Finnish Medicines Agency Research Articles

TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer’s disease

IntroductionA better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an...

Detecting epinephrine auto-injector shortages in Finland 2016-2022: Log-data analysis of online information seeking.

Medicine shortages prevail as a worldwide problem causing life-threatening situations for adults and children. Epinephrine auto-injectors are used for serious allergic reactions called anaphylaxis, and alternative auto-injectors are not always available in pharmacies. Healthcare professionals in Finland use the dedicated internet source, Physician's Database (PD), when seeking medical information in practice, while Health Library (HL) provides health information for citizens (S1 Data). The objectives were to assess whether (1) professionals' searches for epinephrine auto-injectors and (2) citizens' anaphylaxis article openings relate to epinephrine shortages in Finland. Monthly log data on epinephrine auto-injectors (EpiPen®, Jext®, Emerade®) from PD and on openings of anaphylaxis articles from HL were collected during 2016-2022. Professionals' searches of seven auto-injectors and citizens' openings of four anaphylaxis articles were compared to information on epinephrine shortages reported by Finnish Medicines Agency. Professionals' auto-injector prescriptions provided by Social Insurance Institution were also assessed. Total searches in EpiPen® (N = 111,740), Jext® (N = 25,631), and Emerade® (N = 18,329) could be analyzed during 2016-2022. EpiPen® only could visually show seasonal patterns during summertime, peaking vigorously in the summer of 2018 when the major EpiPen® shortage appeared worldwide. Anaphylaxis articles equaled 2,030,855 openings altogether. Openings of one anaphylaxis article ("Bites and Stings") peaked during summertime, while another article ("Anaphylactic Reaction") peaked only once (three-fold increase) at the end of 2020 when COVID-19 vaccinations started, and auto-injector prescriptions were lowest. Fifty EpiPen®, one Jext®, and twelve Emerade® shortages were reported. Almost a two-fold increase in peaks of auto-injector prescriptions was found during summertime. This study shows that (1) epinephrine shortages related to professionals' searching for auto-injectors, and (2) citizens' information seeking on anaphylaxis related to summertime and shortages with lesser prescriptions. Therefore, the dedicated internet databases aimed at professionals and citizens could be used as additional information sources to detect anaphylactic reactions and auto-injector shortages.

PET imaging of unruptured intracranial aneurysm inflammation (PET-IA) study: a feasibility study protocol

IntroductionPositron emission tomography (PET) imaging can be used to evaluate arterial wall inflammation in extracranial vascular diseases. However, the application of PET imaging in unruptured intracranial aneurysms (UIA) remains unexplored....

Barriers to vaccine acceptance in the adult population of mainland Finland, 2021.

There has been a lack of information on vaccine acceptance for Finnish adults. We conducted a secondary analysis of cross-sectional data collected through the Finnish Medicines Agency Medicine Barometer 2021 survey (response rate: 20.6%). We described and explained vaccine acceptance by investigating the associations between socio-demographic factors and statements using logistic regression and conducted a factor analysis. The majority of respondents (n=2081) considered vaccines to be safe (93%), effective (97%), and important (95%). However, 20% and 14% felt they did not have enough information about vaccines and vaccine-preventable diseases (VPDs), respectively. Respondents aged 18-39 were 2.8 times more likely to disagree that they had enough information about VPDs compared to respondents aged 60-79 (p<0.001), while respondents with poorer self-perceived health were 1.8 times more likely to declare not having enough information about vaccines (p<0.001). We generated three-factor dimensions from the eight statements. They were related to 'Confidence and attitudes towards vaccines', 'Access to information on vaccines and VPDs', and 'Debate on vaccine issues', which may reflect the underlying thinking patterns. Access to and understanding of information about vaccines and VPDs need to be improved for Finnish adults to increase vaccine acceptance and uptake, thus preventing the spread of VPDs.

Cost-effectiveness model of trastuzumab deruxtecan as second-line treatment in HER2-positive unresectable and/or metastatic breast cancer in Finland

ObjectivesTrastuzumab deruxtecan (T-DXd) was recently recommended by the Committee for Medicinal Products for Human Use as a treatment for adult patients with unresectable or metastatic HER2-positive breast cancer, who had received a prior anti-HER2-based regimen. In our study, we evaluated the cost-effectiveness of T-DXd compared with ado-trastuzumab emtansine (T-DM1) for this indication in Finland.MethodsA three-state partitioned survival analysis model was developed with a payer’s perspective. Time to event data from the DESTINY-Breast03 (DB-03) trial were extrapolated over a lifetime horizon either directly—for progression-free survival and time to treatment discontinuation—or using an alternative approach utilizing long-term T-DM1 survival data and DB-03 data—for overall survival. Discount rates of 3% were applied for costs and effects. Inputs were sourced from the Medicinal Products Database from Kela, Helsinki University Hospital service price list, Finnish Medicines Agency assessments, clinical experts, and DB-03. Sensitivity analyses were performed to characterize and demonstrate parameter uncertainties in the model.ResultsTotal quality-adjusted life years (QALYs) and life years (LYs) gained for T-DXd compared with T-DM1 were 1.93 and 2.56, respectively. Incremental costs for T-DXd compared with T-DM1 were €106,800, resulting in an ICER of €55,360 per QALY gained and an ICER of €41,775 per LY gained. One-way sensitivity analysis showed the hazard ratio of T-DXd vs T-DM1 for OS was the most influential parameter. The probabilistic sensitivity analysis showed similar results to the base case.ConclusionsT-DXd is cost-effective based on surrogate WTP thresholds of €72,000 and €139,000 per QALY.

Regional variation of potentially inappropriate medication use and associated factors among older adults: A nationwide register study

BackgroundCertain medications should be used with caution in older persons, which challenges rational prescribing. Potentially inappropriate medications (PIMs) are defined as medicines whose potential risk of harm typically outweighs the clinical benefits in geriatric population. Earlier studies have found regional differences in PIM use, but the factors underlying this phenomenon are unclear. ObjectiveTo compare prescription PIM prevalence among Finnish hospital districts and determine which population characteristics and factors related to social and health care are associated with regional variation. MethodsThis nationwide register study was based on the Prescription Centre data on all people aged ≥75 years in 2017–2019. Hospital district (n = 20) characteristics were drawn from the Finnish Institute for Health and Welfare's, Finnish Medical Association's, and Finnish Medicines Agency's publicly open data. PIMs were defined according to the Finnish Meds75+ database. A linear mixed-effect model was used to analyze potential associations of regional characteristics with PIM prevalence. ResultsPrevalence of PIMs varied between 16.4% and 24.8% across regions. The highest prevalence was observed in the southern regions, while the lowest prevalence was on the west coast. Hospital district characteristics associated with higher PIM prevalence were higher share of population living alone, with excessive polypharmacy, or assessed using the Resident Assessment Instrument, shortage of general practitioners in municipal health centers, and low share of home care personnel. Waiting time in health care or share of population with morbidities were not associated with PIM use. Of the total variance in PIM prevalence, 86% was explained by group-level factors related to hospital districts. The regional variables explained 75% of this hospital-district-level variation. ConclusionsPIM prevalence varied significantly across hospital districts. Findings suggest that higher PIM prevalence may be related to challenges in the continuity of care rather than differences in health care accessibility or share of the population with morbidities.

Medical device regulation (MDR) in health technology enterprises – perspectives of managers and regulatory professionals

BackgroundIn the European Union (EU), there are over half a million medical devices, varying from pacemakers to software. Medical devices play an important role in health care as they are used in diagnosis, prevention, monitoring, prediction, prognosis, treatment, or to alleviate disease. Medical devices are regulated in the EU by the Medical Device Regulation (MDR), which came into force on 25 April 2017 and into application on 26 May 2021. The demand for regulation arose from the need to establish a transparent, robust, predictable, and sustainable regulatory framework. This study aims to examine how the managers and regulatory professionals in health technology enterprises perceived the application of the MDR and what were their information needs regarding the MDR.MethodsA link to an online questionnaire was sent to 405 managers and regulatory professionals representing health technology enterprises in Finland. The study included 74 respondents. Descriptive statistics were used to describe and summarise the characteristics of the dataset.ResultsInformation related to the MDR was fragmented and the necessary information was sought from multiple information sources, while the Finnish Medicines Agency (Fimea) was regarded as the most important source of information and training provider. To some extent, the managers and regulatory professionals expressed their dissatisfaction with the performance of Fimea. The managers and regulatory professionals were not very familiar with the ICT systems provided by the EU. The size of an enterprise affected how many medical devices it manufactures and generally affected the views about the MDR.ConclusionsThe managers and regulatory professionals understood the role of the MDR regarding the safety and transparency of medical devices. The available information regarding the MDR did not properly fit the needs of users and there seemed to be a gap in information quality. The managers and regulatory professionals had some difficulties understanding the available information. Based on our findings, we believe it is paramount to evaluate the challenges faced by Fimea and how it could improve its performance. To some extent, the MDR is regarded as a burden for smaller enterprises. It is important to highlight the benefits of ICT systems and to develop them to better meet the information needs of enterprises.

Healthcare costs and mortality associated with serious fluoroquinolone-related adverse reactions.

The aim of this study was to estimate healthcare costs and mortality associated with serious fluoroquinolone‐related adverse reactions in Finland from 2008 to 2019. Serious adverse reaction types were identified from the Finnish Pharmaceutical Insurance Pool’s pharmaceutical injury claims and the Finnish Medicines Agency’s Adverse Reaction Register. A decision tree model was built to predict costs and mortality associated with serious adverse drug reactions (ADR). Severe clostridioides difficile infections, severe cutaneous adverse reactions, tendon ruptures, aortic ruptures, and liver injuries were included as serious adverse drug reactions in the model. Direct healthcare costs of a serious ADR were based on the number of reimbursed fluoroquinolone prescriptions from the Social Insurance Institution of Finland’s database. Sensitivity analyses were conducted to address parameter uncertainty. A total of 1 831 537 fluoroquinolone prescriptions were filled between 2008 and 2019 in Finland, with prescription numbers declining 40% in recent years. Serious ADRs associated with fluoroquinolones lead to estimated direct healthcare costs of 501 938 402 €, including 11 405 ADRs and 3,884 deaths between 2008 and 2019. The average mortality risk associated with the use of fluoroquinolones was 0.21%. Severe clostridioides difficile infections were the most frequent, fatal, and costly serious ADRs associated with the use of fluoroquinolones. Although fluoroquinolones continue to be generally well‐tolerated antimicrobials, serious adverse reactions cause long‐term impairment to patients and high healthcare costs. Therefore, the risks and benefits should be weighed carefully in antibiotic prescription policies, as well as with individual patients.

PMU69 Does the Finose Collaboration Improve Access in Sweden and Norway?

In 2017, three Nordic HTA agencies, Finnish Medicines Agency (Fimea), Norwegian Medicines Agency (NoMA) and the Swedish Dental and Pharmaceutical Benefits Agency (TLV), set up a collaborative network named FINOSE with the aim to write joint assessments. This collaboration was not developed for joint decision-making, but to align agreement on relative effectiveness and where appropriate, health economic impact of a new treatment. In June 2020, FINOSE prolonged this collaboration for an additional three years. In this review study, all available completed FINOSE joint assessments were included and compared to the status of national assessments in Sweden and Norway. Until May 2020, three joint assessments have been published: enzalutamide, atezolizumab and betibeglogene autotemcel. NoMA and TLV authored two and three of the joint assessments, respectively. In the joint assessments FINOSE showed concerns regarding the clinical aspects, including small patient populations, immature data and the lack of long-term efficacy. Uncertainty in the economic aspects included treatment duration, quality of life data and achieved health benefit. These concerns were also reflected in TLV’s and NoMA’s national assessments. To complement the FINOSE report, NoMA (enzalutamide and atezolizumab) and TLV (enzalutamide, atezolizumab and betibeglogene autotemcel) reviewed national aspects such as cost analysis, budget consequences and patient estimates for local decision-making. TLV published their local decision simultaneously with the FINOSE report, whereas NoMA’s report came one to three months after FINOSE’s publication. To date, none of the treatments received a positive recommendation. However, betibeglogene autotemcel has been invited as the first treatment undergoing a joint Nordic contract negotiation. The FINOSE reports are used by national agencies to inform their decision-making and provides manufacturers with the opportunity to reduce duplication of submissions. Despite that the treatments did not receive a positive recommendation; it could potentially increase equal and faster access to Nordic patients in future collaborations.

Psychosis Relapse During Long-Acting Injectable Antipsychotic Treatment: An Individual Participant Data Meta-Analysis of 19 Trials and 5,111 Individuals with Schizophrenia-Spectrum Disorders

Background: Most individuals with schizophrenia-spectrum disorders experience relapses, which increases the risk of morbidity and mortality. Since non-adherence with antipsychotic maintenance treatment may affect up to half of individuals, psychosis relapse can often be confounded by unnoticed treatment interruption. Research of relapse during confirmed antipsychotic exposure has basic clinical and neurobiological implications, yet data are limited. Methods: Systematic review and individual participant data meta-analysis (IPDMA) of clinical trials of long-acting injectable antipsychotics (LAIs) for psychosis relapse-prevention, following IPD-PRISMA guidelines. Datasets were identified by searching relevant repositories up to August/01/2019. Each LAI arm was re-analyzed as a separate cohort, further identifying sub-cohorts of individuals with and without prospectively determined symptom remission (PSR). Pooled incidence rates, incidence rate ratios (IRRs) and hazard ratios (HRs) were derived from within-cohort Poisson, Kaplan-Meyer and Cox regression analyses. Outcomes: Nineteen treatment cohorts (n=5,111), of which 2,938 had PSR, while 2,173 did not (non-PSR), with 3,959·53 actual observed participant years were meta-analyzed. Pooled incidence of relapse was 22·97 per 100 patient-years, being 14·76 per 100 patient-years for the PSR sub-cohort and 31·51 per 100 patient-years for the non-PSR sub-cohort (IRR=0·39, 95%CI=0.29-0·53). The strongest predictors of relapse were having tardive dyskinesia (HR=2·39, 95%CI=1·05-5·42) and comorbid substance use disorder (HR=1·55, 95%CI=1·15-2·10) at treatment onset. Predictors were similar between the PSR and non-PSR sub-cohorts, except for greater impact of substance use disorder in PSR (p<0·01). Interpretation: A sizeable proportion of individuals with schizophrenia-spectrum disorders relapses during confirmed antipsychotic treatment. This risk doubles in individuals not achieving symptom remission, but even in remitted patients, 1 out of 7 patients relapsed in <1 year. Developing tardive dyskinesia and comorbid substance use may have pathophysiological implications for relapse on confirmed antipsychotic treatment. Funding Statement: This study was funded by Northwell Health. Declaration of Interests: Dr Rubio has been a consultant or has received speaker honoraria from: Lundbeck, Teva. He has also received royalties from UpToDate, and grant support from Alkermes. Dr Tiihonen reports personal fees from the Finnish Medicines Agency (Fimea), European Medicines Agency (EMA), Eli Lilly, JanssenCilag, Lundbeck, and Otsuka; is a member of advisory board for Lundbeck, and has received grants from the Stanley Foundation and Sigrid Juselius Foundation. Dr Taipale reports personal fees from JanssenCilag. Dr. Tiihonen and Dr. Taipale have participated in research projects funded by grants from JanssenCilag and Eli Lilly to their employing institution. Dr Malhotra has served as a consultant for Forum Pharmaceuticals and has served on a scientific advisory board for Genomind, Inc. Dr. Correll has been a consultant and/or advisor to or has received honoraria from: Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva. He has provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Rovi, Supernus, and Teva. He received royalties from UpToDate and grant support from Janssen and Takeda. He is also a stock option holder of LB Pharma. Dr Kane has been a consultant and/or advisor for or has received honoraria from Alkermes, Allergan , LB Pharmaceuticals, H. Lundbeck, Intracellular Therapies, Janssen Pharmaceuticals, Johnson and Johnson, Merck, Minerva, Neurocrine, Newron, Otsuka, Pierre Fabre, Reviva, Roche, Sumitomo Dainippon, Sunovion, Takeda, Teva and UpToDate and is a shareholder in LB Pharmaceuticals and Vanguard Research Group. Dr Schoretsanitis, John and Guinart declare no conflict of interest. Ethics Approval Statement: Each data owner obtained ethics committee approval prior to sharing the de-identified data.

Uporedna analiza upotrebe lekova u terapiji hiperlipoproteinemija u Republici Srbiji i Nordijskim zemljama u periodu 2015-2017. godine

Introduction: Cardiovascular diseases are the leading cause of death both in Serbia and in the rest of the world. It has been shown that as many as 80% of them are preventable. Control of serum lipid levels is one of the most important tasks of cardiovascular diseases prevention. Aim: The aim of the study was to analyze the use of serum lipid-modifying drugs in Serbia, Norway and Finland in the period 2015-2017. Methods: Data on drugs use during 2015, 2016 and 2017 were taken from the official websites of national drug regulatory authorities: the Serbian Medicines and Medical Devices Agency, the Norwegian Institute of Public Health and the Finnish Medicines Agency. Use was expressed as DDD/1000 inhabitants/day according to the Anatomical Therapeutic Chemical classification. Results: The share of drugs used for treatment of cardiovascular diseases in total drugs use was the largest in all three countries during the observed period. The use of lipidmodifying agents was 3-4 times lower in Serbia than in Norway or Finland. Of all lipidmodifying drugs, statins are most commonly prescribed in all three countries. Atorvastatin and rosuvastatin are the most widely used in Serbia, and simvastatin and atorvastatin in Norway and Finland. Conclusions: Use of lipid-modifying drugs in Serbia is lower than in Norway and Finland, but it is constantly increasing. This use in Serbia still represents the smallest share of all drugs for the treatment of cardiovascular diseases.

An inventory of collaborative medication reviews for older adults - evolution of practices

BackgroundCollaborative medication review (CMR) practices for older adults are evolving in many countries. Development has been under way in Finland for over a decade, but no inventory of evolved practices has been conducted. The aim of this study was to identify and describe CMR practices in Finland after 10 years of developement.MethodsAn inventory of CMR practices was conducted using a snowballing approach and an open call in the Finnish Medicines Agency’s website in 2015. Data were quantitatively analysed using descriptive statistics and qualitatively by inductive thematic content analysis. Clyne et al’s medication review typology was applied for evaluating comprehensiveness of the practices.ResultsIn total, 43 practices were identified, of which 22 (51%) were designed for older adults in primary care. The majority (n = 30, 70%) of the practices were clinical CMRs, with 18 (42%) of them being in routine use. A checklist with criteria was used in 19 (44%) of the practices to identify patients with polypharmacy (n = 6), falls (n = 5), and renal dysfunction (n = 5) as the most common criteria for CMR. Patients were involved in 32 (74%) of the practices, mostly as a source of information via interview (n = 27, 63%). A medication care plan was discussed with the patient in 17 practices (40%), and it was established systematically as usual care to all or selected patient groups in 11 (26%) of the practices. All or selected patients’ medication lists were reconciled in 15 practices (35%). Nearly half of the practices (n = 19, 44%) lacked explicit methods for following up effects of medication changes. When reported, the effects were followed up as a routine control (n = 9, 21%) or in a follow-up appointment (n = 6, 14%).ConclusionsDifferent MRs in varying settings were available and in routine use, the majority being comprehensive CMRs designed for primary outpatient care and for older adults. Even though practices might benefit from national standardization, flexibility in their customization according to context, medical and patient needs, and available resources is important.

Prospective multicentre cohort trial on acute appendicitis and microbiota, aetiology and effects of antimicrobial treatment: study protocol for the MAPPAC (Microbiology APPendicitis ACuta) trial

IntroductionBased on the epidemiological and clinical data, acute appendicitis can present either as uncomplicated or complicated. The aetiology of these different appendicitis forms remains unknown. Antibiotic therapy has been shown...

A randomised placebo-controlled double-blind multicentre trial comparing antibiotic therapy with placebo in the treatment of uncomplicated acute appendicitis: APPAC III trial study protocol

IntroductionRecent studies show that antibiotic therapy is safe and feasible for CT-confirmed uncomplicated acute appendicitis. Spontaneous resolution of acute appendicitis has already been observed over a hundred years ago. In...

Adherence to Psychotropic Medication in Completed Suicide in Sweden 2006-2013: A Forensic-Toxicological Matched Case-Control Study

Background: The aim of the study was to investigate how incomplete adherence to psychotropic medication influences the risk of completed suicide by comparing person-level information regarding dispensed prescriptions and postmortem toxicological findings among complete-suicide cases and non-suicide controls in Sweden 2006-2013. Method: Using national registries with full coverage on dispensed prescriptions, results of medico-legal autopsies, causes of death, diagnoses from inpatient care and continuous drug use, estimated by the prescription-based algorithm PRE2DUP, psychotropic drug use was compared with forensic-toxicological findings for 30 commonly prescribed psychotropic medications. Subjects who had died by suicide (cases) were matched (1:2) with subjects who had died from other causes (controls) for age, sex, and year of death. Odds ratios were calculated using logistic regression to estimate risk of completed suicide conferred by partial adherence and non-adherence to pharmacotherapy. Adjustments were made for previous inpatient psychiatric and somatic care, and ratio of initiated and discontinued prescriptions prior to death. Outcome: In data from autopsies performed in 5294 suicide cases and 9879 non-suicide controls, dispensation ratios for psychotropic medications (postulated as a measure of continued need of treatment) increased in cases, yet decreased in controls, the months prior to death. After adjustments for the ratio and other covariates, partial adherence and non-adherence to antipsychotics were associated with 6·7-fold and 12·4-fold risks, respectively, of completed suicide. The effect sizes for antidepressants were smaller and not statistically significant. Interpretation: After adjustment for continued need of treatment, biochemically verified incomplete adherence to antipsychotic pharmacotherapy was associated with markedly increased risks of completed suicide. Funding Statement: The study has in part been funded by Psykiatrifonden. Funders of the study had no role in study design, data collection, analysis, and interpretation, or the writing of the report. The corresponding author had full access to all data and final responsibility for the decision to submit the report for publication. Declaration of Interests: HT, JT and AT have participated in research projects funded by Janssen-Cilag and Eli Lilly, with grants paid to the institution where they were employed. AT is a member of the JanssenCilag advisory board. JT has served as a consultant to the European Medical Agency and the Finnish Medicines Agency and has received lecture fees from Eli Lilly, Janssen-Cilag, Lundbeck, and Otsuka, and grants from the Stanley Foundation and the Sigrid Juselius Foundation. JF and TM have no conflict of interest. All studied pharmacological products in this paper were generic substances without exclusive ownership by any company. Ethics Approval Statement: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. In this registry-based postmortem study, all personal information was anonymized, rendering unnecessary the need for formal consent or ethical approval. The study was nonetheless reviewed and approved by the Regional Ethical Review Board in Stockholm (2013/1411‐31/5).

Oncograms Visualize Factors Influencing Long-Term Survival of Cancer Patients Treated with Adenoviral Oncolytic Immunotherapy

The first US Food and Drug Administration (FDA)- and EMA-approved oncolytic virus has been available since 2015. However, there are no markers available that would predict benefit for the individual patient. During 2007–2012, we treated 290 patients with advanced chemotherapy-refractory cancers, using 10 different oncolytic adenoviruses. Treatments were given in a Finnish Medicines Agency (FIMEA)-regulated individualized patient treatment program (the Advanced Therapy Access Program [ATAP]), which required long-term follow-up of patients, which is presented here. Focusing on the longest surviving patients, some key clinical and biological features are presented as “oncograms.” Some key attributes that could be captured in the oncogram are suggested to predict treatment response and survival after oncolytic adenovirus treatment. The oncogram includes immunological laboratory parameters assessed in peripheral blood (leukocytes, neutrophil-to-lymphocyte ratio, interleukin-8 [IL-8], HMGB1, anti-viral neutralizing antibody status), features of the patient (gender, performance status), tumor features (histological tumor type, tumor load, region of metastases), and oncolytic virus-specific features (arming of the virus). The retrospective approach used here facilitates verification in a prospective controlled trial setting. To our knowledge, the oncogram is the first holistic attempt to identify the patients most likely to benefit from adenoviral oncolytic virotherapy.

A national approach to medicines information research: A systematic review.

The Finnish Medicines Agency Fimea published the first National Medicines Information (MI) strategy in 2012. For the purpose of implementing the MI strategy into practice by the national MI Network, a comprehensive inventory of MI research in Finland was needed. To systematically review literature on MI research conducted in Finland by analyzing and classifying the studies, and identifying the gaps in MI research. Medline, Scopus and Medic databases were searched for peer-reviewed MI publications by using key word screening criteria. The search and extraction process followed PRISMA Guidelines and covered the period from January 2000 toJune 2016. Included studies were content analyzed according to MI practices identified, trends over time in research methodology and theory. Included publications (n = 126) applied a variety of research methods, most often cross-sectional surveys (n = 51, 40% of all studies), but more than half of the studies were qualitative (n = 68, 54%). Twelve were intervention studies of which 6 were randomized and had a control group. Studies were categorized into: patient counseling in different settings (n = 45); MI sources and needs of medicine users (n = 25); healthcare professionals' (HCPs) competence in patient counseling and pharmacotherapy (n = 25); MI sources and needs of HCPs (n = 23); MI education and literacy (n = 13); and MI policies and strategies (n = 3). Most of the studies were descriptive, and only 6 studies applied a theory. Regardless of some methodological pitfalls, MI research conducted in Finland since 2000 provides multifaceted understanding of MI practices and their development needs. Research should shift towards larger research lines having a stronger theory base and study designs to deepen the understanding of MI practices and behaviors, and effectiveness of MI in different healthcare settings. Future research should cover also the use of electronic MI sources and services which apply modern information technology to clinical decision making and medication reviews, national MI policy, MI literacy, MI needs of HCPs and consumers.

Real-world effectiveness of antipsychotic treatments among patients with schizophrenia and affective symptoms

IntroductionThe clinical distinction between schizophrenia and affective psychoses is often not clear-cut, and very little is known about the effectiveness of treatments among patients having both schizophrenia and affective symptoms.ObjectivesTo study the comparative real-world effectiveness of antipsychotic treatments among patients having schizophrenia and affective symptoms.MethodsWe studied the risk of all-cause rehospitalization during use of specific antipsychotics during 1996–2012 among all patients who had been previously hospitalized with both schizophrenia and mood disorder diagnoses in Finland since 1987 (n = 28,015). We linked nation-wide databases on hospitalization, mortality, and filled prescriptions. The primary analysis was within-individual analysis, in which each individual was used as his/her own control to eliminate selection bias. The effect of concomitant psychotropic medications, and the temporal orders of exposure and non-exposure periods were adjusted.ResultsWhen 22 specific antipsychotic treatments were compared with the most frequently used antipsychotic quetiapine, the lowest rehospitalization risks were observed during the treatment periods of olanzapine long-acting injection (LAI) (HR: 0.52; 95% CI: 0.34–0.80), risperidone LAI (0.67; 0.56–0.81), and clozapine (0.68; 0.63–0.74). The worst outcome was observed for periciazine (1.19; 0.96–1.48) and no antipsychotic use (1.09; 1.04–1.13).ConclusionsOlanzapine LAI, risperidone LAI, and clozapine use are associated with the lowest risk of rehospitalization among patients with schizophrenia and affective symptoms.Disclosure of interestJari Tiihonen has served as a consultant to The Finnish Medicines Agency Fimea, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, F. Hoffman-La Roche, Janssen-Cilag, Lundbeck, Organon, and Finnish Medicines Agency he has received fees for giving expert testimony to AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Otsuka and Pfizer lecture fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Novartis, Otsuka, Pfizer and grants from Stanley Foundation and Sigrid Jusélius Foundation. Tiihonen is a member of advisory boards for AstraZeneca, Eli Lilly, Janssen-Cilag, and Otsuka, and has research collaboration with Lilly and Janssen. Markku Lähteenvuo is a major shareholder and board member at Genomi Solutions ltd, a Finnish based bioinformatics company. He has also received research grants or awards from Boehringer-Ingelheim, and is working as a coordinator for a research project funded by the Stanley Foundation. Fabian Hoti and Pia Vattulainen are employed by EPID Research, which is a contract research organization that performs commissioned pharmacoepidemiological studies and thus its employees have been and currently are working in collaboration with several pharmaceutical companies. Antti Tanskanen and Heidi Taipale have participated in research projects funded by Janssen with grants paid to the Karolinska Institutet.

Adverse reactions of α2-adrenoceptor agonists in cats reported in 2003–2013 in Finland

ObjectiveTo describe suspected adverse drug reactions in cats associated with use of α2-adrenoceptor agonists. Study designRetrospective study. AnimalsA total of 90 cats. MethodsData were collected from reports on adverse reactions to veterinary medicines sent to the Finnish Medicines Agency during 2003–2013. All reports of suspected adverse reactions associated with use of α2-adrenoceptor agonists in cats were included. Probable pulmonary oedema was diagnosed based on post mortem or radiological examination, or presence of frothy or excess fluid from the nostrils or trachea. If only dyspnoea and crackles on auscultation were reported, possible pulmonary oedema was presumed. ResultsPulmonary oedema was suspected in 61 cases. Of these cats, 37 were categorised as probable and 24 as possible pulmonary oedema. The first clinical signs had been noted between 1 minute and 2 days (median, 15 minutes) after α2-adrenoceptor agonist administration. Many cats probably had no intravenous overhydration when the first clinical signs were detected, as either they presumably had no intravenous cannula or the signs appeared before, during or immediately after cannulation. Of the 61 cats, 43 survived, 14 died and for four the outcome was not clearly stated. Conclusions and clinical relevancePulmonary oedema is a perilous condition that may appear within minutes of an intramuscular administration of sedative or anaesthetic agent in cats. The symptoms were not caused by intravenous overhydration, at least in cats having no venous cannula when the first clinical signs were detected.

Towards interprofessional networking in medication management of the aged: current challenges and potential solutions in Finland

Objective: The Finnish Medicines Agency (Fimea) initiated a programme in 2012 for enhancing interprofessional networking in the medication management of the aged. The goal is to develop national guidelines for interprofessional collaboration with respect to medication management. This study aims to explore the challenges and potential solutions experienced by existing health care teams in managing medication of the aged: (1) at the individual and team level (micro level), (2) organisational level (meso level) and (3) structural level (macro level).Design: Group discussions (n = 10), pair (n = 3) and individual interviews (n = 2). Abductive content analysis combining data and theory was applied. Networking was used as a theoretical framework.Setting: Meetings (n = 15) organised by Fimea in the formation phase of the interprofessional network in 2012.Subjects: Health care professionals (n = 55).Main outcome measures: Challenges and solutions in the medication management of the aged at the micro, meso and macro levels.Results: Challenges in interprofessional collaboration, problems with patient record systems, and the organisation of work and lack of resources were present at all the levels contributing to patients’ medication problems. Participants suggested multiple potential solutions to improve interprofessional collaboration, sharing of tasks and responsibilities, better exploitation of pharmaceutical knowledge and developing tools as being the most commonly mentioned.Conclusions: Optimising medication use of the aged requires new systemic solutions within and between different system levels. The main challenges can be solved by clarifying responsibilities, enhancing communication and applying operational models that involve pharmacists and the use of information technology in medication management.KEY POINTSAn interprofessional team approach has been suggested as a solution to promote rational medicine use among the aged.Fragmented health care system and lack of coordinated patient care are reasons for medication related problems of the aged.Challenges in the implementation of interprofessional collaboration in medication management appear in legislation, information systems, operational models and individuals’ attitudes.Optimising medications requires better interprofessional networking and new systemic solutions within and between macro, meso and micro levels.