Slow rewarming after hypothermia does not ameliorate white matter injury after hypoxia-ischemia in near-term fetal sheep.

BACKGROUND: The optimal rate to rewarm infants after therapeutic hypothermia is unclear. In this study we examined whether slow rewarming after 72 h of hypothermia would attenuate white matter injury. METHODS: Near-term fetal sheep received sham occlusion (n = 8) or cerebral ischemia for 30 min, followed by normothermia (n = 7) or hypothermia from 3-72 h, with either spontaneous fast rewarming (n = 8) within 1 h, or slow rewarming at ~0.5 °C/h (n = 8) over 10 h. Fetuses were euthanized 7 days later. RESULTS: Ischemia was associated with loss of total and mature oligodendrocytes, reduced expression of myelin proteins and induction of microglia and astrocytes, compared with sham controls (P < 0.05). Both hypothermia protocols were associated with a significant increase in numbers of total and mature oligodendrocytes, area fraction of myelin proteins and reduced numbers of microglia and astrocytes, compared with ischemia-normothermia (P < 0.05). There was no difference in the number of oligodendrocytes, microglia or astrocytes or expression of myelin proteins between fast and slow rewarming after hypothermia. CONCLUSION: The rate of rewarming after a clinically relevant duration of hypothermia had no apparent effect on white matter protection by hypothermia after cerebral ischemia in near-term fetal sheep. IMPACT: Persistent white matter injury is a major contributor to long-term disability after neonatal encephalopathy despite treatment with therapeutic hypothermia. The optimal rate to rewarm infants after therapeutic hypothermia is unclear; current protocols were developed on a precautionary basis. We now show that slow rewarming at 0.5 °C/h did not improve histological white matter injury compared with rapid spontaneous rewarming after a clinically established duration of hypothermia in near-term fetal sheep.

Benefits, implementation and sustainability of innovative paediatric models of care for children with type 1 diabetes: a systematic review.

BACKGROUND AND AIM: The evidence about the acceptability and effectiveness of innovative paediatric models of care for Type 1 diabetes is limited. To address this gap, we synthesised literature on implemented models of care, model components, outcomes, and determinants of implementation and sustainability. METHODS: A systematic review was conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Database searches of Medline, CINAHL, EMBASE and Scopus were conducted. Empirical studies focused on Type 1 diabetes paediatric models of care, published from 2010 to 2022 in English were included. RESULTS: Nineteen extant studies reported on models and their associations with health and psychosocial outcomes, patient engagement with healthcare, and healthcare costs. Thirteen studies described multidisciplinary teamwork, education and capacity building that supported self-care. Four studies involved shared decision making between providers and patients, and two discussed outreach support where technology was an enabler. Fourteen studies reported improvements in health outcomes (e.g. glycaemic control), mostly for models that included multidisciplinary teams, education, and capacity building (11 studies), outreach support or shared care (3 studies). Four studies reported improvements in quality of life, three reported increased satisfaction for patients and carers and, and one reported improved communication. Four of five studies describing shared care and decision-making reported improvements in quality of life, support and motivation. Outreach models reported no negative outcomes, however, accessing some models was limited by technological and cost barriers. Eight studies reported on model sustainability, but only half reported implementation determinants; none reported applying a theoretical framework to guide their research. CONCLUSION: Some health and psychosocial benefits were associated with newer models. To address knowledge gaps about implementation determinants and model sustainability, longitudinal studies are needed to inform future adoption of innovative models of care for children with Type 1 diabetes.

Pathophysiological processes underlying hidden hearing loss revealed in Kcnt1/2 double knockout mice.

Presbycusis is a prevalent condition in older adults characterized by the progressive loss of hearing due to age-related changes in the cochlea, the auditory portion of the inner ear. Many adults also struggle with understanding speech in noise despite having normal auditory thresholds, a condition termed "hidden" hearing loss because it evades standard audiological assessments. Examination of animal models and postmortem human tissue suggests that hidden hearing loss is also associated with age-related changes in the cochlea and may, therefore, precede overt age-related hearing loss. Nevertheless, the pathological mechanisms underlying hidden hearing loss are not understood, which hinders the development of diagnostic biomarkers and effective treatments for age-related hearing loss. To fill these gaps in knowledge, we leveraged a combination of tools, including transcriptomic profiling and morphological and functional assessments, to identify these processes and examine the transition from hidden to overt hearing loss. As a novel approach, we took advantage of a recently characterized model of hidden hearing loss: Kcnt1/2 double knockout mice. Using this model, we find that even before observable morphological pathology, hidden hearing loss is associated with significant alteration in several processes, notably proteostasis, in the cochlear sensorineural structures, and increased susceptibility to overt hearing loss in response to noise exposure and aging. Our findings provide the first insight into the pathophysiology associated with the earliest and, therefore, most treatable stages of hearing loss and provide critical insight directing future investigation of pharmaceutical strategies to slow and possibly prevent overt age-related hearing loss.

Retrospective Cohort Study of Additional Procedures and Transplant-Free Survival for Patients With Functionally Single Ventricle Disease Undergoing Staged Palliation in England and Wales.

BACKGROUND: Reinterventions may influence the outcomes of children with functionally single-ventricle (f-SV) congenital heart disease. METHODS AND RESULTS: We undertook a retrospective cohort study of children starting treatment for f-SV between 2000 and 2018 in England, using the national procedure registry. Patients were categorized based on whether they survived free of transplant beyond 1 year of age. Among patients who had transplant-free survival beyond 1 year of age, we explored the relationship between reinterventions in infancy and the outcomes of survival and Fontan completion, adjusting for complexity. Of 3307 patients with f-SV, 909 (27.5%), had no follow-up beyond 1 year of age, among whom 323 (35.3%) had ≥1 reinterventions in infancy. A total of 2398 (72.5%) patients with f-SV had transplant-free survival beyond 1 year of age, among whom 756 (31.5%) had ≥1 reinterventions in infancy. The 5-year transplant-free survival and cumulative incidence of Fontan, among those who survived infancy, were 93.4% (95% CI, 92.4%-94.4%) and 79.3% (95% CI, 77.4%-81.2%), respectively. Both survival and Fontan completion were similar for those with a single reintervention and those who had no reinterventions. Patients who had >1 additional surgery (adjusted hazard ratio, 3.93 [95% CI, 1.87-8.27] P<0.001) had higher adjusted risk of mortality. Patients who had >1 additional interventional catheter (adjusted subdistribution hazard ratio, 0.71 [95% CI, 0.52-0.96] P=0.03) had a lower likelihood of achieving Fontan. CONCLUSIONS: Among children with f-SV, the occurrence of >1 reintervention in the first year of life, especially surgical reinterventions, was associated with poorer prognosis later in childhood.

Shiga toxin-producing Escherichia coli O157:H7 outbreak associated with school field trips at a farm animal exhibit-Tennessee, September-October 2023.

AIMS: In October 2023, the Tennessee Department of Health identified an outbreak of Shiga toxin-producing Escherichia coli (STEC) O157:H7 infections among elementary school students who attended school field trips to the same farm animal exhibit. Our aim was to determine STEC source and prevent additional illnesses by initiating epidemiologic, laboratory and environmental investigations. METHODS AND RESULTS: We identified cases using laboratory-based surveillance and by surveying caregivers of children who attended the exhibit. Probable cases were defined as illness with abdominal cramps or diarrhoea after attendance; confirmed cases were laboratory-confirmed STEC infection in an attendee or household contact. A site visit was conducted, and event organizers were interviewed. Human stool, animal faeces and environmental samples were tested for STEC O157:H7 by real-time polymerase chain reaction (PCR), culture and whole-genome sequencing (WGS). Approximately 2300 elementary school students attended the animal exhibit during 2 days. Field trip activities included contact with different farm animal species, drinking pasteurized milk outside animal enclosures and eating lunch in a separate building onsite. We received survey responses from 399 caregivers for 443 (19%) animal exhibit attendees. We identified 9 confirmed and 55 probable cases with illness onset dates during 26 September to 12 October. Seven children aged 1-7 years were hospitalized. Four children aged 1-6 years experienced haemolytic uraemic syndrome; none died. Laboratory testing identified STEC O157:H7 by culture from eight human stool samples with 0-1 allele difference by WGS. Three environmental samples had Shiga toxin (stx 2) genes detected by PCR, but no STEC isolates were recovered by culture. CONCLUSIONS: This is the largest reported STEC O157:H7 outbreak associated with an animal exhibit in Tennessee. We identified opportunities for educating school staff, event organizers and families about zoonotic disease risks associated with animal contact and published prevention measures.

Bilateral remote ischemic conditioning in children: A two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery.

Objective: The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis. Methods: We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants. Results: Between October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 µg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 µg/L/h, n = 58) (mean difference, 13.2 µg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups. Conclusions: Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery.

Heterogeneity, Bayesian thinking, and phenotyping in critical care: A primer.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To familiarize clinicians with the emerging concepts in critical care research of Bayesian thinking and personalized medicine through phenotyping and explain their clinical relevance by highlighting how they address the issues of frequent negative trials and heterogeneity of treatment effect. SUMMARY: The past decades have seen many negative (effect-neutral) critical care trials of promising interventions, culminating in calls to improve the field's research through adopting Bayesian thinking and increasing personalization of critical care medicine through phenotyping. Bayesian analyses add interpretive power for clinicians as they summarize treatment effects based on probabilities of benefit or harm, contrasting with conventional frequentist statistics that either affirm or reject a null hypothesis. Critical care trials are beginning to include prospective Bayesian analyses, and many trials have undergone reanalysis with Bayesian methods. Phenotyping seeks to identify treatable traits to target interventions to patients expected to derive benefit. Phenotyping and subphenotyping have gained prominence in the most syndromic and heterogenous critical care disease states, acute respiratory distress syndrome and sepsis. Grouping of patients has been informative across a spectrum of clinically observable physiological parameters, biomarkers, and genomic data. Bayesian thinking and phenotyping are emerging as elements of adaptive clinical trials and predictive enrichment, paving the way for a new era of high-quality evidence. These concepts share a common goal, sifting through the noise of heterogeneity in critical care to increase the value of existing and future research. CONCLUSION: The future of critical care medicine will inevitably involve modification of statistical methods through Bayesian analyses and targeted therapeutics via phenotyping. Clinicians must be familiar with these systems that support recommendations to improve decision-making in the gray areas of critical care practice.

Safety, tolerability, viral kinetics, and immune correlates of protection in healthy, seropositive UK adults inoculated with SARS-CoV-2: a single-centre, open-label, phase 1 controlled human infection study.

BACKGROUND: A SARS-CoV-2 controlled human infection model (CHIM) has been successfully established in seronegative individuals using a dose of 1×101 50% tissue culture infectious dose (TCID50) pre-alpha SARS-CoV-2 virus. Given the increasing prevalence of seropositivity to SARS-CoV-2, a CHIM that could be used for vaccine development will need to induce infection in those with pre-existing immunity. Our aim was to find a dose of pre-alpha SARS-CoV-2 virus that induced infection in previously infected individuals. METHODS: Healthy, UK volunteers aged 18-30 years, with proven (quantitative RT-PCR or lateral flow antigen test) previous SARS-CoV-2 infection (with or without vaccination) were inoculated intranasally in a stepwise dose escalation CHIM with either 1×101, 1×102, 1×10³, 1×104, or 1×105 TCID50 SARS-CoV-2/human/GBR/484861/2020, the same virus used in the seronegative CHIM. Post-inoculation, volunteers were quarantined in functionally negative pressure rooms (Oxford, UK) for 14 days and until 12-hourly combined oropharyngeal-nasal swabs were negative for viable virus by focus-forming assay. Outpatient follow-up continued for 12 months post-enrolment, with additional visits for those who developed community-acquired SARS-CoV-2 infection. The primary objective was to identify a safe, well tolerated dose that induced infection (defined as two consecutive SARS-CoV-2 positive PCRs starting 24 h after inoculation) in 50% of seropositive volunteers. This study is registered with ClinicalTrials.gov (NCT04864548); enrolment and follow-up to 12 months post-enrolment are complete. FINDINGS: Recruitment commenced on May 6, 2021, with the last volunteer enrolled into the dose escalation cohort on Nov 24, 2022. 36 volunteers were enrolled, with four to eight volunteers inoculated in each dosing group from 1×101 to 1×105 TCID50 SARS-CoV-2. All volunteers have completed quarantine, with follow-up to 12 months complete. Despite dose escalation to 1×105 TCID50, we were unable to induce sustained infection in any volunteers. Five (14%) of 36 volunteers were considered to have transient infection, based on the kinetic of their PCR-positive swabs. Transiently infected volunteers had significantly lower baseline mucosal and systemic SARS-CoV-2-specific antibody titres and significantly lower peripheral IFNγ responses against a CD8+ T-cell SARS-CoV-2 peptide pool than uninfected volunteers. 14 (39%) of 36 volunteers subsequently developed breakthrough infection with the omicron variant after discharge from quarantine. Most adverse events reported by volunteers in quarantine were mild, with fatigue (16 [44%]) and stuffy nose (16 [44%]) being the most common. There were no serious adverse events. INTERPRETATION: Our study demonstrates potent protective immunity induced by homologous vaccination and homologous or heterologous previous SARS-CoV-2 infection. The community breakthrough infections seen with the omicron variant supports the use of newer variants to establish a model with sufficient rate of infection for use in vaccine and therapeutic development. FUNDING: Wellcome Trust and Department for Health and Social Care.

Hemolytic Properties of Fine Particulate Matter (PM2.5) in In Vitro Systems.

Epidemiological studies have suggested that inhalation exposure to particulate matter (PM) air pollution, especially fine particles (i.e., PM2.5 (PM with an aerodynamic diameter of 2.5 microns or less)), is causally associated with cardiovascular health risks. To explore the toxicological mechanisms behind the observed adverse health effects, the hemolytic activity of PM2.5 samples collected during different pollution levels in Beijing was evaluated. The results demonstrated that the hemolysis of PM2.5 ranged from 1.98% to 7.75% and demonstrated a clear dose-response relationship. The exposure toxicity index (TI) is proposed to represent the toxicity potential of PM2.5, which is calculated by the hemolysis percentage of erythrocytes (red blood cells, RBC) multiplied by the mass concentration of PM2.5. In a pollution episode, as the mass concentration increases, TI first increases and then decreases, that is, TI (low pollution levels) < TI (heavy pollution levels) < TI (medium pollution levels). In order to verify the feasibility of the hemolysis method for PM toxicity detection, the hemolytic properties of PM2.5 were compared with the plasmid scission assay (PSA). The hemolysis results had a significant positive correlation with the DNA damage percentages, indicating that the hemolysis assay is feasible for the detection of PM2.5 toxicity, thus providing more corroborating information regarding the risk to human cardiovascular health.

Antimicrobial resistance in bacterial wound, skin, soft tissue and surgical site infections in Central, Eastern, Southern and Western Africa: A systematic review and meta-analysis.

Antimicrobial resistance (AMR) is a major global threat and AMR-attributable mortality is particularly high in Central, Eastern, Southern and Western Africa. The burden of clinically infected wounds, skin and soft tissue infections (SSTI) and surgical site infections (SSI) in these regions is substantial. This systematic review reports the extent of AMR from sampling of these infections in Africa, to guide treatment. It also highlights gaps in microbiological diagnostic capacity. PubMed, MEDLINE and Embase were searched for studies reporting the prevalence of Staphylococcus aureus, Eschericheria coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii in clinically infected wounds, SSTI and SSI in Central, Eastern, Southern or Western Africa, and studies reporting AMR from such clinical isolates. Estimates for proportions were pooled in meta-analyses, to estimate the isolation prevalence of each bacterial species and the proportion of resistance observed to each antibiotic class. The search (15th August 2022) identified 601 articles: 59 studies met our inclusion criteria. S. aureus was isolated in 29% (95% confidence interval [CI] 25% to 34%) of samples, E. coli in 14% (CI 11% to 18%), K. pneumoniae in 11% (CI 8% to 13%), P. aeruginosa in 14% (CI 11% to 18%) and A. baumannii in 8% (CI 5% to 12%). AMR was high across all five species. S. aureus was resistant to methicillin (MRSA) in >40% of isolates. E. coli and K. pneumoniae were both resistant to amoxicillin-clavulanic acid in ≥80% of isolates and resistant to aminoglycosides in 51% and 38% of isolates respectively. P. aeruginosa and A. baumannii were both resistant to anti-pseudomonal carbapenems (imipenem or meropenem) in ≥20% of isolates. This systematic review found that a large proportion of the organisms isolated from infected wounds, SSTI and SSI in Africa displayed resistance patterns of World Health Organisation (WHO) priority pathogens for critical or urgent antimicrobial development.

Evaluation of Critical Care Pharmacist Evening Services at an Academic Medical Center.

Purpose: Critical care pharmacists are considered essential members of the healthcare team; however, justification and recruitment of new positions, especially in the evening or weekend shifts, remains a significant challenge. The purpose of this study was to investigate the number of interventions, type of interventions, and associated cost savings with the addition of 1 board certified critical care clinical pharmacist to evening shift. Methods: This was a prospective collection and characterization of 1 evening shift critical care pharmacist's clinical interventions over a 12-week period. Interventions were collected and categorized daily from 13:00 to 22:00 Monday through Friday. After collection was complete, cost savings estimates were calculated using pharmacy wholesaler acquisition cost. Results: Interventions were collected on 52 of 60 weekdays. A total of 510 interventions were collected with an average of 9.8 interventions accepted per day. The most common interventions included transitions of care, medication dose adjustment, and antibiotic de-escalation and the highest proportion of interventions occurred in the medical intensive care unit. An estimated associated cost avoidance of $66 537.80 was calculated for an average of $1279.57 saved per day. Additionally, 22 (4.1%) of interventions were considered high yield interventions upon independent review by 2 pharmacists. Conclusion: The addition of 1 board-certified critical care pharmacist to evening shift resulted in multiple interventions across several categories and a significant cost avoidance when calculated using conservative measures.

Advances in Automated Insulin Delivery with the Medtronic 780G: The Australian Experience.

Aim: To assess the real-world performance of MiniMed™ 780G for Australians with type 1 diabetes (T1D) following advanced hybrid closed loop (AHCL) activation and to evaluate the effect of changing from MiniMed 670/770G to 780G. Methods: We analyzed deidentified Carelink™ continuous glucose monitoring (CGM) data from Australian users from January 2020 to December 2022, including the proportion attaining three major consensus targets: Glucose management indicator (GMI <7.0%), time in range (TIR 70-180 mg/dL >70%), and time below range (TBR 70 mg/dL <4%). Results: Comparing 670/770G users (n = 5676) for mean ± standard deviation 364 ± 244 days with 780G users (n = 3566) for 146 ± 145 days, the latter achieved a higher TIR (72.6% ± 10.6% vs. 67.3% ± 11.4%; P < 0.001), lower time above range (TAR) (25.5% ± 10.9% vs. 30.6% ± 11.7%; P < 0.001), and lower GMI (6.9% ± 0.4% vs. 7.2% ± 0.4%; P < 0.001) without compromising TBR (1.9% ± 1.8% vs. 2.0% ± 1.8%; P = 0.0015). Of 1051 670/770G users transitioning to 780G, TIR increased (70.0% ± 10.7% to 74.0% ± 10.2%; P < 0.001), TAR decreased (28.1% ± 10.9% to 24.0% ± 10.7%; P < 0.001), and TBR was unchanged. The percentage of users attaining all three CGM targets was higher in 780G users (50.1% vs. 29.5%; P < 0.001). CGM metrics were stable at 12 months post-transition. Conclusion: Real-world data from Australia shows that a higher proportion of MiniMed 780G users meet clinical targets for CGM consensus metrics compared to MiniMed 670/770G users and glucose control was sustained over 12 months.

Improved Glycemic Outcomes With Diabetes Technology Use Independent of Socioeconomic Status in Youth With Type 1 Diabetes.

OBJECTIVE: Technology use in type 1 diabetes (T1D) is impacted by socioeconomic status (SES). This analysis explored relationships between SES, glycemic outcomes, and technology use. RESEARCH DESIGN AND METHODS: A cross-sectional analysis of HbA1c data from 2,822 Australian youth with T1D was undertaken. Residential postcodes were used to assign SES based on the Index of Relative Socio-Economic Disadvantage (IRSD). Linear regression models were used to evaluate associations among IRSD quintile, HbA1c, and management regimen. RESULTS: Insulin pump therapy, continuous glucose monitoring, and their concurrent use were associated with lower mean HbA1c across all IRSD quintiles (P < 0.001). There was no interaction between technology use and IRSD quintile on HbA1c (P = 0.624), reflecting a similar association of lower HbA1c with technology use across all IRSD quintiles. CONCLUSIONS: Technology use was associated with lower HbA1c across all socioeconomic backgrounds. Socioeconomic disadvantage does not preclude glycemic benefits of diabetes technologies, highlighting the need to remove barriers to technology access.

Mental Health Practitioners' Knowledge of LGBTQA+ Conversion Practices and Their Perceptions of Impacts on Survivors.

The aims of this study were to identify Australian mental health practitioners' knowledge of what LGBTQA+ conversion practices are and their perceptions of impacts on survivors. We interviewed 18 mental health workers from a range of clinical modalities who were practicing in Australia. We used reflexive thematic analytic techniques to identify themes that characterized Australian mental health practitioners' knowledge of LGBTQA+ conversion practices and perceptions of the impacts of such practices on survivors. Practitioners' understandings of what constitutes LGBTQA+ conversion practices were varied and derived from a range of sources, and practitioners' perceptions of the impacts that conversion practices had on survivors ranged from undeveloped to nuanced. Generalist and specialist practitioners provided vastly different responses. We identified the following four themes: (1) inexperienced practitioners' understandings were limited and reliant on stereotypes about conversion practices; (2) specialist practitioners' understandings were refined and match experiences reported by survivors; (3) generalist practitioners emphasized specific and undeveloped negative impacts; (4) specialist practitioners were aware of deeper harms and the need for sustained support. These themes may be translated into strategies to facilitate improved services offered by practitioners, which may assist survivors in managing and coping with the trauma associated with exposure to these practices.

Angiotensin II Type 2 Receptor Agonism Alleviates Progressive Post-stroke Cognitive Impairment in Aged Spontaneously Hypertensive Rats.

Hypertension and aging are leading risk factors for stroke and vascular contributions to cognitive impairment and dementia (VCID). Most animal models fail to capture the complex interplay between these pathophysiological processes. In the current study, we examined the development of cognitive impairment in 18-month-old spontaneously hypertensive rats (SHR) before and following ischemic stroke. Sixty SHRs were housed for 18 months with cognitive assessments every 6 months and post-surgery. MRI scans were performed at baseline and throughout the study. On day 3 post-stroke, rats were randomized to receive either angiotensin II type 2 receptor (AT2R) agonist Compound 21 (C21) or plain water for 8 weeks. SHRs demonstrated a progressive cognitive decline and significant MRI abnormalities before stroke. Perioperative mortality within 72 h of stroke was low. Stroke resulted in significant acute brain swelling, chronic brain atrophy, and sustained sensorimotor and behavioral deficits. There was no evidence of anhedonia at week 8. C21 enhanced sensorimotor recovery and ischemic lesion resolution at week 8. SHRs represent a clinically relevant animal model to study aging and stroke-associated VCID. This study underscores the importance of translational disease modeling and provides evidence that modulation of the AT2R signaling via C21 may be a useful therapeutic option to improve sensorimotor and cognitive outcomes even in aged animals.

Hybrid Closed-Loop Versus Manual Insulin Delivery in Adults With Type 1 Diabetes: A Post Hoc Analysis Using the Glycemia Risk Index.

BACKGROUND: Glycemia risk index (GRI) is a novel composite metric assessing overall glycemic risk, accounting for both hypoglycemia and hyperglycemia and weighted toward extremes. Data assessing GRI as an outcome measure in closed-loop studies and its relation with conventional key continuous glucose monitoring (CGM) metrics are limited. METHODS: A post hoc analysis was performed to evaluate the sensitivity of GRI in assessing glycemic quality in adults with type 1 diabetes randomized to 26 weeks hybrid closed-loop (HCL) or manual insulin delivery (control). The primary outcome was GRI comparing HCL with control. Comparisons were made with changes in other CGM metrics including time in range (TIR), time above range (TAR), time below range (TBR), and glycemic variability (standard deviation [SD] and coefficient of variation [CV]). RESULTS: GRI with HCL (N = 61) compared with control (N = 59) was significantly lower (mean [SD] 33.5 [11.7] vs 56.1 [14.4], respectively; mean difference -22.8 [-27.2, -18.3], P = .001). The mean increase in TIR was +14.8 (11.0, 18.5)%. GRI negatively correlated with TIR for combined arms (r = -.954; P = .001), and positively with TAR >250 mg/dL (r = .901; P = .001), TBR < 54 mg/dL (r = .416; P = .001), and glycemic variability (SD [r = .916] and CV [r = .732]; P = .001 for both). CONCLUSIONS: Twenty-six weeks of HCL improved GRI, in addition to other CGM metrics, compared with standard insulin therapy. The improvement in GRI was proportionally greater than the change in TIR, and GRI correlated with all CGM metrics. We suggest that GRI may be an appropriate primary outcome for closed-loop trials.

Clinical Outcomes with MiniMedTM 780G Advanced Hybrid Closed-Loop Therapy in 2- to 6-Year-Old Children with Type 1 Diabetes.

Advanced hybrid closed-loop (AHCL) therapy with the Medtronic MiniMed™ 780G system improves glycemia; however, the clinical outcomes in younger children remain less established. This pilot study aimed to explore the continuous glucose monitoring (CGM) metrics in very young children on AHCL. Children between 2 and 7 years of age and on insulin pump therapy were recruited. A 2-week phase in manual mode was followed by a 6-week AHCL phase. CGM metrics were analyzed to review glycemic outcomes. Out of 11 participants enrolled [mean (standard deviation [SD]) age 5.3 (0.8) years], 10 completed the study. Time in closed loop was 96.7 (3.9)%. In AHCL, participants had a mean (SD) time in range of 72.6 (7.4)% and spent 3.0 (1.74)% and 0.63 (0.46)% in time <70 and <54 mg/dL, respectively. AHCL is a feasible option for management of young children with type 1 diabetes.

Lessons Learned From Implementation of Mpox Surveillance During an Outbreak Response in Tennessee, 2022.

OBJECTIVES: Mpox surveillance was integral during the 2022 outbreak response. We evaluated implementation of mpox surveillance in Tennessee during an outbreak response and made recommendations for surveillance during emerging infectious disease outbreaks. METHODS: To understand surveillance implementation, system processes, and areas for improvement, we conducted 8 semistructured focus groups and 7 interviews with 36 health care, laboratory, and health department representatives during September 9-20, 2022. We categorized and analyzed session transcription and notes. We analyzed completeness and timeliness of surveillance data, including 349 orthopoxvirus-positive laboratory reports from commercial, public health, and health system laboratories during July 1-August 31, 2022. RESULTS: Participants described an evolving system and noted that existing informatics platforms inefficiently supported iterations of reporting requirements. Clear communication, standardization of terminology, and shared, adaptable, and user-friendly informatics platforms were prioritized for future emerging infectious disease surveillance systems. Laboratory-reported epidemiologic information was often incomplete; only 55% (191 of 349) of reports included patient address and telephone number. The median time from symptom onset to specimen collection was 5 days (IQR, 3-6 d), from specimen collection to laboratory reporting was 3 days (IQR, 1-4 d), from laboratory reporting to patient interview was 1 day (IQR, 1-3 d), and from symptom onset to patient interview was 9 days (IQR, 7-12 d). CONCLUSIONS: Future emerging infectious disease responses would benefit from standardized surveillance approaches that facilitate rapid implementation. Closer collaboration among informatics, laboratory, and clinical partners across jurisdictions and agencies in determining system priorities and designing workflow processes could improve flexibility of the surveillance platform and completeness and timeliness of laboratory reporting. Improved timeliness will facilitate public health response and intervention, thereby mitigating morbidity.