| 1. |
- Malinovschi, Andrei, 1978-, et al.
(författare)
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Assessment of Global Lung Function Initiative (GLI) reference equations for diffusing capacity in relation to respiratory burden in the Swedish CArdioPulmonary bioImage Study (SCAPIS)
- 2020
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Ingår i: European Respiratory Journal. - Lausanne, Switzerland : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 56:2
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Tidskriftsartikel (refereegranskat)abstract
- The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (DLCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired DLCO. We examined if the GLI LLN for DLCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden.Spirometry, DLCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15 040 participants, aged 50–64 years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women).Both the median and LLN for DLCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of DLCO DLCO >GLI LLN but DLCO >GLI LLN but versus 4.5%, p<0.001), chronic airflow limitation (8.5% versus 3.9%, p<0.001) and chronic bronchitis (8.3% versus 4.4%, p<0.01) than subjects (n=13 600) with normal DLCO (>GLI LLN and >SCAPIS LLN). No differences were found with regard to physician-diagnosed asthma.The GLI LLN for DLCO is lower than the estimated LLN in healthy, never-smoking, middle-aged Swedish adults. Individuals with DLCO above the GLI LLN but below the SCAPIS LLN had, to a larger extent, an increased respiratory burden. This suggests clinical implications for choosing an adequate LLN for studied populations.
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| 2. |
- Gullestad, Lars, et al.
(författare)
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Everolimus With Reduced Calcineurin Inhibitor in Thoracic Transplant Recipients With Renal Dysfunction: A Multicenter, Randomized Trial
- 2010
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Ingår i: Transplantation. - : Williams and Wilkins. - 0041-1337 .- 1534-6080. ; 89:7, s. 864-872
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Tidskriftsartikel (refereegranskat)abstract
- Background. The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking. Methods. In a 12-month, open-labeled, multicenter study, maintenance thoracic transplant patients (glomerular filtration rate greater than= 20 mL/min/1.73m(2) and less than90 mL/min/1.73 m(2)) greater than1 year posttransplant were randomized to continue their current CNI-based immunosuppression or start everolimus with predefined CNI exposure reduction. Results. Two hundred eighty-two patients were randomized (140 everolimus, 142 controls; 190 heart, 92 lung transplants). From baseline to month 12, mean cyclosporine and tacrolimus trough levels in the everolimus cohort decreased by 57% and 56%, respectively. The primary endpoint, mean change in measured glomerular filtration rate from baseline to month 12, was 4.6 mL/min with everolimus and -0.5 mL/min in controls (Pless than0.0001). Everolimus-treated heart and lung transplant patients in the lowest tertile for time posttransplant exhibited mean increases of 7.8 mL/min and 4.9 mL/min, respectively. Biopsy-proven treated acute rejection occurred in six everolimus and four control heart transplant patients (P=0.54). In total, 138 everolimus patients (98.6%) and 127 control patients (89.4%) experienced one or more adverse event (P=0.002). Serious adverse events occurred in 66 everolimus patients (46.8%) and 44 controls (31.0%) (P=0.02). Conclusion. Introduction of everolimus with CNI reduction offers a significant improvement in renal function in maintenance heart and lung transplant recipients. The greatest benefit is observed in patients with a shorter time since transplantation.
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| 3. |
- Gullestad, Lars, et al.
(författare)
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Two-Year Outcomes in Thoracic Transplant Recipients After Conversion to Everolimus With Reduced Calcineurin Inhibitor Within a Multicenter, Open-Label, Randomized Trial.
- 2010
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Ingår i: Transplantation. - : Williams and Wilkins. - 1534-6080 .- 0041-1337. ; 90:12, s. 1581-1589
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND.: Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required. METHODS.: In a prospective, open-label, multicenter study, thoracic transplant recipients more than or equal to 1 year posttransplant with mild-to-moderate renal insufficiency were randomized to continue their current CNI-based immunosuppression or convert to everolimus with predefined CNI exposure reduction. After a 12-month core trial, patients were followed up to month 24 after randomization. RESULTS.: Of 245 patients who completed the month 12 visit, 235 patients (108 everolimus and 127 controls) entered the 12-month extension phase. At month 24, mean measured glomerular filtration rate had increased by 3.2±12.3 mL/min from the point of randomization in everolimus-treated patients and decreased by 2.4±9.0 mL/min in controls (P<0.001), a difference that was significant within both the heart and lung transplant subpopulations. During months 12 to 24, 5.6% of everolimus patients and 3.1% of controls experienced biopsy-proven acute rejection (P=0.76). There were no significant differences in the rate of adverse events or serious adverse events (including pneumonia) between groups during months 12 to 24. CONCLUSIONS.: Converting maintenance thoracic transplant recipients to everolimus with low-exposure CNI results in a renal benefit that is sustained to 2 years postconversion, with significantly improved measured glomerular filtration rate in both heart and lung transplant patients. Despite reductions of more than 50% in CNI exposure, there was no marked loss of efficacy. The safety profile of the everolimus-based regimen was acceptable.
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| 4. |
- Gustafsson, Finn, et al.
(författare)
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Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients : Long-term Follow-up From the Randomized SCHEDULE Study
- 2020
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Ingår i: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1534-6080 .- 0041-1337. ; 104:1, s. 154-164
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A calcineurin inhibitor (CNI)-free immunosuppressive regimen has been demonstrated to improve renal function early after heart transplantation, but long-term outcome of such a strategy has not been well described. METHODS: In the randomized SCHEDULE trial, de novo heart transplant recipients received (1) everolimus with reduced-exposure CNI (cyclosporine) followed by CNI withdrawal at week 7-11 posttransplant or (2) standard-exposure cyclosporine, both with mycophenolate mofetil and corticosteroids; 95/115 randomized patients were followed up at 5-7 years posttransplant. RESULTS: Mean measured glomerular filtration rate was 74.7 mL/min and 62.4 mL/min with everolimus and CNI, respectively. The mean difference was in favor of everolimus by 11.8 mL/min in the intent-to-treat population (P = 0.004) and 17.2 mL/min in the per protocol population (n = 75; P < 0.001). From transplantation to last follow-up, the incidence of biopsy-proven acute rejection (BPAR) was 77% (37/48) and 66% (31/47) (P = 0.23) with treated BPAR in 50% and 23% (P < 0.01) in the everolimus and CNI groups, respectively; no episode led to hemodynamic compromise. Coronary allograft vasculopathy (CAV) assessed by coronary intravascular ultrasound was present in 53% (19/36) and 74% (26/35) of everolimus- and CNI-treated patients, respectively (P = 0.037). Graft dimensions and function were similar between the groups. Late adverse events were comparable. CONCLUSIONS: These results suggest that de novo heart transplant patients randomized to everolimus and low-dose CNI followed by CNI-free therapy maintain significantly better long-term renal function as well as significantly reduced CAV than patients randomized to standard CNI treatment. Increased BPAR in the everolimus group during year 1 did not impair long-term graft function.
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| 5. |
- Jansson, Kjell, et al.
(författare)
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Bör kollektivtrafik subventioneras?
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Detta arbete analyserar motiv för subventionering av lokal och regional kollektivtrafik, baserat på ekonomisk teori och på numeriska modellberäkningar, med den huvudsakliga slutsatsen att det är samhällsekonomiskt lönsamt att subventionera kollektivtrafik och att öka turtätheten där efterfrågan är hög. Att lokal och regional kollektivtrafik subventioneras i första hand med skattemedel är vanligt i de flesta industrialiserade länder, ofta i storleksordningen 40–60 procent. I dag subventionerar regionala kollektivtrafikmyndigheter i Sverige kollektivtrafiken med mellan 44 och 80 procent av kostnaderna.Det vi framför som det huvudsakliga samhällsekonomiska motivet för subventionering är att kollektivtrafik utmärks av en positiv extern effekt som kommersiella operatörer inte beaktar (är extern för dem) beroende på deras behov av finansiell vinst. Den positiva externa effekten, ofta kallad Mohring-effekten, består av att befintliga trafikanters väntetid minskar om priset sänks och ytterligare trafikanter motiverar ökad turtäthet. Med optimal nivå på pris och turtäthet täcks inte ens kollektivtrafikens rörliga kostnader, varför kompletterande finansiering via beskattning krävs.För att uppskatta det optimala priset och den optimala subventionsnivån gör vi beräkningar för varje linje med dels en särskild optimeringsmodell för en kollektivtrafiklinje dels en simuleringsmodell för efterfrågberäkningar. De numeriska modellberäkningarna söker välfärdsoptima för priser, turtätheter (frekvenser) och subventioner med hänsyn till väntetider och trängsel i fordonen. För att finna dessa optima kombineras beräkningar med simuleringsmodellen och optimeringsmodellen.Pris, turtäthet och subvention har optimerats för sju olika linjer i Stockholms läns kollektivtrafik, allt ifrån en lågbelastad busslinje i landsbygd till de hårdbelastade linjerna: busslinje 4 i Stockholms innerstad samt en tunnelbane- och en pendeltågslinje. De optimeringsmetoder som används är generellt användbara. De kan dock förväntas ge olika resultat beroende på lokala efterfrågenivåer, tidsvärderingar och driftskostnader. Jämfört med utgångsläget innebär välfärdsoptimum lägre priser än i dag för samtliga sju studerade linjer och högre frekvenser för de flesta, med undantag av busslinjer i mindre tättbefolkade områden med låg efterfrågan.Känslighetsanalyser visar att antaganden om väntetidsvärderingar och samhällsekonomisk kostnad för skattefinansiering (skattefaktor) spelar stor roll för nivån för optimal subvention, pris, turintervall och för välfärdsförändring. Med lägre tidsvärderingar och/eller större skattefaktor är optimal subvention mindre, optimalt pris högre och optimal turtäthet lägre.
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| 6. |
- Jansson, Kjell, 1947-, et al.
(författare)
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Samhällsekonomisk analys av förändrad frekvens och taxa för regionaltågstrafik i Mälardalen
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Under de senaste två decennierna har både utbud av och resande med regionaltåg ökat väsentligt i Sverige. Konsekvenserna av dessa ökningar har hittills endast i begränsad utsträckning analyserats från samhällsekonomisk utgångspunkt. Syftet med denna studie är att med hjälp av efterfrågesimuleringar analysera konsekvenserna av tänkta förändringar av frekvens och taxor nedåt respektive uppåt på två regionala linjer i Mälardalen: Västerås till Stockholm och Hallsberg till Stockholm. Konsekvenserna beskrivs i termer av beräknade förändringar av efterfrågan, resenärernas nytta, intäkter och kostnader för olika kollektiva trafikslag, externa effekter, operatörernas finanser (företagsekonomiska netto), den offentliga sektorns finanser (den offentliga sektorns intäkter minus kostnader) samt samhällsekonomi. Beräkningarna visar att det rent finansiellt skulle löna sig att minska turtätheterna, men tvärtom innebära en förlust att öka dem, samt att båda höjda och sänkta taxor skulle innebära finansiell förlust. Samhällsekonomiskt visar beräkningarna att det, liksom finansiellt, är lönsamt att minska turtätheterna men olönsamt att öka dem. Höjda taxor innebär en förlust både finansiellt och samhällsekonomiskt. Den enda policy för vilken riktningen på de beräknade finansiella och samhällsekonomiska utfallen är olika är en taxesänkning. En taxesänkning bedöms vara företagsekonomiskt olönsam, men beräknas vara samhällsekonomiskt lönsamt.
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| 7. |
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| 8. |
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| 9. |
- Jansson, Kjell, 1956-, et al.
(författare)
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The value of repeated echocardiographic evaluation in patients with idiopathic dilated cardiomyopathy during treatment with metoprolol or captopril
- 2000
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Ingår i: Scandinavian Cardiovascular Journal. - 1401-7431 .- 1651-2006. ; 34:3, s. 293-300
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Tidskriftsartikel (refereegranskat)abstract
- Serial echocardiographic investigations were carried out on patients with idiopathic dilated cardiomyopathy, to evaluate treatment effects on left ventricular (LV) performance during therapy with either metoprolol or captopril. Thirty-two patients (23 males and 9 females) with mild to moderate symptoms of heart failure (NYHA II-III) and a mean age of 49 years were included in the investigation. The patients were investigated with Doppler echocardiography before treatment, after 3 and 6 months of treatment (either metoprolol or captopril) and 1 month after withdrawal of treatment. Intra- and inter-investigator reproducibility was acceptable, with a coefficient of variation of less than 5% for LV dimensions. A reduction in LV dimensions was seen in both treatment groups. In the metoprolol group there was also an increase in LV stroke volume and fractional shortening. The non-invasive data were in accordance with invasive measurements of stroke volume and LV filling pressure. In patients with idiopathic dilated cardiomyopathy and mild to moderate symptoms of heart failure, echocardiography seemed to be sufficiently reproducible to be used for determination of treatment effects in a longitudinal heart failure study. Both metoprolol and captopril were well tolerated and had favourable effects on LV performance.
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| 10. |
- Jansson, Kjell, 1956-
(författare)
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Treatment in Dilated Cardiomyopathy : with special emphasis on beta-adrenergic receptor blockade and angiotensin-converting enzyme inhibition
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dilated cardiomyopathy (DCM) is a heart muscle disease of unknown origin, characterised by ventricular dilatation and impairment of systolic function. The basic treattnent is medical, according to different pharmacological principles. Evaluation of the severity of the disease and the effects of medication are important for optimal management.Fifty-four patients (42 male and 12 female) with DCM were randomized to receive treatment with either a beta-adrenergic receptor blocker (metoprolol) or an angiotensin-converting enzyme (ACE) inhibitor (captopril). Almost all patients had a history of congestive heart failure and were therefore treated with furosemide. Baseline characteristics and the effects of therapy were studied by invasive haemodynamics, echocardiography, neurohormonal function, heart rate variability and quality of life evaluation.There were favourable effects on left ventricular (LV) function with both drugs but metoprolol seemed to be superior to captopril in improving LV stroke volume and reducing LV filling pressure. There was a reduction in both systolic and diastolic dimensions and the non-invasive findings were in accordance with invasive results. Neurohormonal activation was less than expected and the levels of plasma renin activity and angiotensin II were within the normal range while the levels of atrial natriuretic peptide were increased. Urinary excretion of Aldosterone was reduced with both metoprolol and captopril therapy, but treatment with petoprolol reduced the level of ANP during exercise.Both drugs increased heart rate variability but petoprolol was superior to captopril in increasing totaol power and power in the low and very low frequency.Quality of life was assessed by a disease-specific questionnaire and wsa improved in the dimension "emotion" in both groups during treatment. In the captopril group there were also improvements in total score and in the dimension "physical activity". Improvements in quality of life dimensions, however, did not correlate to improvement in LV function.In conclusion both metoprolol and captopril were well tolerated. There were effects of beta-adrenergic receptor blockade on LV performance that were not obtained, at least not equally, during therapy with ACE inhibitor. Itreatment of patients with DCM should therefore include a beta-receptor blocker. Carefully performed, non-invasive methods can be used to evaluate the effects of therapy.
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