Multimorbidity transitions and the associated healthcare cost among the Finnish adult population during a two-year follow-up.

Background: Ageing of the population increases the prevalence and coexistence of many chronic diseases; a condition called multimorbidity. In Finland, information on the significance of multimorbidity and its relation to the sustainability of healthcare is scarce. Aim: To assess the prevalence of multimorbidity, the transitions between patient groups with and without multiple diseases and the associated healthcare cost in Finland in 2017-2019. Methods: A register-based cohort study covering all adults (n = 3,326,467) who used Finnish primary or specialised healthcare services in 2017. At baseline, patients were classified as 'non-multimorbid', 'multimorbid' or 'multimorbid at risk' based on the recordings of a diagnosis of interest. The costs were calculated using the care-related patient grouping and national standard rates. Transition plots were drawn to observe the transition of patients and costs between groups during the two-year follow-up. Results: At baseline, 62% of patients were non-multimorbid, 23% multimorbid and 15% multimorbid at risk. In two years, the proportion of multimorbid patients increased, especially those at risk. Within the multimorbid at-risk group, total healthcare costs were greatest (€5,027 million), accounting for 62% of the total healthcare cost of the overall patient cohort in 2019. Musculoskeletal diseases, cardiometabolic diseases and tumours were the most common and expensive chronic diseases contributing to the onset of multimorbidity. Conclusion: Multimorbidity is causing a heavy burden on Finnish healthcare. The estimates of its effect on healthcare usage and costs should be used to guide healthcare planning.

Can we optimize locations of hospitals by minimizing the number of patients at risk?

BACKGROUND: To reduce risk of death in acute ST-segment elevation myocardial infraction (STEMI), patients must reach a percutaneous coronary intervention (PCI) within 120 min from the start of symptoms. Current hospital locations represent choices made long since and may not provide the best possibilities for optimal care of STEMI patients. Open questions are: (1) how the hospital locations could be better optimized to reduce the number of patients residing over 90 min from PCI capable hospitals, and (2) how this would affect other factors like average travel time. METHODS: We formulated the research question as a facility optimization problem, which was solved by clustering method using road network and efficient travel time estimation based on overhead graph. The method was implemented as an interactive web tool and tested using nationwide health care register data collected during 2015-2018 in Finland. RESULTS: The results show that the number of patients at risk for not receiving optimal care could theoretically be reduced significantly from 5 to 1%. However, this would be achieved at the cost of increasing average travel time from 35 to 49 min. By minimizing average travel time, the clustering would result in better locations leading to a slight decrease in travel time (34 min) with only 3% patients at risk. CONCLUSIONS: The results showed that minimizing the number of patients at risk alone can significantly improve this single factor but, at the same time, increase the average burden of others. A more appropriate optimization should consider more factors. We also note that the hospitals serve also for other operators than STEMI patients. Although optimization of the entire health care system is a very complex optimization problems goal, it should be the aim of future research.

Explaining regional variation in elective hip and knee arthroplasties in Finland 2010 - 2017-a register-based cohort study.

BACKGROUND: A persistent research finding in industrialised countries has been regional variation in medical practices including elective primary hip and knee arthroplasty. The aim of the study was to examine regional variations in elective total hip and knee arthroplasties over time, and the proportions of these variations which can be explained by individual level or area-level differences in need. METHODS: We obtained secondary data from the Care Register for Health Care to study elective primary hip and knee arthroplasties in total Finnish population aged 25 + years between 2010 and 2017. Two-level Poisson regression models - individuals and hospital regions - were used to study regional differences in the incidence of elective hip and knee arthroplasties in two time periods: 2010 - 2013 and 2014 - 2017. The impact of several individual level explanatory factors (age, socioeconomic position, comorbidities) and area-level factors (need and supply of operations) was measured with the proportional change in variance. Predictions of incidence were measured with incidence rate ratios. The relative differences in risk of the procedures in regions were described with median rate ratios. RESULTS: We found small and over time relatively stable regional variation in hip arthroplasties in Finland, while the variation was larger in knee arthroplasties and decreased during the study period. In 2010 - 2013 individual socioeconomic variables explained 10% of variation in hip and 4% in knee arthroplasties, an effect that did not emerge in 2014 - 2017. The area-level musculoskeletal disorder index reflecting the need for care explained a further 44% of the variation in hip arthroplasties in 2010 - 2013, but only 5% in 2014 - 2017 and respectively 22% and 25% in knee arthroplasties. However, our final models explained the regional differences only partially. CONCLUSIONS: Our results suggest that eligibility criteria in total hip and knee arthroplasty are increasingly consistent between Finnish hospital districts. Factors related to individual level and regional level need both had an important role in explaining regional variations. Further study is needed on the effect of health policy on equity in access to care in these operations.

Change in medical practice over time? A register based study of regional trends in hysterectomy in Finland in 2001-2018.

BACKGROUND: A persistent research finding in Finland and elsewhere has been variation in medical practices both between and within countries. Variation seems to exist especially if medical decision making involves discretion and the best treatment cannot be identified unambiguously. This is true for hysterectomy when performed for benign causes. The aim of the current study was to investigate regional trends in hysterectomy in Finland and the potential convergence of rates over time. METHODS: We used hospital discharge register data on hysterectomies performed, diagnoses, age, and region of residence to examine hospital discharges for women undergoing hysterectomy in 2001-2018 among total female population aged 25 years or older in Finland. We examined hysterectomy rates among biannual cohorts by indication, calculated age-standardised rates and used multilevel models to analyse potential convergence over time. RESULTS: Altogether 131,695 hysterectomies were performed in Finland 2001-2018. We found a decreasing trend, with the age-adjusted overall hysterectomy rate decreasing from 553/100,000 person years in 2001-2002 to 289/100,000 py in 2017-2018. Large but converging regional differences were found. The correlations between hospital district intercepts and slopes in time ranged from - 0.71 to - 0.97 (p < 0.001) suggesting diminishing variation. CONCLUSIONS: Our findings demonstrate that change in hysterectomy practices and more uniformity across regions are achievable goals. Regional variation still exists suggesting differences in medical practices.

Concomitant use of drugs known to cause interactions with oral antiplatelets-polypharmacy in acute coronary syndrome outpatients in Finland.

PURPOSE: Use of oral antiplatelets (OAPs) is essential for preventing thrombotic events in patients with acute coronary syndrome (ACS). Effects of clopidogrel, prasugrel, and ticagrelor may be enhanced due to pharmacodynamic interactions, but as CYP substrates, they are prone to pharmacokinetic interactions too. The aim was to study polypharmacy in ACS patients following hospital discharge. METHODS: This observational drug utilization study linked patient-level data from nationwide registers. The study population consisted of adult ACS patients discharged from Finnish hospitals in 2009-2013. Logistic regression was used to model the probability of drug-drug interactions with odd ratios for predefined predictors such as age, gender, and ACS type. RESULTS: In the cohort of 54,416 ACS patients, 91% of those treated with OAP received clopidogrel. Of clopidogrel-treated patients, 12% purchased warfarin at least once while on clopidogrel treatment. Old age, male sex, ST-elevation myocardial infarction as index event, and a history of previous ACS events were associated with an increased risk of warfarin-OAP interaction (p < 0.001 for all). Ibuprofen, and serotonergic drugs tramadol, citalopram, and escitalopram were the next most common drugs causing pharmacodynamic interactions. In general, concomitant use of drugs known to cause pharmacokinetic interactions was rare, but both esomeprazole and omeprazole were prescribed in more than 6% of clopidogrel-treated patients. CONCLUSIONS: Warfarin and ibuprofen were the most commonly used concomitant medications causing pharmacodynamic interactions and potentially increasing the risk of bleeding in OAP-treated patients. Esomeprazole and omeprazole were used in clopidogrel-treated patients although there are alternatives available for gastric protection.

Finland: Health System Review.

This analysis of the Finnish health system reviews developments in its organization and governance, financing, provision of services, health reforms and health system performance. Finland is a welfare state witha high standard of social and living conditions and a low poverty rate. Its health system has a highly decentralized administration, multiple funding sources, and three provision channels for statutory services in first-contact care: the municipal system, the national health insurance system, and occupational health care. The core health system is organized by the municipalities (i.e. local authorities) which are responsible for financing primary and specialized care. Health financing arrangements are fragmented, with municipalities, the health insurance system, employers and households all contributing substantial shares. The health system performs relatively well, as health services are fairly effective, but accessibility may be an issue due to long waiting times and relatively high levels of cost sharing. For over a decade, there has been broad agreement on the need to reform the Finnish health system, but reaching a feasible policy consensus has been challenging.

Usage of PCI and long-term cardiovascular risk in post-myocardial infarction patients: a nationwide registry cohort study from Finland.

BACKGROUND: Despite currently available treatments, the burden of myocardial infarction (MI) morbidity and mortality remains prominent. The aim of this was to investigate the risk of developing subsequent cardiovascular events in MI patients. METHODS: This was an observational, retrospective cohort database linkage study using patient level data from Finland. Cox proportional hazards models were used to assess the association of risk between the preselected covariates and incidence of specific outcomes. The primary endpoints were new MI, stroke, cardiovascular mortality and overall mortality. RESULTS: Finnish adult MI patients alive 7 days after discharge in 2009-2012 were included. The study cohort consisted of 32,909 MI patients, of whom 25,875 (79%) survived 12 months without subsequent MI or stroke. ST-elevation MI (STEMI) was associated with lower risk of subsequent MI and overall mortality compared to non-STEMI patients. Percutaneous coronary intervention (PCI) was used two times more often in STEMI patients, but patients with prior stroke were more than two times less likely to have PCI. Dementia/Alzheimer's disease decreased the use of PCI as much as age over 85 years. Female sex was an independent factor for not undergoing PCI (OR 0.75, P < 0.001 compared to men) but was nevertheless associated with lower risk of new MI and mortality (HR 0.8-0.9, P < 0.001 for all). Increased age was associated with increased event risk and PCI with decreased event risk. CONCLUSIONS: Risk of cardiovascular events and mortality after MI increases steeply with age. Although at higher risk, aging patients and those with cardiovascular comorbidities are less likely to receive PCI after MI. Female sex is associated with better survival after MI regardless of less intensive treatment in women.

Finland: health system review

This analysis of the Finnish health system reviews developments in its organization and governance, financing, provision of services, health reforms and health system performance. Finland is a welfare state with a high standard of social and living conditions and a low poverty rate. Its health system has a highly decentralized administration, multiple funding sources, and three provision channels for statutory services in first-contact care: the municipal system, the national health insurance system, and occupational health care. The core health system is organized by the municipalities (i.e. local authorities) which are responsible for financing primary and specialized care. Health financing arrangements are fragmented, with municipalities, the health insurance system, employers and households all contributing substantial shares. The health system performs relatively well, as health services are fairly effective, but accessibility may be an issue due to long waiting times and relatively high levels of cost sharing. For over a decade, there has been broad agreement on the need to reform the Finnish health system, but reaching a feasiblepolicy consensus has been challenging.

What patients think about choice in healthcare? A study on primary care services in Finland.

BACKGROUND: The ongoing Finnish health and social service reform will expand choice by opening the market for competition between public and private service providers. This study examined the attitudes of primary care patients towards choice and which patient-related factors are associated with these attitudes. METHODS: A sample of attenders during one week in health centres of 12 big cities and municipal consortiums (including seven outsourced local units) and in primary care units of one private company providing outsourced services for municipalities (aged 18-95, n=8128) was used. The questionnaire included questions on choice-related attitudes, sociodemographic factors, health status, use of health services and patient satisfaction. RESULTS: Of the responders, 77% regarded choice to be important, 49% perceived genuine opportunities to make choices and 35% were satisfied with the choice-relevant information. Higher age, low education, having a chronic illness, frequent use of services, having a personal physician and being satisfied with the physician and with waiting times were related to assigning more importance on choice. Younger patients, those with higher education as well as those with chronic illness regarded their opportunities of choosing the service provider and availability of choice-relevant information poorer. CONCLUSIONS: The Finnish primary care patients value choice, but they are critical of the availability of choice-relevant information. Choices of patients with complex health care needs should be supported by developing integrated care alternatives and by increasing the availability of information on existing care alternatives to meet their needs.

Clinical disease presentation and ECG characteristics of LMNA mutation carriers.

OBJECTIVE: Mutations in the LMNA gene encoding lamins A and C of the nuclear lamina are a frequent cause of cardiomyopathy accounting for 5-8% of familial dilated cardiomyopathy (DCM). Our aim was to study disease onset, presentation and progression among LMNA mutation carriers. METHODS: Clinical follow-up data from 27 LMNA mutation carriers and 78 patients with idiopathic DCM without an LMNA mutation were collected. In addition, ECG data were collected and analysed systematically from 20 healthy controls. RESULTS: Kaplan-Meier analysis revealed no difference in event-free survival (death, heart transplant, resuscitation and appropriate implantable cardioverter-defibrillator therapy included as events) between LMNA mutation carriers and DCM controls (p=0.5). LMNA mutation carriers presented with atrial fibrillation at a younger age than the DCM controls (47 vs 57 years, p=0.003). Male LMNA mutation carriers presented with clinical manifestations roughly a decade earlier than females. In close follow-up non-sustained ventricular tachycardia was detected in 78% of LMNA mutation carriers. ECG signs of septal remodelling were present in 81% of the LMNA mutation carriers, 21% of the DCM controls and none of the healthy controls giving a high sensitivity and specificity for the standard ECG in distinguishing LMNA mutation carriers from patients with DCM and healthy controls. CONCLUSIONS: Male LMNA mutation carriers present clinical manifestations at a younger age than females. ECG septal remodelling appears to distinguish LMNA mutation carriers from healthy controls and patients with DCM without LMNA mutations.

Increased ventilatory response to exercise in symptomatic and asymptomatic LMNA mutation carriers: a follow-up study.

BACKGROUND: LMNA mutations are an important cause of cardiomyopathy often leading to cardiac arrhythmias, heart failure and even heart transplantation. An increasing number of asymptomatic mutation carriers are identified, as family members of the index patients are screened. Our aim was to study the disease progression in asymptomatic LMNA mutation carriers and in patients with symptomatic cardiolaminopathy by repeated spiroergometric testing in a prospective clinical follow-up study. METHODS AND RESULTS: We studied 26 LMNA mutation carriers once a year during 5 years up to 6 times by spiroergometry, clinical assessment, laboratory tests and echocardiography. The 23 control subjects underwent clinical assessment and spiroergometry once. Twelve of the mutation carriers were asymptomatic, and 14 had some clinical manifestations of the mutation ranging from clinically relevant rhythm disturbances to DCM and heart failure. Compared to controls, the symptomatic carriers showed a higher slope of the ventilatory equivalent for CO2 (V˙E/V˙CO2 slope) and a lower fraction of end-tidal CO2 (FetCO2 ). The asymptomatic mutation carriers also showed an increased ventilatory response to exercise during the follow-up as indicated by increased V˙E/V˙CO2 slope and decreased FetCO2 . CONCLUSIONS: The study suggests that an increased ventilatory response during exercise might reveal a preclinical manifestation of DCM in LMNA mutation carriers.

The Finnish experience to save asthma costs by improving care in 1987-2013.

The Finnish National Asthma Program 1994-2004 markedly improved asthma care in the 1990s. We evaluated the changes in costs during 26 years from 1987 to 2013. Direct and indirect costs were calculated by using data from national registries. Costs from both the societal and patient perspectives were included. The costs were based on patients with persistent, physician-diagnosed asthma verified by lung function measurements. We constructed minimum and maximum scenarios to assess the effect of improved asthma care on total costs. The number of patients with persistent asthma in the national drug reimbursement register increased from 83,000 to 247,583. Improved asthma control reduced health care use and disability, resulting in major cost savings. Despite a 3-fold increase in patients, the total costs decreased by 14%, from €222 million to €191 million. Costs for medication and primary care visits increased, but overall annual costs per patient decreased by 72%, from €2656 to €749. The theoretical total cost savings for 2013, comparing actual with predicted costs, were between €120 and €475 million, depending on the scenario used. The Finnish Asthma Program resulted in significant cost savings at both the societal and patient levels during a 26-year period.

Clinical factors associated with initiation of and persistence with ADP receptor-inhibiting oral antiplatelet treatment after acute coronary syndrome: a nationwide cohort study from Finland.

OBJECTIVES: To study patient selection for and persistence with ADP receptor-inhibiting oral antiplatelet (OAP) treatment after acute coronary syndrome (ACS). DESIGN: Observational, retrospective, cohort study linking real-life patient-level register data. SETTING: Nationwide drug usage study using data of patients with ACS discharged from hospitals in Finland. PARTICIPANTS: The study population consisted of 54 416 patients (aged ≥18 years) following hospital admission for unstable angina pectoris or myocardial infarction during 2009-2013. Patients were classified as either OAP or non-OAP users based on drug purchases within 7 days of discharge. OUTCOME MEASURES: Initiation of and a 12-month persistence with OAP medication. RESULTS: In total, 49% of patients with ACS received OAP treatment after hospital discharge. Women represented 40% of the population, but only 32% of them became OAP users (adjusted OR for initiation compared with men 0.8; p<0.001). Patients not treated with percutaneous coronary intervention (PCI), elderly and patients with dementia/Alzheimer's disease, atrial fibrillation or warfarin treatment were less likely to be treated with OAP. If initiated, they were less likely to complete the recommended 12 months' medication (adjusted risk increment >38% and p<0.001 for all). The OAP users showed good compliance with immediate initiation (92% within 1 day of discharge) and high mean medication possession rate (99%). Among OAP users, the usage of other secondary prevention drugs after ACS was more common than in non-OAP-treated patients (difference >20 percentage points for each). CONCLUSIONS: Only half of the patients with ACS received guideline-recommended ADP receptor-inhibiting OAP treatment after hospital discharge, suggesting suboptimal treatment practices. Non-PCI-treated patients and patients with increased age, unstable angina, dementia or atrial fibrillation appear to have the highest risk of deficient treatment with OAPs. OAP users, however, showed good compliance during drug usage.

Late gadolinium enhanced cardiovascular magnetic resonance of lamin A/C gene mutation related dilated cardiomyopathy.

BACKGROUND: The purpose of this study was to identify early features of lamin A/C gene mutation related dilated cardiomyopathy (DCM) with cardiovascular magnetic resonance (CMR). We characterise myocardial and functional findings in carriers of lamin A/C mutation to facilitate the recognition of these patients using this method. We also investigated the connection between myocardial fibrosis and conduction abnormalities. METHODS: Seventeen lamin A/C mutation carriers underwent CMR. Late gadolinium enhancement (LGE) and cine images were performed to evaluate myocardial fibrosis, regional wall motion, longitudinal myocardial function, global function and volumetry of both ventricles. The location, pattern and extent of enhancement in the left ventricle (LV) myocardium were visually estimated. RESULTS: Patients had LV myocardial fibrosis in 88% of cases. Segmental wall motion abnormalities correlated strongly with the degree of enhancement. Myocardial enhancement was associated with conduction abnormalities. Sixty-nine percent of our asymptomatic or mildly symptomatic patients showed mild ventricular dilatation, systolic failure or both in global ventricular analysis. Decreased longitudinal systolic LV function was observed in 53% of patients. CONCLUSIONS: Cardiac conduction abnormalities, mildly dilated LV and depressed systolic dysfunction are common in DCM caused by a lamin A/C gene mutation. However, other cardiac diseases may produce similar symptoms. CMR is an accurate tool to determine the typical cardiac involvement in lamin A/C cardiomyopathy and may help to initiate early treatment in this malignant familiar form of DCM.

Serum lipidomics meets cardiac magnetic resonance imaging: profiling of subjects at risk of dilated cardiomyopathy.

Dilated cardiomyopathy (DCM), characterized by left ventricular dilatation and systolic dysfunction, constitutes a significant cause for heart failure, sudden cardiac death or need for heart transplantation. Lamin A/C gene (LMNA) on chromosome 1p12 is the most significant disease gene causing DCM and has been reported to cause 7-9% of DCM leading to cardiac transplantation. We have previously performed cardiac magnetic resonance imaging (MRI) to LMNA carriers to describe the early phenotype. Clinically, early recognition of subjects at risk of developing DCM would be important but is often difficult. Thus we have earlier used the MRI findings of these LMNA carriers for creating a model by which LMNA carriers could be identified from the controls at an asymptomatic stage. Some LMNA mutations may cause lipodystrophy. To characterize possible effects of LMNA mutations on lipid profile, we set out to apply global serum lipidomics using Ultra Performance Liquid Chromatography coupled to mass spectrometry in the same LMNA carriers, DCM patients without LMNA mutation and controls. All DCM patients, with or without LMNA mutation, differed from controls in regard to distinct serum lipidomic profile dominated by diminished odd-chain triglycerides and lipid ratios related to desaturation. Furthermore, we introduce a novel approach to identify associations between the molecular lipids from serum and the MR images from the LMNA carriers. The association analysis using dependency network and regression approaches also helped us to obtain novel insights into how the affected lipids might relate to cardiac shape and volume changes. Our study provides a framework for linking serum derived molecular markers not only with clinical endpoints, but also with the more subtle intermediate phenotypes, as derived from medical imaging, of potential pathophysiological relevance.

The annual costs associated with human papillomavirus types 6, 11, 16, and 18 infections in Finland.

OBJECTIVES: It is known that infections with human papillomavirus (HPV) types 6, 11, 16, and 18, cause cervical cancers (CC), cervical intraepithelial neoplastic lesions (types 1 to 3; CIN 1-3), and genital warts (GW). Together with equivocal cytological abnormalities (ECA), these place a considerable burden on society, but the costs and resource usage are not easily estimated. Therefore, we undertook this study to estimate the burden and costs associated with HPV-related diseases. METHODS: We used Finnish registry-based data for CC, CIN 1-3 and ECA. Data on GW were estimated from associated procedures and medications. The annual burden of disease was estimated from hospitalizations, visits to specialists and primary level care, and pharmaceutical use. The evaluation of costs included health care and screening costs, and productivity lost (separately). Due to the data obtained being fragmented, 2 cost scenarios were constructed. RESULTS: The follow-up of ECA appears to be the most important cost driver. GW should not be underestimated as they affect both genders at an early age. CONCLUSIONS: HPV infections are a burden to society, not only as a result of cancer-related costs, but also costs related to other diseases and indirect costs in the form of lost productivity.

Pregnancy and childbirth in carriers of the lamin A/C-gene mutation.

This retrospective case report describes 11 pregnancies in five women. All of the women were carriers of the lamin A/C gene mutation known to cause dilated cardiomyopathy, often together with atrioventricular conduction disturbances. The penetrance of these mutations is age-dependent but almost complete. We found no major adverse effects or worsening in the cardiac condition during or after the pregnancy in these patients. All babies were healthy except for one with a small ventricular septal defect, one diagnosed with tracheobronchomalasia, and one with a patent ductus arteriosus. None of these defects have been associated with lamin A/C mutations.