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.

Loss of Cln5 leads to altered Gad1 expression and deficits in interneuron development in mice.

The Finnish-variant late infantile neuronal ceroid lipofuscinosis, also known as CLN5 disease, is caused by mutations in the CLN5 gene. Cln5 is strongly expressed in the developing brain and expression continues into adulthood. CLN5, a protein of unknown function, is implicated in neurodevelopment but detailed investigation is lacking. Using Cln5-/- embryos of various ages and cells harvested from Cln5-/- brains we investigated the hitherto unknown role of Cln5 in the developing brain. Loss of Cln5 results in neuronal differentiation deficits and delays in interneuron development during in utero period. Specifically, the radial thickness of dorsal telencephalon was significantly decreased in Cln5-/- mouse embryos at embryonic day 14.5 (E14.5), and expression of Tuj1, an important neuronal marker during development, was down-regulated. An interneuron marker calbindin and a mitosis marker p-H3 showed down-regulation in ganglionic eminences. Neurite outgrowth was compromised in primary cortical neuronal cultures derived from E16 Cln5-/- embryos compared with WT embryos. We show that the developmental deficits of interneurons may be linked to increased levels of the repressor element 1-silencing transcription factor, which we report to bind to glutamate decarboxylase (Gad1), which encodes GAD67, a rate-limiting enzyme in the production of gamma-aminobutyric acid (GABA). Indeed, adult Cln5-/- mice presented deficits in hippocampal parvalbumin-positive interneurons. Furthermore, adult Cln5-/- mice presented deficits in hippocampal parvalbumin-positive interneurons and showed age-independent cortical hyper excitability as measured by electroencephalogram and auditory-evoked potentials. This study highlights the importance of Cln5 in neurodevelopment and suggests that in contrast to earlier reports, CLN5 disease is likely to develop during embryonic stages.

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.

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

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.

Impact of type 2 diabetes treated with non-insulin medication and number of diabetes-coexisting diseases on EQ-5D-5 L index scores in the Finnish population.

BACKGROUND: Type 2 diabetes (T2D) causes significant health and economic burden. In addition to comorbidities there are also coexisting diseases linked to obesity, lifestyle and T2D. The aim of this study was to examine the effect of T2D and T2D-coexisting diseases on health-related quality of life (HRQoL) in the Finnish population and whether it is T2D or the coexisting diseases that have the largest impact on HRQoL. METHODS: The study was based on a national cross-sectional population survey (n = 5305). Respondents' HRQoL was measured using the EQ-5D-5 L instrument. Our study included diabetic respondents treated with non-insulin medications (NI-T2D) with or without insulin and non-diabetic respondents, whereas diabetic respondents not taking any anti-diabetic medications or treated with insulin alone were excluded. A crosswalk algorithm was used to convert EQ-5D-5 L index scores into EQ-5D-3 L index scores as a sensitivity analysis. A two-part model was used to examine the association between T2D and coexisting diseases and HRQoL. RESULTS: The unadjusted mean (SD) EQ-5D-5 L index scores for non-diabetics (n = 4856) was 0.90 (0.13) and 0.85 (0.16) for respondents with NI-T2D (n = 449). With adjustment for demographic factors, the difference in EQ-5D-5 L index scores was 0.036 (95% CI 0.023-0.050). After adjusting for the number of coexisting diseases, the EQ-5D-5 L index scores among respondents with NI-T2D and three or more coexisting diseases were lower when compared to all non-diabetics but not when compared to non-diabetics with similar number of coexisting diseases. The number of T2D-coexisting diseases had a larger effect on EQ-5D-5 L index scores in younger age groups (20 and 40 years old). CONCLUSIONS: Lower EQ-5D-5 L index score is associated with NI-T2D when compared to non-diabetic respondents. When compared to non-diabetics, the disutility associated with NI-T2D increases as more coexisting diseases appear. The disutility effect of coexisting diseases was equally large in non-diabetics and respondents with NI-T2D. Thus, public health interventions targeting the prevention of both T2D and its coexisting diseases have potential to have significant benefits also in terms of HRQoL.

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.

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.

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.

Comparison of Communication Channels for Large-Scale Type 2 Diabetes Risk Screening and Intervention Recruitment: Empirical Study.

BACKGROUND: Clinical trials have shown that type 2 diabetes (T2D) is preventable through lifestyle interventions targeting high-risk people. Nevertheless, large-scale implementation of risk identification followed by preventive interventions has proven to be challenging. Specifically, recruitment of participants into preventive interventions is an important but often overlooked part of the intervention. OBJECTIVE: This study aims to compare the reach and yield of different communication channels to engage people at increased risk of T2D to fill in a digital screening questionnaire, with emphasis on reaching those at most risk. The participants expressing their willingness to participate is the final step in the risk screening test, and we aim to determine which channels had the most participants reach this step. METHODS: We established a stepwise web-based T2D risk screening tool with automated feedback according to the T2D risk level and, for those who were eligible, an invitation to participate in the StopDia prevention intervention study conducted in a primary health care setting. The risk estimate was based on the Finnish Diabetes Risk Score; history of repeatedly measured high blood glucose concentration; or, among women, previous gestational diabetes. We used several channels to invite people to the StopDia web-based screening tool, and respondents were classified into 11 categories based on the channel through which they reported having learned about StopDia. The demographics of respondents reached via different communication channels were compared using variance analysis. Logistic regression was used to study the respondents' likelihood of progressing through risk screening steps. RESULTS: A total of 33,399 persons started filling the StopDia screening tool. Of these, 86.13% (28,768/33,399) completed the test and named at least one communication channel as the source of information about StopDia. Altogether, 26,167 persons filled in sufficient information to obtain risk estimates. Of them, 53.22% (13,925/26,167) were at increased risk, 30.06% (7866/26,167) were men, and 39.77% (10,136/25,485) had low or middle education levels. Most frequently mentioned channels were workplace (n=6817), social media or the internet (n=6712), and newspapers (n=4784). The proportion of individuals at increased risk was highest among those reached via community pharmacies (415/608, 68.3%) and health care (1631/2535, 64.33%). The communication channel reaching the largest percentage of interested and eligible men (1353/3979, 34%) was relatives or friends. Health care (578/1069, 54.07%) and radio or television (225/487, 46.2%) accounted for the largest proportion of people with lower education. CONCLUSIONS: Communication channels reaching a large number of people, such as social media and newspapers, were the most effective channels for identifying at-risk people. Personalized approaches increased the engagement of men and less-educated people. Community pharmacies and health care services reached people with a particularly high T2D risk. Thus, communication and recruitment channels should be selected and modified based on the intended target group. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-019-6574-y.