Risk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19: A Multicenter Cohort Study.

BACKGROUND AND PURPOSE: The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19. METHODS: We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke. RESULTS: We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; P=0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52-2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13-2.15]) than patients without stroke. CONCLUSIONS: In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was ≈2%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.

Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials.

BACKGROUND: Long-term follow-up of randomised trials of aspirin in prevention of vascular events showed that daily aspirin reduced the incidence of colorectal cancer and several other cancers and reduced metastasis. However, statistical power was inadequate to establish effects on less common cancers and on cancers in women. Observational studies could provide this information if results can be shown to be reliable. We therefore compared effects of aspirin on risk and outcome of cancer in observational studies versus randomised trials. METHODS: For this systematic review, we searched for case-control and cohort studies published from 1950 to 2011 that reported associations between aspirin use and risk or outcome of cancer. Associations were pooled across studies by meta-analysis and stratified by duration, dose, and frequency of aspirin use and by stage of cancer. We compared associations from observational studies with the effect of aspirin on 20-year risk of cancer death and on metastasis in the recent reports of randomised trials. FINDINGS: In case-control studies, regular use of aspirin was associated with reduced risk of colorectal cancer (pooled odds ratio [OR] 0·62, 95% CI 0·58-0·67, p(sig)<0·0001, 17 studies), with little heterogeneity (p(het)=0·13) in effect between studies, and good agreement with the effect of daily aspirin use on 20-year risk of death due to colorectal cancer from the randomised trials (OR 0·58, 95% CI 0·44-0·78, p(sig)=0·0002, p(het)=0·45). Similarly consistent reductions were seen in risks of oesophageal, gastric, biliary, and breast cancer. Overall, estimates of effect of aspirin on individual cancers in case-control studies were highly correlated with those in randomised trials (r(2)=0·71, p=0·0006), with largest effects on risk of gastrointestinal cancers (case-control studies, OR 0·62, 95% CI 0·55-0·70, p<0·0001, 41 studies; randomised trials, OR 0·54, 95% CI 0·42-0·70, p<0·0001). Estimates of effects in cohort studies were similar when analyses were stratified by frequency and duration of aspirin use, were based on updated assessments of use during follow-up, and were appropriately adjusted for baseline characteristics. Although fewer observational studies stratified analyses by the stage of cancer at diagnosis, regular use of aspirin was associated with a reduced proportion of cancers with distant metastasis (OR 0·69, 95% CI 0·57-0·83, p(sig)<0·0001, p(het)=0·89, five studies), but not with any reduction in regional spread (OR 0·98, 95% CI 0·88-1·09, p(sig)=0·71, p(het)=0·88, seven studies), consistent again with the findings in randomised trials. INTERPRETATION: Observational studies show that regular use of aspirin reduces the long-term risk of several cancers and the risk of distant metastasis. Results of methodologically rigorous studies are consistent with those obtained from randomised controlled trials, but sensitivity is particularly dependent on appropriately detailed recording and analysis of aspirin use. FUNDING: None.

Quality of life outcomes over time in patients with unruptured intracranial aneurysms with and without preventive occlusion: a prospective cohort study.

OBJECTIVE: In counselling patients with an unruptured intracranial aneurysm (UIA), quality-of-life (QoL) outcomes are important for informed decision-making. We evaluated QoL outcomes in patients with and without preventive aneurysm occlusion at multiple time points during the first year after UIA diagnosis and studied predictors of QoL outcomes. METHODS: We performed a prospective cohort study in patients ≥18 years old with a newly diagnosed UIA in two tertiary referral centers in the Netherlands between 2017 and 2019. Patients were sent QoL questionnaires at 7 (aneurysm occlusion) or 5 (no occlusion) moments during the first year after diagnosis. We collected baseline data on patient and aneurysm characteristics, passive coping style (Utrecht Coping List), occlusion modality, and neurological complications. We assessed health-related QoL (HRQoL) with the EuroQol 5-dimensions (EQ-5D), emotional functioning with the Hospital Anxiety and Depression Scale (HADS), and restrictions in daily activities with the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P). We used a linear mixed effects model to assess the course of QoL over time and to explore predictors of QoL outcomes. RESULTS: Of 153 eligible patients, 99 (65%) participated, of whom 30/99 (30%) underwent preventive occlusion. Patients undergoing occlusion reported higher baseline levels of passive coping, anxiety and depression, and restrictions than patients without occlusion. During recovery after occlusion, patients reported more restrictions compared to baseline (adjusted USER-P decrease one-month post-occlusion: -12.8 (95%CI:-23.8- -1.9). HRQoL and emotional functioning gradually improved after occlusion (EQ-5D increase at one-year: 8.6 (95%CI:0.1-17.0) and HADS decrease at one-year: -5.4 (95%CI:-9.4- -1.5)). In patients without occlusion, the largest HRQoL improvement occurred directly after visiting the outpatient aneurysm clinic (EQ-5D increase: 9.2 (95%CI:5.5-12.8)). At one-year, QoL outcomes were comparable in patients with and without occlusion. Factors associated with worse QoL outcomes were a passive coping style in all patients, complications in patients with occlusion and higher rupture risks in patients without occlusion. CONCLUSIONS: After UIA diagnosis, QoL improves gradually after preventive occlusion and directly after counselling at the outpatient clinic in patients without occlusion, resulting in comparable one-year QoL outcomes. A passive coping style is an important predictor of poor QoL outcomes in all UIA patients.

Development of the SAFETEA Scores for Predicting Risks of Complications of Preventive Endovascular or Microneurosurgical Intracranial Aneurysm Occlusion.

OBJECTIVE: Preventive unruptured intracranial aneurysm occlusion can reduce the risk of subarachnoid hemorrhage, but both endovascular and microneurosurgical treatment carry a risk of serious complications. To improve individualized management decisions, we developed risk scores for complications of endovascular and microneurosurgical treatment based on easily retrievable patient, aneurysm, and treatment characteristics. METHODS: For this multicenter cohort study, we combined individual patient data from unruptured intracranial aneurysm patients ≥18 years undergoing preventive endovascular treatment (standard, balloon-assisted or stent-assisted coiling, Woven EndoBridge-device, or flow-diverting stent) or microneurosurgical clipping at one of 10 participating centers from three continents between 2000-2018. The primary outcome was death from any cause or clinical deterioration from neurological complications ≤30 days. We selected predictors based on previous knowledge about relevant risk factors and predictor performance and studied the association between predictors and complications with logistic regression. We assessed model performance with calibration plots and concordance (c) statistics. RESULTS: Of 1282 included patients, 94 (7.3%) had neurological symptoms that resolved <30 days, 140 (10.9%) had persisting neurological symptoms, and 6 died (0.5%)). At 30 days, 52 patients (4.1%) were dead or dependent. Predictors of procedural complications were: size of aneurysm, aneurysm location, familial subarachnoid hemorrhage, earlier atherosclerotic disease, treatment volume, endovascular modality (for endovascular treatment) or extra aneurysm configuration factors (for microneurosurgical treatment; branching artery from aneurysm neck or unfavorable dome-to-neck ratio), and age (acronym: SAFETEA). For endovascular treatment (n=752), the c-statistic was 0.72 (95%CI:0.67-0.77) and the absolute complication risk ranged from 3.2% (95%CI:1.6%-14.9%;≤1 point) to 33.1% (95%CI:25.4%-41.5%;≥6 points). For microneurosurgical treatment (n=530), the c-statistic was 0.72 (95%CI:0.67-0.77) and the complication risk ranged from 4.9% (95%CI:1.5%-14.9%;≤1 point) to 49.9% (95%CI:39.4%-60.6%;≥6 points). CONCLUSIONS: The SAFETEA risk scores for endovascular and microneurosurgical treatment are based on seven easily retrievable risk factors to predict the absolute risk of procedural complications in patients with unruptured intracranial aneurysms. The scores need external validation before the predicted risks can be properly used to support decision making in clinical practice.

Influence of the vectorcardiogram synthesis matrix on the power of the electrocardiogram-derived spatial QRS-T angle to predict arrhythmias in patients with ischemic heart disease and systolic left ventricular dysfunction.

BACKGROUND AND PURPOSE: Several studies have demonstrated that the spatial mean QRS-T angle (SA) predicts cardiac events and mortality. Spatial mean QRS-T angle is a vectorcardiographic variable. Because in clinical practice, 12-lead standard electrocardiograms (ECGs) are recorded rather than vectorcardiograms (VCGs) according to Frank, VCGs are commonly obtained by synthesizing them from 12-lead ECGs, by using a VCG synthesis matrix. Hence, the thus computed SA is an estimate of the real SA measured in the Frank VCG. Recent studies have shown that Kors VCG synthesis matrix yields better estimates of SA than the inverse Dower VCG synthesis matrix. Our current study aims to compare the predictive power of these SA variants for the occurrence of potentially lethal arrhythmias. METHODS: The study group consisted of patients with ischemic heart disease and left ventricular systolic dysfunction who received an implantable cardioverter-defibrillator (ICD) for primary prevention. During follow-up, the occurrence of appropriate device therapy (occurrence of ventricular arrhythmia) was noted. Alternative SAs were computed in VCGs synthesized from standard 12-lead ECGs by using either the inverse Dower matrix (SA-Dower) or the Kors matrix (SA-Kors). Comparison of the predictive power of SA-Dower and SA- Kors was performed by receiver operating characteristic analysis, by Kaplan-Meier analysis, and by univariate and multivariate Cox regression analysis, using every 10th percentile of SA as a cutoff value. RESULTS: The study group consisted of 412 patients (361 men; mean ± SD age 63 ± 11 years), in which 56 patients had appropriate ICD therapy during follow-up. Receiver operating characteristic analysis revealed that the area under the curve of SA-Kors was significantly larger than area under the curve of SA-Dower (0.646 vs 0.607, P = .043). The discriminative power of SA-Kors for the absence/presence of appropriate ICD therapy in patients during follow-up was generally superior to SA-Dower over a wide range of cutoff values in the Kaplan-Meier analysis and generally yielded stronger hazard ratios in the univariate and multivariate Cox regression analyses. CONCLUSION: If there is no specific reason to use the inverse Dower matrix, VCG synthesis from standard 12-lead ECGs should preferably be done by using the Kors matrix. It is likely to assume that already published studies in which the predictive value of SA-Dower was demonstrated would yield stronger results if the SA-Dower angles were substituted by SA-Kors angles.

Management decisions on unruptured intracranial aneurysms before and after implementation of the PHASES score.

BACKGROUND: In management decisions on saccular unruptured intracranial aneurysms (UIAs) the risk of rupture is an important factor. The PHASES score, introduced in 2014, provides absolute 5-year risks of rupture based on six easily retrievable patient and aneurysm characteristics. We assessed whether management decisions on UIAs changed after implementation of the PHASES score. PATIENT AND METHODS: We included all patients with UIAs who were referred to two Dutch tertiary referral centers for aneurysm care in the Netherlands (University Medical Center Utrecht (UMCU) and Leiden University Medical Center (LUMC)) between 2011 and 2017. Analyses were done on an aneurysm level. We calculated the overall proportion of UIAs with a decision to treat before and after PHASES implementation and studied the influence of age and center on post-implementation management changes. RESULTS: We included 623 patients with 803 UIAs. The proportion of UIAs with a decision to treat was 123/360 (34.2%) before and 117/443 (26.4%) after PHASES implementation (absolute risk difference: -7.8%; 95% CI: -14.1 to -1.4). The decision to treat was made at a higher median PHASES score after implementation (7 points (IQR 5;10) pre- versus 8 points (IQR 5;10) post-implementation; p = 0.14). The reduced proportion with a treatment decision after implementation was most pronounced in patients <50 years (-22.3%; 95% CI: -39.2 to -3.4) and was restricted to treatment decisions made at the UMCU (-10.6%; 95% CI: -18.5 to -2.5). DISCUSSION AND CONCLUSIONS: Management of UIAs changed following implementation of the PHASES score, but the impact of PHASES implementation on treatment decisions differed across age subgroups and centers.

The spatial QRS-T angle in the Frank vectorcardiogram: accuracy of estimates derived from the 12-lead electrocardiogram.

BACKGROUND AND PURPOSE: The spatial QRS-T angle (SA), a predictor of sudden cardiac death, is a vectorcardiographic variable. Gold standard vertorcardiograms (VCGs) are recorded by using the Frank electrode positions. However, with the commonly available 12-lead ECG, VCGs must be synthesized by matrix multiplication (inverse Dower matrix/Kors matrix). Alternatively, Rautaharju proposed a method to calculate SA directly from the 12-lead ECG. Neither spatial angles computed by using the inverse Dower matrix (SA-D) nor by using the Kors matrix (SA-K) or by using Rautaharju's method (SA-R) have been validated with regard to the spatial angles as directly measured in the Frank VCG (SA-F). Our present study aimed to perform this essential validation. METHODS: We analyzed SAs in 1220 simultaneously recorded 12-lead ECGs and VCGs, in all data, in SA-F-based tertiles, and after stratification according to pathology or sex. RESULTS: Linear regression of SA-K, SA-D, and SA-R on SA-F yielded offsets of 0.01 degree, 20.3 degrees, and 28.3 degrees and slopes of 0.96, 0.86, and 0.79, respectively. The bias of SA-K with respect to SA-F (mean +/- SD, -3.2 degrees +/- 13.9 degrees) was significantly (P < .001) smaller than the bias of both SA-D and SA-R with respect to SA-F (8.0 degrees +/- 18.6 degrees and 9.8 degrees +/- 24.6 degrees, respectively); tertile analysis showed a much more homogeneous behavior of the bias in SA-K than of both the bias in SA-D and in SA-R. In pathologic ECGs, there was no significant bias in SA-K; bias in men and women did not differ. CONCLUSION: SA-K resembled SA-F best. In general, when there is no specific reason either to synthesize VCGs with the inverse Dower matrix or to calculate the spatial QRS-T angle with Rautaharju's method, it seems prudent to use the Kors matrix.

Procedural Clinical Complications, Case-Fatality Risks, and Risk Factors in Endovascular and Neurosurgical Treatment of Unruptured Intracranial Aneurysms: A Systematic Review and Meta-analysis.

Importance: The risk of procedural clinical complications and the case-fatality rate (CFR) from preventive treatment of unruptured intracranial aneurysms varies between studies and may depend on treatment modality and risk factors. Objective: To assess current procedural clinical 30-day complications and the CFR from endovascular treatment (EVT) and neurosurgical treatment (NST) of unruptured intracranial aneurysms and risk factors of clinical complications. Data Sources: We searched PubMed, Excerpta Medica Database, and the Cochrane Database for studies published between January 1, 2011, and January 1, 2017. Study Selection: Studies reporting on clinical complications, the CFR, and risk factors, including 50 patients or more undergoing EVT or NST for saccular unruptured intracranial aneurysms after January 1, 2000, were eligible. Data Extraction and Synthesis: Per treatment modality, we analyzed clinical complication risk and the CFR with mixed-effects logistic regression models for dichotomous data. For studies reporting data on complication risk factors, we obtained risk ratios (RRs) or odds ratios (ORs) with 95% CIs and pooled risk estimates with weighted random-effects models. Main Outcomes and Measures: Clinical complications within 30 days and the CFR. Results: We included 114 studies (106 433 patients with 108 263 aneurysms). For EVT (74 studies), the pooled clinical complication risk was 4.96% (95% CI, 4.00%-6.12%), and the CFR was 0.30% (95% CI, 0.20%-0.40%). Factors associated with complications from EVT were female sex (pooled OR, 1.06 [95% CI, 1.01-1.11]), diabetes (OR, 1.81 [95% CI, 1.05-3.13]), hyperlipidemia (OR, 1.76 [95% CI, 1.3-2.37]), cardiac comorbidity (OR, 2.27 [95% CI, 1.53-3.37]), wide aneurysm neck (>4 mm or dome-to-neck ratio >1.5; OR, 1.71 [95% CI, 1.38-2.11]), posterior circulation aneurysm (OR, 1.42 [95% CI, 1.15-1.74]), stent-assisted coiling (OR, 1.82 [95% CI, 1.16-2.85]), and stenting (OR, 3.43 [95% CI, 1.45-8.09]). For NST (54 studies), the pooled complication risk was 8.34% (95% CI, 6.25%-11.10%) and the CFR was 0.10% (95% CI, 0.00%-0.20%). Factors associated with complications from NST were age (OR per year increase, 1.02 [95% CI, 1.01-1.02]), female sex (OR, 0.43 [95% CI, 0.32-0.85]), coagulopathy (OR, 2.14 [95% CI, 1.13-4.06]), use of anticoagulation (OR, 6.36 [95% CI, 2.55-15.85]), smoking (OR, 1.95 [95% CI, 1.36-2.79]), hypertension (OR, 1.45 [95% CI, 1.03-2.03]), diabetes (OR, 2.38 [95% CI, 1.54-3.67]), congestive heart failure (OR, 2.71 [95% CI, 1.57-4.69]), posterior aneurysm location (OR, 7.25 [95% CI, 3.70-14.20]), and aneurysm calcification (OR, 2.89 [95% CI, 1.35-6.18]). Conclusions and Relevance: This study identifies risk factors for procedural complications. Large data sets with individual patient data are needed to develop and validate prediction scores for absolute complication risks and CFRs from EVT and NST modalities.

Female- and Male-Specific Risk Factors for Stroke: A Systematic Review and Meta-analysis.

IMPORTANCE: The incidence of stroke is higher in men than in women. The influence of sex-specific risk factors on stroke incidence and mortality is largely unknown. OBJECTIVE: To conduct a systematic review and meta-analysis of female- and male-specific risk factors for stroke. DATA SOURCES: PubMed, EMBASE, and the bibliographies of articles were searched for studies published between January 1, 1985, and January 26, 2015, reporting on the association between female- and male-specific characteristics and stroke. STUDY SELECTION: Observational studies reporting associations between sex-specific risk factors and stroke were selected. DATA EXTRACTION AND SYNTHESIS: Two authors performed data extraction independently. Estimates were pooled with a generic variance-based, random-effects method. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. In addition, our study adhered to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. MAIN OUTCOMES AND MEASURES: Ischemic stroke, hemorrhagic stroke, any stroke, and stroke mortality. RESULTS: This systematic review and meta-analysis included 78 studies (70 longitudinal and 8 case-control) comprising 10 187 540 persons. In women, the pooled relative risks of ischemic stroke were 1.80 (95% CI, 1.49-2.18) after any hypertensive disorder in pregnancy (HDP) (gestational hypertension [GH], preeclampsia, or eclampsia) and 1.81 (95% CI, 1.44-2.27) after GH vs no HDP. The pooled relative risks of hemorrhagic stroke were 2.24 (95% CI, 1.19-4.21) in women with menopause at the age of at least 55 years vs 50 to 54 years and 5.08 (95% CI, 1.80-14.34) after GH vs no GH. The pooled relative risks of any stroke were 1.42 (95% CI, 1.34-1.50) after oophorectomy vs no oophorectomy, 0.88 (95% CI, 0.85-0.90) after hysterectomy vs no hysterectomy, 1.63 (95% CI, 1.52-1.75) after any vs no HDP, 1.54 (95% CI, 1.39-1.70) after preeclampsia or eclampsia, 1.51 (95% CI, 1.27-1.80) after GH vs no HDP, 1.62 (95% CI, 1.46-1.79) after preterm delivery, and 1.86 (95% CI, 1.15-3.02) after stillbirth vs no pregnancy complications. The pooled relative risk of stroke mortality was 1.57 (95% CI, 1.04-2.39) after GH vs no GH. In men, the pooled relative risks of ischemic stroke were 1.19 (95% CI, 1.05-1.34) after androgen deprivation therapy (ADT) vs no ADT and 1.21 (95% CI, 1.00-1.46) after orchiectomy vs no orchiectomy. The pooled relative risks of any stroke were 1.21 (95% CI, 1.06-1.37) for ADT vs no ADT and 1.35 (95% CI, 1.18-1.53) for erectile dysfunction vs no dysfunction. CONCLUSIONS AND RELEVANCE: Female-specific characteristics increasing stroke risk include HDP for ischemic stroke, late menopause and gestational hypertension for hemorrhagic stroke, and oophorectomy, HDP, preterm delivery, and stillbirth for any stroke. Hysterectomy is possibly protective against any stroke. Male-specific characteristics increasing stroke risk include medical androgen deprivation therapy for ischemic and any stroke and erectile dysfunction for any stroke. Consideration of sex-specific risk factors can improve individualized stroke risk assessment.

[The use of medical journals by medical students. Which medical journals are read?]. / Gebruik van medische bladen door geneeskundestudenten. Welke medisch-wetenschappelijke tijdschriften worden gelezen?

OBJECTIVE: To investigate the role of scientific medical journals in Dutch medical curricula. DESIGN: Descriptive questionnaire study. METHOD: In 2013, medical students (from year 3 onwards) at the Leiden University Medical Centre (LUMC), were invited to respond to an online questionnaire. They were presented with 28 multiple-choice questions and 11 statements about the use of scientific medical journals in the medical curriculum. We calculated the frequencies of the answers per question and analysed differences between medical students using two-by-two tables. RESULTS: The questionnaire was completed by 680 (53.0%) of 1277 invited medical students enrolled at the LUMC. Most of the respondents were those doing clinical rotations (56.6%) and 60.1% had research experience. More than half of the students read at least one scientific journal a few times per month; this percentage was 38.8% among third-year students, 49.3% among fourth-year students, 60.0% among those on clinical rotation, and was higher among students with research experience (63.3%) than among those without research experience (44.1%). Nearly 90% of students agreed with the statement that the development of academic and scientific education should take place in the bachelor's phase of medical school. CONCLUSION: Medical students start to read scientific medical journals at an early phase in the medical curriculum and this increases further when students start to undertake research projects or go on clinical rotation. Medical curricula should be constructed in such a way that medical students learn to select and interpret research findings adequately for themselves before they turn to articles from scientific medical journals.

[Aspirin and cancer: evidence of a prophylactic effect]. / Acetylsalicylzuur en kanker: aanwijzingen voor een preventief effect.

Due to increased life expectancy, the number of new patients diagnosed with cancer is also increasing; this requires effective and inexpensive strategies for preventing cancer. The concept of chemoprevention involves taking medication to reduce cancer risk. By re-assessing aspirin trials that were originally conducted to determine its effect on cardiovascular disease, it appeared that aspirin was associated with a reduction in the incidence of cancer as well as cancer-related mortality. The vascular benefits and risks associated with aspirin are only clinically relevant in the short term; its beneficial effects on cancer risk only become apparent after three years. Aspirin probably has a preventive effect on metastasis. These findings from randomised trials are consistent with results from methodologically rigorous observational studies. Until now, primary prevention in vascular disease has only proven to be cost-effective in certain risk groups. In future cost-effectiveness analyses, the beneficial effect of aspirin on cancer risk needs to be taken into account.

Female risk factors for subarachnoid hemorrhage: a systematic review.

OBJECTIVE: To systematically review the literature on female risk factors and risk of SAH. METHODS: We searched Medline and EMBASE for articles published between January 1985 and July 2011. For all studies fulfilling the predefined criteria, we obtained risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for female risk factors. We pooled crude and adjusted ORs (aORs) with a general variance-based random-effects method. We evaluated methodologic quality with the Newcastle-Ottawa Scale. RESULTS: We included 16 studies; 8 had good quality. Twelve studies had a case-control design, 3 studies had a longitudinal design, and 1 study had a case-crossover design. Overall aORs were 1.31 (95% CI 1.05-1.64; 5 studies, 2 with good quality [GQ]) for current use of combined oral contraceptives (COC), 0.90 (95% CI 0.74-1.09; 7 studies, 4 GQ) for ever COC use, 0.86 (95% CI 0.69-1.08; 6 studies, 3 GQ) for current use of hormone replacement therapy (HRT), 0.74 (95% CI 0.54-1.00; 3 studies, 1 GQ) for ever use of HRT, and 1.29 (95% CI 1.03-1.61; 5 studies, 2 GQ) for postmenopausal women. Data on parity and age at menarche were heterogeneous. Risk of subarachnoid hemorrhage (SAH) was not increased during pregnancy, labor, or puerperium (RR 0.40, 95% CI 0.20-0.90; 1 GQ study). CONCLUSIONS: Female hormone levels might influence risk of SAH, but the pathophysiology of this effect and its influence on the difference in incidence of SAH between the sexes remains unclear. Further studies are needed to identify modifiable risk factors of SAH in women older than age 50.

[Cultural interests of doctors, accountants and lawyers; art, culture and interface with the profession]. / Culturele interesse onder artsen, accountants en juristen: kunst, cultuur en de raakvlakken met het vak.

OBJECTIVE: To investigate the role of art and culture in the recreational activities of doctors, accountants and lawyers. DESIGN: Descriptive questionnaire study. METHOD: In this study, doctors, accountants and lawyers were asked to respond to an online questionnaire. They were presented with 13 questions or statements concerning their recreational activities and their active or passive involvement with art and culture. To gain an impression in which respect doctors, accountants and lawyers could be distinguished from each other, predictive models based on logistic regression with possible results 'doctor', 'accountant' or 'lawyer' were generated. On the basis of these models, a miniquiz was created, which could distinguish the typical doctor, accountant or lawyer after answering of dichotomous questions. RESULTS: Among all respondents, museum and cinema visits were popular, sports or gardening were favourite activities, and apart from newspapers, the Internet was frequently consulted for news. It was remarkable that doctors and lawyers resembled each other in most of the areas investigated, whereas the accountants differed significantly. Doctors and lawyers particularly visited museums and dance, opera or theatre performances, and two-thirds themselves played music. The majority of these 2 groups also had an above average interest in art and culture, this being a significant part of the recreational activity. Therefore, we were able to differentiate between a doctor or lawyer and an accountant, but the difference between doctors and lawyers was less clear. CONCLUSION: Doctors and lawyers seemed to have comparable interests in art and culture, but accountants differed in important respects.