Stockholm, Sweden
Stockholm, Sweden

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Friberg L.,Danderyd Hospital | Bergfeldt L.,Gothenburg University
Stroke | Year: 2013

Background and Purpose: Atrial fibrillation (AF) is a major risk factor for ischemic stroke. This study aims to update the knowledge about AF and associated stroke risk and benefits of anticoagulation. Methods: We extracted data from the hospital, specialized outpatient, and primary healthcare and drug registries in a Swedish region with 1.56 million residents. We identified all individuals who had received an AF diagnosis during the previous 5 years; all stroke events during 2010; and patients with AF aged ≥50 years who had received warfarin during 2009. Results: AF had been diagnosed in 38 446 subjects who were alive at the beginning of 2010 (prevalence of 3.2% in the adult [≥20 years] population); ≈46% received warfarin therapy. In 2010, there were 4565 ischemic stroke events and 861 intracranial hemorrhages. AF had been diagnosed in 38% of ischemic events (≥50% among those aged ≥80 years) and in 23% of intracranial hemorrhages. An AF diagnosis was often lacking in hospital discharge records after stroke events. Warfarin therapy was associated with an odds ratio of 0.50 (confidence interval, 0.43-0.57) for ischemic stroke and, despite an increased risk of intracranial hemorrhage, an odds ratio of 0.57 (confidence interval, 0.50-0.64) for the overall risk for stroke. Conclusions: AF is more common than present guidelines suggest. The attributable risk of AF for ischemic stroke increases with age and is close to that of hypertension in individuals aged ≥80 years. Because a majority of patients with AF with increased risk for stroke had not received anticoagulation therapy, there is a large potential for improvement. © 2013 American Heart Association, Inc.


Wardlaw J.M.,University of Edinburgh | Murray V.,Danderyd Hospital | Berge E.,University of Oslo | Del Zoppo G.,University of Washington | And 3 more authors.
The Lancet | Year: 2012

Background Recombinant tissue plasminogen activator (rt-PA, alteplase) improved functional outcome in patients treated soon after acute ischaemic stroke in randomised trials, but licensing is restrictive and use varies widely. The IST-3 trial adds substantial new data. We therefore assessed all the evidence from randomised trials for rt-PA in acute ischaemic stroke in an updated systematic review and meta-analysis. Methods We searched for randomised trials of intravenous rt-PA versus control given within 6 h of onset of acute ischaemic stroke up to March 30, 2012. We estimated summary odds ratios (ORs) and 95% CI in the primary analysis for prespecifi ed outcomes within 7 days and at the fi nal follow-up of all patients treated up to 6 h after stroke. Findings In up to 12 trials (7012 patients), rt-PA given within 6 h of stroke signifi cantly increased the odds of being alive and independent (modifi ed Rankin Scale, mRS 0-2) at fi nal follow-up (1611/3483 [46.3%] vs 1434/3404 [42.1%], OR 1.17, 95% CI 1.06-1.29; p=0.001), absolute increase of 42 (19-66) per 1000 people treated, and favourable outcome (mRS 0-1) absolute increase of 55 (95% CI 33-77) per 1000. The benefi t of rt-PA was greatest in patients treated within 3 h (mRS 0-2, 365/896 [40.7%] vs 280/883 [31.7%], 1.53, 1.26-1.86, p<0.0001), absolute benefi t of 90 (46-135) per 1000 people treated, and mRS 0-1 (283/896 [31.6%] vs 202/883 [22.9%], 1.61, 1.30-1.90; p<0.0001), absolute benefi t 87 (46-128) per 1000 treated. Numbers of deaths within 7 days were increased (250/2807 [8.9%] vs 174/2728 [6.4%], 1.44, 1.18-1.76; p=0.0003), but by fi nal follow-up the excess was no longer signifi cant (679/3548 [19.1%] vs 640/3464 [18.5%], 1.06, 0.94-1.20; p=0.33). Symptomatic intracranial haemorrhage (272/3548 [7.7%] vs 63/3463 [1.8%], 3.72, 2.98-4.64; p<0.0001) accounted for most of the early excess deaths. Patients older than 80 years achieved similar benefi t to those aged 80 years or younger, particularly when treated early. Interpretation The evidence indicates that intravenous rt-PA increased the proportion of patients who were alive with favourable outcome and alive and independent at fi nal follow-up. The data strengthen previous evidence to treat patients as early as possible after acute ischaemic stroke, although some patients might benefi t up to 6 h after stroke. Funding UK Medical Research Council, Stroke Association, University of Edinburgh, National Health Service Health Technology Assessment Programme, Swedish Heart-Lung Fund, AFA Insurances Stockholm (Arbetsmarknadens Partners Forsakringsbolag), Karolinska Institute, Marianne and Marcus Wallenberg Foundation, Research Council of Norway, Oslo University Hospital.


Lund L.H.,Karolinska Institutet | Lund L.H.,Karolinska University Hospital | Benson L.,Karolinska Institutet | Dahlstrom U.,Linköping University | And 3 more authors.
JAMA - Journal of the American Medical Association | Year: 2014

IMPORTANCE Heart failure with preserved ejection fraction (HFPEF)may be as common and may have similar mortality as heart failure with reduced ejection fraction (HFREF). β-Blockers reduce mortality in HFREF but are inadequately studied in HFPEF. OBJECTIVE To test the hypothesis that β-blockers are associated with reduced all-cause mortality in HFPEF. DESIGN Propensity score-matched cohort study using the Swedish Heart Failure Registry. Propensity scores for β-blocker use were derived from 52 baseline clinical and socioeconomic variables. SETTING Nationwide registry of 67 hospitals with inpatient and outpatient units and 95 outpatient primary care clinics in Sweden with patients entered into the registry between July 1, 2005, and December 30, 2012, and followed up until December 31, 2012. PARTICIPANTS From a consecutive sample of 41 976 patients, 19 083 patients with HFPEF (mean [SD] age, 76 [12] years; 46%women). Of these, 8244 were matched 2:1 based on age and propensity score for β-blocker use, yielding 5496 treated and 2748 untreated patients with HFPEF. Also we conducted a positive-control consistency analysis involving 22 893 patients with HFREF, of whom 6081 were matched yielding 4054 treated and 2027 untreated patients. EXPOSURES β-Blockers prescribed at discharge from the hospital or during an outpatient visit, analyzed 2 ways: without consideration of crossover and per-protocol analysis with censoring at crossover, if applicable. MAIN OUTCOMES AND MEASURES The prespecified primary outcomewas all-cause mortality and the secondary outcome was combined all-cause mortality or heart failure hospitalization. RESULTS Median follow-up in HFPEF was 755 days, overall; 709 days in the matched cohort; no patients were lost to follow-up. In the matched HFPEF cohort, 1-year survival was 80% vs 79% for treated vs untreated patients, and 5-year survival was 45%vs 42%, with 2279 (41%) vs 1244 (45%) total deaths and 177 vs 191 deaths per 1000 patient-years (hazard ratio [HR], 0.93; 95%CI, 0.86-0.996; P =.04). β-Blockers were not associated with reduced combined mortality or heart failure hospitalizations: 3368 (61%) vs 1753 (64%) total for first events, with 371 vs 378 first events per 1000 patient-years (HR, 0.98; 95%CI, 0.92-1.04; P =.46). In the matched HFREF cohort, β-blockers were associated with reduced mortality (HR, 0.89; 95%CI, 0.82-0.97, P=.005) and also with reduced combined mortality or heart failure hospitalization (HR, 0.89; 95%CI, 0.84-0.95; P =.001). CONCLUSIONS AND RELEVANCE In patients with HFPEF, use of β-blockers was associated with lower all-cause mortality but not with combined all-cause mortality or heart failure hospitalization. β-Blockers in HFPEF should be examined in a large randomized clinical trial. © 2014 American Medical Association. All rights reserved.


Friberg L.,Danderyd Hospital | Skeppholm M.,Danderyd Hospital | Terent A.,Uppsala University Hospital
Journal of the American College of Cardiology | Year: 2015

Background Patients with atrial fibrillation (AF) and ≥1 point on the stroke risk scheme CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) are considered at increased risk for future stroke, but the risk associated with a score of 1 differs markedly between studies. Objectives The goal of this study was to assess AF-related stroke risk among patients with a score of 1 on the CHA2DS2-VASc. Methods We conducted this retrospective study of 140,420 patients with AF in Swedish nationwide health registries on the basis of varying definitions of "stroke events." Results Using a wide "stroke" diagnosis (including hospital discharge diagnoses of ischemic stroke as well as unspecified stroke, transient ischemic attack, and pulmonary embolism) yielded a 44% higher annual risk than if only ischemic strokes were counted. Including stroke events in conjunction with the index hospitalization for AF doubled the long-term risk beyond the first 4 weeks. For women, annual stroke rates varied between 0.1% and 0.2% depending on which event definition was used; for men, the corresponding rates were 0.5% and 0.7%. Conclusions The risk of ischemic stroke in patients with AF and a CHA2DS2-VASc score of 1 seems to be lower than previously reported. © 2015 American College of Cardiology Foundation.


Barenius B.,Karolinska Institutet | Ponzer S.,Karolinska Institutet | Shalabi A.,Akademiska Sjukhuset | Bujak R.,Sodersjukhuset | And 2 more authors.
American Journal of Sports Medicine | Year: 2014

Background: The reported prevalence of radiological osteoarthritis (OA) after anterior cruciate ligament (ACL) reconstruction varies from 10% to 90%. Purpose/Hypothesis: To report the prevalence of OA after ACL reconstruction and to compare the OA prevalence between quadrupled semitendinosus tendon (ST) and bone-patellar tendon-bone (BPTB) grafts. The hypothesis was that there would be no difference in OA prevalence between the graft types. The secondary aim was to study whether patient characteristics and additional injuries were associated with long-term outcomes. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Radiological examination results, Tegner activity levels, and Knee injury and Osteoarthritis Outcome Score (KOOS) values were determined in 135 (82%) of 164 patients at a mean of 14 years after ACL reconstruction randomized to an ST or a BPTB graft. Osteoarthritis was defined according to a consensus by at least 2 of 3 radiologists of Kellgren-Lawrence grade >2. Using regression analysis, graft type, sex, age, overweight, time between injury and reconstruction, additional meniscus injury, and a number of other variables were assessed as risk factors for OA 14 years after ACL reconstruction. Results: Osteoarthritis of the medial compartment was most frequent, with 57% of OA cases in the ACL-reconstructed knee and 18% of OA cases in the contralateral knee (P < .001). There was no difference between the graft types: 49% of OA of the medial compartment for BPTB grafts and 65% for ST grafts (P = .073). The KOOS results were lower for patients with OA in all subscales, indicating that OA was symptomatic. No difference in the KOOS between the graft types was found. Meniscus resection was a strong risk factor for OA of the medial compartment (odds ratio, 3.6; 95% CI, 1.4-9.3) in the muttivariable logistic regression analysis. Conclusion: A 3-fold increased prevalence of OA was found after an ACL injury treated with reconstruction compared with the contralateral healthy knee. No differences in the prevalence of OA between the BPTB and quadrupled ST reconstructions were found. An initial meniscus resection was a strong risk factor for OA; the time between injury and reconstruction was not. © 2014 The Author(s).


Gonzalez H.,Danderyd Hospital | Olsson T.,Karolinska Institutet | Borg K.,Danderyd Hospital
The Lancet Neurology | Year: 2010

Postpolio syndrome is characterised by the exacerbation of existing or new health problems, most often muscle weakness and fatigability, general fatigue, and pain, after a period of stability subsequent to acute polio infection. Diagnosis is based on the presence of a lower motor neuron disorder that is supported by neurophysiological findings, with exclusion of other disorders as causes of the new symptoms. The muscle-related effects of postpolio syndrome are possibly associated with an ongoing process of denervation and reinnervation, reaching a point at which denervation is no longer compensated for by reinnervation. The cause of this denervation is unknown, but an inflammatory process is possible. Rehabilitation in patients with postpolio syndrome should take a multiprofessional and multidisciplinary approach, with an emphasis on physiotherapy, including enhanced or individually modified physical activity, and muscle training. Patients with postpolio syndrome should be advised to avoid both inactivity and overuse of weak muscles. Evaluation of the need for orthoses and assistive devices is often required. © 2010 Elsevier Ltd. All rights reserved.


Ingelsson E.,Karolinska Institutet | Lundholm C.,Karolinska Institutet | Johansson A.L.V.,Karolinska Institutet | Altman D.,Karolinska Institutet | Altman D.,Danderyd Hospital
European Heart Journal | Year: 2011

Aim s Hysterectomy for benign indications is one of the commonest surgical procedures in women, but the association between the procedure and cardiovascular disease (CVD) is not fully understood. In this population-based cohort study, we studied the effects of hysterectomy, with or without oopherectomy, on the risk of later life CVD.Methods and resultsUsing nationwide healthcare registers, we identified all Swedish women having a hysterectomy on benign indications between 1973 and 2003 (n 184 441), and non-hysterectomized controls (n 640 043). Main outcome measure was the first hospitalization or death of incident CVD (coronary heart disease, stroke, or heart failure). Occurrence of CVD was determined by individual linkage to the Inpatient Register. In women below age 50 at study entry, hysterectomy was associated with a significantly increased risk of CVD during follow-up [hazard ratio (HR), 1.18, 95 confidence interval (CI), 1.131.23; HR, 2.22, 95 CI, 1.014.83; and HR, 1.25, 95 CI, 1.061.48; in women without oopherectomy, with oopherectomy before or at study entry, respectively, using women without hysterectomy or oopherectomy as reference]. In women aged 50 or above at study entry, there were no significant associations between hysterectomy and incident CVD.Conclusion sHysterectomy in women aged 50 years or younger substantially increases the risk for CVD later in life and oopherectomy further adds to the risk of both coronary heart disease and stroke. © 2010 The Author.


Friberg L.,Danderyd Hospital
Journal of the American College of Cardiology | Year: 2014

Objectives The aim of this study was to examine mortality and liver disease among patients exposed to dronedarone. Background There has been concern about the safety of dronedarone, especially for patients with heart failure and permanent atrial fibrillation (AF). There have also been suspicions about liver toxicity. Methods All 174,995 patients with a diagnosis of AF during 2010 to 2012 were identified in the Swedish Patient Register. Of these, 4,856 patients had received dronedarone according to the Swedish Drug Register, and 170,139 patients who had not were used as a control population. Mean follow-up was 1.6 years, with a minimal follow-up of 6 months. Results Patients prescribed dronedarone were younger (age 65.5 years vs. 75.7 years, p < 0.0001) and healthier than control patients. The annual mortality rate among patients who received dronedarone was 1.3% compared with 14.0% in the control population. There were no sudden cardiac deaths and no deaths related to liver failure among patients who received treatment with dronedarone. After propensity score matching and adjustment for cofactors, patients who received dronedarone had lower mortality than other AF patients (hazard ratio [HR]: 0.41; 95% confidence interval [CI]: 0.33 to 0.51). Dronedarone patients with heart failure had lower mortality than other heart failure patients (HR: 0.40; 95% CI: 0.30 to 0.53). They also had lower mortality than expected from the general population (standardized mortality ratio: 0.67; 95% CI: 0.55 to 0.78), which indicates the selection of low-risk patients. The risk of liver disease was not increased (HR: 0.57; 95% CI: 0.34 to 0.92). Conclusions Dronedarone, as prescribed to AF patients in Sweden, has not exposed patients to increased risks of death or liver disease. © 2014 by the American College of Cardiology Foundation Published by Elsevier Inc.


Aims: Cardiovascular (CV)-related hospitalization has been used as a surrogate endpoint for mortality in recent treatment studies on atrial fibrillation (AF), but our understanding of the relationship between CV-related hospitalization and death is incomplete. We aimed to investigate whether CV-related hospitalization is an independent risk factor and suitable as a surrogate endpoint for death in clinical studies of patients with AF. Method and results: All 2912 patients with a diagnosis of AF in 2002 at one of Swedens largest hospitals were studied for 6.5 years using information about medication from the local medical records. In a sub-study of the last 2.5 years of the study period, we used detailed information about medication from the new National Prescription Register. Information about diagnoses, hospitalizations, and deaths was obtained from national registries. Patients who were re-admitted to hospital with a CV diagnosis within the first 3 months had higher mortality than those who were not (15.6 vs. 9.3 deaths per 100 patient-years at risk, P < 0.0001). Those who spent >2 of their time-at-risk in hospital with a CV diagnosis had higher mortality than those who had spent less time in hospital (36.0 vs. 8.2 deaths per 100 patient years, P < 0.0001). After adjustment for co-factors, mortality was still higher for patients who had been re-hospitalized for CV disease within 3 months than for those who had not [hazard ratio (HR) 1.36; 95 confidence interval (CI) 1.181.57]. When analyses were performed on patients who had survived for 3 years since inclusion, and with the use of detailed information about the exposure to medication, the association between CV-related hospitalization and death was highly significant (HR 2.69, CI 1.963.68). These results were virtually unchanged after propensity score matching, which was done in order to adjust further for residual unidentified confounding. Conclusion: CV-related hospitalization is a marker for patients who are at increased risk of death, and may be used as a valid surrogate endpoint in studies of AF. All rights reserved. © The Author 2011.


Background and purpose Promising results have been reported after volar locked plating of unstable dorsally displaced distal radius fractures. We investigated whether volar locked plating results in better patient-perceived, objective functional and radiographic outcomes compared to the less invasive external fixation. Patients and methods 63 patients under 70 years of age, with an unstable extra-articular or non-comminuted intra-articular dorsally displaced distal radius fracture, were randomized to volar locked plating (n = 33) or bridging external fixation. Patient-perceived outcome was assessed with the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire and the Patient-Rated Wrist Evaluation (PRWE) questionnaire. Results At 3 and 6 months, the volar plate group had better DASH and PRWE scores but at 12 months the scores were similar. Objective function, measured as grip strength and range of movement, was superior in the volar plate group but the differences diminished and were small at 12 months. Axial length and volar tilt were retained slightly better in the volar plate group. Interpretation Volar plate fixation is more advantageous than external fixation, in the early rehabilitation period. © 2011 Nordic Orthopaedic Federation.

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