Outpatient antibiotic prescribing during the first two years of the COVID-19 pandemic: A nationwide register-based time series analysis.

The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. Simultaneously, many countries have reported a decrease in the incidence of other infectious diseases, such as acute respiratory infections, leading to a decline in outpatient antibiotic use. The aim of this study is to assess the impact of the COVID-19 pandemic on outpatient antibiotic prescribing in Finland during the first 2 years of the pandemic. We used nationwide register data, applied descriptive methods, and conducted an interrupted time series analysis (ITSA) using ARIMA modelling. Results from the ARIMA modelling showed that at the baseline, before the pandemic, the level of monthly number of antibiotic prescriptions was 248,560 (95% CI: 224,261 to 272,856; p<0.001) and there was a decreasing trend of 1,202 in monthly number of prescriptions (95% CI: -2,107 to -262; p<0.01). After the COVID-19 pandemic began, there was a statistically significant decline of 48,470 (95% CI: -76,404 to -20,535, p<0.001) prescriptions (-19.5% from the baseline level). The greatest decrease in antibiotic prescribing was observed among children aged 0-17 years. While antibiotic prescribing declined in all antibiotic groups associated with respiratory tract infections, the decrease from 2019 to 2020 was the largest with azithromycin (52.6%), amoxicillin (44.8%), and doxycycline (43.8%). Future studies should continue exploring antibiotic prescribing trends during the COVID-19 pandemic and beyond.

Uptake and availability of new outpatient cancer medicines in 2010-2021 in Nordic countries - survey of competent authorities.

BACKGROUND: Nordic countries excel in cancer care, but studies on uptake, costs, or managed entry agreements of cancer medicines have not been conducted recently. The aim of this study was to examine the uptake and availability of orally administered new cancer medicines in Nordic countries. Orally administered cancer medicines enable and are used in the community as part of outpatient care. Firstly, we studied the distribution, costs and adoption of managed entry agreements of these medicines, and secondly, uptake of and managed entry agreements for cancer medicines used in outpatient care that were granted marketing authorization in Europe in 2010-2021. METHODS: An E-mail survey of competent authorities, meaning pharmaceutical service organizers, payers or other government or non-government actors developing pharmaceutical service operations, in Denmark, Finland, Iceland, Norway, and Sweden in April-June 2022. The data were analysed using frequencies and percentages for descriptive analysis. RESULTS: The distribution of cancer medicines has similarities in Finland, Iceland, Norway, and Sweden, where cancer medicines can be distributed both via hospitals or hospital pharmacies for inpatient use, and via community pharmacies for outpatient use. In Denmark, cancer medicines are predominantly distributed via publicly funded hospitals. In all countries that provided data on the costs, the costs of cancer medicines had notably gone up from 2010 to 2021. The number of reimbursable medicines out of new cancer medicines varied from 36 products in Denmark and Iceland to 51 products in Sweden, out of 67 studied products. Managed entry agreements, often with confidential discounts, were in use in all Nordic countries. The number of agreements and the cancer types for which agreements were most often made varied from three agreements made in Iceland to 35 agreements made in Finland, out of 67 studied products. Average days from authorization to reimbursement of new cancer medicines varied from an average of 416 to 895 days. CONCLUSIONS: Nordic countries share similar characteristics but also differ in terms of the details in distribution, adopted managed entry agreements, market entry, and availability of new orally administered cancer medicines used in the outpatient care. The costs of cancer medicines have increased in all Nordic countries during the last decade. Due to differences in health care and because orally administered cancer medicines can be dispensed at community and hospital pharmacies in all studied countries other than Denmark, the number of reimbursable medicines and managed entry agreements vary between countries. However, Nordic countries show good agreement for 2010 to 2021 in entry and reimbursement decisions of novel cancer medicines.

Medicine shortages: Product life cycle phases and characteristics of medicines in short supply-A register study.

Introduction: Product life cycle refers to all phases of a product from development to active market phase and finally the phase in which products possibly exit the market. The product life cycle of medicines in short supply has not been studied in depth, although there is some indication of mature products and products with lower prices and profit margins being exposed to shortages more often. The aim of this study was to examine the product life cycle phases and characteristics of medicines in short supply as well as the features of medicine shortages in Finland from 2017 to 2019. Material and methods: Register data on medicine shortages of human medicinal products from 2017 to 2019 was combined with timely data on marketing authorizations and reimbursement status to gain data on product life cycle phases and characteristics (e.g., the age and the reimbursement status) of medicines in short supply and the features of medicine shortages. The data were analyzed in descriptive manner using appropriate statistical testing. Results: 3,526 shortages were reported during the 3-year study period and the number of shortages increased annually. The average duration of a shortage was 83 days and shortages affected 660 active pharmaceutical ingredients. Most often, shortages occurred with medicines affecting the nervous system, the cardiovascular system, and the genitourinary system. A majority of shortages (n = 2,689) was reported in the reimbursable medicines group, where shortages increased as the number of patients receiving reimbursements increased (p < 0.001). In the reimbursable medicines group, shortages most commonly involved medicines aged 15-19, 20-24, and 25-29, whereas with both reimbursable and non-reimbursable products the shortages most often occurred in medicines aged 50-54. The frequency of shortages differed between the groups (p < 0.001) when both age and reimbursement status were taken into account. Conclusion: Medicine shortages are common and affect commonly used medicines. Product life cycle phase has an effect on the frequency of shortages: Reimbursable medicines and medicines exposed to changes in life cycle are more likely to face a shortage. The impacts of product life cycle on the availability of medicines and medicine shortages should be studied in more detail.

The comparative and objective measurement of health promotion capacity-building: from conceptual framework to operationalization.

The aim of this study was to analyse and test a theoretical generic health promotion capacity-building framework with empirical data on primary health care. The framework consists of seven dimensions: commitment, management, monitoring and needs assessment, resources, common practices, participation and other core functions. The data were collected in 2014 from all the health centres in Finland, of which 156 (99%) submitted their data. The data were scored by the quality of activities on a scale from 0 to 100, where 100 stands for desirable quality. Individual indicators were nested into subdimensions, which in turn were nested into the dimensions of the theoretical framework. Variables were clustered using the dimensions and subdimensions as initial partitions. The internal consistency of dimensions and subdimensions was tested with standardized Cronbach's alpha both before and after the clustering analysis. The results showed that although the internal consistency of the dimensions was high in the initial classification, it is possible to get even more consistent dimensions. The internal consistency of the initial classification varied from 0.62 in participation to 0.93 in common practices. In the clustering analysis, 45 out of 203 indicators were assigned to a dimension different from the initial partition. The biggest gain in internal consistency was achieved in the subdimension of systematic mass communications by relocating two indicators. This study suggests that it is possible to assess the health promotion capacity-building of organizations in a coherent way with comparable and objective indicators. These analyses also show that the number of indicators can be reduced. It would be interesting to see how the framework works in other governmental structures or political contexts.

Short-term effects of the "Together at School" intervention program on children's socio-emotional skills: a cluster randomized controlled trial.

BACKGROUND: Together at School is a universal intervention program designed to promote socio-emotional skills among primary-school children. It is based on a whole school approach, and implemented in school classes by teachers. The aim of the present study is to examine the short-term effects of the intervention program in improving socio-emotional skills and reducing psychological problems among boys and girls. We also examine whether these effects depend on grade level (Grades 1 to 3) and intervention dosage. METHODS: This cluster randomized controlled trial design included 79 Finnish primary schools (40 intervention and 39 control) with 3 704 children. The outcome measures were the Strengths and Difficulties Questionnaire (SDQ) and the Multisource Assessment of Social Competence Scale (MASCS) with teachers as raters. The intervention dosage was indicated by the frequencies six central tools were used by the teachers. The data was collected at baseline and 6 months later. Intervention effects were analyzed using multilevel modeling. RESULTS: When analyzed across all grades no intervention effect was observed in improving children's socio-emotional skills or in reducing their psychological problems at 6-month follow-up. Among third (compared to first) graders the intervention decreased psychological problems. Stratified analyses by gender showed that this effect was significant only among boys and that among them the intervention also improved third graders' cooperation skills. Among girls the intervention effects were not moderated by grade. Implementing the intervention with intended intensity (i.e. a high enough dosage) had a significant positive effect on cooperation skills. When analyzed separately among genders, this effect was significant only in girls. CONCLUSIONS: These first, short-term results of the Together at School intervention program did not show any main effects on children's socio-emotional skills or psychological problems. This lack of effects may be due to the relatively short follow-up period given the universal, whole school-based approach of the program. The results suggest that the grade level where the intervention is started might be a factor in the program's effectiveness. Moreover, the results also suggest that for this type of intervention program to be effective, it needs to be delivered with a high enough dosage. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02178332 ; Date of registration: 03-April-2014.

Time Series Analysis on the Impact of Generic Substitution and Reference Pricing on Antipsychotic Costs in Finland.

OBJECTIVES: To analyze the medium- to long-term impact of generic substitution and the reference price system on the daily cost of antipsychotics in Finland. The additional impact of reference pricing over and above previously implemented generic substitution was also assessed. METHODS: An interrupted time series design with a control group and segmented regression analysis was used to estimate the effect of the implementation of generic substitution and the reference price system on the daily cost of antipsychotics. The data have 69 monthly values of the average daily cost for each of the studied antipsychotics: 39 months before and 30 months after the introduction of reference pricing. For one of the studied antipsychotic, the time before the introduction of reference pricing could be further divided into time before and after the introduction of generic substitution. RESULTS: According to the model, 2.5 years after the implementation of reference pricing, the daily cost of the studied antipsychotics was 24.6% to 50.6% lower than it would have been if reference pricing had not been implemented. Two and a half years after the implementation of the reference price system, however, the additional impact of reference pricing over and above previously implemented generic substitution was modest, less than 1 percentage point. CONCLUSIONS: Although the price competition induced by reference pricing decreased the prices of antipsychotics in Finland in the short-term, the prices had a tendency to stagnate or even to turn in an upward direction in the medium- to long-term. Furthermore, the additional impact of reference pricing over and above previously implemented generic substitution remained quite modest.

"Together at school"--a school-based intervention program to promote socio-emotional skills and mental health in children: study protocol for a cluster randomized controlled trial.

BACKGROUND: Schools provide a natural context to promote children's mental health. However, there is a need for more evidence-based, high quality school intervention programs combined with an accurate evaluation of their general effectiveness and effectiveness of specific intervention methods. The aim of this paper is to present a study protocol of a cluster randomized controlled trial evaluating the "Together at School" intervention program. The intervention program is designed to promote social-emotional skills and mental health by utilizing whole-school approach and focuses on classroom curriculum, work environment of school staff, and parent-teacher collaboration methods. METHODS/DESIGN: The evaluation study examines the effects of the intervention on children's socio-emotional skills and mental health in a cluster randomized controlled trial design with 1) an intervention group and 2) an active control group. Altogether 79 primary school participated at baseline. A multi-informant setting involves the children themselves, their parents, and teachers. The primary outcomes are measured using parent and teacher ratings of children's socio-emotional skills and psychological problems measured by the Strengths and Difficulties Questionnaire and the Multisource Assessment of Social Competence Scale. Secondary outcomes for the children include emotional understanding, altruistic behavior, and executive functions (e.g. working memory, planning, and inhibition). Secondary outcomes for the teachers include ratings of e.g. school environment, teaching style and well-being. Secondary outcomes for both teachers and parents include e.g. emotional self-efficacy, child rearing practices, and teacher-parent collaboration. The data was collected at baseline (autumn 2013), 6 months after baseline, and will be collected also 18 months after baseline from the same participants. DISCUSSION: This study protocol outlines a trial which aims to add to the current state of intervention programs by presenting and studying a contextually developed and carefully tested intervention program which is tailored to fit a national school system. Identification of effective intervention elements to promote children's mental health in early school years is crucial for optimal later development. TRIAL REGISTRATION: ClinicalTrials.gov register: NCT02178332.

The impact of reference pricing and extension of generic substitution on the daily cost of antipsychotic medication in Finland.

OBJECTIVE: To assess the impact of reference pricing and extension of generic substitution on the daily cost of antipsychotic drugs in Finland during the first year after its launch. Furthermore, the additional impact of reference pricing on prior implemented generic substitution is assessed. METHODS: A retrospective analysis was performed between 2006 and 2010. A segmented linear regression analysis of interrupted time series was used to estimate changes in the levels and trends in the cost of one day of treatment. Of the study drugs, clozapine belonged to generic substitution already at the start of the study period while olanzapine and quetiapine were included in generic substitution alongside with reference pricing in 2009. Risperidone was included in generic substitution in 2008, before reference pricing. RESULTS: A substantial decrease in the daily cost of all four antipsychotic substances was seen after one year of the implementation of reference pricing and the extension of generic substitution. The impact ranged from -29.9% to -66.3%, and it was most substantial on the daily cost of olanzapine. Also in the daily cost of risperidone a substantial decrease of -43.3% was observed. However, most of these savings, -32.6%, were generated by generic substitution which had been adopted prior. CONCLUSIONS: Reference pricing and the extension of generic substitution produced substantial savings on antipsychotic medication costs during the first year after its launch, but the intensity of the impact differed between active substances. Furthermore, our results suggest that the additional cost savings from reference pricing after prior implemented generic substitution, are comparatively low.

Dual role of physical workload and occupational noise in the association of the metabolic syndrome with risk of coronary heart disease: findings from the Helsinki Heart Study.

OBJECTIVES: Previous evidence indicates that occupational exposure to physical workload or noise entails development of hypertension and risk of coronary heart disease (CHD). However, vigorous physical activity lessens the risks of the metabolic syndrome (MetS) and CHD. We explored this issue by studying the joint effect of physical workload or noise and MetS on risk of CHD. METHODS: This 18-year follow-up study comprised 1502 middle-aged men employed in industry who participated in the second screening for the Helsinki Heart Study but were not treated with gemfibrozil, the trial drug. The CHD endpoints (ICD-9 codes 410-414 and ICD-10 codes 120-125) were obtained from official Finnish registers. The Finnish job-exposure matrix FINJEM provided information on occupational exposures. The joint effect of baseline MetS levels and both occupational exposures was estimated using Cox's regression models. RESULTS: Workload and noise increased CHD risk due to increased blood pressure, glucose or body mass index (BMI), separately or combined: the joint effect of workload and MetS defined using these three components yielded an RR of 5.21 (95% CI 2.70 to 10.05). However, when MetS was defined using elevated BMI, high triglycerides and low high-density lipoprotein cholesterol, an RR of 2.19 (95% CI 1.11 to 4.30) among those with MetS only reduced to 1.20 (95% CI 0.61 to 2.35) if concurrently exposed to workload. CONCLUSIONS: Occupational exposure to workload or noise modifies CHD risk differently depending on which definition of MetS is used. In the presence of physical workload or noise, hypertension and blood glucose were the best predictors.

Future lung cancer incidence in Poland and Finland based on forecasts on hypothetical changes in smoking habits.

OBJECTIVE: the aim is to estimate the future lung cancer incidence in Poland and Finland based on forecasts on hypothetical changes in smoking habits. MATERIAL AND METHODS: data on population, lung cancer and smoking prevalence come from known sources. The simulation model utilized for forecasting was based on smoothing the smoking habit - specific risk ratios estimated for males and females in Europe. RESULTS: depending on the analyzed scenario in 2030 in Poland mortality rates among men would range from 8 to 125/10(5) and among women from 7 to 47/10(5); in Finland among men 5 to 60/10(5) and among women 4 to 22/10(5). CONCLUSIONS: the results obtained clearly indicate that cutting down on the number of smokers translates directly into a considerable reduction of the lung cancer incidence rate.

Impact of regulatory safety warnings on the use of antidepressants among children and adolescents in Finland.

OBJECTIVE: The aim of this study was to analyze changes in the prevalence and incidence of antidepressant use among children and adolescents in Finland post October, 2003. METHOD: The sample comprised all children and adolescents in Finland aged < or =19.0 years (n = 27,676) who collected one or more reimbursed prescriptions for an antidepressant in noninstitutional and nonhospital settings between January, 1998, and December, 2005. Time-series models were used to compare antidepressant use 60 months before and 24 months after the health advisory issued by the Food and Drug Administration (FDA) in October, 2003. RESULTS: The annual prevalence (users/1,000 youths) of antidepressant use increased from 5.24 in 2002 to 5.93 in 2005. There was an increase in the monthly incidence (users = 1,000 youths) of selective serotonin reuptake inhibitors (SSRIs) use (+0.02498), fluoxetine use (+0.00691), and sertraline use (+0.00727) post October, 2003. When considering preadvisory trends in antidepressant use, only fluoxetine use was higher than the predicted post October 2003, use (<0.001). The use of all other SSRIs was significantly lower than predicted. CONCLUSIONS: In contrast to many other countries, the use of antidepressants continued to increase among children and adolescents in Finland post October, 2003. While the rate of fluoxetine use increased, there was a decline in the rate at which all other SSRIs were used.

Antipsychotics and antidepressants: an analysis of cost growth in Finland from 1999 to 2005.

BACKGROUND: Antipsychotics and antidepressants are among the fastest-growing therapeutic classes, but the reasons behind recent cost growth are not clear. OBJECTIVE: The aim of this study was to assess the explicit factors behind ambulatory antipsychotic and antidepressant cost growth in Finland, as well as the relative importance of the factors associated with the drug group-specific cost growth. METHODS: The data used in this study were retrospectively collected from the Finnish National Health Insurance's register on reimbursed drug purchases. The study period ranged from January 1, 1999, through December 31, 2005, and the obtained data included information on the patient identity number, total cost of the purchase, Anatomic Therapeutic Chemical classification code of the purchased product, and defined daily dose amount of the purchase. Using the retrieved data, antipsychotic and antidepressant cost growth was disaggregated into price and volume factors to create a formula that includes factors about the size of the population, patients per population, volume of treatment per patient, and the mean cost per 1 day of treatment. The relative effect of the factors associated with the drug group-specific cost growth was also examined. Because the purpose of this work was to analyze the factors contributing to the cost growth, we disregarded factors that were negative. RESULTS: During the study period, the proportion of antipsychotic users of the total population decreased from 2.4% to 2.2% and the mean cost per 1 day of treatment with antipsychotics increased from euro1.37 to euro2.94. The proportion of antidepressant users increased from 4.8% to 6.3%, and mean cost per 1 day of treatment decreased from euro1.06 to euro0.79. In 1999, the consumption of second-generation antipsychotics accounted for 22% of total consumption, and in 2005 their proportion was 62%. Drug choices among anti-depressants did not change substantially. The total cost growth of antipsychotics and antidepressants was 211% and 19%, respectively. Approximately 80% of the antipsychotic cost growth resulted from the rise in the mean cost per 1 day of treatment. The increase in patients per population accounted for approximately 60% of the antidepressant cost growth. CONCLUSION: This retrospective analysis found that the factors associated with the growing antipsychotic and antidepressant expenditures in Finland from 1999 through 2005 varied between these 2 drug classes.

Cost-effectiveness of implementing national guidelines in the treatment of acute otitis media in children.

OBJECTIVES: Acute otitis media (AOM) is one of the most common diseases of childhood, representing a major disease burden on the society. New evidence-based guidelines for AOM, focusing on children under 7 years of age, were introduced in Finland in 1999. The aim of this study was to evaluate the cost-effectiveness of implementing those guidelines in Finland. METHODS: A 5-year prospective trial was conducted in thirty community primary healthcare centers in Finland. All AOM patients between 0 and 6 years of age visiting the study health centers for the first time, for this episode of illness, during 1 week in November 1998 (n = 579) and November 2002 (n = 369) were included in this study. The outcome measure was the percentage of symptom-free patients. RESULTS: The mean direct cost of an AOM episode per patient stayed almost the same after implementing the guidelines, euro152 in 1998 and euro150 in 2002. After implementing the guidelines, the percentage of symptom-free patients was 10 percentage points higher than before the guidelines. The treatment after the implementation of the guidelines, thus, was a dominant strategy. CONCLUSIONS: Implementing the guidelines to the treatment of AOM in children was associated with extra health benefits at slightly lower direct costs and, thus, is a dominant strategy. The focus of this study was on the short-term effects of the treatment; including long-term effects in the analysis might affect the results.

Expanding screening for rare metabolic disease in the newborn: an analysis of costs, effect and ethical consequences for decision-making in Finland.

AIM: Currently, the only metabolic disorder that newborns are screened for in Finland is congenital hypothyroidism. A proposal to start a pilot study on screening for other rare metabolic diseases using tandem mass spectrometry prompted a health technology assessment project on the effect and costs of expanded newborn screening programme options. METHOD: A modelling study using data from current published studies, healthcare registers and expert opinion. RESULTS: The annual running cost of screening 56,000 newborns for the chosen five disorders (congenital adrenal hyperplasia, medium-chain acyl-CoA dehydrogenase deficiency [MCADD], long chain 3-hydroxyacyl-CoA dehydrogenase deficiency [LCHADD], phenylketonuria [PKU] and glutaric aciduria type 1 [GA 1]) was estimated to be euros 2.5 million or euros 45 per newborn when starting costs were included. The costs per quality-adjusted life year (QALY) gained are a maximum of euros 25,500. Prevention of severe handicap in one newborn would reduce the costs to a maximum of euros 18,000 per QALY gained. CONCLUSIONS: Expanding the Finnish neonatal screening programme would require a new organization. The cost-effectiveness, resources, ethics and equity need to be considered when deciding in favour of or against starting a new screening programme.