Gender bias in clinical trials of biological agents for migraine: A systematic review.

Migraine is considered one of the most disabling diseases. Currently, there are few studies on clinical migraine treatment based on sex-related differences, despite the important role of sex in migraine. Our aim was to evaluate gender bias in published clinical trials on monoclonal antibodies (erenumab, galcanezumab, fremanezumab and eptinezumab). We performed a systematic review of controlled clinical trials of erenumab, galcanezumab, fremanezumab and eptinezumab, searching the PubMed/MEDLINE database for articles published before December 2021. The search identified 760 articles, 25 of which met the inclusion criteria. Of all the patients included in these trials, 85.1% were women. Only one study had female lead authors. Two of the 25 studies included a sex-based analysis of the primary endpoint. None of the articles discussed the results separately for men and for women. The proportion of men recruited in trials is scarce and more studies are needed to guarantee the safety and tolerability of monoclonal antibodies used in male migraine. As observed in our study, despite the high number of women recruited, only 2 studies analysed the results separately by sex. Thus, a potential risk of gender bias was found in these clinical trials.

A Rare Case of Drug-induced Erectile Dysfunction with Adalimumab and Certolizumab Solved after Switch to Ustekinumab in a Crohn's Disease Patient.

BACKGROUND: Crohn Disease (CD) is an intestinal inflammatory condition characterized by a complex pathogenesis, with elevated levels of inflammatory cytokines. Adalimumab and certolizumab are two biologic drugs inhibiting TNF-α. OBJECTIVE: We report the first case of a probable relationship, according to Naranjo causality assessment score, between two consecutive treatments with TNF-α inhibitors and induced erectile dysfunction (ED), that disappeared after switching to another biologic drug (ustekinumab). CASE PRESENTATION: This case report describes a possible and important association of two TNF-α inhibitors (certolizumab and adalimumab) and ED in a male patient with CD, with resolution after switching to Ustekinumab (anti-interleukin 12 and 23 biologic drug). A 65 years old man experienced erectile dysfunction during treatment with an anti-TNF. The adverse effect disappeared after discontinuation of the drug. All necessary urologic exams were carried out. Adalimumab was replaced by certolizumab and sexual disfunction symptoms appeared again, improving typically at the end of treatment periods and getting worse with each new dose. RESULTS: Switching to ustekinumab lead to a resolution of the erectile dysfunction. CONCLUSION: We describe for the first time a sexual dysfunction possibly due to two similar anti TNF drugs and its resolution after the switch to another similar but different drug, highlighting the potential difference between biologic drugs.

Unlocking Hidden Awareness: Repurposing fMRI to Detect Levels of Consciousness.

Determining the state of consciousness in patients with disorders of consciousness is a challenging task because for someone to be deemed conscious, both wakefulness and awareness are required. Awareness has traditionally been assessed by examining physical responsiveness but in 2010, Monti et al. explored how using fMRI to measure brain activity in humans could help reclassify the state of consciousness in these patients. The findings, published in The New England Journal of Medicine, show that some brain regions are active when patients respond to an imagery or communication task. This is a seminal study because it demonstrates that patients who behaviourally appear to be in a vegetative or minimally conscious state may still have residual brain functions that would not be apparent from a clinical examination alone. Notably, it exemplified how fMRI can be repurposed as a communication tool for this subset of aware, but 'locked in', patients who appear unresponsive. From an educator's perspective, this paper is valuable because it is relevant to a broad audience, both introductory and advanced level undergraduate students. It introduces key concepts in cognitive and clinical neuroscience and encourages students to consider the connections between social issues and technology development in neuroscience. Finally, educators may use this paper to discuss and debate the nature of consciousness and the ethical implications that the use of fMRI for determining consciousness may have on medical ethics.

Association between Vancomycin Pharmacokinetic Parameters and Clinical and Microbiological Efficacy in a Cohort of Neonatal Patients.

Vancomycin pharmacokinetic/pharmacodynamic (PK/PD) targets have not been validated in the neonatal population as no specifically designed studies are available. The main goal of this study was to analyze the therapeutic vancomycin regimen, the 24-h area under the curve (AUC24), and the trough plasma concentration (Ct) obtained that achieved clinical and microbiological effectiveness in a cohort of neonates. This was an observational, prospective, single-center study covering a period of 2 years. Eligible patients were neonates and young infants who were undergoing treatment with intravenous vancomycin for ≥72 h with ≥1 Ct available. The primary outcome was the association of Ct and AUC24 with clinical and microbiological efficacy at the beginning (early clinical evolution [ECE]) and the end (late clinical evolution [LCE]) of treatment with vancomycin. A total of 43 patients were included, 88.4% of whom were cured. In ECE, the cutoff points of the receiver operating characteristic (ROC) curve were 238 mg · h/L (sensitivity of 61% and specificity of 88%) for AUC24 and 6.8 µg/mL (sensitivity of 61% and specificity of 92%) for Ct. In LCE, the Ct value was 11 µg/mL, with a sensitivity of 80% and a specificity of 92%. In this analysis, AUC24 was not considered a good predictor. Logistic regression showed that a vancomycin Ct of ≤6.8 µg/mL was associated with an unfavorable ECE (P = 0.001), being 18 times more likely to progress poorly compared to those with higher levels. AUC24 and Ct are good predictors of ECE in this population. Concentrations close to 7 µg/mL and an AUC24 of around 240 mg · h/L 48 h after antibiotic initiation seem to be sufficient to achieve clinical cure in most cases.

Efficacy and Safety of Continuous Infusion of Vancomycin in Children: A Systematic Review.

Vancomycin is used to treat a wide variety of infections within the pediatric population. In adults, continuous infusion of vancomycin (CIV) has been evaluated as an alternative to intermittent infusion of vancomycin (IIV) with potential advantages. In children, the use of CIV is increasing; however, data is currently limited. The objective is to provide efficacy and safety evidence for CIV within this population. The review was carried out following PRISMA guidelines. A bibliographic search was performed for studies on PubMed and EMBASE. Clinical trials and observational studies that reported clinical efficacy and/or target attainment of CIV in pediatrics were included. Articles were reviewed to assess their design and target population, characteristics of vancomycin treatment and the main findings in terms of safety and efficacy. A total of 359 articles were identified, of which seven met the inclusion criteria. All of them evaluated the target attainment, six assessed safety but only three assessed clinical efficacy. The best administration method for this antibiotic within the pediatric population is still unknown due to limited evidence. However, studies conducted thus far suggest pharmacokinetic advantages for CIV. Further investigation is required, in particular for studies comparing IIV with CIV for clinical efficacy and toxicity outcomes.

Target Attainment and Clinical Efficacy for Vancomycin in Neonates: Systematic Review.

Vancomycin is commonly used as a treatment for neonatal infections. However, there is a lack of consensus establishing the optimal vancomycin therapeutic regimen and defining the most appropriate PK/PD parameter correlated with the efficacy. A recent guideline recommends AUC-guided therapeutic dosing in treating serious infections in neonates. However, in clinical practice, trough serum concentrations are commonly used as a surrogate PKPD index for AUC24. Despite this, target serum concentrations in a neonatal population remain poorly defined. The objective is to describe the relationship between therapeutic regimens and the achievement of clinical or pharmacokinetic outcomes in the neonatal population. The review was carried out following PRISMA guidelines. A bibliographic search was manually performed for studies published on PubMed and EMBASE. Clinical efficacy and/or target attainment and the safety of vancomycin treatment were evaluated through obtaining serum concentrations. A total of 476 articles were identified, of which 20 met the inclusion criteria. All of them evaluated the target attainment, but only two assessed the clinical efficacy. The enormous variability concerning target serum concentrations is noteworthy, which translates into a difficulty in determining which therapeutic regimen achieves the best results. Moreover, there are few studies that analyze clinical efficacy results obtained after reaching predefined trough serum concentrations, this information being essential for clinical practice.

An Unusual Case of Allergic Reaction to Anakinra in a Patient with Tumor Necrosis Factor Receptor-1 Associated Periodic Syndrome (TRAPS) and Subsequent Canakinumab Treatment.

Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is a rare hereditary systemic autoinflammatory disease (SAID). Treatment is based on corticosteroids, but often requires the addition of a biologic drug (anti-TNF agent, IL-1 receptor antagonist, etc) to achieve symptom control. The addition of the second drug is not clearly defined and must take into account the characteristics and preferences of the patient. We describe a patient with TRAPS and an allergic reaction to anakinra which was difficult to manage clinically while alternative treatment was being identified. LEARNING POINTS: Treatment of tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) often requires adding a biologic drug to corticosteroids to achieve the best efficacy.Currently, IL-1 receptor antagonists are considered the first line of treatment in TRAPS.The most frequent adverse effect of anakinra is a reaction at the injection site.Canakinumab has shown better response compared to placebo in the treatment of TRAPS.

Consideraciones clínicas y terapéuticas sobre gastroenteritis de etiología bacteriana

Se revisan 353 Historias Clínicas correspondientes a egresos vivos y fallecidos por E.D.A. de etilogía bacteriana......(AU)