A pharmacokinetic-pharmacodynamic model for duodenal levodopa infusion

Objective Levodopa in presence of decarboxylase inhibitors is following two-compartment kinetics and its effect is typically modelled using sigmoid Emax models. Pharmacokinetic modelling of the absorption phase of oral distributions is problematic because of irregular gastric emptying. The purpose of this work was to identify and estimate a population pharmacokinetic- pharmacodynamic model for duodenal infusion of levodopa/carbidopa (Duodopa®) that can be used for in numero simulation of treatment strategies. Methods The modelling involved pooling data from two studies and fixing some parameters to values found in literature (Chan et al. J Pharmacokinet Pharmacodyn. 2005 Aug;32(3-4):307-31). The first study involved 12 patients on 3 occasions and is described in Nyholm et al. Clinical Neuropharmacology 2003:26:156-63. The second study, PEDAL, involved 3 patients on 2 occasions. A bolus dose (normal morning dose plus 50%) was given after a washout during night. Plasma samples and motor ratings (clinical assessment of motor function from video recordings on a treatment response scale between -3 and 3, where -3 represents severe parkinsonism and 3 represents severe dyskinesia.) were repeatedly collected until the clinical effect was back at baseline. At this point, the usual infusion rate was started and sampling continued for another two hours. Different structural absorption models and effect models were evaluated using the value of the objective function in the NONMEM package. Population mean parameter values, standard error of estimates (SE) and if possible, interindividual/interoccasion variability (IIV/IOV) were estimated. Results Our results indicate that Duodopa absorption can be modelled with an absorption compartment with an added bioavailability fraction and a lag time. The most successful effect model was of sigmoid Emax type with a steep Hill coefficient and an effect compartment delay. Estimated parameter values are presented in the table. Conclusions The absorption and effect models were reasonably successful in fitting observed data and can be used in simulation experiments.

12-month results from a novel test battery used in a duodenal levodopa infusion trial

A novel test battery consisting of self-assessments and motor tests (tapping and spiral drawing) for patients with Parkinson’s disease (PD) was developed for a hand computer with touch screen in a telemedicine setting. Tests are performed four times per day in the home environment during weeklong test periods. Results are processed into scores for different dimensions of the symptom state and an ‘overall score’ reflecting the global condition of a patient during a test period. The test battery was validated in a separate study recently submitted to Mov Disord. This test battery is currently being used in an open longitudinal trial (DAPHNE, EudraCT No. 2005- 002654-21) by sixty-five patients with advanced PD at nine clinics around Sweden. On inclusion, the patients were either receiving treatment with duodenal levodopa/carbidopa infusion (Duodopa®) (n=36), or they were candidates for receiving this treatment (n=29). We now present interim results for the first twelve months. Test periods were performed in three-month intervals. During most of the periods, UPDRS ratings were performed in afternoons at the start of the week. In twenty of the patients, scores were available during individually optimized oral polypharamacy, before receiving infusion and at least one test period after having started infusion treatment. Usability and compliance with performing tests, this far are good, both with patients and clinical staff. Correlations between test periods 2 and 3 during infusion treatment (three months apart) are stronger for overall test score than for total UPDRS, indicating good reliability. The correlation between overall test score and UPDRS for all test periods is adequate (r=-0.6). In an exact Wilcoxon signed rank test, where the endpoint is the change from the first to the twelve month test period (n=25), there was no change in test results in any of the test battery dimensions for the patients already receiving infusion when included. However, in the patients entering the study before receiving infusion, there was a significant change (improvement) from the baseline to the twelve month test period in dimensions; ‘off’, ‘dyskinesia’ and ‘satisfied’ and in the ‘overall score’ (n=15). The mean improvement in overall score after infusion was 29% (p=0.015). We conclude that the test battery is able to measure a functional improvement with infusion that is sustained over at least twelve months.

Self-reported symptoms and motor tests via telemetry in a 36-month levodopa-carbidopa intestinal gel infusion trial

Objective To investigate if a home environment test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression. Background Seventy-seven patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study at 10 clinics in Sweden and Norway; 40 of them were treated with levodopa-carbidopa intestinal gel (LCIG) and 37 patients were candidates for switching from oral PD treatment to LCIG. They utilized a mobile device test battery, consisting of self-assessments of symptoms and objective measures of motor function through a set of fine motor tests (tapping and spiral drawings), in their homes. Both the LCIG-naïve and LCIG-non-naïve patients used the test battery four times per day during week-long test periods. Methods Assessments The LCIG-naïve patients used the test battery at baseline (before LCIG), month 0 (first visit; at least 3 months after intraduodenal LCIG), and thereafter quarterly for the first year and biannually for the second and third years. The LCIG-non-naïve patients used the test battery from the first visit, i.e. month 0. Out of the 77 patients, only 65 utilized the test battery; 35 were LCIG-non-naïve and 30 LCIG-naïve. In 20 of the LCIG-naïve patients, assessments with the test battery were available during oral treatment and at least one test period after having started infusion treatment. Three LCIG-naïve patients did not use the test battery at baseline but had at least one test period of assessments thereafter. Hence, n=23 in the LCIG-naïve group. In total, symptom assessments in the full sample (including both patient groups) were collected during 379 test periods and 10079 test occasions. For 369 of these test periods, clinical assessments including UPDRS and PDQ-39 were performed in afternoons at the start of the test periods. The repeated measurements of the test battery were processed and summarized into scores representing patients’ symptom severities over a test period, using statistical methods. Six conceptual dimensions were defined; four subjectively-reported: ‘walking’, ‘satisfied’, ‘dyskinesia’, and ‘off’ and two objectively-measured: ‘tapping’ and ‘spiral’. In addition, an ‘overall test score’ (OTS) was defined to represent the global health condition of the patient during a test period. Statistical methods Change in the test battery scores over time, that is at baseline and follow-up test periods, was assessed with linear mixed-effects models with patient ID as a random effect and test period as a fixed effect of interest. The within-patient variability of OTS was assessed using intra-class correlation coefficient (ICC), for the two patient groups. Correlations between clinical rating scores and test battery scores were assessed using Spearman’s rank correlations (rho). Results In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. However, there were no significant changes in mean OTS scores of LCIG-non-naïve patients, except for worse mean OTS at month 36 (p<0.01, n=16). The mean scores of all subjectively-reported dimensions improved significantly throughout the course of the study, except ‘walking’ at month 36 (p=0.41, n=4). However, there were no significant differences in mean scores of objectively-measured dimensions between baseline and other test periods, except improved ‘tapping’ at month 6 and month 36, and ‘spiral’ at month 3 (p<0.05). The LCIG-naïve patients had a higher within-subject variability in their OTS scores (ICC=0.67) compared to LCIG-non-naïve patients (ICC=0.71). The OTS correlated adequately with total UPDRS (rho=0.59) and total PDQ-39 (rho=0.59). Conclusions In this 3-year follow-up study of advanced PD patients treated with LCIG we found that it is possible to monitor PD progression over time using a home environment test battery. The significant improvements in the mean OTS scores indicate that the test battery is able to measure functional improvement with LCIG sustained over at least 24 months.

Emergency department triage scales and their components : a systematic review of the scientific evidence

Emergency department (ED) triage is used to identify patients' level of urgency and treat them based on their triage level. The global advancement of triage scales in the past two decades has generated considerable research on the validity and reliability of these scales. This systematic review aims to investigate the scientific evidence for published ED triage scales. The following questions are addressed: 1. Does assessment of individual vital signs or chief complaints affect mortality during the hospital stay or within 30 days after arrival at the ED? 2. What is the level of agreement between clinicians' triage decisions compared to each other or to a gold standard for each scale (reliability)? 3. How valid is each triage scale in predicting hospitalization and hospital mortality? A systematic search of the international literature published from 1966 through March 31, 2009 explored the British Nursing Index, Business Source Premier, CINAHL, Cochrane Library, EMBASE, and PubMed. Inclusion was limited to controlled studies of adult patients (≥15 years) visiting EDs for somatic reasons. Outcome variables were death in ED or hospital and need for hospitalization (validity). Methodological quality and clinical relevance of each study were rated as high, medium, or low. The results from the studies that met the inclusion criteria and quality standards were synthesized applying the internationally developed GRADE system. Each conclusion was then assessed as having strong, moderately strong, limited, or insufficient scientific evidence. If studies were not available, this was also noted. We found ED triage scales to be supported, at best, by limited and often insufficient evidence. The ability of the individual vital signs included in the different scales to predict outcome is seldom, if at all, studied in the ED setting. The scientific evidence to assess interrater agreement (reliability) was limited for one triage scale and insufficient or lacking for all other scales. Two of the scales yielded limited scientific evidence, and one scale yielded insufficient evidence, on which to assess the risk of early death or hospitalization in patients assigned to the two lowest triage levels on a 5-level scale (validity).

A systematic review of triage-related interventions to improve patient flow in emergency departments

Background Overcrowding in emergency departments is a worldwide problem. A systematic literature review was undertaken to scientifically explore which interventions improve patient flow in emergency departments. Methods A systematic literature search for flow processes in emergency departments was followed by assessment of relevance and methodological quality of each individual study fulfilling the inclusion criteria. Studies were excluded if they did not present data on waiting time, length of stay, patients leaving the emergency department without being seen or other flow parameters based on a nonselected material of patients. Only studies with a control group, either in a randomized controlled trial or in an observational study with historical controls, were included. For each intervention, the level of scientific evidence was rated according to the GRADE system, launched by a WHO-supported working group. Results The interventions were grouped into streaming, fast track, team triage, point-of-care testing (performing laboratory analysis in the emergency department), and nurse-requested x-ray. Thirty-three studies, including over 800,000 patients in total, were included. Scientific evidence on the effect of fast track on waiting time, length of stay, and left without being seen was moderately strong. The effect of team triage on left without being seen was relatively strong, but the evidence for all other interventions was limited or insufficient. Conclusions Introducing fast track for patients with less severe symptoms results in shorter waiting time, shorter length of stay, and fewer patients leaving without being seen. Team triage, with a physician in the team, will probably result in shorter waiting time and shorter length of stay and most likely in fewer patients leaving without being seen. There is only limited scientific evidence that streaming of patients into different tracks, performing laboratory analysis in the emergency department or having nurses to request certain x-rays results in shorter waiting time and length of stay.

Are central bank independence reforms necessary for achieving low and stable inflation?

Using data on the occurence of central bank independence (CBI) reforms in 131 countries during 1980-2005, we test whether they were important in reducing inflation and maintaining price stability. CBI reforms are found to have reduced inflation on average 3.31% when countries with historically high inflation rates are included. But countries with lower inflation have reduced it without institutional reforms granting central banks more independence, undermining the theoretical time-inconsistency case for CBI. There is furthermore no evidence that CBI reforms have helped reduce inflation variability.

When IKEA enters : Do local retailers win or lose?

IKEA is one of the world’s largest retailers, but little is known about how IKEA impact incumbent retailers when deciding to enter a local market. Previous studies on the effects of big-box entry on surrounding retailers have also generated inconclusive results, and mainly been focused towards entry of Wal-Mart in the United States. We contribute to this literature by investigating the effects of IKEA entry on revenues and employment for incumbent retail firms in three Swedish municipalities during 2000-2010. Our results indicate that a new IKEA store increases average revenues for incumbent retailers within the entry municipality by 11%, but also that the effect is highly heterogeneous within the municipality. Retailers that were located up to 1 km from IKEA experienced a 26% increase in revenues when IKEA entered the municipality. However, the positive spillover effect of a new IKEA store on retail revenues diminished with the distance to IKEA, and turned insignificant for retailers in the city centers and those that were located 5-10 km from IKEA. The effects on employment were much less pronounced, and in most cases statistically insignificant.

Krönika : Max Weber – myt och verklighet. Religion, kärlek, pengar och politik

Sociologisk Forsknings digitala arkiv

High-growth firms : Not so vital after all?

High-growth firms have received considerable interest recently since they create most of the new jobs in the economy. The purpose of our paper is to investigate the characteristics of high-growth firms prior to their growth period, and whether these characteristics differ across industries. Using data on a large sample of limited liability firms in Sweden for the period 2007-2010, we find that high-growth firms do not have the characteristics that we typically associate with successful firms. On the contrary, our results indicate that high-growth firms have low profits and a weak financial position. This might explain why studies have found that high-growth firms are seldom capable of sustaining their high growth rates in subsequent periods, and thus question policies that are targeted towards these companies.

Osynliga jobbskapare : En tillväxtpotential för svensk detaljhandel?

Den stora merparten av alla detaljhandelsföretag karakteriseras av ingen eller en marginell tillväxt av antalet anställda. Dessa företag betraktas ofta som en homogen grupp bestående av företag med inga tillväxtambitioner och som näringspolitiken inte bör inriktas gentemot. I denna rapport visar vi dock att de företag som inte växer i själva verket är mycket heterogena. Mer än tio procent av alla detaljhandelsföretag som inte växer under en treårsperiod kännetecknas av en relativt hög lönsamhet. Dessa företag kallar vi för de sovande gasellerna eftersom tidigare studier har visat att hög lönsamhet är en viktig faktor för en långsiktigt hållbar framtida tillväxt av antalet anställda. Andelen sovande gaseller inom detaljhandeln är cirka 1,5 till 2,35 procentenheter fler än i ekonomin som helhet. Hälften av dessa detaljhandelsföretag kommer inte heller att öka antalet anställda i kommande perioder, trots att de fortsätter att ha en hög lönsamhet eller en lönsamhet i paritet med det genomsnittliga företaget. Detta visar att det finns en dold tillväxtpotential inom detaljhandeln i Sverige som inte har realiserat. Resultaten från studien visar också att de sovande gasellerna inom detaljhandeln inte är slumpmässigt dragna ur företagspopulationen, utan att det framförallt är små företag som väljer att inte expandera verksamheten mellan två treårsperioder. De sovande gasellerna är inte heller slumpmässigt fördelade geografiskt i Sverige. De kommuner som har en hög andel sovande gaseller inom detaljhandeln under en tidsperiod tenderar att även ha det i kommande tidsperioder, vilket indikerar att det finns geografiska förklaringar till varför vissa företag inte växer trots att de har en god lönsamhet. Avsaknaden av tillväxt hos dessa företag kan antingen förklaras av att de inte har några tillväxtambitioner, oavsett villkoren för företagande; alternativt att de vill växa, men inte under rådande förutsättningar. Om den senare förklaringen är giltig kan reformer som minskar tillväxtbarriärer för detaljhandelsföretagen generera många nya arbetstillfällen.

Validity and responsiveness of at-home touch-screen assessments in advanced Parkinson's disease

The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on Unified PD Rating Scale (UPDRS) and 39-item PD Questionnaire (PDQ-39) scales. In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non-naïve patients, there were no significant changes in mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS respectively. The trends of the test scores were similar to the trends of clinical rating scores but dropout rate was high. Correlations between OTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS.

Musikfolkhögskolans utbildningsideologier

I denna artikel redogörs för två delstudier i projektet Musikfolkhögskolans utbildningsideologier. Dels behandlas utbildningsideologier bland svenska folkmusiker under 1920-talet (von Wachenfeldt, Brändström & Liljas, 2012a) och dels ges en bild av hur undervisningen av folkmusiker kan gestalta sig i en samtidskontext (von Wachenfeldt, Brändström & Liljas, 2012b).I projektet som helhet anknyts till ett ideologibegrepp som utvecklats av Sven-Erik Liedman. Han menar att det för varje tid fnns två identiferbara grundformer av ideologi: manifesta och latenta (1997; 2006). Manifesta ide-ologier avser explicita och medvetet formulerade utsagor med ideologiskt innehåll som binder samman verklighetspåståenden, värderingar och nor-mer. Latenta eller frusna ideologier är sådant som fnns under ytan och som tas för givet av fältets aktörer.

Manifesta och latenta ideologier om lärande inom svensk spelmansrörelse under 1920-talet

The purpose of this article was to illuminate existing educational ideologies in the Swedish fiddler movement (Spelmansrörelsen) 1923-1927. This period was characterized by the organization and to some extent institutionalization of Swedish folk music. Furthermore, the purpose was to discuss the results in relation to the folk music education of today. The empirical data was taken from the journal Hembygden, which was a magazine for scholars, enthusiasts and practitioners of folk music. Theoretically, the study was based on a concept of ideology developed by Sven-Eric Liedman: in every time there are two basic forms of identifiable ideology, manifest and latent. From the empirical material as a whole (around 900 articles), a selection was made to find articles dealing with aspects of learning among the fiddlers (33 articles). After content analysis the following themes were generated: Fiddlers’ repertoire, Fiddlers’ masters, Rooms for learning, Learning formation. The writers in Hembygden often emphasized the autodidactic aspects of learning and especially the importance of learning by ear. This manifest ideology of authenticity presumed that learning directly from another fiddler by playing together was to prefer to formal schooling. In spite of a tendency towards more ensemble playing, the folk music education of today in Sweden is characterized by a similar retrospective ideology as in the 1920s.

What determines the use of capital budgeting methods? : Evidence from Swedish listed companies

Purpose: This paper aims to extend and contribute to prior research on the association between company characteristics and choice of capital budgeting methods (CBMs). Design/methodology/approach: A multivariate regression analysis on questionnaire data from 2005 and 2008 is used to study which factors determine the choice of CBMs in Swedish listed companies. Findings: Our results supported hypotheses that Swedish listed companies have become more sophisticated over the years (or at least less unsophisticated) which indicates a closing of the theory-practice gap; that companies with greater leverage used payback more often; and that companies with stricter debt targets and less management ownership employed accounting rate of return more frequent. Moreover, larger companies used CBMs more often. Originality/value: The paper contributes to prior research within this field by being the first Swedish study to examine the association between use of CBMs and as many as twelve independent variables, including changes over time, by using multivariate regression analysis. The results are compared to a US and a continental European study.

Real-Time Flood Forecasting Systems In Flanders

As a highly urbanized and flood prone region, Flanders has experienced multiple floods causing significant damage in the past. In response to the floods of 1998 and 2002 the Flemish Environment Agency, responsible for managing 1 400 km of unnavigable rivers, started setting up a real time flood forecasting system in 2003. Currently the system covers almost 2 000 km of unnavigable rivers, for which flood forecasts are accessible online (www.waterinfo.be). The forecasting system comprises more than 1 000 hydrologic and 50 hydrodynamic models which are supplied with radar rainfall, rainfall forecasts and on-site observations. Forecasts for the next 2 days are generated hourly, while 10 day forecasts are generated twice a day. Additionally, twice daily simulations based on percentile rainfall forecasts (from EPS predictions) result in uncertainty bands for the latter. Subsequent flood forecasts use the most recent rainfall predictions and observed parameters at any time while uncertainty on the longer-term is taken into account. The flood forecasting system produces high resolution dynamic flood maps and graphs at about 200 river gauges and more than 3 000 forecast points. A customized emergency response system generates phone calls and text messages to a team of hydrologists initiating a pro-active response to prevent upcoming flood damage. The flood forecasting system of the Flemish Environment Agency is constantly evolving and has proven to be an indispensable tool in flood crisis management. This was clearly the case during the November 2010 floods, when the agency issued a press release 2 days in advance allowing water managers, emergency services and civilians to take measures.