BREATHE-T1D: Using iterative mixed methods to adapt a mindfulness-based intervention for adolescents with type 1 diabetes: Design and development.

BACKGROUND: Negative affect is prevalent among adolescents with type 1 diabetes (T1D) and may impact diabetes self-management and outcomes through stress-related behaviors such as disordered eating. METHODS: We describe the development of and design for the adaptation of a mindfulness-based intervention (MBI) for adolescents with T1D and negative affect. BREATHE-T1D is an MBI designed to target negative affect that has been tailored to address the unique lived experiences of adolescents with T1D. Qualitative interviews with stakeholders and participants were used to inform iterative adaptations to the intervention and control curricula over the course of the study. The primary aim of this paper is to describe the design, development, and protocol of the present pilot feasibility trial. CONCLUSIONS: Iterative, qualitative methodology throughout the adaptation of an intervention is important for ensuring the resulting intervention is relevant and meaningful for the target population. CLINICAL TRIAL REGISTRATION NUMBER: NCT05268393.

Nanoparticle-mediated delivery of tetrahydrobiopterin restores endothelial function in diabetic rats.

Endothelial dysfunction, underlying the vascular complications of diabetes and other cardiovascular disorders, may result from uncoupling of endothelial nitric oxide synthase (eNOS) activity due to decreased levels of tetrahydrobiopterin (BH4), a critical co-factor for eNOS. Some clinical trials attempting to deliver exogenous BH4 as a potential therapeutic strategy in vascular disease states have failed due to oxidation of BH4 in the circulation. We sought to develop a means of protecting BH4 from oxidation while delivering it to dysfunctional endothelial cells. Polymeric and solid lipid nanoparticles (NPs) loaded with BH4 were delivered by injection or oral gavage, respectively, to streptozotocin-induced diabetic rats. BH4 was measured in coronary endothelial cells and endothelium-dependent vascular reactivity was assessed in vascular rings. Lymphatic uptake of orally delivered lipid NPs was verified by sampling mesenteric lymph. BH4-loaded polymeric NPs maintained nitric oxide production by cultured endothelial cells under conditions of oxidative stress. BH4-loaded NPs, delivered via injection or ingestion, increased coronary endothelial BH4 concentration and improved endothelium-dependent vasorelaxation in diabetic rats. Pharmacodynamics assessment indicated peak concentration of solid lipid NPs in the systemic bloodstream 6 hours after ingestion, with disappearance noted by 48 hours. These studies support the feasibility of utilizing NPs to deliver BH4 to dysfunctional endothelial cells to increase nitric oxide bioavailability. BH4-loaded NPs could provide an innovative tool to restore redox balance in blood vessels and modulate eNOS-mediated vascular function to reverse or retard vascular disease in diabetes.

'Snapshot in time': a cross-sectional study exploring stakeholder experiences with environmental scans in health services delivery research.

OBJECTIVE: To describe stakeholder characteristics and perspectives about experiences, challenges and information needs related to the use of environmental scans (ESs). DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A web-based survey platform was used to disseminate an online survey to stakeholders who had experience with conducting ESs in a health services delivery context (eg, researchers, policy makers, practitioners). Participants were recruited through purposive and snowball sampling. The survey was disseminated internationally, was available in English and French, and remained open for 6 weeks (15 October to 30 November 2022). ANALYSIS: Descriptive statistics were used to describe the characteristics and experiences of stakeholders. Thematic analysis was used to analyse the open-text questions. RESULTS: Of 47 participants who responded to the survey, 94% were from Canada, 4% from the USA and 2% from Australia. Respondents represented academic institutions (57%), health agency/government (32%) and non-government organisations or agencies (11%). Three themes were identified: (a) having a sense of value and utility; (b) experiencing uncertainty and confusion; and (c) seeking guidance. The data suggest stakeholders found value and utility in ESs and conducted them for varied purposes including to: (a) enhance knowledge, understanding and learning about the current landscape or state of various features of health services delivery (eg, programmes, practices, policies, services, best practices); (b) expose needs, service barriers, challenges, gaps, threats, opportunities; (c) help guide action for planning, policy and programme development; and (d) inform recommendations and decision-making. Stakeholders also experienced conceptual, methodological and practical barriers when conducting ESs, and expressed a need for methodological guidance delivered through published guidelines, checklists and other means. CONCLUSION: ESs have value and utility for addressing health services delivery concerns, but conceptual and methodological challenges exist. Further research is needed to help advance the ES as a distinct design that provides a systematic approach to planning and conducting ESs.

Deep Brain Stimulation of Bilateral Centromedian Thalamic Nuclei in Pediatric Patients with Lennox-Gastaut Syndrome: An Institutional Experience.

BACKGROUND: Surgical management of pediatric patients with nonlesional, drug-resistant epilepsy, including patients with Lennox-Gastaut syndrome (LGS), remains a challenge given the lack of resective targets in most patients and shows seizure freedom rates <50% at 5 years. The efficacy of deep brain stimulation (DBS) is less certain in children than in adults. This study examined clinical and seizure outcomes for pediatric patients with LGS undergoing DBS targeting of the centromedian thalamic nuclei (CMTN). METHODS: An institutional review board-approved retrospective analysis was performed of patients aged ≤19 years with clinical diagnosis of LGS undergoing bilateral DBS placement to the CMTN from 2020 to 2021 by a single surgeon. RESULTS: Four females and 2 males aged 6-19 years were identified. Before surgery, each child experienced at least 6 years of refractory seizures; 4 children had experienced seizures since infancy. All took antiseizure medications at the time of surgery. Five children had previous placement of a vagus nerve stimulator and 2 had a previous corpus callosotomy. The mean length of stay after DBS was 2 days. No children experienced adverse neurologic effects from implantation; the mean follow-up time was 16.3 months. Four patients had >60% reduction in seizure frequency after surgery, 1 patient experienced 10% reduction, and 1 patient showed no change. No children reported worsening seizure symptoms after surgery. CONCLUSIONS: Our study contributes to the sparse literature describing CMTN DBS for children with drug-resistant epilepsy from LGS. Our results suggest that CMTN DBS is a safe and effective therapeutic modality that should be considered as an alternative or adjuvant therapy for this challenging patient population. Further studies with larger patient populations are warranted.

The chromatin landscape of healthy and injured cell types in the human kidney.

There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidney's active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we note distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3, KLF6, and KLF10 regulates the transition between health and injury, while in thick ascending limb cells this transition is regulated by NR2F1. Further, combined perturbation of ELF3, KLF6, and KLF10 distinguishes two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks.

A Case Series on the Use of Brentuximab Vedotin for the Treatment of Mycosis Fungoides.

BACKGROUND: Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody that appears to be more effective against CD30-expressing cutaneous T-cell lymphoma (CTCL) compared to current standard-of-care treatments.   Objective: To determine the real-world efficacy and adverse effects of BV use in patients with mycosis fungoides (MF) who were treated with BV at Atrium Health Wake Forest Baptist Medical Center. METHODS: Study staff performed a retrospective chart review of patients diagnosed with MF who were prescribed BV at Atrium Health Wake Forest Baptist Comprehensive Cancer Center. RESULTS:   Regardless of their response to BV, all patients in our cohort had higher CD30 positivity on subsequent biopsies compared to their initial skin biopsy.  Conclusions: Improved understanding of appropriate CD30 testing and evaluation will allow for quicker invention of patients with BV responsive CTCL.  J Drugs Dermatol. 2023;22(12):e33-e34.    doi:10.36849/JDD.6981e.

Topical Moisturizer Meaningfully Reduces Disease Severity in Atopic Patients With Xerosis.

BACKGROUND: Repairing the epidermal barrier is critically important in atopic dermatitis (AD), but the effect of moisturizer on quality of life (QOL) is not well characterized.  Objective: To assess whether the use of a moisturizer improves QOL in atopic patients with xerosis.  Methods: Thirty-five (35) adults with xerosis and AD received a moisturizer designed for AD to apply daily for three months. Adherence was assessed with electronic monitors. Quality of life (QOL) was assessed with the Dermatology Life Quality Index (DLQI) at baseline and follow-up.  Results: Mean adherence to the moisturizer was 46%. Dryness improved from 1.9 at baseline to 1.4 at follow-up (P=0.02). DLQI improved from 3.3 at baseline to 1.5 at 3 months (P=0.005). The "feeling self-conscious or embarrassed due to their skin condition" DLQI item improved from 0.79 at baseline to 0.14 at 3 months (P=0.0009).  Conclusion: Moisturizers are the foundation of AD treatment. Even non-medicated topical emollients can improve QOL in patients with AD.  J Drugs Dermatol. 2023;22(12):e51-e52.     doi:10.36849/JDD.7036e.

Topical Ivermectin Is Associated With Improved Erythematotelangiectatic, Papulopustular, and Phymatous Rosacea in a Secondary Analysis.

Rosacea has variable clinical presentation consisting of four overlapping phenotypes: erythematotelangiectatic, papulopustular, phymatous, and ocular.1 Rosacea's pathogenesis involves increased cutaneous density of Demodex folliculorum mites, which drive inflammation through activation of Toll-like receptor-2.1,2 Thus, topical ivermectin (IVM) 1.0% cream's anti-inflammatory and acaricidal activity provides an effective and targeted treatment for moderate-to-severe rosacea. However, literature assessing IVM is limited to efficacy in treating the papulopustular presentation, limiting generalizability.1,3,4 Although our primary endpoint was to assess patient adherence, the objective of this secondary analysis was to assess IVM efficacy in rosacea, regardless of clinical presentation.

The role of traditional social determinants of health in referral patterns, timing of surgery, and Chiari Health Index for Pediatrics-determined quality of life in children with symptomatic Chiari type I malformation.

OBJECTIVE: Understanding the impact of the social determinants of health on the utilization of healthcare resources is an important step in eliminating inequalities. The goal of this study was to determine the role of social determinants of health in referral patterns, timing of consultation/intervention, and quality of life in children with Chiari malformation type I (CM-I). METHODS: A retrospective study was conducted of children aged 0 to 18 years who underwent surgical treatment for CM-I at a single pediatric facility from 2015 to 2019. The variables included demographic and socioeconomic characteristics, referral patterns, timing, and quality of life data based on the Chiari Health Index for Pediatrics (CHIP). RESULTS: The cohort consisted of 103 surgically treated CM-I patients. No differences were seen in race, sex, insurance, or household income when evaluating referral source (community, specialist, or emergency department) or when comparing patients with incidental versus symptomatic findings. In the evaluation of timing from initial evaluation to surgery, no statistical differences were seen between racial, sex, insurance status, or income groups. Children from households of lower median family income were significantly more likely to report pain at the time of consultation (pain group median [interquartile range] $46,660 [$41,004-$50,367] vs nonpain group $53,604 [$41,427-$59,828], p = 0.004). Those in the lower-income group also reported lower CHIP scores corresponding to increased symptomatology in the nonpain physical symptoms (p = 0.004) and psychosocial domains (p = 0.018). CONCLUSIONS: There was no evidence of a difference in referral patterns or a delay in time from clinic presentation to surgery based on the traditional social determinants of health categories. Children from households in the lower-income group were associated with increased severity of pain and nonpain symptoms.

The Patient-Physician Relationship and Adherence: Observations From a Clinical Study.

Improved patient-physician relationships (PPR) are associated with better patient satisfaction and disease outcomes, however, there is limited literature assessing how PPR affects adherence in dermatology. We recruited 30 subjects with a clinical diagnosis of rosacea. Subjects were instructed to use ivermectin 1% cream once daily for 3 months and adherence was measured using the Medication Event Monitoring System cap. The Patient-Doctor Relationship Questionnaire (PDRQ-9), a validated questionnaire assessing patients’ perceived strength of the relationship with their doctor, was completed. Mean adherence for all subjects over three months of the study was 62%. PDRQ-9 scores positively correlated with adherence rates for 3 months of treatment (r(26)=0.52; P=0.006). The perceived strength of the PPR may have a role in patients’ adherence to their medications. Improving the PPR, through empathy and effective communication, may facilitate better medication adherence and treatment outcomes. Perche PO, Singh R, Cook MK, et al. The patient-physician relationship and adherence: observations from a clinical study. J Drugs Dermatol. 2023;22(8):838-839. doi:10.36849/JDD.7103.

Utility of Gynecological Teaching Associates.

Introduction Gynecological teaching associates (GTAs) are trained to teach the pelvic exam using themselves as models, and it has been hypothesized that their use can improve learners' confidence and interpersonal skills. This study aims to gain greater insight into whether the use of GTAs is associated with increased medical students' confidence when performing the pelvic exam during clinical rotations. Methods An email survey was distributed to medical students in two different classes at a single United States Medical Licensing Examination (USMLE)-accredited medical school: one that learned the pelvic exam using GTAs and one that did not. A Fisher's exact test was performed to determine associations between the use of GTAs and confidence in performing the pelvic exam, with a p-value of <0.01. Results Out of the 85 survey participants, 68 had performed a pelvic exam in the clinical setting and thus rated their confidence level. Of the 38 students who learned using a GTA, 66% (p<0.0024) reported a confidence level of four or five (out of five) compared to 50% of the 30 students who were not able to practice using a GTA. There was a statistically significant difference in the confidence levels of students who practiced on GTAs compared to those who did not. Discussion Our findings demonstrated that students who were able to learn the pelvic exam using GTAs reported higher confidence levels when subsequently performing a pelvic exam in a clinical setting. Conclusion Our findings support investment in GTA programming for teaching the pelvic exam in medical school curricula.

The chromatin landscape of healthy and injured cell types in the human kidney.

There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. However, comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measured dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We established a comprehensive and spatially-anchored epigenomic atlas to define the kidney's active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we noted distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3 , KLF6 , and KLF10 regulated the transition between health and injury, while in thick ascending limb cells this transition was regulated by NR2F1 . Further, combined perturbation of ELF3 , KLF6 , and KLF10 distinguished two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks.

Integrated Cytometry With Machine Learning Applied to High-Content Imaging of Human Kidney Tissue for In Situ Cell Classification and Neighborhood Analysis.

The human kidney is a complex organ with various cell types that are intricately organized to perform key physiological functions and maintain homeostasis. New imaging modalities, such as mesoscale and highly multiplexed fluorescence microscopy, are increasingly being applied to human kidney tissue to create single-cell resolution data sets that are both spatially large and multidimensional. These single-cell resolution high-content imaging data sets have great potential to uncover the complex spatial organization and cellular makeup of the human kidney. Tissue cytometry is a novel approach used for the quantitative analysis of imaging data; however, the scale and complexity of such data sets pose unique challenges for processing and analysis. We have developed the Volumetric Tissue Exploration and Analysis (VTEA) software, a unique tool that integrates image processing, segmentation, and interactive cytometry analysis into a single framework on desktop computers. Supported by an extensible and open-source framework, VTEA's integrated pipeline now includes enhanced analytical tools, such as machine learning, data visualization, and neighborhood analyses, for hyperdimensional large-scale imaging data sets. These novel capabilities enable the analysis of mesoscale 2- and 3-dimensional multiplexed human kidney imaging data sets (such as co-detection by indexing and 3-dimensional confocal multiplexed fluorescence imaging). We demonstrate the utility of this approach in identifying cell subtypes in the kidney on the basis of labels, spatial association, and their microenvironment or neighborhood membership. VTEA provides an integrated and intuitive approach to decipher the cellular and spatial complexity of the human kidney and complements other transcriptomics and epigenetic efforts to define the landscape of kidney cell types.

Characteristics of immunisation support programmes in Canada: a scoping review and environmental scan.

OBJECTIVE: To identify, characterise and map the existing knowledge about programmes that provide immunisation support to Canadians and barriers and facilitators to their delivery. DESIGN: Scoping review and environmental scan. INTRODUCTION: Vaccine hesitancy may be associated with unmet support needs of individuals. Immunisation support programmes that provide multicomponent approaches can improve vaccine confidence and equitable access. INCLUSION CRITERIA: Canadian programmes that focus on providing information about immunisation for the general public, but excluding articles targeting health professionals. The primary concept involves mapping the characteristics of programmes and our secondary concept examines barriers and facilitators to programme delivery. METHODS: The Joanna Briggs Institute (JBI) methodology guided this review, reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. A search strategy was developed and translated for six databases in November 2021 (updated October 2022). Unpublished literature was identified through the Canadian Agency for Drugs and Technologies in Health Grey Matters checklist and other relevant sources. Stakeholders (n=124) from Canadian regional health authorities were also contacted by email for publicly accessible information. Two independent raters screened and extracted data from identified material. Results are presented in tabular form. RESULTS: The search strategy and environmental scan resulted in 15 287 sources. A total of 161 full-text sources were reviewed after applying eligibility criteria, resulting in 50 articles. Programmes were delivered in multiple Canadian provinces, focusing on various vaccine types. All programmes aimed to increase vaccine uptake and were mostly provided in person. Multidisciplinary delivery teams based on collaborations among multiple entities were credited as a facilitator to programme delivery across settings. Limitations on programme resources, attitudes of programme staff and participants, and systems organisation were identified as barriers to delivery. CONCLUSIONS: This review highlighted characteristics of immunisation support programmes across various settings and described multiple facilitators and barriers. These findings can inform future interventions that aim to support Canadians in making decisions about immunisation.

Horsefly (genus Tabanus) bite: allergy or infection?

Summer heatwaves are often associated with increased reports of insect bites as people enjoy spending time outdoors. The horsefly (genus Tabanus), or 'cleg' as it is colloquially known, often receives negative publicity due to peak activity in summer. Following an increase in local hospital presentations due to complications of bites, discussion among colleagues suggested a lack of knowledge regarding best management.We present a case of a woman in her 30s with a large erythematous swelling on her thigh following a suspected horsefly bite. Review revealed no clinical evidence of sepsis but a localised inflammatory response. Inflammatory markers were normal and she was treated with intravenous antibiotics and oral antihistamines to good effect.This case highlights secondary care presentation of a common condition and discusses potential complications, pathogenesis and uncertainties around best practice guidelines for treatment. We highlight strategies to aid antibiotic stewardship, reduce complications and secondary care presentation.

The genogram as a recruitment tool for identifying primary caregivers of youth living with sickle cell disease preparing for transition.

AIMS: The purpose of this secondary analysis was to describe the impact of using genograms to identify family caregivers from an original research study which used family caregiver-adolescents/young adults (AYA) dyads. BACKGROUND: Research to improve transition preparation for AYA with chronic disease is essential as 90% will survive into adulthood. Family-based transition research is specifically needed as a majority of transition preparation will occur in the home setting. Dyadic research on transition has not previously described strategies for recruiting appropriate family caregivers. DESIGN: A descriptive, secondary analysis was conducted using genograms developed during the original study conducted between October 2019 and February 2020. METHODS: For this secondary analysis conducted between July 2020 and August 2021, 50 genograms were analysed using descriptive statistics to describe family structures, relationships and responsibilities in families of AYAs living with sickle cell disease. RESULTS: In 43 genograms, there was only one primary caregiver in the family. In seven genograms, there were multiple primary caregivers who met the inclusion criteria for primary caregiver in a single family. In five genograms, there were two appropriate primary caregivers in a single family, and in two genograms, there were three appropriate individuals in a single family who met study criteria as a primary caregiver. CONCLUSIONS: Findings from the analysis of the genograms used in the original study demonstrated potential ability to improve on dyad recruitment by more specifically identifying the family member most involved in supporting the AYA's disease management. IMPACT: Genograms are an established tool for gathering information on families and application with recruitment could improve research in the realm of transition and other family-based research. NO PATIENT OR PUBLIC CONTRIBUTION: This was a secondary analysis that assessed already existing data.

Full-endoscopic spine surgery diminishes surgical site infections - a propensity score-matched analysis.

BACKGROUND CONTEXT: Surgical site infections (SSI) are one the most frequent and costly complications following spinal surgery. The SSI rates of different surgical approaches need to be analyzed to successfully minimize SSI occurrence. PURPOSE: The purpose of this study was to define the rate of SSIs in patients undergoing full-endoscopic spine surgery (FESS) and then to compare this rate against a propensity score-matched cohort from the National Surgical Quality Improvement Program (NSQIP) database. DESIGN: This is a retrospective multicenter cohort study using a propensity score-matched analysis of prospectively maintained databases. PATIENT SAMPLE: A total of 1277 noninstrumented FESS cases between 2015 and 2021 were selected for analysis. In the nonendoscopic NSQIP cohort we selected data of 55,882 patients. OUTCOME MEASURES: The occurrence of any SSI was the primary outcome. We also collected any other perioperative complications, demographic data, comorbidities, operative details, history of smoking, and chronic steroid intake. METHODS: All FESS cases from a multi-institutional group that underwent surgery from 2015 to 2021 were identified for analysis. A cohort of cases for comparison was identified from the NSQIP database using Current Procedural Terminology of nonendoscopic cervical, thoracic, and lumbar procedures from 2015 to 2019. Trauma cases as well as arthrodesis procedures, surgeries to treat pathologies affecting more than 4 levels or spine tumors that required surgical treatment were excluded. In addition, nonelective cases, and patients with wounds worse than class 1 were also not included. Patient demographics, comorbidities, and operative details were analyzed for propensity matching. RESULTS: In the nonpropensity-matched dataset, the endoscopic cohort had a significantly higher incidence of medical comorbidities. The SSI rates for nonendoscopic and endoscopic patients were 1.2% and 0.001%, respectively, in the nonpropensity match cohort (p-value <.011). Propensity score matching yielded 5936 nonendoscopic patients with excellent matching (standard mean difference of 0.007). The SSI rate in the matched population was 1.1%, compared to 0.001% in endoscopic patients with an odds ratio 0.063 (95% confidence interval (CI) 0.009-0.461, p=.006) favoring FESS. CONCLUSIONS: FESS compares favorably for risk reduction in SSI following spinal decompression surgeries with similar operative characteristics. As a consequence, FESS may be considered the optimal strategy for minimizing SSI morbidity.

Perception of accountability decreases with age: observations from a clinical study of patients with rosacea.

Patient adherence to medications usually increases with age, however, it can also be impacted by other factors. Accountability is a psychosocial construct that is defined as the expectation for an individual to account for their actions. Accountability may also influence patients' motivation to adhere to their treatments. We assessed the relationship between age and perception of accountability as well as efficacy of interventions to improve accountability in a clinical study of 30 rosacea patients. Accountability was assessed using the validated Accountability Measurement Tool. Interventions to improve accountability included a digital interaction group and a digital skin analysis group. All patients were given ivermectin cream 1% and informed to apply it daily for 3-months. There was a negative association between age and AMT scores in all intervention groups, including the control group. Younger patients have a baseline greater perception of accountability that responded more to our interventions.