Strategies for the development of tdm for targeted anticancer agents

Most of the novel targeted anticancer agents share classical characteristics that define drugs as candidates for blood concentration monitoring: long-term therapy; high interindividual but restricted intraindividual variability; significant drug-drug and drug- food interactions; correlations between concentration and efficacy/ toxicity with rather narrow therapeutic index; reversibility of effects; and absence of early markers of response. Surprisingly though, therapeutic concentration monitoring has received little attention for these drugs despite reiterated suggestions from clinical pharmacologists. Several issues explain the lack of clinical research and development in this field: global tradition of empiricism regarding treatment monitoring, lack of formal conceptual framework, ethical difficulties in the elaboration of controlled clinical trials, disregard from both drug manufacturers and public funders, limited encouragement from regulatory authorities, and practical hurdles making dosage adjustment based on concentration monitoring a difficult task for prescribers. However, new technologies are soon to help us overcome these obstacles, with the advent of miniaturized measurement devices able to quantify circulating drug concentrations at the point-of-care, to evaluate their plausibility given actual dosage and sampling time, to determine their appropriateness with reference to therapeutic targets, and to advise on suitable dosage adjustment. Such evolutions could bring conceptual changes into the clinical development of drugs such as anticancer agents, while increasing the therapeutic impact of population PK-PD studies and systematic reviews. Research efforts in that direction from the clinical pharmacology community will be essential for patients to receive the greatest benefits and the least harm from new anticancer treatments. The example of imatinib, the first commercialized tyrosine kinase inhibitor, will be outlined to illustrate a potential research agenda for the rational development of therapeutic concentration monitoring.

Pregnancy and childbirth: What changes in the lifestyle of women who become mothers?

Pregnancy is a period influenced by the interaction of several factors, therefore this study aimed to identify changes in lifestyles due to pregnancy and childbirth in Portuguese and immigrant women in Portugal. This is a qualitative study, using the semi-structured interview, with eighty-two Portuguese and immigrant women. Content analysis was used, with verbatim classification supported by Nvivo 10. It was authorized by an Ethics Commission. Results revealed that the primary changes in lifestyles due to pregnancy were in eating habits (nutrition), daily activity, exposure to danger, sleep and rest patterns, social and family relationships, going out, self-care, work, clothing and footwear, travel, health monitoring and sexual activity and substances consumption. The main change after the birth, manifested by these women, was that their lives began to revolve around their baby.

Perception et communication du risque: du diabète à la maladie cardiovasculaire [Risk perception and communication: from diabetes to cardiovascular diseases].

Evidence-based medicine has enabled to approach disease in a more rational and scientific way. Clinical research has identified behaviours and risk factors that could cause disease often "silent" at the beginning, such as diabetes. Despite the clear impact of these evidences on public health, it seems that the individual risk perception level remains weak. To mention as well, the health professionals very often have a different views, which makes it difficult to communicate the risk with patients. In this article we describe the principles of risk perception, the diabetes related risk perception concerning cardiovascular complications, and suggest some practical strategies and tools which could improve risk communication in the everyday practice.

Iowa Influenza Surveillance Network Final Report 2007-2008

The Iowa Influenza Surveillance Network (IISN) was formally established in 2004, though surveillance has been conducted at the Iowa Department of Public Health (IDPH) for more than ten years. The IISN is comprised of four primary surveillance systems- sentinel health care providers, hospital-based, laboratory-based, and school-based. Sentinel health care providers are part of the U.S. Influenza Sentinel Provider Surveillance System. All systems, except certain sentinel sites, report October-March. Schools and long-term care facilities report data weekly into a Web-based reporting system. Schools report the number of students absent due to illness and the total enrolled. Long-term care facilities report cases of influenza and vaccination status of each case. Both passively report outbreaks of illness, including influenza, to IDPH.

Bullying among adolescents in a sub-Saharan middle-income setting.

PURPOSE: This study explored factors associated with self-reported bullying among adolescents in a sub-Saharan country. METHODS: A cross-sectional sample of adolescents (n = 1,427) in the Seychelles was drawn from the Global School-based Student Health Survey. Bullied adolescents were compared with non-bullied adolescents with respect to several sociodemographic factors. Bivariate and multivariate analyses were performed. RESULTS: Within a 30 day period, 38.8% of adolescents reported being bullied. Bullied youths were more likely to be depressed (adjusted odds ratio [aOR] = 1.63; confidence intervals [CI] = 1.27-1.07) and socially deprived (aOR = 1.85; CI = 1.30-2.61). Being older (aOR = .83; CI = .77-.90) and having close friends (aOR = .53; CI = .31-.91) were protective factors. CONCLUSIONS: The prevalence of bullying in the Seychelles is high, and social correlates are similar to those in industrialized settings. More research is needed to examine bullying patterns outside the school environment.

Estimation of water percolation by different methods using TDR

Detailed knowledge on water percolation into the soil in irrigated areas is fundamental for solving problems of drainage, pollution and the recharge of underground aquifers. The aim of this study was to evaluate the percolation estimated by time-domain-reflectometry (TDR) in a drainage lysimeter. We used Darcy's law with K(θ) functions determined by field and laboratory methods and by the change in water storage in the soil profile at 16 points of moisture measurement at different time intervals. A sandy clay soil was saturated and covered with plastic sheet to prevent evaporation and an internal drainage trial in a drainage lysimeter was installed. The relationship between the observed and estimated percolation values was evaluated by linear regression analysis. The results suggest that percolation in the field or laboratory can be estimated based on continuous monitoring with TDR, and at short time intervals, of the variations in soil water storage. The precision and accuracy of this approach are similar to those of the lysimeter and it has advantages over the other evaluated methods, of which the most relevant are the possibility of estimating percolation in short time intervals and exemption from the predetermination of soil hydraulic properties such as water retention and hydraulic conductivity. The estimates obtained by the Darcy-Buckingham equation for percolation levels using function K(θ) predicted by the method of Hillel et al. (1972) provided compatible water percolation estimates with those obtained in the lysimeter at time intervals greater than 1 h. The methods of Libardi et al. (1980), Sisson et al. (1980) and van Genuchten (1980) underestimated water percolation.

Ympäristöterveysvalvonnan järjestäminen kunnallisessa organisaatiossa

Summary: Environmental health monitoring within municipal organizations

Stream Stabilization in Western Iowa: Structure Evaluation and Design Manual, HR-385, 1998

Stream degradation is the action of deepening the stream bed and widening the banks due to the increasing velocity of water flow. Degradation is pervasive in channeled streams found within the deep to moderately deep loess regions of the central United States. Of all the streams, however, the most severe and widespread entrenchment occurs in western Iowa streams that are tributaries to the Missouri River. In September 1995 the Iowa Department of Transportation awarded a grant to Golden Hills Resource Conservation and Development, Inc. The purpose of the grant, HR-385 "Stream Stabilization in Western Iowa: Structure Evaluation and Design Manual", was to provide an assessment of the effectiveness and costs of various stabilization structures in controlling erosion on channeled streams. A review of literature, a survey of professionals, field observations and an analysis of the data recorded on fifty-two selected structures led to the conclusions presented in the project's publication, Design Manual, Streambed Degradation and Streambank Widening in Western Iowa. Technical standards and specifications for the design and construction of stream channel stabilization structures are included in the manual. Additional information on non-structural measures, monitoring and evaluation of structures, various permit requirements and further resources are also included. Findings of the research project and use and applications of the Design Manual were presented at two workshops in the Loess Hills region. Participants in these workshops included county engineers, private contractors, state and federal agency personnel, elected officials and others. The Design Manual continues to be available through Golden Hills Resource Conservation and Development.

On the spot damage detection methodology for highway bridges (tech transfer summary)

The objective of this work was to develop a low-cost portable damage detection tool to assess and predict damage areas in highway bridges. The proposed tool was based on standard vibration-based damage identification (VBDI) techniques but was extended to a new approach based on operational traffic load. The methodology was tested using numerical simulations, laboratory experiments, and field testing.

Improvement of cardiovascular risk prediction: time to review current knowledge, debates, and fundamentals on how to assess test characteristics.

Cardiovascular risk assessment might be improved with the addition of emerging, new tests derived from atherosclerosis imaging, laboratory tests or functional tests. This article reviews relative risk, odds ratios, receiver-operating curves, posttest risk calculations based on likelihood ratios, the net reclassification improvement and integrated discrimination. This serves to determine whether a new test has an added clinical value on top of conventional risk testing and how this can be verified statistically. Two clinically meaningful examples serve to illustrate novel approaches. This work serves as a review and basic work for the development of new guidelines on cardiovascular risk prediction, taking into account emerging tests, to be proposed by members of the 'Taskforce on Vascular Risk Prediction' under the auspices of the Working Group 'Swiss Atherosclerosis' of the Swiss Society of Cardiology in the future.

Examination of Curing Criteria for Cold In-Place Recycling (Phase 3: Calibration of Moisture Loss Indices and Development of Stiffness Gain Model), TR-609, 2011

In the previous study, moisture loss indices were developed based on the field measurements from one CIR-foam and one CIR-emulsion construction sites. To calibrate these moisture loss indices, additional CIR construction sites were monitored using embedded moisture and temperature sensors. In addition, to determine the optimum timing of an HMA overlay on the CIR layer, the potential of using the stiffness of CIR layer measured by geo-gauge instead of the moisture measurement by a nuclear gauge was explored. Based on the monitoring the moisture and stiffness from seven CIR project sites, the following conclusions are derived: 1. In some cases, the in-situ stiffness remained constant and, in other cases, despite some rainfalls, stiffness of the CIR layers steadily increased during the curing time. 2. The stiffness measured by geo-gauge was affected by a significant amount of rainfall. 3. The moisture indices developed for CIR sites can be used for predicting moisture level in a typical CIR project. The initial moisture content and temperature were the most significant factors in predicting the future moisture content in the CIR layer. 4. The stiffness of a CIR layer is an extremely useful tool for contractors to use for timing their HMA overlay. To determine the optimal timing of an HMA overlay, it is recommended that the moisture loss index should be used in conjunction with the stiffness of the CIR layer.

Colorectal Cancer Screening in Switzerland: Cross-Sectional Trends (2007-2012) in Socioeconomic Disparities.

BACKGROUND: Despite universal health care coverage, disparities in colorectal cancer (CRC) screening by income in Switzerland have been reported. However, it is not known if these disparities have changed over time. This study examines the association between socioeconomic position and CRC screening in Switzerland between 2007 and 2012. METHODS: Data from the 2007 (n = 5,946) and 2012 (n = 7,224) population-based Swiss Health Interview Survey data (SHIS) were used to evaluate the association between monthly household income, education, and employment with CRC screening, defined as endoscopy in the past 10 years or fecal occult blood test (FOBT) in the past 2 years. Multivariable Poisson regression was used to estimate prevalence ratios (PR) and 95% Confidence Intervals (CI) adjusting for demographics, health status, and health utilization. RESULTS: CRC screening increased from 18.9% in 2007 to 22.2% in 2012 (padjusted: = 0.036). During the corresponding time period, endoscopy increased (8.2% vs. 15.0%, padjusted:<0.001) and FOBT decreased (13.0% vs. 9.8%, padjusted:0.002). CRC screening prevalence was greater in the highest income (>$6,000) vs. lowest income (≤$2,000) group in 2007 (24.5% vs. 10.5%, PR:1.37, 95%CI: 0.96-1.96) and in 2012 (28.6% vs. 16.0%, PR:1.45, 95%CI: 1.09-1.92); this disparity did not significantly change over time. CONCLUSIONS: While CRC screening prevalence in Switzerland increased from 2007 to 2012, CRC screening coverage remains low and disparities in CRC screening by income persisted over time. These findings highlight the need for increased access to CRC screening as well as enhanced awareness of the benefits of CRC screening in the Swiss population, particularly among low-income residents.

Kestävän kehityksen toimintasuunnitelman laatiminen Lappeenrannan teknilliselle yliopistolle

Työn tavoitteena oli tuottaa kestävän kehityksen toimintasuunnitelman rakentamiseen ja seuraamiseen viitekehys, josta Lappeenrannan teknillisen yliopiston yksiköt saavat tarvittavan tiedon kestävän kehityksen indikaattorien valitsemiseen ja yksikkökohtaisten hallintaohjelmien rakentamiseen. Työssä on selvitetty mitkä ovat yliopiston yksiköiden kestävän kehityksen näkökohdat ja niiden seuraamisessa tarvittavat yksikkökohtaiset indikaattorit sekä miten indikaattoreita ja opetusministeriöiden hyväksymää Baltic 21E –ohjelmaa voitaisiin käytännössä hyödyntää. Kestävän kehityksen toimintasuunnitelma perustuu Global Reporting Initiativen (GRI:n) vuonna 2002 julkaisemaan yhteiskuntavastuun raportointiohjeeseen. Toimintasuunnitelma perustuu osittain myös ympäristöjärjestelmästandardi ISO 14001:een ja työssä on huomioitu opetusministeriön ohjeen mukaisesti Baltic 21E –raportti ja erityisesti opetusministeriön asettaman työryhmän ehdotus Baltic 21E –ohjelman käynnistyssuunnitelmaksi. Työssä teoriaosuuden ja raportointiperusteiden jälkeen on kuvattu GRI:n ohjeiden mukaisesti yliopiston organisaatio, visio, strategia ja hallintajärjestelmät. Pääasiassa haastatteluin tehdyllä kestävän kehityksen katselmuksella on selvitetty Lappeenrannan teknillisen yliopiston yksiköiden kestävän kehityksen näkökohdat. Näkökohdat on jaoteltu ympäristöhallintajärjestelmän mukaisesti toimintoihin, tuotteisiin ja palveluihin. Näkökohdissa on huomioitu Baltic 21E –raportti ja sen tavoite- ja toimenpide-ehdotukset. Kestävän kehityksen näkökohtien ja vaikutusten seuraamiseksi on jokaiselle yksikölle tunnistettu indikaattorit, jotka on muotoiltu GRI:n Sustainability Reporting Guideliness –julkaisun indikaattorien pohjalta. Työssä on selvitetty indikaattorien käyttötarkoitusta ja esimerkein havainnollistettu indikaattorien ja Baltic 21E –ohjelman käyttöönottomahdollisuuksia ISO 14001 –järjestelmän mukaisesti. Haastattelujen ja Baltic 21E –toimintaohjelman perusteella yliopiston kestävän kehityksen näkökohdat liittyvät opetukseen, tutkimukseen, täydennyskoulutukseen ja julkaisutoimintaan sekä yliopistoyhteisön omaan kestävän kehityksen tietoisuuteen ja toimintaperiaatteiden noudattamiseen. Yliopistotoiminnassa kestävä kehitys on myös mukana alueellisessa vuorovaikutuksessa sidosryhmäsuhteiden ja uuden tiedon tuottamisen kautta. Yliopiston yksiköiden kestävää kehitystä mittaavia indikaattoreita tunnistettiin suuri joukko. Eniten tunnistettiin yhteiskunnalliseen vaikutusluokkaan kuuluvia indikaattoreita. Jaoteltaessa indikaattorit käyttötarkoituksittain tarkasteltavien indikaattorien määrä hieman vähenee. Tämän työn jälkeen tulisi GRI:n ohjeiden mukaisesti käydä sidosryhmien välistä vuoropuhelua yksikkökohtaisten merkittävimpien indikaattorien tunnistamiseksi ja kestävän kehityksen päämäärien ja tavoitteiden asettamiseksi. Tämän työn indikaattorien pää-asialliset käyttökohteet olisivat yksiköiden sisäisessä kehittämisessä ja viestinnässä, vähemmässä määrin tuloskeskusteluissa.

Prostate cancer screening in Switzerland: 20-year trends and socioeconomic disparities.

BACKGROUND: Despite important controversy in its efficacy, prostate cancer (PCa) screening has become widespread. Important socioeconomic screening disparities have been reported. However, trends in PCa screening and social disparities have not been investigated in Switzerland, a high risk country for PCa. We used data from five waves (from 1992-2012) of the population-based Swiss Health Interview Survey to evaluate trends in PCa screening and its association with socioeconomic indicators. METHODS: We used multivariable Poisson regression to estimate prevalence ratios (PR) and 95% Confidence Intervals (CI) adjusting for demographics, health status, and use of healthcare. RESULTS: The study included 12,034 men aged ≥50 years (mean age: 63.9). Between 1992 and 2012, ever use of PCa screening increased from 55.3% to 70.0% and its use within the last two years from 32.6% to 42.4% (p-value <0.05). Income, education, and occupational class were independently associated with PCa screening. PCa screening within the last two years was greater in men with the highest (>$6,000/month) vs. lowest income (≤$2,000) (46.5% vs. 38.7% in 2012, PR for overall period =1.29, 95%CI: 1.13-1.48). These socioeconomic disparities did not significantly change over time. CONCLUSIONS: This study shows that about half of Swiss men had performed at least one PCa screening. Men belonging to high socioeconomic status are clearly more frequently screened than those less favored. Given the uncertainty of the usefulness of PCa screening, men, including those with high socioeconomic status, should be clearly informed about benefits and harms of PCa screening, in particular, the adverse effect of over-diagnosis and of associated over-treatment.

Julkinen-yksityinen kumppanuuden vaikutus asiakasarvon muodostumiseen terveydenhuollon toimialalla

Terveydenhuollon toimiala on voimakkaiden muutospaineiden edessä. Huoltosuhteen heikkeneminen asettaa julkiselle terveydenhuollolle suuria haasteita. Uudenlaisten palveluratkaisujen ja teknologian avulla voidaan tuottavuutta sekä tehokkuutta nostaa. Työssä selvitetään julkinen - yksityinen kumppanuuden merkitystä asiakasarvon muodostumiseen terveydenhuollon toimialalla. Työssä on kahden case-esimerkin sekä kirjallisuuslähteiden avulla tutkittu asiakasarvon syntyyn vaikuttavia tekijöitä. Teoreettisina viitekehyksinä on käytetty resurssipohjaista näkemystä. Case-esimerkkeinä käytettiin MedOne Oy:n ja Lahden kaupungin välistä ulkoistussopimusta sekä Effica-potilastietojärjestelmän käyttöönottoa. Kummassakin tapauksessa voidaan katsoa asiakasarvoa syntyneen, muttei täysin ongelmitta.