Abstract The aim of this doctoral thesis is to provide an overall description of Finnish adult asthma patients in the year 2000, including their symptoms, treatment and the resulting costs. The implementation of treatment was evaluated from the perspective adopted in the National Asthma Programme 1994–2004. The research was based on questionnaire data acquired from a sample extracted from the Finnish Social Insurance Institution's asthma register, with which existing register data were combined, so that the eventual series comprised patients suffering from asthma and possibly other chronic obstructive pulmonary diseases. The majority of the asthma patients were women of working age. Smoking was most common among young adults (43% of the men and 35% of the women), while the number who had stopped smoking increased towards the older age groups among the men but remained constant among the women. The older age groups also had more serious asthma, more frequent cases of other chronic pulmonary and somatic illnesses, more problems in coping with everyday life and greater treatment needs than the younger patients. Early retirement for health reasons was common. More than half of the women and one in five of the men aged 65 years or over were living alone. The patients who suffered from asthma alone normally managed relatively well. Their symptoms could be kept under control with anti-inflammatory medication at a moderate overall cost, but concurrent obstructive pulmonary disease almost tripled the direct cost of asthma treatment and increased hospital costs practically five-fold. Smoking led to further expense in the case of those with asthma and obstructive pulmonary disease combined. The transfer of responsibility for asthma treatment from specialized care to the basic health care system would appear in general to be justified. Smoking and its associated chronic obstructive pulmonary diseases present a particular challenge for the management of asthma. / Tiivistelmä Tässä väitöskirjatyössä tutkittiin suomalaisen aikuisen astmapotilaan kokonaiskuva ja selvitettiin hänen oireiluaan, hoitoaan ja tästä aiheutuvia kustannuksia vuonna 2000. Astman hoidon toteutumista arvioitiin Valtakunnallinen astmaohjelma 1994–2004:n näkökulmasta. Tutkimuksessa käytettiin Kelan astmarekisteristä valtakunnallisesti poimitun potilasotoksen kyselyaineistoa rekisteritietoja siihen yhdistäen. Lopullisen tutkimusaineiston muodostivat astmaa ja sen lisäksi mahdollisesti muita pitkäaikaisia ahtauttavia keuhkosairauksia sairastavat potilaat. Enemmistö astmapotilaista oli naisia ja työikäisiä. Tupakointi oli yleisintä nuorilla aikuisilla miehillä (43 %) ja naisilla (35 %). Tupakoinnin lopettaneiden osuus suureni miehillä vanhempiin ikäryhmiin mentäessä, kun taas naisilla osuus pysyi samansuuruisena. Vanhemmissa ikäryhmissä astma oli vaikeampaa ja muu keuhko- ja somaattinen pitkäaikaissairastavuus, toimintakyvyn ongelmaisuus ja hoidon tarve nuorempia runsaampaa. Ennenaikainen eläköityminen oli yleistä. Kuusikymmentäviisi vuotta täyttäneistä ja sitä vanhemmista naisista useampi kuin joka toinen ja miehistä joka viides asui yksin. Pelkkää astmaa sairastava voi yleisesti arvioiden hyvin. Hänen oireilunsa oli hallittavissa anti-inflammatorisella lääkityksellä kohtalaisen vähäisin kokonaishoidon kustannuksin. Samanaikainen keuhkoahtaumatauti lähes kolminkertaisti astman hoidosta aiheutuneet suorat kustannukset ja lähes viisinkertaisti sairaalahoidosta aiheutuneet kustannukset. Astmaa ja keuhkoahtaumatautia sairastavilla tupakointi lisäsi edelleen kustannuksia. Astmapotilaan kokonaisuuden näkökulmasta hoidon päävastuun siirto erikoissairaanhoidosta perusterveydenhuoltoon vaikuttaa tarkoituksenmukaiselta. Tupakointi ja siihen liittyvät muut pitkäaikaiset ahtauttavat keuhkosairaudet muodostavat erityisen haasteen astman hoitojärjestelmälle.

Background: Multimorbidity is defined as suffering from coexistent chronic conditions. Multimorbid patients demand highly complex patient-centered care which often includes polypharmacy, taking an average of six different drugs per day. Adverse drug reactions, adverse drug events and medication errors are all potential consequences of polypharmacy. Our study aims to detect the status quo of the health care situation in Saxony’s general practices for multimorbid patients receiving multiple medications. We will identify the most common clinical profiles as well as documented adverse drug events and reactions that occur during the treatment of patients receiving multiple medications. We will focus on exploring the motives of general practitioners for the prescription of selected drugs in individual cases where there is evidence of potential drug-drug-interactions and potentially inappropriate medications in elderly patients. Furthermore, the study will explore general practitioners’ opinions on delegation of skills to other health professions to support medical care and monitoring of patients receiving multiple medications. Methods/design: This is a retrospective cross sectional study using mixed methods. Socio-demographic data as well as diagnoses, medication regimens and clinically important events will be analyzed retrospectively using general practitioners documentation in patients’ records. Based on these data, short vignettes will be generated and discussed by general practitioners in qualitative telephone interviews. Discussion: To be able to improve outpatient health care management for patients receiving multiple medications, the current status quo of care, risk factors for deficient treatment and characteristics of concerned patients must be investigated. Furthermore, it is necessary to understand the physicians’ decision making process regarding treatment.

Background Polypharmacy is often prescribed for bipolar disorder, yet medication non-adherence remains a serious problem. This study investigated the regularity in the daily dosage taken of mood stabilizers and second generation antipsychotics. Methods Daily self-reported data on medications taken and mood were available from 241 patients with a diagnosis of bipolar disorder who received treatment as usual. Patients who took the same mood stabilizer or second generation antipsychotic for ≥ 100 days were included. Approximate entropy was used to determine serial regularity in daily dosage taken. Generalized estimating equations were used to estimate if demographic or clinical variables were associated with regularity. Results There were 422 analysis periods available from the 241 patients. Patients took drugs on 84.4% of days. Considerable irregularity was found, mostly due to single-day omissions and dosage changes. Drug holidays (missing 3 or more consecutive days) were found in 35.8% of the analysis periods. Irregularity was associated with an increasing total number of psychotropic drugs taken (p = 0.009), the pill burden (p = 0.026), and the percent of days depressed (p = 0.049). Conclusion Despite low missing percent of days, daily drug dosage may be irregular primarily due to single day omissions and dosage changes. Drug holidays are common. Physicians should expect to see partial adherence in clinical practice, especially with complex drug regimens. Daily dosage irregularity may impact the continuity of drug action, contribute to individual variation in treatment response, and needs further study.

Indiana University-Purdue University Indianapolis (IUPUI) / Polypharmacy is a general clinical practice, there is a high chance that multiple administered drugs will interfere with each other, such phenomenon is called drug-drug interaction (DDI). DDI occurs when drugs administered change each other's pharmacokinetic (PK) or pharmacodynamic (PD) response. DDIs in many ways affect the overall effectiveness of the drug or at some times pose a risk of serious side effects to the patients thus, it becomes very challenging to for the successful drug development and clinical patient care. Biomedical literature is rich source for in-vitro and in-vivo DDI reports and there is growing need to automated methods to extract the DDI related information from unstructured text. In this work we present an ontology (PK ontology), which defines annotation guidelines for annotation of PK DDI studies. Using the ontology we have put together a corpora of PK DDI studies, which serves as excellent resource for training machine learning, based DDI extraction algorithms. Finally we demonstrate the use of PK ontology and corpora for extracting PK DDIs from biomedical literature using machine learning algorithms.

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