FDA CAUGHT IN POLITICAL CROSSFIRE

FDA's oversight of medical devices and diagnostics has put it in the hot seat for shortages of critical products for protecting medical personnel and for providing fast and accurate public testing for COVID infection. The result is that the White House has delayed in selecting an FDA commissioner, even though federal rules require Woodcock to vacate her acting position by mid-November unless the administration nominates a new commissioner, permitting her to continue on during the Senate confirmation process. The approval decision by CDER officials was blasted by members of Congress, the medical community and even some patient groups, but justified by the reviewers as likely to provide some benefit to some patients who lacked any alternative treatment for this devastating disease.

BIDEN SEEKS ADDED FUNDING FOR RESEARCH, DISEASE TRACKING

To better prepare for the next pandemic, the White House seeks a significant increase in discretionary funding for the Centers for Disease Control and Prevention (CDC), proposing a $1.6 billion increase to an $8.7 billion budget able to modernize data collection and boost support for local health departments. ARPA-H initially would focus on cancer, diabetes and Alzheimer's disease and is modeled after the military's Defense Advanced Research Projects Agency (DARPA), with project funding decisions made by program managers, as opposed to the peer-review process of NIH research institutes. In addition to funding genomic sequencing capacity on the state and federal level, the new program would build a National Bioinformatics Infrastructure throughout the public health system.

Looking in the Rearview Mirror and to the Road Ahead on Dementia & Living Well

The number of Americans living with Alzheimer's and all other dementias continues to increase. Most of them will need long-term and community-based services as the disease progresses. While medical research is making advances, there is more work to be done to ensure that every person receives care that is person-centered and allows them to live with dignity and respect.

EUROPE SEEKING CLARITY IN ADVANCED TRIALS

EU officials acknowledge that the trial landscape in response to the pandemic has been fragmented, with a multitude of small, national trials, struggling to generate robust and actionable clinical data, with great duplication of efforts and direct competition for shared resources and participant populations. The European drug industry worked on complex clinical trials in 2020 with researchers in the European Organization for Research into Treatments for Cancer and specialists in the Association of Clinical Research Organizations, as well as with the European Union's Clinical Trial Expert Group, composed of national health ministry officials. [...]the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) is developing guidelines on Adaptive Clinical Trials with a timeline of 2023, and on Good Clinical Practice Renovation to address the increasing diversity of clinical trial designs and data sources.

DIAGNOSIS OF MEDICAL CONDITIONS IN PATIENTS USING MACHINE LEARNING MODELS

A variety of patient care and intelligent health systems can benefit from the implementation of artificial intelligence as a tool to aid caregivers. Machine learning and deep learning are two types of AI that are increasingly being used in the medical industry. Artificial intelligence methods require a large amount of clinical data from a range of imaging modalities for correct disease diagnosis. In addition, AI has greatly enhanced the quality of hospital stays, allowing patients to be released sooner and complete their recoveries at home. This article aims to provide the information on the field of AI subset i.e., machine learning-based disease detection with information that will aid them in making better decision making. This helps the researchers to classify the medical conditions in patients with a prominent dataset.

Analysis: FDA's COVID-19 Accelerated Pathways

Current FDA programs to accelerate access In order to accelerate the product approval process, four regulatory programs currently exist to reduce development and review times for products that address unmet medical needs for the treatment of serious or life-threatening conditions. In May 2014, FDA issued a Final Guidance for Industry entitled, "Expedited Programs for Serious Conditions-Drugs and Biologics" which addresses fast track designation, breakthrough therapy designation, priority review designation and accelerated approval.3 In addition to this guidance document, under section 564 of the FD&C Act, 21 U.S.C. 360bbb3, in a situation where the Secretary of Health and Human Services (HHS) issues a declaration of emergency or threat justifying authorization of emergency use for a product caused by chemical, biological, radiological or nuclear (CBRN) agents, as well as an infectious disease, the Commissioner of the FDA may authorize an EUA of an unapproved product or an unapproved use of an approved product. In January 2017, the "Emergency Use Authorization of Medical Products and Related Authorities" guidance was finalized.4 Fast Track designation Section 112 of the Food and Drug Administration Modernization Act of 1997 (FDAMA), entitled "Expediting Study and Approval of Fast Track Drugs," mandates the facilitation of the development and processes to expedite review of therapeutics intended to treat serious or life-threatening conditions presenting with unmet medical needs. [...]a two-tiered system of review times, Standard Review and Priority Review was created.

Frontrunners in Organ-on-a-Chip

Advances in tissue engineering, microfabrication, and biocompatible microfluidic chambers alongside the governmental (2) and regulatory (3) appetite to seek animal-free innovations in the drug development process has fuelled further interest and investment in this marketplace. According to market research, the global O°C market is forecast to be worth US$388 million (€354 million) by 2028 increasing from US$82 million (€75 million) in 2023, with a compound average growth of 36.4% from 2023 to 2028 (4). In March 2022, Lyon-based NETRI, attracted €8 million series A funding to help develop its novel high throughput (HT) compartmentalized microfluidic brain-on-a-chip and skin-on-a-chip technology for use by the pharma and cosmetic industry (15). Global Organ-onChip Market Size, Share, Trends, COVID-19 Impact and Growth Analysis ReportSegmented by Type (Heart-on-chip, Humanon-chip, Intestine-on-chip, Kidney-on-chip, Liver-on-chip and Lung-on-chip), Application and Region (North America, Europe, AsiaPacific, Latin America, Middle East and Africa)-Industry Forecast from 2023 to 2028.

A Watchful Eye on Pharma

Yet, it is also important to remember that bio/pharma companies are not solely focused on COVID-19, even though a significant concerted effort has been made by the industry overall in this area over the past year. "In the last five years we have seen an increase in approvals of innovative medicines at a rate more than double what it was a decade ago," said Mike Ward, global head of Thought Leadership, Life Sciences and Healthcare, Clarivate, in a press release (4). [...]increased collaboration throughout the industry has proven to be invaluable during the COVID-19 pandemic.

Ultra-sensitive Detection of Alzheimer's Biosmarkers Using Plasmonic Optical Fiber Sensors

The emergence of the Covid-19 pandemic has drawn great attention to vulnerable people affected by major diseases. Among them, Alzheimer's disease (AD) is the most prevalent disease. However, a long-standing challenge is to achieve early diagnosis of AD by detecting biomarkers such as amyloid beta (Aβ42), thus avoiding the labor of specialized hospital personnel and the high cost of imaging examinations using positron emission tomography. In this paper, we report a straightforward approach to realize a non-invasive lab-around fiber (LaF) optical sensor for AD biomarker detection, which is based on a tilted fiber Bragg grating (TFBG) combined with a nanoscale metallic thin film. We successfully demonstrated the detection of Aβ42 in complex biological matrices with a detection limit of 5 pg/mL. Therefore, our TFBG-SPR biosensor platform enables large-scale early disease screening and has great potential for clinical applications in early AD diagnosis. © 2022 IEEE.

Enhance-Net: An Approach to Boost the Performance of Deep Learning Model Based on Real-Time Medical Images

Real-time medical image classification is a complex problem in the world. Using IoT technology in medical applications assures that the healthcare sectors improve the quality of treatment while lowering costs via automation and resource optimization. Deep learning is critical in categorizing medical images, which is accomplished by artificial intelligence. Deep learning algorithms allow radiologists and orthopaedic surgeons to make their life easier by providing them with quicker and more accurate findings in real time. Despite this, the classic deep learning technique has hit its performance limits. For these reasons, in this research, we examine alternative enhancement strategies to raise the performance of deep neural networks to provide an optimal solution known as Enhance-Net. It is possible to classify the experiment into six distinct stages. Champion-Net was chosen as a deep learning model from a pool of benchmark deep learning models (EfficientNet: B0, MobileNet, ResNet-18, and VGG-19). This stage helps choose the optimal model. In the second step, Champion-Net was tested with various resolutions. This stage helps conclude dataset resolution and improves Champion-Net performance. The next stage extracts green channel data. In the fourth step, Champion-Net combines with image enhancement algorithms CLAHE, HEF, and UM. This phase serves to improve Enhance-performance. The next stage compares the Enhance-Net findings to the lightness order error (LoE). In Enhance-Net models, the current study combines image enhancement and green channel with Champion-Net. In the final step, radiologists and orthopaedic surgeons use the trained model for real-time medical image prediction. The study effort uses the musculoskeletal radiograph-bone classification (MURA-BC) dataset. Classification accuracy of Enhance-Net was determined for the train and test datasets. These models obtained 98.02 percent, 94.79 percent, and 94.61 percent accuracy, respectively. The 96.74% accuracy was achieved during real-time testing with the unseen dataset.

Football, dementia, . . . and other stories

The increased risk of dementia didn't apply to goalkeepers, which is compatible with the hypothesis that repeated head impacts sustained when heading the ball are part of the cause (Lancet doi:10.1016/S2468-2667(23)00027-0). Mental illness and septic shock A nationwide study of 200 000 adults admitted to intensive care units in French hospitals with septic shock reveals that those with severe mental illness (schizophrenia, bipolar disorder, or major depressive disorder) have substantially lower case fatality, assessed at 30, 90, and 365 days after admission, than controls matched for age, sex, and social deprivation. For vascular dementia, the most consistent precursors were an abnormal electrocardiogram, cardiac dysrhythmias, cerebrovascular disease, non-epithelial skin cancer, depression, and hearing loss (Ann Neurol doi:10.1002/ana.26584).

2021 American Society of Hematology: Program Highlights

Throughout the meeting, a number of awards and lectureships based upon the awardees' work were presented, including: P Wallace H. Coulter Award for Lifetime Achievement in Hematology to Harvey F. Lodish, PhD, professor of biology and biomedical engineering at Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, for his key contributions and studies of the structure and biogenesis of red blood cells;P Ernest Beutler Basic Science Award to Margaret A. Shipp, MD, director of the Dana-Farber/Harvard Cancer Center Lymphoma Research Program, for her work on the genetic basis of PD-1-mediated immune evasion in Hodgkin lymphoma and primary mediastinal B-cell lymphoma;and P Ernest Beutler Translational/Clinical Award to Stephen M. Ansell, MD, PhD, chair of the Mayo Clinic Lymphoma Group, for his work in understanding the tumor microenvironment in lymphomas, including PD-1 blockade. A focus on diversity, equity, and inclusion included informative sessions on barriers to clinical trial design and enrollment, availability of transplantation to minority patients, race and science, and lessons from a global pandemic. Topics of s in the plenary session included: P SARS-CoV-2 and the pathologic mechanism of prothrombotic events caused by the virus;P Studies of the molecular landscape of TP53-mutated leukemic transformation in myeloproliferative neoplasms;P Primary analysis of the ZUMA-7 study (NCT03391466): a phase 3 randomized trial of axicabtagene ciloleucel (axi-cel) versus standardof-care therapy in patients with relapsed/refractory large B-cell lymphoma;P Efficacy and safety of fitusiran, an siRNA therapeutic, in a multicenter phase 3 study in individuals with hemophilia A or B, with inhibitors;P Decreased risk of Alzheimer disease in patients with clonal hematopoiesis of indeterminate potential;and P Profiling of circulating tumor DNA for noninvasive disease detection, risk stratification, and minimal residual disease monitoring in patients with central nervous system lymphoma.

Pediatric Asthma: Where Has Montelukast Gone?

At its introduction in the management of pediatric asthma, montelukast was regarded as a potentially revolutionary drug due to its mechanism of action and easy clinical applicability. Nevertheless, its use in daily practice and evidence from clinical trials have shown that, rather than a radical change in the approach to asthmatic children, montelukast more likely represents a second-line medication that is useful when inhaled steroids alone fail in providing adequate symptom control. Furthermore, increasingly reported side effects have raised concerns regarding its safety. In the last decade, several studies have tried to better define the strengths and drawbacks of montelukast both in preschool wheezing and school-age asthma. The present review summarizes the literature published on this topic since 2010, highlighting the often-controversial results and the unanswered questions regarding the role of montelukast in pediatric asthma. Moreover, advances in the understanding of the mechanisms of action of montelukast are reported. The main finding emerging from the present analysis is that montelukast application is likely to be useful in a subset of asthmatic children rather than in large groups of patients. Future studies should focus on the identification of biomarkers able to predict which patients will benefit from montelukast to achieve a more tailored prescription.

Secure and Efficient Smart Healthcare System Based on Federated Learning

The rapid development of smart healthcare system in the Internet of Things (IoT) has made the early detection of many chronic diseases more convenient, quick, and economical. However, when healthcare organizations collect users' health data through deployed IoT devices, there are issues of compromising users' privacy. In view of this situation, this paper introduces federated learning technology to solve the problem of data security. In this paper, we consider the two main problems of federated learning applications in IoT smart healthcare system: (1) how to reduce the time overhead of system running and (2) how to authenticate that the user device uploading data is deployed by the system itself. To solve the above problems, we propose the first federated learning scheme based on full dynamic secret sharing. First, we use a two-mask protocol to keep the user's local model parameters confidential during federated learning. Then, based on homogeneous linear recursive equation, homomorphic hash function, and elliptic curve cryptosystem, the full dynamic secret sharing and user identity authentication are realized. In addition, our scheme allows users to join or quit during training. Finally, we have carried out simulation test on this scheme. The experimental results show that the efficiency of our scheme is improved by about 60% on average in the case of no user dropping and by about 30% in the case of some users dropping.

Measuring Quality of Life in Residential Aged Care Using the EQ-5D-5L: A Cross-Sectional Study on the Impact of Cognition Level and Proxy Perspective on Interrater Agreement

Quality of life (QoL) is an important outcome in aged care, but self-report is not always possible due to the high prevalence of cognitive impairment in older aged care residents. This study aims to assess the impact of family member proxy perspective (proxy-proxy or proxy-person) on interrater agreement with resident self-report by different cognition levels. The influence of proxy perspective and cognition level is a significant gap in the extant literature which this study seeks to address. A cross-sectional study was undertaken with residents classified into cognition subgroups according to the Mini Mental State Examination. Residents completed the self-report EQ-5D-5L, a well-established generic measure of health-related quality of life (HRQoL). Family member proxies completed EQ-5D-5L proxy version 1 (proxy-proxy perspective, where the proxy responds based on their own opinions) and proxy version 2 (proxy-person perspective, where the proxy responds as they believe the person would). Interrater agreement was assessed using the concordance correlation coefficient (CCC) for utility scores and the weighted kappa for dimension-level responses. Sixty-three residents (n = 22 no cognitive impairment, n = 27 mild impairment, and n = 14 moderate impairment) and proxies participated. EQ-5D-5L utility scores were lower for proxies compared with residents (self-report = 0.522, proxy-proxy = 0.299, and proxy-person = 0.408). Interrater agreement with self-report was higher for proxy-person (CCC = 0.691) than for proxy-proxy (CCC = 0.609). Agreement at the dimension level was higher for more easily observable dimensions, such as mobility, compared to less observable dimensions, such as anxiety/depression. Resident self-reported and proxy family member-reported HRQoL assessments, using the EQ-5D-5L, are different but may be more closely aligned when the proxy is specifically guided to respond from the person's perspective. Further research is needed to address the impact of divergences in self-report and proxy-report ratings of HRQoL for quality assessment and economic evaluation in aged care.

Low-Dimensional Compounds Containing Bioactive Ligands. Part XX: Crystal Structures, Cytotoxic, Antimicrobial Activities and DNA/BSA Binding of Oligonuclear Zinc Complexes with Halogen Derivatives of 8-Hydroxyquinoline

Two tetranuclear [Zn4Cl2(ClQ)6]·2DMF (1) and [Zn4Cl2(ClQ)6(H2O)2]·4DMF (2), as well as three dinuclear [Zn2(ClQ)3(HClQ)3]I3 (3), [Zn2(dClQ)2(H2O)6(SO4)] (4) and [Zn2(dBrQ)2(H2O)6(SO4)] (5), complexes (HClQ = 5-chloro-8-hydroxyquinoline, HdClQ = 5,7-dichloro-8-hydroxyquinoline and HdBrQ = 5,7-dibromo-8-hydroxyquinoline) were prepared as possible anticancer or antimicrobial agents and characterized by IR spectroscopy, elemental analysis and single crystal X-ray structure analysis. The stability of the complexes in solution was verified by NMR spectroscopy. Antiproliferative activity and selectivity of the prepared complexes were studied using in vitro MTT assay against the HeLa, A549, MCF-7, MDA-MB-231, HCT116 and Caco-2 cancer cell lines and on the Cos-7 non-cancerous cell line. The most sensitive to the tested complexes was Caco-2 cell line. Among the tested complexes, complex 3 showed the highest cytotoxicity against all cell lines. Unfortunately, all complexes showed only poor selectivity to normal cells, except for complex 5, which showed a certain level of selectivity. Antibacterial potential was observed for complex 5 only. Moreover, the DNA/BSA binding potential of complexes 1–3 was investigated by UV-vis and fluorescence spectroscopic methods.

Abdominal Pain in the Female Patient: Always Consider Your Differentials

Steadman, L., Coles, K., & Kopf, S. (2023). Abdominal pain in the female patient: Always consider your differentials. Pediatric Nursing, 49(1), 45-47.

Football, dementia, . . . and other stories

The increased risk of dementia didn't apply to goalkeepers, which is compatible with the hypothesis that repeated head impacts sustained when heading the ball are part of the cause (Lancet doi:10.1016/S2468-2667(23)00027-0). Mental illness and septic shock A nationwide study of 200 000 adults admitted to intensive care units in French hospitals with septic shock reveals that those with severe mental illness (schizophrenia, bipolar disorder, or major depressive disorder) have substantially lower case fatality, assessed at 30, 90, and 365 days after admission, than controls matched for age, sex, and social deprivation. For vascular dementia, the most consistent precursors were an abnormal electrocardiogram, cardiac dysrhythmias, cerebrovascular disease, non-epithelial skin cancer, depression, and hearing loss (Ann Neurol doi:10.1002/ana.26584).

Spike proteins . . . and other stories

Among 30 000 people whose dietary habits were assessed with food diaries, food frequency questionnaires, and interviews, adherence neither to conventional dietary recommendations nor to a modified Mediterranean diet was associated with subsequent likelihood of Alzheimer's disease or any other type of dementia (Neurology doi:10.1212/WNL.0000000000201336). Assessments of functional development at age of school entry and subsequent performance on tests of literacy and numeracy in the fourth year of primary school found no evidence that IVF led to an increased risk of developmental vulnerability or poorer educational outcomes (PLoS Med doi:10.1371/journal.pmed.1004148). Renal denervation for resistant hypertension A few weeks ago, Minerva noted a registry study showing that the modest fall in blood pressure induced by catheter based radio frequency renal nerve ablation was sustained over three years of follow-up.