Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Waveform Modelling for the Laser Interferometer Space Antenna

LISA, the Laser Interferometer Space Antenna, will usher in a new era in gravitational-wave astronomy. As the first anticipated space-based gravitational-wave detector, it will expand our view to the millihertz gravitational-wave sky, where a spectacular variety of interesting new sources abound: from millions of ultra-compact binaries in our Galaxy, to mergers of massive black holes at cosmological distances; from the beginnings of inspirals that will venture into the ground-based detectors' view to the death spiral of compact objects into massive black holes, and many sources in between. Central to realising LISA's discovery potential are waveform models, the theoretical and phenomenological predictions of the pattern of gravitational waves that these sources emit. This white paper is presented on behalf of the Waveform Working Group for the LISA Consortium. It provides a review of the current state of waveform models for LISA sources, and describes the significant challenges that must yet be overcome.Comment: 239 pages, 11 figures, white paper from the LISA Consortium Waveform Working Group, invited for submission to Living Reviews in Relativity, updated with comments from communit

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Traumatic brain injury (TBI) and spinal cord injury (SCI) are increasingly recognised as global health priorities in view of the preventability of most injuries and the complex and expensive medical care they necessitate. We aimed to measure the incidence, prevalence, and years of life lived with disability (YLDs) for TBI and SCI from all causes of injury in every country, to describe how these measures have changed between 1990 and 2016, and to estimate the proportion of TBI and SCI cases caused by different types of injury. Methods: We used results from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016 to measure the global, regional, and national burden of TBI and SCI by age and sex. We measured the incidence and prevalence of all causes of injury requiring medical care in inpatient and outpatient records, literature studies, and survey data. By use of clinical record data, we estimated the proportion of each cause of injury that required medical care that would result in TBI or SCI being considered as the nature of injury. We used literature studies to establish standardised mortality ratios and applied differential equations to convert incidence to prevalence of long-term disability. Finally, we applied GBD disability weights to calculate YLDs. We used a Bayesian meta-regression tool for epidemiological modelling, used cause-specific mortality rates for non-fatal estimation, and adjusted our results for disability experienced with comorbid conditions. We also analysed results on the basis of the Socio-demographic Index, a compound measure of income per capita, education, and fertility. Findings: In 2016, there were 27·08 million (95% uncertainty interval [UI] 24·30–30·30 million) new cases of TBI and 0·93 million (0·78–1·16 million) new cases of SCI, with age-standardised incidence rates of 369 (331–412) per 100 000 population for TBI and 13 (11–16) per 100 000 for SCI. In 2016, the number of prevalent cases of TBI was 55·50 million (53·40–57·62 million) and of SCI was 27·04 million (24·98–30·15 million). From 1990 to 2016, the age-standardised prevalence of TBI increased by 8·4% (95% UI 7·7 to 9·2), whereas that of SCI did not change significantly (−0·2% [–2·1 to 2·7]). Age-standardised incidence rates increased by 3·6% (1·8 to 5·5) for TBI, but did not change significantly for SCI (−3·6% [–7·4 to 4·0]). TBI caused 8·1 million (95% UI 6·0–10·4 million) YLDs and SCI caused 9·5 million (6·7–12·4 million) YLDs in 2016, corresponding to age-standardised rates of 111 (82–141) per 100 000 for TBI and 130 (90–170) per 100 000 for SCI. Falls and road injuries were the leading causes of new cases of TBI and SCI in most regions. Interpretation: TBI and SCI constitute a considerable portion of the global injury burden and are caused primarily by falls and road injuries. The increase in incidence of TBI over time might continue in view of increases in population density, population ageing, and increasing use of motor vehicles, motorcycles, and bicycles. The number of individuals living with SCI is expected to increase in view of population growth, which is concerning because of the specialised care that people with SCI can require. Our study was limited by data sparsity in some regions, and it will be important to invest greater resources in collection of data for TBI and SCI to improve the accuracy of future assessments. Funding: Bill & Melinda Gates Foundation

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Association Between Radiological Evidence of Kaplan Fiber Injury, Intraoperative Findings, and Pivot-Shift Grade in the Setting of Acute Anterior Cruciate Ligament Injury

Background: Biomechanical studies have suggested that the Kaplan fibers (KFs) of the iliotibial band play a role in controlling anterolateral rotation of the knee. There is a paucity of clinical information on whether injury to the KF in the setting of anterior cruciate ligament (ACL) rupture contributes to increased rotatory laxity of the knee. Purpose/Hypothesis: The purpose was to evaluate the association among radiological evidence of KF injury, intraoperative arthroscopic findings, and grade of pivot shift at the time of ACL reconstruction (ACLR). It was hypothesized that KF injury would be associated with increased injury to the lateral compartment of the knee and a higher grade of pivot shift. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective magnetic resonance imaging (MRI) analysis was conducted on 267 patients with ACL-injured knees who underwent primary ACLR. Patients who had MRI and surgery within 60 days of injury were included (mean age, 23.6 years); there were 158 (59.2%) male patients. MRI was performed using standard knee protocols, and diagnostic criteria were applied to identify KF injury. Associations were made among MRI findings, intraoperative findings, and grade of pivot shift with the patient examined under anesthesia at the time of ACLR. A comparison was made between patients with and without radiological evidence of KF injury. Results: The prevalence of KF injury was 17.6% (47/267 patients). Arthroscopic evidence of lateral meniscal injury was associated with KF injury (KF intact, 31%; KF injured, 55%; P = .010). The majority of patients in the intact and injured KF groups had a grade 2 pivot shift (75% and 70%, respectively). A minority had grade 3 pivot shift: 5% in the intact group versus 6.4% in the injured group. There was no association between radiological evidence of KF injury and pivot-shift grade ( P = .600). Conclusion: In acute ACL injury, KF injuries were not very common (17.6%), and the rate of grade 3 pivot shift was low (5.2%). When present, KF injuries were not associated with a higher-grade pivot shift. However, there was an association between KF injury and lateral meniscal tears identified at the time of ACLR. The role of KFS in controlling anterolateral rotatory laxity in the acute ACL injury in the clinical setting may be less evident when compared with the biomechanical setting. </jats:sec

Is There an Association in Young Patients Between Quadriceps or Hamstring Strength After ACL Reconstruction and Graft Rupture?

Background: Younger patients who sustain anterior cruciate ligament (ACL) ruptures are at high risk for reinjury after ACL reconstruction. Restoring muscle strength before return to sports (RTS) is regarded as an important factor in reducing the reinjury risk, and quadriceps and hamstring strength assessment is commonly included in RTS testing. However, it is not clear whether reduced strength is a risk factor for subsequent graft rupture in this patient population. Purpose: To investigate the association between quadriceps and hamstring strength at 12 months after primary ACL reconstruction and ACL graft rupture in young patients. Study Design: Case-control study; Level of evidence, 3. Methods: The cohort consisted of 210 patients (100 men and 110 women) who were younger than 20 years at the time of primary ACL reconstruction with a hamstring tendon autograft and who had no previous contralateral ACL injury. Isokinetic strength testing (60 and 180 deg/s) of knee flexors and extensors was performed at 12 months postoperatively, and the limb symmetry index (LSI) for each strength outcome was calculated. RTS rates and the incidence of further ACL graft ruptures were recorded. Results: Measures of central tendency (mean and median) of LSI values ranged from 88 to 98. The percentage of patients with LSI ≥90 was 57% to 69% for quadriceps strength and 45% to 47% for hamstring strength. Overall, 19 patients (9%) sustained an ACL graft rupture. No significant differences were found between the patients who sustained an ACL graft rupture and those who did not in terms of quadriceps and hamstring strength at 12 months. No significant associations were found between achieving LSI ≥90 for quadriceps peak torque and subsequent ACL graft rupture. Conclusion: In young patients who underwent an ACL reconstruction, no association was noted between quadriceps and hamstring strength at 12 months postoperatively and subsequent graft ruptures. The role of strength testing as part of the RTS criteria after ACL reconstruction, and specifically the use of limb symmetry thresholds, warrants further investigation and clarification. </jats:sec

Is There an Association in Young Patients Between Quadriceps or Hamstring Strength After ACL Reconstruction and Graft Rupture?

Background: Younger patients who sustain anterior cruciate ligament (ACL) ruptures are at high risk for reinjury after ACL reconstruction. Restoring muscle strength before return to sports (RTS) is regarded as an important factor in reducing the reinjury risk, and quadriceps and hamstring strength assessment is commonly included in RTS testing. However, it is not clear whether reduced strength is a risk factor for subsequent graft rupture in this patient population. Purpose: To investigate the association between quadriceps and hamstring strength at 12 months after primary ACL reconstruction and ACL graft rupture in young patients. Study Design: Case-control study; Level of evidence, 3. Methods: The cohort consisted of 210 patients (100 men and 110 women) who were younger than 20 years at the time of primary ACL reconstruction with a hamstring tendon autograft and who had no previous contralateral ACL injury. Isokinetic strength testing (60 and 180 deg/s) of knee flexors and extensors was performed at 12 months postoperatively, and the limb symmetry index (LSI) for each strength outcome was calculated. RTS rates and the incidence of further ACL graft ruptures were recorded. Results: Measures of central tendency (mean and median) of LSI values ranged from 88 to 98. The percentage of patients with LSI ≥90 was 57% to 69% for quadriceps strength and 45% to 47% for hamstring strength. Overall, 19 patients (9%) sustained an ACL graft rupture. No significant differences were found between the patients who sustained an ACL graft rupture and those who did not in terms of quadriceps and hamstring strength at 12 months. No significant associations were found between achieving LSI ≥90 for quadriceps peak torque and subsequent ACL graft rupture. Conclusion: In young patients who underwent an ACL reconstruction, no association was noted between quadriceps and hamstring strength at 12 months postoperatively and subsequent graft ruptures. The role of strength testing as part of the RTS criteria after ACL reconstruction, and specifically the use of limb symmetry thresholds, warrants further investigation and clarification