Umberto Scoditti

Long-term outcomes of patients with cerebral vein thrombosis: a multicenter study

Summary.  Background:  Little information is available on the long‐term clinical outcome of cerebral vein thrombosis (CVT).

Venous Thromboembolic Events After Cerebral Vein Thrombosis

Background and Purpose— After cerebral vein and dural sinus thrombosis (CVT), there is an increased risk of further venous thromboembolic events (VTEs). Time to a second cerebral or systemic venous thrombotic event and risk factors for recurrence have not been investigated in large prospective studies. Methods— We used the International Study on Cerebral Vein and Dural sinus Thrombosis, which included 624 patients with CVT followed up for a median of 13.9 months. Outcome measures included all symptomatic VTEs and CVT recurrence. Potential predictors of recurrence, including demographic characteristics, imaging features, thrombophilic abnormalities, other risk factors for CVT, and anticoagulation, were analyzed by Cox survival analysis. Results— Of the 624 included patients, 36 (5.8%) had at least 1 venous thromboembolic event. The rate of VTEs after the initial CVT was 4.1 per 100 person-years. Of all VTEs, 63.2% (n=24) occurred within the first year. Fourteen patients (2.2%) had an episode of recurrent CVT and the rate of recurrence was 1.5 per 100 person-years. Nine (64.3%) of these CVT recurrences occurred within the first year. Male gender (hazard ratios=2.6; 95% CI, 1.4 to 5.1; P=0.004) and polycythemia/thrombocythemia (hazard ratios=4.4; 95% CI, 1.6 to 12.7; P=0.005) were the only factors associated with a significant higher risk of VTEs in multivariate survival analysis. Conclusions— The risk of recurrence of CVT is low but is moderate for other VTEs. Recurrence of venous thrombosis after CVT is more frequent among men and in patients with polycythemia/thrombocythemia.

The poor outcome of ischemic stroke in very old people: a cohort study of its determinants.

OBJECTIVES: To assess how much of the excess risk of poor outcome from stroke in people aged 80 and older aging per se explains, independent of other prognostic determinants.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Effect of Anticoagulation and Its Timing: The RAF Study

Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

The THRombolysis and STatins (THRaST) study

Objective: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis. Methods: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale [mRS] ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death. Results: Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.26–2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11–1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18–2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19–0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28–0.82; p = 0.007). Conclusion: Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome.

How to promote, improve and test adherence to scientific evidence in clinical practice

BackgroundNegative variation in the management of patients with the same clinical condition is frequent, and affects quality of care. Recent studies indicate that single interventions are not an effective solution. We aim to demonstrate that a multifaceted strategy can favor the introduction of research into practice, and to assess its long-term effects on a set of common medical conditions exhibiting significant negative variation at our institution.MethodsThe strategy, devised and agreed upon by a multidisciplinary group, was first applied to one relevant medical condition – cerebral ischemic stroke. To test its effectiveness a quasi-experimental study was conducted, comparing an intervention group with historical controls. After validation the strategy was extended to other pathologies, and its long-term effect measured using evidence-based quality indicators. Adherence to each indicator was determined prospectively on a six-month basis for a period of at least two consecutive years. Measures are expressed as proportions with 95% confidence intervals.ResultsValidation findings demonstrated that the strategy improved compliance with scientific evidence: the percentage of patients who received a CT scan within 24 hours of hospital presentation rose from 56% to 75%, (χ2 = 7.43 p < 0.01); admissions to selected wards increased from 45% to 64%, (χ2 = 7.81 p < 0.01); the number of physical medicine visits within 24 hours of the request grew from 59% to 91% (χ2 = 14,40 p < 0.001). Over a four-year period the program was gradually applied to 14 medical conditions. Except for 3 cases, compliance with the pathway, i.e. number of eligible patients for whom data on the care process is collected, was above the minimum requirement of 75%. Indicator adherence generally exhibited a positive trend, though variability was observed both among different conditions and between different semesters for the same pathology.ConclusionAccording to our experience, incorporation of research into practice can be favored by systematically applying a shared, multifaceted strategy, involving multidisciplinary teams supported by central coordination. Institutions should device a tailor-made approach, should train personnel on implementation strategies, and create cultural acceptance of change. Just like for experimental trials, human and economic resources should be allocated within health care services to allow the achievement of this objective.

Cerebral venous thrombosis and myeloproliferative neoplasms: results from two large databases.

INTRODUCTION Myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Patients with MPNs are prone to develop arterial and venous thrombosis either at diagnosis or during follow-up; in particular splancnic vein is strongly associated with MPN. Conversely, presence of MPN is uncommon in patients with deep vein thrombosis of the lower extremities and with pulmonary embolism. Only few studies with conflicting results have evaluated the prevalence of an underlying MPN in patients with cerebral venous thrombosis (CVT), and limited evidence exists on the incidence of CVT in patients with established MPN. METHODS We assessed the frequency of MPNs in a series of 706 patients with cerebral vein thrombosis (CVT) and the frequency of CVT in a cohort of 2,143 MPNs patients. RESULTS Twenty-seven CVT patients (3.8%) were diagnosed with MPN: 9 before CVT (1.3%), 4 concomitantly (0.6%), and 14 after CVT (2.0%). Nine CVT cases (0.4%) were diagnosed in the MPN cohort, with a slightly higher frequency in PV (five of 735, 0.7%) than in ET (three of 964, 0.3%) and in PMF (one of 444, 0.2%). CONCLUSION Considering the analyses of these databases jointly, the results obtained suggest a weak association between CVT and MPNs and ultimately suggest that a thorough investigation looking for an underlying MPN may not be warranted in all the patients with CVT without overt myeloproliferative features.

Impact of gender-age interaction on the outcome of ischemic stroke in an Italian cohort of patients treated according to a standardized clinical pathway.

BACKGROUND Stroke outcome has been reported as worse in women, especially in terms of disability. As for mortality, the data are conflicting, with some reports suggesting a female advantage. Our objective was to explore such issues in an Italian cohort of patients managed by a standardized clinical pathway (CPW) and, as such, homogeneous in terms of clinical management. METHODS Data from a cohort of 1993 patients (987 women and 1006 men) with first-ever ischemic stroke, consecutively referred to an in-hospital Clinical Pathway Program from January 1, 2001 to December 31, 2009, were retrospectively analyzed. The relationship between female gender and one-month outcome was assessed with adjustment for age, stroke severity and premorbid disability. RESULTS The outcome was worse in women in terms of disability (age-adjusted odds ratio 2.03, 95% CI 1.69-2.46), while no difference was found for mortality. In multivariate models, female gender turned out to be associated with a lower case-fatality rate (adjusted hazard ratio 0.65, 95% CI 0.48-0.89, P=0.007), whereas the odds ratio for disability decreased but remained significant (OR 1.30; 95% CI 1.01-1.69). We found a significant interaction between gender and age in the case-fatality rate, and a female survival advantage was apparent only below 50 years. CONCLUSIONS Our study confirms the excess risk of disability after stroke in women, although it is mostly explained by the occurrence of the most severe clinical syndromes. As for mortality, female gender seems to play a protective role, at least in the short-term and in younger patients.

Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants (RAF-NOACs) Study

Background The optimal timing to administer non–vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. Methods and Results Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA 2 DS 2‐VASc score >4 and less reduced renal function. Thirty‐two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated >14 days after acute stroke. Conclusions In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.

Validity of the modified Charlson Comorbidity Index as predictor of short-term outcome in older stroke patients.

The modified Charlson Comorbidity Index (MCCI) has been proposed as a tool for adjusting the outcomes of stroke for comorbidity, but its validity in such a context has been evaluated in only a few studies and needs to be further explored, especially in elderly patients. We aimed to retrospectively assess the validity of the MCCI as a predictor of the short-term outcomes in a cohort of 297 patients with first-ever ischemic stroke, older than 60 years, and managed according to a clinical pathway. The poor outcome (PO) at 1 month, defined as a modified Rankin Scale score of 3-6, was the primary end point. Furthermore, a new comorbidity index has been developed, specific to our cohort, according to the same statistical approach used for the original CCI. The MCCI showed a positive association with PO (odds ratio [OR] 1.62; 95% confidence interval [CI] .98-2.68) and mortality (hazard ratio [HR] 1.85; 95% CI .94-3.61), not statistically significant and totally dependent on its association with the severity of neurologic impairment at onset. The new comorbidity index showed, as expected, a significant association with the PO and mortality with higher point estimates of OR (2.74; 95% CI 1.64-4.59) and HR (2.73; 95% CI 1.51-4.94), but this association was also dependent on stroke severity and premorbid disability. Our results do not support the validity of the MCCI as a predictor of the short-term outcomes in elderly stroke patients nor could we develop a more valid index from the available data. This suggests the need for development of disease- and age-specific indexes, possibly according to a prospective design. In any case, initial stroke severity, a strong predictor of outcome, is associated with the degree of comorbidity.