Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial.

BACKGROUND: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. METHODS: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. FINDINGS: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9-19·7, p=0·059). INTERPRETATION: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis. FUNDING: Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation.

Human papillomavirus infection: Epidemiology, biology, host interactions, cancer development, prevention, and therapeutics.

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide. It is caused by the HPV, a DNA virus that infects epithelial cells in various mucous membranes and skin surfaces. HPV can be categorised into high-risk and low-risk types based on their association with the development of certain cancers. High-risk HPV types, such as HPV-16 and HPV-18, are known to be oncogenic and are strongly associated with the development of cervical, anal, vaginal, vulvar, penile, and oropharyngeal cancers. These types of HPV can persist in the body for an extended period and, in some cases, lead to the formation of precancerous lesions that may progress to cancer if left untreated. Low-risk HPV types, such as HPV-6 and HPV-11, are not typically associated with cancer but can cause benign conditions like genital warts. Genital warts are characterised by the growth of small, cauliflower-like bumps on the genital and anal areas. Although not life-threatening, they can cause discomfort and psychological distress. HPV is primarily transmitted through sexual contact, including vaginal, anal, and oral sex. It can also be transmitted through non-penetrative sexual activities that involve skin-to-skin contact. In addition to sexual transmission, vertical transmission from mother to child during childbirth is possible but relatively rare. Prevention of HPV infection includes vaccination and safe sexual practices. HPV vaccines, such as Gardasil and Cervarix, are highly effective in preventing infection with the most common high-risk HPV types. These vaccines are typically administered to adolescents and young adults before they become sexually active. Safe sexual practices, such as consistent and correct condom use and limiting the number of sexual partners, can also reduce the risk of HPV transmission. Diagnosis of HPV infection can be challenging because the infection is often asymptomatic, especially in men. In women, HPV testing can be done through cervical screening programs, which involve the collection of cervical cells for analysis. Abnormal results may lead to further diagnostic procedures, such as colposcopy or biopsy, to detect precancerous or cancerous changes. Overall, HPV infection is a prevalent sexually transmitted infection with significant implications for public health. Vaccination, regular screening, and early treatment of precancerous lesions are key strategies to reduce the burden of HPV-related diseases and their associated complications. Education and awareness about HPV and its prevention are crucial in promoting optimal sexual health. This study aimed to carry out a literature review considering several aspects involving HPV infection: Global distribution, prevalence, biology, host interactions, cancer development, prevention, therapeutics, coinfection with other viruses, coinfection with bacteria, association with head and neck squamous cell carcinomas, and association with anal cancer.

Temporal trends in respiratory pathogens following the COVID-19 pandemic and climate variables: A unicentric retrospective evaluation of 24 pathogens in a temperate subtropical region.

Temperature and humidity are studied in the context of seasonal infections in temperate and tropical zones, but the relationship between viral trends and climate variables in temperate subtropical zones remains underexplored. Our retrospective study analyzes respiratory pathogen incidence and its correlation with climate data in a subtropical zone. Retrospective observational study at Moinhos de Vento Hospital, South Brazil, aiming to assess seasonal trends in respiratory pathogens, correlating them with climate data. The study included patients of all ages from various healthcare settings, with data collected between April 2022 and July 2023. Biological samples were analyzed for 24 pathogens using polymerase chain reaction and hybridization techniques; demographic variables were also collected. The data was analyzed descriptively and graphically. Spearman tests and Poisson regression were used as correlation tests. Tests were clustered according to all pathogens, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses, rhinovirus, and respiratory syncytial virus (RSV). Between April 2022 and July 2023, 3329 tests showed a 71.6% positivity rate. Rhinovirus and RSV predominated, exhibiting seasonal patterns. Temperature was inversely correlated with the viruses, notably rhinovirus, but SARS-CoV-2 was positively correlated. Air humidity was positively correlated with all pathogens, RSV, rhinovirus, and atmospheric pressure with all pathogens and rhinovirus. Our results showed statistically significant correlations, with modest effect sizes. Our study did not evaluate causation effects. Despite the correlation between climate and respiratory pathogens, our work suggests additional factors influencing transmission dynamics. Our findings underscore the complex interplay between climate and respiratory infections in subtropical climates.

Neurologists Preferences on Basic and Advanced Cardiac Imaging Utilization in Ischemic Stroke Patients.

INTRODUCTION: It is unknown how cardiac imaging studies are used by neurologists to investigate cardioembolic sources in ischemic stroke patients. METHODS: Between August 12, 2023, and December 8, 2023, we conducted an international survey among neurologists from Europe, North America, South America, and Asia, to investigate the frequency of utilization of cardiac imaging studies for the detection of cardioembolic sources of ischemic stroke. Questions were structured into deciles of percentage utilization of transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), ECG-gated cardiac computed tomography (G-CCT), and cardiac magnetic resonance imaging (CMRI). We estimated the weighted proportion (x¯) of utilization of each cardiac imaging modality, both globally and by continent. We also investigated the use of head and neck computed tomography angiography (CTA) as an emerging approach to the screening of cardioembolic sources. RESULTS: A total of 402 neurologists from 64 countries completed the survey. Globally, TTE was the most frequently used cardiac imaging technology (x¯ = 71.2%), followed by TEE (x¯ = 15.8%), G-CCT (x¯ = 10.9%), and CMRI (x¯ = 7.7%). Findings were consistent across all continents. A total of 288 respondents routinely used a CTA in the acute ischemic stroke phase (71.6%), but the CTA included a non-gated CCT in only 15 cases (5.2%). CONCLUSIONS: This survey suggests that basic cardiac imaging is not done in all ischemic stroke patients evaluated in 4 continents. We also found a substantially low utilization of advanced cardiac imaging studies. Easier to adopt screening methods for cardioembolic sources of embolism are needed.

World Stroke Organization Brain & hEart globAl iniTiative Program.

INTRODUCTION: The World Stroke Organization (WSO) Brain & Heart Task Force developed the Brain & hEart globAl iniTiative (BEAT), a pilot feasibility implementation program to establish clinical collaborations between cardiologists and stroke physicians who work at large healthcare facilities. METHODS: The WSO BEAT pilot project focused on atrial fibrillation (AF) and patent foramen ovale (PFO) detection and management, and poststroke cardiovascular complications known as the stroke-heart syndrome. The program included 10 sites from 8 countries: Brazil, China, Egypt, Germany, Japan, Mexico, Romania, and the USA The primary composite feasibility outcome was the achievement of the following 3 implementation metrics (1) developing site-specific clinical pathways for the diagnosis and management of AF, PFO, and the stroke-heart syndrome; (2) establishing regular Neurocardiology rounds (e.g., monthly); and (3) incorporating a cardiologist to the stroke team. The secondary objectives were (1) to identify implementation challenges to guide a larger program and (2) to describe qualitative improvements. RESULTS: The WSO BEAT pilot feasibility program achieved the prespecified primary composite outcome in 9 of 10 (90%) sites. The most common challenges were the limited access to specific medications (e.g., direct oral anticoagulants) and diagnostic (e.g., prolonged cardiac monitoring) or therapeutic (e.g., PFO closure devices) technologies. The most relevant qualitative improvement was the achievement of a more homogeneous diagnostic and therapeutic approach. CONCLUSION: The WSO BEAT pilot program suggests that developing neurocardiology collaborations is feasible. The long-term sustainability of the WSO BEAT program and its impact on quality of stroke care and clinical outcomes needs to be tested in a larger and longer duration program.

Economic Analysis of Falls in a Private Hospital in Southern Brazil-A Case-Control Study.

INTRODUCTION: In-hospital falls represent significant health and economic concerns, but previous studies regarding the economic cost of falls do not account for other cofounders (comorbidities and clinical aspects) in this cost evaluation. AIM: The aim of this study is to analyse the cost of in-hospital falls comparing those who had falls to nonfalls patients while accounting for several risk factors associated with falls. METHODS: Data were collected from January 2020 to December 2022, in a private hospital in Brazil. The sample was divided into two groups: one with patients who fell and the other with nonfallers on a 1:2 ratio, and these groups were matched to avoid confounding variables. RESULTS: The median cost for patients who experienced falls was US$7520.26 compared to US$6144.24 for those without falls (p < 0.01). This trend was especially marked in men aged 20-40 who suffered falls and showed a significantly elevated median cost of US$29 722.02 distinguishing them from those without falls with a median cost of US$1179.48 (p < 0.01). CONCLUSION: Hospital falls significantly increase financial costs compared to nonfall cases, irrespective of comorbidities, length of stay or case-mix variations. The findings recommend a universal precautions approach to fall prevention in hospitals, targeting all hospitalised patients to effectively minimise the economic burden associated with in-hospital falls.

Molecular evolution of dengue virus: a Bayesian approach using 1581 whole-genome sequences from January 1944 to July 2022.

Dengue is a viral disease transmitted by mosquitoes that has spread rapidly across all continents in recent years. There are four distinct but closely related serotypes of the virus that causes dengue (DENV-1, DENV-2, DENV-3, and DENV-4). In the present study, we evaluated temporal spreading and molecular evolution of dengue virus (DENV) serotypes. Bayesian coalescent analysis was performed to study viral evolution, and it was estimated that the most recent common ancestor of DENV-1 was present in 1884 in Southeast Asia, that of DENV-2 was present in 1723 in Europe, that of DENV-3 was present in 1921 in Southeast Asia, and that of DENV-4 was present in 1876 in Southeast Asia. DENV appears to have originated in Spain in approximately 1682, and it was disseminated in Asia and Oceania in approximately 1847. After this period, the virus was introduced into North America in approximately 1890. In South America, it was first disseminated to Ecuador in approximately 1897 and then to Brazil in approximately 1910. Dengue has had a significant impact on global health worldwide, and the present study provides an overview of the molecular evolution of DENV serotypes.

Factors Associated with Low Volumes of Mother's Own Milk at Neonatal Intensive Care Unit Discharge of Very Low Birth Weight Infants-a Cohort Study.

Background: Mother's own milk (MOM) provides health benefits for infants with very low birth weight (VLBW). This study aimed to describe the incidence and factors associated with low volumes of MOM (<50% of total diet volume) at discharge for VLBW infants. Methods: A prospective cohort study of infants with VLBW and gestational age of <30 weeks, who survived to discharge and had no contraindication to MOM. We conducted bivariate analyses to investigate associations with the volume of MOM at discharge, using chi-square, t, and Mann-Whitney tests. All p-value analyses were two-tailed. The variables significantly associated with "low volumes of MOM" entered the multivariable analysis. Univariate and multivariate relative risk (confidence interval [CI] 95%) estimates were obtained from Poisson regression with a robust estimate of variance and controlled by the length of hospital stay. Results: Of 414 infants included and followed until discharge, 32.9% (n = 136) received less than 50% of the total daily volume of MOM. This outcome was associated with gestational age <28 weeks, lower birth weight, multiple births, developing bronchopulmonary dysplasia, and longer lengths of stay. After Poisson regression, low volumes of MOM at discharge were associated only with being born multiples (RR 2.01; CI 95% 1.53-2.64, p < 0.001) and with longer length of stay (RR 1.07; CI 95% 1.01-1.14, p = 0.01). Conclusions: Most VLBW infants were discharged home receiving predominantly MOM. Each neonatal intensive care unit (NICU) should acknowledge which clinical characteristics of mothers and VLBW infants are associated with difficulties maintaining MOM volumes until discharge.

Improving door-to-reperfusion time in acute ischemic stroke during the COVID-19 pandemic: experience from a public comprehensive stroke center in Brazil.

Background: The global COVID-19 pandemic has had a devastating effect on global health, resulting in a strain on healthcare services worldwide. The faster a patient with acute ischemic stroke (AIS) receives reperfusion treatment, the greater the odds of a good functional outcome. To maintain the time-dependent processes in acute stroke care, strategies to reorganize infrastructure and optimize human and medical resources were needed. Methods: Data from AIS patients who received thrombolytic therapy were prospectively assessed in the emergency department (ED) of Hospital de Clínicas de Porto Alegre from 2019 to 2021. Treatment times for each stage were measured, and the reasons for a delay in receiving thrombolytic therapy were evaluated. Results: A total of 256 patients received thrombolytic therapy during this period. Patients who arrived by the emergency medical service (EMS) had a lower median door-to-needle time (DNT). In the multivariable analysis, the independent predictors of DNT >60 min were previous atrial fibrillation (OR 7) and receiving thrombolysis in the ED (OR 9). The majority of patients had more than one reason for treatment delay. The main reasons were as follows: delay in starting the CT scan, delay in the decision-making process after the CT scan, and delay in reducing blood pressure. Several actions were implemented during the study period. The most important factor that contributed to a decrease in DNT was starting the bolus and continuous infusion of tPA on the CT scan table (decreased the median DNT from 74 to 52, DNT ≤ 60 min in 67% of patients treated at radiology service vs. 24% of patients treated in the ED). The DNT decreased from 78 min to 66 min in 2020 and 57 min in 2021 (p = 0.01). Conclusion: Acute stroke care continued to be a priority despite the COVID-19 pandemic. The implementation of a thrombolytic bolus and the start of continuous infusion on the CT scan table was the main factor that contributed to the reduction of DNT. Continuous monitoring of service times is essential for improving the quality of the stroke center and achieving better functional outcomes for patients.

Reperfusion therapy for acute ischemic stroke: where are we in 2023?

Over the last three decades, stroke care has undergone significant transformations mainly driven by the introduction of reperfusion therapy and the organization of systems of care. Patients receiving treatment through a well-structured stroke service have a much higher chance of favorable outcomes, thereby decreasing both disability and mortality. In this article, we reviewed the scientific evidence for stroke reperfusion therapy, including thrombolysis and thrombectomy, and its implementation in the public health system in Brazil.

Nas últimas três décadas, o tratamento do AVC sofreu transformações significativas, impulsionadas principalmente pela introdução das terapias de reperfusão e pela organização dos serviços de AVC. Os pacientes que recebem tratamento em um serviço de AVC bem estruturado têm uma probabilidade muito maior de resultados favoráveis, diminuindo assim a incapacidade funcional e a mortalidade. Neste artigo, revisamos as evidências científicas para as terapias de reperfusão do AVC, incluindo trombólise e trombectomia e sua implementação no sistema público de saúde no Brasil.

Disparities in Stroke Patient-Reported Outcomes Measurement Between Healthcare Systems in Brazil.

Introduction: Acute stroke interventions, such as stroke units and reperfusion therapy, have the potential to improve outcomes. However, there are many disparities in patient characteristics and access to the best stroke care. Thus, we aim to compare patient-reported outcome measures (PROMs) after stroke in two stroke centers representing the public and private healthcare systems in Brazil. Methods: PROMs through the International Consortium for Health Outcomes Measures (ICHOM) were assessed at 90 days after the stroke to compare two Brazilian hospitals in southern Brazil: a public university and a private stroke center, both with stroke protocols and stroke units. Results: When compared with the private setting (n = 165), patients from the public hospital (n = 175) were younger, had poorer control of risk factors, had more frequent previous strokes, and arrived with more severe strokes. Both hospitals had a similar percentage of IV thrombolysis treatment. Only 5 patients received mechanical thrombectomy (MT), all in the private hospital. Public hospital patients presented significantly worse outcomes at 3 months, including worse quality of life and functional dependence (60 vs. 48%, p = 0.03). Poor outcome, as measured by the mRS score, was significantly associated with older age, higher NIHSS score, and the presence of heart failure. However, the public practice was a strong predictor of any self-reported disability. Conclusion: Patients assisted at a good quality public stroke center with the same protocol used in the private hospital presented worse disability as measured by mRS and patient-reported outcome measures, with greater inability to communicate, dress, toilet, feed, and walk.

Parkinsonism-hyperpyrexia Syndrome After Amantadine Withdrawal: Case Report and Review of the Literature.

INTRODUCTION: Parkinsonism-hyperpyrexia syndrome (PHS) is a rare and potentially fatal complication of Parkinson disease (PD) characterized by a neuroleptic malignant-like syndrome due to abrupt discontinuation of antiparkinsonian medications. CASE REPORT: A 79-year-old woman with late-stage PD presented at the hospital with neuropsychiatric and uncontrolled parkinsonian motor symptoms. Soon after the abrupt discontinuation of amantadine, the patient suddenly presented with global rigidity, global unresponsiveness, diaphoresis, tachycardia, recurrent hyperpyrexia, and a mildly elevated creatine kinase, which lead to the diagnosis of PHS. Amantadine was then reinitiated and her symptoms resolved within 10 days. CONCLUSIONS: Amantadine is an antiparkinsonian medication scarcely associated with PHS. The few reported cases are further summarized and discussed in this article. This case highlights the importance of early recognition of PHS, which may be caused by changes in other antiparkinson agents such as amantadine, and the need to slowly titrate such agents.

Reperfusion therapy for acute ischemic stroke: where are we in 2023? / Terapia de reperfusão para o acidente vascular isquêmico agudo: onde estamos em 2023?

Abstract Over the last three decades, stroke care has undergone significant transformations mainly driven by the introduction of reperfusion therapy and the organization of systems of care. Patients receiving treatment through a well-structured stroke service have a much higher chance of favorable outcomes, thereby decreasing both disability and mortality. In this article, we reviewed the scientific evidence for stroke reperfusion therapy, including thrombolysis and thrombectomy, and its implementation in the public health system in Brazil.

Resumo Nas últimas três décadas, o tratamento do AVC sofreu transformações significativas, impulsionadas principalmente pela introdução das terapias de reperfusão e pela organização dos serviços de AVC. Os pacientes que recebem tratamento em um serviço de AVC bem estruturado têm uma probabilidade muito maior de resultados favoráveis, diminuindo assim a incapacidade funcional e a mortalidade. Neste artigo, revisamos as evidências científicas para as terapias de reperfusão do AVC, incluindo trombólise e trombectomia e sua implementação no sistema público de saúde no Brasil.

Racial and social disparities in the access to automated peritoneal dialysis - results of a national PD cohort.

The prevalence of patients on automated peritoneal dialysis (APD) is increasing worldwide and may be guided by clinical characteristics, financial issues and patient option. Whether socioeconomic factors at the patient level may influence the decision for the initial peritoneal dialysis (PD) modality is unknown. This is a prospective cohort study. The primary outcome of interest was the probability to start PD on APD. The inclusion criteria were adult patients incident in PD. Exclusion criteria were missing data for either race or initial PD modality. We used a mixed-model analysis clustering patients according to their PD center and region of the country. We included 3,901 patients of which 1,819 (46.6%) had APD as their first modality. We found a significant disparity for race and educational level with African American patients less likely to start on APD (Odds ratio 0.74 CI95% 0.58-0.94) compared to Whites whilst those with greater educational levels were more likely to start on APD (Odds ratio 3.70, CI95% 2.25-6.09) compared to illiterate patients. Limiting the use of APD in disadvantaged population may be unethical. Demographics and socioeconomic status should not be necessarily part of the decision-making process of PD modality choice.