Artificial intelligence for diagnostic and prognostic neuroimaging in dementia: a systematic review

Introduction: Artificial intelligence (AI) and neuroimaging offer new opportunities for diagnosis and prognosis of dementia. Methods: We systematically reviewed studies reporting AI for neuroimaging in diagnosis and/or prognosis of cognitive neurodegenerative diseases. Results: A total of 255 studies were identified. Most studies relied on the Alzheimer's Disease Neuroimaging Initiative dataset. Algorithmic classifiers were the most commonly used AI method (48%) and discriminative models performed best for differentiating Alzheimer's disease from controls. The accuracy of algorithms varied with the patient cohort, imaging modalities, and stratifiers used. Few studies performed validation in an independent cohort. Discussion: The literature has several methodological limitations including lack of sufficient algorithm development descriptions and standard definitions. We make recommendations to improve model validation including addressing key clinical questions, providing sufficient description of AI methods and validating findings in independent datasets. Collaborative approaches between experts in AI and medicine will help achieve the promising potential of AI tools in practice. Highlights: There has been a rapid expansion in the use of machine learning for diagnosis and prognosis in neurodegenerative disease Most studies (71%) relied on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset with no other individual dataset used more than five times There has been a recent rise in the use of more complex discriminative models (e.g., neural networks) that performed better than other classifiers for classification of AD vs healthy controls We make recommendations to address methodological considerations, addressing key clinical questions, and validation We also make recommendations for the field more broadly to standardize outcome measures, address gaps in the literature, and monitor sources of bias

Performance of ChatGPT on the Situational Judgement Test—A Professional Dilemmas–Based Examination for Doctors in the United Kingdom

BackgroundChatGPT is a large language model that has performed well on professional examinations in the fields of medicine, law, and business. However, it is unclear how ChatGPT would perform on an examination assessing professionalism and situational judgement for doctors. ObjectiveWe evaluated the performance of ChatGPT on the Situational Judgement Test (SJT): a national examination taken by all final-year medical students in the United Kingdom. This examination is designed to assess attributes such as communication, teamwork, patient safety, prioritization skills, professionalism, and ethics. MethodsAll questions from the UK Foundation Programme Office’s (UKFPO’s) 2023 SJT practice examination were inputted into ChatGPT. For each question, ChatGPT’s answers and rationales were recorded and assessed on the basis of the official UK Foundation Programme Office scoring template. Questions were categorized into domains of Good Medical Practice on the basis of the domains referenced in the rationales provided in the scoring sheet. Questions without clear domain links were screened by reviewers and assigned one or multiple domains. ChatGPT's overall performance, as well as its performance across the domains of Good Medical Practice, was evaluated. ResultsOverall, ChatGPT performed well, scoring 76% on the SJT but scoring full marks on only a few questions (9%), which may reflect possible flaws in ChatGPT’s situational judgement or inconsistencies in the reasoning across questions (or both) in the examination itself. ChatGPT demonstrated consistent performance across the 4 outlined domains in Good Medical Practice for doctors. ConclusionsFurther research is needed to understand the potential applications of large language models, such as ChatGPT, in medical education for standardizing questions and providing consistent rationales for examinations assessing professionalism and ethics

Allergen immunotherapy for respiratory allergy: Quality appraisal of observational comparative effectiveness studies using the REal Life Evidence AssessmeNt Tool. An EAACI methodology committee analysis

Background Observational comparative effectiveness studies in allergen immunotherapy (AIT) represent an important evidence source answering research questions that can be challenging to obtain from randomized controlled trials (RCTs), such as long-term benefits of AIT, the effects on asthma prevention and the onset of new allergen sensitizations. However, observational studies are prone to several sources of bias, which limit their reliability. The REal Life Evidence AssessmeNt Tool (RELEVANT) was recently developed to assist in quality appraisal of observational comparative research to enable identification of useful nonrandomized studies to be considered within guideline development. Objective To systematically appraise the quality of published observational comparative AIT studies using RELEVANT. Methods Observational studies comparing AIT to pharmacotherapy for respiratory allergies, assessing as outcome measures reduction of symptoms and/or medication use reduction, were retrieved by computerized bibliographic searches. According to RELEVANT, a failure to meet any one of primary items (background, design, measures, analysis, results, discussion/interpretation, and conflict of interest) represents a critical flaw, significantly undermining the validity of the study results. Results The 14 studies identified supported the benefit of AIT in real-life, which persists after treatment discontinuation. However, none of them met all the 7 primary RELEVANT criteria. The main defects were reported in the design (28.6% of studies), measures and analysis (64.3% of studies), and results (78.6% of studies) items, due to selection bias and lack of methods for adjusting controls. Half of the studies did not report on conflict of interest. Conclusion There is a need for more robust observational research in AIT. RELEVANT appears as an easy-to-use and sensitive tool for quality appraisal in AIT studies

Biologics in severe asthma : the role of real-world evidence from registries

Funding Information: Conflict of interest: G. Paoletti reports no conflict of interest. J. Pepys reports no conflict of interest. M. Casini reports no conflict of interest. D. Di Bona reports no conflict of interest. E. Heffler reports personal fees from AstraZeneca, Sanofi, Novartis, Teva, GSK, Circassia, Boehringer Ingelheim, Valeas, and Nestlè Purina, outside the submitted work. C.Y.Y. Goh reports no conflicts of interest. D.B. Price has board membership with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Viatris, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, and Thermofisher; consultancy agreements with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Viatris, Mundipharma Novartis, Pfizer, Teva Pharmaceuticals, and Theravance; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Viatris, Mundipharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, Theravance, and UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Viatris, Mundipharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, and Teva Pharmaceuticals; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Circassia, Mundipharma, Novartis, Teva Pharmaceuticals, and Thermofisher; funding for patient enrolment or completion of research from Novartis; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. G.W. Canonica has received grants and consultancy fees from A. Menarini, ALK-Abelló, Allergy Therapeutics, AstraZeneca-Medimmune, Boehringer Ingelheim, Chiesi Farmaceutici, Genentech, Guidotti-Malesci, GlaxoSmithKline, Hal Allergy, Merck Sharp & Dohme, Mundipharma, Novartis, Orion, Sanofi-Aventis, Sanofi Genzyme/Regeneron, Stallergenes Greer, Uriach Pharma, Teva, Valeas and Vifor Pharma. Funding Information: To overcome the aforementioned limitations, the International Severe Asthma Registry (ISAR) was created [77–79]. ISAR (www.isaregistries.org) is the first global adult severe asthma registry aiming to achieve sufficient statistical power to answer important research questions, and to standardise data, making them comparable across countries and regions. The global reach of ISAR is achieved by the already established collaboration with 25 countries, including national or regional registries from Europe, plus registries from the Americas, Asia, the Middle East and the Australasian Severe Asthma Web-based Database registry of Australia, New Zealand and Singapore [78]. ISAR’s research is overseen by the ISAR steering committee (ISC), consisting of global severe asthma experts, and is governed by the Respiratory Effectiveness Group via the Anonymised Data Ethics and Protocol Transparency committee [78]. ISAR is cofunded by Optimum Patient Care Global and AstraZeneca; however, ISAR is open to independent projects not funded by AstraZeneca. Participating countries may also have multiple additional sources of funding. Core variables for standardised data collection were derived from a modified Delphi process [79]; additional variables are also collected from some countries to assess patient safety and the impact of steroid reduction. Prospective data collection for the ISAR registry was initiated in 2018 in Italy, the United States, South Korea (www.severeasthmawg.com) and the United Kingdom (UK) to better standardise data fields, increase the accuracy of cross-country comparisons and reduce any data incongruence in datasets [80].Peer reviewedPublisher PD

Biologics and airway remodeling in severe asthma

Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction. This highlights the need to distinguish a "fixed" airflow obstruction due to structural changes unresponsive to current therapies, from a "reversible" one as demonstrated by lung function normalization during biological therapies not previously obtained even with high-dose systemic glucocorticoids. The mechanisms by which exposure to environmental factors initiates the inflammatory responses that trigger airway remodeling are still incompletely understood. Alarmins represent epithelial-derived cytokines that initiate immunologic events leading to inflammatory airway remodeling. Biological therapies can improve airflow obstruction by addressing these airway inflammatory changes. In addition, biologics might prevent and possibly even revert "fixed" remodeling due to structural changes. Hence, it appears clinically important to separate the therapeutic effects (early and late) of biologics as a new paradigm to evaluate the effects of these drugs and future treatments on airway remodeling in severe asthma

Short-Term Adverse Events and Antibody Response to the BNT162b2 SARS-CoV-2 Vaccine in 4156 Health Care Professionals

Short-term adverse events are common following the BNT162b2 vaccine for SARS-Cov-2 and have been possibly associated with IgG response. We aimed to determine the incidence of adverse reactions to the vaccine and the impact on IgG response. Our study included 4156 health-care professionals who received two doses of the BNT162b2 vaccine 21 days apart and obtained 6113 online questionnaires inquiring about adverse events. The serum response was tested in 2765 subjects 10 days after the second dose. Adverse events, most frequently a local reaction at the site of injection, were reported by 39% of subjects. Multivariate analysis showed that female sex (odds ratio—OR—1.95; 95% confidence interval—CI—1.74–2.19; p < 0.001), younger age (OR 0.98 per year, p < 0.001), second dose of vaccine (OR 1.36, p < 0.001), and previous COVID-19 infection (OR 1.41, p < 0.001) were independently associated with adverse events. IgG response was significantly higher in subjects with adverse events (1110 AU/mL—IQR 345-1630 vs. 386 AU/mL, IQR 261-1350, p < 0.0001), and the association was more pronounced in subjects experiencing myalgia, fever, and lymphadenopathy. We demonstrate that a more pronounced IgG response is associated with specific adverse events, and these are commonly reported by health care professionals after the BNT162b2 vaccine for SARS-Cov-2

Low-pH Cola Beverages Do Not Affect Women's Iron Absorption from a Vegetarian Meal

Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11–54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation

Antigen-induced B cell apoptosis is independent of complement C4

Deficiencies in early complement components are associated with the development of systemic lupus erythematosus (SLE) and therefore early complement components have been proposed to influence B lymphocyte activation and tolerance induction. A defect in apoptosis is a potential mechanism for breaking of peripheral B cell tolerance, and we hypothesized that the lack of the early complement component C4 could initiate autoimmunity through a defect in peripheral B lymphocyte apoptosis. Previous studies have shown that injection of a high dose of soluble antigen, during an established primary immune response, induces massive apoptotic death in germinal centre B cells. Here, we tested if the antigen-induced apoptosis within germinal centres is influenced by early complement components by comparing complement C4-deficient mice with C57BL/6 wild-type mice. We demonstrate that after the application of a high dose of soluble antigen in wild-type mice, antibody levels declined temporarily but were restored almost completely after a week. However, after antigen-induced apoptosis, B cell memory was severely limited. Interestingly, no difference was observed between wild-type and complement C4-deficient animals in the number of apoptotic cells, restoration of antibody levels and memory response