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Central retinal artery occlusion (CRAO) is a subtype of ischaemic stroke that results in acute monocular vision loss. Although open-label studies and meta-analyses have suggested that early intravenous thrombolysis might improve visual acuity, no randomised controlled trials have yet confirmed this benefit. We aimed to compare the safety and efficacy of intravenous alteplase with oral aspirin in patients with CRAO treated within 4·5 h of onset of severe vision loss. THEIA was a multicentre, double-dummy, patient-blinded, assessor-blinded, randomised, controlled, phase 3 trial conducted across 16 hospitals with stroke units in France. Adults (aged ≥18 years) presenting with sudden, severe, and persistent monocular vision loss (Snellen <20/400) due to suspected non-arteritic acute CRAO were eligible for inclusion. Participants were randomly assigned (1:1), stratified by centre, to receive either 0·9 mg/kg of bodyweight intravenous alteplase and oral placebo (alteplase group) or 300 mg oral aspirin and intravenous saline placebo (aspirin group) within 4·5 h of symptom onset. Patients, outcome assessors, and the study sponsor were masked to treatment allocation; treating nurses and neurologists were unmasked. The primary efficacy outcome was improvement in visual acuity of at least 0·3 logarithm of the minimum angle of resolution (LogMAR) from baseline to 1 month, analysed in the full analysis set, which included all patients who received the complete intervention and a visual acuity assessment at baseline. Safety outcomes included serious adverse events, particularly intracranial and extracranial bleeding, analysed in all randomly assigned participants. This study is registered at ClinicalTrials.gov (NCT03197194) and is completed. Between June 8, 2018, and Oct 2, 2023, 70 patients (mean age 70 years [SD 9]; 25 [36%] women and 45 [64%] men) were enrolled and randomly assigned to either the alteplase group (35 [50%]) or the aspirin group (35 [50%]). In total, 65 (93%) patients received the allocated treatment: 34 (97%) in the alteplase group and 31 (89%) in the aspirin group. Mean time from symptom onset to treatment initiation was 232·4 min (SD 43·6). Among 56 patients with available data on the primary endpoint, 19 (66%) of 29 patients in the alteplase group and 13 (48%) of 27 patients in the aspirin group showed an improvement in visual acuity of at least 0·3 LogMAR at 1 month (unadjusted risk difference 17·4 [95% CI –11·8 to 46·5]; adjusted odds ratio 1·1 [95% CI 0·07 to 18·39]; p=0·95). One asymptomatic intracranial haemorrhage related to study treatment was reported in the alteplase group. 14 serious adverse events unrelated to treatment occurred in 11 patients overall (six [17%] in the aspirin group and five [14%] in the alteplase group). No symptomatic haemorrhages or major bleeding related to study treatment were reported. Intravenous alteplase administered within 4·5 h of CRAO onset was not associated with a significant improvement in visual acuity compared with aspirin, despite a higher rate of improvement in the alteplase group. However, the study was likely underpowered to detect a statistical difference. Although no safety concerns related to alteplase were identified, the overall modest recovery rates underscore the need for individual patient-level data meta-analyses with forthcoming randomised controlled trials to clarify the potential benefit of thrombolysis or aspirin in patients with acute CRAO. French Ministry of Health and Boehringer Ingelheim, France.

Regulatory harmonization and convergence have been identified as the key driver in promoting efficient evaluation of medicines, reducing workload, and supporting earlier access to medicines on the African continent. There has been great progress to date in enhancing regulatory harmonization and convergence on the African continent via the Regional Economic Communities (RECs) and with the establishment of the Africa Medicines Agency (AMA). In this article, the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Africa Regulatory Network (ARN) presents its perspective based on the available literature review and results from a survey conducted with innovative biopharmaceutical companies to gather experiences using regional joint assessment procedures (JAPs) in Africa, such as the East African Community Medicines Regulatory Harmonization (EAC-MRH), the West African Medicines Regulatory Harmonization (WA-MRH), and the Southern African Development Community Medicines Regulatory Harmonization (SADC-MRH) initiative through the ZAZIBONA Collaborative Procedure for Medicines Registration (ZaZiBoNa), and provides best practices in this evolving landscape. The article also assesses other collaborative registration pathways available to facilitating registration of pharmaceutical products in African countries, such as WHO Collaborative Registration Procedures (CRP), Swissmedic’s Marketing Authorisation for Global Health Products (MAGHP) and EU Medicines for All (EU-M4ALL). Benefits and challenges of each of the existing pathways are discussed in this article. Main benefits include building more expert capacity and improved collaboration amongst experts, as well as shorter review timelines in some cases. Key challenges include the lack of predictability in the adherence to procedural timelines as defined per guidelines, lengthy timeline to achieve national marketing authorization following joint assessment, the lack of dedicated personnel, administrative issues during the submission process as well as additional country-specific requirements on top of JAP-specific requirements. Our recommendations for improvements include harmonization of requirements across countries and regions and with international standards, appropriate resource allocation for JAP activities to ensure adherence to timelines, use of JAPs throughout the entire product lifecycle and all product categories, adequate use of digital technologies, and improved communication and transparency with applicants. These improvements will allow industry to better plan their filing strategies for the region which will lead to overall improved usability of the JAPs in Africa and enable faster patient access.

A look at the artistic legacy of the Tudors, revealing the dynasty's influence on the arts in Renaissance England and beyond. Ruling successively from 1485 through 1603, the five Tudor monarchs changed England indelibly, using the visual arts to both legitimize and glorify their tumultuous rule - from Henry VII's bloody rise to power, through Henry VIII's breach with the Roman Catholic Church, to the reign of the 'virgin queen' Elizabeth I. With incisive scholarship and sumptuous new photography, the book explores the politics and personalities of the Tudors, and how they used art in their diplomacy at home and abroad.

Background In the treatment of phenylketonuria (PKU), there was disparity between UK dietitians regarding interpretation of how different foods should be allocated in a low phenylalanine diet (allowed without measurement, not allowed, or allowed as part of phenylalanine exchanges). This led to variable advice being given to patients. Methodology In 2015, British Inherited Metabolic Disease Group (BIMDG) dietitians ( n  = 70) were sent a multiple-choice questionnaire on the interpretation of protein from food-labels and the allocation of different foods. Based on majority responses, 16 statements were developed. Over 18-months, using Delphi methodology, these statements were systematically reviewed and refined with a facilitator recording discussion until a clear majority was attained for each statement. In Phase 2 and 3 a further 7 statements were added. Results The statements incorporated controversial dietary topics including: a practical ‘scale’ for guiding calculation of protein from food-labels; a general definition for exchange-free foods; and guidance for specific foods. Responses were divided into paediatric and adult groups. Initially, there was majority consensus (≥86%) by paediatric dietitians ( n  = 29) for 14 of 16 statements; a further 2 structured discussions were required for 2 statements, with a final majority consensus of 72% ( n  = 26/36) and 64% ( n  = 16/25). In adult practice, 75% of dietitians agreed with all initial statements for adult patients and 40% advocated separate maternal-PKU guidelines. In Phase 2, 5 of 6 statements were agreed by ≥76% of respondents with one statement requiring a further round of discussion resulting in 2 agreed statements with a consensus of ≥71% by dietitians in both paediatric and adult practice. In Phase 3 one statement was added to elaborate further on an initial statement, and this received 94% acceptance by respondents. Statements were endorsed by the UK National Society for PKU. Conclusions The BIMDG dietitians group have developed consensus dietetic statements that aim to harmonise dietary advice given to patients with PKU across the UK, but monitoring of statement adherence by health professionals and patients is required.

\"In celebration of the 50th anniversary of the Apollo 11 landing, the endlessly-mysterious moon is explored in this reprint short science fiction anthology from award-winning editor and anthologist Neil Clarke ... On July 20, 1969, mankind made what had only years earlier seemed like an impossible leap forward: when Apollo 11 became the first manned mission to land on the moon, and Neil Armstrong the first person to step foot on the lunar surface. While there have only been a handful of new missions since, the fascination with our planet's satellite continues, and generations of writers and artists have imagined the endless possibilities of lunar life. From adventures in the vast gulf of space between the earth and the moon, to journeys across the light face to the dark side, to the establishment of permanent residences on its surface, science fiction has for decades given readers bold and forward-thinking ideas about our nearest interstellar neighbor and what it might mean to humankind, both now and in our future. [This book] collects the best stories written in the fifty years since mankind first stepped foot on the lunar surface, serving as a shining reminder that the moon is and always has been our most visible and constant example of all the infinite possibility of the wider universe\"-- Provided by publisher.

The respiratory system examination showed normal chest skin, the right side was moving less, tactile vocal resonance was more on the right side, percussion note was dull on the right lower side, and there was decreased air entry at the right side but no added sounds. Showing massive swelling affecting the knee region, studded with multiple sinuses discharging purulent and seropurulent discharge containing black grains. https://doi.org/10.1371/journal.pntd.0010867.g001 Her full blood count showed WBCS of 5.7 * 103 micro/L, RBCs of 5.10 * 106 micro/L, haemoglobin of 10.4 g/dl, MCV of 66.7 fL, MCH of 20.4, MCHC of 30.6 pg, platelets of 339103 micro/L, neutrophils of 59%, lymphocytes of 31%, and monocytes of 8%. Photograph showing the secondary right inguinal mycetoma lesion. https://doi.org/10.1371/journal.pntd.0010867.g005 At a recent presentation to the MRC, on general examination, he looked unwell, pale, and vitally stable, with pulse rate of 72 beats/minute, respiratory rate of 20 breaths/minute, and blood pressure of 131/87 mm Hg. The renal profile showed blood urea of 11 mg/dl, low creatinine of 0.3 mg/dl with slightly low Na+ of 134 mmol/l, and K+ of 3.1 mmol/l.

Children under the age of four are emotionally vulnerable to global disasters such as the COVID-19 pandemic because of the lack of socialization opportunities and coping mechanisms, and susceptibility to heightened caregiver stress. Currently, the extent to which the pandemic impacted the mental health of treatment-seeking young children is unknown. To evaluate how children’s mental health outcomes were impacted during the pandemic, 1,343 interRAI Early Years assessments were obtained from 11 agencies across the Province of Ontario, during pre-pandemic and pandemic timepoints. Findings demonstrated that the number of assessments declined during the pandemic. Further, children’s emotional concerns differed before and during the pandemic, whereby children exhibited greater emotional dysregulation during the pandemic. However, there were no significant differences when examining caregiver distress, parenting strengths, child distractibility/inattention or behavioural issues. Clinical implications for young children and their families, clinicians, and educators are discussed.

There is an increasing number of adults and elderly patients with phenylketonuria (PKU) who are either early, late treated, or untreated. The principal treatment is a phenylalanine-restricted diet. There is no established UK training for dietitians who work with adults within the specialty of Inherited Metabolic Disorders (IMDs), including PKU. To address this, a group of experienced dietitians specializing in IMDs created a standard operating procedure (SOP) on the dietetic management of adults with PKU to promote equity of care in IMD dietetic services and to support service provision across the UK. The group met virtually over a period of 12 months until they reached 100% consensus on the SOP content. Areas of limited evidence included optimal blood phenylalanine reporting times to patients, protein requirements in older adults, management of weight and obesity, and management of disordered eating and eating disorders. The SOP does not include guidance on maternal PKU management. The SOP can be used as a tool for training dietitians new to the specialty and to raise the standard of education and care for patients with PKU in the UK.