| 1. |
- Connolly, Stuart J., et al.
(författare)
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Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage
- 2024
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 390:19, s. 1745-1755
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. Methods We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. Results A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P=0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P=0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. Conclusions Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).
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| 2. |
- Hambraeus, Johan, 1959-
(författare)
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Interventional pain management focused on zygapophysial joint pain : a health-economic evaluation
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The pain-system is a central mechanism in our life. Chronic pain is one of the major causes of impaired health-related quality of life according to the World Health Organization’s “Global Burden of Disease”-studies. Zygapophysial joint pain has been shown to account for the pain in 30% - 50% of patients with chronic pain. There are several well-established, evidence-based methods to treat zygapophysial joint pain in the cervical and lumbar regions.This thesis originates from this and starts by exploring whether the treatment of zygapophysial joint pain can improve health-related quality of life. This thesis describes methods for the diagnosis and treatment of zygapophysial joint pain in the thoracic region that can be applied to the treatment of all pain-foci localized to the zygapophysial joints. I show that the health-related quality of life was significantly improved after treatment, and that the clinical methods used for treating thoracic pain were similar to the methods that have been established previously for cervical and lumbar pain.In order to better understand the patients’ experiences we performed qualitative interviews with patients who underwent diagnostic tests and treatments. The overall theme revealed by these interviews was that of empowerment, in which the patients were empowered by the process of diagnostic tests and treatments.The next question was whether the method was cost-effective or not. In the first cost-effectiveness analysis, the patients served as their own controls and we evaluated the results against the limits set by the Swedish national board of health and welfare. The results showed that it was cost-effective in the moderate to low range.Finally, we compared the treatment to the “gold standard” for pain management in Sweden; i.e.pain rehabilitation. We mimicked a randomized controlled trial by using propensity score weighting to compare 254 patients agains 15,357 patients registered in the Swedish National Register of Pain Rehabilitation. The results showed that interventional pain management was cost-effective in the moderate (12 months after treatment) to low (≥24 months after) range whereas pain rehabilitation was in the very high range (after 12 months) and became cost-effective in the high range after 24 months of treatment. Currently, interventional pain management accounts for just 2% of all specialized pain management procedures in Sweden. If this could be increased to 25%, it may be possible to save 106 million SEK annually, while simultaneously gain 14 quality adjusted life years of health. If an interventional pain assessment is performed early in the process, treatable patients could be directed toward interventional treatment and away from interdisciplinary pain management programs, with the potential for further reductions in costs.
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| 3. |
- Hankey, Graeme J., et al.
(författare)
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Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF
- 2012
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Ingår i: Lancet Neurology. - 1474-4465. ; 11:4, s. 315-322
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Tidskriftsartikel (refereegranskat)abstract
- Background In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA). Methods In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2-0-3.0). Patients and investigators were masked to treatment allocation. Between Dec 18,2006, and June 17,2009,14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, number NCT00403767. Findings 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2.79% rivaroxaban vs 2.96% warfarin; hazard ratio [HR] 0-94,95% CI 0.77-1.16) and those without (1.44% vs 1.88%; 0.77, 0.58-1-01; interaction p=0.23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13.31% rivaroxaban vs 13.87% warfarin; HR 0.96,95% CI 0.87-1-07) and those without (16.69% vs 15.19%; 1.10, 0.99-1.21; interaction p=0.08). Interpretation There was no evidence that the relative efficacy and safety of rivaroxaban compared with warfarin was different between patients who had a previous stroke or TIA and those who had no previous stroke or TIA. These results support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial stroke in patients with AF.
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| 4. |
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| 5. |
- Kechagias, Stergios, 1969-
(författare)
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Clinical Pharmacokinetics of Small Doses of Ethanol : Role of Gastric Emptying and Other Influences in the Upper Gastrointestinal Tract
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis deals with the clinical pharmacokinetics of small doses of ethanol as influenced by conditions in the proximal gut. The bioavailability of orally administered ethanol depends to a large extent on gastric emptying, which is influenced by pre-treatment with drugs and other clinically relevant factors in the upper gastrointestinal tract.The impact of the relative amount of carbohydrate, fat or protein in a test meal on the pharmacokinetics of a small dose of ethanol was studied in nine healthy male subjects. Drinking ethanol after eating a meal was compared with intake of the same dose consumed on an empty stomach or given intravenously. The peak blood alcohol concentration (BAC) and the area under the curve (AUC) were greatest when ethanol was given intravenously (100% availability). Drinking ethanol after a meal resulted in considerably lower peak BAC and AUC compared with drinking on an empty stomach. However, the macronutrient composition of the meal had no significant effect on the pharmacokinetics of ethanol as reflected in almost identical blood alcohol curves after high-fat, high-protein, or high-carbohydrate meals.The decreased bioavailability of ethanol after oral administration compared to intravenous infusion of the same dose can be explained by a first-pass metabolism (FPM). Some investigators attribute this FPM to the presence of alcohol dehydrogenase (ADH) in the gastric mucosa. Gastric ADH activity was studied in mucosal biopsies from 76 patients referred for upper gastrointestinal endoscopy. Those patients (n = 36) infected with H. pylori received treatment to eradicate the bacterium and repeat biopsies were obtained 2 months and one year later. There were no significant differences in gastric ADH activity between males and females and between different age groups. Gastric ADH activity was significantly decreased in the antrum among patients with H. pylori infection. After eradication of H. pylori, gastric ADH activity in the antrum was normalised within two months. No significant differences in the ADH activity were found in biopsies from the corpus. Histological examination of gastric biopsies showed that those exhibiting the most pronounced inflammation and histologic changes had significantly lower ADH activity compared with biopsies judged to have normal histology.Several drugs inhibit gastric ADH in vitro. Among them acetylsalicylic acid (ASA) was suggested to increase the bioavailability of orally administered ethanol. We studied the effect of low-dose ASA on the pharmacokinetics of a small dose of ethanol in 10 healthy men. Low-dose ASA (75 mg) decreased significantly the peak BAC and the time to reach peak BAC was also prolonged. The underlying mechanism appears to be delayed gastric emptying which was assessed by the paracetamol absorption test. To evaluate the effect of accelerating gastric emptying on ethanol pharmacokinetics, the prokinetic substance cisapride was given to the same 10 subjects. When ethanol was ingested 60 min after a meal pre-treatment with cisapride significantly increased peak BAC. However, this increase in BAC after cisapride was modest compared with the BAC reached when the same dose of ethanol was ingested on an empty stomach. The corresponding serum paracetamol curves indicated that a faster rate of gastric emptying was the main factor responsible for the differences in ethanol pharmacokinetics.Analysis of breath alcohol concentration (BrAC) is a practical and non-invasive method to estimate the BAC and this technique is used worldwide for forensic purposes. The reliability of BrAC measurements in subjects with gastroesophageal reflux disease (GERD) has been questioned. We therefore compared simultaneously obtained breath and venous blood alcohol concentrations in 10 patients with severe GERD scheduled for antireflux surgery. In one of the experiments gastroesophageal reflux was provoked by applying abdominal compression. Although some patients complained of pronounced reflux symptoms the breath instrument readings of BrAC did not deviate from the corresponding BAC in the two test situations, that is, with and without provocation of reflux.This thesis has established that measuring alcohol in breath can be used to monitor blood alcohol concentration also in subjects with severe GERD. The relative amount of fat, carbohydrate, or protein in a test meal does not influence the pharmacokinetics of a small dose of ethanol as long as the caloric contents of the meals are similar. The rate of gastric emptying is a major factor determining the bioavailability of orally administered ethanol. Treatment with low-dose ASA (75 mg) delayed gastric emptying and caused a lowering of the peak BAC. The prokinetic drug cisapride, administered under conditions that resemble clinical use, increased the peak BAC by accelerating gastric emptying. However, the drug-induced increase in BAC was much less than the BAC observed after drinking the same dose of ethanol on an empty stomach. H. pylori infection is associated with decreased antral ADH activity related to gastritis. Eradication of H. pylori normalises antral ADH activity within two months.
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| 6. |
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| 7. |
- Mäki-Torkko, Elina, 1961-, et al.
(författare)
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Hearing impairment among adults : extent of the problem and scientific evidence on the outcome of hearing aid rehabilitation
- 2001
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Ingår i: Scandinavian audiology. Supplementum. - : Taylor & Francis. - 0107-8593 .- 0105-0397. ; 30:54
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Tidskriftsartikel (refereegranskat)abstract
- Scientific surveys on current and estimated prevalence of hearing impairment (HI) in adult populations (> or = 18 years of age) in Denmark, Finland, Norway, Sweden and the United Kingdom, and scientific reports on the outcome of hearing aid (HA) rehabilitation worldwide were reviewed. Only a few of the studies meet strict scientific criteria, and many locally clinically relevant studies cannot be generalized to larger populations. Population-based studies indicate an increase in prevalence of HI with age, but because of differences in study populations and available national population statistics, the studies do not allow reliable comparisons between countries or estimation of future prevalence of HI. Studies on HA prescription or outcomes do not provide uniform data in favour of non-linear amplification, but they do show some subject preference for the newer technology. No conclusions can be drawn regarding the degree of HI and the effects of amplification. The literature review alone gives only limited information regarding the extent of the problem of HI in adult populations in the target countries. Similarly, only a few studies on HA outcome meet strict scientific criteria and even fewer studies correlate rehabilitation outcome with the degree of HI, disability or handicap.
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| 8. |
- Niemensivu, Riina, et al.
(författare)
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Health-related quality of life in adults with hearing impairment before and after hearing-aid rehabilitation in Finland
- 2015
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Ingår i: International Journal of Audiology. - : TAYLOR & FRANCIS LTD. - 1499-2027 .- 1708-8186. ; 54:12, s. 967-975
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to evaluate health-related quality of life (HRQoL) in adults with hearing impairment in Finland before and after hearing rehabilitation. Design: The study was prospective with hearing-aid rehabilitation as the intervention. The data was collected, using the 15D instrument, before and six months after hearing-aid rehabilitation. The data was analysed using t-tests and multiple linear regression methods. Study sample: The study sample included 949 adults with hearing impairment, and the control group included a sample of age- and gender-standardized general population. Results: The study population had significantly poorer HRQoL on most dimensions of the 15D when compared to the control group both before and after hearing-aid rehabilitation. Hearing-aid rehabilitation resulted in improved mean scores on the dimensions of hearing and in the overall 15D score that were statistically significant, although the mean improvement in the overall score was marginal. Self-reported hearing ability can better predict the change in HRQoL, as a result of a hearing aid, when compared with measured hearing sensitivity. Conclusions: The study supports the hypothesis that on average, use of a unilateral hearing aid results in improved subjective hearing and marginal improvement in HRQoL in adults with hearing impairment.
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| 9. |
- Putaala, Jukka, et al.
(författare)
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Searching for Explanations for Cryptogenic Stroke in the Young : Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design
- 2017
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 2:2, s. 116-125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.
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| 10. |
- Sandset, Else Charlotte, et al.
(författare)
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Angiotensin receptor blockade in acute stroke. The Scandinavian Candesartan Acute Stroke Trial : rationale, methods and design of a multicentre, randomised- and placebo-controlled clinical trial (NCT00120003)
- 2010
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 5:5, s. 423-427
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Tidskriftsartikel (refereegranskat)abstract
- Background Elevated blood pressure following acute stroke is common, and yet early antihypertensive treatment is controversial. ACCESS suggested a beneficial effect of the angiotensin receptor blocker candesartan in the acute phase of stroke, but these findings need to be confirmed in new, large trials. Aims and design The Scandinavian Candesartan Acute Stroke Trial is an international randomised, placebo-controlled, double-blind trial of candesartan in acute stroke. We plan to recruit 2500 patients presenting within 30 h of stroke (ischaemic or haemorrhagic) and with systolic blood pressure >= 140 mmHg. The recruited patients are randomly assigned to candesartan or placebo for 7-days (doses increasing from 4 to 16 mg once daily). Randomisation is performed centrally via a secure web interface. The follow-up period is 6-months. Patients are included from the following nine North-European countries: Norway, Sweden, Denmark, Belgium, Germany, Poland, Lithuania, Estonia and Finland. Study outcomes There are two co-primary effect variables:center dot Functional status at 6-months, measured by the modified Rankin Scale, and center dot vascular death, myocardial infarction or stroke during the first 6-months.Secondary outcome variables:Secondary effect variables include center dot the Barthel index (functional status)center dot EuroQol (quality of life) and center dot Mini-mental state examination (cognition) at 6-months center dot Health economic costs during the first 6-months Funding The Scandinavian Candesartan Acute Stroke Trial receives basic funding from Norwegian health authorities. AstraZeneca supplies the trial drugs, and AstraZeneca and Takeda support the trial with limited, unrestricted grants. Summary The Scandinavian Candesartan Acute Stroke Trial is the first large trial of angiotensin receptor blockers in patients with elevated blood pressure and acute stroke, and aims to answer whether treatment with angiotensin receptor blockers is beneficial for this indication.
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