Two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT open-label extension study.

STUDY QUESTION: What is the efficacy and safety of long-term treatment (up to 2 years) with relugolix combination therapy (CT) in women with moderate to severe endometriosis-associated pain? SUMMARY ANSWER: For up to 2 years, treatment with relugolix CT improved menstrual and non-menstrual pain, dyspareunia, and function in women with endometriosis; after an initial decline of <1%, the mean bone mineral density (BMD) remained stable with continued treatment. WHAT IS KNOWN ALREADY: Endometriosis is a chronic condition characterized by symptoms of dysmenorrhea, non-menstrual pelvic pain (NMPP), and dyspareunia, which have a substantial impact on the lives of affected women, their partners, and families. SPIRIT 1 and 2 were phase 3, randomized, double-blind, placebo-controlled studies of once-daily relugolix CT (relugolix 40 mg, oestradiol 1 mg, norethisterone acetate 0.5 mg) in premenopausal women (age 18-50 years) with endometriosis and moderate-to-severe dysmenorrhea and NMPP. These trials demonstrated a significant improvement of dysmenorrhea, NMPP, and dyspareunia in women treated with relugolix CT, with minimal decline (<1%) in BMD versus placebo at 24 weeks. STUDY DESIGN, SIZE, DURATION: Patients participating in this open-label, single-arm, long-term extension (LTE) study of the 24-week SPIRIT pivotal studies (SPIRIT 1 and 2) received up to an additional 80 weeks of once-daily oral relugolix CT treatment between May 2018 and January 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Premenopausal women with confirmed endometriosis and moderate to severe dysmenorrhea and NMPP who completed the 24-week pivotal studies (SPIRIT 1 and 2 trials; Giudice et al., 2022) and who met all entry criteria were eligible to enrol. Two-year results were analysed by treatment group based on original randomization in pivotal studies: relugolix CT, delayed relugolix CT (relugolix 40 mg monotherapy for 12 weeks, followed by relugolix CT), or placebo→relugolix CT (placebo for 24 weeks followed by relugolix CT). The primary endpoints of the LTE study were the proportion of dysmenorrhea and NMPP responders at Week 52 and Week 104/end-of-treatment (EOT). A responder was a participant who achieved a predefined, clinically meaningful reduction from baseline in Numerical Rating Scale (NRS) scores (0 = no pain, 10 = worst pain imaginable) for the specific pain type with no increase in analgesic use. The predefined clinically meaningful threshold for dysmenorrhea was 2.8 points and for NMPP was 2.1 points. Secondary efficacy endpoints included change from baseline in Endometriosis Health Profile-30 (EHP-30) pain domain scores, a measure of the effects of endometriosis-associated pain on daily activities (function), NRS scores for dysmenorrhea, NMPP, dyspareunia, and overall pelvic pain, and analgesic/opioid use. Safety endpoints included adverse events and changes in BMD. MAIN RESULTS AND THE ROLE OF CHANCE: Of 1261 randomized patients, 1044 completed the pivotal studies, 802 enrolled in the LTE, 681 completed 52 weeks of treatment, and 501 completed 104 weeks of treatment. Demographics and baseline characteristics of the extension population were consistent with those of the original randomized population. Among patients randomized to relugolix CT at pivotal study baseline who continued in the LTE (N = 277), sustained improvements in endometriosis-associated pain were demonstrated through 104 weeks. The proportion of responders at Week 104/EOT for dysmenorrhea and NMPP was 84.8% and 75.8%, respectively. Decreases in dyspareunia and improvement in function assessed by EHP-30 pain domain were also sustained over 2 years. At Week 104/EOT, 91% of patients were opioid-free and 75% of patients were analgesic-free. Relugolix CT over 104 weeks was well tolerated with a safety profile consistent with that observed over the first 24 weeks. After initial least squares mean BMD loss <1% at Week 24, BMD plateaued at Week 36 and was sustained for the duration of 104 weeks of treatment. Efficacy and safety results were generally consistent in women in the placebo→relugolix CT and delayed relugolix CT groups. LIMITATIONS, REASONS FOR CAUTION: The study was conducted as an open-label study without a control group over the 80 weeks of the extension period. Of the 802 patients who were enrolled in this LTE study, 681 patients (84.9%) and 501 patients (62.5%) of patients completed 52 and 104 weeks of treatment, respectively. In addition, there currently are no comparative data to other hormonal medications. Finally, a third (37.4%) of the study population terminated participation early. WIDER IMPLICATIONS OF THE FINDINGS: In conclusion, relugolix CT offers an additional option to help address an important unmet clinical need for effective, safe, and well-tolerated medical treatments for endometriosis that can be used longer-term, reducing the need for opioids and improving quality of life. The findings from this study may help support the care of women with endometriosis seeking longer-term effective medical management of their symptoms. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Myovant Sciences GmbH (now Sumitomo Pharma Switzerland GmbH). C.M.B. reports fees from Myovant, grants from Bayer Healthcare, fees from ObsEva, and Chair of ESHRE Endometriosis Guideline Group (all funds went to the University of Oxford); N.P.J. reports personal fees from Myovant Sciences, during the conduct of the study, personal fees from Guerbet, personal fees from Organon, personal fees from Roche Diagnostics; S.A.-S. reports personal fees from Myovant Sciences, personal fees from Bayer, personal fees from Abbvie, personal fees from UpToDate; J.S.P., and R.B.W. are employees and shareholders of Myovant Sciences; J.C.A.F. and S.J.I. are shareholders of Myovant Sciences (but at time of publicaion are no longer employess of Myovant Sciences); M.S.A. and K.W. have no conflicts to declare; V.M. is a consultant to Myovant; L.C.G. reports personal fees from Myovant Sciences, Inc and Bayer. The authors did not receive compensation for manuscript writing, review, and revision. TRIAL REGISTRATION NUMBER: NCT03654274.

No evidence of compensatory changes in energy balance, despite reductions in body weight and liver fat, during dapagliflozin treatment in type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled, cross-over trial (ENERGIZE).

AIM: This study assessed the impact of dapagliflozin on food intake, eating behaviour, energy expenditure, magnetic resonance imaging (MRI)-determined brain response to food cues and body composition in patients with type 2 diabetes mellitus (T2D). MATERIALS AND METHODS: Patients were given dapagliflozin 10 mg once daily in a randomized, double-blind, placebo-controlled trial with short-term (1 week) and long-term (12 weeks) cross-over periods. The primary outcome was the difference in test meal food intake between long-term dapagliflozin and placebo treatment. Secondary outcomes included short-term differences in test meal food intake, short- and long-term differences in appetite and eating rate, energy expenditure and functional MRI brain activity in relation to food images. We determined differences in glycated haemoglobin, weight, liver fat (by 1 H magnetic resonance spectroscopy) and subcutaneous/visceral adipose tissue volumes (by MRI). RESULTS: In total, 52 patients (43% were women) were randomized; with the analysis of 49 patients: median age 58 years, weight 99.1 kg, body mass index 35 kg/m2 , glycated haemoglobin 49 mmol/mol. Dapagliflozin reduced glycated haemoglobin by 9.7 mmol/mol [95% confidence interval (CI) 3.91-16.27, p = .004], and body weight (-2.84 vs. -0.87 kg) versus placebo. There was no short- or long-term difference in test meal food intake between dapagliflozin and placebo [mean difference 5.7 g (95% CI -127.9 to 139.3, p = .933); 15.8 g (95% CI -147.7 to 116.1, p = .813), respectively] nor in the rate of eating, energy expenditure, appetite, or brain responses to food cues. Liver fat (median reduction -4.7 vs. 1.95%), but not subcutaneous/visceral adipose tissue, decreased significantly with 12 weeks of dapagliflozin. CONCLUSIONS: The reduction in body weight and liver fat with dapagliflozin was not associated with compensatory adaptations in food intake or energy expenditure.

Which Complex Patients Should Be Referred for Intensive Care Management? A Mixed-Methods Analysis.

BACKGROUND: A large and increasing proportion of health care costs are spent caring for a small segment of medically and socially complex patients. To date, it has been difficult to identify which patients are best served by intensive care management. OBJECTIVE: To characterize factors that best identify which complex patients are most suited for intensive care management. DESIGN: We conducted a mixed-methods study involving 35 care managers (CMs; 10 licensed social workers and 25 registered nurses) working in intensive care management programs within Kaiser Permanente Northern California (KPNC) outpatient medical centers. We asked CMs to review a randomly selected list of up to 50 patients referred to them in the prior year and to categorize each patient as either (1) "good candidates" for care management, (2) "not needing" intensive care management, or (3) "needing more" than traditional care management could provide. We then conducted semi-structured interviews to understand how CMs separated patients into these three groups. RESULTS: CMs assigned 1178 patients into the 3 referral categories. Less than two thirds (62%, n = 736) of referred patients were considered good candidates, with 18% (n = 216) categorized as not needing care management and 19% (n = 226) as needing more. Compared to the other two categories, good candidates were older (76.2 years vs. 73.2 for not needing and 69.8 for needing more, p < 0.001), prescribed more medications (p = 0.02) and had more prior year outpatient visits (p = 0.04), while the number of prior year hospital and emergency room admissions were greater than not needing but less than needing more (p < 0.001). A logistic regression model using available electronic record data predicted good candidate designation with a c statistic of 0.75. Several qualitative themes emerged that helped define appropriateness for referral, including availability of social support, patient motivation, non-medical transitions, recent trajectory of medical condition, and psychiatric or substance use issues. CONCLUSION: Many apparently complex patients are not good candidates for intensive care management. Current electronic medical records do not capture several of the most salient characteristics that determine appropriateness for care management. Our findings suggest that systematic collection of social support, patient motivation, and recent non-medically related life change information may help identify which complex patients are most likely to benefit from care management.

Topical oxygen therapy results in complete wound healing in diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are a significant problem in an aging population. Fifteen percent of diabetics develop a DFU over their lifetime, which can lead to potential amputation. The 5-year survival rate after amputation is 31%, which is greater than the lifetime risk of mortality from cancer. Topical oxygen is a promising technique for the adjunctive therapy of chronic wounds including DFUs, but few controlled studies exist to support its clinical adoption. The aim of this study was to compare a portable topical oxygen delivery system in patients with nonhealing DFUs to standard best practice. Twenty patients were randomized into a topical oxygen group (n = 10), and a nonplacebo control group with regular dressings and standard care (n = 10), and attended the diabetic foot clinic once weekly for 8 weeks. Ulcer surface area over time was analyzed using standardized digital imaging software. DFUs were present without healing for a mean duration of 76 weeks prior to the study. They found a significant difference in healing rate between patients receiving topical oxygen and those receiving standard care. Topical oxygen, therefore, represents a potentially exciting new technology to shorten healing time in patients with nonhealing DFUs. More prospective randomized and powered studies are needed to determine the benefits of topical oxygen, but our current results are very promising.

Forces shaping the antibiotic resistome.

Antibiotic resistance has become a problem of global scale. Resistance arises through mutation or through the acquisition of resistance gene(s) from other bacteria in a process called horizontal gene transfer (HGT). While HGT is recognized as an important factor in the dissemination of resistance genes in clinical pathogens, its role in the environment has been called into question by a recent study published in Nature. The authors found little evidence of HGT in soil using a culture-independent functional metagenomics approach, which is in contrast to previous work from the same lab showing HGT between the environment and human microbiome. While surprising at face value, these results may be explained by the lack of selective pressure in the environment studied. Importantly, this work suggests the need for careful monitoring of environmental antibiotic pollution and stringent antibiotic stewardship in the fight against resistance.

Promoting medical students' reflection on competencies to advance a global health equities curriculum.

BACKGROUND: The move to frame medical education in terms of competencies - the extent to which trainees "can do" a professional responsibility - is congruent with calls for accountability in medical education. However, the focus on competencies might be a poor fit with curricula intended to prepare students for responsibilities not emphasized in traditional medical education. This study examines an innovative approach to the use of potential competency expectations related to advancing global health equity to promote students' reflections and to inform curriculum development. METHODS: In 2012, 32 medical students were admitted into a newly developed Global Health and Disparities (GHD) Path of Excellence. The GHD program takes the form of mentored co-curricular activities built around defined competencies related to professional development and leadership skills intended to ameliorate health disparities in medically underserved settings, both domestically and globally. Students reviewed the GHD competencies from two perspectives: a) their ability to perform the identified competencies that they perceived themselves as holding as they began the GHD program and b) the extent to which they perceived that their future career would require these responsibilities. For both sets of assessments the response scale ranged from "Strongly Disagree" to "Strongly Agree." Wilcoxon's paired T-tests compared individual students' ordinal rating of their current level of ability to their perceived need for competence that they anticipated their careers would require. Statistical significance was set at p < .01. RESULTS: Students' ratings ranged from "strongly disagree" to "strongly agree" that they could perform the defined GHD-related competencies. However, on most competencies, at least 50 % of students indicated that the stated competencies were beyond their present ability level. For each competency, the results of Wilcoxon paired T-tests indicate - at statistically significant levels - that students perceive more need in their careers for GHD-program defined competencies than they currently possess. CONCLUSION: This study suggests congruence between student and program perceptions of the scope of practice required for GHD. Students report the need for enhanced skill levels in the careers they anticipate. This approach to formulating and reflecting on competencies will guide the program's design of learning experiences aligned with students' career goals.

Evaluating the Differences of Wound Related Complications in Robotically Assisted Radical Cystectomy vs Open Radical Cystectomy.

OBJECTIVE: To determine whether robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) compared to open radical cystectomy (ORC) or RARC with extracorporeal urinary diversion (ECUD) would result in a decreased rate of surgical site complications. RARC has been shown to be non-inferior to ORC. Both RARC and ORC are complicated by a high rate of perioperative morbidity, including wound-related complications, which may be decreased by a robotic approach with intracorporeal diversion. METHODS: A retrospective review of our bladder cancer database for patients undergoing radical cystectomy from 2013-2021. Patients were stratified by surgical technique as RARC with ICUD vs ORC vs RARC with ECUD. Surgical site complications were measured at both 30- and 90-day intervals. RESULTS: Of the 269 patients, 127 (47.2%) had RARC with ICUD, 118 (43.7%) had ORC, and 24 (8.9%) had RARC with ECUD (mean ages 71.0, 69.5, and 67.5, respectively). A comparison of the 3 groups demonstrated statistical significance at both the 30-day (P <.001) and 90-day (P <.001) timeframes for total surgical site complications, with RARC with ICUD having the fewest amount of patients experiencing a surgical site complication (0.8%) followed by ORC (25.4%) and RARC with ECUD (29.2%). CONCLUSION: Overall, we observed lower surgical site complication rates among patients undergoing RARC with ICUD compared to patients who underwent ORC or RARC with ECUD. This study suggests that decreased surgical site complications may be one benefit of the minimally invasive approach, particularly in patients at high risk for surgical site complications after radical cystectomy.

Impact of Relugolix Combination Therapy on Functioning and Quality of Life in Women with Endometriosis-Associated Pain.

OBJECTIVE: To evaluate the effect of relugolix combination therapy (relugolix CT; 40 mg relugolix, 1 mg estradiol, and 0.5 mg norethisterone acetate) for up to 2 years in the SPIRIT long-term extension (LTE) study on functioning and health-related quality of life (QoL), using the Endometriosis Health Profile (EHP)-30 questionnaire, and assess how changes in QoL domains correlated with improvements in dysmenorrhea and non-menstrual pelvic pain (NMPP). DESIGN: Long-term extension (LTE) study of the SPIRIT phase 3 trials. SUBJECTS: Premenopausal women with moderate-to-severe endometriosis pain who previously completed the randomized SPIRIT trials were eligible to enroll in an 80-week LTE where all women received relugolix CT. INTERVENTIONS: Relugolix combination therapy (relugolix CT: relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) MAIN OUTCOME MEASURE(S): Least square (LS) mean changes in the EHP-30 domain and total scores from baseline (pivotal) were analyzed using a mixed-effects model. Results up to104 weeks are reported by pivotal trial treatment group with a focus on the relugolix CT group (ie, relugolix CT or placebo for 24 weeks, or delayed relugolix CT [relugolix 40 mg monotherapy for 12 weeks, followed by relugolix CT for 12 weeks]). In addition, the relationships between changes in dysmenorrhea and NMPP and changes in EHP-30 scores were assessed. RESULTS: In the 277 women treated with relugolix CT, LS mean EHP-30 pain domain scores improved by 57.8% (LS mean change:-32.8; 95% CI:-35.5, -30.1), 66.4% (LS mean change:-37.7; 95% CI:-40.3,-35.0); and 72.2% (LS mean change:-41.3; 95% CI:-43.9,-38.7) at Weeks 24, 52, and 104, respectively. The proportions of women with clinically meaningful improvement on the EHP-30 pain domain were 75.9%, 83.6% and 88.6% at weeks 24, 52, and 104, respectively. Non-pain EHP-30 domain and total scores likewise improved. A positive correlation between changes in dysmenorrhea/NMPP and all EHP -30 domain scores was observed. Results were similar for the delayed relugolix CT and placebo→relugolix CT groups. CONCLUSIONS: Sustained reduction of endometriosis-associated pain with relugolix CT observed up to 104 weeks was accompanied by improvements in functioning and health-related QoL. These findings complement the results of the pivotal SPIRIT trials, which showed relugolix combination therapy significantly reduced dysmenorrhea, non-menstrual pelvic pain (NMPP) and dyspareunia vs placebo in premenopausal women with endometriosis-associated pain.

End-to-end multimodal 3D imaging and machine learning workflow for non-destructive phenotyping of grapevine trunk internal structure.

Quantifying healthy and degraded inner tissues in plants is of great interest in agronomy, for example, to assess plant health and quality and monitor physiological traits or diseases. However, detecting functional and degraded plant tissues in-vivo without harming the plant is extremely challenging. New solutions are needed in ligneous and perennial species, for which the sustainability of plantations is crucial. To tackle this challenge, we developed a novel approach based on multimodal 3D imaging and artificial intelligence-based image processing that allowed a non-destructive diagnosis of inner tissues in living plants. The method was successfully applied to the grapevine (Vitis vinifera L.). Vineyard's sustainability is threatened by trunk diseases, while the sanitary status of vines cannot be ascertained without injuring the plants. By combining MRI and X-ray CT 3D imaging with an automatic voxel classification, we could discriminate intact, degraded, and white rot tissues with a mean global accuracy of over 91%. Each imaging modality contribution to tissue detection was evaluated, and we identified quantitative structural and physiological markers characterizing wood degradation steps. The combined study of inner tissue distribution versus external foliar symptom history demonstrated that white rot and intact tissue contents are key-measurements in evaluating vines' sanitary status. We finally proposed a model for an accurate trunk disease diagnosis in grapevine. This work opens new routes for precision agriculture and in-situ monitoring of tissue quality and plant health across plant species.

Glycopeptide sulfation evades resistance.

The incidence of antibiotic resistance among pathogenic microorganisms is increasing at an alarming rate. Resistance against front-line therapeutics such as the glycopeptide antibiotic vancomycin has emerged and has spread to highly virulent pathogens, including Staphylococcus aureus. Glycopeptide antibiotics are natural products from the Actinomycetes that have a characteristic heptapeptide core. The chemical diversity of the class is achieved through glycosylation, halogenation, methylation, and acylation of the core, modifications that are implicated in improved solubility, stability, or activity of the molecule. Sulfation is yet another modification observed infrequently in glycopeptides, but its role is not known. Although glycopeptide sulfotransferases are found in the environmental metagenome and must therefore serve an evolutionary purpose, all previous studies have reported decreased antibiotic activity with sulfation. We report that sulfation of glycopeptides has little effect on the compound's ability to bind its target, the d-Ala-d-Ala peptidoglycan precursors of the bacterial cell wall. However, sulfation does impact glycopeptide dimerization, and importantly, sulfated glycopeptides are significantly less potent inducers of the resistance gene cluster vanHAX in actinomycetes. Our results begin to unravel the mystery of the biological role of glycopeptide sulfation and offer a potential new strategy for the development of new antibiotics that avoid resistance.

Going Virtual: Transitioning an Older Adult Community Health Clinical Course to Online During COVID-19.

BACKGROUND: Nursing students in a community health course implemented a quality improvement project with active older adults (AOA). This article describes a process for transitioning an in-person community health quality improvement (QI) project to online. METHOD: To communicate with AOA, students created a blog, "Healthy Living From Home," that enabled communication among the AOA, partner organizations staff, and students. A quick response code was created that linked to the 6-week program. At the end of the 6 weeks, participants were asked to complete a survey. RESULTS: Data collected from the QI project website tracked more than 1,000 visits to the blog. Participants rated project enjoyment, helpfulness, and educational content as 4.5 on a 5-point Likert scale. CONCLUSION: Using a multifocal online format to engage with AOA was successful and can continue to be used in the future. [J Nurs Educ. 2023;62(X):XXX-XXX.].

Social Media Usage and Its Effects on the Psychological Health of Adolescents.

Social media usage is ubiquitous among adolescents. Although social media may appeal to adolescents due to the ability to connect with peers and develop relationships, many teens also report feelings of exclusion or victimization associated with their social media use. High usage of social media may act as a forum for negative behaviors and psychological detriments. Awareness and understanding of how social media affects adolescents' psychological well-being will help parents and school staff better support teenagers and develop programs to improve coping skills and self-regulation of social media for adolescents.

Transitioning Community Health Clinical Experiences to an Online Format During COVID-19.

BACKGROUND: This article describes how nursing students in a community health course transitioned to an online clinical experience when coronavirus disease 2019 limited in-person gatherings. METHOD: A weekly video series was created to provide content to help educate 18 at-risk women using the Plan-Do-Study-Act cycle. RESULTS: Objectives for the nursing students were met. Successful implementation occurred, and objectives for the community health class were met; however, engagement was more difficult to achieve. CONCLUSION: Transitioning to online video conferencing allowed the nursing students to still engage with the study participants. Using the PDSA cycle allowed for structured changes to be made. [J Nurs Educ. 2022;61(3):159-161.].

Simulated Home Visit to Promote Chronic Disease Management Competencies in Prelicensure Nursing Students.

BACKGROUND: Conducting a best possible medication history (BPMH), while using effective patient communication skills, falls within the nursing scope of practice and is recommended at all care levels. Nursing students should be taught these skills before entering clinical practice, but evidence about effective teaching strategies is limited. APPROACH: A standardized patient-facilitated home visit simulation was utilized in a prelicensure nursing program to practice a BPMH while using effective patient communication skills. OUTCOMES: All students correctly identified medications listed on the patient history, and most identified omitted medications (90.1%), transposed medications (91.6%), and incorrect medication usage (91.6%). All students demonstrated effective patient communication skills-using open-ended questions and inquiring about medication usage. CONCLUSION: Incorporating a standardized patient-facilitated home visit BPMH simulation allows students the opportunity to practice and achieve BPMH competency essential for nurses.

Does a humoral correlate of protection exist for SARS-CoV-2? A systematic review.

BACKGROUND: A correlate of protection (CoP) is an immunological marker associated with protection against infection. Despite an urgent need, a CoP for SARS-CoV-2 is currently undefined. OBJECTIVES: Our objective was to review the evidence for a humoral correlate of protection for SARS-CoV-2, including variants of concern. METHODS: We searched OVID MEDLINE, EMBASE, Global Health, Biosis Previews and Scopus to January 4, 2022 and pre-prints (using NIH iSearch COVID-19 portfolio) to December 31, 2021, for studies describing SARS-CoV-2 re-infection or breakthrough infection with associated antibody measures. Two reviewers independently extracted study data and performed quality assessment. RESULTS: Twenty-five studies were included in our systematic review. Two studies examined the correlation of antibody levels to VE, and reported values from 48.5% to 94.2%. Similarly, several studies found an inverse relationship between antibody levels and infection incidence, risk, or viral load, suggesting that both humoral immunity and other immune components contribute to protection. However, individual level data suggest infection can still occur in the presence of high levels of antibodies. Two studies estimated a quantitative CoP: for Ancestral SARS-CoV-2, these included 154 (95% confidence interval (CI) 42, 559) anti-S binding antibody units/mL (BAU/mL), and 28.6% (95% CI 19.2, 29.2%) of the mean convalescent antibody level following infection. One study reported a CoP for the Alpha (B.1.1.7) variant of concern of 171 (95% CI 57, 519) BAU/mL. No studies have yet reported an Omicron-specific CoP. CONCLUSIONS: Our review suggests that a SARS-CoV-2 CoP is likely relative, where higher antibody levels decrease the risk of infection, but do not eliminate it completely. More work is urgently needed in this area to establish a SARS-CoV-2 CoP and guide policy as the pandemic continues.

Utilizing Academic-Community Partnerships With Nursing Students to Improve Hand Hygiene in Elementary Students to Reduce Transmission of COVID-19.

Coronavirus disease 2019 (COVID-19) has raised awareness about the vital role school nurses have in improving the overall health of children. School nurses provide health promotion within schools, yet over 60% of schools have only a part-time nurse or no nurse. Nursing students may be valuable partners for health promotion and academic-community partnerships may be mutually beneficial to schools of nursing and local schools. Using a nursing student team to teach hand hygiene while school health staff were present provided an opportunity for hands-on training to help the staff master curriculum content and ensure competency. This article describes a collaborative partnership initiative that expanded access to health promotion education in schools to increase knowledge about reducing the spread of infectious disease, such as COVID-19, while providing valuable clinical experiences for nursing students.

Peptide alarmone signalling triggers an auto-active bacteriocin necessary for genetic competence.

The induction of genetic competence is a strategy used by bacteria to increase their genetic repertoire under stressful environmental conditions. Recently, Streptococcus pneumoniae has been shown to co-ordinate the uptake of transforming DNA with fratricide via increased expression of the peptide pheromone responsible for competence induction. Here, we document that environmental stress-induced expression of the peptide pheromone competence-stimulating peptide (CSP) in the oral pathogen Streptococcus mutans. We showed that CSP is involved in the stress response and determined the CSP-induced regulon in S. mutans by microarray analysis. Contrary to pneumococcus, S. mutans responds to increased concentrations of CSP by cell lysis in only a fraction of the population. We have focused on the mechanism of cell lysis and have identified a novel bacteriocin as the 'death effector'. Most importantly, we showed that this bacteriocin causes cell death via a novel mechanism of action: intracellular action against self. We have also identified the cognate bacteriocin immunity protein, which resides in a separate unlinked genetic locus to allow its differential regulation. The role of the lytic response in S. mutans competence is also discussed. Together, these findings reveal a novel autolytic pathway in S. mutans which may be involved in the dissemination of fitness-enhancing genes in the oral biofilm.

Topical Oxygen Therapy Shifts Microbiome Dynamics in Chronic Diabetic Foot Ulcers.

INTRODUCTION: Bacterial biofilm in wounds prevents healing by acting as a physical barrier to wound closure and hyperactivating local inflammatory processes, thus making its removal a high priority. The authors previously have shown that adding topical oxygen to standard wound care increased healing of Texas Grade II and III diabetic foot ulcers (DFUs), which they hypothesized was a result of alterations of the wound microbiome/biofilm. OBJECTIVE: This study aims to determine the mechanism of action of topical oxygen in DFUs by examining the diversity of bacterial genera present in DFUs treated with topical oxygen. MATERIALS AND METHODS: Six patients with chronic DFUs had their wounds swabbed weekly over an 8-week period of continuous topical oxygen treatment, and microbiome diversity was assessed by metagenomic 16S rDNA sequencing using a next-generation sequencing platform. RESULTS: The wound microbiome shifted toward a diverse flora dominated by aerobes and facultative anaerobes with oxygen therapy in 5 healed wounds. In contrast, anaerobic flora persisted in a single nonhealing ulcer in the present study cohort. CONCLUSIONS: Although the sample size was small, this study suggests topical oxygen therapy may have the ability to encourage the growth of aerobic members of the wound microbiome and be an effective alternative to antibiotics in this area.

Faculty-Led Role-Play Simulation: Going Live to Teach Patient-Centered Care to Nursing Students.

BACKGROUND: Nursing education of patient-centered care (PCC) principles is recommended to improve the quality and safety of patient care. Role-playing simulations within safe classroom learning environments may increase student competence and confidence in delivering PCC. METHOD: This innovative strategy included course faculty brief role-play scenarios. Students received opportunities to analyze the effectiveness of the PCC portrayed, reenact the scenarios, and consider the value of the simulation in enhancing PCC knowledge and skills. RESULTS: Following a scenario, students correctly identified ineffective PCC components, suggested alternative interactions, and demonstrated therapeutic PCC communication techniques during reenactments. During debriefing, students shared strategies for implementing PCC skills in nursing practice. In the clinical setting, faculty observed students applying PCC principles. Student course evaluations indicated role-play was an effective teaching method. CONCLUSIONS: Use of role-play simulation in prelicensure nursing education creates an engaging approach for reinforcing PCC principles, which may increase implementation of PCC in the clinical setting. [J Nurs Educ. 2019;58(11):665-668.].

Assessing the Need for Mobile Health (mHealth) in Monitoring the Diabetic Lower Extremity.

BACKGROUND: Complications of the diabetic lower extremity (such as diabetic foot ulcers, DFUs) occur when monitoring is infrequent, and often result in serious sequelae like amputation or even death. OBJECTIVE: To evaluate the potential application of mobile health (mHealth) to diabetic foot monitoring. We surveyed the self-management routines of a group of diabetic patients, as well as patient and clinician opinions on the use of mHealth in this context. METHODS: Patients with DFUs in Toronto, Ontario, Canada completed a 25-item questionnaire addressing their foot care practices, mobile phone use, and views on mHealth. Wound care clinicians across Canada were also surveyed using a 9-item questionnaire. RESULTS: Of the patients surveyed, 59/115 (51.3%) spend less than a minute checking their feet, and 17/115 (15%) of patients find it difficult to see their doctor or get to the hospital regularly. Mobile phone use was widespread in our patient cohort (93/115, 80.9%). Of mobile phone users, 68/93 (73.1%) would use a device on their mobile phone to help them check their feet. Of the clinicians who completed the questionnaire, only 7/202 (3.5%) were familiar with mHealth; however, 181/202 (92%) of clinicians expressed interest in using mHealth to monitor their patients between visits. CONCLUSIONS: Patient education or motivation and clinician training were identified as the major barriers to mHealth use in the diabetic lower extremity, which may be a viable mechanism to improve DFU monitoring practices.