K0.72Na1.71Ca5.79Si6O19 - the first oligosilicate based on [Si6O19]-hexamers and its stability compared to cyclosilicates.

Synthesis experiments were conducted in the quaternary system K2O-Na2O-CaO-SiO2, resulting in the formation of a previously unknown compound with the composition K0.72Na1.71Ca5.79Si6O19. Single crystals of sufficient size and quality were recovered from a starting mixture with a K2O:Na2O:CaO:SiO2 molar ratio of 1.5:0.5:2:3. The mixture was confined in a closed platinum tube and slowly cooled from 1150°C at a rate of 0.1°C min-1 to 700°C before being finally quenched in air. The structure has tetragonal symmetry and belongs to space group P4122 (No. 91), with a = 7.3659 (2), c = 32.2318 (18) Å, V = 1748.78 (12) Å3, and Z = 4. The silicate anion consists of highly puckered, unbranched six-membered oligomers with the composition [Si6O19] and point group symmetry 2 (C2). Although several thousands of natural and synthetic oxosilicates have been structurally characterized, this compound is the first representative of a catena-hexasilicate anion, to the best of our knowledge. Structural investigations were completed using Raman spectroscopy. The spectroscopic data was interpreted and the bands were assigned to certain vibrational species with the support of density functional theory at the HSEsol level of theory. To determine the stability properties of the novel oligosilicate compared to those of the chemically and structurally similar cyclosilicate combeite, we calculated the electronegativity of the respective structures using the electronegativity equalization method. The results showed that the molecular electronegativity of the cyclosilicate was significantly higher than that of the oligostructure due to the different connectivities of the oxygen atoms within the molecular units.

Novel engineered IL-2 Nemvaleukin alfa combined with PD1 checkpoint blockade enhances the systemic anti-tumor responses of radiation therapy.

BACKGROUND: Combining interleukin-2 (IL-2) with radiotherapy (RT) and immune checkpoint blockade (ICB) has emerged as a promising approach to address ICB resistance. However, conventional IL-2 cytokine therapy faces constraints owing to its brief half-life and adverse effects. RDB 1462, the mouse ortholog of Nemvaleukin alfa, is an engineered IL-2 with an intermediate affinity that selectively stimulates antitumor CD8 T and NK cells while limiting regulatory T cell expansion. This study aimed to evaluate the antitumor activity and mechanism of action of the combination of RDB 1462, RT, and anti-PD1 in mouse tumor models. METHODS: Two bilateral lung adenocarcinoma murine models were established using 344SQ-Parental and 344SQ anti-PD1-resistant cell lines. Primary tumors were treated with RT, and secondary tumors were observed for evidence of abscopal effects. We performed immune phenotyping by flow cytometry, analyzed 770 immune-related genes using NanoString, and performed T cell receptor (TCR) repertoire analysis. Serum pro-inflammatory cytokine markers were analyzed by 23-plex kit. RESULTS: Compared to native IL-2 (RDB 1475), RDB 1462 demonstrated superior systemic antitumoral responses, attributable, at least in part, to augmented levels of CD4 and CD8 T cells with the latter. Our findings reveal substantial reductions in primary and secondary tumor volumes compared to monotherapy controls, with some variability observed among different dosing schedules of RDB 1462 combined with RT. Blood and tumor tissue-based flow cytometric phenotyping reveals an increase in effector memory CD8 and CD4 T cells and a decrease in immunosuppressive cells accompanied by a significant increase in IL-2, IFN-γ, and GM-CSF levels in the combination group. Transcriptomic profiling and TCR sequencing reveal favorable gene expression and T cell repertoire patterns with the dual combination. Furthermore, integrating anti-PD1 therapy with RT and RDB 1462 further reduced primary and secondary tumor volumes, prolonged survival, and decreased lung metastasis. Observations of immune cell profiles indicated that RT with escalating doses of RDB 1462 significantly reduced tumor growth and increased tumor-specific immune cell populations. CONCLUSION: The addition of Nemvaleukin therapy may enhance responses to RT alone and in combination with anti-PD1.

Results from A Comparative Study to Evaluate the Treatment Effectiveness of a Non-Pneumatic Compression Device versus an Advanced Pneumatic Compression Device for Lower Extremity Lymphedema Swelling (TEAYS study).

OBJECTIVES: Advanced pneumatic compression devices (APCDs) have been shown to be effective in treatment of lower extremity lymphedema in the home setting. However, adherence to self-care has been poor, and APCD's require patients to remain immobile during treatment. We evaluated the safety and efficacy of a novel non-pneumatic compression device (NPCD) for treating lower extremity lymphedema vs and APCD. METHODS: A randomized, crossover head-to-head study was performed at nine sites in 2023. Patients were randomized to either the NPCD or a commercially available APCD. Patients used the randomly assigned initial device for 28 days with a 4-week washout period before a comparable 28-day use of the second device. RESULTS: A total of 71 patients (108 affected limbs) with lower extremity lymphedema were analyzed. Compared with the APCD, the NPCD was associated with a greater mean reduction in limb edema volume (a mean limb volume reduction of 369.9 (± 68.19) mL p<0.05 vs 83.1 (± 67.99 mL) p<0.05). Significant improvement in Quality of Life was achieved for NPCD and but not for APCD treatment (score improvement of 1.01 (± 0.23) (p<0.05) for NPCD vs 0.17 (± 0.18) (p>0.05) for APCD). Patients reported greater adherence (81% vs 56%, p<0.001) and satisfaction with the NPCD (78% vs 22%) compared to APCD. No device related adverse events were reported. CONCLUSIONS: The novel NPCD is an effective treatment for reducing limb volume in patients with lower extremity lymphedema. The NPCD was more effective than an APCD and resulted in superior limb volume reduction, greater improved QoL, adherence, mobility, and patient satisfaction.

Hepatic Amyloid Beta-42-Metabolizing Proteins in Liver Steatosis and Metabolic Dysfunction-Associated Steatohepatitis.

Amyloid beta (Aß) plays a major role in the pathogenesis of Alzheimer's disease and, more recently, has been shown to protect against liver fibrosis. Therefore, we studied Aß-42 levels and the expression of genes involved in the generation, degradation, and transport of Aß proteins in liver samples from patients at different stages of metabolic dysfunction-associated liver disease (MASLD) and under steatotic conditions in vitro/in vivo. Amyloid precursor protein (APP), key Aß-metabolizing proteins, and Aß-42 were analyzed using RT-PCR, Western blotting, Luminex analysis in steatotic in vitro and fatty liver mouse models, and TaqMan qRT-PCR analysis in hepatic samples from patients with MASLD. Hepatocytes loaded with palmitic acid induced APP, presenilin, and neprilysin (NEP) expression, which was reversed by oleic acid. Increased APP and NEP, decreased BACE1, and unchanged Aß-42 protein levels were found in the steatotic mouse liver compared to the normal liver. Aß-42 concentrations were low in MASLD samples of patients with moderate to severe fibrosis compared to the livers of patients with mild or no MASLD. Consistent with the reduced Aß-42 levels, the mRNA expression of proteins involved in APP degradation (ADAM9/10/17, BACE2) and Aß-42 cleavage (MMP2/7/9, ACE) was increased. In the steatotic liver, the expression of APP- and Aß-metabolizing proteins is increased, most likely related to oxidative stress, but does not affect hepatic Aß-42 levels. Consistent with our previous findings, low Aß-42 levels in patients with liver fibrosis appear to be caused by the reduced production and enhanced non-amyloidogenic processing of APP.

Perceptions of exercise behavior and well-being in anomalous aortic origin of coronary arteries.

Anomalous aortic origin of a coronary artery (AAOCA) is associated with sudden death in the young. Risk stratification and management decision-making remain challenging. Data addressing post-diagnosis perceptions of exercise behavior and safety are lacking. We aimed to determine how AAOCA affects exercise behaviors, safety perceptions, and emotional well-being of patients/parents. Qualitative and quantitative analysis of AAOCA patient-/parent-specific survey was conducted to examine exercise frequency/restrictions, perceived safety of competitive/recreational exercise, and psychosocial well-being. Subgroups stratified by AAOCA subtype, surgical intervention, and physician-driven restrictions were compared using chi-squared and Fisher's exact tests. Cohen's kappa determined agreement in parent/child responses. AAOCA subtypes included 13 (24%) left AAOCA, 36 (67%) right AAOCA, and 5 (9%) other/unknown. Of 54 parents and 41 paired child responses, 22% of patients were physician-restricted from exercise. Parents imposed restrictions on competitive/recreational exercise 34%/26% of the time, respectively. Children without physician restrictions still self-restricted exercise 35% of the time. Parents reported feeling their child was unsafe exercising 61% competitively and 33% recreationally. Twenty-two percent of children reported feeling unsafe exercising, with good agreement to parental perceptions of competitive exercise safety (kappa = 0.779, p < 0.001). One-third of parents and children reported feeling sad, angry, or lonely, and about half reported feeling different. Importantly, 47% of children desired to exercise more. No difference was seen across restriction status, AAOCA subtype, or surgical management strategy. CONCLUSION: There are different perceptions of exercise behavior and safety following AAOCA evaluation, regardless of risk category or management strategy, impacting their well-being. These unmet needs should be at the forefront of care. WHAT IS KNOWN: • AAOCA is one of the leading causes of sudden cardiac death in the young. • Exercise restriction varies according to AAOCA subtype and its perceived risk of inducing myocardial ischemia. WHAT IS NEW: • There are different perceptions of exercise behavior and safety in patients and parents following a diagnosis of AAOCA, impacting their well-being. • Risk category or management strategy has no effect in patients' and parents' perception of exercise safety. • These unmet needs in this population should be at the forefront of care.

Ex vivo host transcriptomics during Cryptococcus neoformans, Cryptococcus gattii, and Candida albicans infection of PBMCs from South African volunteers.

Cryptococcus neoformans, Cryptococcus gattii and Candida albicans are opportunistic fungal pathogens associated with infections in immunocompromised hosts. Cryptococcal meningitis (CM) is the leading fungal cause of HIV-related deaths globally, with the majority occurring in Africa. The human immune response to C. albicans infection has been studied extensively in large genomics studies whereas cryptococcal infections, despite their severity, are comparatively understudied. Here we investigated the transcriptional response of immune cells after in vitro stimulation with in vitro C. neoformans, C. gattii and C. albicans infection of peripheral blood mononuclear cells (PBMCs) collected from healthy South African volunteers. We found a lower transcriptional response to cryptococcal stimuli compared to C. albicans and unique expression signatures from all three fungal stimuli. This work provides a starting point for further studies comparing the transcriptional signature of CM in immunocompromised patients, with the goal of identifying biomarkers of disease severity and possible novel treatment targets.

Use of Pulmonary Rehabilitation After COPD Hospitalization: An Analysis of Statewide Patient and Hospital Data.

RATIONALE: Pulmonary rehabilitation (PR) is a clinically and cost-effective outpatient treatment for COPD that remains highly underutilized. Existing analyses of PR utilization patterns have been largely focused on patient characteristics, however hospital level analysis is lacking, and is needed to inform interventions aimed at improving utilization after COPD hospitalization. OBJECTIVE: To evaluate PR utilization across hospitals after COPD hospitalization in the state of Michigan, with the goal of characterizing hospital level variation and identifying the characteristics of high-performing hospitals. METHODS: This is a retrospective study of patients with a COPD hospitalization between 1/1/18 and 12/31/21 using claims data from the Michigan Value Collaborative (MVC) and hospital data from the American Hospital Association annual survey. Our primary outcome was initiation of PR within 30 days of discharge. Chi-square tests and ANOVA were used to test for differences in patient and hospital covariates. Multilevel logistic regression was used to analyze associations between patient covariates and the primary outcome, and to characterize hospital level variation. RESULTS: A total of 36,389 patients and 99 hospitals were included in the analysis. The majority of patients were older than 65 years of age, female, White, and Medicare fee-for-service insured. The rate of PR initiation within 30 days after hospitalization was 0.8%. Adjusted rates of PR initiation by hospital ranged from 0.4-2.0%. Compared to the set reference groups, being female, in the 5th Distressed Community Index quintile, and being older than 85 years of age independently decreased the odds of initiating PR. Some variation in initiation rate was attributed to the hospital level (7% ICC 0.07, 95% CI 0.03-0.15). The median odds ratio was 1.6 for PR initiation by hospital. CONCLUSIONS: Rates of PR initiation after COPD hospitalization are universally low across all hospitals, though there is some variation. Interventions targeted at patients alone are not sufficient to improve utilization. Hospital-based strategies to improve PR utilization after discharge, adapted from those being successfully used with cardiac rehabilitation, should be further explored.

Examiner-Examinee Gender Concordance Does Not Impact Ratings on the American Board of Surgery Vascular Surgery Certifying Examination.

OBJECTIVE: Implicit bias is a potential factor in the severity of examinee rating during oral examinations. Ratings may be impacted by examinee characteristics, such as gender, that are independent of examinee knowledge-base, clinical judgment or test-taking ability. The effects of examiner-examinee gender concordance in the Vascular Surgery Certifying Examination (VCE) have not been previously studied. We explored whether examiner ratings and likelihood of passing the exam were influenced by gender concordance amongst examiners and examinees. METHODS: Data collected from examinees who first attempted the VCE between 2018 and 2023 were analyzed. There were 1,005 examinees (69.3% male, 30.1% female) and 121 examiners (71.9% male, 28.1% female). Linear Mixed- Effects Models and Generalized Linear Mixed-Effects Models were used to evaluate the effects of examinee and examiner gender on VCE ratings and likelihood of passing the exam. RESULTS: Examiner-examinee gender concordance had no significant impact on examiner ratings or likelihood of passing the exam. Additionally, examinee gender alone had no significant impact on VCE rating or pass rates. Only Vascular Qualifying Exam (VQE) scores explained more than 1% of the variance in total VCE scores for the gender model (F(1,1003.5)=71.08, p-value < 0.01, R2 = 3%). VQE scores were positively related to total VCE scores. CONCLUSIONS: While implicit bias has the potential to impact examiner scoring, there is no evidence that this is the case with respect to gender in the Vascular Surgery Certifying Examination of the American Board of Surgery.

Prevalence of human filovirus infections in sub-Saharan Africa: A systematic review and meta-analysis protocol.

BACKGROUND: Recent outbreaks of Ebola virus disease (EVD) and Marburg virus disease (MVD) in sub-Saharan Africa illustrate the need to better understand animal reservoirs, burden of disease, and human transmission of filoviruses. This protocol outlines a systematic literature review to assess the prevalence of filoviruses that infect humans in sub-Saharan Africa. A secondary aim is to qualitatively describe and evaluate the assays used to assess prevalence. METHODS: The data sources for this systematic review include PubMed, Embase, and Web of Science. Titles, abstracts, and full texts will be reviewed for inclusion by a primary reviewer and then by a team of secondary reviewers, and data will be extracted using a pre-specified and piloted data extraction form. The review will include human cross-sectional studies, cohort studies, and randomized controlled trials conducted in sub-Saharan Africa up until March 13, 2024 that have been published in peer-reviewed scientific journals, with no language restrictions. Prevalence will be stratified by pathogen, population, assay, and sampling methodology and presented in forest plots with estimated prevalence and 95% confidence intervals. If there are enough studies within a stratum, I2 statistics will be calculated (using R statistical software), and data will be pooled if heterogeneity is low. In addition, assays used to detect infection will be evaluated. All studies included in the review will be assessed for quality and risk of bias using the JBI Prevalence Critical Appraisal Tool and for certainty using the GRADE certainty ratings. DISCUSSION: Accurately measuring the rate of exposure to filoviruses infecting humans in sub-Saharan Africa using prevalence provides an essential understanding of natural history, transmission, and the role of subclinical infection. This systematic review will identify research gaps and provide directions for future research seeking to improve our understanding of filovirus infections. Understanding the natural history, transmission, and the role of subclinical infection is critical for predicting the impact of an intervention on disease burden. SYSTEMATIC REVIEW REGISTRATION: In accordance with the guidelines outlined in the PRISMA-P methodology, this protocol was registered with PROSPERO on April 7, 2023 (ID: CRD42023415358).

Heat tolerance, oxidative stress response tuning and robust gene activation in early-stage Drosophila melanogaster embryos.

In organisms with complex life cycles, life stages that are most susceptible to environmental stress may determine species persistence in the face of climate change. Early embryos of Drosophila melanogaster are particularly sensitive to acute heat stress, yet tropical embryos have higher heat tolerance than temperate embryos, suggesting adaptive variation in embryonic heat tolerance. We compared transcriptomic responses to heat stress among tropical and temperate embryos to elucidate the gene regulatory basis of divergence in embryonic heat tolerance. The transcriptomes of tropical and temperate embryos differed in both constitutive and heat-stress-induced responses of the expression of relatively few genes, including genes involved in oxidative stress. Most of the transcriptomic response to heat stress was shared among all embryos. Embryos shifted the expression of thousands of genes, including increases in the expression of heat shock genes, suggesting robust zygotic gene activation and demonstrating that, contrary to previous reports, early embryos are not transcriptionally silent. The involvement of oxidative stress genes corroborates recent reports on the critical role of redox homeostasis in coordinating developmental transitions. By characterizing adaptive variation in the transcriptomic basis of embryonic heat tolerance, this study is a novel contribution to the literature on developmental physiology and developmental genetics.

Evaluating the added value of concurrent contrast-enhanced diagnostic CT for PSMA-PET/CT Interpretation.

RATIONALE AND OBJECTIVES: To determine whether concurrent contrast-enhanced diagnostic CT (DxCT) confers added diagnostic certainty compared to PSMA-PET/CT alone. MATERIALS AND METHODS: This retrospective multi-reader study analyzed imaging comprising combined F-18-piflufolastat PSMA-PET/CT with diagnostic chest/abdominopelvic CT from prostate cancer patients within the first 6 months of FDA-approval of the PET agent. Six nuclear radiology readers were randomly presented with PSMA-PET/CT studies with or without DxCT and asked to report their diagnostic certainty for PSMA-avid lesions found on PET. Subsequently, readers re-reviewed the same study after an interlude (with the CT if not previously presented and vice-versa) to determine if DxCT altered their diagnostic assessment. Inter-rater concordance was assessed on a subset of images read by all readers. Diagnostic certainties for PSMA-PET/CT with and without DxCT were compared, and the variables for which DxCT may add value were examined. RESULTS: Good inter-rater concordance across readers was noted for both PET/CT (Finn's coefficient of reliability for overall scan certainty: 0.85,p < 0.01) and combined DxCT-PET/CT (0.59,p < 0.01). Overall certainty and concordance between PET/CT and combined DxCT-PET/CT datasets were similar (overall scan certainty: 92% ± 16 vs. 92% ± 17,p = 0.43), with no significant advantage for adding DxCT across different anatomic locations or clinical parameters. A slight predilection for combined DxCT-PET/CT was noted when interpreting images acquired for the initial staging of prostate cancer (89% ± 16 vs. 93% ± 17,p = 0.08). CONCLUSION: Good inter-reader concordance can be achieved across different training levels with PSMA-PET/CT. Furthermore, using DxCT concurrent with PSMA-PET/CT does not significantly improve diagnostic certainty for most indications but may be useful for initial staging.

Age-associated contraction of tumor-specific T cells impairs antitumor immunity.

Progressive decline of the adaptive immune system with increasing age coincides with a sharp increase in cancer incidence. In this study, we set out to understand whether deficits in antitumor immunity with advanced age promote tumor progression and/or drive resistance to immunotherapy. We found that multiple syngeneic cancers grew more rapidly in aged versus young adult mice, driven by dysfunctional CD8+ T-cell responses. By systematically mapping immune cell profiles within tumors, we identified loss of tumor antigen-specific CD8+ T cells as a primary feature accelerating the growth of tumors in aged mice and driving resistance to immunotherapy. When antigen-specific T cells from young adult mice were administered to aged mice, tumor outgrowth was delayed and the aged animals became sensitive to PD-1 blockade. These studies reveal how age-associated CD8+ T-cell dysfunction may license tumorigenesis in elderly patients and have important implications for the use of aged mice as pre-clinical models of aging and cancer.

The role of pressure and friction forces in automated insertion of cochlear implants.

Objectives: Despite the success of cochlear implant (CI) surgery for hearing restoration, reducing CI electrode insertion forces is an ongoing challenge with the goal to further reduce post-implantation hearing loss. While research in this field shows that both friction and quasistatic pressure forces occur during CI insertion, there is a lack of studies distinguishing between these origins. The present study was conducted to analyze the contribution of both force phenomena during automated CI insertion. Methods: Five MED-EL FLEX28 CI electrode arrays were inserted into both a regular and uncoiled version of the same average scala tympani (ST). Both ST models had a pressure release hole at the apical end, which was kept open or closed to quantify pressure forces. ST models were filled with different sodium dodecyl sulfate (SDS) lubricants (1, 5, and 10% SDS, water). The viscosity of lubricants was determined using a rheometer. Insertions were conducted with velocities ranging from v= 0.125 mm/s to 2.0 mm/s. Results: Viscosity of SDS lubricants at 20°C was 1.28, 1.96, and 2.51 mPas for 1, 5, and 10% SDS, respectively, which lies within the values reported for human perilymph. In the uncoiled ST model, forces remained within the noise floor (maximum: 0.049 × 10-3 N ± 1.5 × 10-3 N), indicating minimal contribution from quasistatic pressure. Conversely, forces using the regular, coiled ST model were at least an order of magnitude larger (minimum: Fmax = 28.95 × 10-3 N, v = 1 mm/s, 10% SDS), confirming that friction forces are the main contributor to total insertion forces. An N-way ANOVA revealed that both lubricant viscosity and insertion speed significantly reduce insertion forces (p < 0.001). Conclusion: For the first time, this study demonstrates that at realistic perilymph viscosities, quasistatic pressure forces minimally affect the total insertion force profile during insertion. Mixed friction is the main determinant, and significantly decreases with increaseing insertion speeds. This suggests that in clinical settings with similar ST geometries and surgical preparation, quasistatic pressure plays a subordinate role. Moreover, the findings indicate that managing the hydrodynamics of the cochlear environment, possibly through pre-surgical preparation or the use of specific lubricants, could effectively reduce insertion forces.

Continuous Flow Approach for Benzylic Photo-oxidations Using Compressed Air.

A continuous flow approach for the aerobic photo-oxidation of benzylic substrates to ketone and aldehyde products is presented. The resulting process exploits UV-A LEDs (375 nm) in combination with a Corning AFR reactor that ensures effective gas-liquid mixing and leads to short residence times of 1 min. A variety of benzylic substrates are converted to their corresponding carbonyl products, and scalability is demonstrated to produce multigram quantities of products within a few hours. Overall, this continuous flow approach offers several improvements over alternative oxidation methods due to the combined use of air as an oxidant and SAS (sodium anthraquinone-2 sulfonate) as a water-soluble photocatalyst. The use of greener and safer conditions together with process intensification principles renders this flow approach attractive for further industrial applications.

Development and optimization of a diluted whole blood ELISpot assay to test immune function.

Sepsis remains a leading cause of death worldwide with no proven immunomodulatory therapies. Stratifying Patient Immune Endotypes in Sepsis ('SPIES') is a prospective, multicenter observational study testing the utility of ELISpot as a functional bioassay specifically measuring cytokine-producing cells after stimulation to identify the immunosuppressed endotype, predict clinical outcomes in septic patients, and test potential immune stimulants for clinical development. Most ELISpot protocols call for the isolation of PBMC prior to their inclusion in the assay. In contrast, we developed a diluted whole blood (DWB) ELISpot protocol that has been validated across multiple laboratories. Heparinized whole blood was collected from healthy donors and septic patients and tested under different stimulation conditions to evaluate the impact of blood dilution, stimulant concentration, blood storage, and length of stimulation on ex vivo IFNγ and TNFα production as measured by ELISpot. We demonstrate a dynamic range of whole blood dilutions that give a robust ex vivo cytokine response to stimuli. Additionally, a wide range of stimulant concentrations can be utilized to induce cytokine production. Further modifications demonstrate anticoagulated whole blood can be stored up to 24 h at room temperature without losing significant functionality. Finally, we show ex vivo stimulation can be as brief as 4 h allowing for a substantial decrease in processing time. The data demonstrate the feasibility of using ELISpot to measure the functional capacity of cells within DWB under a variety of stimulation conditions to inform clinicians on the extent of immune dysregulation in septic patients.

Barriers to Effective Infection Prevention in the Neonatal Intensive Care Unit: A Qualitative Study.

BACKGROUND: Infection prevention (IP) behaviors such as hand hygiene (HH) and mobile device disinfection are important to reduce the risk of infection transmission from both family members and hospital staff to critically ill neonates. PURPOSE: To inform the design of educational interventions to improve both patient family and staff IP behaviors, we engaged separate groups of nurses and family members to understand perceptions about the spread of infection and barriers to implementing effective IP strategies. METHODS: This was a qualitative study using focus groups to gather data from neonatal nurses and patient family members. Data were triangulated with hospital-wide survey data and analyzed using inductive content analysis. RESULTS: Twelve nurses and 4 patient family members participated. Themes related to communication about IP between staff and family members emerged: stakeholders expressed discomfort with the timing and nature of just-in-time HH education. These communication challenges contributed to stress levels within the neonatal intensive care unit. This finding was reflected in the hospital-wide survey. IMPLICATIONS FOR PRACTICE AND RESEARCH: Steps should be taken to improve communication about IP behaviors between patient family members and frontline staff. Reducing nurse burden of providing just-in-time HH reminders to patient family members through increased IP education may decrease stress and facilitate IP behaviors. This has the potential to decrease infection spread and improve patient outcomes. The development of interventions targeting stakeholder communication is therefore warranted, but additional research is needed to understand the timing and process for delivery of the educational material.

Patient-reported outcomes in studies of diabetes technology: What matters.

In recent years, diabetes technologies have revolutionized the care of people with type 1 diabetes (T1D). Emerging evidence suggests that people with type 2 diabetes (T2D) can experience similar benefits from these advances in technology. While glycaemic outcomes are often a primary focus, the lived experience of the person with diabetes is equally important. In this review, we describe the impact of diabetes technologies on patient-reported outcome measures (PROMs). We highlight that most of the published studies investigated PROMs as secondary outcomes. Continuous glucose monitoring systems may have an important role in improving PROMs in individuals with T1D, which may be driven by the prevention or proactive management of hypoglycaemia. In people with T2D, continuous glucose monitoring may also have an important role in improving PROMs, particularly in those treated with insulin therapy. The impact of insulin pumps on PROMs seems positive in T1D, while there is limited evidence in T2D. Studies of hybrid closed-loop therapies suggest increased treatment satisfaction, improved quality of life and decreased diabetes-related distress in T1D, but it is unclear whether these benefits are because of a 'class-effect' or individual systems. We conclude that PROMs deserve a more central role in trials and clinical practice, and we discuss directions for future research.