Effect of Spinal Cord Burst Stimulation vs Placebo Stimulation on Disability in Patients With Chronic Radicular Pain After Lumbar Spine Surgery: A Randomized Clinical Trial.

Importance: The use of spinal cord stimulation for chronic pain after lumbar spine surgery is increasing, yet rigorous evidence of its efficacy is lacking. Objective: To investigate the efficacy of spinal cord burst stimulation, which involves the placement of an implantable pulse generator connected to electrodes with leads that travel into the epidural space posterior to the spinal cord dorsal columns, in patients with chronic radiculopathy after surgery for degenerative lumbar spine disorders. Design, Setting, and Participants: This placebo-controlled, crossover, randomized clinical trial in 50 patients was conducted at St Olavs University Hospital in Norway, with study enrollment from September 5, 2018, through April 28, 2021. The date of final follow-up was May 20, 2022. Interventions: Patients underwent two 3-month periods with spinal cord burst stimulation and two 3-month periods with placebo stimulation in a randomized order. Burst stimulation consisted of closely spaced, high-frequency electrical stimuli delivered to the spinal cord. The stimulus consisted of a 40-Hz burst mode of constant-current stimuli with 4 spikes per burst and an amplitude corresponding to 50% to 70% of the paresthesia perception threshold. Main Outcomes and Measures: The primary outcome was difference in change from baseline in the self-reported Oswestry Disability Index (ODI; range, 0 points [no disability] to 100 points [maximum disability]; the minimal clinically important difference was 10 points) score between periods with burst stimulation and placebo stimulation. The secondary outcomes were leg and back pain, quality of life, physical activity levels, and adverse events. Results: Among 50 patients who were randomized (mean age, 52.2 [SD, 9.9] years; 27 [54%] were women), 47 (94%) had at least 1 follow-up ODI score and 42 (84%) completed all stimulation randomization periods and ODI measurements. The mean ODI score at baseline was 44.7 points and the mean changes in ODI score were -10.6 points for the burst stimulation periods and -9.3 points for the placebo stimulation periods, resulting in a mean between-group difference of -1.3 points (95% CI, -3.9 to 1.3 points; P = .32). None of the prespecified secondary outcomes showed a significant difference. Nine patients (18%) experienced adverse events, including 4 (8%) who required surgical revision of the implanted system. Conclusions and Relevance: Among patients with chronic radicular pain after lumbar spine surgery, spinal cord burst stimulation, compared with placebo stimulation, after placement of a spinal cord stimulator resulted in no significant difference in the change from baseline in self-reported back pain-related disability. Trial Registration: ClinicalTrials.gov Identifier: NCT03546738.

Incidence and case fatality of aneurysmal subarachnoid hemorrhage admitted to hospital between 2008 and 2014 in Norway.

BACKGROUND: To provide age- and sex-specific incidence and case fatality rates for non-traumatic aneurysmal subarachnoid hemorrhage (aSAH) in Norway. We also studied time trends in incidence and case fatality, as well as predictors of death following aSAH. METHODS: A nationwide study using discharge data for patients admitted with aSAH between 2008 and 2014. RESULTS: A total of 1732 patients with aSAH were included. The mean age was 60 years (SD 14) and 63% were females. Crude annual incidence was 5.7 per 100,000 person-years (95% CI 5.4-6.0) and was higher in females (6.3 per 100,000, 95% CI 5.9-6.7) compared with males (4.9 per 100,000, 95% CI 4.5-5.3). The annual decline in aSAH incidence was 3.2% per year (p = 0.007). The cumulative proportions of fatalities at days 30, 90, and 1 year were 22%, 25%, and 37%, respectively. The 30-day mortality rate did not change during the study period. Age (HR 0.7-2.2) and aneurysms in the posterior circulation (HR 1.7, 95% CI 1.3-2.3, p = 0.001) were associated with higher 30-day case fatality following aSAH, while aneurysm repair (HR 0.2, 95% CI 0.2-0.3, p < 0.001) was associated with lower risk. CONCLUSIONS: The incidence of aSAH declined in Norway between 2008 and 2014. Case fatality following aSAH continues to be high, and the 30-day mortality during the study period was unchanged. Increasing age and aneurysms in the posterior circulation were associated with increased risk of death within 30 days following aSAH.

Migraine and risk of stroke.

Migraine and stroke are two common and heterogeneous neurovascular disorders responsible for a significant burden for those affected and a great economic cost for the society. There is growing evidence that migraine increases the overall risk of cerebrovascular diseases. In this review, based on available literature through a PubMed search, we found that ischaemic stroke in people with migraine is strongly associated with migraine with aura, young age, female sex, use of oral contraceptives and smoking habits. The risk of transient ischaemic attack also seems to be increased in people with migraine, although this issue has not been extensively investigated. Although migraine appears to be associated with haemorrhagic stroke, the migraine aura status has a small influence on this relationship. Neuroimaging studies have revealed a higher prevalence of asymptomatic structural brain lesions in people with migraine. They are also more likely to have unfavourable vascular risk factors; however, the increased risk of stroke seems to be more apparent among people with migraine without traditional risk factors. The mechanism behind the migraine-stroke association is unknown. In light of the higher risk of stroke in people with migraine with aura, it is important to identify and modify any vascular risk factor. There is currently no direct evidence to support that a migraine prophylactic treatment can reduce future stroke in people with migraine.

Functional outcome and survival following spontaneous intracerebral hemorrhage: A retrospective population-based study.

BACKGROUND: Accurate and reliable clinical and radiological predictors of intracerebral hemorrhage (ICH) outcomes are needed to optimize treatment of ICH. The aim of this study was to investigate functional outcome and identify predictors of severe disability or death following ICH. MATERIALS AND METHODS: Retrospective population-based study of spontaneous ICH. Clinical and radiological data were obtained from electronic medical records, and functional outcome estimated using the modified Rankin Scale (mRS) before ICH and at 3 and 12 months after ICH. RESULTS: Four hundred and fifty-two patients were included (mean age 74.8 years, 45.6% females). Proportion of fatal outcome at 1 week was 22.1%, at 3 months 39.2%, and at 12 months 44.9%. Median mRS score before the ICH was 1 (interquartile range [IQR] 2); for survivors at 3 months, it was 5 (IQR 3); and at 12 months, it was 3 (IQR 2). Independent predictors of severe disability (mRS of 5) or death (mRS of 6) were use of oral antithrombotic drugs (OR 2.2, 95% CI 1.3-3.8, p = 0.04), mRS score before the ICH (OR 1.8, 95% CI 1.4-2.2, p < 0.001), Glasgow Coma Scale (GCS) on admission (OR 8.3, 95% CI 3.5-19.7, p < 0.001), hematoma volume >60 ml (OR 4.5, 05% CI 2.0-10.2, p < 0.001), and intraventricular hematoma extension (OR 1.8, 95% CI 0.8-4.2, p < 0.001). CONCLUSION: Intracerebral hemorrhage is associated with high mortality, and more than one third of survivors end up with severe disability or death 3 months later. Predictors of severe disability or death were use of oral antithrombotic drugs, functional disability prior to ICH, low GCS on admission, larger hematoma volume, and intraventricular hematoma extension.

Risk of intracranial hemorrhage (RICH) in users of oral antithrombotic drugs: Nationwide pharmacoepidemiological study.

BACKGROUND: The risks of intracranial haemorrhage (ICH) associated with antithrombotic drugs outside clinical trials are gaining increased attention. The aim of this nationwide study was to investigate the risk of ICH requiring hospital admission in users of antithrombotic drugs. METHODS AND FINDINGS: Data from the Norwegian Patient Registry and Norwegian Prescription Database were linked on an individual level. The primary outcome was incidence rates of ICH associated with use of antithrombotic drugs. Secondary endpoints were risk of ICH and fatal outcome following ICH assessed by Cox models. Among 3,131,270 individuals ≥18 years old observed from 2008 through 2014, there were 729,818 users of antithrombotic medications and 22,111 ICH hospitalizations. Annual crude ICH rates per 100 person-years were 0.076 (95% CI, 0.075-0.077) in non-users and 0.30 (95% CI, 0.30-0.31) in users of antithrombotic medication, with the highest age and sex adjusted rates observed for aspirin-dipyridamole plus clopidogrel (0.44; 95% CI, 0.19-0.69), rivaroxaban plus aspirin (0.36; 95% CI, 0.16-0.56), warfarin plus aspirin (0.34; 95% CI, 0.26-0.43), and warfarin plus aspirin and clopidogrel (0.33; 95% CI, 0.073-0.60). With no antithrombotic medication as reference, the highest adjusted hazard ratios (HR) for ICH were observed for aspirin-dypiridamole plus clopidogrel (6.29; 95% CI 3.71-10.7), warfarin plus aspirin and clopidogrel (4.38; 95% CI 2.71-7.09), rivaroxaban plus aspirin (3.82; 95% CI, 2.46-5.95), and warfarin plus aspirin (3.40; 95% CI, 2.99-3.86). All antithrombotic medication regimens were associated with an increased risk of ICH, except dabigatran monotherapy (HR 1.20; 95% CI, 0.88-1.65) and dabigatran plus aspirin (HR 1.79; 95% CI, 0.96-3.34). Fatal outcome within 90 days was more common in users (2,603 of 8,055) than non-users (3,228 of 14,056) of antithrombotic medication (32.3% vs 23.0%, p<0.001), and was associated with use of warfarin plus aspirin and clopidogrel (HR 2.89; 95% CI, 1.49-5.60), warfarin plus aspirin (HR 1.37; 95% CI, 1.11-1.68), aspirin plus clopidogrel (HR 1.30; 95% CI, 1.05-1.61), and warfarin (HR 1.19; 95% CI, 1.09-1.31). Increased one-year mortality was observed in users of antithrombotic medication following hemorrhagic stroke, subdural hemorrhage, subarachnoid hemorrhage, and traumatic ICH (all p<0.001). Limitations include those inherent to observational studies including the inability to make causal inferences, certain assumptions regarding drug exposure, and the possibility of residual confounding. CONCLUSIONS: The real-world incidence rates and risks of ICH were generally higher than reported in randomized controlled trials. There is still major room for improvement in terms of antithrombotic medication safety (clinicaltrials.gov NCT02481011).

Validation of intracranial hemorrhage in the Norwegian Patient Registry.

Objectives: Administrative health registries need to have accurate diagnoses and sufficient coverage in the population they serve in order to be useful in research. In this study, we investigated the proportion of discharge diagnoses of intracranial hemorrhage (ICH) that were coded correctly in the Norwegian Patient Registry (NPR). Materials and Methods: We reviewed the electronic medical records and diagnostic imaging of all admissions to St. Olavs University Hospital, Trondheim, Norway, between January 1, 2008, to December 31, 2014, with a discharge diagnosis of ICH in the NPR, and estimated positive predictive values (PPVs) for primary and secondary diagnoses. Separate calculations were made for inpatient and outpatient admissions. Results: In total, 1,419 patients with 1,458 discharge diagnoses of ICH were included in our study. Overall, 1,333 (91.4%) discharge diagnoses were coded correctly. For inpatient admissions, the PPVs for primary discharge codes were 96.9% for hemorrhagic stroke, 95.3% for subarachnoid hemorrhage, and 97.9% for subdural hemorrhage. The most common cause of incorrect diagnosis was previous stroke that should have been coded as rehabilitation or sequela after stroke. There were more false-positive diagnoses among outpatient consultations and secondary diagnoses. Conclusion: Coding of ICH discharge diagnoses in the NPR is of high quality, showing that data from this registry can safely be used for medical research.

Lumbar Microdiscectomy in Obese Patients: A Multicenter Observational Study.

OBJECTIVE: To evaluate the association between obesity and outcomes after microdiscectomy for lumbar disc herniation. METHODS: The primary outcome measure was change in Oswestry Disability Index (ODI) at 1 year after surgery. Obesity was defined as body mass index (BMI) ≥30. Prospective data were retrieved from the Norwegian Registry for Spine Surgery. RESULTS: We enrolled 4932 patients, 4018 nonobese and 914 obese. For patients with complete 1-year follow-up (n = 3381) the mean improvement in ODI was 31.2 points (95% confidence interval 30.4-31.9, P < 0.001). Improvement in ODI was 31.4 points in nonobese and 30.1 points in obese patients (P = 0.182). Obese and nonobese patients were as likely to achieve a minimal clinically important difference (84.2 vs. 82.7%, P = 0.336) in ODI (≥10 points improvement). Obesity was identified as a negative predictor for ODI improvement in a multiple regression analysis (BMI 30-34.99; P < 0.001, BMI ≥35; P = 0.029). Obese and nonobese patients experienced similar improvement in Euro-Qol-5 scores (0.48 vs. 0.49 points, P = 0.441) as well as back pain (3.7 vs. 3.5 points, P = 0.167) and leg pain (4.7 vs. 4.8 points, P = 0.654), as measured by the Numeric Rating Scale. Duration of surgery was shorter for nonobese patients (55.7 vs. 65.3 minutes, P ≤ 0.001). Nonobese patients experienced fewer complications compared with obese patients (6.1% vs. 8.3%, P = 0.017). Obese patients had slightly longer hospital stays (2.0 vs. 1.8 days, P = 0.004). CONCLUSIONS: Although they had more minor complications, obese individuals experienced improvement after lumbar microdiscectomy for lumbar disc herniation similar to that of nonobese individuals.

Risk of intracranial hemorrhage in users of oral antithrombotic drugs: Study protocol for a nationwide study.

Background A wide range of antithrombotic medications can be used in the prevention and treatment of thrombosis. Among hemorrhagic complications of antithrombotic drugs, intracranial hemorrhage may have particularly devastating consequences with high morbidity, disability and mortality rates. The incidence and risks of intracranial hemorrhage in patients on antithrombotic treatments from regular clinical practice outside clinical trials remain largely unknown. It is not known if results from clinical trials can be extrapolated to everyday clinical practice. We will conduct a nationwide study to investigate the risks and incidence rates of intracranial hemorrhage in users oral antithrombotic drugs in Norway from 2008 through 2014.   Methods and design The aim of this nationwide study is to investigate the incidence rates of intracranial hemorrhage requiring hospitalization in users of oral antithrombotic drugs. The study will be conducted within the approximately 4.7 million inhabitants of Norway from January 1 (st), 2008, to December 31 (st), 2014. Treatment and outcome data are obtained from the Norwegian patient registry and the Norwegian prescription database.   Trial registration number Clinicaltrials.gov (NCT02481011).