Thrombolytic Treatment in Wake-Up Stroke: A Propensity Score-Matched Analysis of Treatment Effectiveness in the Norwegian Stroke Registry.

BACKGROUND: Previous clinical trials found improved outcome of thrombolytic treatment in patients with ischemic wake-up stroke (WUS) selected by advanced imaging techniques. The authors assessed the effectiveness of thrombolytic treatment in patients with WUS in a nationwide stroke registry. METHODS AND RESULTS: Using propensity score matching, the authors assessed the effectiveness and safety of thrombolytic treatment versus no thrombolytic treatment in 726 patients (363 matched pairs) with WUS in the Norwegian Stroke Registry in 2014 to 2019. Thrombolytic treatment in WUS versus known-onset stroke was compared in 730 patients (365 matched pairs). Functional outcomes were assessed by the modified Rankin Scale (mRS) at 3 months. A significant benefit of thrombolytic treatment in WUS was seen in ordinal analysis (odds ratio [OR], 1.48 [95% CI, 1.15-1.91]; P=0.003) and for mRS 0 to 2 (OR, 1.81 [95% CI, 1.29-2.52]; P=0.001) but not for mRS 0 or 1 (OR, 1.32 [95% CI, 1.00-1.74]; P=0.050). The proportion of patients with mRS 0 or 1 was lower in patients with WUS who underwent thrombolysis versus those with known-onset stroke (50.4% versus 59.5%; OR, 0.69 [95% CI, 0.52-0.93]; P=0.013), while outcomes were similar between groups for mRS 0 to 2 and ordinal analysis. Symptomatic intracranial hemorrhage after thrombolytic treatment occurred in 4.4% of patients with WUS and 3.9% of patients with known-onset stroke (OR, 1.14 [95% CI, 0.54-2.41]; P=0.726). CONCLUSIONS: Thrombolytic treatment in patients with WUS was associated with improved functional outcome compared with patients with no thrombolytic treatment and was not associated with increased rates of symptomatic intracranial hemorrhage compared with known-onset stroke. The results indicate that thrombolytic treatment is effective and safe in WUS in a real-life setting.

Risk of myocardial infarction after invasive outpatient procedures.

OBJECTIVE: To assess the short-term risk of acute myocardial infarction (AMI) associated with procedures performed at outpatient specialised hospital clinics. METHODS: In this case-crossover, population-based study, we identified first-time AMI cases aged ≥40 years via patient registries and linked them to their surgical intervention in Norway (2008-2016) and Sweden (2001-2014), respectively. The number of individuals with AMI who underwent procedures 0-7 days (hazard period) prior to the AMI diagnosis was compared with cases who were exposed 29-36 days (control period) before the AMI. A total of 6176 patients with AMI who underwent a procedure either during the defined hazard or control period contributed to the analyses. ORs with 95% CIs were computed using conditional logistic regression. RESULTS: The mean age of the total population was 74.7 years and 64.6% were male. The relative risk was higher following procedures performed under general/regional anaesthesia for gastrointestinal endoscopy (ORsummary, 4.23, 95% CI 1.58 to 11.31), vascular (ORsummary, 3.12, 95% CI 1.10 to 8.90), urological/gynaecological (ORsummary, 2.30, 95% CI 1.50 to 3.53) and orthopaedic (ORsummary,1.78, 95% CI 1.30 to 2.44) procedures, and for ENT (ear, nose and throat) and mouth procedures (ORsummary, 1.53, 95% CI 1.19 to 1.99) performed under local anaesthesia. CONCLUSION: This large population-based register study from two countries suggests that outpatient procedures are generally safe with regard to the postoperative risk of AMI. However, some procedures, such as gastrointestinal endoscopy, vascular procedures and urological/gynaecological procedures may increase the risk of AMI by twofold or threefold within the first 8 days after the procedures. Further studies are warranted to assess whether the effect is modified by cardiovascular medication or other clinical factors.

Data from national health registers as endpoints for the Tromsø Study: Correctness and completeness of stroke diagnoses.

AIM: To assess whether stroke diagnoses in national health registers are sufficiently correct and complete to replace manual collection of endpoint data for the Tromsø Study, a population-based epidemiological study. METHOD: Using the Tromsø Study Cardiovascular Disease Register for 2013-2014 as the gold standard, we calculated correctness (defined as positive predictive value, PPV) and completeness (defined as sensitivity) of stroke cases in four different data subsets derived from the Norwegian Patient Register and the Norwegian Stroke Register. We calculated the sensitivity and PPV with 95% confidence intervals (CIs) assuming a normal approximation of the binomial distribution. RESULTS: In the Norwegian Stroke Register we found a sensitivity of 79.8% (95% CI 74.2-85.4) and a PPV of 97.5% (95% CI 95.1-99.9). In the Norwegian Patient Register the sensitivity was 86.4% (95% CI 81.6-91.1) and the PPV was 84.2% (95% CI 79.2-89.2). The overall highest levels were found in a subset based on a linkage between the Norwegian Stroke Register and the Norwegian Patient Register, with a sensitivity of 88.9% (95% CI 84.5-93.3), and a PPV of 89.3% (95% CI 85.0-93.6). CONCLUSIONS: Data from the Norwegian Patient Register and from the linked data set between the Norwegian Patient Register and the Norwegian Stroke Register had acceptable levels of correctness and completeness to be considered as endpoint sources for the Tromsø Study Cardiovascular Disease Register. The benefits of using data from national registers as endpoints in epidemiological studies must be weighed against the impact of potentially decreased data quality.

Wake-up stroke and unknown-onset stroke; occurrence and characteristics from the nationwide Norwegian Stroke Register.

Introduction: Population-based knowledge of the characteristics of wake-up stroke and unknown-onset stroke is limited. We compared occurrence and characteristics of ischaemic and haemorrhagic wake-up stroke, unknown-onset stroke and known-onset stroke in a nationwide register-based study. Patients and methods: We included patients registered in the Norwegian Stroke Register from 2012 through 2019. Age, sex, risk factors, clinical characteristics, acute stroke treatment and discharge destination were compared according to stroke type and time of onset. Results: Of the 60,320 patients included, 11,451 (19%) had wake-up stroke, 11,098 (18.4%) had unknown time of onset and 37,771 (62.6%) had known symptom onset. The proportion of haemorrhagic stroke was lower among wake-up stroke patients (1107/11,451, 9.7%, 95% CI: 9.1-10.2) than for known-onset stroke (5230/37,771, 13.8%, 95% CI: 13.5-14.2) and for unknown-onset stroke (1850/11,098, 16.7%, 95% CI: 16.0-17.4). Mild stroke (NIHSS <5) was more frequent in ischaemic wake-up stroke (5364/8308, 64.6%, 95% CI: 63.5-65.5) than in known-onset (16,417/26,746, 61.4%, 95% CI: 60.8-62.0) and unknown-onset stroke (3242/5853, 55.4%, 95% CI: 54.1-56.7), while baseline characteristics were otherwise similar to known-onset stroke. Unknown-onset stroke patients were more often female, lived alone and had more severe strokes compared to wake-up stroke and known-onset stroke patients. Unknown-onset stroke patients were more often in need of community-based health care on discharge and had a higher in-hospital mortality. Discussion and conclusions: Ischaemic wake-up strokes shared baseline characteristics with known-onset strokes, but tended to be milder. Ischaemic unknown-onset stroke patients differed significantly from wake-up stroke, emphasising the importance of considering them as separate entities.

Risk for Acute Myocardial Infarction After Ophthalmologic Procedures.

BACKGROUND: Preoperative cardiovascular evaluations are frequently done before ambulatory ophthalmologic procedures. However, whether these procedures can trigger an acute myocardial infarction (AMI) is unknown. OBJECTIVE: To assess the short-term risk for AMI associated with ophthalmologic procedures. DESIGN: Case-crossover design. SETTING: Population-based nationwide study from Norway and Sweden. PARTICIPANTS: First-time patients with AMI, aged 40 years and older, identified via inpatient registries and linked to outpatient surgical procedures in Norway (2008 to 2014) and Sweden (2001 to 2014), respectively. MEASUREMENTS: Using self-matching, for each participant, exposure to ophthalmologic procedures in the 0 to 7 days before AMI diagnosis (hazard period) was compared with an 8-day period 30 days earlier, that is, days 29 to 36 before AMI (control period) to estimate the relative risk for an AMI the week after an ophthalmologic procedure. The odds ratios (ORs) with 95% CIs were calculated, using conditional logistic regression. Only patients who had a procedure of interest during either the hazard or control period were included. RESULTS: For the 806 patients with AMI included in this study, there was a lower likelihood of AMI in the week after an ophthalmologic procedure than during the control week (OR, 0.83; 95% CI, 0.75 to 0.91). Furthermore, there was no evidence of increased risk for AMI when analyses were stratified by surgery subtype, anesthesia (local or general), duration, invasiveness (low, intermediate, or high), patient's age (<65 years or ≥65 years), or comorbidity (none vs. any). LIMITATION: Potential bias from time-varying confounders between the hazard and the control periods. CONCLUSION: Ophthalmologic procedures done in an outpatient setting did not seem to be associated with an increased risk for AMI. PRIMARY FUNDING SOURCE: Central Norway Regional Health Authority and the Swedish Research Council.

Validating Acute Myocardial Infarction Diagnoses in National Health Registers for Use as Endpoint in Research: The Tromsø Study.

PURPOSE: To assess whether acute myocardial infarction (MI) diagnoses in national health registers are sufficiently correct and complete to replace manual collection of endpoint data for a population-based, epidemiological study. PATIENTS AND METHODS: Using the Tromsø Study Cardiovascular Disease Register for 2013-2014 as gold standard, we calculated correctness (defined as positive predictive value (PPV)) and completeness (defined as sensitivity) of MI cases in the Norwegian Myocardial Infarction Register and the Norwegian Patient Register separately and in combination. We calculated the sensitivity and PPV with 95% confidence intervals using the Clopper-Pearson Exact test. RESULTS: We identified 153 MI cases in the gold standard. In the Norwegian Myocardial Infarction Register, we found a PPV of 97.1% (95% confidence interval (CI) 92.8-99.2) and a sensitivity of 88.2% (95% CI 82.0-92.9). In the Norwegian Patient Register, the PPV was 96.3% (95% CI 91.6-98.8) and the sensitivity was 85.6% (95% CI 79.0-90.8). The combined dataset of the Norwegian Myocardial Infarction Register and the Norwegian Patient Register had a PPV of 96.6% (95% CI 92.1-98.9) and a sensitivity of 91.5% (95% CI 85.9-95.4). CONCLUSION: MI diagnoses in both the Norwegian Myocardial Infarction Register and the Norwegian Patient Register were highly correct and complete, and each of the registers could be considered as endpoint sources for the Tromsø Study. A combination of the two national registers seemed, however, to represent the most comprehensive data source overall. The benefits of using data from national registers as endpoints in epidemiological studies include faster, less resource-intensive access to nationwide data and considerably lower loss to follow-up, compared to manual data collection in a limited geographical area.

Influenza vaccination and risk for cardiovascular events: a nationwide self-controlled case series study.

BACKGROUND: US and European guidelines diverge on whether to vaccinate adults who are not at high risk for cardiovascular events against influenza. Here, we investigated the associations between influenza vaccination and risk for acute myocardial infarction, stroke and pulmonary embolism during the 2009 pandemic in Norway, when vaccination was recommended to all adults. METHODS: Using national registers, we studied all vaccinated Norwegian individuals who suffered AMI, stroke, or pulmonary embolism from May 1, 2009 through September 30, 2010. We defined higher-risk individuals as those using anti-diabetic, anti-obesity, anti-thrombotic, pulmonary or cardiovascular medications (i.e. individuals to whom vaccination was routinely recommended); all other individuals were regarded as having lower-risk. We estimated incidence rate ratios with 95% CI using conditional Poisson regression in the pre-defined risk periods up to 180 days following vaccination compared to an unexposed time-period, with adjustment for season or daily temperature. RESULTS: Overall, we observed lower risk for cardiovascular events following influenza vaccination. When stratified by baseline risk, we observed lower risk across all three outcomes in association with vaccination among higher-risk individuals. In this subgroup, relative risks were 0.72 (0.59-0.88) for AMI, 0.77 (0.59-0.99) for stroke, and 0.73 (0.45-1.19) for pulmonary embolism in the period 1-14 days following vaccination when compared to the background period. These associations remained essentially the same up to 180 days after vaccination. In contrast, the corresponding relative risks among subjects not using medications were 4.19 (2.69-6.52), 1.73 (0.91-3.31) and 2.35 (0.78-7.06). CONCLUSION: In this nationwide study, influenza vaccination was associated with overall cardiovascular benefit. This benefit was concentrated among those at higher cardiovascular risk as defined by medication use. In contrast, our results demonstrate no comparable inverse association with thrombosis-related cardiovascular events following vaccination among those free of cardiovascular medications at baseline. These results may inform the risk-benefit balance for universal influenza vaccination.

Stroke in Norway 2015­16 ­ treatment and outcomes. / Hjerneslag i Norge 2015­16 ­ behandling og resultater.

BACKGROUND: Treatment of stroke in Norway is decentralised; patients with stroke are treated at 50 different hospitals. We have surveyed the treatment of stroke in these hospitals and collated this with data from the Norwegian Stroke Registry. We wished to investigate whether there was any variation in treatment interventions and treatment outcomes between university hospitals and local hospitals. MATERIAL AND METHOD: A questionnaire survey among all Norwegian hospitals examined treatment interventions and resource availability. Data from the Norwegian Stroke Registry in 2015-2016 (n = 17 183) were used to compare patient characteristics and treatment outcomes for patients in university hospitals (n = 5 312) and local hospitals (n = 11 871). Treatment quality was measured using the quality indicators in the Norwegian Stroke Registry. RESULTS: The median age in the university hospitals was 75 years (interquartile range 65-83), and 44.1% of the patients were women. The median age in the local hospitals was 76 years (interquartile range 67-85); 46.7% women. Goal achievement on five out of ten quality indicators was high; for example, more than 90% of the patients were treated in a stroke unit, irrespective of the type of hospital. At the university hospitals, 1 038 (19.0%) of patients received thrombolytic therapy, compared to 1 612 (17.2%) in the local hospitals. Adjusted for age and level of consciousness, the probability of being self-reliant three months after the stroke was higher in local hospitals (OR 1.15, CI 1.04-1.27). INTERPRETATION: The decentralised stroke treatment in Norway accomplishes high and moderate goal achievement on the Norwegian Stroke Registry's quality indicators. The quality of treatment in local hospitals appears to be equally good or better than that provided in university hospitals.

Percutaneous Coronary Intervention as a Trigger for Stroke.

Percutaneous coronary intervention (PCI) is a plausible triggering factor for stroke, yet the magnitude of this excess risk remains unclear. This study aimed to quantify the transient change in risk of stroke for up to 12 weeks after PCI. We applied the case-crossover method, using data from the Norwegian Patient Register on all hospitalizations in Norway in the period of 2008 to 2014. The relative risk (RR) of ischemic stroke was highest during the first 2 days after PCI (RR 17.5, 95% confidence interval [CI] 4.2 to 72.8) and decreased gradually during the following weeks. The corresponding RR was 2.0 (95% CI 1.2 to 3.3) 4 to 8 weeks after PCI. The RR for women was more than twice as high as for men during the first 4 postprocedural weeks, RR 10.5 (95% CI 3.8 to 29.3) and 4.4 (95% CI 2.7 to 7.2), respectively. Our results were compatible with an increased RR of hemorrhagic stroke 4 to 8 weeks after PCI, but the events were few and the estimates were very imprecise, RR 3.0 (95% CI 0.8 to 11.1). The present study offers new knowledge about PCI as a trigger for stroke. Our estimates indicated a substantially increased risk of ischemic stroke during the first 2 days after PCI. The RR then decreased gradually but stayed elevated for 8 weeks. Increased awareness of this vulnerable period after PCI in clinicians and patients could contribute to earlier detection and treatment for patients suffering a postprocedural stroke.

Comparison of the validity of stroke diagnoses in a medical quality register and an administrative health register.

AIMS: Health registers are essential sources of data used in a wide range of stroke research, including epidemiological, clinical and healthcare studies. Regardless of the type of register, the data must be of high quality to be useful. In this study, we investigated and compared the correctness and completeness of the Norwegian Patient Register (an administrative health register) and the Norwegian Stroke Register (a medical quality register for acute stroke). METHODS: We reviewed the medical records for 5192 admissions to hospital in 2012 and defined cases of stroke in the two registers as true positive, false positive, true negative or false negative. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value with 95% confidence intervals assuming a normal approximation of the binomial distribution. RESULTS: The Norwegian Stroke Register was highly correct and relatively complete (sensitivity 88.1%, specificity 100% and PPV 98.6%). The Norwegian Patient Register was more complete, but less correct, when we included both the main and secondary diagnoses of stroke (sensitivity 96.8%, specificity 99.6% and PPV 79.7%); restricting the analyses to the main diagnoses of stroke resulted in less complete and more correct registrations (sensitivity 86.1%, specificity 99.9% and PPV 93.5%). CONCLUSIONS: The Norwegian Stroke Register and the Norwegian Patient Register are adequately complete and correct to serve as valuable sources of data for epidemiological, clinical and healthcare studies, as well as for administrative purposes.

Inter-rater reliability of a national acute stroke register.

BACKGROUND: Medical quality registers are useful sources of knowledge about diseases and the health services. However, there are challenges in obtaining valid and reliable data. This study aims to assess the reliability in a national medical quality register. METHODS: We randomly selected 111 patients having had a stroke in 2012. An experienced stroke nurse completed the Norwegian Stroke Register paper forms for all 111 patients by review of the medical records. We then extracted all registered data on the same patients from the Norwegian Stroke Register and calculated Cohen's kappa and Gwet's AC(1) with 95 % confidence intervals for 51 nominal variables and Cohen's quadratic weighted kappa and Gwet's AC(2) for three ordinal variables. For two time variables, we calculated the Intraclass Correlation Coefficient. RESULTS: Substantial to excellent reliability (kappa > 0.60/AC(1)> 0.80) was observed for most variables related to past medical history, functional status, stroke subtype and discharge destination. Although excellent reliability was observed for time of stroke onset (ICC 0.93), this variable was hampered with a substantial amount of missing values. Some variables related to treatment and examinations in hospital displayed low levels of agreement. This applies to heart rate monitoring (kappa 0.17/AC(1) 0.46), swallowing test performed (kappa 0.19/AC(1) 0.27) and mobilized out of bed within 24 h after admission (kappa 0.04/AC(1) -0.11). CONCLUSION: A majority of the variables in The Norwegian Stroke Register have substantial to excellent reliability. The problem areas seem to be the lack of completeness in the time variable indicating stroke onset and poor reliability in some variables concerning examinations and treatment received in hospital.