Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage.

BACKGROUND: Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. METHODS: We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. RESULTS: A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P = 0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P = 0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. CONCLUSIONS: Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).

Neuro-COVID frequency and short-term outcome in the Northern Portuguese population.

BACKGROUND AND PURPOSE: COVID-19-related acute neurological phenotypes are being increasingly recognised, with neurological complications reported in more than 30% of hospitalised patients. However, multicentric studies providing a population-based perspective are lacking. METHODS: We conducted a retrospective multicentric study at five hospitals in Northern Portugal, representing 45.1% of all hospitalised patients in this region, between 1 March and 30 June 2020. RESULTS: Among 1261 hospitalised COVID-19 patients, 457 (36.2%) presented neurological manifestations, corresponding to a rate of 357 per 1000 in the North Region. Patients with neurologic manifestations were younger (68.0 vs. 71.2 years, p = 0.002), and the most frequent neurological symptoms were headache (13.4%), delirium (10.1%), and impairment of consciousness (9.7%). Acute well-defined central nervous system (CNS) involvement was found in 19.1% of patients, corresponding to a rate of 217 per 1000 hospitalised patients in the whole region. Assuming that all patients with severe neurological events were hospitalised, we extrapolated our results to all COVID-19 patients in the region, estimating that 116 will have a severe neurological event, corresponding to a rate of nine per 1000 (95% CI = 7-11). Overall case fatality in patients presenting neurological manifestations was 19.8%, increasing to 32.6% among those with acute well-defined CNS involvement. CONCLUSIONS: We characterised the population of hospitalised COVID-19 patients in Northern Portugal and found that neurological symptoms are common and associated with a high degree of disability at discharge. CNS involvement with criteria for in-hospital admission was observed in a significant proportion of patients. This knowledge provides the tools for adequate health planning and for improving COVID-19 multidisciplinary patient care.

Web-based cognitive training: patient adherence and intensity of treatment in an outpatient memory clinic.

BACKGROUND: Cognitive training has been playing an increasing role in the treatment of patients with cognitive deficits. This type of intervention, namely its intensity, can be optimized by incorporating information technology-based systems. OBJECTIVE: The intent of the study was to determine the treatment intensity and patient adherence to home-based cognitive training strategies (Web-based cognitive training). METHODS: A cohort of 45 patients with neurologic and psychiatric diseases attending an outpatient memory clinic (average age 50.7 years, SD 17.0; average education 7.8 years, SD 4.9) was followed over 18 months. Participants were challenged to use a Web-based cognitive training system, "COGWEB", on a daily basis, and fulfilled at least four weeks of training supervised remotely. Additionally, 11 patients attended face-to-face sessions. RESULTS: The average duration of continuous cognitive training was 18.8 weeks (SD 18.9). Each patient performed on average 363.5 minutes/week (SD 136.6). At 6-month follow-up, 82.8% complied with their treatment plan. The average proportion of complete weeks was 0.75 (SD 0.22). Patients with dementia trained more intensively (444.6 minutes/week), followed by patients with static brain lesion (414.5 minutes/week; P=.01). The group that held face-to-face sessions performed more training overall (481.4 vs 366.9 minutes/week), achieving a stronger expression and statistical significance in the last week of training (652.6 versus 354.9 minutes/week, P=.027). CONCLUSIONS: Overall, the weekly training intensity was high. Patients with dementia and static lesions performed more cognitive training. Face-to-face sessions were associated with higher intensities. The combination of classical methods with information technology systems seems to ensure greater training intensity.

Validation of a web-based self-administered test for cognitive assessment in a Swedish geriatric setting.

Computerized cognitive tests have the potential to cost-effectively detect and monitor cognitive impairments and thereby facilitate treatment for these conditions. However, relatively few of these tests have been validated in a variety of populations. Brain on Track, a self-administered web-based test, has previously been shown to have a good ability to differentiate between healthy individuals and patients with cognitive impairment in Portuguese populations. The objective of this study was to validate the differential ability and evaluate the usability of Brain on Track in a Swedish memory clinic setting. Brain on Track was administered to 30 patients with mild cognitive impairment/mild dementia and 30 healthy controls, all scheduled to perform the test from home after one week and after three months. To evaluate the usability, the patient group was interviewed after completion of the testing phase. Patients scored lower than healthy controls at both the first (median score 42.4 vs 54.1, p<0.001) and the second test (median score 42.3 vs 55.0, p<0.001). The test-retest intra-class correlation was 0.87. A multiple logistic regression model accounting for effects of age, gender and education rendered an ability of Brain on Track to differentiate between the groups with an area under the receiver operation characteristics curve of 0.90 for the first and 0.88 for the second test. In the subjective evaluation, nine patients left positive comments, nine were negative whereas five left mixed comments regarding the test experience. Sixty percent of patients had received help from relatives to log on to the platform. In conclusion, Brain on Track performed well in differentiating healthy controls from patients with cognitive impairment and showed a high test-retest reliability, on par with results from previous studies. However, the substantial proportion of patients needing help to log in could to some extent limit an independent use of the platform.

Association between sociodemographic and clinical features, health behaviors, and health literacy of patients with prostate cancer and prostate cancer prognostic stage.

Patient characteristics may influence access and acceptance of Prostate Specific Antigen test, and therefore, the timing of prostate cancer (PCa) diagnosis. A group of 361 patients from a cohort (n = 451) diagnosed with PCa in 2018-2020 at the Portuguese Institute of Oncology of Porto was evaluated before treatment, using a structured interview, the Medical Term Recognition Test, and the EORTC Quality of Life Questionnaire QLQ-PR25. PCa prognostic stages (I, II, III, IV) were attributed according to the American Joint Committee on Cancer eighth edition. Multinomial logistic regression was used to compute the odds ratio and 95% confidence interval (OR [95% CI]), considering PCa stage II, the most frequent, as reference. Older age (OR = 4.21 [2.24-7.93]), living outside the Porto Metropolitan Area while having low income (OR = 6.25 [1.53-25.62]), and erectile dysfunction (OR = 2.22 [0.99-4.99]) were associated with stage III, while urination during the night (OR = 3.02 [1.42-6.41]) was associated with stage IV. Urine leakage was less frequent in stage III (OR = 0.23 [0.08-0.68]), and living with a partner (OR = 0.41 [0.19-0.88]) and family history of cancer (OR = 0.25 [0.07-0.86]) in stage IV. Health literacy was not associated with PCa stage but lower education was less frequent in stage I (OR = 0.27 [0.11-0.69]). Patient sociodemographic and clinical characteristics should be considered as targets to improve PCa early detection and prognosis.

Long-term neurological complications in COVID-19 survivors: study protocol of a prospective cohort study (NeurodegCoV-19).

BACKGROUND: Evidence suggests an association between SARS-CoV-2 infection and worse performance on cognitive tests, and a higher risk of Parkinson's disease (PD) and dementia up to 6 and 12 months after infection, respectively. Longer follow-ups with comparison groups are needed to clarify the potentially increased risk of neurodegenerative diseases in COVID-19 survivors, namely those infected before mass vaccination. METHODS: A prospective study started in July 2022 with four cohorts of 150 individuals each, defined according to SARS-CoV-2 infection and hospitalisation status between March 2020 and February 2021: cohort 1-hospitalised due to SARS-CoV-2 infection; cohort 2-hospitalised, COVID-19-free; cohort 3-infected, not hospitalised; cohort 4-not infected, not hospitalised. Cohort 2 will be matched to cohort 1 according to age, sex, level of hospitalisation care and length of stay; cohort 4 will be age-matched and sex-matched to cohort 3. Baseline, 1-year and 2-year follow-up evaluations will include: cognitive performance assessed with the Montreal Cognitive Assessment (MoCA) and neuropsychological tests; the assessment of prodromal markers of PD with Rapid Eye Movement Sleep Behaviour Disorder single-question Screen and self-reported olfactory and gustative alterations; screening of PD with the 9-item PD screening questionnaire; gait evaluation with Timed Up&Go test. Suspected cases of cognitive impairment and PD will undergo a clinical evaluation by a neurologist. Frequency measures of neurological complications, prodromal markers and diagnoses of dementia and PD, will be presented. The occurrence of cognitive decline-the difference between baseline and 1-year MoCA scores 1.5 SD below the mean of the distribution of the variation-will be compared between cohorts 1 and 2, and cohorts 3 and 4 with OR estimated using multivariate logistic regression. ETHICS AND DISSEMINATION: This study received ethics approval from the Ethics Committees of the health units Unidade Local de Saúde de Matosinhos and Centro Hospitalar de Entre Douro e Vouga, and informed consent is signed for participating. Results will be disseminated among the scientific community and the public.

From healthcare system to individuals through stroke rehabilitation pathways.Outcomes, information, and satisfaction along 12 months prospective cohort in Portugal.

BACKGROUND: The nature and quality of stroke survivor rehabilitation varies throughout Europe, including in Portugal, having not been widely monitored or benchmarked. OBJECTIVES: This study analyses the stroke care pathway from three perspectives: healthcare system, process, and patient. METHODS: The study uses data from a one-year single-center prospective cohort of first stroke patients, assessed at baseline, 3, 6, and 12 months. Care pathways and settings were described in terms of organizational model, funding, patient involvement, frequency and intensity and multidisciplinary team. Patient-level information and satisfaction were evaluated using a 10-point numeric rating scale. Kruskal - Wallis and post-hoc tests were used to compare EQ-5D-3 L, National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), Barthel Index, Mini-Mental State Examination scores between pathways and settings. RESULTS: A total of 391 acute stroke patients, with a mean disability of 3.7 (mRS) and severity of 11.7 (NIHSS) participated. Six pathways and eight settings were described. A lack of compliance between guidelines and care was identified. There were significant differences in the four outcomes between the six pathways (p-values 0.007 to 0.020) suggesting inefficiency and inequalities, with an inadequate level of information and patient satisfaction. After post-hoc analysis, pathways 1 and 2 showed highest outcomes (p-values 0.001 to 0.002). Within settings, short-term units showed high scores, followed by rehabilitation center, outpatient hospital, and community clinic (p-values 0.001 to 0.040). CONCLUSION: A multilevel characterization of the post-stroke rehabilitation pathway showed a more complete perspective on stroke management which may contribute to future rehabilitation and stroke policies.

Polypill use for the prevention of cardiovascular disease: A position paper.

Cardiovascular (CV) guidelines stress the need for global intervention to manage risk factors and reduce the risk of major vascular events. Growing evidence supports the use of polypill as a strategy to prevent cerebral and cardiovascular disease, however it is still underused in clinical practice. This paper presents an expert consensus aimed to summarize the data regarding polypill use. The authors consider the benefits of polypill and the significant claims for clinical applicability. Potential advantages and disadvantages, data regarding several populations in primary and secondary prevention, and pharmacoeconomic data are also addressed.

Freeze the stroke: public awareness program for immediate detection of first symptoms.

BACKGROUND AND PURPOSE: The capacity of the general population to identify stroke signs is a major determinant for success of prehospital emergency pathways. Previous educational strategies using the media were usually short-lived and expensive. Tailoring information programs for special subgroups like acute stroke relatives may improve this situation. METHODS: A poster was assembled that included a list of stroke signs and instructions to call 911. Consecutive admissions to the stroke unit were randomized. Intervention consisted of an educational session with relatives, in which a nurse delivered 5 posters and asked for their placement on the freezer door at the kitchen of the patient's house and each of 4 neighboring houses. One month later, a questionnaire was administered to both groups. RESULTS: Sixty admissions were randomized (30 interventions), and 150 posters were distributed. One month after discharge, response rates were 81% for intervention group and 48% for control group. In the intervention arm, 64.5% had all the 4 answers correct, and 74.2% identified all first signs of stroke. For the control group, these values were 8% and 20%, respectively (P<0.001). CONCLUSIONS: This stroke unit-based information strategy improved awareness of relatives and neighbors when compared with the usual discharge plan. The program avoids the media and explores regional health care structure and family and social organizations, and it targets a subgroup keen to receive and spread information. The low cost, ease of use, and duration of the stimulus facilitate further testing and evaluation of impact on hospital presentation and thrombolytic treatment rates.

Anxiety and Depression in Patients with Prostate Cancer, at Cancer Diagnosis and after a One-Year Follow-Up.

Prostate cancer (PCa) is the most prevalent among men, and psychological symptoms may affect many patients. This study aims to describe the prevalence of probable anxiety and depression before PCa treatments and after one year and to identify sociodemographic and clinical factors associated with these outcomes. Between February 2018 and March 2020, 292 patients recently diagnosed with PCa were recruited at the Instituto Português de Oncologia-Porto. The Hospital Anxiety and Depression Scale (HADS) was used to define probable anxiety and depression (cutoff = 11). The prevalence of probable anxiety remained stable from baseline to one year (7.8% vs. 8.5%, p = 0.866) while there was an increase in probable depression (3.1% vs. 6.8%, p = 0.012). After one year, probable depression persisted in 55.6% of patients with probable depression at baseline and 47.8% of those with probable anxiety at the first assessment had normal anxiety scores. At baseline, anxiety was more frequent among dwellers in rural areas (adjusted odds ratio-aOR, 95%CI: 2.80, 0.91-8.58) and less frequent in patients with body mass index 25-29.9 kg/m2 (aOR, 95%CI: 0.33, 0.12-0.91) compared to 18.5-24.9 Kg/m2, while those living alone had higher odds of depression (aOR, 95%CI: 6.35, 1.43-28.30). The frequency of anxiety and depression fluctuated during the course of treatment. Monitoring these symptoms would identify the most affected patients, contributing for a better use of mental health services.

Prevalence of Cognitive Impairment before Prostate Cancer Treatment.

Cognitive impairment is common among patients with different types of cancer, even before cancer treatment, but no data were reported among patients with prostate cancer (PCa), who may be at high risk due to advanced age. This study aims to estimate the prevalence of cognitive impairment before PCa treatment. Between February 2018 and April 2021, the NEON-PC cohort recruited 605 patients with PCa proposed for treatment at the Portuguese Institute of Oncology of Porto. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance. Participants with a MoCA < 1.5 standard deviations (SD) of age- and education-specific normative values were considered to have probable cognitive impairment (PCI) and were referred for a comprehensive neuropsychological assessment. Data from the population-based cohort EPIPorto (n = 351 men aged ≥40 years, evaluated in 2013−2015) were used for comparison. The prevalence of PCI was 17.4% in EPIPorto and 14.7% in NEON-PC (age- and education-adjusted odds ratio: 0.82, 95%CI: 0.58,1.18). Neuropsychological assessment was performed in 63 patients with PCa: 54.0% had cognitive impairment. These results suggest that the impact of PCa on cognitive performance could be negligible in the short term, contrary to what other studies have reported regarding other types of cancer.

Development of a self-administered web-based test for longitudinal cognitive assessment.

Sequential testing with brief cognitive tools has been recommended to improve cognitive screening and monitoring, however the few available tools still depend on an external evaluator and periodic visits. We developed a self-administered computerized test intended for longitudinal cognitive testing (Brain on Track). The test can be performed from a home computer and is composed of several subtests, expected to evaluate different cognitive domains, all including random elements to minimize learning effects. An initial (A) and a refined version of the test (B) were applied to patients with mild cognitive impairment or early dementia (n = 88) and age and education-matched controls. A subsample of a population-based cohort (n = 113) performed the test at home every three months to evaluate test-retest reliability. The test's final version Cronbach's alpha was 0.90, test scores were significantly different between patients and controls (p = 0.001), the area under the receiver operating characteristic curve was 0.75 and the smallest real difference (43.04) was lower than the clinical relevant difference (56.82). In the test-retest reliability analysis 9/10 subtests showed two-way mixed single intraclass consistency correlation coefficient >0.70. These results imply good internal consistency, discriminative ability and reliability when performed at home, encouraging further longitudinal clinical and population-based studies.

A novel system for automatic classification of upper limb motor function after stroke: an exploratory study.

In the early post-stroke phase, when clinicians attempt to evaluate interventions and accurately measure motor performance, reliable tools are needed. Therefore, the development of a system capable of independent, repeated and automatic assessment of motor function is of increased importance. This manuscript explores the potential of a newly designed device for automatic assessment of motor impairment after stroke. A portable motion capture system was developed to acquire three-dimensional kinematics data of upper limb movements. These were then computed through an automatic decision tree classifier, with features inferred from the Functional Ability Score (FAS) of the Wolf Motor Function Test (WMFT). Five stroke patients were tested on both sides across five selected tasks. The system was compared against a trained clinician, operating simultaneously and blinded. Regarding performance time, the mean difference (system vs clinician) was 0.17s (sd=0.14s). For FAS evaluation, there was agreement in 4 out of 5 patients in the two tasks evaluated. The prototype tested was able to automatically classify upper limb movement, according to a widely used functional motor scale (WMFT) in a relevant clinical setting. These results represent an important step towards a system capable of precise and independent motor evaluation after stroke. The portability and low-cost design will contribute for its usability in ambulatory clinical settings and research trials.

Implementation and Outcomes of a Collaborative Multi-Center Network Aimed at Web-Based Cognitive Training - COGWEB Network.

BACKGROUND: Cognitive care for the most prevalent neurologic and psychiatric conditions will only improve through the implementation of new sustainable approaches. Innovative cognitive training methodologies and collaborative professional networks are necessary evolutions in the mental health sector. OBJECTIVE: The objective of the study was to describe the implementation process and early outcomes of a nationwide multi-organizational network supported on a Web-based cognitive training system (COGWEB). METHODS: The setting for network implementation was the Portuguese mental health system and the hospital-, academic-, community-based institutions and professionals providing cognitive training. The network started in August 2012, with 16 centers, and was monitored until September 2013 (inclusions were open). After onsite training, all were allowed to use COGWEB in their clinical or research activities. For supervision and maintenance were implemented newsletters, questionnaires, visits and webinars. The following outcomes were prospectively measured: (1) number, (2) type, (3) time to start, and (4) activity state of centers; age, gender, level of education, and medical diagnosis of patients enrolled. RESULTS: The network included 68 professionals from 41 centers, (33/41) 80% clinical, (8/41) 19% nonclinical. A total of 298 patients received cognitive training; 45.3% (n=135) female, mean age 54.4 years (SD 18.7), mean educational level 9.8 years (SD 4.8). The number enrolled each month increased significantly (r=0.6; P=.031). At 12 months, 205 remained on treatment. The major causes of cognitive impairment were: (1) neurodegenerative (115/298, 38.6%), (2) structural brain lesions (63/298, 21.1%), (3) autoimmune (40/298, 13.4%), (4) schizophrenia (30/298, 10.1%), and (5) others (50/298, 16.8%). The comparison of the patient profiles, promoter versus all other clinical centers, showed significant increases in the diversity of causes and spectrums of ages and education. CONCLUSIONS: Over its first year, there was a major increase in the number of new centers and professionals, as well as of the clinical diversity of patients treated. The consolidation of such a national collaborative network represents an innovative step in mental health care evolution. Furthermore, it may contribute to translational processes in the field of cognitive training and reduce disease burden.

Spasticity as the first manifestation of ischaemic lesions involving the cingulum.

Background and Purpose. Spasticity is a positive sign of upper motor neuron syndrome that usually develops weeks after a stroke. The mechanisms that lead to its appearance are not completely understood, namely, the cortical regions whose lesion may induce spasticity. Summary of Cases. We report two patients with an ischaemic stroke entailing the anterior cingulate gyrus (pericallosal artery territory), who presented with acute hemiplegia and spasticity since symptom onset. Spasticity resolved within days after onset. Conclusions. The acute destruction of the anterior cingulate region, interrupting inhibitory projections towards lower motor centres, probably explains the acute onset of spasticity that occurred in these two patients. Further studies addressing the role of this region in acute and chronic disturbances of muscular tone are necessary.

[Neuro-Behçet: MR study of a group of patients]. / Neuro-Behçet: características imagiológicas.

Behçet's disease is a chronic inflammatory, multisystemic disease of unknown aetiology. Central nervous system involvement occurs in a variable proportion of cases (4 to 49%) and is due to intracranial hypertension secondary to dural sinus thrombosis, inflammatory parenquimal lesions or recurrent meningoencephalitis. We reviewed 12 patients, 7 men and 5 women, aged between 27 to 40 years at the time of diagnosis. Neurological manifestations were secondary to parenquimal lesions in 7 patients, meningoencephalitis in 3 patients (including one with extensive medullary lesion) and dural sinus thrombosis in 2. Magnetic Resonance (MR) findings in Neuro-Behçet are non-specific. Nevertheless, MR has a role in characterizing brain lesions topography, helping in the diagnosis and in the follow-up of these patients.