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1.
  • Gunduz, C., et al. (författare)
  • Hyperlipidaemia prevalence and cholesterol control in obstructive sleep apnoea: Data from the European sleep apnea database (ESADA)
  • 2019
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 676-688
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objective Obstructive sleep apnoea (OSA) and hyperlipidaemia are independent risk factors for cardiovascular disease. This study investigates the association between OSA and prevalence of hyperlipidaemia in patients of the European Sleep Apnea Database (ESADA) cohort. Methods The cross-sectional analysis included 11 892 patients (age 51.9 +/- 12.5 years, 70% male, body mass index (BMI) 31.3 +/- 6.6 kg/m(2), mean oxygen desaturation index (ODI) 23.7 +/- 25.5 events/h) investigated for OSA. The independent odds ratio (OR) for hyperlipidaemia in relation to measures of OSA (ODI, apnoea-hypopnoea index, mean and lowest oxygen saturation) was determined by means of general linear model analysis with adjustment for important confounders such as age, BMI, comorbidities and study site. Results Hyperlipidaemia prevalence increased from 15.1% in subjects without OSA to 26.1% in those with severe OSA, P < 0.001. Corresponding numbers in patients with diabetes were 8.5% and 41.5%, P < 0.001. Compared with ODI quartile I, patients in ODI quartiles II-IV had an adjusted OR (95% CI) of 1.33 (1.15-1.55), 1.37 (1.17-1.61) and 1.33 (1.12-1.58) (P < 0.001), respectively, for hyperlipidaemia. Obesity was defined as a significant risk factor for hyperlipidaemia. Subgroups of OSA patients with cardio-metabolic comorbidities demonstrated higher prevalence of HL. In addition, differences in hyperlipidaemia prevalence were reported in European geographical regions with the highest prevalence in Central Europe. Conclusion Obstructive sleep apnoea, in particular intermittent hypoxia, was independently associated with the prevalence of hyperlipidaemia diagnosis.
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  • Fietze, I, et al. (författare)
  • Management of obstructive sleep apnea in Europe
  • 2011
  • Ingår i: Sleep Medicine. - : Elsevier. - 1389-9457 .- 1878-5506. ; 12:2, s. 190-197
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: In Europe, the services provided for the investigation and management of obstructive sleep apnoea (OSA) varies from country to country. The aim of this questionnaire-based study was to investigate the current status of diagnostic pathways and therapeutic approaches applied in the treatment of OSA in Europe, qualification requirements of physicians involved in diagnosis and treatment of OSA, and reimbursement of these services. Methods: Two questionnaires were sent to 39 physicians in 22 countries in Europe. In order to standardize the responses, the questionnaire was accompanied by an example. Results: Sleep centers from 21 countries (38 physicians) participated. A broad consistency among countries with respect to the following was found: pathways included referral to sleep physicians/sleep laboratories, necessity for objective diagnosis (primarily by polysomnography), use of polygraphic methods, analysis of polysomnography (PSG), indications for positive airway pressure (PAP) therapy, application of standard continuous PAP (CPAP) therapy (100% with an CPAP/APAP ratio of 2.24:1), and the need (90.5%) and management of follow-up. Differences were apparent in reimbursement of the diagnostic procedures and follow-up, in the procedures for PAP titration from home APAP titration with portable sleep apnea monitoring (38.1%) up to hospital monitoring with PSG and APAP (85.7%), and in the qualification requirements of sleep physicians. Conclusions: Management of OSA in different European countries is similar except for reimbursement rules, qualification of sleep specialists and procedures for titration of the CPAP treatment. A European network (such as the one accomplished by the European Cooperation in Science and Technology [COST] B26 Action) could be helpful for implementing these findings into health-service research in order to standardize management in a cost effective perspective.
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  • Gunduz, C., et al. (författare)
  • Long-term positive airway pressure therapy is associated with reduced total cholesterol levels in patients with obstructive sleep apnea: data from the European Sleep Apnea Database (ESADA)
  • 2020
  • Ingår i: Sleep Medicine. - : Elsevier BV. - 1389-9457. ; 75, s. 201-209
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aim: Obstructive sleep apnea (OSA) is an independent risk factor for dyslipidemia. The current study examined the effects of positive airway pressure (PAP) treatment on lipid status in the European Sleep Apnea Database (ESADA). Methods: The prospective cohort study enrolled 1564 OSA subjects (74% male, mean age 54 ± 11y, body mass index (BMI) 32.7 ± 6.6 kg/m2 and apnea-hypopnea index (AHI) 40.3 ± 24.4 n/h) undergoing PAP therapy for at least three months (mean 377.6 ± 419.5 days). Baseline and follow-up total cholesterol (TC) from nine centers were analyzed. Repeated measures and logistic regression tests (adjusted for age, sex, weight changes, lipid lowering medication, PAP compliance, and treatment duration) were used to compare changes in TC concentration. Incident risk for a coronary heart disease event (CHD) was used to compute a Framingham CHD risk score (estimated from age, BMI, blood pressure, and TC). Results: Adjusted means of TC decreased from 194.2 mg/dl to 189.3 mg/dl during follow-up (p = 0.019). A clinically significant (10%) reduction of TC at PAP follow-up was observed in 422 patients (27%). Duration of PAP therapy was identified as independent predictor for TC reduction, which implies an approximately 10% risk reduction for incident CHD events (from 26.7% to 24.1% in men and from 11.2% to 10.1% in women, p < 0.001 respectively). Conclusion: This observational study demonstrates a reduction of TC after long-term PAP treatment. The close association between TC concentration and cardiovascular (CV) mortality suggests that identification and treatment of OSA may have a beneficial effect on overall CV risk due to this mechanism. This possibility needs to be evaluated in prospective randomized studies. © 2020 Elsevier B.V.
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  • Lombardi, C., et al. (författare)
  • Periodic limb movements during sleep and blood pressure changes in sleep apnoea: Data from the European Sleep Apnoea Database
  • 2020
  • Ingår i: Respirology. - : Wiley. - 1323-7799 .- 1440-1843. ; 25:8, s. 872-879
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objective OSA and PLMS are known to induce acute BP swings during sleep. Our current study aimed to address the independent effect of PLMS on BP in an unselected OSA patient cohort. Methods This cross‐sectional analysis included 1487 patients (1110 males, no previous hypertension diagnosis or treatment, mean age: 52.5years, mean BMI: 30.5kg/m2) with significant OSA (defined as AHI≥10) recruited from the European Sleep Apnoea Cohort. Patients underwent overnight PSG. Patients were stratified into two groups: patients with significant PLMS (PLMSI>25 events/hour of sleep) and patients without significant PLMS (PLMSI<25 events/hour of sleep). SBP, DBP and PP were the variables of interest. For each of these, a multivariate regression linear model was fitted to evaluate the relationship between PLMS and outcome adjusting for sociodemographic and clinical covariates (gender, age, BMI, AHI, ESS, diabetes, smoking and sleep efficiency). Results The univariate analysis of SBP showed an increment of BP equal to 4.70mm Hg (P<0.001) in patients with significant PLMS compared to patients without significant PLMS. This increment remained significant after implementing a multivariate regression model (2.64mm Hg, P = 0.044). No significant increment of BP was observed for DBP and PP. Conclusion PLMS is associated with a rise in SBP regardless of AHI, independent of clinical and sociodemographic confounders. A PLMS phenotype may carry an increased risk for cardiovascular disease in OSA patients.
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  • Saaresranta, T., et al. (författare)
  • Clinical Phenotypes and Comorbidity in European Sleep Apnoea Patients
  • 2016
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Clinical presentation phenotypes of obstructive sleep apnoea (OSA) and their association with comorbidity as well as impact on adherence to continuous positive airway pressure (CPAP) treatment have not been established. A prospective follow-up cohort of adult patients with OSA (apnoea-hypopnoea index (AHI) of >= 5/h) from 17 European countries and Israel (n = 6,555) was divided into four clinical presentation phenotypes based on daytime symptoms labelled as excessive daytime sleepiness ("EDS") and nocturnal sleep problems other than OSA (labelled as "insomnia"): 1) EDS (daytime+/nighttime-), 2) EDS/insomnia (daytime+/nighttime+), 3) non-EDS/noninsomnia (daytime-/nighttime-), 4) and insomnia (daytime-/nighttime+) phenotype. The EDS phenotype comprised 20.7%, the non-EDS/non-insomnia type 25.8%, the EDS/insomnia type 23.7%, and the insomnia phenotype 29.8% of the entire cohort. Thus, clinical presentation phenotypes with insomnia symptoms were dominant with 53.5%, but only 5.6% had physician diagnosed insomnia. Cardiovascular comorbidity was less prevalent in the EDS and most common in the insomnia phenotype (48.9% vs. 56.8%, p<0.001) despite more severe OSA in the EDS group (AHI 35.0 +/- 25.5/h vs. 27.9 +/- 22.5/h, p<0.001, respectively). Psychiatric comorbidity was associated with insomnia like OSA phenotypes independent of age, gender and body mass index (HR 1.5 (1.188-1.905), p<0.001). The EDS phenotype tended to associate with higher CPAP usage (22.7 min/d, p = 0.069) when controlled for age, gender, BMI and sleep apnoea severity. Phenotypes with insomnia symptoms comprised more than half of OSA patients and were more frequently linked with comorbidity than those with EDS, despite less severe OSA. CPAP usage was slightly higher in phenotypes with EDS.
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  • Arnardottir, E. S., et al. (författare)
  • The Sleep Revolution project: the concept and objectives
  • 2022
  • Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 31:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Obstructive sleep apnea is linked to severe health consequences such as hypertension, daytime sleepiness, and cardiovascular disease. Nearly a billion people are estimated to have obstructive sleep apnea with a substantial economic burden. However, the current diagnostic parameter of obstructive sleep apnea, the apnea-hypopnea index, correlates poorly with related comorbidities and symptoms. Obstructive sleep apnea severity is measured by counting respiratory events, while other physiologically relevant consequences are ignored. Furthermore, as the clinical methods for analysing polysomnographic signals are outdated, laborious, and expensive, most patients with obstructive sleep apnea remain undiagnosed. Therefore, more personalised diagnostic approaches are urgently needed. The Sleep Revolution, funded by the European Union's Horizon 2020 Research and Innovation Programme, aims to tackle these shortcomings by developing machine learning tools to better estimate obstructive sleep apnea severity and phenotypes. This allows for improved personalised treatment options, including increased patient participation. Also, implementing these tools will alleviate the costs and increase the availability of sleep studies by decreasing manual scoring labour. Finally, the project aims to design a digital platform that functions as a bridge between researchers, patients, and clinicians, with an electronic sleep diary, objective cognitive tests, and questionnaires in a mobile application. These ambitious goals will be achieved through extensive collaboration between 39 centres, including expertise from sleep medicine, computer science, and industry and by utilising tens of thousands of retrospectively and prospectively collected sleep recordings. With the commitment of the European Sleep Research Society and Assembly of National Sleep Societies, the Sleep Revolution has the unique possibility to create new standardised guidelines for sleep medicine.
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  • Eliasson, T, et al. (författare)
  • Myocardial turnover of endogenous opioids and calcitonin-gene-related peptide in the human heart and the effects of spinal cord stimulation on pacing-induced angina pectoris.
  • 1998
  • Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 89:3, s. 170-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Earlier studies have shown that spinal cord stimulation (SCS) has antianginal and anti-ischemic effects in severe coronary artery disease. In the present study, 14 patients were subjected to right-sided atrial catheterization and atrial pacing. The patients were paced to angina during a control session and during spinal cord stimulation. Myocardial extraction of beta-endorphin (BE) during control pacing (8 +/- 22%) changed to release at the maximum pacing rate during treatment (-21 +/- 47%, a negative value representing release). Furthermore, the results indicate local myocardial turnover of leuenkephalin, BE and calcitonin-gene-related peptide. In addition, it is implied that SCS may induce myocardial release of BE which could explain the beneficial effects in myocardial ischemia.
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  • Hirsch, Jan M, et al. (författare)
  • Hemodynamic effects of the use of oral snuff
  • 1992
  • Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 52:4, s. 394-401
  • Tidskriftsartikel (refereegranskat)abstract
    • The hemodynamic effects during rest and exercise of oral snuff were investigated in an open, placebo-controlled study of nine habitual users of oral snuff. Blood pressure, heart rate, and central hemodynamics were measured noninvasively. Plasma concentrations of nicotine, cotinine, norepinephrine, and epinephrine, as well as neuropeptide Y-like immunoreactivity were measured before and after snuff intake during rest and exercise. Snuff intake induced a significant increase in heart rate and blood pressure and a decrease in stroke volume during rest. Hemodynamic changes were unrelated to nicotine or cotinine concentrations. Resting levels of norepinephrine and neuropeptide Y-like immunoreactivity were similar with or without snuff, whereas epinephrine was slightly increased 30 minutes after snuff intake. The exercise-induced increase in norepinephrine and neuropeptide Y-like immunoreactivity did not differ between the days subjects received snuff and the days they received placebo. In contrast, maximum work load was associated with a slight increase in circulating epinephrine after snuff intake. The findings suggest that snuff intake is associated with significant hemodynamic effects during rest but not during exercise. These effects could not be readily explained by activation of the sympathetic nervous system.
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  • Marrone, O., et al. (författare)
  • Fixed But Not Autoadjusting Positive Airway Pressure Attenuates the Time-dependent Decline in Glomerular Filtration Rate in Patients With OSA
  • 2018
  • Ingår i: Chest. - : Elsevier BV. - 0012-3692. ; 154:2, s. 326-334
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The impact of treating OSA on renal function decline is controversial. Previous studies usually included small samples and did not consider specific effects of different CPAP modalities. The aim of this study was to evaluate the respective influence of fixed and autoadjusting CPAP modes on estimated glomerular filtration rate (eGFR) in a large sample of patients derived from the prospective European Sleep Apnea Database cohort. METHODS: In patients of the European Sleep Apnea Database, eGFR prior to and after follow-up was calculated by using the Chronic Kidney Disease-Epidemiology Collaboration equation. Three study groups were investigated: untreated patients (n = 144), patients receiving fixed CPAP (fCPAP) (n = 1,178), and patients on autoadjusting CPAP (APAP) (n = 485). RESULTS: In the whole sample, eGFR decreased over time. The rate of eGFR decline was significantly higher in the subgroup with eGFR above median (91.42 mL/min/1.73 m(2)) at baseline (P < .0001 for effect of baseline eGFR). This decline was attenuated or absent (P < .0001 for effect of treatment) in the subgroup of patients with OSA treated by using fCPAP. A follow-up duration exceeding the median (541 days) was associated with eGFR decline in the untreated and APAP groups but not in the fCPAP group (P < .0001 by two-way ANOVA for interaction between treatment and follow-up length). In multiple regression analysis, eGFR decline was accentuated by advanced age, female sex, cardiac failure, higher baseline eGFR, and longer follow-up duration, whereas there was a protective effect of fCPAP. CONCLUSIONS: fCPAP but not APAP may prevent eGFR decline in OSA.
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  • Tasbakan, M. S., et al. (författare)
  • Positive airway pressure (PAP) treatment reduces glycated hemoglobin (HbA1c) levels in obstructive sleep apnea patients with concomitant weight loss: Longitudinal data from the ESADA
  • 2021
  • Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 30:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with obstructive sleep apnea (OSA) are at increased risk of developing metabolic disease such as diabetes. The effects of positive airway pressure on glycemic control are contradictory. We therefore evaluated the change in glycated hemoglobin (HbA1c) in a large cohort of OSA patients after long-term treatment with positive airway pressure. HbA1c levels were assessed in a subsample of the European Sleep Apnea Database [n=1608] at baseline and at long-term follow up with positive airway pressure therapy (mean 378.9±423.0 days). In a regression analysis, treatment response was controlled for important confounders. Overall, HbA1c decreased from 5.98±1.01% to 5.93±0.98% (p=0.001). Patient subgroups with a more pronounced HbA1c response included patients with diabetes (−0.15±1.02, p=0.019), those with severe OSA baseline (−0.10±0.68, p=0.005), those with morbid obesity (−0.20±0.81, p<0.001). The strongest HbA1c reduction was observed in patients with a concomitant weight reduction >5 kilos (−0.38±0.99, p<0.001). In robust regression analysis, severe OSA (p=0.038) and morbid obesity (p=0.005) at baseline, and weight reduction >5 kilos (p<0.001) during follow up were independently associated with a reduction of HbA1c following PAP treatment. In contrast, PAP treatment alone without weight reduction was not associated with significant Hb1Ac reduction. In conclusion, positive airway pressure therapy is associated with HbA1c reduction in patients with severe OSA, in morbidly obese patients. and most obviously in those with significant weight lost during the follow-up. Our study underlines the importance to combine positive airway pressure use with adjustments in lifestyle to substantially modify metabolic complications in OSA. © 2021 European Sleep Research Society
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  • Alonderis, A, et al. (författare)
  • Medico-legal implications of sleep apnoea syndrome: Driving license regulations in Europe.
  • 2008
  • Ingår i: Sleep medicine. - : Elsevier BV. - 1389-9457 .- 1878-5506. ; 9:4, s. 362-75
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Sleep apnoea syndrome (SAS), one of the main medical causes of excessive daytime sleepiness, has been shown to be a risk factor for traffic accidents. Treating SAS results in a normalized rate of traffic accidents. As part of the COST Action B-26, we looked at driving license regulations, and especially at its medical aspects in the European region. METHODS: We obtained data from Transport Authorities in 25 countries (Austria, AT; Belgium, BE; Czech Republic, CZ; Denmark, DK; Estonia, EE; Finland, FI; France, FR; Germany, DE; Greece, GR; Hungary, HU; Ireland, IE; Italy, IT; Lithuania, LT; Luxembourg, LU; Malta, MT; Netherlands, NL; Norway, EC; Poland, PL; Portugal, PT; Slovakia, SK; Slovenia, SI; Spain, ES; Sweden, SE; Switzerland, CH; United Kingdom, UK). RESULTS: Driving license regulations date from 1997 onwards. Excessive daytime sleepiness is mentioned in nine, whereas sleep apnoea syndrome is mentioned in 10 countries. A patient with untreated sleep apnoea is always considered unfit to drive. To recover the driving capacity, seven countries rely on a physician's medical certificate based on symptom control and compliance with therapy, whereas in two countries it is up to the patient to decide (on his doctor's advice) to drive again. Only FR requires a normalized electroencephalography (EEG)-based Maintenance of Wakefulness Test for professional drivers. Rare conditions (e.g., narcolepsy) are considered a driving safety risk more frequently than sleep apnoea syndrome. CONCLUSION: Despite the available scientific evidence, most countries in Europe do not include sleep apnoea syndrome or excessive daytime sleepiness among the specific medical conditions to be considered when judging whether or not a person is fit to drive. A unified European Directive seems desirable.
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17.
  • Andersson, Bert, 1952, et al. (författare)
  • Exercise hemodynamics and myocardial metabolism during long-term beta-adrenergic blockade in severe heart failure.
  • 1991
  • Ingår i: Journal of the American College of Cardiology. - 0735-1097 .- 1558-3597. ; 18:4, s. 1059-66
  • Tidskriftsartikel (refereegranskat)abstract
    • Hemodynamics and myocardial metabolism at rest and during exercise were investigated in 21 patients with heart failure. The patients were evaluated before and after long-term treatment (14 +/- 7 months) with the beta-adrenergic blocking agent metoprolol. Clinical improvement with increased functional capacity occurred during treatment. Maximal work load increased by 25% (104 to 130 W; p less than 0.001). Hemodynamic data showed an increased cardiac index (3.8 to 4.6 liters/min per m2; p less than 0.02) during exercise. Pulmonary capillary wedge pressure decreased at rest (20 to 13 mm Hg; p less than 0.01) and during exercise (32 to 28 mm Hg; p = NS). Stroke volume index (30 to 39 g.m/m2; p less than 0.006) and stroke work index (28 to 46 g.m/m2; p less than 0.006) increased during exercise and long-term metoprolol treatment. The arterial norepinephrine concentration decreased at rest (3.72 to 2.19 nmol/liter; p less than 0.02) but not during exercise (13.2 to 11.1 nmol/liter; p = NS). The arterial-coronary sinus norepinephrine difference suggested a decrease in myocardial spillover during metoprolol treatment (-0.28 to -0.13 nmol/liter; p = NS at rest and -1.13 to -0.27 nmol/liter; p less than 0.05 during exercise). Coronary sinus blood flow was unchanged during treatment. Four patients produced myocardial lactate before the study, but none produced lactate after beta-blockade (p less than 0.05). There was no obvious improvement in a subgroup of patients with ischemic cardiomyopathy. In summary, there were signs of increased myocardial work load without higher metabolic costs after treatment with metoprolol.
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  • Bailly, S., et al. (författare)
  • Clusters of sleep apnoea phenotypes: A large pan-European study from the European Sleep Apnoea Database (ESADA)
  • 2021
  • Ingår i: Respirology. - : Wiley. - 1323-7799 .- 1440-1843. ; 26:4, s. 378-387
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objective: To personalize OSA management, several studies have attempted to better capture disease heterogeneity by clustering methods. The aim of this study was to conduct a cluster analysis of 23 000 OSA patients at diagnosis using the multinational ESADA. Methods: Data from 34 centres contributing to ESADA were used. An LCA was applied to identify OSA phenotypes in this European population representing broad geographical variations. Many variables, including symptoms, comorbidities and polysomnographic data, were included. Prescribed medications were classified according to the ATC classification and this information was used for comorbidity confirmation. Results: Eight clusters were identified. Four clusters were gender-based corresponding to 54% of patients, with two clusters consisting only of men and two clusters only of women. The remaining four clusters were mainly men with various combinations of age range, BMI, AHI and comorbidities. The preferred type of OSA treatment (PAP or mandibular advancement) varied between clusters. Conclusion: Eight distinct clinical OSA phenotypes were identified in a large pan-European database highlighting the importance of gender-based phenotypes and the impact of these subtypes on treatment prescription. The impact of cluster on long-term treatment adherence and prognosis remains to be studied using the ESADA follow-up data set. © 2020 Asian Pacific Society of Respirology
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  • Bonsignore, M. R., et al. (författare)
  • Clinical presentation of patients with suspected obstructive sleep apnea and self-reported physician-diagnosed asthma in the ESADA cohort
  • 2018
  • Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 27:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Obstructive sleep apnea (OSA) and asthma are often associated and several studies suggest a bidirectional relationship between asthma and OSA. This study analyzed the characteristics of patients with suspected OSA from the European Sleep Apnea Database according to presence/absence of physician-diagnosed asthma. Cross-sectional data in 16,236 patients (29.1% female) referred for suspected OSA were analyzed according to occurrence of physician-diagnosed asthma for anthropometrics, OSA severity and sleepiness. Sleep structure was assessed in patients studied by polysomnography (i.e. 48% of the sample). The prevalence of physician-diagnosed asthma in the entire cohort was 4.8% (7.9% in women, 3.7% in men, p < 0.0001), and decreased from subjects without OSA to patients with mild-moderate and severe OSA (p = 0.02). Obesity was highly prevalent in asthmatic women, whereas BMI distribution was similar in men with and without physician-diagnosed asthma. Distribution of OSA severity was similar in patients with and without physician-diagnosed asthma, and unaffected by treatment for asthma or gastroesophageal reflux. Asthma was associated with poor sleep quality and sleepiness. Physician-diagnosed asthma was less common in a sleep clinic population than expected from the results of studies in the general population. Obesity appears as the major factor raising suspicion of OSA in asthmatic women, whereas complaints of poor sleep quality were the likely reason for referral in asthmatic men.
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  • Bouloukaki, I., et al. (författare)
  • Mild obstructive sleep apnea increases hypertension risk, challenging traditional severity classification
  • 2020
  • Ingår i: Journal of Clinical Sleep Medicine. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 16:6, s. 889-898
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Objectives: The association of mild obstructive sleep apnea (OSA) with important clinical outcomes remains unclear. We aimed to investigate the association between mild OSA and systemic arterial hypertension (SAH) in the European Sleep Apnea Database cohort. Methods: In a multicenter sample of 4,732 participants, we analyzed the risk of mild OSA (subclassified into 2 groups: mild(AHI) (5-<)(11)(/h) (apnea-hypopnea index [AHI], 5 to <11 events/h) and mild(AHI) (1)(1-<15/h) (AHI, >= 11 to <15 events/h) compared with nonapneic snorers for prevalent SAH after adjustment for relevant confounding factors including sex, age, smoking, obesity, daytime sleepiness, dyslipidemia, chronic obstructive pulmonary disease, type 2 diabetes, and sleep test methodology (polygraphy or polysomnography). Results: SAH prevalence was higher in the mild(AHI) (11-<15/h) OSA group compared with the mild(AHI 5-<11/h) group and nonapneic snorers (52% vs 45% vs 30%; P < .001). Corresponding adjusted odds ratios for SAH were 1.789 (mild(AHI) (11-<15/h); 95% confidence interval [CI], 1.49-2.15) and 1.558 (mild 1.34-1.82), respectively (P < .001). In sensitivity analysis, mild(AHI) (11-<15/h) OSA remained a significant predictor for SAH both in the polygraphy (odds ratio, 1.779; 95% CI, 1.403-2.256; P < .001) and polysomnography groups (odds ratio, 1.424; 95% CI, 1.047-1.939; P = .025). Conclusions: Our data suggest a dose-response relationship between mild OSA and SAH risk, starting from 5 events/h in polygraphy recordings and continuing with a further risk increase in the 11- to <150-events/h range. These findings potentially introduce a challenge to traditional thresholds of OSA severity and may help to stratify participants with OSA according to cardiovascular risk.
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  • Clark, C A, et al. (författare)
  • Endothelial cell protein C receptor-mediated redistribution and tissue-level accumulation of factor VIIa.
  • 2012
  • Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 10:11, s. 2383-2391
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Recent studies show that FVIIa binds to endothelial cell protein C receptor (EPCR) on vascular endothelium; however, the importance of this interaction in hemostasis or pathophysiology is unknown. Objective, The aim of the present study is to investigate the role of FVIIa interaction with EPCR on the endothelium in mediating FVIIa transport from the circulation to extravascular tissues. Methods: Wild-type, EPCR-deficient or ECPR-over expressing mice were injected with human rFVIIa (120 μg/kg b.w.) via tail vein. At varying time intervals following rFVIIa administration, blood and various tissues were collected to measure FVIIa antigen and activity levels. Tissue sections were analyzed by immunohistochemistry for FVIIa and EPCR. Results: The data reveal that, following intravenous injection, rFVIIa rapidly disappears from blood and associates with the endothelium in an EPCR-dependent manner. Immunohistochemical analyses revealed that association of FVIIa with the endothelium was maximal at 30 min and thereafter progressively declined. FVIIa association with the endothelium was undetectable at time points exceeding 24 h post FVIIa administration. The levels of rFVIIa accumulated in tissue correlates with expression levels of EPCR in mice and FVIIa associated with tissues remained functionally active for periods of at least 7 days. Conclusions: The observation that EPCR-dependent association of FVIIa with the endothelium is most pronounced soon after rFVIIa administration and subsequently declines temporally, combined with the retention of functionally-active FVIIa in tissue homogenates for extended periods, indicates that FVIIa binding to EPCR on the endothelium facilitates the transport of FVIIa from circulation to extravascular tissues where TF resides. © 2012 International Society on Thrombosis and Haemostasis.
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  • Dauvilliers, Y., et al. (författare)
  • Pitolisant for Daytime Sleepiness in Patients with Obstructive Sleep Apnea Who Refuse Continuous Positive Airway Pressure Treatment A Randomized Trial
  • 2020
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 201:9, s. 1135-1145
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Excessive daytime sleepiness is a common disabling symptom in obstructive sleep apnea syndrome. Objectives: To evaluate the efficacy and safety of pitolisant, a selective histamine H3 receptor antagonist with wake-promoting effects, for the treatment of daytime sleepiness in patients with moderate to severe obstructive sleep apnea refusing continuous positive airway pressure treatment. Methods: In an international, multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial, pitolisant was individually titrated at up to 20 mgld over 12 weeks. The primary endpoint was the change in the Epworth Sleepiness Scale score. Key secondary endpoints were maintenance of wakefulness assessed on the basis of the Oxford Sleep Resistance test, safety, Clinical Global Impression of severity, patient's global opinion, EuroQol quality-of-life questionnaire, and Pichot fatigue questionnaire. Measurements and Main Results: A total of 268 patients with obstructive sleep apnea (75% male; mean age, 52 yr; apnea-hypopnea index, 49/h; baseline sleepiness score, 15.7) were randomized (200 to pitolisant and 68 to placebo) and analyzed on an intention-to-treat basis. The Epworth Sleepiness Scale score was reduced more with pitolisant than with placebo (-2.8; 95% confidence interval, -4.0 to -1.5; P < 0.001). Wake maintenance tests were not improved. The Pichot fatigue score was reduced with pitolisant. The overall impact of pitolisant was confirmed by both physicians' and patients' questionnaires. Adverse event incidence, mainly headache, insomnia, nausea, and vertigo, was similar in the pitolisant and placebo groups (29.5% and 25.4%, respectively), with no cardiovascular or other significant safety concerns. Conclusions: Pitolisant significantly reduced self-reported daytime sleepiness and fatigue and improved patient-reported outcomes and physician disease severity assessment in sleepy patients with obstructive sleep apnea refusing or nonadherent to continuous positive airway pressure.
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27.
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28.
  • Edvinsson, Lars, et al. (författare)
  • Neuropeptide Y in sympathetic co-transmission: recent advances in the search for neuropeptide Y antagonists
  • 1994
  • Ingår i: Pharmacology and Toxicology. - 1600-0773. ; 74:4-5, s. 193-201
  • Tidskriftsartikel (refereegranskat)abstract
    • Since the discovery of neuropeptide Y which is co-stored and co-operate with noradrenaline (NA) in sympathetic nerve fibers, several scientific groups have searched for structures with neuropeptide Y antagonistic properties. Research has mainly focused on various peptide fragments which originate from or are related to the neuropeptide Y sequence. Some non-peptide antagonists have been proposed but they are mostly of low potency and non-selective. Our recent observations that alpha-trinositol (D-myo-inositol 1.2.6-trisphosphate) is an inhibitor of neuropeptide Y effects will hopefully lead to the development of useful non-peptide neuropeptide Y inhibitors. As a novel approach the highly selective approach of down-regulating neuropeptide Y receptors with antisense oligodeoxynucleotides is also discussed. Neuropeptide Y antagonistic agents would help us to understand the physiological role of neuropeptide Y and may serve as useful medication in circulation disorders.
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29.
  • Eskandari, Davoud, et al. (författare)
  • Independent associations between arterial bicarbonate, apnea severity and hypertension in obstructive sleep apnea
  • 2017
  • Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-993X. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Obstructive sleep apnea is characterized by intermittent hypoxia and hypercapnia. CO2 production, transport and elimination are influenced by the carbonic anhydrase enzyme. We hypothesized that elevated standard bicarbonate, a proxy for increased carbonic anhydrase activity, is associated with apnea severity and higher blood pressure in patients with obstructive sleep apnea. Methods: A retrospective analysis of a sleep apnea cohort (n = 830) studied by ambulatory polygraphy. Office systolic/diastolic blood pressure, lung function, and arterial blood gases were assessed during daytime. Results: Arterial standard bicarbonate was increased with apnea severity (mild/moderate/severe 24.1 +/- 1.8, 24.4 +/- 1.7 and 24.9 +/- 2.9 mmol/l, respectively, Kruskal-Wallis test p < 0.001). Standard bicarbonate was independently associated with apnea hypopnea index after adjustment for sex, age, body mass index, smoking, alcohol, hypertension, pO(2) and pCO(2) (standard bicarbonate quartile 1 vs. quartile 4, beta = 10.6, p < 0.001). Log-transformed standard bicarbonate was associated with a diagnosis of hypertension or diastolic blood pressure but not systolic blood pressure adjusting for cofounders (p = 0.007, 0.048 and 0.45, respectively). Conclusions: There was an independent association between sleep apnea severity and arterial standard bicarbonate. The link between high standard bicarbonate and daytime hypertension suggests that carbonic anhydrase activity may constitute a novel mechanism for blood pressure regulation in sleep apnea.
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30.
  • Everts, B, et al. (författare)
  • A comparison of metoprolol and morphine in the treatment of chest pain in patients with suspected acute myocardial infarction--the MEMO study
  • 1998
  • Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Ltd. - 0954-6820 .- 1365-2796. ; 245:2, s. 133-141
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. To compare the analgesic effect of metoprolol and morphine in patients with chest pain due to suspected or definite acute myocardial infarction after initial treatment with intravenous metoprolol. Design. All patients, regardless of age, admitted to the coronary care unit at Uddevalla Central Hospital due to suspected acute myocardial infarction were evaluated for inclusion in the MEMO study (metoprolol–morphine). The effects on chest pain and side-effects of the two treatments were followed during 24 h. Pain was assessed by a numerical rating scale. Results. A total of 265 patients were randomized in this prospective double-blind study and 59% developed a confirmed acute myocardial infarction. In both treatment groups, there were rapid reductions of pain intensity. However, in the patient group treated with morphine, there was a more pronounced pain relief during the first 80 min after start of double-blind treatment. The side-effects were few and were those expected from each therapeutic regimen. During the first 24 h, nausea requiring anti-emetics was more common in the morphine-treated patients. Conclusion. In suspected acute myocardial infarction, if chest pain persists after intravenous beta-adrenergic blockade treatment, standard doses of an opioid analgesic such as morphine will offer better pain relief than increased dosages of metoprolol.
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31.
  • Everts, B, et al. (författare)
  • Effects and pharmacokinetics of high dose metoprolol on chest pain in patients with suspected or definite acute myocardial infarction
  • 1997
  • Ingår i: European Journal of Clinical Pharmacology. - : Springer. - 0031-6970 .- 1432-1041. ; 53:1, s. 23-31
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Pain intensity and the plasma concentrations of metoprolol and its major metabolite alpha-hydroxymetoprolol as well as noradrenaline (NA), adrenaline (A) and neuropeptide Y (NPY) were determined in patients with pain due to definite or suspected acute myocardial infarction (AMI) after graded metoprolol infusion. Pain intensity and metoprolol kinetics were assessed over 8 h. METHODS: Twenty-seven patients of either sex, aged 48-84 years with ongoing chest pain upon arrival to the Coronary Care Unit (CCU) were subdivided into two groups: (1) patients with ECG signs of threatening transmural myocardial damage (n = 15); and (2) patients without such ECG signs (n = 12). Pain intensity was assessed by a numerical rating scale (NRS) and venous blood was obtained for determination of plasma catecholamine and NPY concentrations. A continuous infusion of metoprolol (3 mg.min-1 i.v) was started and serial blood samples for plasma catecholamines, NPY as well as metoprolol and its major metabolite alpha-hydroxymetoprolol were obtained from the contralateral arm. RESULTS: Initial pain intensity was 5.9 (arbitrary units) and 5.4 in the groups with and without signs of transmural myocardial damage, respectively. One third of the patients with ST changes reported full pain relief (NRS = 0) within 70 min after starting metoprolol infusion (accumulated dose, 15-180 mg). Among the patients without ST changes upon arrival, full pain relief was obtained in 70% (accumulated dose, 30-120 mg). There was a dose-dependent relation between accumulated metoprolol dose and pain relief. The diagnosis of acute myocardial infarction (AMI) was confirmed in all 15 patients with ECG signs on arrival of transmural myocardial damage. The mean metoprolol dose in this group was 91(12) mg. The mean metoprolol dose in the 12 patients without ST changes was 64(8) mg. In all, seven of these patients developed definite AMI. The terminal half-life of unchanged metoprolol ranged from 2.5 to 8.5 h in group 1 and from 2.2 to 5.2 h in group 2. In group 1, metoprolol half-life was 4.5 h and total plasma clearance (CL) 54.1 1.h-1. In group 2, the metoprolol half-life was 3.7 h and total plasma clearance 75.4 1.h-1. There was a significant difference in clearance between the groups. After the intravenous metoprolol infusion, alpha-hydroxymetoprolol concentrations increased gradually. In groups 1 and 2, maximal concentrations in plasma (Cmax) were 143 and 135 nmol.1(-1) for alpha-hydroxymetoprolol and 2830 and 1653 nmol.1(-1) for metoprolol, respectively. Plasma NA or NPY did not differ between the groups. In contrast, plasma A was significantly higher during the initial 90 min of observation in patients with ECG signs of transmural myocardial damage. CONCLUSION: High-dose intravenous metoprolol was well tolerated in patients with suspected AMI. There was a more rapid and almost complete pain relief in patients without signs of transmural ischaemia compared with the patients with ECG signs of transmural AMI at arrival. In the later group of patients, plasma clearance of metoprolol was significantly reduced.
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32.
  • Everts, B, et al. (författare)
  • Localization of pain in suspected acute myocardial infarction in relation to final diagnosis, age and sex, and site and type of infarction
  • 1996
  • Ingår i: Heart & Lung. - : Heart & Lung. - 0147-9563 .- 1527-3288. ; 25:6, s. 430-437
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To describe the localization of pain in consecutive patients admitted to the coronary care unit for possible acute myocardial infarction (AMI) and to relate it to the development of AMI, age, and gender. DESIGN: Prospective evaluation. SETTING: Sahlgrenska Hospital, covering half the area of the city of Göteborg, with half a million inhabitants. SUBJECTS: Nine hundred three consecutive patients admitted to the coronary care unit for possible AMI between 24 and 87 years old with a mean age of 64 years. OUTCOME MEASURES: Localizations of pain according to a self-constructed figure. Patient were approached between 1 and 14 days after onset of symptoms and asked to describe the localization of pain according to the figure, including nine positions on the chest, left and right arm, neck, and back. RESULTS: AMI developed in 50% of patients during the first 3 days in hospital. Patients in whom AMI developed localized their pain to an extent similar to those without AMI in seven of nine chest areas. However, patients with AMI reported pain in the upper right square of the chest more frequently (p < 0.001) and in the middle left square of the chest less frequently (p < 0.01) than did patients without AMI. Pain in both the right (p < 0.001) and left arms (p < 0.01) was more frequently reported by patients who had AMI. Among patients with AMI, women reported pain in the neck (p < 0.05) and in the back (p < 0.01) more frequently than did men. Compared with elderly patients, younger patients reported pain more frequently in the left arm (p < 0.01), right arm (p < 0.01), and neck (p < 0.05). CONCLUSIONS: Among consecutive patients with possible AMI admitted to the coronary care unit, patients who had confirmed AMI reported pain in both arms more frequently than did patients without AMI. However, both groups described their chest surface distribution of pain similarly in the majority of positions, thereby indicating that the localization of chest pain is of limited use in predicting which patients will eventually have AMI.
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33.
  • Everts, B, et al. (författare)
  • Morphine use and pharmacokinetics in patients with chest pain due to suspected or definite acute myocardial infarction. The Memo Study
  • 1998
  • Ingår i: European Journal of Pain. - : Elsevier Ltd. - 1090-3801 .- 1532-2149. ; 2:2, s. 115-125
  • Tidskriftsartikel (refereegranskat)abstract
    • The characteristics of chest pain due to suspected acute myocardial infarction and morphine use during the first 3 hospital days are described in a population of 2988 consecutive patients admitted to hospital. The duration of pain was usually less than 24h (mean 20.9±0.55h), and only 24.8% of patients experienced chest pain of longer duration. The majority of patients had only one attack of pain, but 34.4% experienced four or more attacks during hospitalization. A mean morphine dose of 6.7±0.2mg was administered over the 3 hospitalization days, but surprisingly 52.4% of all patients required no morphine analgesia at all. Independent predictors of an increased morphine consumption were initial degree of suspicion of acute myocardial infarction, ST changes on admission ECG, male sex, a history of angina pectoris and a history of congestive heart failure. In a separate pharmacokinetic/pharmacodynamic study in 10 patients, plasma concentrations of morphine and its major metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), were measured after intravenous administration of morphine. In this patient group, terminal half-life of unchanged morphine ranged from 0.77 to 3.22h. M3G and M6G plasma concentrations increased gradually up to 60–90 min after the intravenous morphine injection. Initial pain intensity by numerical rating scale was 6.6±0.6 (arbitrary units), and after morphine administration, there was a rapid and significant decrease in pain intensity. After 20 min, pain relief was 69±11% and remained at this level during the following 8 h observation period. It is concluded that the need for morphine administration in patients with suspected or definite acute myocardial infarction, differs among subgroups of patients and, in particular, higher doses are needed in those with a strong suspicion of myocardial infarction at arrival. When intravenous morphine is given, it attains full effect 20 min after injection. Furthermore, the active morphine metabolites M3G and M6G appear rapidly in thecirculation, which could influence the analgesic response to morphine treatment.
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34.
  • Everts, B, et al. (författare)
  • Pain recollection after chest pain of cardiac origin
  • 1999
  • Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 92:2, s. 115-120
  • Tidskriftsartikel (refereegranskat)abstract
    • Memory for pain is an important research and clinical issue since patients ability to accurately recall pain plays a prominent role in medical practice. The purpose of this prospective study was to find out if patients, with an episode of chest pain due to suspected acute myocardial infarction could accurately retrieve the pain initially experienced at home and during the first day of hospitalization after 6 months. A total of 177 patients were included in this analysis. The patients rated their experience of pain on a numerical rating scale. The maximal pain at home was retrospectively assessed, thereafter pain assessments were made at several points of time after admission. After 6 months they were asked to recall the intensity of pain and once again rate it on the numerical rating scale. The results from the initial and 6-month registrations were compared. In general, patients rated their maximal intensity of chest pain as being higher at the 6-month recollection as compared with the assessments made during the initial hospitalization. In particular, in patients with a high level of emotional distress, there was a systematic overestimation of the pain intensity at recall.
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35.
  • Feng, Q P, et al. (författare)
  • Cardiac neuropeptide Y and noradrenaline balance in patients with congestive heart failure.
  • 1994
  • Ingår i: British heart journal. - 0007-0769. ; 71:3, s. 261-7
  • Tidskriftsartikel (refereegranskat)abstract
    • To measure plasma concentrations of noradrenaline and neuropeptide Y-like immunoreactivity in relation to cardiac function in patients with congestive heart failure.Retrospective analysis of plasma noradrenaline concentrations and neuropeptide Y-like immunoreactivity in the arterial and coronary circulations, in patients with a high or low ejection fraction (31.3% (1.3%) or 17.7% (1.1%) respectively) and in healthy volunteers.Cardiology department of a university hospital.41 patients with congestive heart failure with various aetiologies. Ten healthy volunteers served as a reference group.Concentrations of noradrenaline measured by high performance liquid chromatography and of neuropeptide Y-like immunoreactivity measured by radioimmunoassay. Cardiac index, pulmonary capillary wedge pressure, pulmonary vascular resistance, and systemic vascular resistance were derived by catheterisation of the right heart. Ejection fraction was measured by radionuclide angiography, cineangiography, or M mode echocardiography.There were pronounced and significant increases in circulating arterial concentrations of neuropeptide Y-like immunoreactivity and noradrenaline in both the high and low ejection fraction groups compared with the healthy subjects. In the patients myocardial release of neuropeptide Y-like immunoreactivity tended to be greater compared with normal subjects, but not significantly so. While normal subjects showed myocardial noradrenaline uptake, patients with congestive heart failure showed significant and progressive myocardial noradrenaline release. Arterial as well as coronary sinus concentrations of neuropeptide Y-like immunoreactivity correlated significantly with plasma noradrenaline concentrations from the respective sites. Plasma noradrenaline concentrations in the artery and coronary sinus were negatively correlated with ejection fraction and cardiac index; no such relations were found for concentrations of neuropeptide Y-like immunoreactivity.Both circulating concentrations of neuropeptide Y-like immunoreactivity and noradrenaline are significantly increased in moderate to severe forms of congestive heart failure. Plasma concentrations of neuropeptide Y-like immunoreactivity correlated with plasma noradrenaline concentrations, but plasma noradrenaline concentrations alone correlated with ejection fraction and cardiac index. Thus plasma noradrenaline concentration seems to be a more sensitive index of cardiac dysfunction than the concentration of neuropeptide Y-like immunoreactivity in congestive heart failure.
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36.
  • Gopalakrishnan, R., et al. (författare)
  • Bio-distribution of pharmacologically administered recombinant factor VIIa (rFVIIa)
  • 2010
  • Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 8:2, s. 301-310
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Recent clinical studies suggest that the prophylactic use of recombinant factor VIIa (rFVIIa) markedly reduces the number of bleeding episodes in hemophilic patients with inhibitors. Given the short biological half-life of rFVIIa, it is unclear how rFVIIa could be effective in prophylactic treatment. Objectives: To examine the extravascular distribution of pharmacologically administered rFVIIa to obtain clues on how rFVIIa could work in prophylaxis. Methods: Recombinant mouse FVIIa tagged with AF488 fluorophore (AF488-FVIIa) was administered into mice via the tail vein. At different time intervals following the administration, mice were exsanguinated and various tissues were collected. The tissue sections were processed for immunohistochemistry to evaluate distribution of rFVIIa. Results: rFVIIa, immediately following the administration, associated with the endothelium lining of large blood vessels. Within 1 h, rFVIIa bound to endothelial cells was transferred to the perivascular tissue surrounding the blood vessels and thereafter diffused throughout the tissue. In the liver, rFVIIa was localized to sinusoidal capillaries and accumulated in hepatocytes. In bone, rFVIIa was accumulated in the zone of calcified cartilage and some of it was retained there for a week. The common finding of the present study is that rFVIIa in extravascular spaces was mostly localized to regions that contain TF expressing cells. Conclusions: The present study demonstrates that pharmacologically administered rFVIIa readily associates with the vascular endothelium and subsequently enters into extravascular spaces where it is likely to bind to TF and is retained for extended time periods. This may explain the prolonged pharmacological effect of rFVIIa.
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37.
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38.
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39.
  • Grote, Ludger, 1964, et al. (författare)
  • National Knowledge-Driven Management of Obstructive Sleep Apnea-The Swedish Approach
  • 2023
  • Ingår i: Diagnostics. - : MDPI AG. - 2075-4418. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: This paper describes the development of "Swedish Guidelines for OSA treatment" and the underlying managed care process. The Apnea Hypopnea Index (AHI) is traditionally used as a single parameter for obstructive sleep apnea (OSA) severity classification, although poorly associated with symptomatology and outcome. We instead implement a novel matrix for shared treatment decisions based on available evidence. Methods: A national expert group including medical and dental specialists, nurses, and patient representatives developed the knowledge-driven management model. A Delphi round was performed amongst experts from all Swedish regions (N = 24). Evidence reflecting treatment effects was extracted from systematic reviews, meta-analyses, and randomized clinical trials. Results: The treatment decision in the process includes a matrix with five categories from a "very weak"" to "very strong" indication to treat, and it includes factors with potential influence on outcome, including (A) OSA-related symptoms, (B) cardiometabolic comorbidities, (C) frequency of respiratory events, and (D) age. OSA-related symptoms indicate a strong incitement to treat, whereas the absence of symptoms, age above 65 years, and no or well-controlled comorbidities indicate a weak treatment indication, irrespective of AHI. Conclusions: The novel treatment matrix is based on the effects of treatments rather than the actual frequency of respiratory events during sleep. A nationwide implementation of this matrix is ongoing, and the outcome is monitored in a prospective evaluation by means of the Swedish Sleep Apnea Registry (SESAR).
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48.
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49.
  • Hansson, L, et al. (författare)
  • Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension : the Nordic Diltiazem (NORDIL) study
  • 2000
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 356:9227, s. 359-365
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Calcium antagonists are a first-line treatment for hypertension. The effectiveness of diltiazem, a nondihydropyridine calcium antagonist, in reducing cardiovascular morbidity or mortality is unclear. We compared the effects of diltiazem with that of diuretics, beta-blockers, or both on cardiovascular morbidity and mortality in hypertensive patients. Methods In a prospective, randomised, open, blinded endpoint study, we enrolled 10 881 patients, aged 50-74 years, at health centres in Norway and Sweden, who had diastolic blood pressure of 100 mm Hg or more. We randomly assigned patients diltiazem, or diuretics, beta-blockers, or both. The combined primary endpoint was fatal and non-fatal stroke, myocardial infarction, and other cardiovascular death. Analysis was done by intention to treat. Findings Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups (reduction 20.3/18.7 vs 23.3/18.7 mm Hg, difference in systolic reduction p<0.001). A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group (16.6 vs 16.2 events per 1000 patient-years, relative risk 1.00 [95% CI 0.87-1.15], p=0.97). Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group (6.4 vs 7.9 events per 1000 patient-years, 0.80 [0.65-0.99], p=0.04) and fatal and non-fatal myocardial infarction in 183 and 157 patients (7.4 vs 6.3 events per 1000 patient-years, 1.16 [0.94-1.44], p=0.17). Interpretation Diltiazem was as effective as treatment based on diuretics, beta-blockers, or both in preventing the combined primary endpoint of all stroke, myocardial infarction, and other cardiovascular death.
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50.
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