Machine-learning-derived heart and brain age are independently associated with cognition.

BACKGROUND AND PURPOSE: A heart age biomarker has been developed using deep neural networks applied to electrocardiograms. Whether this biomarker is associated with cognitive function was investigated. METHODS: Using 12-lead electrocardiograms, heart age was estimated for a population-based sample (N = 7779, age 40-85 years, 45.3% men). Associations between heart delta age (HDA) and cognitive test scores were studied adjusted for cardiovascular risk factors. In addition, the relationship between HDA, brain delta age (BDA) and cognitive test scores was investigated in mediation analysis. RESULTS: Significant associations between HDA and the Word test, Digit Symbol Coding Test and tapping test scores were found. HDA was correlated with BDA (Pearson's r = 0.12, p = 0.0001). Moreover, 13% (95% confidence interval 3-36) of the HDA effect on the tapping test score was mediated through BDA. DISCUSSION: Heart delta age, representing the cumulative effects of life-long exposures, was associated with brain age. HDA was associated with cognitive function that was minimally explained through BDA.

Intravenous thrombolytic treatment and endovascular thrombectomy for ischaemic wake-up stroke.

BACKGROUND: About one in five strokes occur during sleep (wake-up stroke). People with wake-up strokes have previously been considered to be ineligible for thrombolytic treatment because the time of stroke onset is unknown. However, recent studies suggest benefit from recanalisation therapies in selected patients. OBJECTIVES: To assess the effects of intravenous thrombolysis and endovascular thrombectomy versus control in people with acute ischaemic stroke presenting on awakening from sleep. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last search 24 of May 2021). In addition, we searched the following electronic databases in May 2021: Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 4 of 12, April 2021) in the Cochrane Library, MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We searched the Stroke Trials Registry (last search 7 December 2017, as the site is currently inactive). We also screened references lists of relevant trials, contacted trialists, and undertook forward tracking of relevant references. SELECTION CRITERIA: Randomised controlled trials (RCTs) of intravenous thrombolytic drugs or endovascular thrombectomy treatments in people with acute ischaemic stroke presenting upon awakening. DATA COLLECTION AND ANALYSIS: Two review authors applied the inclusion criteria, extracted data, and assessed risk of bias and the certainty of the evidence using the GRADE approach. We obtained both published and unpublished data for participants with wake-up strokes. We excluded participants with strokes of unknown onset if the symptoms did not begin upon awakening. MAIN RESULTS: We included seven trials with a total of 980 participants, of which five trials with 775 participants investigated intravenous thrombolytic treatment and two trials with 205 participants investigated endovascular thrombectomy in large vessel occlusion in the anterior intracranial circulation. All trials used advanced imaging for selecting patients to treat. For intravenous thrombolytic treatment, good functional outcome (defined as modified Rankin Scale score 0 to 2) at 90 days follow-up was observed in 66% of participants randomised to thrombolytic treatment and 58% of participants randomised to control (risk ratio (RR) 1.13, 95% confidence interval (CI) 1.01 to 1.26; P = 0.03; 763 participants, 5 RCTs; high-certainty evidence). Seven per cent of participants randomised to intravenous thrombolytic treatment and 10% of participants randomised to control had died at 90 days follow-up (RR 0.68, 95% CI 0.43 to 1.07; P = 0.09; 763 participants, 5 RCTs; high-certainty evidence). Symptomatic intracranial haemorrhage occurred in 3% of participants randomised to intravenous thrombolytic treatment and 1% of participants randomised to control (RR 3.47, 95% CI 0.98 to 12.26; P = 0.05; 754 participants, 4 RCTs; high-certainty evidence). For endovascular thrombectomy of large vessel occlusion, good functional outcome at 90 days follow-up was observed in 46% of participants randomised to endovascular thrombectomy and 9% of participants randomised to control (RR 5.12, 95% CI 2.57 to 10.17; P < 0.001; 205 participants, 2 RCTs; high-certainty evidence). Twenty-two per cent of participants randomised to endovascular thrombectomy and 33% of participants randomised to control had died at 90 days follow-up (RR 0.68, 95% CI 0.43 to 1.07; P = 0.10; 205 participants, 2 RCTs; high-certainty evidence). AUTHORS' CONCLUSIONS: In selected patients with acute ischaemic wake-up stroke, both intravenous thrombolytic treatment and endovascular thrombectomy of large vessel occlusion improved functional outcome without increasing the risk of death. However, a possible increased risk of symptomatic intracranial haemorrhage associated with thrombolytic treatment cannot be ruled out. The criteria used for selecting patients to treatment differed between the trials. All studies were relatively small, and six of the seven studies were terminated early. More studies are warranted in order to determine the optimal criteria for selecting patients for treatment.

Endovascular thrombectomy and intra-arterial interventions for acute ischaemic stroke.

BACKGROUND: Most disabling strokes are due to a blockage of a large artery in the brain by a blood clot. Prompt removal of the clot with intra-arterial thrombolytic drugs or mechanical devices, or both, can restore blood flow before major brain damage has occurred, leading to improved recovery. However, these so-called endovascular interventions can cause bleeding in the brain. This is a review of randomised controlled trials of endovascular thrombectomy or intra-arterial thrombolysis, or both, for acute ischaemic stroke. OBJECTIVES: To assess whether endovascular thrombectomy or intra-arterial interventions, or both, plus medical treatment are superior to medical treatment alone in people with acute ischaemic stroke. SEARCH METHODS: We searched the Trials Registers of the Cochrane Stroke Group and Cochrane Vascular Group (last searched 1 September 2020), CENTRAL (the Cochrane Library, 1 September 2020), MEDLINE (May 2010 to 1 September 2020), and Embase (May 2010 to 1 September 2020). We also searched trials registers, screened reference lists, and contacted researchers. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any endovascular intervention plus medical treatment compared with medical treatment alone in people with definite ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors (MBR and MJ) applied the inclusion criteria, extracted data, and assessed trial quality. Two review authors (MBR and HL) assessed risk of bias, and the certainty of the evidence using GRADE. We obtained both published and unpublished data if available. Our primary outcome was favourable functional outcome at the end of the scheduled follow-up period, defined as a modified Rankin Scale score of 0 to 2. Eighteen trials (i.e. all but one included trial) reported their outcome at 90 days. Secondary outcomes were death from all causes at in the acute phase and by the end of follow-up, symptomatic intracranial haemorrhage in the acute phase and by the end of follow-up, neurological status at the end of follow-up, and degree of recanalisation. MAIN RESULTS: We included 19 studies with a total of 3793 participants. The majority of participants had large artery occlusion in the anterior circulation, and were treated within six hours of symptom onset with endovascular thrombectomy. Treatment increased the chance of achieving a good functional outcome, defined as a modified Rankin Scale score of 0 to 2: risk ratio (RR) 1.50 (95% confidence interval (CI) 1.37 to 1.63; 3715 participants, 18 RCTs; high-certainty evidence). Treatment also reduced the risk of death at end of follow-up: RR 0.85 (95% CI 0.75 to 0.97; 3793 participants, 19 RCTs; high-certainty evidence) without increasing the risk of symptomatic intracranial haemorrhage in the acute phase: RR 1.46 (95% CI 0.91 to 2.36; 1559 participants, 6 RCTs; high-certainty evidence) or by end of follow-up: RR 1.05 (95% CI 0.72 to 1.52; 1752 participants, 10 RCTs; high-certainty evidence); however, the wide confidence intervals preclude any firm conclusion. Neurological recovery to National Institutes of Health Stroke Scale (NIHSS) score 0 to 1 and degree of recanalisation rates were better in the treatment group: RR 2.03 (95% CI 1.21 to 3.40; 334 participants, 3 RCTs; high-certainty evidence) and RR 3.11 (95% CI 2.18 to 4.42; 268 participants, 3 RCTs; high-certainty evidence), respectively. AUTHORS' CONCLUSIONS: In individuals with acute ischaemic stroke due to large artery occlusion in the anterior circulation, endovascular thrombectomy can increase the chance of survival with a good functional outcome without increasing the risk of intracerebral haemorrhage or death.

Readmissions to a cardiology department. / Reinnleggelser ved en hjertemedisinsk avdeling.

BACKGROUND: Patient readmissions may be an indication of inappropriate patient care pathways or quality failure. The aim of the study was to determine whether we could identify improvement areas by reviewing 50 non-planned readmissions. MATERIAL AND METHOD: We reviewed 50 consecutive non-planned readmissions in the Department of Cardiology at the University Hospital of North Norway. The medical records were reviewed based on a simplified version of the '50 most recent deaths' methodology. RESULTS: Altogether 29 patients had at least one extrinsic risk factor for readmission, the most frequent of which were lack of post-discharge follow-up and failure to transfer information to the municipal health service. Insufficient registration and follow-up of abnormal blood test results, new symptoms immediately before discharge, and missing information in discharge summaries and for patients were other risk factors for readmission. INTERPRETATION: Review of readmissions can serve as an instrument to identify areas for improvement of treatment quality in hospitals. Failure in communication between the hospital, municipal health service and patient was the main contributory factor for readmissions.

Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke.

BACKGROUND: Most ischaemic strokes are caused by blockage of a cerebral artery by a thrombus. Intravenous administration of recombinant tissue plasminogen activator given within 4.5 hours is now standard treatment for this condition. Percutaneous vascular interventions use an intra-arterial, mechanical approach for thrombus disruption or removal (thrombectomy). Recent randomised trials indicate that percutaneous vascular interventions are superior to usual care (usual care usually included intravenous thrombolysis). However, intravenous thrombolysis was usually given in both arms of the trial and there was a lack of direct comparison of percutaneous vascular interventions with intravenous thrombolysis. OBJECTIVES: To assess the effectiveness and safety of percutaneous vascular interventions compared with intravenous thrombolytic treatment for acute ischaemic stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last search: August 2018). In addition, in September 2017, we searched the following electronic databases: CENTRAL, MEDLINE, Embase, and Science Citation Index; and Stroke Trials Registry, and US National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) that directly compared a percutaneous vascular intervention with intravenous thrombolytic treatment in people with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors applied the inclusion criteria, extracted data, and assessed risk of bias. We obtained both published and unpublished data. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included four trials with 450 participants. Data on functional outcome and death at end of follow-up were available for 443 participants from three trials. Compared with intravenous thrombolytic therapy, percutaneous vascular intervention did not improve the proportion of participants with good functional outcome (modified Rankin Scale score 0 to 2, risk ratio (RR) 1.01, 95% confidence interval (CI) 0.82 to 1.25, P = 0.92). The quality of evidence was low (outcome assessment was blinded, but not the treating physician or participants). At the end of follow-up, there was a non-significant increase in the proportion of participants who died in the percutaneous vascular intervention group (RR 1.34, 95% CI 0.84 to 2.14, P = 0.21). The quality of evidence was low (wide confidence interval). There was no difference in the proportion of participants with symptomatic intracranial haemorrhages between the intervention and control groups (RR 0.99, 95% CI 0.50 to 1.95, P = 0.97). The quality of evidence was low (wide confidence interval). Data on vascular status (recanalisation rate) were only available for seven participants from one trial; we considered this inadequate for statistical analyses. AUTHORS' CONCLUSIONS: The present review directly compared intravenous thrombolytic treatment with percutaneous vascular interventions for ischaemic stroke. We found no evidence from RCTs that percutaneous vascular interventions are superior to intravenous thrombolytic treatment with respect to functional outcome. Quality of evidence was low (outcome assessment was blinded, but not the treating physician or participants). New trials with adequate sample sizes are warranted because of the rapid development of new techniques and devices for such interventions.

Recanalisation therapies for wake-up stroke.

BACKGROUND: About one in five strokes occur during sleep (wake-up stroke). People with wake-up strokes have traditionally been considered ineligible for thrombolytic treatment because the time of stroke onset is unknown. However, some studies suggest that these people may benefit from recanalisation therapies. OBJECTIVES: To assess the effects of intravenous thrombolysis and other recanalisation therapies versus control in people with acute ischaemic stroke presenting on awakening. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last search: 9 January 2018). In addition, we searched the following electronic databases in December 2017: Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 11) in the Cochrane Library, MEDLINE, Embase, US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the ISRCTN registry, and Stroke Trials Registry. We also screened references lists of relevant trials, contacted trialists, undertook forward tracking of relevant references, and contacted manufacturers of relevant devices and equipment. SELECTION CRITERIA: Randomised controlled trials of intravenous thrombolytic drugs or intra-arterial therapies in people with acute ischaemic stroke presenting upon awakening. DATA COLLECTION AND ANALYSIS: Two review authors applied the inclusion criteria, extracted data, and assessed trial quality and risk of bias using the GRADE approach. We obtained both published and unpublished data. MAIN RESULTS: We included one pilot trial with nine participants. The trial was a feasibility trial that included participants with an unknown onset of stroke and signs on perfusion computed tomography of ischaemic tissue at risk of infarction, who were randomised to alteplase (0.9 mg/kg) or placebo. One trial was prematurely terminated due to signs of efficacy of the intervention arm; we did not include this trial because we were not able to obtain data for the portion of the participants with wake-up stroke after requesting this information from the trial authors. We identified six ongoing trials. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised controlled trials for recommendations concerning recanalisation therapies for wake-up stroke. Results from ongoing trials will hopefully establish the efficacy and safety of such therapies.

Reoperation-requiring postoperative intracranial haemorrhage after posterior fossa craniotomy: Retrospective case-series.

Introduction: Studies report rates of treatment-requiring postoperative intracranial haemorrhage after craniotomy around 1-2%, but do not distinguish between supratentorial and posterior fossa operations. Reports about intracranial haemorrhages' temporal occurrence show conflicting results. Recommendations for duration of postoperative monitoring vary. Research question: To determine the rate, temporal pattern and clinical presentation of reoperation-requiring postoperative intracranial posterior fossa haemorrhage. Material and methods: This retrospective case-series identified cases operated with posterior fossa craniotomy or craniectomy between January 1, 2007 and December 31, 2021 by an electronic search in the patient administrative database, and collected data about patient- and treatment-characteristics, postoperative monitoring, and the occurrence of haemorrhagic and other serious postoperative complications. Results: We included 62 (n = 34, 55% women) cases with mean age 48 (interquartile range 50) years operated for tumours (n = 34, 55%), Chiari malformations (n = 18, 29%), ischemic stroke (n = 6, 10%) and other lesions (n = 3, 5%). One (2%) 66-year-old woman who was a daily smoker operated with decompressive craniectomy and infarct resection, developed a reoperation-requiring postoperative intracranial haemorrhage after 25.5 h. In four (6%) cases, other serious complications requiring reoperation or transfer from the post anaesthesia care unit or regular bed wards to the intensive care unit occurred after 0.5, 6, 9 and 54 h, respectively. Discussion and conclusion: Treatment-requiring postoperative intracranial haemorrhage and other serious complications after posterior fossa craniotomies occur over a wide timespan and are difficult to capture with a standardized postoperative monitoring time. This indicates that the duration of monitoring should be individualized based on assessment of risk factors.

Joint effect of modifiable risk factors on the risk of aneurysmal subarachnoid hemorrhage: a cohort study.

BACKGROUND AND PURPOSE: The joint effect of risk factors on the risk of aneurysmal SAH (aSAH) has been studied sparsely. METHODS: We examined the potential synergism between cigarette smoking, hypertension, and regular alcohol consumption and the risk of aSAH in a prospective, population-based cohort of participants from the Nord-Trøndelag Health Study and the Tromsø Study in Norway. Interaction was assessed on additive and multiplicative scales. RESULTS: We identified 122 cases of aSAH over 977 895 person-years of follow-up. Interaction was observed between current smoking and hypertension on the additive scale, (relative excess risk because of interaction, 6.40; 95% CI, 0.88-11.92, adjusted for sex and age). We found no significant interaction between hypertension and regular alcohol consumption or current cigarette smoking and regular alcohol consumption on the additive scale. No significant interaction was detected on the multiplicative scale. CONCLUSIONS: The joint effect of current smoking and hypertension on the risk of aSAH was stronger than was the sum of the independent effects of each factor. Persons at risk of aSAH should be advised of a markedly stronger risk for aSAH with the combination of current smoking and hypertension. In addition, the finding suggests that combining smoking cessation and blood pressure lowering may have an extra risk reduction effect on preventing aSAH.

Prevalence of age-related macular degeneration in elderly Caucasians: the Tromsø Eye Study.

PURPOSE: To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD). DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Caucasian adults aged 65 to 87 years from the 6th Tromsø Study, a population-based study conducted in 2007-2008 in the municipality of Tromsø, Norway. METHODS: Digital color fundus photographs were graded for predominant phenotype based on drusen size, geographic atrophy, and neovascular AMD. MAIN OUTCOME MEASURES: Age-related macular degeneration. RESULTS: A total of 3025 subjects participated; 89% of those were invited to the eye examinations. Gradable photographs were available for 2631 persons (mean age 72.3 years). Drusen 63-125 µm as the predominant phenotype were found in 34.9% of participants (95% confidence interval [CI], 33.1-36.8), drusen >125 µm were found in 24.1% (95% CI, 22.5-25.8), geographic atrophy was found in 1.0% of participants (95% CI, 0.6-1.4), and neovascular AMD was found in 2.5% of participants (95% CI, 1.9-3.1). Bilateral involvement of late AMD was present in 1.1% of the sample. Eyes with late AMD had a significantly lower refractive error (spherical equivalent 0.078 vs. 0.99 diopters, P<0.0001), and 42.5% of eyes had Snellen visual acuity ≤ 0.32. CONCLUSIONS: The prevalence of AMD among the elderly persons in this study was similar to rates in other Caucasian populations. Late AMD was present in 10.9% of subjects aged 80 years or more. No sex differences in prevalence rates of large drusen or late AMD were observed. Lower refractive error was observed in eyes with late AMD than in eyes without late AMD.

QT interval and the risk of myocardial infarction and all-cause death: a cohort study.

INTRODUCTION: The relationship between QT interval and cardiovascular disease is controversial. METHODS: All male residents aged 20-61 years and female residents aged 20-56 years were invited to the Tromsø Study in 1986-1987. A total of 15,558 participants free of heart disease were prospectively followed over 20 years for myocardial infarction and death. QT interval at baseline was measured on lead I of the electrocardiogram. Hazard ratios (HRs) with 95% confidence intervals (CIs) per standard deviation change in QT interval were calculated using a Cox regression model. RESULTS: We identified 756 cases of myocardial infarction and 1,183 all-cause deaths. Prolonged QT interval was present in 792 (5%) participants. QT interval was not associated with increased risk of myocardial infarction (HR: 0.95, 95% CI: 0.84-1.07, after adjustment for potential confounders). Heart-rate-corrected QT interval was a significant predictor for all-cause death in men (HR: 1.15, 95% CI: 1.03-1.29), but not in women (HR: 1.04, 95% CI: 0.91-1.18), after adjustment for potential confounders. CONCLUSIONS: The findings suggest that the previously observed relationship between QT interval and increased risk of cardiovascular death is not mediated by increased risk of myocardial infarction. The clinical utility of the QT interval to identify individuals at high risk for coronary events is limited in a general population without prior heart disease.

Outcomes after coronary angiography for unstable angina compared to stable angina, myocardial infarction and an asymptomatic general population.

Background: The outcomes of real-world unstable angina (UA) in the high-sensitivity troponin era are unclear. We aimed to investigate the outcomes of UA referred to coronary angiography compared to stable angina (SA), non-ST-segment elevation myocardial infarction (NSTEMI), STEMI and a general population. Methods: We included the 9,694 patients with no prior coronary artery disease (CAD) referred to invasive or CT coronary angiography from 2013 to 2018 in Northern Norway (51% SA, 12% UA, 23% NSTEMI and 14% STEMI), and 11,959 asymptomatic individuals recruited from the Tromsø Study. We used Cox models to estimate the hazard ratios (HR) for all-cause mortality and major adverse cardiovascular events (MACE), defined as cardiovascular death, MI or obstructive CAD. Results: The median follow-up time was 2.8 years. The incidence rate of death was 8.5 per 1000 person-years (95 % confidence interval [CI] 8.0-9.0) in the general population, 9.7 (95 % CI 8.3-11.5) in SA, 14.9 (95 % CI 11.4-19.6) in UA, 29.7 (95 % CI 25.6-34.3) in NSTEMI and 36.5 (95 % CI 30.9-43.2) in STEMI. In multivariable adjusted analyses, compared with UA, SA had a 38 % lower risk of death and a non-significant lower risk of MACE (HR 0.62, 95 % CI 0.44-0.89; HR 0.86, 95 % CI 0.66-1.11). NSTEMI had a 2.4-fold higher risk of death (HR 2.39, 95 % CI 1.38-4.14) and a 1.6-fold higher risk of MACE (HR 1.62, 95 % CI 1.11-2.38) compared tox UA during the first year after coronary angiography, but a similar risk thereafter. There was no difference in the risk of death for UA with non-obstructive CAD and obstructive CAD (HR 0.78, 95 % CI 0.39-1.57). Conclusion: UA had a higher risk of death but a similar risk of MACE compared to SA and a lower 1-year risk of death and MACE compared to NSTEMI.

Low Pain Tolerance Is Associated With Coronary Angiography, Coronary Artery Disease, and Mortality: The Tromsø Study.

Background The initial presentation to coronary angiography and extent of coronary artery disease (CAD) vary greatly among patients, from ischemia with no obstructive CAD to myocardial infarction with 3-vessel disease. Pain tolerance has been suggested as a potential mechanism for the variation in presentation of CAD. We aimed to investigate the association between pain tolerance, coronary angiography, CAD, and death. Methods and Results We identified 9576 participants in the Tromsø Study (2007-2008) who completed the cold-pressor pain test, and had no prior history of CAD. The median follow-up time was 10.4 years. We applied Cox-regression models with age as time-scale to calculate hazard ratios (HR). More women than men aborted the cold pressor test (39% versus 23%). Participants with low pain tolerance had 19% increased risk of coronary angiography (HR, 1.19 [95% CI, 1.03-1.38]) and 22% increased risk of obstructive CAD (HR, 1.22 [95% CI, 1.01-1.47]) adjusted by age as time-scale and sex. Among women who underwent coronary angiography, low pain tolerance was associated with 54% increased risk of obstructive CAD (HR, 1.54 [95% CI, 1.09-2.18]) compared with high pain tolerance. There was no association between pain tolerance and nonobstructive CAD or clinical presentation to coronary angiography (ie, stable angina, unstable angina, and myocardial infarction). Participants with low pain tolerance had increased risk of mortality after adjustment for CAD and cardiovascular risk factors (HR, 1.40 [95% CI, 1.19-1.64]). Conclusions Low cold pressor pain tolerance is associated with a higher risk of coronary angiography and death.

Tenecteplase in wake-up ischemic stroke trial: Protocol for a randomized-controlled trial.

BACKGROUND: Patients with wake-up ischemic stroke who have evidence of salvageable tissue on advanced imaging can benefit from intravenous thrombolysis. It is not known whether patients who do not fulfil such imaging criteria might benefit from treatment, but studies indicate that treatment based on non-contrast CT criteria may be safe. Tenecteplase has shown promising results in patients with acute ischemic stroke. The aim of the Tenecteplase in Wake-up Ischemic Stroke Trial (TWIST) is to compare the effect of thrombolytic treatment with tenecteplase and standard care versus standard care alone in patients with wake-up ischemic stroke selected by non-contrast CT. METHODS/DESIGN: TWIST is an international, investigator-initiated, multi-centre, prospective, randomized-controlled, open-label, blinded end-point trial of tenecteplase (n = 300) versus standard care (n = 300) in patients who wake up with an acute ischemic stroke and can be treated within 4.5 h upon awakening. Seventy-seven centres in 10 countries (Denmark, Estonia, Finland, Latvia, Lithuania, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom) participate. The primary outcome is the modified Rankin Scale on the ordinal scale (0-6) at three months. DISCUSSION: TWIST aims to determine the effect and safety of thrombolytic treatment with tenecteplase in patients with wake-up ischemic stroke selected by non-contrast CT. TRIAL REGISTRATION: ClinicalTrials.gov NCT03181360. EudraCT Number 2014-000096-80.

[Treatment practice in primary hyperparathyroidism]. / Behandlingspraksis ved primaer hyperparatyreoidisme.

BACKGROUND: A recent study found considerable regional differences in treatment of primary hyperparathyroidism in Norway. There is no consensus on specific indications for operation in these patients. We surveyed opinions among Norwegian endocrine surgeons and endocrinologists on the indications for surgical treatment of primary hyperparathyroidism. MATERIAL AND METHODS: A questionnaire on preoperative evaluation, indications for surgery and treatment of patients with primary hyperparathyroidism was sent to the chief consultants of surgical departments that operated on parathyroid glands in 2005. The questionnaire was also sent to endocrinologists at the same hospitals. RESULTS: In 2006, 415 parathyroid gland operations were performed in 17 Norwegian hospitals, with a median of 18 operations per hospital. A total of 46 surgeons operated on the parathyroid glands, with a median of two surgeons per hospital. Hospitals differed with respect to preoperative evaluations and indications for operative treatment; but these differences did not coincide with regional differences in the frequency of parathyroid surgery. There was a good correlation between endocrine surgeons and endocrinologists on the indications for surgery in primary hyperparathyroidism, but neither group adhered unconditionally to the international guidelines for surgical treatment of patients with primary hyperparathyroidism. Patients in the hospitals that operated most frequently were initially diagnosed in a surgical department. INTERPRETATION: Our survey did not reveal differences that could explain the large regional variations in the frequency of parathyroid surgery.

Genome-wide association study reveals dynamic role of genetic variation in infant and early childhood growth.

Infant and childhood growth are dynamic processes with large changes in BMI during development. By performing genome-wide association studies of BMI at 12 time points from birth to eight years (9286 children, 74,105 measurements) in the Norwegian Mother, Father, and Child Cohort Study, replicated in 5235 children, we identify a transient effect in the leptin receptor (LEPR) locus: no effect at birth, increasing effect in infancy, peaking at 6-12 months (rs2767486, P6m = 2.0 × 10-21, ß6m = 0.16 sd-BMI), and little effect after age five. We identify a similar transient effect near the leptin gene (LEP), peaking at 1.5 years (rs10487505, P1.5y = 1.3 × 10-8, ß1.5y = 0.079 sd-BMI). Both signals are protein quantitative trait loci for soluble-LEPR and LEP in plasma in adults independent from adult traits mapped to the respective genes, suggesting key roles of common variation in the leptin signaling pathway for healthy infant growth.

Small and large vessel disease in persons with unrecognized compared to recognized myocardial infarction: The Tromsø Study 2007-2008.

BACKGROUND: Unrecognized myocardial infarction (MI) is a frequent condition with unknown underlying reason. We hypothesized the lack of recognition of MI is related to pathophysiology, specifically differences in underlying small and large vessel disease. METHODS: 6128 participants were examined with retinal photography, ultrasound of the carotid artery and a 12­lead electrocardiography (ECG). Small vessel disease was defined as narrower retinal arterioles and/or wider retinal venules measured on retinal photographs. Large vessel disease was defined as carotid artery pathology. We defined unrecognized MI as ECG-evidence of MI without a clinically recognized event. We analyzed the cross-sectional relationship between MI recognition and markers of small and large vessel disease, adjusted for age and sex. RESULTS: Unrecognized MI was present in 502 (8.2%) and recognized MI in 326 (5.3%) of the 6128 participants. Compared to recognized MI, unrecognized MI was associated with small vessel disease indicated by narrower retinal arterioles (OR 1.66, 95% CI 1.05-2.62, highest vs. lowest quartile). Unrecognized MI was less associated with wider retinal venules (OR 0.55, 95% CI 0.35-0.87, lowest vs. highest quartile). Compared to recognized MI, unrecognized MI was less associated with large vessel disease indicated by presence of plaque in the carotid artery (OR for presence of carotid artery plaque in unrecognized MI 0.51, 95% CI 0.37-0.69). No significant sex interaction was present. CONCLUSIONS: Unrecognized MI was more associated with small vessel disease and less associated with large vessel disease compared to recognized MI. These findings suggest that the pathophysiology behind unrecognized and recognized MI may differ.