Colchicine for secondary prevention of ischaemic stroke and atherosclerotic events: a meta-analysis of randomised trials.

Background: Guidelines recommend low-dose colchicine for secondary prevention in cardiovascular disease, but uncertainty remains concerning its efficacy for stroke, efficacy in key subgroups and about uncommon but serious safety outcomes. Methods: In this trial-level meta-analysis, we searched bibliographic databases and trial registries form inception to May 16, 2024. We included randomised trials of colchicine for secondary prevention of ischaemic stroke and major adverse cardiovascular events (MACE: ischaemic stroke, myocardial infarction, coronary revascularisation, or cardiovascular death). Secondary outcomes were serious safety outcomes and mortality. A fixed-effect inverse-variance model was used to generate a pooled estimate of relative risk (RR) with 95% confidence intervals (CI). This study is registered with PROSPERO, CRD42024540320. Findings: Six trials involving 14,934 patients with prior stroke or coronary disease were included. In all patients, colchicine compared with placebo or no colchicine reduced the risk for ischaemic stroke by 27% (132 [1.8%] events versus 186 [2.5%] events, RR 0.73 [95% CI 0.58-0.90]) and MACE by 27% (505 [6.8%] events versus 693 [9.4%] events, with RR 0.73 [0.65-0.81]). Efficacy was consistent in key subgroups (females versus males, age below versus above 70, with versus without diabetes, statin versus non-statin users). Colchicine was not associated with an increase in serious safety outcomes: hospitalisation for pneumonia (109 [1.5%] versus 106 [1.5%], RR 0.99 [0.76-1.30]), cancer (247 [3.5%] versus 255 [3.6%], RR 0.97 [0.82-1.15]), and gastro-intestinal events (153 [2.1%] versus 135 [1.9%]), RR 1.15 [0.91-1.44]. There was no difference in all-cause death (201 [2.7%] versus 181 [2.4%], RR 1.09 [0.89-1.33]), cardiovascular death (70 [0.9%] versus 80 [1.1%], RR 0.89 [0.65-1.23]), or non-cardiovascular death (131 [1.8%] versus 101 [1.4%], RR 1.26 [0.98-1.64]). Interpretation: In patients with prior stroke or coronary disease, colchicine reduced ischaemic stroke and MACE, with consistent treatment effect in key subgroups, and did not increase serious safety events or death. Funding: There was no funding source for this study.

Detection rates of asymptomatic carotid artery stenosis and atrial fibrillation by selective screening of patients without cardiovascular disease.

BACKGROUND: Individuals with significant asymptomatic carotid artery stenosis (ACAS) and atrial fibrillation (AF) could benefit from specific interventions to prevent heart attack and stroke, but are often clinically 'silent'. We aimed to determine detection rate of ACAS and AF by screening, targeting a population at increased cardiovascular risk. METHODS: Data on adults who attended voluntary and self-funded commercial screening clinics in the United States or the United Kingdom between 2008 and 2013 were used. The Atherosclerotic Cardiovascular Disease (ASCVD) risk equation was applied to each participants and detection rates of targeted screening for ≥50% ACAS and AF to those at highest risk of CVD was assessed. RESULTS: Among 0.4 million individuals between 40 and 80 years, without CVD, 6191 (1.6%) had ACAS and 1026 (0.3%) had AF. Selective screening of participants with a predicted 10-year CVD risk of ≥20% identified 40% of ACAS cases, a prevalence of 3.7%, leading to a number needed to screen (NNS) of 27, as well as 39% of AF cases, a prevalence of 0.6%, with a NNS of 170. Selective screening of those with a predicted 10-year CVD risk of ≥15% identified 54% of ACAS cases, a prevalence of 3.3%, and an NNS of 31, as well as 51% of AF cases, a prevalence of 0.5%, with an NNS of 195. CONCLUSIONS: Selective screening for ACAS and AF implemented in ASCVD risk assessment greatly reduces the NNS when compared with population-level screening with detection rates of ACAS and AF substantially greater in people at higher predicted CVD risk.

Temporal Trends and Determinants of Stroke Risk in Patients With Medically Treated Asymptomatic Carotid Stenosis.

BACKGROUND: Effectiveness of carotid procedures (surgery and stenting) in patients with asymptomatic carotid artery stenosis (ACAS) depends on the absolute risk reduction that patients might receive from these procedures. We aimed to quantify the risk of ipsilateral ischemic stroke and examined temporal trends and determinants of these risks in patients with ACAS treated conservatively. METHODS: We conducted a systematic review from inception to March 9, 2023, of peer-reviewed trials and cohort studies describing ipsilateral ischemic stroke risk in medically treated patients with ACAS of ≥50%. Risk of bias was assessed with an adapted version of the Quality in Prognosis Studies tool. We calculated the annual incidence rates of ipsilateral ischemic stroke. We explored temporal trends and associations of sex and degree of stenosis with ipsilateral ischemic stroke using Poisson metaregression analysis and incidence rate ratios, respectively. RESULTS: After screening 5915 reports, 73 studies describing ipsilateral ischemic stroke rates of 28 625 patients with midyear of recruitment ranging from 1976 to 2014 were included. The incidence of ipsilateral ischemic stroke was 0.98 (95% CI, 0.93-1.04) per 100 patient-years (median duration of follow-up, 3.3 years). The incidence decreased 24% with every 5 years more recent midyear of recruitment (rate ratio, 0.76 [95% CI, 0.73-0.78]). Incidence rates of ipsilateral ischemic stroke were lower in female patients (rate ratio, 0.74 [95% CI, 0.63-0.87]) and in patients with moderate versus severe stenosis when assessed in cohort studies, with incidence rate ratios of 0.41 ([95% CI, 0.35-0.49] cutoff, 70%) and 0.42 ([95% CI, 0.30-0.59] cutoff, 80%). CONCLUSIONS: Reported risks of ipsilateral ischemic stroke in patients with ACAS have declined 24% every 5 years from mid-1970s onward, further challenging the routine use of carotid procedures. Risks were lower in female patients and more than twice as high with severe compared with moderate ACAS. Inclusion of these findings in individualized risk assessment can help to determine the benefit of carotid procedures in selected individual patients with ACAS. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021222940.

Risks of Stroke and Heart Disease Following Hysterectomy and Oophorectomy in Chinese Premenopausal Women.

BACKGROUND: Little is known about the long-term risks of stroke and ischemic heart disease (IHD) in women who had a hysterectomy alone (HA) or with bilateral oophorectomy (HBO) for benign diseases, particularly in China where the burden of cardiovascular diseases (CVD) is high. We assessed mean levels of cardiovascular risk factors and relative risks of stroke and IHD in Chinese women who had a HA or HBO. METHODS: A total of 302 510 women, aged 30 to 79 years were enrolled in the China Kadoorie Biobank from 2004 to 2008 and followed up for a mean of 9.8 years. The analysis involved premenopausal women without prior cardiovascular disease or cancer at enrollment. We calculated adjusted hazard ratios for incident cases of CVD and their pathological types (ischemic stroke, hemorrhagic stroke, and IHD) after HA and HBO. Analyses were stratified by age and region and adjusted for levels of education, household income, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diabetes, self-reported health, and number of pregnancies. RESULTS: Among 282 722 eligible women, 8478 had HA, and 1360 had HBO. Women who had HA had 9% higher risk of CVD after HA (hazard ratio, 1.09 [95% CI, 1.06-1.12]) and 19% higher risk of CVD after HBO (1.19 [95% CI, 1.12-1.26]) compared with women who did not. Both HA and HBO were associated with higher risks of ischemic stroke and IHD but not with hemorrhagic stroke. The relative risks of CVD associated with HA and HBO were more extreme at younger age of surgery. CONCLUSIONS: Women who had either HA or HBO have higher risks of ischemic stroke and IHD, and these risks should be evaluated when discussing these interventions. Additional screening for risk factors for CVD should be considered in women following HA and HBO operations, especially if such operations are performed at younger age.

Interleukin-6 Predicts Carotid Plaque Severity, Vulnerability, and Progression.

BACKGROUND: IL-6 (interleukin-6) has important roles in atherosclerosis pathophysiology. To determine if anti-IL-6 therapy warrants evaluation as an adjuvant stroke prevention strategy in patients with carotid atherosclerosis, we tested whether circulating IL-6 levels predict carotid plaque severity, vulnerability, and progression in the prospective population-based CHS (Cardiovascular Health Study). METHODS: Duplex carotid ultrasound was performed at baseline and 5 years. Baseline plaque severity was scored 0 to 5 based on North American Symptomatic Carotid Endarterectomy Trial grade of stenosis. Plaque vulnerability at baseline was the presence of markedly irregular, ulcerated, or echolucent plaques. Plaque progression at 5 years was a ≥1 point increase in stenosis severity. The relationship of baseline plasma IL-6 levels with plaque characteristics was modeled using multivariable linear (severity) or logistic (vulnerability and progression) regression. Risk factors of atherosclerosis were included as independent variables. Stepwise backward elimination was used with P>0.05 for variable removal. To assess model stability, we computed the E-value or minimum strength of association (odds ratio scale) that unmeasured confounders must have with log IL-6 and the outcome to suppress the association. We performed internal validation with 100 bootstrap samples. RESULTS: There were 4334 participants with complete data (58.9% women, mean age: 72.7±5.1 years), including 1267 (29.2%) with vulnerable plaque and 1474 (34.0%) with plaque progression. Log IL-6 predicted plaque severity (ß=0.09, P=1.3×10-3), vulnerability (OR, 1.21 [95% CI, 1.05-1.40]; P=7.4×10-3, E-value=1.71), and progression (OR, 1.44 [95% CI, 1.23-1.69], P=9.1×10-6, E-value 2.24). In participants with >50% predicted probability of progression, mean log IL-6 was 0.54 corresponding to 2.0 pg/mL. Dichotomizing IL-6 levels did not affect the performance of prediction models. CONCLUSIONS: Circulating IL-6 predicts carotid plaque severity, vulnerability, and progression. The 2.0 pg/mL cutoff could facilitate the selection of individuals that would benefit from anti-IL-6 drugs for stroke prevention.

Surgery for cerebral cavernous malformations: a systematic review and meta-analysis.

BACKGROUND: We sought to quantify the risks of neurosurgical excision of cerebral cavernous malformations (CCMs) in a systematic review of cohort studies. METHODS: We updated our previous systematic review by searching OVID Medline, OVID EMBASE, and the Cochrane Library from 1 January 2013 to 30 April 2019. The primary outcome was a composite of death attributed to CCM or surgery, non-fatal symptomatic intracerebral haemorrhage (ICH), or new or worsened persistent non-haemorrhagic focal neurological deficit (FND). RESULTS: We included 70 cohorts, 67 reporting surgery alone, and three compared surgery to conservative management. A total of 5,089 patients (median age 36 years, 52% female) underwent surgery (total follow-up 19,404 patient-years). The annual rate of the composite outcome was 4.2% (95% CI 2.9 to 5.7; 46 cohorts; I2 = 93%), which was higher in cohorts reporting exclusively brainstem CCM (6.0%, 95% CI 4.1-8.3; 25 cohorts, I2 = 92%) versus predominantly supratentorial CCM (2.4%, 95% CI 1.3-3.8, 21 cohorts, I2 = 86%, phet = 0.001). The annual rate of the composite outcome was higher in cohorts with > 95% presenting with ICH (6.1%, 95% CI 4.2-8.4; 23 cohorts, I2 = 93%) versus others (2.3%, 95% CI 1.2-3.7; 23 cohorts, I2 = 83%, phet = 0.001). The incidence of the composite outcome did not change over time in cohorts of exclusively brainstem CCM (p = 0.7) or predominantly supratentorial CCM (p = 0.5). CONCLUSIONS: The risk of death, ICH, or FND after CCM excision is ~ 4%. This risk is higher for brainstem CCM and CCM that have caused ICH but has not changed over time. TRIAL REGISTRATION: This systematic review was registered (PROSPERO CRD42019131246).

Development and Internal Validation of a Risk Score to Detect Asymptomatic Carotid Stenosis.

OBJECTIVE: Asymptomatic carotid stenosis (ACS) is associated with an increased risk of ischaemic stroke and myocardial infarction. Risk scores have been developed to detect individuals at high risk of ACS, thereby enabling targeted screening, but previous external validation showed scope for refinement of prediction by adding additional predictors. The aim of this study was to develop a novel risk score in a large contemporary screened population. METHODS: A prediction model was developed for moderate (≥50%) and severe (≥70%) ACS using data from 596 469 individuals who attended screening clinics. Variables that predicted the presence of ≥50% and ≥70% ACS independently were determined using multivariable logistic regression. Internal validation was performed using bootstrapping techniques. Discrimination was assessed using area under the receiver operating characteristic curves (AUROCs) and agreement between predicted and observed cases using calibration plots. RESULTS: Predictors of ≥50% and ≥70% ACS were age, sex, current smoking, diabetes mellitus, prior stroke/transient ischaemic attack, coronary artery disease, peripheral arterial disease, blood pressure, and blood lipids. Models discriminated between participants with and without ACS reliably, with an AUROC of 0.78 (95% confidence interval [CI] 0.77-0.78) for ≥ 50% ACS and 0.82 (95% CI 0.81-0.82) for ≥ 70% ACS. The number needed to screen in the highest decile of predicted risk to detect one case with ≥50% ACS was 13 and that of ≥70% ACS was 58. Targeted screening of the highest decile identified 41% of cases with ≥50% ACS and 51% with ≥70% ACS. CONCLUSION: The novel risk model predicted the prevalence of ACS reliably and performed better than previous models. Targeted screening among the highest decile of predicted risk identified around 40% of all cases with ≥50% ACS. Initiation or intensification of cardiovascular risk management in detected cases might help to reduce both carotid related ischaemic strokes and myocardial infarctions.

Validation of Risk Prediction Models to Detect Asymptomatic Carotid Stenosis.

Background Significant asymptomatic carotid stenosis (ACS) is associated with higher risk of strokes. While the prevalence of moderate and severe ACS is low in the general population, prediction models may allow identification of individuals at increased risk, thereby enabling targeted screening. We identified established prediction models for ACS and externally validated them in a large screening population. Methods and Results Prediction models for prevalent cases with ≥50% ACS were identified in a systematic review (975 studies reviewed and 6 prediction models identified [3 for moderate and 3 for severe ACS]) and then validated using data from 596 469 individuals who attended commercial vascular screening clinics in the United States and United Kingdom. We assessed discrimination and calibration. In the validation cohort, 11 178 (1.87%) participants had ≥50% ACS and 2033 (0.34%) had ≥70% ACS. The best model included age, sex, smoking, hypertension, hypercholesterolemia, diabetes mellitus, vascular and cerebrovascular disease, measured blood pressure, and blood lipids. The area under the receiver operating characteristic curve for this model was 0.75 (95% CI, 0.74-0.75) for ≥50% ACS and 0.78 (95% CI, 0.77-0.79) for ≥70% ACS. The prevalence of ≥50% ACS in the highest decile of risk was 6.51%, and 1.42% for ≥70% ACS. Targeted screening of the 10% highest risk identified 35% of cases with ≥50% ACS and 42% of cases with ≥70% ACS. Conclusions Individuals at high risk of significant ACS can be selected reliably using a prediction model. The best-performing prediction models identified over one third of all cases by targeted screening of individuals in the highest decile of risk only.

A systematic review and meta-analysis of complication rates after carotid procedures performed by different specialties.

OBJECTIVE: Different competencies and skills are required and obtained during medical specialization. However, whether these have an impact on procedural outcomes of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. We assessed the reported association between operator specialization and procedural outcomes after CEA or CAS to determine whether CEA and CAS should be performed by specific specialties. METHODS: We systematically searched PubMed and Embase up to August 21, 2017, for randomized clinical trials and observational studies that compared two or more specialties performing CEA or CAS for symptomatic and asymptomatic carotid artery stenosis. The composite primary outcome was procedural stroke or death (ie, occurring within 30 days of the procedure or before discharge). Risk estimates were pooled with a generic inverse variance random effects model. RESULTS: A total of 35 studies (26 providing data on CEA, 8 providing data on CAS, and 1 providing data on both CEA and CAS) were included, describing 256,033 CEA and 38,605 CAS procedures. For CEA, decreased risk of procedural stroke or death for operations performed by vascular surgeons was found with pooled unadjusted relative risk (RR) of 0.63 (95% confidence interval [CI], 0.46-0.86; seven studies) compared with neurosurgeons and RR of 0.81 (95% CI, 0.66-0.99; six studies) compared with general surgeons. An increased risk of procedural stroke or death for operations performed by neurosurgeons compared with cardiothoracic surgeons was found with a pooled unadjusted RR of 1.22 (95% CI, 1.02-1.46). No studies adjusted for potential confounding, and no significant unadjusted associations were found in other comparisons of operator specialty for the primary outcome. For CAS, no differences in procedural stroke or death were found by operator specialty. CONCLUSIONS: Studies were at high risk of bias mainly because of potential confounding by patient selection for CEA and CAS. Current evidence is insufficient to restrict CEA or CAS to specific specialties.

Stereotactic radiosurgery for cerebral cavernous malformations: A systematic review.

OBJECTIVE: The efficacy of stereotactic radiosurgery (SRS) for the treatment of cerebral cavernous malformations (CCMs) is uncertain, so we set out to quantify clinical outcomes after SRS for CCM and compare them to microsurgical excision or conservative management. METHODS: We searched Ovid Medline and Ovid EMBASE from inception until June 1, 2018, for peer-reviewed publications describing clinical outcomes after SRS for ≥10 people with CCM in cohorts with or without a comparison group treated with neurosurgical excision or conservative management. Two reviewers independently extracted data from the included studies to quantify cohort characteristics and the incidence of the primary outcome (death attributable to CCM or its treatment) and secondary outcomes (incident nonfatal symptomatic intracerebral hemorrhage [ICH] and incident nonhemorrhagic persistent focal neurologic deficit [FND]). We assessed whether comparative studies showed a dramatic association (meaning the conventionally calculated probability comparing 2 differently managed patient groups from the same population was <0.01 with a rate ratio greater than 10). RESULTS: We included 30 cohort studies involving a total of 1,576 patients undergoing SRS for CCM. Four nonrandomized studies compared SRS to other treatment strategies, but did not demonstrate dramatic associations. During a median follow-up of 48 (interquartile range 35-62) months after SRS, the annual incidences (95% confidence interval) of outcomes were death 0.18% (0.10-0.31), ICH 2.40% (2.05-2.80), FND 0.71% (0.53-0.96), and the composite of death, ICH, or FND 3.63% (3.17-4.16). Outcomes did not differ by CCM location or type of SRS. CONCLUSION: After SRS for CCM, the annual incidences of death, ICH, and FND are <5% and seem comparable to outcomes without SRS. A randomized trial of SRS for CCM is needed.

High Operator and Hospital Volume Are Associated With a Decreased Risk of Death and Stroke After Carotid Revascularization: A Systematic Review and Meta-analysis.

OBJECTIVE: To examine the association between operator or hospital volume and procedural outcomes of carotid revascularization. BACKGROUND: Operator and hospital volume have been proposed as determinants of outcome after carotid endarterectomy (CEA) or carotid artery stenting (CAS). The magnitude and clinical relevance of this relationship are debated. METHODS: We systematically searched PubMed and EMBASE until August 21, 2017. The primary outcome was procedural (30 days, in-hospital, or perioperative) death or stroke. Obtained or estimated risk estimates were pooled with a generic inverse variance random-effects model. RESULTS: We included 87 studies. A decreased risk of death or stroke following CEA was found for high compared to low operator volume with a pooled adjusted odds ratio (OR) of 0.50 (95% confidence interval [CI] 0.28-0.87; 3 cohorts), and a pooled unadjusted relative risk (RR) of 0.59 (95% CI 0.42-0.83; 9 cohorts); for high compared to low hospital volume with a pooled adjusted OR of 0.62 (95% CI 0.42-0.90; 5 cohorts), and a pooled unadjusted RR of 0.68 (95% CI 0.51-0.92; 9 cohorts). A decreased risk of death or stroke after CAS was found for high compared to low operator volume with an adjusted OR of 0.43 (95% CI 0.20-0.95; 1 cohort), and an unadjusted RR of 0.50 (95% CI 0.32-0.79; 1 cohort); for high compared to low hospital volume with an adjusted OR of 0.46 (95% CI 0.26-0.80; 1 cohort), and no significant decreased risk in a pooled unadjusted RR of 0.72 (95% CI 0.49-1.06; 2 cohorts). CONCLUSIONS: We found a decreased risk of procedural death and stroke after CEA and CAS for high operator and high hospital volume, indicating that aiming for a high volume may help to reduce procedural complications. REGISTRATION: This systematic review has been registered in the international prospective registry of systematic reviews (PROSPERO): CRD42017051491.

Primary Epstein-Barr virus infection in immunocompetent patients with acute transverse myelitis and a combination of polyradiculitis and anterior horn syndrome as neurological manifestations.

Neurological manifestations of a primary Epstein-Barr virus (EBV) infection are rare. We describe a case with acute transverse myelitis and another case with a combination of polyradiculitis and anterior horn syndrome as manifestations of a primary EBV infection.The first case is a 50-year-old immunocompetent male diagnosed with acute transverse myelitis, 2 weeks after he was clinically diagnosed with infectious mononucleosis. The second case is an 18-year-old immunocompetent male diagnosed with a combination of polyradiculitis and anterior horn syndrome while he had infectious mononucleosis. The first patient was treated with methylprednisolone. After 1 year, he was able to stop performing clean intermittent self-catheterisation. The second patient completely recovered within 6 weeks without treatment.Primary EBV infection should be considered in immunocompetent patients presenting with acute transverse myelitis and a combination of polyradiculitis and anterior horn syndrome. Antiviral treatment and steroids are controversial, and the prognosis of neurological sequelae is largely unknown.

Plasma fibrinogen level as a potential predictor of hemorrhagic complications after catheter-directed thrombolysis for peripheral arterial occlusions.

BACKGROUND: The benefit of catheter-directed thrombolysis for peripheral arterial occlusions is limited by hemorrhagic complications. Plasma fibrinogen level (PFL) has been suggested as a predictor of these hemorrhagic complications, but the accurateness of prediction is unknown. We summarized the available evidence on the predictive value of PFL for hemorrhagic complications after catheter-directed thrombolysis for acute or subacute peripheral native artery or arterial bypass occlusions. METHODS: We systematically searched PubMed and Embase until January 2016 for peer-reviewed publications on adults undergoing thrombolysis for acute or subacute peripheral native artery or arterial bypass occlusions, assessing the predictive value of PFL for hemorrhagic complications. Two authors independently performed data extraction. Risk of bias was assessed with the Quality in Prognosis Studies (QUIPS) tool. RESULTS: In total, six studies (two randomized clinical trials and four cohort studies) reported on 613 patients undergoing 623 thrombolytic interventions for peripheral native artery or arterial bypass occlusions. No risk estimates for PFL and hemorrhagic complications were reported, two risk estimates were calculated, and nine associations between PFL and hemorrhagic complications were reported. For PFL <100 mg/dL compared with ≥100 mg/dL, the calculated relative risk was 0.33 (95% confidence interval, 0.05-2.25) for major bleeding and 1.39 (95% confidence interval, 1.06-1.81) for any bleeding. There were considerable differences in the time point of PFL measurement, the thrombolytic agents, the doses of the agents, and the definition of outcomes. PFL seems inaccurate in predicting hemorrhagic complications. Overall, the included studies were at high risk of bias. CONCLUSIONS: Based on the current literature, the predictive value of PFL for predicting hemorrhagic complications after catheter-directed thrombolysis for acute or subacute peripheral native artery and arterial bypass occlusions is unproven.

First-line non-cytotoxic therapy in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: a systematic review of 10 randomised clinical trials.

The aim of this study is to systematically evaluate all available treatment options in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC). We systematically searched PubMed, EMBASE, and the Cochrane libraries up to 1 March 2016 for peer-reviewed publications on randomised clinical trials (RCTs). RCTs were included if progression-free survival (PFS), overall survival (OS), quality of life (QoL), or adverse events (AEs) were quantitatively evaluated. We assessed the risk of bias with the Cochrane Collaboration's tool and graded the evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group's approach. We included 25 articles, reporting on 10 unique RCTs describing seven different comparisons. In one RCT, a prolonged OS and PFS (high quality) were found with abiraterone and prednisone compared to placebo plus prednisone. In one RCT, a prolonged OS and PFS (high quality) were found with enzalutamide compared to placebo. In two RCTs, a prolonged OS (high and moderate quality) was found with 223 radium compared to placebo, but its effect on PFS is unknown. In three RCTs, a prolonged OS (moderate quality) was found with sipuleucel-T compared to placebo, but no prolonged PFS (low quality). In one RCT a prolonged PFS (high quality) was found with orteronel compared to placebo, but no prolonged OS (moderate quality). In one RCT, a prolonged OS (moderate quality) was found with bicalutamide compared to placebo, but its effect on PFS is unknown. In one RCT, a prolonged PFS (high quality) was found with enzalutamide compared to bicalutamide, but its effect on OS is unknown. The best evidence was found for abiraterone and enzalutamide for effective prolongation of OS and PFS to treat chemotherapy-naive patients with mCRPC. However, taking both QoL and AEs into consideration, other treatment modalities could be considered for individual patients.

Second-line therapy in patients with metastatic castration-resistant prostate cancer with progression after or under docetaxel: A systematic review of nine randomized controlled trials.

Treatment decisions are challenging in patients with metastatic castration-resistant prostate cancer with progression after or under docetaxel. The current review systematically searched the published literature on all treatment options, and assessed the risk of bias and quality of evidence. It found the best available evidence for effective prolongation of overall survival and progression-free survival for abiraterone acetate plus prednisone versus placebo plus prednisone and enzalutamide versus placebo. Other treatment modalities could be beneficial for individual patients by taking into consideration the: selection criteria of the randomized clinical trials, risk of bias, subgroup analyses, and quality of life and adverse events. Further research is needed to determine the sequence, timing asnd combination of different treatments.

Treatment of cerebral cavernous malformations: a systematic review and meta-regression analysis.

OBJECTIVE: The reported effects of treating cerebral cavernous malformations (CCMs) by neurosurgical excision or stereotactic radiosurgery are imprecise and vary between studies. METHODS: We searched Ovid Medline, EMBASE and The Cochrane Library for peer-reviewed publications of cohort studies describing outcomes of treating 20 or more patients with CCM with at least 80% completeness of follow-up. Two reviewers extracted data to quantify the incidence of a composite outcome (death, non-fatal intracranial haemorrhage, or new/worse persistent focal neurological deficit) after CCM treatment. We explored associations between summary measures of study characteristics and outcome using Poisson meta-regression analyses. RESULTS: We included 63 cohorts, involving 3424 patients. The incidence of the composite outcome was 6.6 (95% CI 5.7 to 7.5) per 100 person-years after neurosurgical excision (median follow-up 3.3 years) and 5.4 (95% CI 4.5 to 6.4) after stereotactic radiosurgery (median follow-up 4.1 years). After neurosurgical excision the incidence of the composite outcome increased with every per cent point increase in patients with brainstem CCM (rate ratio (RR) 1.03, 95% CI 1.01 to 1.05), and decreased with each more recent study midyear (RR 0.91, 95% CI 0.85 to 0.98) and each per cent point increase in patients presenting with haemorrhage (RR 0.98, 95% CI 0.96 to 1.00). We did not find significant associations in studies of stereotactic radiosurgery. CONCLUSIONS: The reported risks of CCM treatment (and the lower risks of neurosurgical excision over time, from recently bled CCMs, and for CCMs outside the brainstem) compare favourably with the risks of recurrent haemorrhage from CCM. Long-term effects, especially important for stereotactic radiosurgery, are unknown.