Promoting a Sleep-friendly Environment by Minimizing Overnight Room Entries.

Introduction: Despite its importance in illness recovery, the sleep of hospitalized children is frequently interrupted. This quality improvement intervention aimed to reduce overnight room entries by minimizing unnecessary interventions. Methods: This study occurred at a university-affiliated children's hospital on the hospital medicine services from March 26, 2021, to April 14, 2022. The intervention included order set changes and the implementation of a rounding checklist designed to address factors most closely associated with sleep disruption and overnight room entries. The outcome measure was overnight (10 pm to 6 am) room entries, counted using room entry sensors. Process measures reflected the intervention targets (overnight vital sign orders, medication administration, and intravenous fluid use). The method of analysis was statistical process control charting. Results: After identifying special cause variation, the average number of overnight room entries decreased from 8.1 to 6.8, a 16% decrease. This decrease corresponded with the implementation of a rounding checklist. However, there continued to be variability in average room entries, suggesting a process lacking ongoing stability. During this period, avoidance of overnight medications and intravenous fluid increased by 28% and 17%, respectively. Conclusions: Implementing a rounding checklist to a broad patient population decreased overnight room entries. However, future work is needed to better understand the factors associated with sustaining such an improvement.

Secondary immunodeficiencies and infectious considerations of biologic immunomodulatory therapies.

Biologic immunomodulatory medications have rapidly expanded in the previous decades, providing new treatment options for individuals with a spectrum of oncologic, allergic, rheumatologic, and neurologic conditions. Biologic therapies alter immune function and can impair key host defense mechanisms, resulting in secondary immunodeficiency and increased infectious risks. Biologic medications can increase general risk for upper respiratory tract infections but can also be associated with unique infectious risks owing to distinct mechanisms of action. With the widespread use of these medications, providers in every area of medicine will likely care for individuals receiving biologic therapies and understanding their potential infectious complications can help mitigate these risks. This practical review discusses the infectious implications of biologics by class of medication and provides recommendations regarding the examination and screening both before therapy initiation and while the patient is receiving the medication. With this knowledge and background, providers can reduce risk whereas patients receive the treatment benefits of these biologic medications.

Rechallenge of Elexacaftor/Tezacaftor/Ivacaftor After Skin Rash in Two Pediatric Patients.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have revolutionized care for patients with cystic fibrosis (CF). The triple combination product elexacaftor/tezacaftor/ivacaftor is a highly effective CFTR modulator that is generally well tolerated. However, in clinical trials of pediatric and adult patients, 4% to 12% developed rash after initiation of therapy. Few reports have described approaches to management of this adverse effect. In this report, we describe 2 children with CF who developed a pruritic, maculopapular rash after initiating elexacaftor/tezacaftor/ivacaftor. These patients were successfully rechallenged after rash resolution with a practical titration schedule.

Real World Experience of Pseudomonas aeruginosa Eradication at an Urban Pediatric Cystic Fibrosis Center.

OBJECTIVES: Clinical practice guidelines for eradication of Pseudomonas aeruginosa (PA) in patients with cystic fibrosis (CF) have been established, but current studies have not assessed how these guidelines translate into clinical practice. This study aimed to characterize the real-world eradication strategies, eradication rates, and microbiologic outcomes of patients with first acquisition of PA at an urban pediatric CF center. METHODS: The Cystic Fibrosis Foundation Patient Registry was used to identify patients with CF who received care between January 2014 and September 2018 and had PA isolated from an airway culture. Patients were included if they had a first positive PA culture or the first positive culture in 2 years. Data regarding patient demographics, timing and results of airway cultures, and treatment regimens were collected. RESULTS: Over a 3.75-year period, 75 patients had an initial positive culture for PA. Of those patients, 74 (98.7%) received eradication treatment. Tobramycin inhalation solution (TIS) monotherapy was the most common regimen prescribed (52.7%) followed by TIS plus an oral fluoroquinolone (28.4%) (TIS + FQ). Of those treated, 62 (83.8%) patients had eradication of PA at first follow-up culture (median, 58 days; IQR, 49-77 days). Eradication rates (84.6% vs 76.2%, p = 0.421) and times to recurrence (6.37 months vs 5.1 months, p = 0.726) were comparable between TIS and TIS + FQ cohorts. CONCLUSIONS: The eradication rate for PA in clinical practice is similar to that published in the literature. Consistent with published guidelines, these microbiologic outcomes do not support the addition of an oral FQ to TIS for initial PA eradication.

Off-label use of intravenous antimicrobials for inhalation in patients with cystic fibrosis.

Management of infections in patients with cystic fibrosis (CF) presents challenges for healthcare providers, including the eradication of initial acquisition, treatment of acute exacerbations, and chronic infection with suppressive therapy. Inhaled antimicrobial therapy for infections in patients with CF has been used in these capacities, often in an effort to achieve optimal concentrations in sputum for antimicrobial efficacy while mitigating potential toxicities associated with systemic therapy. Unfortunately, there are few commercially available products formulated for inhalation, resulting in the off-label use of other formulations, such as intravenous products, administered via nebulization. This review aims to examine the evidence supporting the efficacy of these off-label formulations for management of acute and chronic infections associated with CF, as well as adverse effects associated with their use.

Dinutuximab: An Anti-GD2 Monoclonal Antibody for High-Risk Neuroblastoma.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, and formulary considerations for dinutuximab. DATA SOURCES: MEDLINE was searched (1964 to January 2016) using the terms ch14.18, dinutuximab, immunotherapy, and neuroblastoma. Other information was identified from package insert, Biologics License Application, abstracts, news releases, and ClinicalTrials.gov. STUDY SELECTION AND DATA EXTRACTION: Identified English-language articles were reviewed. Selected studies included phase I through III. DATA SYNTHESIS: High-risk neuroblastoma is primarily a childhood cancer with 5-year survival rates of 40% to 50%. Treatment for high-risk neuroblastoma includes induction chemotherapy, surgery, myeloablative chemotherapy with autologous hematopoietic stem cell transplant, and radiation therapy. For patients achieving clinical remission, limited treatments exist for preventing relapse. Dinutuximab is a chimeric, human-murine, anti-GD2 monoclonal antibody approved in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), aldesleukin (interleukin-2 [IL-2]), and isotretinoin (13-cis-retinoic acid [RA]) for maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy. In phase III trials, dinutuximab increased 2-year event-free survival and overall survival when compared to standard treatment. Severe adverse effects of dinutuximab include pain, hypersensitivity reactions, capillary leak syndrome, and hypotension. CONCLUSIONS: Dinutuximab is the first anti-GD2 monoclonal antibody approved in combination with GM-CSF, IL-2, and RA for maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy. Ongoing research will determine if dinutuximab could be used earlier in treatment, in nonresponders to initial therapies, in combination with chemotherapy, or in other cancers.

Direct-growth carbon nanotubes on 3D structural microelectrodes for electrophysiological recording.

A novel 3D carbon nanotube (CNT) microelectrode was developed through direct growth of CNTs on a gold pin-shaped 3D microelectrode at a low temperature (400 °C) for applications in neural and cardiac recording. With an electroplated Ni catalyst layer covering the entire surface of the pin-shaped structure, CNTs were synthesized on a 3D microelectrode by catalytic thermal chemical vapor deposition (CVD). According to the analyses by electrochemical impedance spectroscopy, the impedance of 3D microelectrodes after CNT growth and UV/O3 treatment decreased from 9.3 Ω mm(-2) to 1.2 Ω mm(-2) and the capacitance increased largely from 2.2 mF cm(-2) to 73.3 mF cm(-2). The existence of UVO3-treated CNT led to a large improvement of interfacial capacitance, contributing to the decrease of impedance. The electrophysiological detection capability of this 3D CNT microelectrode was demonstrated by the distinguished P waves, QRS complex and T waves in the electrocardiogram of the zebrafish heart and the action potential recorded from individual rat hippocampal neurons. The compatibility of integration with ICs, high resolution in space, electrophysiological signals, and non-invasive long-term recording suggest that the 3D CNT microelectrode exhibits promising potential for applications in electrophysiological research and clinical trials.

Kinetic studies of oxygen atom transfer reactions from trans-dioxoruthenium(VI) porphyrins to sulfides.

The kinetics of the reactions of three trans-dioxoruthenium(VI) porphyrin derivatives with organic sulfides were measured. The dioxo systems studied were 5,10,15,20-tetramesityl porphyrin-dioxoruthenium(VI) (2a), 5,10,15,20-tetraphenylporphyrin-dioxoruthenium(VI) (2b), and 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin-dioxoruthenium(VI) (2c). Species 2 were competent oxidants and reacted rapidly with thioanisoles to generate the corresponding sulfoxides. Typical second-order rate constants determined from pseudo-first-order kinetic studies for sulfoxidation reactions are 8-60 M(-1)s(-1), which are 3 orders of magnitude larger in comparison with those of well studied alkene epoxidations and activated C-H bond oxidations by the same dioxo species. For a given sulfide substrate, the reactivity order for the dioxoruthenium(VI) species was 2a<2b<2c, which is in agreement with expectation on the basis of the electron-withdrawing and steric effects of the porphyrin macrocycles. Various para-substituted thioanisoles react in a narrow kinetic range with the same dioxo species. The kinetic results obtained in this study indicate a concerted oxygen atom transfer and/or electron transfer followed by oxygen transfer mechanism from oxidant to sulfide. Competition kinetic reactions with a catalytic amount of porphyrin ruthenium(II) species and a terminal oxidant give relative rate constants for sulfoxidations of competing substrates that are somewhat smaller than the ratios of absolute rate constants, implying a multiple oxidant model for sulfoxidation reactions.

Gonadotrophin-releasing hormone analogues for pain associated with endometriosis.

EDITORIAL NOTE: See https://pubmed.ncbi.nlm.nih.gov/37341141/ for a more recent review that covers this topic and has superseded this review. BACKGROUND: Endometriosis is a common gynaecological condition, characterised by the presence of endometrial tissue in sites other than the uterine cavity (excluding adenomyosis) that frequently presents with pain. The gonadotrophin-releasing hormone analogues (GnRHas) comprise one intervention that has been offered for pain relief in pre-menopausal women. GnRHas can be administered intranasally, by subcutaneous, or intramuscular injection. They are thought to result in down regulation of the pituitary and induce a hypogonadotrophic hypogonadal state. OBJECTIVES: To determine the effectiveness and safety of GnRHas in the treatment of the painful symptoms associated with endometriosis. SEARCH STRATEGY: Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group specialist register, CENTRAL, MEDLINE, EMBASE, PSYCInfo and CINAHL were conducted in April 2010 to identify relevant randomised controlled trials (RCTs). SELECTION CRITERIA: RCTs of GnRHas as treatment for pain associated with endometriosis versus no treatment, placebo, danazol, intra-uterine progestagens, or other GnRHas were included. Trials using add-back therapy, oral contraceptives, surgical intervention, GnRH antagonists or complementary therapies were excluded. DATA COLLECTION AND ANALYSIS: Quality assessment and data extraction were performed independently by two reviewers. The primary outcome was pain relief. Relative risk was used as the measure of effect for dichotomous data. For continuous data, mean differences or standardised mean differences were used. MAIN RESULTS: Forty one trials (n=4935 women) were included. The evidence suggested that GnRHas were more effective at symptom relief than no treatment/placebo. There was no statistically significant difference between GnRHas and danazol for dysmenorrhoea RR 0.98 (95%CI 0.92 to 1.04; P = 0.53). This equates to 3 fewer women per 1000 (95%CI 12 to 6) with symptomatic pain relief in the GnRHa group. More adverse events were reported in the GnRHa group. There was a benefit in overall resolution for GnRHas RR1.10 (95%CI 1.01 to 1.21, P=0.03) compared with danazol. There was no statistically significant difference in overall pain between GnRHas and levonorgestrel SMD -0.25 (95%CI -0.60 to 0.10, P=0.46). Evidence was limited on optimal dosage or duration of treatment for GnRHas. No route of administration appeared superior to another. AUTHORS' CONCLUSIONS: GnRHas appear to be more effective at relieving pain associated with endometriosis than no treatment/placebo. There was no evidence of a difference in pain relief between GnRHas and danazol although more adverse events reported in the GnRHa groups. There was no evidence of a difference in pain relief between GnRHas and levonorgestrel and no studies compared GnRHas with analgesics.