RDS showed moderately strong correlations. The factor interpreted to reflect "Breathing-related physical activity", based on high loadings of "breathing", RDS, SAQ-PL, "mobility", "vitality", and "usual activities", explained 19.2% of the total variance. Correlations between 1-year changes in scores were fair. The factor of "Breathing-related physical activity", with significant loading of RDS, SAQ-PL, "breathing, "usual activities", "vitality", "sexual activity", "mobility", and disease-specific quality of life explained 20.5% of the total variance in 1-year change in scores. The correlation of angina frequency measured by SAQ-7 and the 15D instrument was poor. CONCLUSIONS: The 15D detects dyspnea and depression similarly to RDS and PHQ-2 but not angina similarly to the SAQ-7. This may call for supplementing the 15D instrument with a disease-specific instrument when studying CAD patients.

Hip Fracture Risk in Antiepileptic Drug Initiators and Non-Initiators with Alzheimer's Disease.

OBJECTIVE: To determine the risk of hip fracture in persons with Alzheimer´s disease (AD) who initiated antiepileptic drugs (AEDs). METHODS: In the Medication use and AD (MEDALZ) cohort of 70,719 Finnish community dwellers with clinically verified incident AD diagnosis in 2005-2011, we identified all incident users of AEDs using national Prescription register. AEDs were classified as older (valproate, carbamazepine, clonazepam, phenytoin, levetiracetam, primidone) or newer (pregabalin, gabapentin, oxcarbazepine, lamotrigine, topiramate). We matched each user to 2 non-users. Incident hip fractures until 2015 were identified from the Care register for health care. We calculated inverse probability of treatment weighted hazard ratios (HR), with 95% confidence intervals, using Cox regression. RESULTS: Altogether 5522 incident users were identified and matched to 11,044 non-users (in both groups, women: 65%; median age: 81 years). Altogether 53.3% of users initiated with newer AEDs (pregabalin 79.8%, gabapentin 10.2%) while 46.7% initiated with older AEDs (valproate 67.6%, carbamazepine 13.0%). Age- and sex-adjusted IR of hip fracture per 100 person-years was 1.8 (95% CI 1.6-1.9) in non-users and 2.0 (95% CI 1.8-2.2) in users. Increased risk of hip fracture was observed in users (HR 1.17, 95% CI 1.05-1.30) compared with non-users. The risk was higher for short duration of use (<14 weeks, HR 3.64, 95% CI 2.90-4.58) than for medium duration (14 to <64 weeks, HR 1.74, 95% CI 1.48-2.05) or ≥64 weeks' use (HR 1.23, 95% CI 1.08-1.40), compared to non-users with same follow-up time. Older AEDs had HR of 1.46 (1.03-2.08) compared with newer AEDs. CONCLUSION: Our results imply that AED use is associated with an increased risk of hip fracture in people with AD. These findings prompt careful consideration before prescribing AEDs to persons with AD. Persons with AD treated with antiepileptics should be carefully monitored due to their increased risk of falling and fractures.