6-month Period Research Articles

T cell hybrid immunity against SARS-CoV-2 in children: a longitudinal study

Hybrid immunity to SARS-CoV-2, resulting from both vaccination and natural infection, remains insufficiently understood in paediatric populations, despite increasing rates of breakthrough infections among vaccinated children. We conducted a prospective longitudinal study to investigate the magnitude, specificity, and cytokine profile of antigen-specific T cell responses elicited by breakthrough SARS-CoV-2 infection in a cohort of mRNA-vaccinated children (n=29) aged 5-11. This longitudinal analysis involved six distinct time points spanning a 16-month period post-vaccination, during which we analysed a total of 159 blood samples. All children who were followed for at least 12months (n=26) experienced a breakthrough infection. We conducted cytokine release assays using minimal blood samples, and we verified the cellular origin of these responses through intracellular cytokine staining. After breakthrough infection, children who had received mRNA vaccines showed enhanced Th1 responses specific to Spike peptides. Additionally, their Spike-specific T cells exhibited a distinctive enrichment of CD4+ IFN-γ+IL10+ cells, a characteristic akin to adults with hybrid immunity. Importantly, vaccination did not impede the development of multi-specific T cell responses targeting Membrane, Nucleoprotein, and ORF3a/7/8 antigens. Children, previously primed with a Spike-based mRNA vaccine and experiencing either symptomatic or asymptomatic breakthrough infection, retained the ability to enhance and diversify Th1/IL-10 antigen-specific T cell responses against multiple SARS-CoV-2 proteins. These findings mirror characteristics associated with hybrid cellular immunity in adults, known to confer resistance against severe COVID-19. This study was funded by the National Medical Research Council (NMRC) Singapore (COVID19RF-0019, MOH-000019, MOH-000535, OFLCG19May-0034 and MOH-OFYIRG19nov-0002).

Continuous training in young athletes decreases hepcidin secretion and is positively correlated with serum 25(OH)D and ferritin

Continuous training in young athletes decreases hepcidin secretion and is positively correlated with serum 25(OH)D and ferritin

Role of the forcing sources in morphodynamic modelling of an embayed beach

Abstract. The sensitivity of a 2DH coastal area (XBeach) and a reduced-complexity (Q2Dmorfo) morphodynamic model to using different forcing sources is studied. The models are tested by simulating the morphodynamic response of an embayed beach in the NW Mediterranean over a 6-month period. Wave and sea-level forcing from in situ data, propagated buoy measurements, and hindcasts, as well as combinations of these different data sources, are used, and the outputs are compared to in situ bathymetric measurements. Results show that when the two models are calibrated with in situ measurements, they accurately reproduce the morphodynamic evolution with a “good” Brier skill score (BSS). The calibration process reduces the errors by 65 %–85 % compared with the default setting. The wave data propagated from the buoy also produce reliable morphodynamic simulations but with a slight decrease in the BSS. Conversely, when the models are forced with hindcast wave data, the mismatch between the modelled and observed beach evolution increases. This is attributed to a large extent to biased mean directions in hindcast waves. Interestingly, in this small tide site, the accuracy of the simulations hardly depends on the sea-level data source, and using filtered or non-filtered tides also yields similar results. These results have implications for long-term morphodynamic studies, like those needed to validate models for climate change projections, emphasizing the need to use accurate forcing sources such as those obtained by propagating buoy data.

Obtainment of prescribed analgesics among patients with Lyme neuroborreliosis; a nationwide, population-based matched cohort study

BackgroundRadicular pain is the most predominant symptom among adults with Lyme neuroborreliosis (LNB) but the duration preceding and following diagnosis remains unknown. We aimed to investigate whether patients with LNB have increased obtainment of analgesics before and after diagnosis and for how long. MethodsWe performed a nationwide, population-based, matched cohort study (2009–2021). all Danish residents with LNB (positive Borrelia burgdorferi intrathecal antibody index test and cerebrospinal fluid pleocytosis) were included. To form a comparison cohort, individuals from the general population were randomly extracted and matched 10:1 to patients with LNB on age and sex. Outcomes were obtainment of simple analgesics, antiepileptics, tricyclic antidepressants, serotonin and noradrenaline reuptake inhibitors, tramadol, and other opioids. We calculated monthly and six-monthly proportions of individuals with obtainment of analgesics and absolute risk differences. Results1,056 patients with LNB and 10,560 comparison cohort members were included. An increased proportion of patients with LNB obtained analgesics from 3 months before study inclusion, especially simple analgesics, tramadol, and other opioids. Within the 0–1-month period after study inclusion, patients with LNB most frequently obtained simple analgesics (15 %), antiepileptics (11 %), and tramadol (10 %). Thereafter, obtainment of analgesics declined within a few months. A slightly larger proportion of patients with LNB obtained antiepileptics up to 2.5 years after diagnosis. ConclusionsUp to 3 months preceding diagnosis, LNB was preceded by increased obtainment of analgesics, which suggests diagnostic delay. Importantly, most patients with LNB did not obtain analgesics after the immediate disease course, although obtainment remained more frequent up to 2.5 years after.

Effects of whole-body vibration on body composition, microbiota, cardiometabolic markers, physical fitness, and quality of life after bariatric surgery: protocol for a randomized controlled trial

BackgroundMorbid obesity is a complex chronic condition characterized by a body mass index of 40 kg/m2 or higher. The incidence of the condition is on the rise in developed countries, and bariatric surgery has been proposed as a potential solution to address this trend. Nonetheless, bariatric surgery may also result in adverse effects, including a reduction in bone mineral density (BMD) and muscle mass, as well as an increased risk of fractures. The present study aims to elucidate the effects of bariatric surgery and whole-body vibration (WBV) training on body composition, microbiota, physical fitness, quality of life, and cardiometabolic markers.MethodsTwenty-eight participants (14 females), aged 18 to 50 years, will undergo sleeve gastrectomy surgery. They will be randomly allocated into a control group or a WBV training group. The WBV group will train three times per week with increasing intensities and duration ranging from 30 to 45 min over the 4-month training period. Measurements of body composition (dual-energy X-ray absorptiometry and peripheral quantitative computed tomography), physical fitness (muscular strength, agility, cardiorespiratory fitness, and balance), gait biomechanics, cardiometabolic markers, gut microbiota, quality of life, and physical activity levels will be collected at four different time points: (1) prior to the surgery, (2) 45 days post-surgery, (3) 6 months post-surgery, and (4) 18 months post-surgery.DiscussionBoth groups are expected to experience improvements in most of the aforementioned variables. Nonetheless, we expect the WBV group to show larger improvements proving that the training is effective and safe.Trial registrationClinicaltrials.gov NCT05695599. Registered on January 25, 2023.

Modeling the economic performance of small ruminant pastoralist flocks and financial impact of changes in reproductive performance and mortalities in Kajiado county, Kenya

This study investigated the economic performance of pastoralist small ruminant flocks in Kajiado county, Kenya, and the financial impact of mortalities and changes in performance indicators. A survey of 129 pastoralist small ruminant flocks captured production and economic data for a 12-month period via interview. Simulation models were then developed for flocks with different performance levels and trading activities. Their gross margins, and the financial impact from mortalities, were estimated. Sensitivity analyses were conducted for select performance indicators to assess their relative economic importance. On average, pastoralists who were not purchasing supplementary feed (79% of flocks) had gross margins of KSh 3,016 – KSh 3,123 per reproductive female. Goat production generated 2.43–2.51 times greater returns than sheep production. High efficiency mixed flocks achieved 2.04–2.06 times greater returns than medium efficiency flocks, and 12.19–14.25 times greater returns than low efficiency flocks. Pastoralist-only flocks had 3.82–4.01 times greater returns than pastoralist-traders. Financial losses due to mortality were on average 17.81% of the starting flock value. Fecundity and abortion rates in sheep, and parturition rate in goats, had the greatest economic impact. The developed models could support decision-making toward improving the economic performance of pastoralist flocks and the evaluation of interventions and external shocks.

Written communication and the ICU team experience (WRITE): A pre-post intervention study

ObjectiveFamilies of critically ill patients may benefit from receiving a written update of patient care each day. Our objective was to develop a system to facilitate care provider creation of written updates and to determine the effect of implementing this process on the care provider experience. DesignThe experiences of ICU care providers (nurses, advanced practice providers, and physicians) were measured monthly during a 3-month pre-intervention and a 3-month intervention period. During the intervention period, written updates were sent to families each day and posted in the electronic medical record. Study investigators assisted by editing and distributing the written communication to families. SettingAn urban academic medical center in the United States. Main outcome measuresNurse-Physician Collaboration Scale (NPCS) and Maslach Burnout Inventory (MBI). ResultsOver the 3-month intervention period, care providers created written communication for families of 152 patients (average 5 ICU days per family). NPCS scores among the 65 participating care providers were significantly lower, indicating greater collaboration during the intervention vs. pre-intervention period: 49.9 (95 % CI 46.4–53.6) vs. 55.4 (95 % CI 51.5–59.3), p = 0.002. MBI scores were similar during the intervention vs. pre-intervention periods. A subset of care providers participated in individual interviews. Care providers reported that the process of creating written communication was acceptable and had clear benefits for both families and the medical team. ConclusionsUse of written communication as a supplement to verbal communication improves collaboration among ICU care providers without affecting symptoms of burnout. Implications for practiceWe created a system to facilitate written communication with ICU families that was acceptable to care providers and improved aspects of their experience. In the future, use of written communication can be enhanced with refinements to the process that reduce the time spent creating written updates while highlighting the benefits to families and care providers.

Comparative Data of Procedural and Midterm Outcomes in Patients Who Underwent Percutaneous Left Atrial Appendage Closure Between the WATCHMAN FLX and WATCHMAN 2.5 Devices - Insight From the OCEAN-LAAC Registry.

Limited data are available regarding clinical outcomes after percutaneous left atrial appendage closure using WATCHMAN FLX (WM-FLX) and WATCHMAN-2.5 (WM2.5) devices in Asian patients.Methods and Results: Data of 1,464 consecutive patients (WM-FLX, n=909; WM2.5, n=555) were extracted from a Japanese multicenter registry, and clinical data were compared between the 2 groups. No in-hospital deaths, periprocedural stroke, or device embolization occurred. Procedural success was significantly higher in the WM-FLX than WM2.5 group (95.8% vs. 91.9%; P=0.002) owing to the lower incidence of periprocedural pericardial effusion (0.55% vs. 1.8%; P=0.021). No significant differences in all-cause death, postprocedural stroke, and device-related thrombus were observed between the 2 groups. However, the cumulative bleeding rate at 1 year was substantially lower in the WM-FLX group (7.8% vs. 16.4%; P<0.001). Landmark analysis of bleeding events highlighted lower bleeding rates in the WM-FLX than WM2.5 group within the first 6 months (6.4% vs. 14.8%; P<0.001), with comparable bleeding rates over the 6- to 12-month period (1.5% vs. 3.2%, respectively; P=0.065). This study demonstrated higher early safety and lower 1-year bleeding rates in the WM-FLX than WM2.5 group. The lower bleeding events with WM-FLX are likely due to multiple factors other than purely difference in devices, such as postprocedural drug regimen.

Comparison of Stored and Fresh Injectable Acellular Adipose Matrix in Soft Tissue Reconstruction in a Murine Model.

We previously showed comparable volume effects of injections of acellular adipose matrix (AAM), an adipose tissue-derived extracellular matrix, and conventional fat grafting in a murine model. Thus, AAM could be a novel allogenic injectable product. However, its retention rate poses a concern, as repeated AAM injections may be required in some cases. This study investigated the biological properties and therapeutic value of stored AAM and compared them with those of fresh AAM, in a murine model. AAM was manufactured from fresh human abdominoplasty fat. Fresh and stored injectable AAM was prepared within 24 h and 3 months after generation, respectively. Either fresh or stored injectable AAM was injected into the scalp of athymic nude mice (0.2 mL/sample, n = 6 per group). After 8 weeks, graft retention was assessed through weight measurement, and histological analysis was performed, including immunofluorescence staining for CD31 and perilipin. Retention rate was significantly reduced in the stored compared to the fresh injectable AAM group. Nevertheless, histological analysis revealed comparable inflammatory cell presence, with minimal capsule formation, in both groups. Adipogenesis occurred in both groups, with no significant difference in the blood vessel area (%) between groups. Although the volume effects of stored AAM for soft tissue reconstruction were limited compared to those of fresh injectable AAM, stored AAM had similar capacity for adipogenesis and angiogenesis. This promising allogeneic injectable holds the potential to serve as an effective "off-the-shelf" alternative for repeated use within a 3-month storage period. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://link.springer.com/journal/00266 .

Hydroxychloroquine Dose and Hospitalizations for Active Lupus.

We sought to determine the impact of hydroxychloroquine (HCQ) dose on the risk of hospitalizations for systemic lupus erythematosus (SLE). We conducted a case-crossover study within an academic health system, including patients with SLE who used HCQ and had ≥ 1 hospitalization for active SLE between January 2011 and December 2021. Case periods ended in hospitalization for SLE, whereas control periods did not. The exposures were the average weight-based HCQ dose, categorized as ≤5 or >5 mg/kg/day, and non-weight-based HCQ dose, categorized as <400 or 400 mg/day, assessed during each 6-month case or control period. Odds ratios (OR) were calculated using conditional logistic regression and adjusted for prior disease activity, kidney function, glucocorticoid use and other immunosuppressant use. Of 2,974 patients with SLE who used HCQ (mean age 36.5 years; 92% female), 584 had ≥1 hospitalization with primary discharge diagnosis of SLE. Of these, 122 had ≥1 hospitalization for active SLE while using HCQ and had ≥1 control period with HCQ use during the study period. Lower HCQ weight-based dose (≤5 vs. >5 mg/kg/day) and non-weight-based dose (<400 vs. 400 mg/day) were each associated with increased hospitalizations for active SLE (adjusted OR 4.20 [95% CI 1.45-12.19] and 3.39 [95% CI 1.31-8.81]). The use of lower doses of HCQ was associated with an increased risk of hospitalizations for active SLE. Although the long-term risk of HCQ retinopathy must be acknowledged, this must be balanced with the short-term and cumulative risks of increased SLE activity.

First-line treatment for femoroacetabular impingement syndrome and hip-related quality of life: study protocol for a multicentre randomised controlled trial comparing a 6-month supervised strength exercise intervention to usual care (the Better Hip Trial)

IntroductionFemoroacetabular impingement syndrome (FAIS) is a motion-related and position-related clinical condition of the hip associated with pain, reduced physical function and hip-related quality of life (QoL). Interestingly, higher maximal muscle...

Engagement of culturally diverse communities in primary care research.

The underrepresentation of ethnic minorities and low-income groups in primary care (PC) research hinders the development of effective treatments for diverse populations. To develop a framework that general practice staff and researchers can use to improve the participation of underserved groups in PC research. This study was undertaken across 10 GP practices in South London serving 150 658 patients. Practices are distributed across ethnically diverse and highly deprived communities. A mixed-methods approach was utilised. Retrospective data were collected on patient participation in research studies across the practices between July 2022 and July 2023. Professional and patient focus groups, and a patient questionnaire, were undertaken to understand awareness and knowledge of, enablers for, and barriers to research participation. Over the 12-month period, 627 patients participated in PC research studies across the 10 practices. Black African and Black Caribbean patients accounted for 26% of the practices' patient population but were significantly underrepresented in research, comprising only 11% of participants. Patients of Asian backgrounds accounted for 11% of the practices' population but made up 20% of research participants. Lack of awareness of research participation opportunities, fear of side effects, language barriers, and mistrust of researchers were some of the barriers to participation. Participants highlighted that trust in their GP, education, and transparency of research processes were key to building long-term engagement. This study provides insights into poor recruitment of specific ethnic minorities into primary care studies. The authors identified adaptations to research engagement activities, which are required to ensure that participation is improved.

“Are you here for performance or are you here for well-being?” Using participatory research to promote thriving in a British Olympic sport organization

To support the growing calls to safeguard athlete health and well-being in the pursuit of sporting success, empirical research into thriving may offer practitioners potential mechanisms to promote both outcomes simultaneously. Yet, given that elite sport environments are increasingly characterized as complex and volatile, applying theoretical knowledge is often not straightforward. In this novel study we aimed to bridge the gap between theory and practice by partnering with a sport psychologist to explore their experiences of promoting thriving within an Olympic sport organization. Using a participatory research approach in a typically inaccessible context, we sought to support the specific needs of the practitioner through a form of collaborative inquiry. Together, over a 9-month period, we navigated the complexities of translating knowledge into practice and present novel insights into the realities of effectively creating systems-level change. Namely, the need for practitioners to deftly negotiate complex interpersonal relationships and organizational cultures, and to democratize responsibility for psychological change to wider stakeholders. Regarding thriving, we demonstrate that the promotion of thriving requires an in-depth understanding of the athletic environment and organizational systems. Further, an array of athlete perspectives is needed when determining what contributes to and constitutes a thriving experience. Through our collaboration with an applied practitioner, this study makes a significant contribution toward bridging the gap between theory and practice. In doing so, we draw attention to the complex and challenging scenarios practitioners face when promoting change at an environmental level within elite sport organizations.

(025) DEVELOPING AND TESTING AN ONLINE PRIMARY CARE TOOLKIT FOR COMMUNITY MANAGEMENT OF VULVODYNIA

Abstract Introduction Vulvodynia is a chronic vulvar pain condition that affects 8-10% of women and people with vulvas. Despite its prevalence, healthcare providers (HCPs) often lack awareness, knowledge, and confidence in managing vulvodynia. This knowledge gap can lead to diagnostic delays, misdiagnoses, and reflex referrals to specialists. Moreover, research shows that patients feel invalidated in healthcare settings and perceive that their HCPs’ lack of vulvodynia awareness negatively impacts their care. Thus, there is a need for educational resources about vulvodynia that can be applied in healthcare settings. Specifically, community-based primary care providers could greatly benefit from vulvodynia resources because they are often a point of entry into the healthcare system. Objective To develop and test a new, online toolkit tailored to supporting community-based primary care providers with the assessment, diagnosis, and management of vulvodynia. In this pilot study, we sought to evaluate the adoption, acceptability, and preliminary efficacy of the vulvodynia toolkit in a pilot sample of community-based family physicians. Methods A working group of HCPs (family physicians, gynecologists, physiotherapist, psychologists) and patient partners with vulvodynia expertise developed the toolkit. The toolkit was designed in an online, modular format that could be integrated into short healthcare visits. A sample of 19 family physicians completed online surveys before and after piloting the toolkit in their community practice for 6 months. Adoption was measured in the post-toolkit survey by assessing the frequency and timing of toolkit use during the pilot period. Acceptability was measured in the post-toolkit survey by assessing physicians’ satisfaction with the toolkit content and quality. Preliminary efficacy was assessed by comparing physicians’ self-reported level of confidence with diagnosing, treating, and supporting patients with vulvodynia before and after the pilot period. Results Adoption. During the pilot period, physicians used the toolkit in advance of patient appointments (52.6%), during patient appointments (5.3%), or used a combination of both timepoints (42.1%). Over the 6-month pilot period, physicians used the toolkit an average of 2.61 times (SD = 1.50) in advance of seeing patients and 1.63 times (SD = 2.19) during patient appointments. Acceptability. Most physicians reported that they were satisfied or very satisfied with the toolkit overall (79.0%) and that it contained the right amount of information (68.4%). On average, the physicians rated their likelihood of recommending the toolkit to a colleague as 8/10 (SD = 1.75). Preliminary efficacy. Using repeated-measures MANOVAs, we found significant pre-toolkit to post-toolkit increases in physician’s confidence for diagnosing vulvodynia, p = .003, ηp 2 = .59, treating vulvodynia, p &amp;lt; .001, ηp2 = .72, and supporting patients with vulvodynia, p &amp;lt; .001, ηp2 = .73. Conclusions In this pilot study, we developed and tested an online vulvodynia toolkit tailored to educating community-based primary care providers. The toolkit demonstrated high acceptability and preliminary efficacy amongst a pilot group of family physicians, with large effect sizes. The results of this study exemplify the value of tailored education for improving physicians’ confidence with managing vulvodynia in community practice and lay the foundation for upscaling this tool to a wider population of HCPs. Disclosure No.

Evaluating usability of and satisfaction with mHealth app in rural and remote areas-Germany GIZ collaboration in Bosnia-Herzegovina to optimize type 1 diabetes care.

Type 1 diabetes mellitus (T1DM) management in children and adolescents requires intensive supervision and monitoring to prevent acute and late diabetes complications and to improve quality of life. Digital health interventions, in particular diabetes mobile health apps (mHealth apps) can facilitate specialized T1DM care in this population. This study evaluated the initial usability of and satisfaction with the m-Health intervention Diabetes: M app, and the ease of use of various app features in supporting T1DM care in rural and remote areas of Bosnia-Herzegovina with limited access to specialized diabetes care. This cross-sectional study, performed in February-March 2023, evaluated T1DM pediatric patients who used the Diabetes: M app in a 3-month mHealth-based T1DM management program, along with their parents and healthcare providers (HCPs). All participants completed self-administered online questionnaires at the end of the 3-month period. Data were analyzed by descriptive statistics. The study population included 50 T1DM patients (children/parents and adolescents) and nine HCPs. The mean ± SD age of the T1DM patients was 14 ± 4.54 years, with 26 (52%) being female. The mean ± SD age of the HCPs was 43.4 ± 7.76 years; all (100%) were women, with a mean ± SD professional experience of 17.8 ± 8.81 years. The app was reported usable in the domains of ease-of-use and satisfaction by the T1DM children/parents (5.82/7.0), T1DM adolescents/young adults (5.68/7.0), and HCPs (5.22/7.0). Various app features, as well as the overall app experience, were rated positively by the participants. The results strongly support the usability of mHealth-based interventions in T1DM care, especially in overcoming care shortage and improving diabetes management and communications between HCPs and patients. Further studies are needed to compare the effectiveness of apps used to support T1DM management with routine care.

The effect of platelet-rich fibrin (PRF) versus freeze-dried bone allograft (FDBA) used in alveolar ridge preservation on the peri-implant soft and hard tissues: a randomized clinical trial

BackgroundThe effectiveness of alveolar ridge preservation on bone regeneration and tissue healing has been thoroughly documented in the literature. This study aimed to evaluate the peri-implant soft and hard tissue changes after alveolar ridge preservation using either platelet-rich fibrin (PRF) or freeze-dried bone allograft (FDBA) over a 12-month period following the prosthetic loading of implants.MethodsIn this randomized clinical trial, 40 individuals were recruited for alveolar ridge preservation using (1) FDBA or (2) PRF in incisal/premolar areas. At two follow-up sessions (six- and 12-months post-implant insertion), radiographic imaging and clinical examinations assessed marginal bone loss and soft tissue factors, including gingival recession and bleeding on probing. The differences between study groups were analyzed using Generalized estimating Equations, the Binary logistic regression model, and Cochran’s Q test.ResultsThere was a statistically significant difference regarding gingival recession at both follow-up evaluations; values in the PRF group were considerably lower compared to the FDBA group (p < 0.05). The mean values for vertical marginal bone loss and bleeding on probing showed no significant differences between the two study groups (p > 0.05).ConclusionsExcept for gingival recession, applying PRF yielded comparable clinical results to FDBA after one year of implant loading and could be recommended as a potential biomaterial for alveolar ridge preservation following tooth extractions.Clinical trial registrationThe research protocol was registered in the Protocol Registration and Results System on 13/08/2021, available at https://clinicaltrials.gov/ (NCT05005377).

Impact of pharmacist-evaluated clinical decision support system alerts on potentially missing or inappropriately prescribed proton pump inhibitors at hospital discharge: a retrospective cross-sectional study.

Proton pump inhibitors (PPIs) are among the most prescribed drugs. A clinical decision support system (CDSS) could improve their rational use. The impact of an electronic algorithm (e-algorithm) implemented in a CDSS on potentially missing or inappropriately prescribed PPIs at hospital discharge, its specificity and sensitivity, and the outcome of the alerts issued were analysed. An e-algorithm continuously monitored patients of a tertiary care hospital for missing or inappropriate PPIs. Following relevance assessment by a pharmacist, the alerts raised were either displayed in the patients' electronic record or dismissed. After a three-month period, all adult patients' records were retrospectively reviewed for missing or inappropriate PPIs at discharge. The results were compared with a corresponding period before CDSS introduction. Sensitivity, specificity and outcome of alerts were quantified. In a 3-month period with 5018 patients, the CDSS created 158 alerts for missing PPIs and 464 alerts for inappropriate PPIs. PPI prescribing was proposed 81 times and PPI termination 122 times, with acceptance rates of 73% and 34%, respectively. A specificity of 99.4% and sensitivity of 92.0% for missing PPIs and a specificity of 97.1% and a sensitivity of 69.7% for inappropriate PPIs were calculated. The algorithm reduced incidents of missing PPIs by 63.4% (p < 0.001) and of inappropriate PPIs by 16.2% (p = 0.022). The algorithm identified patients without necessary gastroprotection or inappropriate PPIs with high specificity and acceptable sensitivity. It positively impacted the rational use of PPIs by reducing incidents of missing and inappropriate PPIs.

Study protocol for the Treating Opioid Patients' Pain and Sadness (TOPPS) study — A randomized control trial to lower depression and chronic pain interference, and increase care retention among persons receiving buprenorphine

BackgroundPersons receiving prescription buprenorphine for opioid use disorder experience high rates of comorbid conditions such as chronic pain and depression, which present barriers to buprenorphine care retention. This paper describes the protocol of the TOPPS (Treating Opioid Patients' Pain and Sadness) study, which compares a values-based, behavioral activation intervention with a health education contact-control condition, with the aim of decreasing chronic pain and depression, and increasing buprenorphine care retention for persons with opioid use disorder. MethodsThis randomized controlled trial (RCT) enrolls and randomizes up to 250 participants currently being treated with buprenorphine to receive three months of either TOPPS, a six-session phone-based behavioral intervention, or a health education (HE) control condition. We compare the TOPPS intervention to HE on the following outcomes: 1) pain interference and pain severity over the 3-month treatment phrase; 2) depressive symptoms over the 3-month treatment phase; and 3) sustained improvements in pain interference, depressive symptoms, and buprenorphine treatment retention over the 12-month study period. We also examine mechanisms by which the intervention may reduce pain interference. DiscussionThis RCT explores a novel intervention to address chronic pain and depression for individuals receiving buprenorphine in office-based settings. TOPPS may lead to improved pain, depression, and substance use outcomes, and can utilize providers available within buprenorphine programs, broadening the disseminability of this intervention and heightening its public health impact. Clinical Trial#NCT03698669

Efficiency of Orthopaedic Audits in a Level-1 Trauma Centre Using a Modified Clavien–Dindo Complications Classification

Background: Complications are an inevitable part of orthopaedic surgery, and how one defines complications can have an impact on the ability to learn from them. There have been issues with a commonly used classification system first outlined by Clavien and Dindo. Our aim was to evaluate a modification of this classification system developed for use in our department, with our hypothesis being that this could make our audit presentations more efficient. Methods: A modified Clavien–Dindo Classification was prospectively applied to all complications recorded in the orthopaedic departmental audits at our institution for a 12-month period. The audit discussion was recorded and analysed and compared with the complication audits for the preceding 12-month period. Results: We analysed eight audit presentations before and eight audit presentations after the introduction of a modified Clavien–Dindo classification to our orthopaedic complications over a 2-year period. The number of PowerPoint™ slides (103 vs. 84, p = 0.03) and the time spent on each presentation (88 vs. 71 min, p = 0.02) decreased significantly with the introduction of the modified classification. The novel system was found to have high inter-observer reliability. Conclusions: The modified Clavien–Dindo classification system is a reproducible classification system for orthopaedic complications. It made our audit presentations more efficient.

Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study.

Diabetic osteopathy is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The association between T2DM and increased fracture risk has led to study the impact of new antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetic drugs which have many pleiotropic properties. The relationship between GLP-1RAs and bone is very complex: while in vitro and animal studies have demonstrated a protective effect on bone, human studies are scarce. We led a 12months longitudinal study evaluating bone changes in 65 patients withT2DM for whom a therapy with GLP-1RAs had been planned. Fifty-four T2DM patients completed the 12-month study period; of them, 30 had been treated with weekly dulaglutide and 24 with weekly semaglutide. One-year therapy with GLP-1RAs resulted in a significant reduction in weight and BMI. Bone mineral density (BMD), bone metabolism, trabecular bone score (TBS), adiponectin, and myostatin were evaluated before and after 12months of GLP-1RAs therapy. After 12months of therapy bone turnover markers and adiponectin showed a significant increase, while myostatin values showed a modest but significant reduction. BMD-LS by DXA presented a significant reduction while the reduction in BMD-LS by REMS was not significant and TBS values showed a marginal increase. Both DXA and REMS techniques showed a modest but significant reduction in femoral BMD. In conclusion, the use of GLP-1RAs for 12months preserves bone quality and reactivates bone turnover. Further studies are needed to confirm whether GLP-1RAs could represent a useful therapeutic option for patients with T2DM and osteoporosis.