The safety of recombinant human hyaluronidase PH20 in nonclinical models: An overview of toxicology, pharmacology, and impact of anti-PH20 antibodies.

Hyaluronan (HA) is a glycosaminoglycan that forms a gel-like barrier in the subcutaneous (SC) space, limiting bulk fluid flow and the dispersion of SC-administered therapeutics. Recombinant human hyaluronidase PH20 (rHuPH20) facilitates the rapid delivery of co-administered therapeutics by depolymerizing HA in the SC space. Administration of rHuPH20 can induce the formation of anti-rHuPH20 antibodies, or anti-drug antibodies (ADAs), with the potential to bind endogenous PH20 hyaluronidase in the adult testes and epididymis. Using a variety of relevant animal models and multiple dose regimens of rHuPH20 across the full spectrum of animal development, we demonstrated that rHuPH20 administration resulted in the formation of ADAs. Although these ADAs can bind both the recombinant rHuPH20 enzyme and recombinant versions of animal model-specific hyaluronidases, they had no impact on fertility parameters (as measured by sperm concentration and motility, litter size, and litter viability) or fetal development. We present the result of our nonclinical studies in order of the developmental lifecycle, beginning with adults. Toxicology studies that extend beyond the standard package are also presented. These studies demonstrate the favorable safety profile of rHuPH20 and ADAs in nonclinical models. Additionally, we identified substantial safety margins for therapeutically relevant doses of rHuPH20.

Clusters of emerging multidrug-resistant organisms in US health care facilities during the initial months of the SARS-CoV-2 pandemic.

BACKGROUND: Outbreaks of emerging multidrug-resistant organisms (eMDROs), including carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter baumannii, and Candida auris, have been reported among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. We describe eMDRO clusters in SARS-CoV-2 units and associated infection control (IC) practices early in the SARS-CoV-2 pandemic. METHODS: We conducted a retrospective survey of a convenience sample of health departments in 11 states to describe clusters of eMDROs that began before November 1, 2020 and involved SARS-CoV-2 units. Cluster characteristics and IC practices during the cluster period were assessed using a standardized outbreak report form, and descriptive analyses were performed. RESULTS: Overall, 18 eMDRO clusters (10 carbapenem-resistant Enterobacterales, 6 C auris, 1 carbapenem-resistant Pseudomonas aeruginosa, and 1 carbapenem-resistant A baumannii) in 18 health care facilities involving 397 patients were reported from 10 states. During the cluster period, 60% of facilities reported a shortage of isolation gowns, 69% extended use of gowns, and 67% reported difficulty obtaining preferred disinfectants. Reduced frequency of hand hygiene audits was reported in 85% of acute care hospitals during the cluster period compared with before the pandemic. CONCLUSIONS: Changes in IC practices and supply shortages were identified in facilities with eMDRO outbreaks during the SARS-CoV-2 pandemic and might have contributed to eMDRO transmission.

A Proposal of Utilizing Six Types of Involvement Model to Guide Kindergarten to 12th Grade School Parental Communication and Support During a Pandemic.

Background: Effective communication between schools and parents Is crucial for fostering understanding, trust, and collaboration to enhance educational outcomes and student well-being, especially during crises such as the COVID-19 pandemic. Moreover, the current level of communication between schools and families is frequently insufficient, exacerbating the difficulties in parental engagement, comprehension, and certain policy implementation. This deficiency becomes even more pronounced during crises due to the added stressors. This study aims to highlight the challenges of parental engagement and communication during the pandemic and propose a viable solution for school districts and schools to enhance trust, understanding, and collaboration in schools to prepare for future crises. Method: The study employs a mixed-methods approach, Including a scoping review of literature and policies on school communication during the pandemic, a survey study conducted among the Connecticut Independent Schools, and the Integration of results from both sources. The scoping review provides key themes and frameworks, while the survey collects quantitative and qualitative data to identify challenges and concerns. The proposed solution utilizes Epstein's Six Types of Involvement Framework for school districts and schools to guide effective communication and collaboration between schools and parents. Results: The scoping review and survey findings reveal several key Issues, Including hesitant parental perception of disease control strategies, the burden on parents in supporting online learning, the lack of resources and guidance for online learning, and the absence of central communication guidelines. The proposed solution, Epstein's Six Types of Involvement Framework, addresses these challenges by emphasizing parenting, communication, volunteering, learning at home, decision-making, and community collaboration. Conclusion: The study highlights the importance of effective communication between schools and parents during crises and proposes Epstein's Six Types of Involvement Framework as a comprehensive solution. By implementing this framework, schools can foster understanding, trust, and collaboration, leading to better educational outcomes for students. The findings have implications for school administrators, policymakers, and educators seeking to improve communication during crises and can facilitate more effective communication and parental engagement beyond health crises. Further research Is needed to evaluate the effectiveness and impact of implementing the framework in real-world crises. Moreover, healthcare professionals like pediatricians, psychologists, and school nurses are crucial in disease control in schools. The study proposes using Epstein's framework to Involve them directly, enhancing collaboration and trust, and empowering them to lead efforts in safeguarding students and staff health.

Betaine for the prevention and treatment of insulin resistance and fatty liver in a high-fat dietary model of insulin resistance in C57BL mice.

Aim: The aim was to investigate mechanisms by which betaine improves hepatic insulin signaling in a dietary mouse model of insulin resistance and fatty liver. Methods: C57BL 6J mice were fed a standard diet (SF), a standard diet with betaine (SFB), a nutritionally complete high fat (HF) diet, or a high fat diet with betaine (HFB) for 14 weeks. In a separate experiment, mice were fed high fat diet for 18 weeks, half of whom received betaine for the final 4 weeks. Activation of insulin signaling in the liver was assessed by western blot. Insulin signaling was also assessed in insulin resistant primary human hepatocytes treated with betaine. Results: As compared with SF, mice receiving HF diet were heavier, had more hepatic steatosis, and abnormal glucose tolerance test (GTT). Betaine content in liver and serum was 50% lower in HF than in SF; betaine supplementation restored serum and liver betaine content. Betaine treatment of HF reduced whole body insulin resistance as measured by GTT. Betaine treatment of HF increased tyrosine phosphorylation of insulin receptor substrate-1 and phosphorylation (activation) of Akt, and increased hepatic glycogen content. In vitro, betaine reversed insulin resistance in primary human hepatocytes by increasing insulin-stimulated tyrosine phosphorylation of IRS1 and of Akt. Conclusion: Betaine supplementation reduced whole body insulin resistance and increased activation of insulin signaling pathways in the liver in a mouse model of insulin resistance and fatty liver created by feeding a nutritionally complete high fat diet for 14 weeks. Betaine also reduced liver injury as assessed by ALT and by liver histology. In vitro, betaine reversed insulin resistance by increasing insulin-stimulated tyrosine phosphorylation of IRS1 and activation of downstream proteins in the insulin signaling cascade in insulin resistant primary human hepatocytes.

Natural History of Cavernous Carotid Artery Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND: Cavernous carotid artery aneurysms (CCAAs) represent a common condition seen in clinical practice with significant practice variability. The aim of this systematic review and meta-analysis was to aggregate current evidence on the natural history of CCAAs. METHODS: MEDLINE/PubMed, EMBASE, and Cochrane Library were queried from inception until December 2023. The primary outcome of this study was CCAA-related mortality. The secondary outcomes of this study were aneurysm growth, intracranial ischemic and hemorrhagic events, improved non-cerebrovascular symptoms, and new or worsened non-cerebrovascular symptoms during follow-up. RESULTS: Ten studies met our inclusion criteria, involving 835 patients and 975 CCAAs. CCAA-related mortality had an incidence rate of 0.28 (95% confidence interval 0.12-0.64) per 100 person-years (PYs) of follow-up. The incidence rate of CCAA growth was 2.91 (1.05-8.07) per 100 PYs of follow-up. The incidence rate of CCAA-related intracranial ischemic events was 0.4 (0.16-1.01) per 100 PYs of follow-up. The incidence rate of CCAA-related intracranial hemorrhagic events was 0.54 (0.33-0.87) per 100 PYs of follow-up. The incidence rate of improved non-cerebrovascular symptoms was 2.51 (1.18-5.33) per 100 PYs of follow-up. The incidence rate of new or worsened non-cerebrovascular symptoms was 3.41 (2.03-5.73) per 100 PYs of follow-up. CONCLUSIONS: CCAAs are typically benign lesions with a low risk of rupture and life-threatening complications. CCAAs tend to follow an indolent course regarding non-cerebrovascular outcomes, and new or worsening symptoms are infrequent during the clinical course. However, spontaneous resolution of non-cerebrovascular symptoms and cranial nerve deficits at presentation is uncommon.

Online retail nudges to help parents with lower-income choose healthy beverages for their children: A randomized clinical trial.

BACKGROUND: Nudges offer a promising tool to reduce sugary drink intake among children who are most at risk for diet-related disease. OBJECTIVE: To examine the impact of online store nudges on purchases of sugary drinks for children in lower-income households. METHODS: Caregivers with lower-income were recruited to an online shopping experiment and instructed to spend $10-$30 on three beverages for their child aged 1-5 years. Participants were randomized to navigate an online supermarket in its standard version (n = 1106) or a version with nudges (n = 1135), including a product placement nudge (i.e. placing healthy beverages in prominent positions) and a swap nudge (i.e. offering a swap of water, plain milk and/or 100% fruit juice upon selection of sugary drinks). RESULTS: On average, participants purchased 1887 (SD = 2113) and 620 (SD = 1528) calories from sugary drinks per basket in the control and experimental conditions, respectively. Model-based results indicate that those in the experimental condition purchased 1267 (95% CI: 1419, 1114) fewer calories from sugary drinks, and fewer grams of total sugar (ß = -253.5 g (95% CI: -286.3, -220.6)) and added sugar (ß = -287.8 g (95% CI: -323.1, -252.5)) purchased from sugary drinks. CONCLUSION: Nudges may be an effective, acceptable, scalable strategy for leading caregivers in lower-income households to purchase fewer sugary drinks for their children.

CSF Proteomics in Patients With Progressive Supranuclear Palsy.

BACKGROUND AND OBJECTIVES: Identification of fluid biomarkers for progressive supranuclear palsy (PSP) is critical to enhance therapeutic development. We implemented unbiased DNA aptamer (SOMAmer) proteomics to identify novel CSF PSP biomarkers. METHODS: This is a cross-sectional study in original (18 clinically diagnosed PSP-Richardson syndrome [PSP-RS], 28 cognitively healthy controls]), validation (23 PSP-RS, 26 healthy controls), and neuropathology-confirmed (21 PSP, 52 non-PSP frontotemporal lobar degeneration) cohorts. Participants were recruited through the University of California, San Francisco, and the 4-Repeat Neuroimaging Initiative. The original and neuropathology cohorts were analyzed with the SomaScan platform version 3.0 (5026-plex) and the validation cohort with version 4.1 (7595-plex). Clinical severity was measured with the PSP Rating Scale (PSPRS). CSF proteomic data were analyzed to identify differentially expressed targets, implicated biological pathways using enrichment and weighted consensus gene coexpression analyses, diagnostic value of top targets with receiver-operating characteristic curves, and associations with disease severity with linear regressions. RESULTS: A total of 136 participants were included (median age 70.6 ± 8 years, 68 [50%] women). One hundred fifty-five of 5,026 (3.1%), 959 of 7,595 (12.6%), and 321 of 5,026 (6.3%) SOMAmers were differentially expressed in PSP compared with controls in original, validation, and neuropathology-confirmed cohorts, with most of the SOMAmers showing reduced signal (83.1%, 95.1%, and 73.2%, respectively). Three coexpression modules were associated with PSP across cohorts: (1) synaptic function/JAK-STAT (ß = -0.044, corrected p = 0.002), (2) vesicle cytoskeletal trafficking (ß = 0.039, p = 0.007), and (3) cytokine-cytokine receptor interaction (ß = -0.032, p = 0.035) pathways. Axon guidance was the top dysregulated pathway in PSP in original (strength = 1.71, p < 0.001), validation (strength = 0.84, p < 0.001), and neuropathology-confirmed (strength = 0.78, p < 0.001) cohorts. A panel of axon guidance pathway proteins discriminated between PSP and controls in original (area under the curve [AUC] = 0.924), validation (AUC = 0.815), and neuropathology-confirmed (AUC = 0.932) cohorts. Two inflammatory proteins, galectin-10 and cytotoxic T lymphocyte-associated protein-4, correlated with PSPRS scores across cohorts. DISCUSSION: Axon guidance pathway proteins and several other molecular pathways are downregulated in PSP, compared with controls. Proteins in these pathways may be useful targets for biomarker or therapeutic development.

Readability and Information Quality in Cancer Information From a Free vs Paid Chatbot.

Importance: The mainstream use of chatbots requires a thorough investigation of their readability and quality of information. Objective: To identify readability and quality differences in information between a free and paywalled chatbot cancer-related responses, and to explore if more precise prompting can mitigate any observed differences. Design, Setting, and Participants: This cross-sectional study compared readability and information quality of a chatbot's free vs paywalled responses with Google Trends' top 5 search queries associated with breast, lung, prostate, colorectal, and skin cancers from January 1, 2021, to January 1, 2023. Data were extracted from the search tracker, and responses were produced by free and paywalled ChatGPT. Data were analyzed from December 20, 2023, to January 15, 2024. Exposures: Free vs paywalled chatbot outputs with and without prompt: "Explain the following at a sixth grade reading level: [nonprompted input]." Main Outcomes and Measures: The primary outcome measured the readability of a chatbot's responses using Flesch Reading Ease scores (0 [graduate reading level] to 100 [easy fifth grade reading level]). Secondary outcomes included assessing consumer health information quality with the validated DISCERN instrument (overall score from 1 [low quality] to 5 [high quality]) for each response. Scores were compared between the 2 chatbot models with and without prompting. Results: This study evaluated 100 chatbot responses. Nonprompted free chatbot responses had lower readability (median [IQR] Flesh Reading ease scores, 52.60 [44.54-61.46]) than nonprompted paywalled chatbot responses (62.48 [54.83-68.40]) (P < .05). However, prompting the free chatbot to reword responses at a sixth grade reading level was associated with increased reading ease scores than the paywalled chatbot nonprompted responses (median [IQR], 71.55 [68.20-78.99]) (P < .001). Prompting was associated with increases in reading ease in both free (median [IQR], 71.55 [68.20-78.99]; P < .001)and paywalled versions (median [IQR], 75.64 [70.53-81.12]; P < .001). There was no significant difference in overall DISCERN scores between the chatbot models, with and without prompting. Conclusions and Relevance: In this cross-sectional study, paying for the chatbot was found to provide easier-to-read responses, but prompting the free version of the chatbot was associated with increased response readability without changing information quality. Educating the public on how to prompt chatbots may help promote equitable access to health information.

Efficacy of a nurse-led sexual rehabilitation intervention for women with gynaecological cancers receiving radiotherapy: results of a randomised trial.

BACKGROUND: The multicentre randomised SPARC trial evaluated the efficacy of a nurse-led sexual rehabilitation intervention on sexual functioning, distress, dilator use, and vaginal symptoms after radiotherapy for gynaecological cancers. METHODS: Eligible women were randomised to the rehabilitation intervention or care-as-usual. Four intervention sessions were scheduled over 12 months, with concurrent validated questionnaires and clinical assessments. Primary outcome was the Female Sexual Function Index (FSFI). A generalised-mixed-effects model compared groups over time. RESULTS: In total, 229 women were included (n = 112 intervention; n = 117 care-as-usual). No differences in FSFI total scores were found between groups at any timepoint (P = 0.37), with 12-month scores of 22.57 (intervention) versus 21.76 (care-as-usual). The intervention did not significantly improve dilator use, reduce sexual distress or vaginal symptoms compared to care-as-usual. At 12 months, both groups had minimal physician-reported vaginal stenosis; 70% of women were sexually active and reported no or mild vaginal symptoms. After radiotherapy and brachytherapy, 85% (intervention) versus 75% (care-as-usual) of participants reported dilation twice weekly. DISCUSSION: Sexual rehabilitation for women treated with combined (chemo)radiotherapy and brachytherapy improved before and during the SPARC trial, which likely contributed to comparable study groups. Best practice involves a sexual rehabilitation appointment 1 month post-radiotherapy, including patient information, with dilator guidance, preferably by a trained nurse, and follow-up during the first year after treatment. CLINICAL TRIAL REGISTRATION: NCT03611517.

A chemogenetic approach for dopamine imaging with tunable sensitivity.

Genetically-encoded dopamine (DA) sensors enable high-resolution imaging of DA release, but their ability to detect a wide range of extracellular DA levels, especially tonic versus phasic DA release, is limited by their intrinsic affinity. Here we show that a human-selective dopamine receptor positive allosteric modulator (PAM) can be used to boost sensor affinity on-demand. The PAM enhances DA detection sensitivity across experimental preparations (in vitro, ex vivo and in vivo) via one-photon or two-photon imaging. In vivo photometry-based detection of optogenetically-evoked DA release revealed that DETQ administration produces a stable 31 minutes window of potentiation without effects on animal behavior. The use of the PAM revealed region-specific and metabolic state-dependent differences in tonic DA levels and enhanced single-trial detection of behavior-evoked phasic DA release in cortex and striatum. Our chemogenetic strategy can potently and flexibly tune DA imaging sensitivity and reveal multi-modal (tonic/phasic) DA signaling across preparations and imaging approaches.

Multimodality assessment of the coronary microvasculature with TIMI frame count versus perfusion PET highlights coronary changes characteristic of coronary microvascular disease.

Background: The diagnosis of coronary microvascular disease (CMVD) remains challenging. Perfusion PET-derived myocardial blood flow (MBF) reserve (MBFR) can quantify CMVD but is not widely available. Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) is an angiography-based method that has been proposed as a measure of CMVD. Here, we compare TFC and PET-derived MBF measurements to establish the role of TFC in assessing for CMVD. We use coronary modeling to elucidate the relationship between MBFR and TFC and propose TFC thresholds for identifying CMVD. Methods: In a cohort of 123 individuals (age 58 ± 12.1, 63% women, 41% Caucasian) without obstructive coronary artery disease who had undergone perfusion PET and coronary angiography for clinical indications, we compared TFC and perfusion PET parameters using Pearson correlation (PCC) and linear regression modeling. We used mathematical modeling of the coronary circulation to understand the relationship between these parameters and performed Receiver Operating Curve (ROC) analysis. Results: We found a significant negative correlation between TFC and MBFR. Sex, race and ethnicity, and nitroglycerin administration impact this relationship. Coronary modeling showed an uncoupling between TFC and flow in epicardial vessels. In ROC analysis, TFC performed well in women (AUC 0.84-0.89) and a moderately in men (AUC 0.68-0.78). Conclusions: We established an inverse relationship between TFC and PET-derived MBFR, which is affected by patient selection and procedural factors. TFC represents a measure of the volume of the epicardial coronary compartment, which is increased in patients with CMVD, and performs well in identifying women with CMVD.

Educational Debt and Income Among Pharmacists and Other Health Professionals.

OBJECTIVE: Given the substantial increases in student educational loan debt in recent years, the objective was to assess trends in educational debt-to-income ratios for graduates of pharmacy, medicine, dentistry, optometry, and veterinary medicine programs in the United States in the 2017-2022 period. METHODS: A retrospective analysis of 2017-2022 data for educational debt and income for select health professions was conducted. Annual income data were collected from the American Community Survey, and educational debt data were collected from health professions organizations. Educational debt-to-income ratios for each health profession were calculated, as was the mean change per year in debt-to-income ratio. RESULTS: With the exception of medicine, educational debt consistently exceeded income across the selected health professions in the 2017-2022 period. Debt-to-income ratios of pharmacists and the remaining health professionals decreased on average per year between 2017 and 2022. Physicians had the lowest debt-to-income ratios and dentists had the highest debt-to-income ratios in the study period. CONCLUSION: Debt-to-income ratios fell below the 2017 levels for the health professions of interest, suggesting that average growth in income outpaced that of debt for the study period. Regardless, debt remains high and may influence health care professionals' postgraduate training and career decisions, and in turn affect access to health care. Therefore, a call to action is proposed to address educational debt burden. Several strategies are suggested, including federal policy changes, implementing tuition reductions or minimal increases, facilitating financial aid options, and reducing underlying costs of health professions programs.

Engineering microvascular networks using a KLF2 reporter to probe flow-dependent endothelial cell function.

Shear stress generated by the flow of blood in the vasculature is a potent regulator of endothelial cell function and vascular structure. While vascular responses to flow are complex and context-dependent, endothelial cell signaling in response to shear stress induced by laminar flows is coordinated by the transcription factor KLF2. The flow-dependent expression of KLF2 in endothelial cells is associated with a quiescent, anti-inflammatory phenotype and has been well characterized in two-dimensional systems but has not been studied in three-dimensional in vitro systems. Here we develop engineered microvascular networks (MVNs) that incorporate a KLF2-based endothelial cell flow sensor within a microfluidic chip, apply continuous flow using an attached microfluidic pump, and study the effects of this flow on vascular structure and function. We found that application of flow to MVNs for 48 h resulted in increased expression of the KLF2 reporter, larger vessel diameters, and decreased vascular branching and resistance. Notably, vessel diameters after the application of flow were independent of initial MVN morphologies. Finally, we found that MVNs exposed to flow have improved vascular barrier function and decreased platelet adhesion. MVNs with KLF2-based flow sensors represent a novel, powerful tool for evaluating the structural and functional effects of flow on engineered three-dimensional vascular systems.

Improving preparedness for introducing and scaling up long-acting HIV pre-exposure prophylaxis in Asia.

Long-acting injectable PrEP, particularly cabotegravir (CAB-LA), has the potential to enhance HIV prevention in Asia, and was the topic of a roundtable held in Singapore in June 2023. Despite proven efficacy, CAB-LA's impact in Asia is hindered by regulatory, manufacturing, and cost barriers. There is an urgent need to address these challenges to expedite CAB-LA's introduction and scale-up, including collaborative research, streamlined regulatory processes, and increased manufacturing capacity. We call for better preparedness in long-acting PrEP in research and implementation science, product licensing and accessibility, and capacity readiness for scale-up, to meet the significant demand among key populations in Asia.

Missed opportunities for guidance on sexually transmitted infection services: a global review of national HIV PrEP guidance.

OBJECTIVES: People who use or would benefit from pre-exposure prophylaxis (PrEP) for HIV infection are disproportionately affected by sexually transmitted infections (STIs). Integrating STI services when offering PrEP fosters synergies and efficiencies in response to HIV/STI and promotes people-centred care. Including guidance on STI interventions for people on PrEP may facilitate implementation and uptake. We conducted a global review of national PrEP guidance documents and analysed the inclusion of recommendations for the provision of STI services by country level of income. METHODS: We searched national PrEP guidance documents published by WHO Member States through the WHO, the Joint United Nations Programme on HIV/AIDS (UNAIDS) databases, the PrEPWatch repository and Google. Information on a range of STI-related interventions was extracted from documents available by October 2023. RESULTS: Of the 113 national PrEP guidance documents retrieved, STIs were mentioned in 77% (90/117). Viral hepatitis B testing and vaccination were recommended by most high-income countries (HICs) and low-income and middle-income countries (LMICs). Recommendation for syphilis testing was prominent in HICs (91%) and moderately noted in LMICs (68%). Gonorrhoea and chlamydia testing was recommended frequently in HICs (88%) and 42% in LMICs. However, the review noted that, to a much lesser extent, specific type of testing for these pathogens was mentioned. Recommendation for quarterly STI testing for syphilis, gonorrhoea and chlamydia was ubiquitous, while the need to offer STI partner services was rarely mentioned. CONCLUSIONS: PrEP services offer an opportunity for improved and expanded STI services, increasing person-centred care and addressing STI epidemics alongside HIV. Our review highlights the strengths and gaps in incorporating critical STI interventions into national PrEP normative guidance. Addressing these gaps through a stepwise approach and increasing targeted testing and partner services can help improve quality of care and support an effective response to HIV and other STIs.

Adherence with post-hospitalization follow-up after pediatric critical illness due to respiratory failure.

BACKGROUND: Adherence with follow-up appointments after a pediatric intensive care unit (PICU) admission is likely a key component in managing post-PICU sequalae. However, prior work on PICU follow-up adherence is limited. The objective of this study is to identify hospitalization characteristics, discharge child health metrics, and follow-up characteristics associated with full adherence with recommended follow-up at a quaternary care center after a PICU admission due to respiratory failure. METHODS: We conducted a retrospective cohort study of patients ≤ 18 years with respiratory failure admitted between 1/2013-12/2014 to a quaternary care PICU. Post-hospitalization full adherence with recommended follow-up in the two years post discharge (1/2013-3/2017) at the quaternary care center was quantified and compared by demographics, baseline child health metrics, hospitalization characteristics, discharge child health metrics, and follow-up characteristics in bivariate and multivariate analyses. Patients were dichotomized into being non-adherent with follow-up (patients who attended less than 100% of recommended appointments at the quaternary care center) and fully adherent (patients who attended 100% of recommended appointments at the quaternary care center). RESULTS: Of 155 patients alive at hospital discharge, 140 (90.3%) were recommended to follow-up at the quaternary care center. Of the 140 patients with recommended follow-up at the quaternary care center, 32.1% were non-adherent with follow-up and 67.9% were fully adherent. In a multivariable logistic regression model, each additional recommended unique follow-up appointment was associated with lower odds of being fully adherent with follow-up (OR 0.74, 95% CI 0.60-0.91, p = 0.005), and each 10% increase in the proportion of appointments scheduled before discharge was associated with higher odds of being fully adherent with follow-up (OR 1.02, 95% CI 1.01-1.03, p = 0.004). CONCLUSIONS: After admission for acute respiratory failure, only two-thirds of children were fully adherent with recommended follow-up at a quaternary care center. Our findings suggest that limiting the recommended follow-up to only key essential healthcare providers and working to schedule as many appointments as possible before discharge could improve follow-up adherence. However, a better understanding of the factors that lead to non-adherence with follow-up appointments is needed to inform broader system-level approaches could help improve PICU follow-up adherence.

Racial and Ethnic Differences in Time to Completion of Academic Enrichment Program Applications.

INTRODUCTION: Diversity in healthcare and research is integral to serving our increasingly diverse population. Access to academic enrichment programs, an important pathway to science, technology, engineering, and mathematics (STEM) careers promotes educational attainment through academic preparation and increased interest, useful strategies for improving diverse representation in higher learning. Given this important pathway to STEM fields, attention to equity in enrichment programs admissions is as important as the increasing focus on mitigating racial/ethnic disparities in undergraduate and graduate admissions.  Methods: In a retrospective cohort study at the University of Washington, we used descriptive and Chi-Square statistics to compare a hybrid competitive summer application program with stipend with an asynchronous first-come, first-served enrollment program in injury and violence prevention research. The three main outcomes were: 1) time to application, measured by number of days to apply/enroll after application or enrollment period start date, 2) percentage of application/enrollment period, measured by when application or enrollment occurred in relation to the total application or enrollment period, and 3) differences in Black, Hispanic, and Native American applicants and enrollees.  Results: In a study examining two injury and violence prevention programs, which reached educational institutions including Historically Black Colleges and Universities (HBCU) and Tribal Colleges: 1) Applicants were 9.6% and 6.4% Black (application vs enrollment programs; p<0.0001), 0.4% and 0% Native American to the application and enrollment programs, and 9.1% and 10.3% Hispanic (application vs enrollment programs; p=0.6), 2) Across all racial and ethnic groups, students applied later (last 15% percent of application period) in the competitive application program than to the first-come first-served enrollment program in which students enrolled throughout the enrollment period, and 3) Across both program types, there were racial and ethnic differences in time to application and enrollment start and completion. CONCLUSION: Findings show that free enrollment programs alone do not incentivize educational attainment for all groups and that application rolling admissions processes may not equally promote racial and ethnic diversity for all groups.

Cancer misinformation on social media.

Social media is widely used globally by patients, families of patients, health professionals, scientists, and other stakeholders who seek and share information related to cancer. Despite many benefits of social media for cancer care and research, there is also a substantial risk of exposure to misinformation, or inaccurate information about cancer. Types of misinformation vary from inaccurate information about cancer risk factors or unproven treatment options to conspiracy theories and public relations articles or advertisements appearing as reliable medical content. Many characteristics of social media networks-such as their extensive use and the relative ease it allows to share information quickly-facilitate the spread of misinformation. Research shows that inaccurate and misleading health-related posts on social media often get more views and engagement (e.g., likes, shares) from users compared with accurate information. Exposure to misinformation can have downstream implications for health-related attitudes and behaviors. However, combatting misinformation is a complex process that requires engagement from media platforms, scientific and health experts, governmental organizations, and the general public. Cancer experts, for example, should actively combat misinformation in real time and should disseminate evidence-based content on social media. Health professionals should give information prescriptions to patients and families and support health literacy. Patients and families should vet the quality of cancer information before acting upon it (e.g., by using publicly available checklists) and seek recommended resources from health care providers and trusted organizations. Future multidisciplinary research is needed to identify optimal ways of building resilience and combating misinformation across social media.

Accelerated Orthodontic Treatment using Biomodulation: A Randomized Clinical Trial.

Background: Orthodontic treatment often spans several months or even years, which can be burdensome for patients. Biomodulation techniques have emerged as potential strategies to expedite orthodontic tooth movement. Materials and Methods: A randomized clinical trial was conducted with a sample of 60 orthodontic patients, aged 12-30 years, requiring fixed appliance therapy. Patients were randomly assigned to either the biomodulation group (n = 30) or the control group (n = 30). The biomodulation group received low-level laser therapy (LLLT) along with traditional orthodontic treatment, while the control group received conventional orthodontic treatment without LLLT. Treatment duration, pain perception, and orthodontic tooth movement were assessed during the study period. Results: The results demonstrated a significant reduction in treatment duration in the biomodulation group compared to the control group. The biomodulation group exhibited a 30% reduction in overall treatment time, with an average treatment duration of 8.4 months, while the control group required an average of 12 months (P < 0.001). Pain perception during orthodontic adjustments was lower in the biomodulation group. Additionally, biomodulation was associated with a statistically significant increase in the rate of tooth movement, as evidenced by a 20% reduction in the time required to achieve desired tooth alignment (P < 0.01). Conclusion: Biomodulation through low-level laser therapy represents a promising adjunct to traditional orthodontic treatment, significantly accelerating tooth movement and reducing treatment duration.