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In the United States (U.S.), 90% of annual health care expenditures are devoted to people with chronic physical and mental health conditions. For people with HIV (PWH), two common, chronic comorbidities are pain and depression. This report assesses the impact of a brief psychotherapy intervention for PWH and comorbid chronic pain and depression on health care service utilization. Data from the HIV Pain and Sadness Study (HIV-PASS) randomized trial were used. Electronic health records were reviewed to tabulate use of the following services: (a) outpatient rehabilitation; (b) outpatient psychiatric; and (c) hospital-based (e.g., emergency department). Estimated average marginal effects were analyzed to determine how many times a participant accessed the service and the charge at each event. The sample consisted of 187 adults recruited from three U.S. sites. Individuals randomized to the three-month, seven session HIV-PASS intervention had average charges for hospital-based services that were significantly less during the post-treatment phase (months 4-12; 95%CI: -$16,612, -$131; p =.046) than those randomized to the comparison condition. On average, comparison condition participants were charged $8,371 more for hospital services in the 8-month period following intervention. No significant differences between treatment conditions were observed in use of outpatient rehabilitation, outpatient psychiatric services, or hospital-based care. Consistent with predictions, lower health care charges among those randomized to the HIV-PASS behavioral intervention were incurred for hospital services, indicating that a brief behavioral intervention could lead to decreased use of more emergent and expensive care services among persons with HIV, depression, and chronic pain., Competing Interests: Declarations Conflict of Interest Dr. Uebelacker’s spouse is employed by Abbvie Pharmaceuticals. Dr. Weisberg is the Chief Clinical Officer for RealizedCare. RealizedCare makes virtual reality-based behavioral health interventions for common problems including pain and depression. The authors declare no other relevant financial or non-financial interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Annually, tens of thousands of U.S. children and adolescents are hospitalized with seasonal influenza virus infection. Both influenza vaccination and early initiation of antiviral treatment can reduce complications of influenza. Using data from two U.S. influenza surveillance networks for children and adolescents aged <18 years with medically attended, laboratory-confirmed influenza for whom antiviral treatment is recommended, the percentage who received treatment was calculated. Trends in antiviral treatment of children and adolescents hospitalized with influenza from the 2017-18 to the 2023-2024 influenza seasons were also examined. Since 2017-18, when 70%-86% of hospitalized children and adolescents with influenza received antiviral treatment, the proportion receiving treatment notably declined. Among children and adolescents with influenza during the 2023-24 season, 52%-59% of those hospitalized received antiviral treatment. During the 2023-24 season, 31% of those at higher risk for influenza complications seen in the outpatient setting in one network were prescribed antiviral treatment. These findings demonstrate that influenza antiviral treatment is underutilized among children and adolescents who could benefit from treatment. All hospitalized children and adolescents, and those at higher risk for influenza complications in the outpatient setting, should receive antiviral treatment as soon as possible for suspected or confirmed influenza., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Janet A. Englund reports institutional support from AstraZeneca, Pfizer, Moderna, and GlaxoSmithKline; receipt of consulting fees from AstraZeneca, GlaxoSmithKline, Merck, Meissa Vaccines, Moderna, Pfizer, and Sanofi Pasteur; and receipt of honoraria from Pfizer. Natasha B. Halasa reports institutional support from Merck, and receipt of an honorarium from CSL Seqirus for service on an advisory board. Sue Kim reports grants from the Michigan Department of Health and Human Services. Ruth Lynfield reports receipt of a fee for serving as an Associate Editor for the American Academy of Pediatrics Redbook, which was then donated to the Minnesota Department of Health. Leila C. Sahni reports travel support from the Gates Foundation. Elizabeth P. Schlaudecker reports institutional support from Pfizer; receipt of an honorarium from Sanofi Pasteur for service on an advisory board; and travel support for meeting attendance from the World Society for Pediatric Infectious Diseases, the European Society for Paediatric Infectious Diseases, and Pediatric Infectious Diseases Society; uncompensated membership of a National Institutes of Health Data Safety Monitoring Board; and membership on the board of the World Society for Pediatric Infectious Diseases. Jennifer E. Schuster reports institutional support from the National Institutes of Health, the Food and Drug Administration and the State of Missouri; receipt of a consulting fee from the Association of Professionals in Infection Control and Epidemiology and a speaking honorarium from the Missouri Chapter of the American Academy of Pediatrics; membership on the Association of American medical Colleges advisory board. Rangaraj Selvarangan reports institutional support from Abbot, Cepheid, Biomerieux, Hologic, BioRad, Qiagen, Diasorin, and Merck; receipt of payment from GlaxoSmithKline, Baebies Biomerieux and Abbot; and travel support from Biomerieux and Hologic. Mary A. Staat reports institutional support from the National Institutes of Health, Cepheid, and Merck; royalties from UpToDate; and consulting fees from Merck. Dawud Ujamaa reports consulting fees from Goldbelt, Inc. Geoffrey A. Weinberg reports institutional support from the New York State Department of Health; consulting fees from the New York State Department of Health, Inhalon Biopharma, and ReViral; honorarium from Merck; and participation on an Emory University Data Safety Monitoring Board. No other potential conflicts of interest were disclosed.

Lysosomal storage diseases (LSDs) comprise ~50 monogenic disorders marked by the buildup of cellular material in lysosomes, yet systematic global molecular phenotyping of proteins and lipids is lacking. We present a nanoflow-based multi-omic single-shot technology (nMOST) workflow that quantifies HeLa cell proteomes and lipidomes from over two dozen LSD mutants. Global cross-correlation analysis between lipids and proteins identified autophagy defects, notably the accumulation of ferritinophagy substrates and receptors, especially in NPC1 -/- and NPC2 -/- mutants, where lysosomes accumulate cholesterol. Autophagic and endocytic cargo delivery failures correlated with elevated lyso-phosphatidylcholine species and multi-lamellar structures visualized by cryo-electron tomography. Loss of mitochondrial cristae, MICOS-complex components, and OXPHOS components rich in iron-sulfur cluster proteins in NPC2 -/- cells was largely alleviated when iron was provided through the transferrin system. This study reveals how lysosomal dysfunction affects mitochondrial homeostasis and underscores nMOST as a valuable discovery tool for identifying molecular phenotypes across LSDs., Competing Interests: DECLARATION OF INTERESTS J.W.H. is a consultant and founder of Caraway Therapeutics (a wholly owned subsidiary of Merck & Co, Inc) and is a member of the scientific advisory board for Lyterian Therapeutics. B.A.S. is a co-founding scientific advisory board member of Interline Therapeutics and on the scientific advisory boards of Biotheryx and Proxygen. J.M.P. holds a position on the advisory board of Thermo Fisher Scientific. J.J.C. is a consultant for Thermo Fischer Scientific. Other authors declare no competing interests. S.P.G. is on the advisory board for Thermo Fisher Scientific, Cedilla Therapeutics, Casma Therapeutics, Cell Signaling Technology, and Frontier Medicines.

Background: Type 1 diabetes (T1D) management is challenging for young adults, who are expected to transfer from the pediatric to adult T1D healthcare system while also managing typical developmental demands (e.g., social, financial, work/school, residential). Many young adults have extended gaps in care before following up in adult care, increasing risk for poor health outcomes. There are few evidence-based programs to support young adults with T1D to promote a timelier transition during this period. This paper reports on the design of DiaBetter Together, a randomized controlled trial to evaluate a 12-month Peer Mentor-delivered intervention compared to usual care among young adults with T1D during the transfer from pediatric to adult care., Methods: One-hundred young adults (age 17-25) with T1D and 29 Peer Mentors enrolled in this randomized clinical trial. Peer Mentors are experienced, older young adults with T1D, trained by the study team to share transition experiences and strategies to successfully navigate the adult healthcare system, help young adults prepare for the first adult care visit, and use strengths-based support strategies to teach and model skills for managing T1D-related challenges., Results: The primary outcome of the trial is HbA1c, and secondary outcomes include time to adult care, engagement in diabetes self-management behaviors, and psychosocial well-being., Conclusion: The goal of this research is to evaluate a developmentally appropriate, supportive intervention that can improve T1D self-management and successful transfer of care during the difficult young adult years and promote optimal T1D health outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Nontuberculous mycobacteria (NTM) cause pulmonary and extrapulmonary infections. Although isolation of NTM from clinical specimens has increased nationally, few studies delineated the molecular characteristics of extrapulmonary NTM., Methods: Extrapulmonary isolates were collected by four Emerging Infections Program sites from October 2019 to March 2020 and underwent laboratory characterization, including matrix-assisted laser desorption ionization-time of flight mass spectrometry, Sanger DNA sequencing, and whole genome sequencing. Bioinformatics analyses were employed to identify species, sequence types (STs), antimicrobial resistance (AR), and virulence genes; isolates were further characterized by phylogenetic analyses., Results: Among 45 isolates, the predominant species were Mycobacterium avium (n=20, 44%), Mycobacterium chelonae (n=7, 16%), and Mycobacterium fortuitum (n=6, 13%). The collection represented 31 STs across 10 species; the most common ST was ST11 (M. avium, n=7). Mycobacterium fortuitum and Mycobacterium abscessus isolates harbored multiple genes conferring resistance to aminoglycosides, beta-lactams, and macrolides. No known AR mutations were detected in rpoB, 16S, or 23S rRNAs. Slow-growing NTM species harbored multiple virulence genes including type-VII secretion components, adhesion factors, and phospholipase C., Conclusion: Continued active laboratory- and population-based surveillance will further inform the prevalence of NTM species and STs, monitor emerging clones, and allow AR characterization., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: The use of intranasal dexmedetomidine is hampered by a limited understanding of its absorption pharmacokinetics., Methods: We examined the pharmacokinetics and feasibility of intranasal dexmedetomidine administered in the supine position to adult patients undergoing general anaesthesia. Twenty-eight patients between 35 and 80 years of age, ASA 1-3 and weight between 50 and 100 kg, who underwent elective unilateral total hip or knee arthroplasty under general anaesthesia were recruited. All patients received 100 μg of intranasal dexmedetomidine after anaesthesia induction. Six venous blood samples (at 0, 5, 15, 45, 60, 240 min timepoints from dexmedetomidine administration) were collected from each patient and dexmedetomidine plasma concentrations were measured. Concentration-time profiles after nasal administration were pooled with earlier data from a population analysis of intravenous dexmedetomidine (n = 202) in order to estimate absorption parameters using nonlinear mixed effects. Peak concentration (C MAX ) and time (T MAX ) were estimated using simulation (n = 1000) with parameter estimates and their associated variability., Results: There were 28 adult patients with a mean (SD) age of 66 (8) years and weight of 83 (10) kg. The mean weight-adjusted dose of dexmedetomidine was 1.22 (0.15) μg kg -1 . C MAX 0.273 μg L -1 was achieved at 98 min after intranasal administration (T MAX ). The relative bioavailability of dexmedetomidine was 80% (95% CI 75-91%). The absorption half-time (T ABS  = 120 min; 95% CI 90-147 min) was slower than that in previous pharmacokinetic studies on adult patients. Perioperative haemodynamics of all patients remained stable., Conclusions: Administration of intranasal dexmedetomidine in the supine position during general anaesthesia is feasible with good bioavailability. This administration method has slower absorption when compared to awake patients in upright position, with consequent concentrations attained after T MAX for several hours., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Infants aged <6 months are at increased risk for severe COVID-19 disease but are not yet eligible for COVID-19 vaccination; these children depend upon transplacental transfer of maternal antibody, either from vaccination or infection, for protection. COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) data were analyzed to estimate COVID-19-associated hospitalization rates and identify demographic and clinical characteristics and maternal vaccination status of infants aged <6 months hospitalized with laboratory-confirmed COVID-19. During October 2022-April 2024, COVID-NET identified 1,470 COVID-19-associated hospitalizations among infants aged <6 months. COVID-19-associated hospitalization rates among young infants were higher than rates among any other age group, except adults aged ≥75 years, and are comparable to rates among adults aged 65-74 years. The percentage of hospitalized infants whose mothers had been vaccinated during pregnancy was 18% during October 2022-September 2023 and decreased to <5% during October 2023-April 2024. Severe outcomes among infants hospitalized with COVID-19 occurred frequently: excluding newborns hospitalized at birth, approximately one in five young infants hospitalized with COVID-19 required admission to an intensive care unit, nearly one in 20 required mechanical ventilation, and nine infants died during their COVID-19-associated hospitalization. To help protect pregnant persons and infants too young to be vaccinated, prevention for these groups should focus on ensuring that pregnant persons receive recommended COVID-19 vaccines., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Andrea George reports grants from the Council of State and Territorial Epidemiologists during the study. Lauren Leegwater reports grants from the Michigan Department of Health and Human Services during the study. No other potential conflicts of interest were disclosed.

Australia and New Zealand are two countries in the Southern Pacific region. They share many pediatric anesthesia similarities in terms of medical organizational systems, education, training, and research, however there are important differences between the two nations in relation to geography, the First Nations populations and the history of colonization. While the standards for pediatric anesthesia and the specialty training requirements are set by the Australian and New Zealand College of Anesthetists and the Society for Pediatric Anesthesia in New Zealand and Australia, colonization has created distinct challenges that each nation now faces in order to improve the anesthetic care of its pediatric population. Australia generally has a high standard of living and good access to health care; disparities exist for First Nations People and for those living in rural or remote areas. Two influences have shaped training within New Zealand over the past 40 years; establishment of a national children's hospital in 1990 and, more importantly, acknowledgement that the First Nations people of New Zealand (Māori) have suffered because of failure to recognize their rights consequent to establishing a partnership treaty between Māori and the British Crown in 1840. Health inequities among Māori in New Zealand and First Nations People in Australia have implications for the health system, culturally appropriate approaches to treatment, and the importance of having an appreciation of First Nations people's history and culture, language, family structure, and cultural safety. Trainees in both countries need to be adequately supported in these areas in order for the sub-specialty of pediatric anesthesia to develop further and improve the anesthetic and surgical outcomes of our children., (© 2024 The Authors. Pediatric Anesthesia published by John Wiley & Sons Ltd.)

Cardiopulmonary bypass (CPB) can alter pharmacokinetic (PK) parameters and the drug may adsorb to the CPB device, altering exposure. Cefazolin is a beta-lactam antibiotic used for antimicrobial prophylaxis during cardiac surgery supported by CPB. Adsorption of cefazolin could result in therapeutic failure. An ex vivo study was undertaken using CPB devices primed and then dosed with cefazolin and samples were obtained over 1 hour of recirculation. Twelve experimental runs were conducted using different CPB device sizes (neonate, infant, child, and adult), device coatings (Xcoating™, Rheoparin®, PH.I.S.I.O), and priming solutions. The time course of saturable binding, using B max (binding capacity), K d (dissociation constant), and T2 off (half-time of dissociation), described cefazolin adsorption. B max estimates for the device sizes were neonate 40.0 mg (95% CI 24.3, 67.4), infant 48.6 mg (95% CI 5.97, 80.2), child 77.8 mg (95% CI 54.9, 103), and adult 196 mg (95% CI 191, 199). The Xcoating™ K d estimate was 139 mg/L (95% CI 27.0, 283) and the T2 off estimate was 98.4 min (95% CI 66.8, 129). The Rheoparin® and PH.I.S.I.O coatings had similar binding parameters with K d and T2 off estimates of 0.169 mg/L (95% CI 0.01, 1.99) and 4.94 min (95% CI 0.17, 59.4). The B max was small (< 10%) relative to a typical total patient dose during cardiac surgery supported by CPB. A dose adjustment for cefazolin based solely on drug adsorption is not required. This framework could be extended to other PK studies involving CPB., (© 2024 The Author(s). CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Chlorhexidine (CHD) is commonly included in surgical antiseptics and can be associated with adverse reactions ranging from contact dermatitis to anaphylaxis. A 32-year-old female presented to the OR for facial fat grafting. Surgical sites were prepped with CHD gluconate or topical iodine. Donor and recipient sites were infiltrated with local anesthetic injection prior to fat harvest and facial injection. Eleven days later, she presented with new painful, pruritic rash over donor sites where CHD had been applied prior to local anesthetic infiltration. Treatment with topical clobetasol and prednisone taper resulted in complete symptom resolution. This patient's response most likely represented a delayed type IV, T-cell mediated hypersensitivity. CHD is a known trigger of allergic reactions. Infiltration of local anesthetic may introduce skin prep into the subcutaneous tissue akin to intradermal testing. For those with delayed cutaneous reactions, steroids may provide symptomatic relief., Competing Interests: The authors declare they have no conflict of interest., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Aims: We assessed association between how teens with type 1 diabetes (T1D) perceived a text-messaging (TM) reminder system to check glucose levels and how their perceptions related to their responsiveness to TM reminders to check glucose levels., Methods: Teens received TM reminders 1-4 times daily to check glucose levels and to reply with the result. Qualitative assessments were performed quarterly. Teens were categorized by perceptions expressed at the majority of the visits and their TM responsiveness over 18 months., Results: There were 135 teens (51 % male), with a mean age of 14.8 ± 1.2 years, receiving TM reminders. Distribution of participants' perceptions was 37 % positive (POS), 35 % neutral (with both positive and negative responses (POS/NEG)), and 28 % negative (NEG). Teens with POS perceptions about TM reminders were more likely to respond with a glucose value to the TM reminders than teens with NEG or POS/NEG perceptions (p = 0.002). Youth with POS perceptions and TM responsiveness on ≥ 50 % of days had an 0.81 % improvement in their HbA1c (p = 0.004) over 18 months., Conclusions: Teens with POS perceptions to TM reminders were likely to respond and their responsiveness yielded glycemic benefit, suggesting need to consider opinions of teens with T1D to maximize their intervention engagement and resulting benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objectives: Milrinone is an inotrope and vasodilator used for prophylaxis or treatment of low cardiac output syndrome after weaning from cardiopulmonary bypass (CPB). It is renally eliminated and has an acceptable therapeutic range of 100-300 μg/L, but weight-based dosing alone is associated with poor target attainment. We aimed to develop a population pharmacokinetic model for milrinone from premature neonates to adolescents, and to evaluate how age, renal function and recovery from CPB may impact dose selection., Methods: Fifty paediatric patients (aged 4 days to 16 years) were studied after undergoing cardiac surgery supported by CPB. Data from 29 premature neonates (23-28 weeks' postmenstrual age) treated for prophylaxis of low systemic blood flow were available for a pooled pharmacokinetic analysis. Population parameters were estimated using non-linear mixed effects modelling (NONMEM 7.5.1)., Results: There were 369 milrinone measurements available for analysis. A one-compartment model with zero-order input and first-order elimination was used to describe milrinone disposition. Population parameters were clearance 17.8 L/70 kg [95% CI 15.8-19.9] and volume 20.4 L/h/70 kg [95% CI 17.8-22.1]. Covariates included size, postmenstrual age and renal function for clearance, and size and postnatal age for volume. Milrinone clearance is reduced by 39.5% [95% CI 24.0-53.7] immediately after bypass, and recovers to baseline clearance with a half-time of 12.0 h [95% CI 9.7-15.2]. Milrinone volume was 2.07 [95% CI 1.87-2.27] times greater at birth than the population standard and decreased over the first days of life with a half-time of 0.977 days [95% CI 0.833-1.12]., Conclusion: Milrinone is predominately renally eliminated and so renal function is an important covariate describing variability in clearance. Increasing clearance over time likely reflects increasing cardiac output and renal perfusion due to milrinone and return to baseline following CPB., (© 2024. The Author(s).)

Objective: Patients treated for oropharyngeal cancer (OPC) have historically demonstrated high feeding tube rates for decreased oral intake and malnutrition. We re-examined feeding tube practices in these patients., Study Design: Retrospective analysis of prospective cohort from 2015 to 2021., Setting: Single-institution NCI-Designated Comprehensive Cancer Center., Methods: With IRB approval, patients with new oropharyngeal squamous cell cancer or (unknown primary with neck metastasis) were enrolled. Baseline swallowing was assessed via videofluoroscopy and Performance Status Scale for Head and Neck Cancer (PSSHN). G-tubes or nasogastric tubes (NGT) were placed for weight loss before, during, or after treatment. Prophylactic NGT were placed during transoral robotic surgery (TORS). Tube duration was censored at last disease-free follow-up. Multivariate regression was performed for G-tube placement (odds ratio [OR] [95% confidence interval [CI]) and removal (Cox hazard ratio, hazard ratio [HR] [95% CI])., Results: Of 924 patients, most had stage I to II (81%), p16+ (89%), node-positive (88%) disease. Median follow-up was 2.6 years (interquartile range 1.5-3.9). Most (91%) received radiation/chemoradiation, and 16% received TORS. G-tube rate was 27% (5% after TORS). G-tube risk was increased with chemoradiation (OR 2.78 [1.87-4.22]) and decreased with TORS (OR 0.31 [0.15-0.57]) and PSSHN-Diet score ≥60 (OR 0.26 [0.15-0.45]). G-tube removal probability over time was lower for T3 to T4 tumors (HR 0.52 [0.38-0.71]) and higher for PSSHN-Diet score ≥60 (HR 1.65 [1.03-2.66])., Conclusions: In this modern cohort of patients treated for OPC, 27% received G-tubes-50% less than institutional rates 10 years ago. Patients with preserved baseline swallowing and/or those eligible for TORS may have lower G-tube risk and duration., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

As lipidomics experiments increase in scale and complexity, data processing tools must support workflows for new liquid chromatography-mass spectrometry (LC-MS) methods while simultaneously supporting quality controls to maximize the confidence in lipid identifications. LipiDex 2 improves lipidomics data processing algorithms from LipiDex 1 and introduces new tools for spectral matching and peak annotation functions, with improvements in speed and user-friendliness. In silico spectral library generation now supports tandem mass spectral (MS n ) tree-based fragmentation methods, and the LipiDex 2 workflow fully integrates the fragmentation logic into the data processing steps to enable lipid identification at the appropriate level of structural resolution. Finally, LipiDex 2 features new modules for automated quality control checks that also allow users to visualize data quality in a data dashboard user interface.

Introduction: Adults with depression have higher rates of cigarette smoking and are more likely to relapse than those without depression. Pharmacological, psychological, and combined interventions have largely yielded small improvements in smoking outcomes for adults with depression. Aerobic exercise (AE) may facilitate smoking cessation in this subpopulation., Methods: This study was a 12-week two-arm randomized controlled trial that evaluated the effect of a moderate-intensity AE program compared to a health education contact (HEC) control on smoking cessation in adults with elevated depressive symptoms (mild to severe). Participants (n = 231) were randomized to AE or HEC and received smoking cessation treatment (telephone counseling and nicotine replacement therapy). Primary (biologically confirmed 7-day point prevalence abstinence) and secondary (depressive symptoms, objective and self-reported physical activity, and cardiorespiratory fitness) outcomes were assessed at baseline, 3, 6, and 12 months. Data were analyzed with mixed-effects generalized linear models controlling for age, gender, nicotine dependence, history of major depression disorder, and month of follow-up assessment., Results: There were no significant differences in primary or secondary outcomes between the AE and HEC groups., Conclusions: The AE program was not superior to HEC in facilitating smoking cessation, increases in physical activity, or improved depressive symptoms. Given evidence for the positive acute effects of exercise on mood and smoking urges, future research should consider testing alternative exercise approaches for aiding smoking cessation beyond structured, AE programs., Implications: This study found that an adjunctive aerobic exercise (AE) program was not superior to a health education contact control for adults with elevated depressive symptoms, all of whom also received standard smoking cessation treatment. This finding adds to the growing body of literature that structured AE programs for smoking cessation may have limited efficacy for cessation outcomes. Future research is needed to test alternative methods of integrating AE into smoking cessation treatment, such as strategically using exercise to manage cravings and low mood in the moment., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Youth-onset type 2 diabetes is associated with poor glycemic control and early onset of complications. Identification of psychosocial factors associated with poor glycemic control is needed to inform efficacious interventions., Objective: To identify psychosocial factors associated with glycated hemoglobin (HbA1c) levels in young adults with youth-onset type 2 diabetes., Design, Setting, and Participants: For the iCount cohort study, HbA1c levels were measured twice (at baseline [T1] and at 1 year [T2]) during the last years (2017-2019) of the observational phase of the multicenter Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY2) study. Participants were young adults who had been diagnosed with type 2 diabetes during childhood or adolescence. Data were analyzed from December 2021 to September 2023., Main Outcomes and Measures: Glycemic control was examined categorically (high [≥8.0%] vs low [<8.0%] HbA1c), continuously (HbA1c level), and over time (change in HbA1c: decreased ≥0.5%, remained stable, or increased ≥0.5%). Psychosocial measures included beliefs about medicines, depression and anxiety symptoms, diabetes distress, diabetes self-efficacy, self-management support, and unmet material needs. Multivariable logistic and linear regression models evaluated the association of each psychosocial factor with the probability of T2 HbA1c of 8.0% or greater, T2 HbA1c level, and change in HbA1c., Results: Of the 411 TODAY2 participants approached, 381 enrolled in the iCount study, and 348 with T1 and T2 HbA1c data comprised the analysis group. The 348 participants had a mean (SD) age of 26.1 (2.5) years and a mean (SD) HbA1c of 9.4% (2.8%). Most participants (229 [65.8%]) were women. In adjusted multivariable regressions, greater beliefs that diabetes medicines are necessary (odds ratio [OR], 1.19 [95% CI, 1.03-1.37]; P = .02), concerns about medicines (OR, 1.20 [95% CI, 1.00-1.45]; P = .049), diabetes distress (OR, 1.08 [95% CI, 1.02-1.15]; P = .006), and high distress (OR, 2.18 [95% CI, 1.15-4.13]; P = .02) increased the odds of high HbA1c at T2. Greater support (OR, 0.67 [95% CI, 0.46-0.97]; P = .04) and diabetes self-efficacy (OR, 0.91 [95% CI, 0.84-0.99]; P = .02) decreased the odds of high HbA1c at T2. Diabetes distress was associated with higher HbA1c level at T2 (coefficient, 0.08 [95% CI, 0.02-0.13]; P = .01). Beliefs that diabetes medicines are necessary (OR, 1.20 [95% CI, 1.03-1.39]; P = .02) and concerns about medicines (OR, 1.22 [95% CI, 1.00-1.47]; P = .048) increased the odds of an HbA1c decrease of at least 0.5% over 1 year., Conclusions and Relevance: In this cohort study of young adults with youth-onset type 2 diabetes, beliefs about medicines, high diabetes distress, low diabetes self-efficacy, and self-management support were associated with high HbA1c over time. Future research should assess whether interventions that address these factors result in improved glycemic control in this at-risk group.

Background: Sleep disruption, a common symptom among patients requiring cardiovascular surgery, is a potential risk factor for the development of postoperative delirium. Postoperative delirium is a disorder of acute disturbances in cognition associated with prolonged hospitalization, cognitive decline, and mortality., Objective: The aim of this study was to evaluate the feasibility and acceptability of using polysomnography (PSG) to capture sleep in patients with scheduled cardiothoracic surgery., Methods: Wireless limited PSG assessed sleep at baseline (presurgery at home), postoperatively in the intensive care unit, and at home post hospital discharge. Primary outcomes were quality and completeness of PSG signals, and acceptability by participants and nursing staff., Results: Among 15 patients, PSG data were of high quality, and mean percentage of unscorable data was 5.5% ± 11.1%, 3.7% ± 5.4%, and 3.7% ± 8.4% for baseline, intensive care unit, and posthospitalization measurements, respectively. Nurses and patients found the PSG monitor acceptable., Conclusions: Wireless, limited PSG to capture sleep across the surgical continuum was feasible, and data were of high quality. Authors of future studies will evaluate associations of sleep indices and development of postoperative delirium in this high-risk population., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To determine the distribution of diagnosed SARS-CoV-2 infections by testing modality (at-home rapid antigen [home tests] versus laboratory-based tests in clinical settings [clinical tests]), assess factors associated with clinical testing, and estimate the true total number of diagnosed infections in New York State (NYS)., Methods: We conducted an online survey among NYS residents and analyzed data from 1012 adults and 246 children with diagnosed infection July 13-December 7, 2022. Weighted descriptive and logistic regression model analyses were conducted. Weighted percentages and prevalence ratios by testing modality were generated. The percent of infections diagnosed by clinical tests via survey data were synthesized with daily lab-reported results to estimate the total number of diagnosed SARS-CoV-2 infections in NYS July 1-December 31, 2022., Results: Over 70% of SARS-CoV-2 infections in NYS during the study period were diagnosed exclusively with home tests. Diagnosis with a clinical test was associated with age, race/ethnicity, and region among adults, and sex, age, and education among children. We estimate 4.1 million NYS residents had diagnosed SARS-CoV-2 infection July 1-December 31, 2022, compared to 1.1 million infections reported over the same period., Conclusions: Most SARS-CoV-2 infections in NYS were diagnosed exclusively with home tests. Surveillance metrics using laboratory-based reporting data underestimate diagnosed infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Therapeutic RNAs are routinely modified during their synthesis to ensure proper drug uptake, stability, and efficacy. Phosphorothioate (PS) RNA, molecules in which one or more backbone phosphates are modified with a sulfur atom in place of standard nonbridging oxygen, is one of the most common modifications because of ease of synthesis and pharmacokinetic benefits. Quality assessment of RNA synthesis, including modification incorporation, is essential for drug selectivity and performance, and the synthetic nature of the PS linkage incorporation often reveals impurities. Here, we present a comprehensive analysis of PS RNA via tandem mass spectrometry (MS). We show that activated ion-negative electron transfer dissociation MS/MS is especially useful in diagnosing PS incorporation, producing diagnostic a- and z-type ions at PS linkage sites, beyond the standard d- and w-type ions. Analysis using resonant and beam-type collision-based activation reveals that, overall, more intense sequence ions and base-loss ions result when a PS modification is present. Furthermore, we report increased detection of b- and x-type product ions at sites of PS incorporation, in addition to the standard c- and y-type ions. This work reveals that the gas-phase chemical stability afforded by sulfur alters RNA dissociation and necessitates inclusion of additional product ions for MS/MS of PS RNA., Competing Interests: Conflict of interest J. J. C. is a consultant for Thermo Fisher Scientific, 908 Devices, and Seer. All other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Since the 1970s, a plethora of tools have been introduced to support the medication use process. However, automation initiatives to assist pharmacists in prospectively reviewing medication orders are lacking. The review of many medications may be protocolized and implemented in an algorithmic fashion utilizing discrete data from the electronic health record (EHR). This research serves as a proof of concept to evaluate the capability and effectiveness of an electronic prospective medication order review (EPMOR) system compared to pharmacists' review., Materials and Methods: A subset of the most frequently verified medication orders were identified for inclusion. A team of clinical pharmacist experts developed best-practice EPMOR criteria. The established criteria were incorporated into conditional logic built within the EHR. Verification outcomes from the pharmacist (human) and EPMOR (automation) were compared., Results: Overall, 13 404 medication orders were included. Of those orders, 13 133 passed pharmacist review, 7388 of which passed EPMOR. A total of 271 medication orders failed pharmacist review due to order modification or discontinuation, 105 of which passed EPMOR. Of the 105 orders, 19 were duplicate orders correctly caught by both EPMOR and pharmacists, but the opposite duplicate order was rejected, 51 orders failed due to scheduling changes., Discussion: This simulation was capable of effectively discriminating and triaging orders. Protocolization and automation of the prospective medication order review process in the EHR appear possible using clinically driven algorithms., Conclusion: Further research is necessary to refine such algorithms to maximize value, improve efficiency, and minimize safety risks in preparation for the implementation of fully automated systems., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Intranasal diamorphine is a potential treatment for breakthrough pain but few paediatric data are available to assist dose estimation., Aim: To determine an intranasal diamorphine dose in children through an understanding of pharmacokinetics., Design: A systematic review of the literature was undertaken to seek diamorphine pharmacokinetic parameters in neonates, children and adults. Parenteral and enteral diamorphine bioavailability were reviewed with respect to formation of the major metabolite, morphine. Clinical data quantifying equianalgesic effects of diamorphine and morphine were reviewed., Review Sources: PubMed (1960-2020); EMBASE (1980-2020); IPA (1973-2020) and original human research studies that reported diacetylmorphine and metabolite after any dose or route of administration., Results: The systematic review identified 19 studies: 16 in adults and 1 in children and 2 neonatal reports. Details of study participants were extracted. Age ranged from premature neonates to 67 years and weight 1.4-88 kg. Intranasal diamorphine bioavailability was predicted as 50%. The equianalgesic intravenous conversion ratio of morphine:diamorphine was 2:1. There was heterogeneity between pharmacokinetic parameter estimates attributed to routes of administration, lack of size standardisation, methodology and pharmacokinetic analysis. Estimates of the pharmacokinetic parameters clearance and volume of distribution were reduced in neonates. There were insufficient paediatric data to characterise clearance or volume maturation of either diamorphine or its metabolites., Conclusions: We estimate equianalgesic ratios of intravenous morphine:diamorphine 2:1, intravenous morphine:intranasal diamorphine 1:1 and oral morphine:intranasal diamorphine of 1:3. These ratios are based on adult literature, but are reasonable for deciding on an initial dose of 0.1 mg/kg in children 4-13 years., Competing Interests: Competing interests: Professor Ian Wong is the founder of Therakind Ltd which was funded by Wockhardt Pharmaceutical to conduct the clinical studies for Ayendi® (diamorphine hydrochloride) licensing application., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Persons with HIV (PWH) are at increased risk for bacterial infections, and previous publications document an increased risk for invasive meningococcal disease (IMD) in particular. This analysis provides evidence that PWH face a 6-fold increase in risk for IMD based on Active Bacterial Core surveillance data collected during 2009-2019., Competing Interests: Potential conflicts of interest. Lee H. Harrison reports reimbursement for travel to attend meetings for Merck, Pfizer, Sanofi, and GSK and participation on a Merck data safety monitoring board. Ruth Lynfield reports receiving payment for work as an associate editor for the American Academy of Pediatrics’ (AAP) Red Book, which was donated to the Minnesota Department of Health, support from the Council of State and Territorial Epidemiologists for travel to meetings as president and vice president, travel support to ID Week by the Infectious Diseases Society of America, and support from AAP for travel to a committee meeting on infectious diseases in her role as associate editor. William Schaffner reports payment from the National Foundation for Infectious Disease for a leadership or fiduciary role. No other potential conflicts of interest were disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: The effect of the anticoagulant, dabigatran, and its antagonist, idarucizumab, on coagulation remains poorly quantified. There are few pharmacokinetic-pharmacodynamic data available to determine dabigatran dose in humans or animals undergoing cardiopulmonary bypass., Methods: Five sheep were given intravenous dabigatran 4 mg/kg. Blood samples were collected for thromboelastometric reaction time (R-time) and drug assay at 5, 15, 30, 60, 120, 240, 480 min, and 24 h. Plasma dabigatran concentrations and R-times were analyzed using an integrated pharmacokinetic-pharmacodynamic model using non-linear mixed effects. The impact of idarucizumab 15 mg/kg administered 120 min after dabigatran 4 mg/kg and its effect on R-time was observed., Results: A 2-compartment model described dabigatran pharmacokinetics with a clearance (CL 0.0453 L/min/70 kg), intercompartment clearance (Q 0.268 L/min/70 kg), central volume of distribution (V1 2.94 L/70 kg), peripheral volume of distribution (V2 9.51 L/70 kg). The effect compartment model estimates for a sigmoid E MAX model using Reaction time had an effect site concentration (Ce 50 64.2 mg/L) eliciting half of the maximal effect (E MAX 180 min). The plasma-effect compartment equilibration half time (T 1/2 keo) was 1.04 min. Idarucizumab 15 mg/kg reduced R-time by approximately 5 min., Conclusions: Dabigatran reversibly binds to the active site on the thrombin molecule, preventing activation of coagulation factors. The pharmacologic target concentration strategy uses pharmacokinetic-pharmacodynamic information to inform dose. A loading dose of dabigatran 0.25 mg/kg followed by a maintenance infusion of dabigatran 0.0175 mg/kg/min for 30 min and a subsequent infusion dabigatran 0.0075 mg/kg/min achieves a steady state target concentration of 5 mg/L in a sheep model., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Jet injection is a drug delivery system without a needle. A compressed liquid drug formulation pierces the skin, depositing the drug into the subcutaneous or intramuscular tissues. We investigated the pharmacokinetics and patient experience of dexmedetomidine administered using jet injection in six healthy adult study participants. This needleless jet injection device was used to administer dexmedetomidine 0.5 μg/kg to the subcutaneous tissues overlying the deltoid muscle. Serum concentrations of dexmedetomidine were assayed at approximately 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours after administration. Pharmacokinetic interrogation of concentration time profiles estimated an absorption half time for jet-injected dexmedetomidine of 21 minutes (coefficient of variation 69.4%) with a relative bioavailability assumed unity. In our samples the measured median peak (range) concentration was 0.164 μg/l (0.011-0.325 μg/l), observed in the sample taken at a median (range) of 13.5 minutes (11-30 minutes). The Richmond agitation sedation scale was used to assess the sedative effect, and scored 0 (alert and calm) or -1 (drowsy) in all participants. Five of the six participants stated they would prefer jet injection to needle injection in the future and one had no preference. The findings suggest that the use of a larger dose (>2 μg/kg) would be required to achieve the clinically relevant target concentration of 1 μg/l necessary to achieve deeper sedation (Richmond agitation sedation scale ≤3)., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.