Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life.

BACKGROUND: There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). METHODS: From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. RESULTS: Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1% vs. 13.6%), medically-attended (30.2% vs. 11.8%) and recurrent wheeze outcomes (4.0% vs. 0.6%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR% of 14.1%, 12.3% and 35.9%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). CONCLUSIONS: A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.

Minimally invasive non-surgical periodontal therapy of intrabony defects: A prospective multi-centre cohort study.

AIM: To assess the potential benefits of minimally invasive non-surgical therapy (MINST) in teeth with intrabony defects and to explore factors associated with the outcomes. MATERIALS AND METHODS: A multi-centre trial was conducted in 100 intrabony defects in periodontitis patients in private practice. Steps 1 and 2 periodontal therapy including MINST were provided. Clinical and radiographic data were analysed at baseline and 12 months after treatment, with the primary aim being change in radiographic defect depth at 12 months. RESULTS: Eighty-four patients completed the 12-month follow up. The mean total radiographic defect depth reduced by 1.42 mm and the defect angle increased by 3° (both p < .05). Statistically significant improvements in probing pocket depth (PPD) and clinical attachment level (CAL) were seen at 12 months compared to baseline (p < .001). Fifty-six defects (66.7%) achieved pocket closure (PPD ≤ 4 mm) and 49 defects (58.3%) achieved the composite outcome (PPD ≤ 4 mm and CAL gain ≥3 mm). Deeper and narrower angled defects were positively correlated with radiographic and clinical improvements, respectively. CONCLUSIONS: Improvements in clinical and radiographic outcomes were seen after MINST. This study highlights the generalizability and wide applicability of this approach, further supporting its effectiveness in the treatment of intrabony defects. CLINICAL TRIAL REGISTRATION: NCT03741374. https://clinicaltrials.gov/study/NCT03741374?cond=minimally%20invasive%20non%20surgical%20therapy&locStr=UK&country=United%20Kingdom&distance=50&rank=2.

Vitamin D Deficiency, Chronic Kidney Disease and Periodontitis.

Vitamin D has important anti-inflammatory, anti-microbial properties and plays a central role in the host immune response. Due to the crucial role of the kidneys in the metabolism of vitamin D, patients with chronic kidney disease (CKD) are prone to vitamin D deficiency. The resultant reduction in the production of calcitriol, the activated form of vitamin D, in patients with CKD is responsible for exacerbating the existing renal impairment and periodontal inflammation. Recent evidence suggests a bidirectional, causal relationship between periodontitis and renal functional status. Both conditions have shared pathophysiological mechanisms including oxidative stress, increases in the systemic inflammatory burden and impaired host response. This review explores the association between vitamin D, CKD and periodontitis. The review summarises the current evidence base for the classical and non-classical vitamin D metabolic pathways, the biological mechanisms linking vitamin D deficiency, CKD and periodontitis, as well as the bidirectional relationship between the two chronic inflammatory conditions. Finally, the paper explores the impact of vitamin D deficiency on CKD, periodontitis, and related co-morbidities.

The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation.

Neuronal protein synthesis is required for long-lasting plasticity and long-term memory consolidation. Dephosphorylation of eukaryotic initiation factor 2α is one of the key translational control events that is required to increase de novo protein synthesis that underlies long-lasting plasticity and memory consolidation. Here, we interrogate the molecular pathways of translational control that are triggered by neuronal stimulation with brain-derived neurotrophic factor (BDNF), which results in eukaryotic initiation factor 2α (eIF2α) dephosphorylation and increases in de novo protein synthesis. Primary rodent neurons exposed to BDNF display elevated translation of GADD34, which facilitates eIF2α dephosphorylation and subsequent de novo protein synthesis. Furthermore, GADD34 requires G-actin generated by cofilin to dephosphorylate eIF2α and enhance protein synthesis. Finally, GADD34 is required for BDNF-induced translation of synaptic plasticity-related proteins. Overall, we provide evidence that neurons repurpose GADD34, an effector of the integrated stress response, as an orchestrator of rapid increases in eIF2-dependent translation in response to plasticity-inducing stimuli.

Kidney Transplant Clinicians' Perceptions of Palliative Care for Patients With Failing Allografts in the US: A Mixed Methods Study.

RATIONALE & OBJECTIVE: Kidney transplant patients with failing allografts have a physical and psychological symptom burden as well as high morbidity and mortality. Palliative care is underutilized in this vulnerable population. We described kidney transplant clinicians' perceptions of palliative care to delineate their perceived barriers to and facilitators of providing palliative care to this population. STUDY DESIGN: National explanatory sequential mixed methods study including an online survey and semistructured interviews. SETTING & PARTICIPANTS: Kidney transplant clinicians in the United States surveyed and interviewed from October 2021 to March 2022. ANALYTICAL APPROACH: Descriptive summary of survey responses, thematic analysis of qualitative interviews, and mixed methods integration of data. RESULTS: A total of 149 clinicians completed the survey, and 19 completed the subsequent interviews. Over 90% of respondents agreed that palliative care can be helpful for patients with a failing kidney allograft. However, 46% of respondents disagreed that all patients with failing allografts benefit from palliative care, and two-thirds thought that patients would not want serious illness conversations. More than 90% of clinicians expressed concern that transplant patients and caregivers would feel scared or anxious if offered palliative care. The interviews identified three main themes: (1) transplant clinicians' unique sense of personal and professional responsibility was a barrier to palliative care engagement, (2) clinicians' uncertainty regarding the timing of palliative care collaboration would lead to delayed referral, and (3) clinicians felt challenged by factors related to patients' cultural backgrounds and identities, such as language differences. Many comments reflected an unfamiliarity with the broad scope of palliative care beyond end-of-life care. LIMITATIONS: Potential selection bias. CONCLUSIONS: Our study suggests that multiple barriers related to patients, clinicians, health systems, and health policies may pose challenges to the delivery of palliative care for patients with failing kidney transplants. This study illustrates the urgent need for ongoing efforts to optimize palliative care delivery models dedicated to kidney transplant patients, their families, and the clinicians who serve them. PLAIN-LANGUAGE SUMMARY: Kidney transplant patients experience physical and psychological suffering in the context of their illnesses that may be amenable to palliative care. However, palliative care is often underutilized in this population. In this mixed-methods study, we surveyed 149 clinicians across the United States, and 19 of them completed semistructured interviews. Our study results demonstrate that several patient, clinician, system, and policy factors need to be addressed to improve palliative care delivery to this vulnerable population.

Scaffolding competence-based learning design in the dental simulation curriculum.

INTRODUCTION: Learning in a clinical domain in dentistry is complex and learners may face uncertain clinical scenarios. A simulation curriculum can be designed to have simple clinical scenarios and learning activities which progress in complexity and employ competence assessments of simulated clinical practice before students can undertake authentic practice on patients. This paper presents how scaffolding of competence can be used for designing learning with simulators (haptics and phantom head) demonstrated in a specific domain in restorative dentistry. METHODS: A collaborative workshop as a research approach was undertaken to inform the iterative analysis, development, and discussion on scaffolding the learning design with respect to competence assessments of learning cavity preparation with simulation-based learning technologies. A workshop was conducted, which was collaborative and involved design negotiations between researchers, technologists, and teachers/practitioners in developing the simulation curriculum. RESULTS: A competence assessment with feedback in a specific domain in preparing interproximal caries was used as a context to describe how the learning activities and outcomes were designed to meet assessment of competence with varied levels of simple to complex learning activities and structured sessions. CONCLUSION: Simulation curriculum can be designed and implemented by scaffolding the level of competence that can be learned using simulation between haptics and phantom-head. This brings impetus to the need in meeting the relevant competence criteria in context to a specific affordance of the simulation-based learning technologies to provide optimal patient-centred holistic care.

Modified Tunnel Procedure to Facilitate Ridge Reconstruction of an Extraction Socket Associated with Buccal Dehiscence and Gingival Recession: A Case Report with a 6-year Follow-Up.

Introduction: Extraction sockets associated with buccal dehiscences and gingival recessions pose particular surgical and restorative challenges. In these cases, unassisted healing following flapless tooth extraction results in severe bone and soft tissue deformities and an aesthetic compromise. Root coverage procedures prior to ridge reconstruction may enable predictable alveolar augmentation. Case Presentation. This is the first case report describing the utilisation of modified tunnel procedure to facilitate ridge reconstruction consisting of ovate pontic and xenograft, of tooth #25 in a 38-year-old-male. The 6 months and 1-year reviews showed optimal soft tissue aesthetics, 100% root coverage of the tooth #25, and bone augmentation, which enabled placement of 10.0 mm × 4.0 mm (3i) implant in a prosthetically driven position. The 6-year review continued to show favourable clinical outcomes. Conclusion: Compromised extraction sockets containing buccal dehiscence and associated with gingival recessions may benefit from soft tissue augmentation procedures to enhance the clinical outcome of ridge reconstruction.

The role of vitamin D in periodontal health and disease.

Vitamin D plays an essential role in calcium and bone metabolism, immune regulation and possesses profound anti-inflammatory effects. Evidence suggests that low serum vitamin D is associated with increased severity of periodontitis, a chronic inflammatory condition characterised by destruction of the supporting tissues surrounding the tooth, which has several shared risk factors with other chronic non-communicable diseases. The biological functions of vitamin D are mediated by its strong anti-microbial, anti-inflammatory, and host modulatory properties. Experimental periodontitis models involving targeted deletion of 1α-hydroxylase, the enzyme responsible for the conversion of inactive substrate to active 1,25(OH)2 D3 (calcitriol), showed augmented alveolar bone loss and gingival inflammation. Vitamin D receptor (VDR) gene polymorphisms have also been associated with increased severity of periodontitis. Thus, the involvement of vitamin D in the pathogenesis of periodontitis is biological plausible. Clinical studies have consistently demonstrated an inverse relationship between serum 25OHD3 and periodontal disease inflammation. However, due to the paucity of well-designed longitudinal studies, there is less support for the impact of vitamin D status on periodontal disease progression and tooth loss. The evidence emphasises the importance of maintaining vitamin D sufficiency in supporting periodontal health. This review aims to first examine the biological mechanisms by which vitamin D might influence the pathogenesis of periodontal disease and second, discuss the clinical evidence which implicate the role of vitamin D in periodontal disease.

Stressful Life Events, Postpartum Depressive Symptoms, and Partner and Social Support Among Pregnant People with Disabilities.

INTRODUCTION: As an increasing number of people with disabilities become pregnant and give birth, understanding their vulnerabilities for poor mental health and life stress can help to improve their health and well-being. We examined whether people with disabilities are more likely to experience stressful life events 12 months before childbirth, postpartum depressive symptoms (PDS), and lack of postpartum partner and social support, and compared these associations by race/ethnicity. METHODS: Using the Massachusetts Pregnancy Risk Assessment Monitoring System 2016-2020 data (n = 6,483), we used univariate and multivariable logistic regression models to estimate the associations of disability with stressful life events, PDS, and postpartum partner and social support, and calculated risk ratio (RR), adjusted RR, and 95% confidence interval (CI). We also conducted stratified analyses by race/ethnicity. RESULTS: The prevalence of disability was 10.7% overall, and 8.8% among White non-Hispanic people, 14.3% among Black non-Hispanic people, 15.5% among Hispanic people, and 8.3% among Asian non-Hispanic people. Compared with people without disabilities, those with disabilities were more likely to report emotional stress (RR, 1.54; 95% CI, 1.36-1.74), partner-related stress (RR, 2.55; 95% CI, 2.23-2.91), financial stress (RR, 1.55; 95% CI, 1.44-1.68), traumatic stress (RR, 2.27; 95% CI, 1.85-2.79), and PDS (RR, 3.77; 95% CI, 3.13-4.53). People with disabilities were also more likely to lack a partner's emotional support (RR, 2.57; 95% CI, 2.21-2.97), financial support from the newborn's father (RR, 2.89; 95% CI, 2.39-3.51), and social support while feeling tired or frustrated (RR, 2.05; 95% CI, 1.68-2.52). These associations remained statistically significant after adjustment for maternal factors and newborn's birth year. Strong associations of disability with stressful life events (including emotional stress and partner-related stress), PDS, lacking partner's emotional support, and social support existed across racial/ethnic groups. CONCLUSIONS: Pregnant people with disabilities may benefit from additional screening for stressful life events and depression during pregnancy and postpartum. Multidisciplinary efforts that combine mental health screening and treatment, peer support groups, increased health care provider training about caring for people with disabilities during pregnancy, and better access to care for pregnant people with disabilities are needed to improve their health and support their desire to become parents.

Near-Peer Teaching in Conjunction with Flipped Classroom to Teach First-Year Medical Students Basic Surgical Skills.

Background: There is increasing evidence that students are completing medical school with insufficient surgical education. Near-peer tutoring and flipped classroom formatting may be used to enhance learning while simultaneously relieving faculty burden of teaching. Here, we qualitatively evaluate a 3-month course that integrates the use of near-peer teaching and flipped classroom formatting, with the goal of increasing first-year medical students' self-perceived confidence in performing basic sutures and knot-ties as well as interest in surgery. Methods: Twenty-one first-year medical students participated in a suturing and knot-tying course led by senior medical students. The course consisted of 2-h sessions held every 2 weeks for a total of five sessions. Students were sent publicly available videos prior to each session by which to learn the upcoming techniques and received live feedback from instructors during sessions. Questionnaires were completed pre-course and post-course. Results: Compared to pre-course ratings, post-course ratings of self-perceived confidence to perform various knot-ties and sutures all increased significantly (p < 0.05). All students stated that the course strengthened their desire to pursue a career in surgery. Student feedback of the course was overall positive. Conclusions: Near-peer teaching can be used in conjunction with flipped classroom to increase first-year medical students' self-perceived confidence in surgical suturing and knot-tying as well as interest in surgery. This curriculum may serve as an outline for student-led courses at other institutions.

Wastewater surveillance of SARS-CoV-2 in dormitories as a part of comprehensive university campus COVID-19 monitoring.

Wastewater-based epidemiology is an effective tool for monitoring infectious disease spread or illicit drug use within communities. At the Ohio State University, we conducted a SARS-CoV-2 wastewater surveillance program in the 2020-2021 academic year and compared results with the university-required weekly COVID-19 saliva testing to monitor COVID-19 infection prevalence in the on-campus residential communities. The objectives of the study were to rapidly track trends in the wastewater SARS-CoV-2 gene concentrations, analyze the relationship between case numbers and wastewater signals when adjusted using human fecal viral indicator concentrations (PMMoV, crAssphage) in wastewater, and investigate the relationship of the SARS-CoV-2 gene concentrations with wastewater parameters. SARS-CoV-2 nucleocapsid and envelope (N1, N2, and E) gene concentrations, determined with reverse transcription droplet digital PCR, were used to track SARS-CoV-2 viral loads in dormitory wastewater once a week at 6 sampling sites across the campus during the fall semester in 2020. During the following spring semester, research was focused on SARS-CoV2 N2 gene concentrations at 5 sites sampled twice a week. Spearman correlations both with and without adjusting using human fecal viral indicators showed a significant correlation (p < 0.05) between human COVID-19 positive case counts and wastewater SARS-CoV-2 gene concentrations. Spearman correlations showed significant relationships between N1 gene concentrations and both TSS and turbidity, and between E gene concentrations and both pH and turbidity. These results suggest that wastewater signal increases with the census of infected individuals, in which the majority are asymptomatic, with a statistically significant (p-value <0.05) temporal correlation. The study design can be utilized as a platform for rapid trend tracking of SARS-CoV-2 variants and other diseases circulating in various communities.

Kidney Supportive Care in Peritoneal Dialysis: Developing a Person-Centered Kidney Disease Care Plan.

Individuals receiving peritoneal dialysis (PD)-similar to those receiving hemodialysis -may experience high mortality coupled with a high symptom burden and reduced health-related quality of life. In this context, a discussion of the risks, benefits, and tradeoffs of PD and/or other kidney treatment modalities should be explored based on individual goals and preferences. Through these principles, kidney supportive care provides a person-centered approach to kidney disease care throughout the spectrum of kidney failure and earlier stages of chronic kidney disease. Kidney supportive care is offered in conjunction with life-prolonging therapies, including dialysis and kidney transplants, and is increasingly recognized as an integral part of advancing the care of PD patients. Using "My Kidney Care Roadmap" for shared decision making, kidney supportive care guides patients undergoing PD and their clinicians to (1) elicit patient goals, values, and priorities; (2) convey medical prognosis and suitable treatment options; and (3) ask "Which of these kidney treatment options will best help me achieve my goals and priorities?" to inform both current and future decisions, including choice of dialysis modalities, time-limited trials, and/or nondialysis management. Recognizing that patient priorities and choices may evolve, this framework ultimately allows patients to continually reassess their PD care to better achieve goal-directed dialysis.

Preoperative Visual Measures of Verbal Learning and Memory and their Relations to Speech Recognition After Cochlear Implantation.

OBJECTIVES: This study examined the performance of a group of adult cochlear implant (CI) candidates (CIC) on visual tasks of verbal learning and memory. Preoperative verbal learning and memory abilities of the CIC group were compared with a group of older normal-hearing (ONH) control participants. Relations between preoperative verbal learning and memory measures and speech recognition outcomes after 6 mo of CI use were also investigated for a subgroup of the CICs. DESIGN: A group of 80 older adult participants completed a visually presented multitrial free recall task. Measures of word recall, repetition learning, and the use of self-generated organizational strategies were collected from a group of 49 CICs, before cochlear implantation, and a group of 31 ONH controls. Speech recognition outcomes were also collected from a subgroup of 32 of the CIC participants who returned for testing 6 mo after CI activation. RESULTS: CICs demonstrated poorer verbal learning performance compared with the group of ONH control participants. Among the preoperative verbal learning and memory measures, repetition learning slope and measures of self-generated organizational clustering strategies were the strongest predictors of post-CI speech recognition outcomes. CONCLUSIONS: Older adult CI candidates present with verbal learning and memory deficits compared with older adults without hearing loss, even on visual tasks that are independent from the direct effects of audibility. Preoperative verbal learning and memory processes reflecting repetition learning and self-generated organizational strategies in free recall were associated with speech recognition outcomes 6 months after implantation. The pattern of results suggests that visual measures of verbal learning may be a useful predictor of outcomes in postlingual adult CICs.

Chronic Exertional Compartment Syndrome of the Lower Extremity: Diagnosis and Surgical Treatment.

Background: Chronic exertional compartment syndrome of the lower extremity is a condition that characteristically presents as recurrent anterior, posterior, and/or lateral lower-extremity pain on repetitive activity and physical exertion1. This condition is commonly seen in athletes, runners, and military personnel2. Open fasciotomy has been demonstrated to be a highly effective surgical treatment for patients with this condition who do not experience symptomatic relief after a thorough trial of nonoperative treatment3. Description: Diagnostic compartment pressure management is achieved through direct insertion of a compartment-pressure-measuring device into the anterior, lateral, and posterior compartments of the lower extremity4. Surgical treatment of the anterior and lateral compartments with use of open fasciotomy employs longitudinal proximal and distal incisions that are made on the lateral surface of the leg approximately 3 finger-breadths distal and proximal to the fibular flare, respectively, and 3 finger-breadths lateral to the tibial crest. Surgical treatment of the posterior compartments with use of open fasciotomy employs a single, mid-shaft incision made approximately 2.5 cm medial to the tibial ridge. Dissection is carried down to the deep fascia at both sites, beginning at the distal operative site. Care is taken to avoid transection of the superficial peroneal nerve at the distal anterolateral incision and saphenous vein and nerve at the medial incision. Once down to the deep fascia, a scalpel is utilized to incise the fascia. Metzenbaum scissors are then employed under the incision, spreading the scissors while sliding them over the muscles proximally and distally to release the muscular attachments from the fascia as well as to release the fascia itself3. This process is repeated in the anterior, lateral, and superficial posterior compartments through the proximal and distal incisions. In the deep posterior compartment, the fascia is released from the tibial ridge with a large Cobb elevator. Closure is achieved with deep dermal and superficial sutures. Alternatives: Nonoperative alternatives have been reported to include nonpharmacological modalities such as walking modification and shoe inserts, pharmacological therapy with nonsteroidal anti-inflammatory drugs, and physical therapy targeted at conditioning the lower extremity5. Nonoperative intervention has been demonstrated to increase endurance in select patients; however, most patients must either stop the activity associated with the compartment syndrome altogether or proceed to surgery for complete resolution of symptoms5. There are a few surgical alternatives that differ in their utilization of minimally invasive approaches versus a direct open approach6; however, all existing surgical treatments of this condition involve physical release of the fascial compartment. Rationale: Diagnostic compartment-pressure measurement is useful in confirming or ruling out the presence of this condition in patients with unclear symptoms4. Furthermore, diagnostic compartment-pressure management ensures accuracy in diagnosis and validates invasive treatment when patients desire surgical intervention. Surgical management of exertional compartment syndrome of the lower extremity is indicated in patients when nonoperative treatment has failed despite clinically notable symptoms and objectively elevated lower-extremity compartment pressures. Open fasciotomy has been postulated to prevent compression of local vasculature and effectively prevent ischemia; however, the definitive mechanism is unclear1. Expected Outcomes: Surgical treatment of chronic exertional compartment syndrome with use of open fasciotomy is highly successful in the civilian population. One study showed excellent return to activity/sport in 15 of 16 patients (25 of 26 limbs; 96%), with patients often reporting no symptoms postoperatively3. Military personnel have been reported to experience satisfactory results, with another study showing positive subjective feedback in 35 (76%) of 46 patients on long-term follow-up; however, only 19 patients (41%) were able to return to full active duty postoperatively7. Important Tips: Balloting the fascial compartment with ∼1 cc of saline solution can be helpful in determining successful placement of the pressure-measuring device at the time of needle entry.Identifying the course of the superficial peroneal nerve via physical examination can help avoid iatrogenic injury to this important superficial structure during the dissection leading to the distal fasciotomy.Deep posterior compartment release with use of open fasciotomy may not provide symptomatic relief; patients who demonstrate elevation of pressures in this specific compartment should be counseled accordingly. Acronyms & Abbreviations: ROM = range of motionSPN = superficial peroneal nerve.

Safety Profile of GSK's Inactivated Quadrivalent Seasonal Influenza Vaccine in Belgium, Germany and Spain: Passive Enhanced Safety Surveillance Study for the 2019/2020 Influenza Season.

INTRODUCTION: Seasonal influenza infects millions annually in Europe. Annual influenza vaccination is the most effective measure to reduce the risk of infection and its complications, especially among young children and older adults. OBJECTIVE: We assessed adverse event (AE) frequency after receiving GSK's inactivated quadrivalent seasonal influenza vaccine (IIV4). METHODS: A passive enhanced safety surveillance study was conducted in Belgium, Germany, and Spain. Adults who had received GSK's IIV4 or the parent(s)/guardian(s)/legally acceptable representative(s) of children given the vaccine were invited to complete an adverse drug reaction (ADR) card to document AEs experienced within 7 days post vaccination. RESULTS: A total of 1082 participants (51.6% females) received GSK's IIV4, including 115 children < 9 years of age who received two doses. The ADR card return rate was 97.0% (n = 1049) after dose 1 and 100% (n = 115) after dose 2. All participants in Belgium and Germany were adults. In Spain, 71.2% were children. After dose 1, 39.2% reported one or more AE. The most frequent AEs category was "general disorders and administration site conditions" (GDASC). AEs were most frequently reported in adults aged 18-65 years (47.2%), followed by children aged 6 months-17 years (38.1%), and adults aged > 65 years (31.6%). After dose 2, 7.8% reported one or more AE, and GDASC was again the most frequent AE category. There were no serious AEs related to GSK's IIV4 within 7 days post vaccination. CONCLUSION: No serious AEs related to GSK's IIV4 within 7 days post vaccination were reported. This study supports the favourable risk-benefit safety profile of GSK's IIV4.

Seasonal influenza infects millions annually in Europe, especially young children and older adults. Annual influenza vaccination is the most effective measure to reduce the risk of infection and its complications. As the wild influenza virus strains change every year, the composition of the influenza vaccine changes as well. Since the vaccine is produced in the same way over the years, extensive safety studies are no longer required by regulatory authorities. Instead, monitoring of any unwanted medical incidents (adverse events) after vaccination is required. For the 2019/2020 season, we monitored the adverse events reported by a representative sample of people in Belgium, Germany, and Spain within 7 days after receiving GSK's seasonal influenza vaccine.Of the 1082 people who received the first dose of the vaccine, 39% reported at least one adverse event, such as pain and swelling at the injection site, tiredness, fever, headache, or dizziness. A total of 115 children under 9 years of age received two doses 4 weeks apart. After their second dose, few of these children (8%) reported adverse events. The most frequent adverse events were fever, swelling and pain at the injection site, runny nose, or irritability. No serious adverse events were reported after either the first or second dose.No serious adverse events related to GSK's seasonal influenza vaccine within the 7 days after vaccination were reported. This study supports the favourable risk­benefit safety profile of GSK's seasonal influenza vaccine.

Comparing the impact of an icon array versus a bar graph on preference and understanding of risk information: Results from an online, randomized study.

BACKGROUND: Few studies have examined the best way to convey the probability of serious events occurring in the future (i.e., risk of stroke or death) to persons with low numeracy or graph literacy proficiency. To address this gap, we developed and user-tested a bar graph and compared it to icon arrays to assess its impact on understanding and preference for viewing risk information. OBJECTIVES: To determine the: (i) formats' impact on participants' understanding of risk information; (ii) formats' impact on understanding and format preference across numeracy and graph literacy subgroups; (iii) rationale supporting participants' preference for each graphical display format. METHODS: An online sample (evenly made up of participants with high and low objective numeracy and graph literacy) was randomized to view either the icon array or the bar graph. Each format conveyed the risk of major stroke and death five years after choosing surgery, a stent, or medication to treat carotid artery stenosis. Participants answered questions to assess their understanding of the risk information. Lastly, both formats were presented in parallel, and participants were asked to identify their preferred format to view risk information and explain their preference. RESULTS: Of the 407 participants, 197 were assigned the icon array and 210 the bar graph. Understanding of risk information and format preference did not differ significantly between the two trial arms, irrespective of numeracy and graph literacy proficiency. High numeracy and graph literacy proficiency was associated with high understanding (p<0.01) and a preference for the bar graph (p = 0.01). CONCLUSION: We found no evidence to demonstrate the superiority of one format over another on understanding. The majority of participants preferred viewing the risk information using the bar graph format.

Nonopioid Approaches to Pain Management in Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) and end-stage renal disease experience high pain and symptom burden, but management of chronic pain in this population remains challenging. Recent studies have shown a high rate of opioid prescription and use in patients with kidney disease. However, the concern for opioid-related morbidity and mortality suggests a need to reconsider the safety and efficacy of opioid use in patients with CKD. In this review, we describe the current approaches to pain management in CKD, highlight the evolving opioid-related risks and kidney-specific concerns, and offer both pharmacologic and nonpharmacologic nonopioid strategies for pain management in patients with kidney disease, emphasizing the importance of using a multimodal approach to optimize pain control.

Opioid Management in CKD.

Patients with chronic kidney disease (CKD) experience a high pain and symptom burden. Concurrently, opioid prescription and use in patients with CKD continues to increase, leading to concern for opioid-related risks. Nephrologists increasingly face challenging clinical situations requiring further evaluation and treatment of pain, for which opioid use may be indicated. However, nephrologists are not commonly trained in pain management and may find it difficult to compile the necessary information and tools to effectively assess and treat potentially multidimensional pain. In these situations, they may benefit from using an evidence-based stepwise approach proposed in this article. We address current approaches to opioid use for pain management in CKD and offer a stepwise approach to individualized opioid assessment, focusing on kidney-specific concerns. This includes thorough evaluation of the pain experience, opioid use history, and treatment goals. We subsequently discuss considerations when initiating opioid therapy, strategies to reduce opioid-related risks, and recommended best practices for opioid stewardship in CKD. Using this sequential approach to opioid management, nephrologists can thereby gain a broad overview of key patient considerations, the foundation for understanding implications of opioid use, and a patient-tailored plan for opioid therapy.

Development of an in vitro model of the dentogingival junction using 3D organotypic constructs.

OBJECTIVES: The overall aim was to propose a plausible model of the dentogingival junction (DGJ) to deepen our understanding of the extrinsic influences responsible for the development of the junctional epithelial phenotype. The specific objective was to test the hypothesis that epithelial migration and proliferation would be inhibited by periodontal ligament (PDL) fibroblasts in an in vitro model of the DGJ consisting of 3D organotypic cultures. BACKGROUND: Previously, we showed that 3D organotypic cultures containing human gingival fibroblasts (HGF) supported the development of a multi-layered epithelium, while constructs containing human periodontal ligament fibroblasts (HPDLF) resulted in epithelial atrophy (Lu EMC, Hobbs C, Dyer CJ, Ghuman M, Hughes FJ. J Perio Res., 2020). However, changes in epithelial phenotype have not been studied within an in vitro model of the DGJ. METHODS: The in vitro model of the DGJ comprised of a donor HGF construct (H400 epithelium overlying HGF-collagen matrix) supported by a dimensionally larger recipient collagen bed enriched with HPDLF. Samples were harvested, fixed and processed for immunohistochemistry. The changes in epithelial migration and proliferation following contact with HPDLF were assessed by measuring the horizontal extension of the epithelial outgrowth on the recipient collagen matrix. RESULTS: Within our in vitro model of the DGJ, epithelial migration and proliferation were inhibited following contact with the recipient HPDLF. By contrast, the control set-up showed a relative increase in epithelial growth, where the epithelium came into contact with the recipient HGF. Overall, there were limited changes in the molecular expression of keratin markers. CONCLUSION: This study has proposed a plausible in vitro model of the DGJ to illustrate the role of different fibroblasts in the regulation of dentogingival epithelia. Furthermore, it suggests that the anatomical positional stability of the JE and its apparent resistance to apical migration could be associated with its interaction with the PDL.