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Abstract Background Inherited epidermolysis bullosa (EB) is a cluster of rare, genetic skin and mucosal fragility disorders with multi-system and secondary effects, in which blistering and erosions occur in response to friction/mechanical trauma. Considering the incurable and potentially life-limiting nature of the condition and the challenges posed by its symptoms, a palliative approach to EB-related care is necessary. However, knowledge and experience related to the provision of EB palliative care is minimal. Evidence-based, best care guidelines are needed to establish a base of knowledge for practitioners to prevent or ease suffering while improving comfort at all stages of the illness, not just the end of life. Methods This consensus guideline (CG) was begun at the request of DEBRA International, an international organization dedicated to improvement of care, research, and dissemination of knowledge for EB patients, and represents the work of an international panel of medical experts in palliative care and EB, people living with EB, and people who provide care for individuals living with EB. Following a rigorous, evidence-based guideline development process, the author panel identified six clinical outcomes based on the results of a survey of people living with EB, carers, and medical experts in the field, as well as an exhaustive and systematic evaluation of literature. Recommendations for the best clinical provision of palliative care for people living with EB for each of the outcomes were reached through panel consensus of the available literature. Results This article presents evidence-based recommendations for the provision of palliative healthcare services that establishes a base of knowledge and practice for an interdisciplinary team approach to ease suffering and improve the quality of life for all people living with EB. Any specific differences in the provision of care between EB subtypes are noted. Conclusions Because there is yet no cure for EB, this evidence-based CG is a means of optimizing and standardizing the IDT care needed to reduce suffering while improving comfort and overall quality of life for people living with this rare and often devastating condition.

Abstract Background Mutations in the NMDA receptor are known to disrupt glutamatergic signaling crucial for early neurodevelopment, often leading to severe global developmental delay/intellectual disability, epileptic encephalopathy, and cerebral palsy phenotypes. Both seizures and movement disorders can be highly treatment-refractory. Results We describe a targeted ABA n-of-1 treatment trial with intrathecal MgSO4, rationally designed based on the electrophysiologic properties of this gain of function mutation in the GRIN1 NMDA subunit. Conclusion Although the invasive nature of the trial necessitated a short-term, non-randomized, unblinded intervention, quantitative longitudinal neurophysiologic monitoring indicated benefit, providing class II evidence in support of intrathecal MgSO4 for select forms of GRIN disorders.

Antibiotic resistance is a serious global health problem that poses a threat to the successful treatment of various bacterial infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Conventional treatment of MRSA and VRE infections is challenging and often requires alternative or combination therapies that may have limited efficacy, higher costs, and/or more adverse effects. Therefore, there is an urgent need to find new strategies to combat antibiotic-resistant bacteria. Probiotics and antimicrobial peptides (AMPs) are two promising approaches that have shown potential benefits in various diseases. Probiotics are live microorganisms that confer health benefits to the host when administered in adequate amounts. AMPs, usually produced with probiotic bacteria, are short amino acid sequences that have broad-spectrum activity against bacteria, fungi, viruses, and parasites. Both probiotics and AMPs can modulate the host immune system, inhibit the growth and adhesion of pathogens, disrupt biofilms, and enhance intestinal barrier function. In this paper, we review the current knowledge on the role of probiotics and AMPs in targeting multi-drug-resistant bacteria, with a focus on MRSA and VRE. In addition, we discuss future directions for the clinical use of probiotics.

ObjectivesContinuous renal replacement therapy (CRRT) is commonly employed in critically ill children and is known to affect antimicrobial pharmacokinetics. There is a lack of readily available, evidence-based antimicrobial dosing recommendations in pediatric CRRT. This study aims to quantify commonly used antimicrobial drugs in pediatric CRRT and identify gaps between contemporary literature-based dosing recommendations and those presented in a frequently used dosing reference.MethodsThe Pediatric Health Information System (PHIS) database was queried from July 1, 2018 through June 30, 2021 to identify admissions in which antimicrobials were billed on the same day as CRRT. Drugs of interest were selected if at least 10% of admission involved administration on at least one CRRT day, with additional clinically important antimicrobials selected by the authors. A comprehensive literature search was performed to identify antimicrobial pharmacokinetic (PK) studies in children for each selected drug. For identified articles, dosing recommendations were extracted and compared to those in a popular tertiary dosing reference (Lexi-Comp Online database). The level of agreement of the dosing recommendations was assessed.Results77 unique antimicrobial agents were identified amongst 812 admissions from 20 different PHIS hospitals. Fifteen antimicrobials were billed on the same day as CRRT in ≥10% of admissions, with 4 additional drugs deemed clinically relevant by the authors. Twenty PK studies were identified for these 19 drugs, and dosing recommendations were included in 8 (42.1%) of them. Seventeen agents (89.5%) had some type of CRRT-specific dosing guidance in Lexi-Comp, with only 1 directly based on a pediatric CRRT study. For the 8 agents with PK data available, Lexi-Comp recommendations matched primary literature dosing guidance in 3 (37.5%). Two (25%) lacked agreement between the Lexi-Comp and primary literature, and the remaining 3 (37.5%) had partial agreement with multiple dosing regimens suggested in the primary literature and at least one of these regimens recommended by Lexi-Comp.ConclusionSignificant gaps exist in the data supporting antimicrobial dosing recommendations for children receiving CRRT. Future studies should focus on antimicrobial dosing in pediatric CRRT, emphasizing provision of robust data from which dosing recommendations can be promptly incorporated into tertiary dosing references.