Medicines information sources and services for consumers : A special focus on the Internet and people with depression

The range of consumer health and medicines information sources has diversified along with the increased use of the Internet. This has led to a drive to develop medicines information services and to better incorporate the Internet and e-mail into routine practice in health care and in community pharmacies. To support the development of such services more information is needed about the use of online information by consumers, particularly of those who may be the most likely to use and to benefit from the new sources and modes of medicines communication. This study explored the role and utilization of the Internet-based medicines information and information services in the context of a wider network of information sources accessible to the public in Finland. The overall aim was to gather information to develop better and more accessible sources of information for consumers and services to better meet the needs of consumers. Special focus was on the needs and information behavior among people with depression and using antidepressant medicines. This study applied both qualitative and quantitative methods. Consumer medicines information needs and sources were identified by analyzing the utilization of the University Pharmacy operated national drug information call center (Study I) and surveying Finnish adults (n=2348) use of the different medicines information sources (Study II). The utilization of the Internet as a source of antidepressant information among people with depression was explored by focus group discussions among people with depression and with current or past use of the antidepressant(s) (n=29, Studies III & IV). Pharmacy response to the needs of consumers in term of providing e-mail counseling was assessed by conducting a virtual pseudo customer study among the Finnish community pharmacies (n=161, Study V). Physicians and pharmacists were the primary sources of medicines information. People with mental disorders were more frequent users of telephone- and Internet-based medicines information sources and patient information leaflets than people without mental disorders. These sources were used to complement rather than replace information provided face-to-face by health professionals. People with depression used the Internet to seek facts about antidepressants, to share experiences with peers, and for the curiosity. They described that the access to online drug information was empowering. Some people reported lacking the skills necessary to assess the quality of online information. E-mail medication counseling services provided by community pharmacies were rare and varied in quality. Study results suggest that rather than discouraging the use of the Internet, health professionals should direct patients to use accurate and reliable sources of online medicines information. Health care providers, including community pharmacies should also seek to develop new ways of communicating information about medicines with consumers. This study determined that people with depression and using antidepressants need services enabling interactive communication not only with health care professionals, but also with peers. Further research should be focused on developing medicines information service facilitating communication among different patient and consumer groups.

Characterization of Ion-Exchange Fibers for Controlled Drug Delivery

Increasing attention has been focused on methods that deliver pharmacologically active compounds (e.g. drugs, peptides and proteins) in a controlled fashion, so that constant, sustained, site-specific or pulsatile action can be attained. Ion-exchange resins have been widely studied in medical and pharmaceutical applications, including controlled drug delivery, leading to commercialisation of some resin based formulations. Ion-exchangers provide an efficient means to adjust and control drug delivery, as the electrostatic interactions enable precise control of the ion-exchange process and, thus, a more uniform and accurate control of drug release compared to systems that are based only on physical interactions. Unlike the resins, only few studies have been reported on ion-exchange fibers in drug delivery. However, the ion-exchange fibers have many advantageous properties compared to the conventional ion-exchange resins, such as more efficient compound loading into and release from the ion-exchanger, easier incorporation of drug-sized compounds, enhanced control of the ion-exchange process, better mechanical, chemical and thermal stability, and good formulation properties, which make the fibers attractive materials for controlled drug delivery systems. In this study, the factors affecting the nature and strength of the binding/loading of drug-sized model compounds into the ion-exchange fibers was evaluated comprehensively and, moreover, the controllability of subsequent drug release/delivery from the fibers was assessed by modifying the conditions of external solutions. Also the feasibility of ion-exchange fibers for simultaneous delivery of two drugs in combination was studied by dual loading. Donnan theory and theoretical modelling were applied to gain mechanistic understanding on these factors. The experimental results imply that incorporation of model compounds into the ion-exchange fibers was attained mainly as a result of ionic bonding, with additional contribution of non-specific interactions. Increasing the ion-exchange capacity of the fiber or decreasing the valence of loaded compounds increased the molar loading, while more efficient release of the compounds was observed consistently at conditions where the valence or concentration of the extracting counter-ion was increased. Donnan theory was capable of fully interpreting the ion-exchange equilibria and the theoretical modelling supported precisely the experimental observations. The physico-chemical characteristics (lipophilicity, hydrogen bonding ability) of the model compounds and the framework of the fibrous ion-exchanger influenced the affinity of the drugs towards the fibers and may, thus, affect both drug loading and release. It was concluded that precisely controlled drug delivery may be tailored for each compound, in particularly, by choosing a suitable ion-exchange fiber and optimizing the delivery system to take into account the external conditions, also when delivering two drugs simultaneously.

External signal-activated liposomal drug delivery systems

Modern drug discovery gives rise to a great number of potential new therapeutic agents, but in some cases the efficient treatment of patient may not be achieved because the delivery of active compounds to the target site is insufficient. Thus, drug delivery is one of the major challenges in current pharmaceutical research. Numerous nanoparticle-based drug carriers, e.g. liposomes, have been developed for enhanced drug delivery and targeting. Drug targeting may enhance the efficiency of the treatment and, importantly, reduce unwanted side effects by decreasing drug distribution to non-target tissues. Liposomes are biocompatible lipid-based carriers that have been studied for drug delivery during the last 40 years. They can be functionalized with targeting ligands and sensing materials for triggered activation. In this study, various external signal-assisted liposomal delivery systems were developed. Signals can be used to modulate drug permeation or release from the liposome formulation, and they provide accurate control of time, place and rate of activation. The study involved three types of signals that were used to trigger drug permeation and release: electricity, heat and light. Electrical stimulus was utilized to enhance the permeation of liposomal DNA across the skin. Liposome/DNA complex-mediated transfections were performed in tight rat epidermal cell model. Various transfection media and current intensities were tested, and transfection efficiency was evaluated non-invasively by monitoring the concentration of secreted reporter protein in cell culture medium. Liposome/DNA complexes produced gene expression, but electrical stimulus did not enhance the transfection efficiency significantly. Heat-sensitive liposomal drug delivery system was developed by coating liposomes with biodegradable and thermosensitive poly(N-(2-hydroxypropyl) methacrylamide-mono/dilactate polymer. Temperature-triggered liposome aggregation and contents release from liposomes were evaluated. The cloud point temperature (CP) of the polymer was set to 42 °C. Polymer-coated liposome aggregation and contents release were observed above CP of the polymer, while non-coated liposomes remained intact. Polymer precipitates above its CP and interacts with liposomal bilayers. It is likely that this induces permeabilization of the liposomal membrane and contents release. Light-sensitivity was introduced to liposomes by incorporation of small (< 5 nm) gold nanoparticles. Hydrophobic and hydrophilic gold nanoparticles were embedded in thermosensitive liposomes, and contents release was investigated upon UV light exposure. UV light-induced lipid phase transitions were examined with small angle X-ray scattering, and light-triggered contents release was shown also in human retinal pigment epithelial cell line. Gold nanoparticles absorb light energy and transfer it into heat, which induces phase transitions in liposomes and triggers the contents release. In conclusion, external signal-activated liposomes offer an advanced platform for numerous applications in drug delivery, particularly in the localized drug delivery. Drug release may be localized to the target site with triggering stimulus that results in better therapeutic response and less adverse effects. Triggering signal and mechanism of activation can be selected according to a specific application.

Adjektiiveihin liittyvät kollokaatit kuntien Internet-sivujen esittelyteksteissä. Korpuslingvististen menetelmien mahdollisuudet ja rajat kvalitatiivisessa tutkimuksessa.

Tarkastelen kuntien esittelyteksteissä esiintyviä, adjektiiveihin ja adjektiiviryhmiin liittyviä kollokaatioita ja kolligaatioita, eli myötäilmauksia. Adjektiiveja käsittelen adjektiiviryhmittäin, joita on kuusi. Laskevassa kokojärjestyksessä aineistossani esiintyvät adjektiiviryhmät ovat seuraavat: suhteelliset, absoluuttiset, yksilöivät, taipumattomat, suhteutusadjektiivit sekä proadjektiivit. Kiinnitän huomiota erityisesti siihen, millaisia kollokaatiosuhteita (nousevat ja laskevat kollokaatiot) eri adjektiiveihin ja eri adjektiiviryhmiin liittyy. Käyttämäni tekstiaineisto on pienehkö sähköinen tekstikorpus, joka koostuu suomalaisten kuntien Internet-sivuilta kerätyistä esittelyteksteistä. Korpuksessa on yhteensä 119 tekstiä, ja niissä on kyse kunnan esittelystä Internet-sivustojen lukijoille, eli tavallisesti erilaisesta oman kunnan markkinoinnista. Aineistooni kuuluvien kuntien väkiluku on vähemmän kuin 3000 asukasta, eli tutkimuskunnissa kyse on kaikkein pienimmistä Suomen kunnista. Tutkimusaineistooni, eli sähköiseen korpukseen, kuuluvat tekstit on käsitelty Fintwol-ohjelmalla, jolloin niihin on tehty koneavusteinen morfologinen analyysi. Jokaiseen saneeseen on siis lisätty sille kuuluva morfologinen tulkinta. Tarkoitukseni onkin havainnoida myös tietokoneen mahdollistamia sähköisiä tutkimusmenetelmiä kvalitatiivisen kielentutkimuksen välineenä. Kollokaatioiden tutkimuksessa tekstikorpuksia on käytetty pitkään, mutta aiemmin morfologinen analyysi on tavallisesti tehty käsin ja analyysit perustuneet esimerkiksi tiettyjen lekseemien tarkasteluun. Tutkimuksessani selvitän, millaisia mahdollisuuksia tietokoneavusteinen analyysi tuo kvalitatiiviseen kielentutkimukseen sekä millaisia rajoituksia sillä on. Adjektiivi-kollokaatti-esiintymien avulla kuvaillaan esittelyteksteissä usein kuntaa joko suoraan tai välillisesti. Tietokoneavusteisesta analyysista saadut tulokset ovat lähinnä kvantitatiivisia, mutta käytän tarkastelun apuna konkordanssilistaa, eli niin kutsuttua KWIC-listaa (Key Word In Context), jonka tarkasteluvälin pituudeksi olen rajannut viisi sanaa. Tämä pituus sisältää tarkasteltavan lekseemin (adjektiivi) sekä kaksi sanaa sen edellä ja jäljessä. Havainnoin sähköisestä korpuksesta saamieni tilastollisten tulosten avulla myös sitä, millainen aineisto ja tekstilaji esittelytekstit ovat. Vertailen saamiani tuloksia muista korpuksista saatuihin tilastollisiin tuloksiin. Adjektiiviryhmiin liittyvät nousevat kollokaatiosuhteet, joissa kollokaatti on adjektiivia yleisempi, toistuvat läpi aineiston samanlaisina: Näissä kollokaatiosuhteissa adjektiivit kollokoivat useimmiten sellaisen sanaston kanssa, joka on varsin yleistä koko aineistossani. Esimerkiksi substantiivit kunta ja palvelu, jotka ovat koko aineiston yleisimpiä sanoja, esiintyvät kaikkien adjektiiviryhmien adjektiivien kollokaatteina toistuvasti. Ne myös ilmaisevat sellaisia esittelyteksteissä toistuvia aiheita, jotka ovat kunnille tärkeitä ja joita käsitellään monessa esittelytekstissä. Laskevat kollokaatiosuhteet taas ilmaisevat lähinnä esittelyteksteissä yleisiä, adjektiivien merkitystä määrittäviä leksikaalisia suhteita, kuten adjektiivi-kollokaatti-parit hyvät liikenneyhteydet tai kaunis maisema. Esittelytekstiaineistoni käsittelyyn tietokoneavusteinen analyysi soveltui vain osittain. Suurin ongelma aiheutui paikannimistä (esim.

Multi-user resource-sharing problem for the Internet

In this thesis we study a series of multi-user resource-sharing problems for the Internet, which involve distribution of a common resource among participants of multi-user systems (servers or networks). We study concurrently accessible resources, which for end-users may be exclusively accessible or non-exclusively. For all kinds we suggest a separate algorithm or a modification of common reputation scheme. Every algorithm or method is studied from different perspectives: optimality of protocols, selfishness of end users, fairness of the protocol for end users. On the one hand the multifaceted analysis allows us to select the most suited protocols among a set of various available ones based on trade-offs of optima criteria. On the other hand, the future Internet predictions dictate new rules for the optimality we should take into account and new properties of the networks that cannot be neglected anymore. In this thesis we have studied new protocols for such resource-sharing problems as the backoff protocol, defense mechanisms against Denial-of-Service, fairness and confidentiality for users in overlay networks. For backoff protocol we present analysis of a general backoff scheme, where an optimization is applied to a general-view backoff function. It leads to an optimality condition for backoff protocols in both slot times and continuous time models. Additionally we present an extension for the backoff scheme in order to achieve fairness for the participants in an unfair environment, such as wireless signal strengths. Finally, for the backoff algorithm we suggest a reputation scheme that deals with misbehaving nodes. For the next problem -- denial-of-service attacks, we suggest two schemes that deal with the malicious behavior for two conditions: forged identities and unspoofed identities. For the first one we suggest a novel most-knocked-first-served algorithm, while for the latter we apply a reputation mechanism in order to restrict resource access for misbehaving nodes. Finally, we study the reputation scheme for the overlays and peer-to-peer networks, where resource is not placed on a common station, but spread across the network. The theoretical analysis suggests what behavior will be selected by the end station under such a reputation mechanism.

Analysis of Heterogeneous IP Traffic in Wireless Environment

Wireless access is expected to play a crucial role in the future of the Internet. The demands of the wireless environment are not always compatible with the assumptions that were made on the era of the wired links. At the same time, new services that take advantage of the advances in many areas of technology are invented. These services include delivery of mass media like television and radio, Internet phone calls, and video conferencing. The network must be able to deliver these services with acceptable performance and quality to the end user. This thesis presents an experimental study to measure the performance of bulk data TCP transfers, streaming audio flows, and HTTP transfers which compete the limited bandwidth of the GPRS/UMTS-like wireless link. The wireless link characteristics are modeled with a wireless network emulator. We analyze how different competing workload types behave with regular TPC and how the active queue management, the Differentiated services (DiffServ), and a combination of TCP enhancements affect the performance and the quality of service. We test on four link types including an error-free link and the links with different Automatic Repeat reQuest (ARQ) persistency. The analysis consists of comparing the resulting performance in different configurations based on defined metrics. We observed that DiffServ and Random Early Detection (RED) with Explicit Congestion Notification (ECN) are useful, and in some conditions necessary, for quality of service and fairness because a long queuing delay and congestion related packet losses cause problems without DiffServ and RED. However, we observed situations, where there is still room for significant improvements if the link-level is aware of the quality of service. Only very error-prone link diminishes the benefits to nil. The combination of TCP enhancements improves performance. These include initial window of four, Control Block Interdependence (CBI) and Forward RTO recovery (F-RTO). The initial window of four helps a later starting TCP flow to start faster but generates congestion under some conditions. CBI prevents slow-start overshoot and balances slow start in the presence of error drops, and F-RTO reduces unnecessary retransmissions successfully.

Viivesietoisten verkkojen nykytila ja tulevaisuuden haasteet

Delay and disruption tolerant networks (DTNs) are computer networks where round trip delays and error rates are high and disconnections frequent. Examples of these extreme networks are space communications, sensor networks, connecting rural villages to the Internet and even interconnecting commodity portable wireless devices and mobile phones. Basic elements of delay tolerant networks are a store-and-forward message transfer resembling traditional mail delivery, an opportunistic and intermittent routing, and an extensible cross-region resource naming service. Individual nodes of the network take an active part in routing the traffic and provide in-network data storage for application data that flows through the network. Application architecture for delay tolerant networks differs also from those used in traditional networks. It has become feasible to design applications that are network-aware and opportunistic, taking an advantage of different network connection speeds and capabilities. This might change some of the basic paradigms of network application design. DTN protocols will also support in designing applications which depend on processes to be persistent over reboots and power failures. DTN protocols could also be applicable to traditional networks in cases where high tolerance to delays or errors would be desired. It is apparent that challenged networks also challenge the traditional strictly layered model of network application design. This thesis provides an extensive introduction to delay tolerant networking concepts and applications. Most attention is given to challenging problems of routing and application architecture. Finally, future prospects of DTN applications and implementations are envisioned through recent research results and an interview with an active researcher of DTN networks.

Architectural Solutions for Mobile RFID Services on Internet of Things

Mobile RFID services for the Internet of Things can be created by using RFID as an enabling technology in mobile devices. Humans, devices, and things are the content providers and users of these services. Mobile RFID services can be either provided on mobile devices as stand-alone services or combined with end-to-end systems. When different service solution scenarios are considered, there are more than one possible architectural solution in the network, mobile, and back-end server areas. Combining the solutions wisely by applying the software architecture and engineering principles, a combined solution can be formulated for certain application specific use cases. This thesis illustrates these ideas. It also shows how generally the solutions can be used in real world use case scenarios. A case study is used to add further evidence.

The Catholic Internet discussion on cloning : A study in cognitive rhetoric

This work combines the cognitive theory of folk-theoretical thought with the classical Aristotelian theory of artistic proof in rhetoric. The first half of the work discusses the common ground shared by the elements of artistic proof (logos, pathos, ethos) and the elements of folk-theoretical thought (naïve physics, folk biology, folk psychology, naïve sociology). Combining rhetoric with the cognitive theory of folk-theoretical thought creates a new point of view for argumentation analysis. The logos of an argument can be understood as the inferential relations established between the different parts of an argument. Consequently, within this study the analysis of logos is to be viewed as the analysis of the inferential folk-theoretical elements that make the suggested factual states-of-things appear plausible within given argumentative structures. The pathos of an argumentative structure can be understood as determining the quality of the argumentation in question in the sense that emotive elements play a great part in what can be called a distinction between good and deceptive rhetoric. In the context of this study the analysis of pathos is to be viewed as the analysis of the emotive content of argumentative structures and of whether they aim at facilitating surface- or deep cognitive elaboration of the suggested matters. The ethos of an argumentative structure means both the speaker-presentation and audience-construct that can be discerned within a body of argumentation. In the context of this study, the analysis of ethos is to be understood as the analysis of mutually manifest cognitive environments in the context of argumentation. The theory is used to analyse Catholic Internet discussion concerning cloning. The discussion is divided into six themes: Human Dignity, Sacred Family, Exploitation / Dehumanisation, Playing God, Monsters and Horror Scenarios and Ensoulment. Each theme is analysed for both the rhetorical and the cognitive elements that can be seen creating persuasive force within the argumentative structures presented. It is apparent that the Catholic voices on the Internet extensively oppose cloning. The voices utilise rhetoric that is aggressive and pejorative more often than not. Furthermore, deceptive rhetoric (in the sense presented above) plays a great part in argumentative structures of the Catholic voices. The theory of folk-theoretical thought can be seen as a useful tool for analysing the possible reasons why the Catholic speakers think about cloning and choose to present cloning in their argumentation as they do. The logos utilized in the argumentative structures presented can usually be viewed as based on folk-theoretical inference concerning biology and psychology. The structures of pathos utilized generally appear to aim at generating fear appeal in the assumed audiences, often incorporating counter-intuitive elements. The ethos utilised in the arguments generally revolves around Christian mythology and issues of social responsibility. These structures can also be viewed from the point of view of folk psychology and naïve sociological assumptions.

Preterm delivery and selected biomarkers : phosphorylated insulin-like growth factor-binding protein-1 and matrix metalloproteinase-8 – in cervical fluid

Premature delivery is a major cause of neonatal morbidity and mortality. The incidence of premature deliveries has increased around the world. In Finland 5.3%, or about 3,000 children per year are born prematurely, before 37 weeks of gestation. The corresponding figure in the United States is about 13%. The morbidity and mortality are highest among infants delivered before 32 weeks of gestation - about 600 children each year in Finland. Approximately 70% of premature deliveries are unexplained. Preterm delivery can be caused by an asympto-matic infection between uterus and the fetal membranes, such can begin already in early pregnancy. It is difficult to predict preterm delivery, and many patients are therefore unnecessarily admitted to hospital for observation and exposed to medical treatments. On the other hand, the high risk women should be identified early for the best treatment of the mother and preterm infant. --- In the prospective study conducted at the Department of Obstetric and Gynecology, Helsinki University Central Hospital two biochemical inflammation related markers were measured in the lower genital tract fluids of asymp-tomatic women in early and mid pregnancy in an order to see whether these markers could identify women with an increased risk of preterm delivery. These biomarkers were phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) and matrix metalloproteinase-8 (MMP-8). The study involved 5180 asymptomatic pregnant women, examined during the first and second ultrasound screening visits. The study samples were taken from the vagina and cervicix. In addition, 246 symptomatic women were studied (pregnancy weeks 22 – 34). The study showed that increased phIGFBP-1 concentration in cervical canal fluid in early pregnancy increased the risk for preterm delivery. The risk for very premature birth (before 32 weeks of gestation) was nearly four-fold. Low MMP-8 concentration in mid pregnancy increased the risk of subsequent premature preterm rupture of fetal membranes (PPROM). Significantly high MMP-8 concentrations in the cervical fluid increased the risk for prema-ture delivery initiated by preterm labour with intact membranes. Among women with preterm contractions the shortened cervical length measured by ultrasound and elevated cervical fluid phIGFBP-1 both predicted premature delivery. In summary, because of the relatively low sensitivity of cervical fluid phIGFBP-1 this biomarker is not suitable for routine screening, but provides an additional tool in assessing the risk of preterm delivery. Cervical fluid MMP-8 is not useful in early or mid pregnancy in predicting premature delivery because of its dual role. Further studies on the role of MMP-8 are therefore needed. Our study confirms that phIGFBP-1 testing is useful in predicting pre-term delivery.