Results Of Clinical Trials Research Articles

Characteristic of clinical trials related to traumatic brain injury registered on ClinicalTrials.gov over the past two decades (2004-2023).

The aim of this report is to provide a comprehensive overview of clinical trials and protocols related to traumatic brain injury over the past two decades. We collected information on clinical trials related to traumatic brain injury (TBI) from the ClinicalTrials.gov database, identified key categorical variables, and assessed their characteristics. A total of 367 TBI-related trials were identified for analysis. All identified trials were interventional clinical trials. Most trials were small-scale, with 75.2% enrolling 1-100 participants, and only about 20% were funded by industry or the National Institutes of Health (NIH). In most trials, participants were gender-neutral (96.5%), and the primary age group was adults and older adults (56.9%). Of all identified TBI trials, 78.2% were randomized, and 69.4% were blinded. Additionally, the primary purpose of 297 trials (80.9%) was treatment, with drug therapy as the most common intervention. A total of 153 trials (41.7%) were completed; however, only 58 trials submitted results to the registry. Furthermore, 81 trials (22.1%) were discontinued early, primarily due to recruitment problems. Clinical trials started between 2004 and 2013 reported a higher proportion of results compared with those started between 2014 and 2023 (35.1% vs. 11.1%, p < 0.001). In addition, between 2014 and 2023, there was an increase in trials for diagnostic purposes (2.4% vs. 6.5%, p < 0.001). Based on the data collected from the ClinicalTrials.gov, our study reveals that most clinical trials related to TBI focus on drug-related treatments, underreporting remains a significant concern, and greater emphasis should be placed on improving the publication and dissemination of clinical trial results.

Lipoprotein (a) is associated with increased risk of Abdominal Aortic Aneurysm.

Lipoprotein(a) (Lp(a)) is a circulating apolipoprotein B (ApoB) containing particle that has been observationally linked to atherosclerotic cardiovascular disease and is the target of emerging therapeutics. Recent work has highlighted the role of circulating lipoproteins in abdominal aortic aneurysm (AAA). We sought to triangulate human observational and genetic evidence to evaluate the role of Lp(a) in AAA. We tested the association between circulating levels of Lp(a) and clinically diagnosed abdominal aortic aneurysms while controlling for traditional AAA risk factors and levels of ApoB using logistic regression among 795 individuals with and 374,772 individuals without AAA in the UK Biobank (UKB). Multivariable Mendelian randomization (MVMR) was used to test for putatively causal associations between Lp(a) and AAA controlling for ApoB. Genetic instruments for Lp(a) and ApoB were created from genome-wide association studies (GWAS) of Lp(a) and ApoB comprising 335,796 and 418,505 UKB participants, respectively. The instruments were tested for association with AAA using data from a GWAS of 39,221 individuals with and 1,086,107 without AAA. Elevated Lp(a) levels were observationally associated with an increased risk of AAA (OR 1.04 per 10 nmol/L Lp(a); 95%CI 1.02-1.05; P<0.01). Clinically elevated Lp(a) levels (>150nmol/L) were likewise associated with an increased risk of AAA (OR 1.47; 95% CI 1.15-1.88; P < 0.01) when compared to individuals with Lp(a) levels <150nmol/L. MVMR confirmed a significant, ApoB-independent association between increased Lp(a) and increased risk of AAA (OR 1.13 per SD increase in Lp(a); 95%CI 1.02-1.24; P<0.02). Both observational and genetic analyses support an association between increased Lp(a) and AAA risk that is independent of ApoB. These findings suggest that Lp(a) may be a therapeutic target for AAA and drive the inclusion of AAA as an outcome in clinical trials of Lp(a) antagonists.

A - 81 Gender Bias in Collateral Informant Ratings of the Lawton &amp; Brody Instrumental Activities of Daily Living Scale Varies by Ethnolinguistic Group

Abstract Objective Building on our prior work showing that sociocultural factors influence the nature of one’s daily activities and the degree of assistance rendered once cognitive difficulties emerge, the present study aimed to examine gender differences in the frequency of abnormal IADLS ratings [Not Applicable (N/A), Requires Assistance (R/A), Dependent] in cognitively healthy older adults from different ethnic (Hispanic vs. Non-Hispanic) and linguistic (English vs. Spanish) groups. Method Baseline data from 1060 healthy older adults [Non-Hispanic English-speakers (NE) = 597; Hispanic English-speakers (HE) = 249; Hispanic Spanish-speakers (HS) = 214] 50–90 years of age enrolled in the Texas Alzheimer’s Research and Care Consortium were analyzed using univariate analyses of variance and multivariate chi-squares within each ethnolinguistic group. Results Women obtained significantly (p &amp;lt; 0.001) higher IADLS total scores (indicative of greater impairment) than men in each ethnolinguistic group. A significant difference (p &amp;lt; 0.01) was found between gender across the sample for items related to Food Preparation, Housekeeping, and Laundry, wherein 7–25% of all men vs. &amp;lt; 1% of all women received “N/A” ratings. Significantly more HE men vs. women also received “N/A” ratings for Finances (4:1) and Medications (7:1), while a similar trend was observed in the NH and HS groups but did not reach statistical significance. No participants received an “N/A” rating and no significant gender differences were observed for remaining IADLs. Conclusion(s) Obtained findings highlight considerable gender bias on the Lawton &amp; Brody IADLS in healthy older adults, which clearly limits the utility of this instrument in the provision of patient-centered neuropsychological services and may confound the interpretation of clinical trial outcomes.

Induced pluripotent stem cell therapies in heart failure treatment: ameta-analysis and systematic review.

Background: Heart failure (HF) causes over 266,400 deaths annually. Despite treatment advancements, HF mortality remains high. Induced pluripotent stem cells (iPSCs) offer promising new options. This review assesses iPSC-based treatments for HF.Method: the review included studies from PubMed, ScienceDirect and Web of Science.Results: Analysis of 25 studies with 553 animals showed a baseline ejection fraction (EF) of 39.2±8.9%. iPSC treatment significantly improved EF (MD=8.6, p<0.001) and fractional shortening (MD=6.38, p<0.001), and reduced ventricular remodeling without increasing arrhythmia risk.Conclusion: iPSC-based therapy improves heart function and reduces ventricular volumes in HF animal models, aligning with promising early clinical trial outcomes.

Analysis of Trends in the Use of Artificial Intelligence in Diagnosis and Treatment

AI in healthcare has improved, making diagnostics more accurate and increasing the effectiveness of treatments. The present study discusses the AI trends in diagnostic and therapeutic applications and focuses on the presented practical applications and their effects on patient care. The purpose of this particular review is to focus on the current developments in the implementation of AI in the field of health care, present main use cases and successes, as well as discuss about the issues and concerns in the topic at hand. Previous studies on AI in healthcare with specific consideration of diagnostic image analysis and interpretation, histology and molecular pathology, whole-genome sequencing, and therapeutic decision support are discussed. The selection criteria included papers with data gathered from real-life AI cases and quantitative findings. Study materials were obtained from e-journals, conference papers, and established online sources with descriptive analysis being done on the data collected. A summary of the findings revealed a number of highly impactful subcategories focused on the use of artificial intelligence diagnostic imaging, especially in radiology, pathology, and genomics. The AI applications used in the fields of operations and drug discovery revealed the ability to accurately predict clinical trial outcomes and to create effective treatments. First of all, AI can become a game changer in healthcare by enhancing diagnostics accuracy and treatment outcomes. The future research questions include further developing the methods that explain the AI models’ decisions, protecting the privacy of patient information, and reducing algorithmic bias for better fair healthcare for all. Therefore, better interactions between creators of AI and clinicians and regulatory authorities are pertinent to make sure that the full advantages of AI are realized in clinical practice to advance patient care.

Sex and gender reporting in UK emergency medicine trials from 2010 to 2023: a systematic review

BackgroundFemale participants are underrepresented in randomised control trials conducted in urgent care settings. Although sex and gender are frequently reported within demographic data, it is less common for primary outcomes...

Phage-specific antibodies: are they a hurdle for the success of phage therapy?

Phage therapy has attracted attention again owing to the increasing number of drug-resistant bacteria. Although the efficacy of phage therapy has been reported, numerous studies have indicated that the generation of phage-specific antibodies resulting from phage administration might have an impact on clinical outcomes. Phage-specific antibodies promote phage uptake by macrophages and contribute to their rapid clearance from the body. In addition, phage-specific neutralizing antibodies bind to the phages and diminish their antibacterial activity. Thus, phage-specific antibody production and its role in phage therapy have been analyzed both in vitro and in vivo. Strategies for prolonging the blood circulation time of phages have also been investigated. However, despite these efforts, the results of clinical trials are still inconsistent, and a consensus on whether phage-specific antibodies influence clinical outcomes has not yet been reached. In this review, we summarize the phage-specific antibody production during phage therapy. In addition, we introduce recently performed clinical trials and discuss whether phage-specific antibodies affect clinical outcomes and what we can do to further improve phage therapy regimens.

KRASG 12C-inhibitor-based combination therapies for pancreatic cancer: insights from drug screening.

Pancreatic ductal adenocarcinoma (PDAC) has limited treatment options, emphasizing the urgent need for effective therapies. The predominant driver in PDAC is mutated KRAS proto-oncogene, KRA, present in 90% of patients. The emergence of direct KRAS inhibitors presents a promising avenue for treatment, particularly those targeting the KRASG12C mutated allele, which show encouraging results in clinical trials. However, the development of resistance necessitates exploring potent combination therapies. Our objective was to identify effective KRASG12C-inhibitor combination therapies through unbiased drug screening. Results revealed synergistic effects with son of sevenless homolog 1 (SOS1) inhibitors, tyrosine-protein phosphatase non-receptor type 11 (PTPN11)/Src homology region 2 domain-containing phosphatase-2 (SHP2) inhibitors, and broad-spectrum multi-kinase inhibitors. Validation in a novel and unique KRASG12C-mutated patient-derived organoid model confirmed the described hits from the screening experiment. Our findings propose strategies to enhance KRASG12C-inhibitor efficacy, guiding clinical trial design and molecular tumor boards.

Data collection methods for patient-reported outcome measures in cancer randomised controlled trials: a protocol for a rapid scoping review

BackgroundThere are different modes and ways to assess patient-reported outcomes (PROs) in clinical trials. However, there is little systematic information on how often different modes of assessment (MOA) are used...

Myosin Isoform-Dependent Effect of Omecamtiv Mecarbil on the Regulation of Force Generation in Human Cardiac Muscle.

Omecamtiv mecarbil (OM) is a small molecule that has been shown to improve the function of the slow human ventricular myosin (MyHC) motor through a complex perturbation of the thin/thick filament regulatory state of the sarcomere mediated by binding to myosin allosteric sites coupled to inorganic phosphate (Pi) release. Here, myofibrils from samples of human left ventricle (β-slow MyHC-7) and left atrium (α-fast MyHC-6) from healthy donors were used to study the differential effects of μmolar [OM] on isometric force in relaxing conditions (pCa 9.0) and at maximal (pCa 4.5) or half-maximal (pCa 5.75) calcium activation, both under control conditions (15 °C; equimolar DMSO; contaminant inorganic phosphate [Pi] ~170 μM) and in the presence of 5 mM [Pi]. The activation state and OM concentration within the contractile lattice were rapidly altered by fast solution switching, demonstrating that the effect of OM was rapid and fully reversible with dose-dependent and myosin isoform-dependent features. In MyHC-7 ventricular myofibrils, OM increased submaximal and maximal Ca2+-activated isometric force with a complex dose-dependent effect peaking (40% increase) at 0.5 μM, whereas in MyHC-6 atrial myofibrils, it had no effect or-at concentrations above 5 µM-decreased the maximum Ca2+-activated force. In both ventricular and atrial myofibrils, OM strongly depressed the kinetics of force development and relaxation up to 90% at 10 μM [OM] and reduced the inhibition of force by inorganic phosphate. Interestingly, in the ventricle, but not in the atrium, OM induced a large dose-dependent Ca2+-independent force development and an increase in basal ATPase that were abolished by the presence of millimolar inorganic phosphate, consistent with the hypothesis that the widely reported Ca2+-sensitising effect of OM may be coupled to a change in the state of the thick filaments that resembles the on-off regulation of thin filaments by Ca2+. The complexity of this scenario may help to understand the disappointing results of clinical trials testing OM as inotropic support in systolic heart failure compared with currently available inotropic drugs that alter the calcium signalling cascade.

Approaches to anticancer therapy based on modulation of DNA methylation

Background. DNA methylation is a crucial mechanism of epigenetic regulation of transcription. Disturbances in DNA methylation mechanism are associated with various malignancies such as acute myeloid leukaemia, breast cancer, prostate cancer, etc. Influencing the functional status of DNA methyltransferases (DNMTs) enzymes and TET family proteins (TETs), which regulate DNA methylation and demethylation, is the basis of epigenetic anticancer therapy approach. In this review, we have considered the challenges and prospects of nucleoside and non-nucleoside inhibitors of DNMTs as well as TETs inhibitors. The results of clinical trials on the efficacy of DNMTs inhibitors used individually and as part of combination chemotherapy conducted over the last 15 years are also evaluated. Material and Methods. Sources were searched in PubMed, ScienceDirect, Web of Science, eLibrary, CyberLeninka. More than 700 publications were used in the analysis, but the review included mainly works of the last 10 years. A number of articles published earlier than 2015 were used for historical reference. Results. The review provides information on current advances in the development and study of epigenetically active compounds whose action is aimed at the regulation of DNA methylation. Data on the in vitro and in vivo effects of agents considered for use in the therapy of various malignancies are presented. In addition, the data of clinical trials of the most promising epigenetic modulators are presented.

Cost-effectiveness of ace inhibitors versus ARBs in heart failure management.

Heart failure is a chronic condition that imposes a significant burden on healthcare systems worldwide. Effective management is crucial for improving patient outcomes and reducing costs. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are widely used to manage heart failure by reducing cardiac strain and preventing disease progression. Despite their common use, ACE inhibitors and ARBs differ in mechanisms, cost, and potential side effects. ACE inhibitors have long been the standard treatment, while ARBs are often prescribed to patients intolerant to ACE inhibitors, particularly due to side effects like cough. Given these differences, evaluating the cost-effectiveness of these treatments is essential. This study compares the cost-effectiveness of ACE inhibitors and ARBs from a healthcare system perspective, considering both direct medical costs and health outcomes. A cost-effectiveness analysis was conducted using a decision-analytic Markov model to simulate heart failure progression in a hypothetical cohort. Data inputs included clinical trial outcomes, real-world effectiveness data, direct medical costs (medications, hospitalizations, monitoring), and utility values for quality of life. The primary outcome measures were the cost per quality-adjusted life year gained and the incremental cost-effectiveness ratio. Sensitivity analyses tested the robustness of results, and subgroup analyses were conducted based on age and disease severity. The base-case analysis showed that ACE inhibitors were associated with lower overall costs and slightly higher quality-adjusted life years than ARBs. Sensitivity analyses revealed that variations in key parameters, such as transition probabilities, mortality rates, and healthcare expenses, had limited impact on the overall cost-effectiveness conclusions. Subgroup analyses indicated that ACE inhibitors and ARBs exhibited similar cost-effectiveness profiles for patients aged <65 and ≥65 years. However, among patients with severe heart failure, ARBs demonstrated a higher incremental cost-effectiveness ratio compared with ACE inhibitors, suggesting reduced cost-effectiveness in this subgroup. ACE inhibitors are likely a more cost-effective option for managing heart failure than ARBs, particularly from a healthcare system perspective. The findings underscore the importance of tailoring treatment decisions to individual patient factors, preferences, and clinical conditions, providing valuable insights for healthcare policy and practice, particularly regarding cost-effectiveness across patient subgroups.

Anything is better than nothing’: exploring attitudes towards novel therapies in leukodystrophy clinical trials

Background/AimLeukodystrophies comprise a group of genetic white matter disorders that lead to progressive motor and cognitive impairment. Recent development of novel therapies has led to an increase in clinical trials for leukodystrophies. To enable recruitment of individuals with a leukodystrophy into clinical trials, clinical trial acceptability should be ascertained. We sought therefore, to identify the motivations for and barriers to clinical trial participation in addition to clinical trial features that may be of concern to individuals with a leukodystrophy and/or their carers.MethodsAdults with a leukodystrophy and parents/carers of individuals with a leukodystrophy were recruited through the Australian Leukodystrophy Registry and through online advertisements. Qualitative semi-structured interviews were used to explore participants views on what clinical trials involve, the perceived risks and benefits of clinical trials, their desire to participate in clinical trials and their personal experience with leukodystrophy. Thematic analysis of data was performed with co-coding of interview transcripts.Results5 interviews were held with parents of children with leukodystrophy, 4 with parents of adults with leukodystrophy and 3 with adults diagnosed with leukodystrophy. Motivations for clinical trial enrolment include access to potentially lifesaving novel treatments and improved prognostic outcomes. Participants were concerned about adverse clinical trial outcomes, including side effects and exacerbation of illness. Despite this, majority of participants were willing to try anything in clinical trials, demonstrating a high tolerance for first in human trials and trials utilising invasive treatment options.ConclusionsInterviewees communicated a strong desire to participate in interventional clinical trials involving novel therapies. To support enrolment into future leukodystrophy clinical trials we suggest the provision of transparent information regarding clinical trial treatments, consideration of alternative trial control measures, and inclusion of treating clinicians in the trial recruitment process. Clinicians play an integral role in initiating transparent conversations regarding trial risks and adverse outcomes.

The Effect of Chia Seed on Blood Pressure, Body Composition, and Glycemic Control: A GRADE-Assessed Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

Numerous studies have demonstrated the positive effects on metabolic factors of consuming chia seeds. However, the results of clinical trials have been inconsistent. The aim of this study was to conduct a systematic review and meta-analysis of available randomized controlled trials to explore the effects of chia seed consumption on body weight (BW), body composition, blood pressure, and glycemic control. A comprehensive search was conducted on the Scopus, PubMed, Medline via Ovid, ISI Web of Science, and Scholar Google databases up to August 2023. The outcomes of interest included systolic blood pressure (SBP), diastolic blood pressure (DBP), BW, body mass index (BMI), body fat percentage, waist circumference (WC), fasting blood glucose (FBG), and hemoglobin A1c (HbA1c). Weighted mean difference (WMD) and 95% CIs were used to determine the effect size. A total of 8 eligible studies were included in the analysis. The findings revealed a significant reduction in SBP (WMD: -7.19 mmHg; 95% CI, -10.63 to -3.73; P < .001) and DBP (WMD: -6.04 mmHg, 95% CI, -9.58 to -2.49; P = .001). However, no significant effects were observed on BW, body fat percentage, WC, BMI, FBG, and HbA1c. Subgroup analysis indicated that the effect of chia seed on SBP was significant in participants with a baseline SBP of less than 140 mmHg, but the effect was not dependent on the administered dose. Chia seed consumption has positive effects on SBP and DBP but does not significantly impact BW, body composition, or glycemic parameters. However, the limited amount of data from included studies should be considered as a limitation while interpreting these findings. PROSPERO registration no. CRD42023462575.

Update on the management of ductal carcinoma in situ of the breast: current approach and future perspectives.

The standard treatment for ductal carcinoma in situ became well established through the results of several valuable clinical trials, and its therapeutic benefits have now come to be taken for granted. Ductal carcinoma in situ has an extremely good prognosis with the current treatment approach, with a 10-year breast cancer-specific survival rate of 97-98%. According to one retrospective cohort study, the breast cancer-specific survival rate of patients with low-grade ductal carcinoma in situ does not differ significantly between patients undergoing and not undergoing surgery. Some patients with ductal carcinoma in situ are not at a risk of progression to invasive cancer, but the predictors of such progression have not yet been clearly identified. Therefore, the same therapeutic strategies have been used to treat ductal carcinoma in situ and under the assumption that they have risks of invasive breast cancer, and a well-balanced risk/benefit ratio in respect of treatment has not yet been achieved. Based on the results of several recent clinical trials aimed at ensuring provision of a well-balanced treatment for patients with ductal carcinoma in situ which carries a good prognosis, de-escalation of postoperative adjuvant therapy has now begun. Currently, not only is the optimization of postoperative adjuvant therapy accelerating, but also clinical trials to de-escalate basic surgical treatments are under way. There is a possibility of achieving individualized treatment for patients with ductal carcinoma in situ of the breast with reduced treatment intervention. In this review, we present an overview of the current treatment approaches and potential future management strategies for ductal carcinoma in situ of the breast.

Food and Drug Administration (FDA) Approvals of Biological Drugs in 2023.

An increase in total drug (small molecules and biologics) approvals by the Food and Drug Administration (FDA) was seen in 2023 compared with the previous year. Cancer remained the disease most targeted by monoclonal antibodies (mAbs), followed by autoimmune conditions. Our data reveal the prevalence of approvals for biologics even during years when the total number of authorizations was low, such as in 2022. Over half the drugs that received the green light in 2023 benefited from expedited programs, as the incidence of many diseases increased. In addition, over half of the biologics approved received Orphan Drug Designation from the FDA. This narrative review delves into details of the most significant approvals in 2023, including mAbs, enzymes, and proteins, explaining their mechanisms of action, differences from previous drugs, placebo, and standards of care, and outcomes in clinical trials. Given the varying number of drugs authorized annually by the U.S. health authority, this review also examines the limits of external influences over the FDA's decisions and independence regarding drug approvals and withdrawals.

A study of Antibiotics and Neem-Chirata Extracts in clinical trials of Salmonella typhi

The purpose of this study is to provide light on the possible benefits that Neem and Chirata may have over conventional antibiotics on the market. Investigations into the length of therapy and dose selection, as well as detailed examinations of safety profiles, will be used to attain this goal. As part of the therapeutic care of Salmonella typhi infections, an investigation of the efficacy of a number of medicinal and botanical extracts, including Neem and Chirata, is described. An in-depth investigation of the efficacy and safety of a number of different drugs, with a specific emphasis on how they affect S. typhi, is the purpose of this study. After it has been carried out, mechanistic study will assist in shedding light on the particular antibacterial processes that these drugs utilize. The abstract provides a concise summary of the aims of the study, which include evaluating the overall outcomes of clinical trials, comparing these interventions to standard treatments, investigating the synergistic benefits of combination therapy, monitoring the growth of antibiotic resistance, and evaluating the efficacy of combination therapy. And last, the abstract provides a concise analysis of the objectives of the clinical research as well as the possible future contributions that these investigations might make to the treatment of infectious diseases. This is accomplished by providing a synopsis of all the significant and substantial aspects of the clinical trials that are being taken into consideration.

Chios Mastic Gum: A Promising Phytotherapeutic for Cardiometabolic Health.

Chios mastic gum (CMG) is a resin obtained from the Pistacia lentiscus var. Chia tree that grows in the Mediterranean. For millennia, it has been renowned for its medicinal properties, but recently, CMG has gained attention due to its pronounced anti-inflammatory and antioxidative properties and its use in oral health, inflammatory bowel disease, cancer, and risk factors related to cardiovascular and metabolic diseases. This narrative review seeks to briefly overview its bioactive constituents and examine and describe its potential as a cardiometabolic disease (CMD) phytotherapeutic. The results of clinical trials and in vivo, in vitro, and in silico studies provide accumulating evidence of the mechanisms underlying CMG's impacts on lipid and glucose metabolism, cardiovascular and hepatic health, inflammation, oxidative stress, body composition, and microbiota. Despite the relatively limited studies with mixed results, they have provided the foundation to understand the strengths, weaknesses, and opportunities moving forward that may help to establish CMG and its bioactives as viable therapeutics for CMD.

European Respiratory Society statement on preschool wheezing disorders: updated definitions, knowledge gaps and proposed future research directions.

Since the publication of the European Respiratory Society (ERS) task force reports on the management of preschool wheezing in 2008 and 2014, a large body of evidence has accumulated suggesting that the clinical phenotypes that were proposed (episodic (viral) wheezing and multiple-trigger wheezing) do not relate to underlying airway pathology and may not help determine response to treatment. Specifically, using clinical phenotypes alone may no longer be appropriate, and new approaches that can be used to inform clinical care are needed for future research. This ERS task force reviewed the literature published after 2008 related to preschool wheezing and has suggested that the criteria used to define wheezing disorders in preschool children should include age of diagnosis (0 to <6 years), confirmation of wheezing on at least one occasion, and more than one episode of wheezing ever. Furthermore, diagnosis and management may be improved by identifying treatable traits, including inflammatory biomarkers (blood eosinophils, aeroallergen sensitisation) associated with type-2 immunity and differential response to inhaled corticosteroids, lung function parameters and airway infection. However, more comprehensive use of biomarkers/treatable traits in predicting the response to treatment requires prospective validation. There is evidence that specific genetic traits may help guide management, but these must be adequately tested. In addition, the task force identified an absence of caregiver-reported outcomes, caregiver/self-management options and features that should prompt specialist referral for this age group. Priorities for future research include a focus on identifying 1) mechanisms driving preschool wheezing; 2) biomarkers of treatable traits and efficacy of interventions in those without allergic sensitisation/eosinophilia; 3) the need to include both objective outcomes and caregiver-reported outcomes in clinical trials; 4) the need for a suitable action plan for children with preschool wheezing; and 5) a definition of severe/difficult-to-treat preschool wheezing.

Oméga-3 et psychiatrie : que dit la littérature ?

Psychiatry is faced with a lack of new treatments despite a great deal of research and is re-exploring the use of old molecules and dietary supplements. Our aim here is to present a narrative review of the indications for omega-3 supplementation in various psychiatric disorders. Omega-3s belong to the family of polyunsaturated fatty acids (PUFAs). The 3 important omega-3 PUFAs in psychiatry are α-linolenic acid (ALA): C18:3n-3, eicosapentaenoic acid (EPA) C20:5n-3 and docosahexaenoic acid (DHA) C22:6n-3. In psychosis, a distinction must be made between 3 categories of patients: patients who have chronic schizophrenia (SCZ), patients with a first psychotic episode (FEP) and patients at ultra-high risk of psychosis (UHR).The data in the literature indicate that omega-3 supplementation is well tolerated. However, there is an increased risk of atrial fibrillation at doses over 4g/d, mainly in people over the age of 65.Omega-3 supplementation is not recommended for eating disorders, attention deficit hyperactivity disorder or autism spectrum disorders. Omega-3 supplementation could be beneficial in borderline personality disorder and psychotic disorders, particularly in patients at ultra-high risk of psychotic transition (UHR) to prevent psychotic transition and FEP to improve remission, and in bipolar disorder. It is now recommended for unipolar depression by the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce. There are a large number of clinical trials of omega-3 supplementation. However, these trials use different types of supplementation (EPA alone, DHA alone, EPA+DHA, etc.) with different dosages and EPA/DHA ratios and over variable durations. In addition, the origin of the omega-3s may vary, although most of the studies used omega-3s of marine origin (fish). Finally, it has not been studied whether the time of day (fasting, during a meal, morning, evening, etc.) impacts the efficacy of the treatment.Confounding factors are often not taken into account. For example, some studies suggest a link between the response to omega-3 supplementation and the inflammation or oxidative stress level. Omega-3 supplementation acts on numerous biological pathways: inflammation, oxidative stress, monocarbon metabolism (vitamin B9, B12, homocysteine), myelination,... For psychotic disorders, meta-analyses tend not to distinguish between UHR, PEP and schizophrenic patients.There have not been enough studies to validate the doses and duration of supplementation. The doses and durations in the recommendations are based solely on incomplete data from published studies. Further studies are needed to optimize these recommendations. Except for UHR patients and those with borderline personality disorder, omega-3 supplementation is always used as a complement to psychotropic treatment.In conclusion, the results of clinical trials, meta-analyses and recommendations are heterogeneous and may be divergent. Omega-3 supplementation in psychiatry is still extensively studied, with numerous studies and meta-analyses published recently. Omega-3 supplementation could be part of the goal of personalized medicine, as some studies are already suggesting. In the future, the efficacy of omega-3 supplementation could be improved by targeting sub-groups of patients: patients with inflammatory profiles, high levels of oxidative stress and low blood omega-3 concentrations. Due to the increasing number of studies published on omega-3 supplementation in psychiatric disorders, the conclusions of this review are provisional and will need to be updated.