Single-Administration Self-Boosting Microneedle Patch for The Treatment of Obesity.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are one of the most effective treatments for obesity. The current therapy associated with repeated subcutaneous injections to maintain the drug therapeutic effect causes patient compliance issues and raises environmental concerns (due to sharp biohazard waste from disposed syringes/needles). Herein, we report a programmable scheduled release microneedles (PSR-MNs) system for delivering Semaglutide (a GLP-1 RA agent with a half-life of ~ 7 days) to manage and treat obesity. A single skin administration of a PSR-MNs patch (2 cm × 2 cm) which contains 4 programmable core-shell MNs patches (1 cm2 each, so-called pixels) enables the repeated release of Semaglutide every 7 days and sustains the drug efficacy for an unprecedented one-month period, simulating the effect of using four bolus injections spaced 7 days apart. Our PSR-MNs system provides an advanced injection-free platform to significantly enhance the current treatment of obesity with GLP-1RAs, addressing concerns related to pain, needle phobia, high cost and the need of medical facilities/personnel in traditional injections to administer the drug.

Variants in the Late Cornified Envelope Gene Locus Are Associated With Elevated T-helper 17 Responses in Patients With Postinfectious Lyme Arthritis.

BACKGROUND: Postinfectious Lyme arthritis (LA) is associated with dysregulated immunity and autoreactive T- and B-cell responses in joints. Here we explored the role of host genetic variation in this outcome. METHODS: The frequency of 253 702 single-nucleotide polymorphisms (SNPs) was determined in 147 patients with LA (87 with postinfectious LA and 60 with antibiotic-responsive LA), and for comparison in 90 patients with erythema migrans or the general population (n = 2504). Functional outcome of candidate SNPs was assessed by evaluating their impact on clinical outcome and on immune responses in blood and synovial fluid in patients with LA. RESULTS: Six SNPs associated with late cornified envelope (LCE3) genes were present at greater frequency in patients with postinfectious LA compared to those with antibiotic-responsive LA (70% vs 30%; odds ratio, 2; P < .01). These SNPs were associated with heightened levels of inflammatory Th17 cytokines in serum but lower levels of interleukin 27, a regulatory cytokine, implying that they may contribute to dysregulated Th17 immunity in blood. Moreover, in patients with postinfectious LA, the levels of these Th17 mediators correlated directly with autoantibody responses in synovial fluid, providing a possible link between LCE3 SNPs, maladaptive systemic Th17 immunity, and autoreactive responses in joints. CONCLUSIONS: Variation in the LCE3 locus, a known genetic risk factor in psoriasis and psoriatic arthritis, is associated with dysregulated systemic Th17 immunity and heightened autoantibody responses in joints. These findings underscore the importance of host genetic predisposition and systemic Th17 immunity in the pathogenesis of postinfectious (antibiotic-refractory) Lyme arthritis.

Clinical Trends in Granulomatous Mastitis Incidence, Prevalence, and Treatment: A Retrospective Study Highlighting Ethnic Differences in Care.

INTRODUCTION: This study focuses on granulomatous mastitis (GM), a rare inflammatory condition of the breast that has been increasingly diagnosed over the recent years. This research attempts to understand the incidence and prevalence of GM and its treatments. METHODS: This is a retrospective study over 9 y (January 2015-December 2023). We utilized the anonymized data collected by TriNetX Analytic Network, a global federated health research network. The database was queried for patients diagnosed with GM and 3058 patients were returned. The incidence and prevalence of GM by age, race, and ethnicity were analyzed. The most common treatments for GM (antibiotics, steroids, incision and drainage, breast excision, and methotrexate) were analyzed. RESULTS: Hispanic and Latinos have a six-fold increased likelihood of developing GM compared to their non-Hispanic and non-Latino counterparts (0.006% compared to 0.001%). Treatment approaches reveal that antibiotics are the primary choice, while methotrexate is less commonly used. Antibiotics showed no significant differences between Hispanics and Latinos when compared to non-Hispanics and non-Latinos. Steroids showed a decreased prevalence in Hispanics and Latinos (P < 0.05). Incision and drainage showed an increased incidence in Hispanics and Latinos (P < 0.05). Excision showed no significant differences between the two groups. Methotrexate showed a higher incidence of usage among Hispanics and Latinos (P < 0.05). CONCLUSIONS: GM has the highest incidence and prevalence among Hispanics and Latinos. Despite that, the treatments do not directly reflect these differences which underscore the need for personalized treatment strategies, particularly among Hispanic or Latino populations, and underscores the importance of further research to elucidate contributing factors to these differences.

Oxytocin differentially modulates the early neural responses to faces and non-social stimuli.

Oxytocin (OT) alters social cognition partly through effects on the processing and appraisal of faces. It is debated whether the hormone also impacts the processing of other, non-social, visual stimuli. To this end, we conducted a randomized, counter-balanced, double-blind, placebo (PL)-controlled within-subjects' electro-encephalography (EEG) study with cismale participants (to control for gender dimorphic hormonal effects; n = 37). Participants received intranasal OT (24IU) and completed a one-back task viewing emotional (fearful/ happy) and neutral faces, and threat (snakes/spiders) and non-threat (mushrooms/flowers) non-social stimuli. OT differentially impacted event-related potentials (ERP)s to faces and non-social stimuli. For faces regardless of emotion, OT evoked greater occipital N1 and anterior P1 amplitudes at ∼155 ms than after PL, and lead to sustained differences over anterior, bilateral parietal and occipital sites from 205 ms onwards. For all non-social stimuli, OT evoked greater right parietal N1 amplitudes, and later only impacted threat stimuli over right parietal and occipital sites. None of these OT-induced modulations was related to individual anxiety levels. This pattern of results indicates that OT differentially modulates the processing of faces and non-social stimuli, and that the hormone's effect on visual processing and cognition does not occur as a function of non-clinical levels of anxiety.

"Giving Me the Self-Confidence to Tackle It": Mothers' Experiences Participating In The Engaged Eaters Program, A Caregiver-Mediated Feeding Intervention.

The purpose of this study was to understand caregivers' experience of participating in a caregiver-mediated in-home feeding intervention, the Engaged Eaters Program, for their young autistic child. This qualitative study utilized a thematic approach to analyze post-intervention semi-structured interviews with thirteen mothers of autistic children between the ages of 2 to 7 years after they participated in the intervention. Interview questions focused on the child and family experience, what worked well, what could be improved, and how the intervention integrated into family routines. Four major themes were identified: In-Home Intervention, Parent Skill and Knowledge, Increased Social Participation, and Parent Responsibilities and Challenges. Sub-themes provided descriptions of learning practical tools to support their child, increasing self-efficacy, and impacts on family life. Mothers described an increase in tangible skills that were easily practiced in the home environment that improved their confidence and self-efficacy in feeding their children. They also described how participation did require more work and time commitment for them beyond their regular responsibilities. The caregiver experience is essential to understand for intervention effectiveness while simultaneously addressing child, caregiver, and family needs. By focusing on the mothers' experiences, individualized needs, and self-efficacy, we were able to better understand how integrating an intervention into the family context and daily routines may be beneficial for the whole family.

Utility of a pharmacist-managed Anticoagulation Program in patients with congenital heart disease.

BACKGROUND: Warfarin remains the preferred anticoagulant for many patients with CHD. The complexity of management led our centre to shift from a nurse-physician-managed model with many providers to a pharmacist-managed model with a centralized anticoagulation team. We aim to describe the patient cohort managed by our Anticoagulation Program and evaluate the impact of implementation of this consistent, pharmacist-managed model on time in therapeutic range, an evidence-based marker for clinical outcomes. METHODS: A single-centre retrospective cohort study was conducted to evaluate the impact of the transition to a pharmacist-managed model to improve anticoagulation management at a tertiary pediatric heart centre. The percent time in therapeutic range for a cohort managed by both models was compared using a paired t-test. Patient characteristics and time in therapeutic range of the program were also described. RESULTS: After implementing the pharmacist-managed model, the time in therapeutic range for a cohort of 58 patients increased from 65.7 to 80.2% (p < .001), and our Anticoagulation Program consistently maintained this improvement from 2013 to 2022. The cohort of patients managed by the Anticoagulation Program in 2022 included 119 patients with a median age of 24 years (range 19 months-69 years) with the most common indication for warfarin being mechanical valve replacement (n = 81, 68%). CONCLUSIONS: Through a practice change incorporating a collaborative, centralized, pharmacist-managed model, this cohort of CHD patients on warfarin had a fifteen percent increase in time in therapeutic range, which was sustained for nine years.

Experience of irreproducibility as a risk factor for poor mental health in biomedical science doctoral students: A survey and interview-based study.

High rates of irreproducibility and of poor mental health in graduate students have been reported in the biomedical sciences in the past ten years, but to date, little research has investigated whether these two trends interact. In this study, we ask whether the experience of failing to replicate an expected finding impacts graduate students' mental health. Using an online survey paired with semi-structured qualitative interviews, we examined how often biomedical science doctoral students at a large American public university experienced events that could be interpreted as failures to replicate and how they responded to these experiences. We found that almost all participants had experience with irreproducibility: 84% had failed to replicate their own results, 70% had failed to replicate a colleague's finding, and 58% had failed to replicate a result from the published literature. Participants reported feelings of self-doubt, frustration, and depression while experiencing irreproducibility, and in 24% of cases, these emotional responses were strong enough to interfere with participants' eating, sleeping, or ability to work. A majority (82%) of participants initially believed that the anomalous results could be attributed to their own error. However, after further experimentation, most participants concluded that the original result was wrong (38%), that there was a key difference between the original experiment and their own (17%), or that there was a problem with the protocol (17%). These results suggest that biomedical science graduate students may be biased towards initially interpreting failures to replicate as indicative of a lack of skill, which may trigger or perpetuate feelings of anxiety, depression, or impostorism.

New patient privacy curtains to provide passive infection prevention.

Background: Cloth privacy curtains represent a potentially overlooked high touch surface. Inconsistent cleaning schedules paired with frequent contact allow curtains to provide a surface for the transmission of healthcare associated pathogens. Privacy curtains integrated with antimicrobial and sporicidal agents are shown to reduce the number of bacteria found on the surface of the curtains. The purpose of this initiative is to utilize antimicrobial and sporicidal privacy curtains to mitigate the transmission of healthcare associated pathogens from curtains to patients. Methods: The pre/post-test study design compared the bacterial and sporicidal burden of cloth curtains to the bacterial and sporicidal burden of Endurocide curtains following 20-weeks of use within the inpatient setting of a large military medical hospital. The Endurocide curtains were installed on two inpatient units in the organization. We also compared the overall costs associated with the two different types of curtains. Results: The antimicrobial and sporicidal curtains had a significant reduction in bacterial contamination (32.6 CFUs vs 0.56 CFUs, P < 0.05) after instillation on both units. There were no additional hospital associated infections during the study period. In addition, the direct cost savings of replacing the antimicrobial and sporicidal curtains is estimated to be $20,079.38 annually with a reduction of 66.95 hours in environmental services workload. Conclusion: These curtains represent a cost-effective intervention effective at reducing CFUs with the potential to mitigate the transmission of hospital associated pathogens to patients.

Hierarchical status is rapidly assessed from behaviourally dominant faces.

Recognition of social hierarchy is a key feature that helps us navigate through our complex social environment. Neuroimaging studies have identified brain structures involved in the processing of hierarchical stimuli, but the precise temporal dynamics of brain activity associated with such processing remains largely unknown. In this investigation, we used event-related potentials (ERPs) to examine the effect of social hierarchy on the neural responses elicited by dominant and nondominant faces. Participants played a game where they were led to believe that they were middle-rank players, responding alongside other alleged players, whom they perceived as higher or lower-ranking. ERPs were examined in response to dominant and nondominant faces, and low-resolution electromagnetic tomography (LORETA) was used to identify the implicated brain areas. The results revealed that the amplitude of the N170 component was enhanced for faces of dominant individuals, showing that hierarchy influences the early stages of face processing. A later component, the late positive potential (LPP) appearing between 350-700 ms, also was enhanced for faces of higher-ranking players. Source localisation suggested that the early modulation was due to an enhanced response in limbic regions. These findings provide electrophysiological evidence for enhanced early visual processing of socially dominant faces.

Efficacy of the Tuned In music emotion regulation program in international university students.

OBJECTIVE: Moving overseas to study can be exciting, however many international students find this transition stressful. Therefore, empirically supported strategies to assist with managing stress and supporting well-being are needed. Motivated music listening is an effective stress management strategy, and is linked with international student well-being. Tuned In is a group program designed to increase emotion awareness and regulation using motivated music listening. METHODS AND MEASURES: We evaluated a 4-session online version of Tuned In for motivated music use, emotion regulation, and well-being in international students. The study used a 2 (Treatment; Waitlist) x 3 (timepoints: pre = T1; +4 weeks = T2; +8 weeks = T3) randomised controlled cross-over design. Treatment participants (n = 23) completed Tuned In between T1 and T2, Waitlist participants (n = 27) completed Tuned In between T2 and T3. RESULTS: Between T1 and T2, motivated music use increased in Treatment participants but not for the Waitlist. Treatment participants were also more confident in maintaining happiness and in having healthy ways of managing emotions at T2. All participants enjoyed Tuned In. CONCLUSIONS: Tuned In, a group-based music listening program, even when delivered online, provides benefits for international students. With student well-being at risk as they begin university, enjoyable programs that help develop skills for students' academic journey should be a priority.

A Systematic Review of the Efficacy and Safety of Ketamine in Total Joint Arthroplasty.

BACKGROUND: Ketamine is administered intraoperatively to treat pain associated with primary total hip (THA) and knee arthroplasty (TKA). The purpose of this study was to evaluate the efficacy and safety of ketamine in primary THA and TKA to support the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons (AAHKS), American Academy of Orthopaedic Surgeons (AAOS), Hip Society, Knee Society, and the American Society of Regional Anesthesia and Pain Management (ASRA). METHODS: The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for studies published prior to 2020 on ketamine in THA and TKA. All included studies underwent qualitative assessment and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of ketamine. After a critical appraisal of 136 publications, 7 high-quality studies were included for analyses. RESULTS: High-quality evidence demonstrates that intraoperative ketamine decreases postoperative opioid consumption. Four of 7 studies found that ketamine reduces postoperative pain. Intraoperative ketamine is not associated with an increase in adverse events and may reduce postoperative nausea and vomiting (relative risk [RR] 0.68; 95% CI 0.50-0.92). CONCLUSION: High-quality evidence supports the use of ketamine intraoperatively in THA and TKA to reduce postoperative opioid consumption. Most studies found ketamine reduces postoperative pain, nausea, and vomiting. Moderate quality evidence supports the safety of ketamine, but it should be used cautiously in patients at risk for postoperative delirium, such as the elderly.

Reverse Abdominoplasty for Reconstruction Following Oncologic Resection of Extensive Breast Disease.

We present two cases of patients with extensive breast disease who underwent a reverse abdominoplasty for closure following resection: one of Paget's disease extending beyond the breast borders and another of a locally recurrent triple-negative invasive ductal carcinoma following mastectomy in a patient who previously had an ipsilateral thoracotomy. The reverse abdominoplasty flap is a reconstructive option not readily considered for closure following mastectomy. However, we believe that the reverse abdominoplasty flap should be considered when evaluating patients for anterior chest wall reconstruction because it is a simple and versatile coverage option.

Accessibility and Inclusion for Families with Children with Autism Spectrum Disorders in Cultural Institutions.

This project aimed to develop a comprehensive set of evaluation tools to assess the accessibility and inclusion of families with children on the autism spectrum in cultural institutions. A stakeholder team conducted interviews, reviewed museum artifacts, and observed museum programming. An evaluation toolkit was constructed by incorporating best practices from current literature and collected data. Tools were piloted and revised after being implemented in the museum context. The Toolkit to Increase Accessibility and Inclusion for Children on the Autism Spectrum and with Sensory Processing Differences in Cultural Institutions was developed with five unique tools, the Dimensions of Accessibility framework, and further resources to provide a self-assessment of cultural institutions. The toolkit can be used broadly across many types of institutions and self-assessment can lead to proactive development of public spaces, institutions, and programming that is accessible and inclusive of diverse groups of people, beyond families with children on the autism spectrum.

The Efficacy and Safety of Corticosteroids in Total Joint Arthroplasty: A Direct Meta-Analysis.

BACKGROUND: Corticosteroids are commonly used intraoperatively to treat pain and reduce opioid consumption and nausea associated with primary total joint arthroplasty (TJA). The purpose of this study was to evaluate the efficacy and safety of corticosteroids in primary TJA to support the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and the American Society of Regional Anesthesia and Pain Management. METHODS: The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for studies published before February 2020 on corticosteroids in TJA. All included studies underwent qualitative and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of corticosteroids. RESULTS: Critical appraisal of 1,581 publications revealed 23 studies regarded as the best available evidence for analysis. Intraoperative dexamethasone reduces postoperative pain, opioid consumption, and nausea and vomiting. Multiple doses lead to further reduction in pain, opioid consumption, nausea and vomiting. There is insufficient evidence on the risk of adverse events with perioperative dexamethasone in TJA. CONCLUSION: Strong evidence supports the use of a single dose or multiple doses of intravenous dexamethasone to reduce postoperative pain, opioid consumption, nausea and vomiting after primary TJA. There is insufficient evidence on perioperative dexamethasone in primary TJA to determine the optimal dose, number of doses, or risk of postoperative adverse events.

The Efficacy and Safety of Regional Nerve Blocks in Total Knee Arthroplasty: Systematic Review and Direct Meta-Analysis.

BACKGROUND: Regional nerve blocks are widely used in primary total knee arthroplasty (TKA) to reduce postoperative pain and opioid consumption. The purpose of our study was to evaluate the efficacy and safety of regional nerve blocks after TKA in support of the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and American Society of Regional Anesthesia and Pain Management. METHODS: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for studies published before March 24, 2020 on femoral nerve block, adductor canal block, and infiltration between Popliteal Artery and Capsule of Knee in primary TKA. All included studies underwent qualitative and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of the regional nerve blocks compared to a control, local peri-articular anesthetic infiltration (PAI), or between regional nerve blocks. RESULTS: Critical appraisal of 1,673 publications yielded 56 publications representing the best available evidence for analysis. Femoral nerve and adductor canal blocks are effective at reducing postoperative pain and opioid consumption, but femoral nerve blocks are associated with quadriceps weakness. Use of a continuous compared to single shot adductor canal block can improve postoperative analgesia. No difference was noted between an adductor canal block or PAI regarding postoperative pain and opioid consumption, but the combination of both may be more effective. CONCLUSION: Single shot adductor canal block or PAI should be used to reduce postoperative pain and opioid consumption following TKA. Use of a continuous adductor canal block or a combination of single shot adductor canal block and PAI may improve postoperative analgesia in patients with concern of poor postoperative pain control.

The Efficacy and Safety of Regional Nerve Blocks in Total Hip Arthroplasty: Systematic Review and Direct Meta-Analysis.

BACKGROUND: Regional nerve blocks may be used as a component of a multimodal analgesic protocol to manage postoperative pain after primary total hip arthroplasty (THA). The purpose of our study was to evaluate the efficacy and safety of regional nerve blocks after THA in support of the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and American Society of Regional Anesthesia and Pain Management. METHODS: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for studies published prior to March 24, 2020 on fascia iliaca, lumbar plexus, and quadratus lumborum blocks in primary THA. All included studies underwent qualitative and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of the regional nerve blocks. RESULTS: An initial critical appraisal of 3,382 publications yielded 11 publications representing the best available evidence for an analysis. Fascia iliaca, lumbar plexus, and quadratus lumborum blocks demonstrate the ability to reduce postoperative pain and opioid consumption. Among the available comparisons, no difference was noted between a regional nerve block or local periarticular anesthetic infiltration regarding postoperative pain and opioid consumption. CONCLUSION: Local periarticular anesthetic infiltration should be considered prior to a regional nerve block due to concerns over the safety and cost of regional nerve blocks. If a regional nerve block is used in primary THA, a fascia iliaca block is preferred over other blocks due to the differences in technical demands and risks associated with the alternative regional nerve blocks.

The Efficacy and Safety of Periarticular Injection in Total Joint Arthroplasty: A Direct Meta-Analysis.

BACKGROUND: Periarticular injection (PAI) is administered intraoperatively to help reduce postoperative pain and opioid consumption after primary total joint arthroplasty (TJA). The purpose of this study was to evaluate the efficacy and safety of PAI in primary TJA to support the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and American Society of Regional Anesthesia and Pain Medicine. METHODS: The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for studies published prior to March 2020 on PAI in TJA. All included studies underwent qualitative and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of PAI. RESULTS: Three thousand six hundred and ninety nine publications were critically appraised to provide 60 studies regarded as the best available evidence for an analysis. The meta-analysis showed that intraoperative PAI reduces postoperative pain and opioid consumption. Adding ketorolac or a corticosteroid to a long-acting local anesthetic (eg, ropivacaine or bupivacaine) provides an additional benefit. There is no difference between liposomal bupivacaine and other nonliposomal long-acting local anesthetics. Morphine does not provide any additive benefit in postoperative pain and opioid consumption and may increase postoperative nausea and vomiting. There is insufficient evidence to draw conclusions on the use of epinephrine and clonidine. CONCLUSION: Strong evidence supports the use of a PAI with a long-acting local anesthetic to reduce postoperative pain and opioid consumption. Adding a corticosteroid and/or ketorolac to a long-acting local anesthetic further reduces postoperative pain and may reduce opioid consumption. Morphine has no additive effect and there is insufficient evidence on epinephrine and clonidine.

A Mixed Methods Assessment of Home-Based Video Pretransplant Lung Education.

Introduction: Patients awaiting lung transplantation must learn new information to successfully navigate the transplant process. A supplemental video series was piloted to patients at home during the Covid-19 pandemic to improve pre-transplant education. Methods: A mixed methods study was undertaken to assess patient experiences with this method of education, confirm the ideal timing of the education, and identify gaps that require further attention. Semi-structured interviews were conducted with 17 one-on-one or dyadic (patients and caregivers) who viewed the video series at home. A third-party researcher (not involved in creation of the educational materials) conducted the interviews by phone, which were audio recorded and then transcribed verbatim. NVivo 12 Pro for Windows software was used to code the data and identify emerging themes. Results: Participants indicated that home-based videos were applicable, and informative and helpful (4.7 on 5-point Likert scale) and appreciated the advice and experiences of real patients. They were satisfied with their transplant education (4.2/5). While there were few aspects that the participants disliked about the videos, the interviews elicited outstanding questions about the transplant process (eg, logistical aspects of travel) and transplant concerns (eg, medications, expenses, and precautions in daily life). Conclusion: Patients being assessed or listed for lung transplant valued the novel electronic video education, and we will implement the home-based process into standard of care after the patient's initial visit with the transplant respirologist. Pre-transplant education will be tailored to help address the outstanding gaps identified in this program evaluation.