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Background and objectives: Long COVID, characterized by persistent symptoms beyond the acute infection phase, remains poorly characterized in children. Our study aim is to determine if children who exhibit any symptoms/conditions associated with Long COVID after acute COVID-19 infection have higher Emergency Department (ED) utilization compared to those who do not exhibit these symptoms. Methods: Data from the HealthJump ambulatory database from the COVID-19 Research Database Consortium was utilized to identify pediatric COVID-19 cases from March 2020 to May 2023. Long COVID cases were defined based on symptoms/conditions occurring 30–180 days after initial COVID diagnosis. Descriptive statistics and multivariable logistic regression models were used to model the relationship between Long COVID and child ED utilization. Results: Out of 130,010 children diagnosed with COVID-19, 43,645 (33.6%) exhibited at least one Long COVID symptom/condition. Children with Long COVID symptoms/conditions had 152% higher odds (OR: 2.52, CI: 2.32–2.73) of ED visits, while those with specific symptoms including "chest pain" had 255% higher odds (AOR: 3.55, CI: 2.73–4.54) and "fluid and electrolyte disturbances" had 229% higher odds (AOR: 3.29, CI: 2.23–4.73) compared to those without those symptoms/conditions. Conclusion: This study reveals that children with Long COVID symptoms had notably higher odds of ED visits, with chest pain, fluid imbalances, and generalized pain being most closely linked to such visits. This study highlights the burden of Long COVID on ED providers and underscores the importance of improved guidance for managing Long COVID symptoms in children. [ABSTRACT FROM AUTHOR]

Abstract Background and objectives Long COVID, characterized by persistent symptoms beyond the acute infection phase, remains poorly characterized in children. Our study aim is to determine if children who exhibit any symptoms/conditions associated with Long COVID after acute COVID-19 infection have higher Emergency Department (ED) utilization compared to those who do not exhibit these symptoms. Methods Data from the HealthJump ambulatory database from the COVID-19 Research Database Consortium was utilized to identify pediatric COVID-19 cases from March 2020 to May 2023. Long COVID cases were defined based on symptoms/conditions occurring 30–180 days after initial COVID diagnosis. Descriptive statistics and multivariable logistic regression models were used to model the relationship between Long COVID and child ED utilization. Results Out of 130,010 children diagnosed with COVID-19, 43,645 (33.6%) exhibited at least one Long COVID symptom/condition. Children with Long COVID symptoms/conditions had 152% higher odds (OR: 2.52, CI: 2.32–2.73) of ED visits, while those with specific symptoms including “chest pain” had 255% higher odds (AOR: 3.55, CI: 2.73–4.54) and “fluid and electrolyte disturbances” had 229% higher odds (AOR: 3.29, CI: 2.23–4.73) compared to those without those symptoms/conditions. Conclusion This study reveals that children with Long COVID symptoms had notably higher odds of ED visits, with chest pain, fluid imbalances, and generalized pain being most closely linked to such visits. This study highlights the burden of Long COVID on ED providers and underscores the importance of improved guidance for managing Long COVID symptoms in children.

Camiler, dini işlevlerine göre ibadet mekânı olma özelliğinden dolayı Türk-İslam mimarisinde önemli bir yapı türü olarak karşımıza çıkmaktadır. Bu yapı türlerinin dini işlevinin yanında simgesel ve politik niteliği ile kamusal alan özelliğinde olması farklı işlevlerde kullanımına olanak sağlamaktadır. Özellikle yakın tarihte ülkemizde gerçekleşen 6 Şubat 2023 Kahramanmaraş merkezli depremlerden sonra ayakta kalabilen kültür varlıklarının acil durumlarda afetzedeler için barınma amaçlı kullanımı önem kazanmıştır. Bu çalışmada, Osmanlı mimarisinde sıkça karşımıza çıkan ve Anadolu’nun birçok yerinde örneğine rastlanan tabhaneli camiler ele alınmıştır. Çalışma kapsamında bu yapıların plan şemaları üzerinden elde edilen çıkarımlarla acil durumlarda kullanım potansiyelleri değerlendirilmiştir. Çalışmada amaç, camilerin afet ve sonrası kullanımlar için mekânsal niteliklerini tabhaneli camiler özelinde analiz etmek ve tartışmaya açmaktır.

Background: Prompted by the Covid-19 pandemic and the need to ensure timely and safe access to medicines during a pandemic, the aim of this study was to compare and contrast the EU and US regulations, processes, and outcomes pertaining to the granting of accelerated Marketing Authorizations (MAs) for COVID-19 vaccines and treatments with a view to determining how effective these regulations were in delivering safe medicines in a timely manner. Methods: MAs for medicines approved for Covid-related indications in the first two pandemic years (March 2020–February 2022) were identified using the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) websites. Authorization reports and utilized regulations were reviewed to determine and compare approval timelines, facilitated pathways, accepted clinical evidence, and effectiveness of the regulations by assessing them against time and safety standards. Results: By the end of February 2022, the EMA and FDA had granted 12 and 14 MAs, respectively. Two EU and two US approvals were issued in relation to new indications for already-approved treatments; the remaining ones were first-time approvals of novel vaccines and treatments. The median time to approval was 24 days for the EMA's conditional MAs and 36 days for the USFDA's Emergency Use Authorizations (EUA) for all Covid-19 medicines. This is compared with 23 and 28 days, respectively, specifically for first-time novel vaccines and treatments authorized by both USFDA and EMA. The USFDA and EMA differed markedly in terms of the time taken to approve new indications of already-approved treatment; the USFDA took 65 days for such approval, compared with 133 days for the EMA. Where MAs were issued by both authorities, USFDA approvals were issued before EMA approvals; applications for approval were submitted to the FDA before submission to the EMA. Three EU and two US MAs were based on data from two or more phase 3 clinical trials; the remaining ones were based on single trial data. Only six EU and four US trials had been completed by the time of authorization. This was in line with regulations. While the applicable regulations shared many similarities, there were marked differences. For instance, the EU's conditional MA regulation pertains only to first approvals of new treatments. It does not cover new indications of already-approved treatments. This contrasts with the US, where the EUA regulation applies to both types of applications, something that may have impacted approval timelines. Overall, both EU and US utilized regulations were considered to be effective. For most cases, utilizing such regulations for Covid-19 MAs resulted in faster approval timelines compared to standard MAs. They were flexible enough to manage the process of granting emergency approvals while maintaining strict requirements and allowing comprehensive reviews of the supporting evidence. Conclusion: US and EU regulations were effective in ensuring timely accelerated market access to Covid-19 medicines during the pandemic without compromising the approval standards related to safety or efficacy. The population in both regions will receive comparable access to medicines during a pandemic if sponsors submit their applications to both authorities in parallel. [ABSTRACT FROM AUTHOR]

Background: It is important to understand and address patient and caregiver perceptions about and attitudes toward generic substitution of drug–device combination products. Objective: The goal of this study was to explore how differences in design and usability features of epinephrine autoinjectors (EAIs) affect patients’ and caregivers’ views of product quality, efficacy, and device usability in an emergency setting and to better understand attitudes about and perceptions of EAI substitution. Methods: This qualitative, enhanced focus group study was conducted in the United States among adult and adolescent EAI users. A journey mapping exercise was used to explore patient and caregiver perceptions of and barriers to switching to a generic EAI. Discussion topics also focused on questions participants would ask, challenges they would face, and actions they would take if they were switched to a generic EAI. Results: While patients and caregivers were interested in the potential cost savings and increased access to treatment offered by generic EAIs, they wanted to be informed by their prescriber or pharmacist about generic substitution before or when it occurs. In terms of design differences, participant feedback most often related to differences in look and feel (eg, size, force to execute user tasks, hand grip) or functionality and design differences (eg, the generic version has a twist-off cap at the needle end, and the brand-name EpiPen does not). Conclusion: Outcomes from these focus groups suggest opportunities for the US Food and Drug Administration, health care professional organizations, and patient advocacy organizations to improve generic drug literacy among adults, adolescents, and health care providers.

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This commentary aims to elaborate challenges in the regulatory approaches for accessing and investigating COVID-19 potential therapies either with off-label use, compassionate use, emergency use or for clinical trials. Since no therapies have been formally approved and completely effective and safe to date, the best clinical choice is acquired only after consistent and fair communication and collaboration between licensed clinicians, researchers, regulatory authorities, manufacturers and patients.

With a scientific background from filoviruses, paramyxoviruses, SARS-CoV, and MERS-CoV, remdesivir entered into the COVID-19 battle to become one of the favorable therapeutic candidates with potential antiviral activity in the treatment of this disease. Globally, remdesivir was accessed and investigated through clinical research (clinical trials) and clinical practice (compassionate use, expanded access, early access scheme, and emergency use). Currently, remdesivir approval status differs between states. This paper aims to review and analyze regulatory approaches for accessing and investigating remdesivir, by communicating regulatory variability between countries in terms of terminology, modalities, and protocols.

There were no formal regulatory approvals for antivirals for the COVID-19 pandemic as of June 2020. We compare the first regulatory approvals for remdesivir, through emergency pathways available to three of the main regulators in the world, the U.S., Japan, and the EU. We look at the data supporting the decisions and how authorities exchanged information and collaborated to speed up approvals. Based only on topline data available as of 29 April 2020, regulators granted approvals to remdesivir based on very limited but robust data and waiting for more safety and efficacy data. This included the Emergency Use Authorization in the U.S. on 1 May, the Special Approval for Emergency in Japan on 7 May, and Compassionate Use (3 April) followed by a Conditional Marketing Authorization in Europe (Opinion 25th June, Decision (3 July)). While the regulatory approvals were clearly based on evidence, regulators used agile methods to speed up approval, and make the first antiviral with reliable data available to patients in their constituencies in a very short time frame. More data and wider patient access are still necessary for this product, and more treatments are needed for patients affected by COVID-19. [ABSTRACT FROM AUTHOR]

This commentary aims to elaborate challenges in the regulatory approaches for accessing and investigating COVID-19 potential therapies either with off-label use, compassionate use, emergency use or for clinical trials. Since no therapies have been formally approved and completely effective and safe to date, the best clinical choice is acquired only after consistent and fair communication and collaboration between licensed clinicians, researchers, regulatory authorities, manufacturers and patients. [ABSTRACT FROM AUTHOR]

Background: It is important to understand and address patient and caregiver perceptions about and attitudes toward generic substitution of drug-device combination products., Objective: The goal of this study was to explore how differences in design and usability features of epinephrine autoinjectors (EAIs) affect patients' and caregivers' views of product quality, efficacy, and device usability in an emergency setting and to better understand attitudes about and perceptions of EAI substitution., Methods: This qualitative, enhanced focus group study was conducted in the United States among adult and adolescent EAI users. A journey mapping exercise was used to explore patient and caregiver perceptions of and barriers to switching to a generic EAI. Discussion topics also focused on questions participants would ask, challenges they would face, and actions they would take if they were switched to a generic EAI., Results: While patients and caregivers were interested in the potential cost savings and increased access to treatment offered by generic EAIs, they wanted to be informed by their prescriber or pharmacist about generic substitution before or when it occurs. In terms of design differences, participant feedback most often related to differences in look and feel (eg, size, force to execute user tasks, hand grip) or functionality and design differences (eg, the generic version has a twist-off cap at the needle end, and the brand-name EpiPen does not)., Conclusion: Outcomes from these focus groups suggest opportunities for the US Food and Drug Administration, health care professional organizations, and patient advocacy organizations to improve generic drug literacy among adults, adolescents, and health care providers.

Here, we report a dual-route vaccination approach for plague, able to induce a rapid response involving systemic and mucosal immunity, whilst also providing ease of use in those resource-poor settings most vulnerable to disease outbreaks. This novel vaccine (VypVaxDuo) comprises the recombinant F1 and V proteins in free association. VypVaxDuo has been designed for administration via a sub-cutaneous priming dose followed by a single oral booster dose and has been demonstrated to induce early onset immunity 14 days after the primary immunisation; full protective efficacy against live organism challenge was achieved in Balb/c mice exposed to 2 × 10 4 median lethal doses of Yersinia pestis Co92, by the sub-cutaneous route at 25 days after the oral booster immunisation. This dual-route vaccination effectively induced serum IgG and serum and faecal IgA, specific for F1 and V, which constitute two key virulence factors in Y. pestis , and is therefore suitable for further development to prevent bubonic plague and for evaluation in models of pneumonic plague. This is an essential requirement for control of disease outbreaks in areas of the world endemic for plague and is supported further by the observed exceptional stability of the primary vaccine formulation in vialled form under thermostressed conditions (40 °C for 29 weeks, and 40 °C with 75% relative humidity for 6 weeks), meaning no cold chain for storage or distribution is needed. In clinical use, the injected priming dose would be administered on simple rehydration of the dry powder by means of a dual barrel syringe, with the subsequent single booster dose being provided in an enteric-coated capsule suitable for oral self-administration. [ABSTRACT FROM AUTHOR]

We discuss the term "compassionate use" (CU) as an example of terminology having a huge impact on drug regulation. CU is used in many confusing situations, and its meaning varies significantly. We ethically affirm the necessity of CU. We insist that CU should be properly placed in exceptional status. The regulation of CUs is much more lenient than that of clinical trials because of the difference in the purpose. Whether consciously or unconsciously, abuse results in confusion and is never acceptable. The World Health Organization (WHO) proposed not to use the previous term CU but to replace it with another one. WHO also proposed the term MEURI (monitored emergency use of unregistered and experimental interventions). However, this was extremely incomplete, and WHO used the term CU subsequently. The main purpose of the proposal needs to be thoroughly implemented. In the context of the COVID-19 pandemic and beyond, expectations regarding WHO's role and leadership in global health issues are rising. We hope that WHO will play a major role in promoting research ethics preparedness while discontinuing the use of confusing terms such as CU and will develop alternative terms and their content. We discuss the evaluation of MEURI, the Japanese version of CU, and appropriate and inappropriate terminology related to the therapeutic use of unapproved drugs. We also discuss the expected appearance of CU including its name. It is appropriate to target group/cohort patients and unapproved drugs in the late stage of development. It is also important to solve the problem of incentives for CUs of pharmaceutical companies that are rushing to obtain marketing approval. The UK's Early Access to Medicine Scheme has provided many suggestions. We believe that our opinion can contribute to WHO's efforts to resolve the confusion and promote research ethics preparedness in health emergencies., Competing Interests: None, (Copyright © Japan Medical Association.)

• The use of state-of-the-art sequencing and reverse genetics can reduce the development time of conventional vaccines during epidemics. • The platform, adjuvant(s), form of administration, age, and pre-existing cross-reactive immunity essentially determine the safety of a vaccine. • Vaccine-resistant variants might emerge, meaning that COVID-19 vaccines may need an update. • Vaccination needs to achieve sufficient equality between all countries for the world to return to a pre-pandemic status. COVID-19 pandemic has resulted in millions of deaths and a social-economic crisis. A worldwide effort was made to develop efficient vaccines for this disease. A vaccine should produce immune responses with specific and neutralizing antibodies, and without harmful effects such as the antibody-dependent enhancement that may be associated with severe acute respiratory syndrome. Vaccine design involves the selection of platforms that includes viral, viral-vector, protein, nucleic acid, or trained immunity-based strategies. Its development initiates at a pre-clinical stage, followed by clinical trials when successful. Only if clinical trials show no significant evidence of safety concerns, vaccines can be manufactured, stored, and distributed to immunize the population. So far, regulatory authorities from many countries have approved nine vaccines with phase 3 results. In the current pandemic, a paradigm for the COVID-19 vaccine development has arisen, as many challenges must be overcome. Mass-production and cold-chain storage to immunize large human populations should be feasible and fast, and a combination of different vaccines may boost logistics and immunization. In silico trials is an emerging and innovative field that can be applied to predict and simulate immune, molecular, clinical, and epidemiological outcomes of vaccines to refine, reduce, and partially replace steps in vaccine development. Vaccine-resistant variants of SARS-CoV-2 might emerge, leading to the necessity of updates. A globally fair vaccine distribution system must prevail over vaccine nationalism for the world to return to its pre-pandemic status. [ABSTRACT FROM AUTHOR]

Two major legislative actions since 2015, the 21st Century Cures Act of 2016 and the U.S. Food and Drug Administration (FDA) Reauthorization Act of 2017, contain significant provisions that potentially streamline drug development times, and by extension, may reduce costs. Evidence suggests, however, that development times have already been significantly affected by previous legislation and FDA programs, through accelerated approval pathways and adoption of more flexible definitions of clinical evidence of efficacy. The COVID-19 pandemic is pushing researchers and commercial entities to further test the limits of drug and vaccine development times and approvals, at an as yet unknown level of risk to patients. COVID-19 drug and vaccine trials are even now making use of accelerated drug approval programs, blended trials, and adaptive trial design to accelerate approval of therapeutics in the pandemic., (© 2020 The Author.)

The COVID-19 (coronavirus disease-2019) pandemic has presented unprecedented challenges to regulatory organizations, the biotech and pharmaceutical industry, and the publishing industry. This Translational Perspectives paper attempts to highlight some of the challenges and perils of moving extraordinarily fast in an effort to save human lives in the midst of a global pandemic. As with the development of all new therapeutic approaches, it will take time to assess the risks and benefits of developing new therapies at "warp speed"., (© 2020 The Author.)

To drive a totally implantable artificial heart for a long period with transcutaneous energy transmission, it is necessary that the temperature rise of devices implanted inside the human body is minimized. In this paper we study the properties of a transcutaneous DC-DC converter which transfers energy from an external source to a vibrating flow pump within the body, The temperature rise of the internal rectifying circuit has been rectified by as much as 30% to 50% by employing synchronous rectifiers rather than Schottky diodes, In addition, we have investigated a method for controlling the vibrating flow pump (VFP). This pump would be a constituent part of a totally implantable artificial heart. Also, the use and current limitation of an implanted rechargeable battery for emergency use is discussed. [ABSTRACT FROM PUBLISHER]