Clinical Intervention Studies Research Articles

P120 Characteristics of difficult-to-treat rheumatoid arthritis: results from a systematic literature review

Abstract Background/Aims Estimates predict between 10-20% of RA patients meet difficult-to-treat Rheumatoid Arthritis (D2T-RA) classification, representing a clinically distinct cohort. There is a significant unmet need in the identification and management of these patients. Discerning significant characteristics across cohorts may identify predictors for D2T-RA, which may prompt earlier clinical recognition and patient-tailored, holistic management to improve clinical outcomes. This review aims to describe the clinical characteristics of patients with EULAR-defined D2T-RA to help identify and manage predictors, contributory factors, or consequences of difficult-to-treat disease. Methods A systematic literature search of PubMed, Embase and Web of Science databases for studies pertaining to characteristics of D2T-RA was undertaken from database inception to May 2023. Results were screened against strict inclusion/exclusion criteria. Risk-of-bias (RoB) assessments were performed using the Newcastle-Ottawa Scale (NOS) and a modified version for cross-sectional studies (mNOS). Significant (p < 0.05) baseline characteristics between D2T-RA and non-D2T patients were extracted for comparison following thematic analysis. Where there was conflict in the direction of the extracted characteristics; the number and quality of studies were used to resolve evidential disagreements. Results 1687 studies were identified, of which seven fulfilled the inclusion criteria. Included studies were observational, published between 2021 and 2023, with mean D2T and non-D2T sample sizes of 83 and 417 patients, respectively. Five of the seven cohorts were European, with two from Japan. Following RoB and dispute resolution, all seven identified studies were included for analysis. Key themes elucidated are shown in table 1. Of note, significant characteristics included female sex, autoantibody positivity, greater annual bone erosion progression, interstitial lung disease, mental health conditions, and non-adherence. Conclusion Greater awareness of clinical characteristics of D2T-RA patients will assist clinicians by promoting the assessment of traits associated with poor treatment response. This is the first review to systematically describe characteristics of D2T-RA patients across multiple cohorts. Several commonly recorded, modifiable characteristics were associated with D2T-RA. Evidential disagreements and heterogeneous study designs were analytical barriers, and clinical intervention studies are needed to determine if addressing these factors in the routine clinical setting improves clinical outcomes and prevention in D2T-RA. Disclosure S. Chambers: None. A.P. Croft: None. R. Singh: None.

Surgical stabilization for degenerative lesions of the lumbar spine in patients with reduced bone mineral density: a systematic literature review

Objective. To analyze methods contributing to the improvement of clinical and radiological outcomes of surgical stabilization of the lumbar spine in conditions of reduced bone mineral density (BMD).Material and Methods. A search for publications presenting the results of clinical studies of surgical treatment of patients with degenerative lesions of the lumbar spine and reduced BMD was conducted in English and Russian in the MEDLINE and Russian Science Citation Index (RSCI) databases using key words “osteoporosis”, “osteopenia”, “spinal surgery”, “spinal fusion” and related terms in titles and abstracts with a search depth of 20 years. After applying the inclusion and exclusion criteria, 17 clinical studies were selected for analysis.Results. Among the large number of techniques and implant-associated factors affecting the success of surgical intervention for degenerative lesions of the lumbar spine and reduced BMD, high-quality clinical studies have proven the effectiveness of expandable screws, spinal fusion with cortical screw placement and cement augmentation with polymethyl methacrylate.Conclusion. The combination of techniques for cortical pedicle screw placement, cement augmentation and the use of expandable screws makes it possible to achieve results in surgical treatment of patients with degenerative lesions of the lumbar spine with reduced BMD comparable with those in patients with normal BMD. Of particular importance is the preoperative assessment of the regional state of bone tissue, which should be carried out using quantitative CT or MRI studies.

Modification of Polyethylene Glycol-Hydroxypropyl Methacrylate Polymeric Micelles Loaded with Curcumin for Cellular Internalization and Cytotoxicity to Wilms Tumor 1-Expressing Myeloblastic Leukemia K562 Cells.

Curcumin loaded in micelles of block copolymers of ω-methoxypoly(ethylene glycol) and N-(2-hydroxypropyl) methacrylamide modified with aliphatic dilactate (CD) or aromatic benzoyl group (CN) were previously reported to inhibit human ovarian carcinoma (OVCAR-3), human colorectal adenocarcinoma (Caco-2), and human lymphoblastic leukemia (Molt-4) cells. Myeloblastic leukemia cells (K562) are prone to drug resistance and differ in both cancer genotype and phenotype from the three mentioned cancer cells. In the present study, CD and CN micelles were prepared and their effects on K562 and normal cells were explored. The obtained CD and CN showed a narrow size distribution with diameters of 63 ± 3 and 50 ± 1 nm, respectively. The curcumin entrapment efficiency of CD and CN was similarly high, above 80% (84 ± 8% and 91 ± 3%). Both CD and CN showed suppression on WT1-expressing K562 and high cell-cycle arrest at the G2/M phase. However, CD showed significantly higher cytotoxicity to K562, with faster cellular uptake and internalization than CN. In addition, CD showed better compatibility with normal red blood cells and peripheral blood mononuclear cells than CN. The promising CD will be further investigated in rodents and possibly in clinical studies for leukemia treatment.

Abstract 1454: Expanding the therapeutic application of PARP inhibitor: AI evaluation of real-word clinico-genomic data from spontaneous canine tumors

Abstract The widespread application of Poly-ADP ribose polymerase (PARP) inhibitors in anti-cancer therapy is constantly increasing their role as a treatment strategy across various neoplasms, the majority of which are linked with BRCA deficiency. While the most significant advantages are observed in cancers with BRCA1/2 mutations, it is evident that the benefits extend beyond this specific group. Preclinical evidence encourages the exploration of PARP inhibitors in neoplasms demonstrating BRCAness or homologous recombination deficiency (HRD), both as monotherapy and in combination with chemotherapy. This study employs spontaneous canine tumors as a complementary model for cancer research, aiming to seamlessly bridge the transition from preclinical investigations to clinical application. Leveraging the FidoCure® Precision Medicine Platform, we identified biomarkers associated with prognosis and treatment prediction, specifically with the PARP inhibitor olaparib, facilitating a smoother translation from laboratory findings to practical clinical use. Analyzing real-world clinico-genomic data from 1278 dogs with cancer revealed intriguing insights of specific targeted treatments developed for humans showing a positive prognosis when applied to canine tumors with specific genomic alterations. Notably, olaparib exhibited efficacy in TP53 and BRCA1-mutated cases (OS HR 0.34, P < 0.001; HR 0.39, P = 0.004), while rapamycin (mTOR inhibitor) demonstrated promising outcomes in TP53 and RB1-mutated canine tumors (OS HR 0.73, P = 0.028; HR 0.32, P = 0.024). Further stratification by tumor types unveiled noteworthy correlations. TP53 mutant osteosarcomas exhibited improved prognosis with olaparib treatment (OS HR 0.11, P < 0.001), and soft tissue sarcomas with TP53 mutations demonstrated favorable responses to rapamycin and olaparib therapy (OS HR 0.11, P = 0.012; HR 0.07, P = 0.011). These findings underscore the potential of leveraging canine tumor models and clinico-genomic analyses to inform targeted treatment strategies, offering valuable insights for advancing precision medicine in both veterinary and human oncology. Further investigation into the association between TP53 mutation and olaparib response is warranted. The intriguing aspect lies in the role TP53 mutation has been linked in previous studies to heightened chromosomal instability and elevated HRD scores. Utilizing real-world evidence and data tools within the FidoCure dataset, we have effectively pinpointed correlations between gene mutations and survival, particularly in relation to responses to targeted therapy treatment. Canine models, mirroring human diseases with intact immune systems and comparable tumor genomic profiles, as verified by the FidoCure database, expedite clinical studies of novel treatments that face significant scalability challenges. Citation Format: Lucas Rodrigues, Kevin Wu, Garrett Harvey, Gerald Post, Abigail Hull, Aubrey Miller, Lindsay Lambert, Christina Lopes, James Zou. Expanding the therapeutic application of PARP inhibitor: AI evaluation of real-word clinico-genomic data from spontaneous canine tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1454.

Lacosamide and pregnancy: Data from spontaneous and solicited reports.

In pregnancy, it is important to balance the risks of uncontrolled epileptic seizures to the mother and fetus against the potential teratogenic effects of antiseizure medications. Data are limited on pregnancy outcomes among patients taking lacosamide (LCM), particularly when taken as monotherapy. The objective of this analysis was to evaluate the pregnancy outcomes of LCM-exposed pregnancies. This analysis included all reports in the UCB Pharma pharmacovigilance database of exposure to LCM during pregnancy from spontaneous sources (routine clinical settings) or solicited reports from interventional clinical studies and noninterventional postmarketing studies. Prospective and retrospective reports were analyzed separately. At the data cutoff (August 31, 2021), there were 202 prospective pregnancy cases with maternal exposure to LCM and known outcomes. Among these cases, 44 (21.8%) patients received LCM monotherapy and 158 (78.2%) received LCM polytherapy. Most patients received LCM during the first trimester (LCM monotherapy: 39 [88.6%]; LCM polytherapy: 143 [90.5%]). From the prospective pregnancy cases with maternal LCM exposure, there were 204 reported outcomes (two twin pregnancies occurred in the polytherapy group). The proportion of live births was 84.1% (37/44) in patients who received LCM as monotherapy, and 76.3% (122/160) for LCM polytherapy. The overall proportion of abortions (for any reason) was 15.9% (7/44) with LCM monotherapy, and 22.5% (36/160) with LCM polytherapy. Congenital malformations were reported in 2.3% (1/44) of known pregnancy outcomes with maternal exposure to LCM monotherapy, and 6.9% (11/160) with polytherapy. Our preliminary data do not raise major concerns on the use of LCM during pregnancy. Most pregnancies with LCM exposure resulted in healthy live births, and no new safety issues were identified. These findings should be interpreted with caution, as additional data are needed to fully evaluate the safety profile of LCM in pregnancy.

A Study of Clinical Profile and Treatment in Adult Hemophilia Patients with Special Reference to the Inhibitor Levels.

Introduction Hemophilia is an uncommon, X-linked recessive bleeding condition characterized by a lack of either factor VIII or factor IX. It is more prevalent in men. Due to the substantial impact inhibitor development has on patient prognosis, the primary treatment for hemophilia is the transfusion of recombinant factors. The aim of our study is to investigate 40 adult patients with hemophilia in terms of their clinical profile, clinically relevant risk factors for inhibitor development, therapy-related aspects such as treatment duration, factor requirements, transfusion frequency, presence of inhibitors, and complications. Methods Thiscross-sectional observational study involving 40patients ofhemophilia over 12 years of age was conducted at a tertiary care hospital in Gujarat. Data on sociodemographic characteristics, presenting complaints, bleeding episodes, hemophilia type, and medical history were gathered over a one-year span. Patients were stratified into mild, moderate, and severe groups based on their respective levels of factor activity. Various parameters, including the frequency of factor therapy, percentage of factor concentrate, inhibitor presence, and disease and therapy-related complications, were analyzed. The distribution of patients across these parameters was calculated and illustrated using pie charts. Results Nineteen out of 40 patients were from 20 to 40 years of age. The majority of cases (n=24), however, had been diagnosed before the patients reached the age of 10. All patients were male, and half of the patients (n=20) suffered from mild disease. The most common site of bleeding was the knee joint, and 33 cases had one to 10 bleeding episodes per year. Thirty-twoout of 40 patients needed less than 40 factor vial transfusions, whereaseight needed more than 40 factor vial transfusions. Two cases of severe disease were positive for inhibitors of factor VIII, whereas one patient was found to have a hepatitis B virus (HBV) infection. Conclusions Hemophilia, a rare bleeding disorder, has primarily been studied in pediatric populations. This study, however, shifts the focus toward adult individuals. Our cohort consisted exclusively of male patients, with the predominant group diagnosed with hemophilia A and falling within the age range of 20 to 40 years. Most patients had been diagnosed before 10 years of age. The primary complication observed was joint bleeding, with the knee joint being the most commonly affected site. Approximately two-thirds of cases had a history of minor trauma necessitating factor replacement, yet only 5% exhibited the presence of inhibitors.

Chinese Expert Consensus on Second-line Treatment for Non-small Cell Lung Cancer with Negative Driver Gene Mutations

For advanced non-small cell lung cancer (NSCLC) patients with negative driver gene mutations, chemotherapy has always been the standard treatment option, and immune checkpoint inhibitors (ICIs) provide other treatment option for these patients. At present, the first-line treatment can choose chemotherapy, anti-angiogenic drugs or immunotherapy. Although the initial treatment can achieve a certain clinical curative effect, disease progression or treatment failure is eventually unavoidable. The second-line and subsequent treatments have poor efficacy and more effective drugs are needed clinically. An expert panel of respiratory medicine, pathology and medical oncology organized by Expert Committee on Non-small Cell Lung Cancer of the Chinese Society of Clinical Oncology conducted an in-depth discussion on evidences of clinical studies for second-line treatment of NSCLC patients with negative driver gene mutations, aiming to provide guidances for Chinese clinicians in choosing second-line treatment for NSCLC patients with negative driver gene mutations. .

Animal models of eosinophilic esophagitis, review and perspectives.

Eosinophilic oesophagitis (EoE) is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction. Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response, the exact pathogenesis is complex, and the efficacy of existing treatments is unsatisfactory. Therefore, the study of the pathophysiological process of EOE has received increasing attention. Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents. To maximize the use of existing animal models of EOE, it is important to understand the advantages or limitations of each modeling approach. This paper systematically describes the selection of experimental animals, types of allergens, and methods of sensitization and excitation during the preparation of animal models of EoE. It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.

Intake of dietary advanced glycation end products may be associated with depression and sleep quality in young adults

BackgroundThis study examined the relationship between dietary intake of advanced glycation end products (dAGEs) and depression and sleep quality in young adults. MethodsThis study, which included 420 university students (F = 80.2 %; M = 19.8 %), is observational and cross-sectional. Dietary AGEs intakes of individuals were taken with a 24-h food consumption record system. Measuring the depression status of the participants was evaluated with the Beck Depression Inventory (BDI), and the assessment of their sleep quality was evaluated with the Pittsburg Sleep Quality Index (PSQI). Individuals' dAGEs intakes were divided into three equal groups (low, medium, and high). The energy was adjusted in all analyzes of dAGEs intake. Study data were analyzed with the SPSS (27.0 version) and GraphPad program (8.0 version). ResultsThe BDI and PSQI total score averages of individuals in the high dAGEs intake group were higher than the other groups, and this difference was statistically significant (p < 0.001). There is no significant difference between individuals' dAGEs intakes and energy and macronutrient intakes. Students' dAGEs intake was affected by BDI (β = 0.722, 95 % Cl = 0.639;0.811) and PSQI (β = 0.286, 95 % Cl = 0.179;0.431) scores (p < 0.001). This effect persisted even when various confounding factors were included (age, gender, smoking, body mass index, chronic disease) (p < 0.001). LimitationsThese data are cross-sectional, which limits the generalizability of results and establishing cause-effect relationships. ConclusionThere may be an association between dAGEs intake and the development of depression and sleep quality in young adults. Clinical intervention studies using objective measurement methods should be conducted on this issue in the future.

PerSurge (NOA-30) phase II trial of perampanel treatment around surgery in patients with progressive glioblastoma

BackgroundGlioblastoma is the most frequent and a particularly malignant primary brain tumor with no efficacy-proven standard therapy for recurrence. It has recently been discovered that excitatory synapses of the AMPA-receptor subtype form between non-malignant brain neurons and tumor cells. This neuron-tumor network connectivity contributed to glioma progression and could be efficiently targeted with the EMA/FDA approved antiepileptic AMPA receptor inhibitor perampanel in preclinical studies. The PerSurge trial was designed to test the clinical potential of perampanel to reduce tumor cell network connectivity and tumor growth with an extended window-of-opportunity concept.MethodsPerSurge is a phase IIa clinical and translational treatment study around surgical resection of progressive or recurrent glioblastoma. In this multicenter, 2-arm parallel-group, double-blind superiority trial, patients are 1:1 randomized to either receive placebo or perampanel (n = 66 in total). It consists of a treatment and observation period of 60 days per patient, starting 30 days before a planned surgical resection, which itself is not part of the study interventions. Only patients with an expected safe waiting interval are included, and a safety MRI is performed. Tumor cell network connectivity from resected tumor tissue on single cell transcriptome level as well as AI-based assessment of tumor growth dynamics in T2/FLAIR MRI scans before resection will be analyzed as the co-primary endpoints. Secondary endpoints will include further imaging parameters such as pre- and postsurgical contrast enhanced MRI scans, postsurgical T2/FLAIR MRI scans, quality of life, cognitive testing, overall and progression-free survival as well as frequency of epileptic seizures. Further translational research will focus on additional biological aspects of neuron-tumor connectivity.DiscussionThis trial is set up to assess first indications of clinical efficacy and tolerability of perampanel in recurrent glioblastoma, a repurposed drug which inhibits neuron-glioma synapses and thereby glioblastoma growth in preclinical models. If perampanel proved to be successful in the clinical setting, it would provide the first evidence that interference with neuron-cancer interactions may indeed lead to a benefit for patients, which would lay the foundation for a larger confirmatory trial in the future.Trial registrationEU-CT number: 2023-503938-52-00 30.11.2023.

P722 The steep ramp test is a valid practical test to assess cardiorespiratory fitness in patients with inflammatory bowel disease

Abstract Background Comprehensive disease management of inflammatory bowel disease (IBD) requires a holistic approach that extends beyond achieving endoscopic healing. Monitoring health-related physical fitness (HRPF) parameters (i.e. body composition, cardiorespiratory fitness, muscular strength, muscular endurance, and flexibility) may lead to a more proactive approach to managing IBD, as IBD may affect HRPF due to e.g. chronic inflammation, malnutrition, corticosteroid use, and reduced physical activity. Yet, knowledge regarding HRPF in patients with IBD is limited. Assessment of cardiorespiratory fitness (CRF), a key component of HRPF in other chronic diseases, could offer valuable insights into physical capacity and overall health. However, the gold standard, measuring oxygen uptake at peak exercise (VO2peak) achieved during cardiopulmonary exercise testing (CPET) is impractical for widespread implementation in clinical practice. The steep ramp test (SRT), a short-term maximal exercise test on a cycle ergometer, might serve as a less demanding assessment method to facilitate routine assessment of CRF in clinical practice and deliver more practical endpoints for intervention studies. This study aimed to examine the criterion validity of the SRT as compared with CPET in evaluating CRF in patients with IBD. Methods From August 2022 to October 2023, adult patients with IBD in remission or with mild-to-moderate clinical disease activity were consecutively enrolled. Each participant performed a SRT and a CPET within 14 days to examine CRF. The main outcome measures were the achieved work rate at peak exercise (WRpeak) for the SRT (SRT-WRpeak) and VO2peak as well as WRpeak for CPET (CPET-VO2peak and CPET-WRpeak). Validity of the SRT was evaluated with Pearson’s correlation coefficients between SRT-WRpeak and CPET-VO2peak and SRT-WRpeak and CPET-WRpeak. Results A total of 50 participants, with a mean age of 42.9 years and 56% diagnosed with CD, were included (Table 1). One participant was excluded from the analysis due to the inability to achieve a maximal effort during CPET. Mean (±SD) WRpeak attained at the SRT was 4.32 (±1.06) W·kg-1, and mean (±SD) VO2peak and WRpeak achieved during CPET were 33.47 (±9.85) mL·kg-1·min-1 and 2.90 (±0.95) W·kg-1, respectively. Figure 1 illustrates robust linear relationships with very strong correlations between SRT-WRpeak and CPET- VO2peak (r=0.945, p&amp;lt;0.001) and SRT-WRpeak and CPET-WRpeak (r=0.960, p&amp;lt;0.001). Conclusion Results of this study suggest that the SRT is a valid alternative test for examining CRF in patients with IBD, indicating its potential application in both clinical practice and intervention studies. Further research should explore the criterion validity of practical tests for other components of HRPF.

Ultraviolet-C (UV-C) Effectiveness for Bacterial Decontamination in The Hospital Setting: A Systematic Review

Introduction: Bacteria are the most common agent reported to cause hospital-acquired infection (HAI) and nurses play a key role in achieving optimal decontamination. Ultraviolet-C (UV-C) is a promising candidate to reduce the bacteria infection burden. Therefore, this review aims to explore the UV-C application and its effectiveness in reducing bacteria contamination on various objects that can act as sources of HAI transmission. Methods: Searches were conducted on the PubMed, ScienceDirect, Scopus, and Cumulative Index to Nursing and Allied Health Literature databases. The inclusion criteria were randomized clinical trials, and non-randomized clinical intervention studies, written in English and published between January 2018 and March 2023. The search strategy used a population (P), intervention (I), comparator (C), and outcome (O) approach. Results: A total of 21 eligible studies were included in this review with four being related to decontaminating medical devices, two to personal equipment, nine to communication devices, and the remaining six to the environment. The exposure to UV-C radiation varies ranging from 24 s to 24 h (continuously) and it reduced the level of bacteria even up to 100%. Meanwhile, previously the objects were detected to be contaminated with pathogenic and resistant bacteria. Conclusion: UV-C exposure can be effectively used to decontaminate various objects in hospitals. However, special consideration should be given to semi-critical devices due to contact with mucosal tissue. Further studies are needed regarding the application of doses and duration of UV-C exposure to eliminate bacteria completely.

Tooth Wear in Older Adults: A Review of Clinical Studies.

Tooth wear is a prevalent dental condition among older adults, leading to pain and adversely affecting aesthetics, functionality, and their overall quality of life. This review aims to update the information on tooth wear in older adults from the past five years and to provide guidance on the clinical management of tooth wear in older adults. A literature search was conducted in three electronic databases, Scopus, Pubmed, and Embase, for English publications from January 2019 to December 2023 on clinical studies with participants aged 65 or above on tooth wear. A total of 307 articles were retrieved and 14 articles were finally included as references for this study. This review highlights the common causes of tooth wear and various risk factors, such as medical conditions, hyposalivation, dietary habits, oral hygiene practices, parafunctional habits, and occlusal factors, associated with tooth wear. It is crucial for oral health care professionals to diagnose and manage tooth wear at an early stage through a risk assessment and a clinical examination to avoid complex restorative procedures. Tooth wear management should prioritize prevention, aiming to control etiological and risk factors while employing non-restorative treatments. Restorative intervention, if indicated, should be simple, minimally invasive, and cost-effective. Tooth wear progression should be monitored regularly to determine if a further intervention is needed. Since the clinical studies on tooth wear in older adults over the past five years are limited and mainly cross-sectional, more interventional clinical studies are warranted to provide more clinical guidance on tooth wear management in older adults.

Advances with Platelet-Rich Plasma for Bone Healing.

Despite significant advances in the understanding and delivery of osteosynthesis, fracture non-union remains a challenging clinical problem in orthopaedic surgery. To bridge the gap, basic science characterization of fracture healing provides a platform to identify and target biological strategies to enhance fracture healing. Of immense interest, Platelet-rich plasma (PRP) is a point of care orthobiologic that has been extensively studied in bone and soft tissue healing given its relative ease of translation from the benchtop to the clinic.The aim of this narrative review is to describe and relatepre-clinicalin-vitro and in-vivo findings to clinical observations investigating the efficacy of PRP to enhance bone healing for primary fracture management and non-union treatment. A particular emphasis is placed on the heterogeneity of PRP preparation techniques, composition, activation strategies, and delivery.In the context of existing data, the routine use of PRP to enhance primary fracture healing and non-union management cannot be supported. However, it is acknowledged that extensive heterogeneity of PRP treatments in clinical studies adds obscurity; ultimately, refinement (and consensus) of PRP treatments for specific clinical indications, including repetition studies are warranted.

Communication, Cognition and Competency Development in Healthcare: A Model for Integrating Cognitive Ethnography and Communication Skills Training in Clinical Interventions.

The aim of this study was to conduct and evaluate the Blended Learning communication skills training program. The key objective was to investigate (i) how clinical intervention studies can be designed to include cognitive, organizational, and interactive processes, and (ii) how researchers and practitioners could work with integrated methods to support the desired change. The method combined design and implementation of a 12-week Blended Learning communication skills training program based on the Calgary-Cambridge Guide. The training was implemented in a patient clinic at a Danish university hospital and targeted all healthcare professionals at the clinic. Cognitive ethnography was used to document and evaluate healthcare professionals' implementation and individual competency development, and support the design of in-situ simulation training scenarios. Thirteen participants completed the program. The synergy within the teams, as well as the opportunities for participants to coordinate, share, discuss, and reflect on the received knowledge with a colleague or on-site researcher, affected learning positively. The knowledge transfer process was affected by negative feedback loops, such as time shortages, issues with concept development and transfer, disjuncture between the expectations of participants and instructors of the overall course structure, as well as participant insecurity and a gradual loss of motivation and compliance. We propose a novel 3-step model for clinical interventions based on our findings and literature review. This model will effectively support the implementation of educational interventions in health care by narrowing the theory-practice gap. It will also stimulate desired change in individual behavior and organizational culture over time. Furthermore, it will work for the benefit of the clinic and may be more suitable for the implementation of communication projects than, for example, randomized setups.

Introduction to dynamic retinal vessel analyses

Retinal vessels possess the same structure and function as cerebral vessels and reflect the status of the central microcirculation. In the pre‐, post‐ and capillary areas, the behaviour of retinal vessels does influence blood flow and flow‐related metabolism through changes in arterial and venous diameter. In dynamic retinal vessel analysis, the function and structure of retinal vessels are subjected to a non‐invasive functional and structural examination over a period before, during and after a specific vascular stimulation. The use of several methodological modalities together with their relevant quantitative biomarkers represents a promising approach for the evaluation of ocular and systemic diseases of vascular origin as well as cerebro‐ or cardiovascular morbidity and mortality. Dynamic retinal vessel analysis has been employed in cross‐sectional and interventional clinical studies in ophthalmology and interdisciplinary in other branches of the medicine including cardiology, neurology, neurosurgery, nephrology, diabetology, hypertensiology, gynaecology and others. The paper aims to give a brief overview in the technology and the methodology of dynamic retinal vessel analysis.

The therapeutic effect and metabolic mechanism analysis of Guilingji on idiopathic oligo-asthenoteratozoospermia

IntroductionGuilingji, a famous traditional Chinese medicine (TCM) formula, has been used to combat aging and male sexual dysfunction in China for centuries. To date, there has been little evidence-based clinical research on the use of Guilingji to treat idiopathic oligo-asthenoteratozoospermia (OAT), and the therapeutic mechanism from a metabolic perspective needs to be investigated further. MethodsThis was a multicenter, double-blind, randomized controlled clinical study of 240 patients with idiopathic OAT recruited from four hospitals between January 2020 and January 2022. Patients were randomly assigned in a 1꞉1 ratio to receive oral Guilingji capsules or placebo for 12 weeks. The total progressive motile sperm count (TPMSC) was considered the primary outcome, and the other sperm parameters, seminal plasma parameters and serum hormones were considered the secondary outcome. A nontargeted metabolomics analysis of serum from OAT patients before and after Guilingji administration was performed by HPLC–MS to identify key metabolites. Furthermore, we used a rat model to show spermatogenesis phenotypes to validate the effect of the key metabolites screened from the patients. ResultsAt weeks 4, 8 and 12, TPMSC and other sperm parameters were significantly improved in the Guilingji group compared with the placebo group (P < 0.05 for all comparisons). At week 4, superoxide dismutase (SOD) and acrosomal enzyme activity of seminal plasma were significantly elevated in the Guilingji group compared with the placebo group, while reactive oxygen species (ROS) levels were significantly reduced (P < 0.05). Lactate dehydrogenase-X (LDHX) levels appeared to be significantly increased after 12 weeks continuous medication compared with Placebo group (P = 0.032). The metabolomics analysis of serum from OAT patients before and after Guilingji administration showed that the glucose-6-phosphate (G6P) concentration in patients' serum was significantly elevated after Guilingji treatment. Compared to the control, when Kidney-Yang deficiency model rats were treated with Guilingji or its key intermediate metabolite G6P, their sperm concentration and spermatozoic activity were improved similarly, and their structural damage of rat's testicular and epididymal tissues were recovered. ConclusionThis study provided valuable clinical evidence for the utility of Guilingji as a treatment for OAT. These findings thus demonstrate that G6P is involved in the therapeutic mechanism of Guilingji in OAT treatment based on clinical and rat intervention studies.

Abdominal massage for chronic constipation in the elderly: a systematic review and meta-analysis protocol

IntroductionChronic constipation (CC) is a highly prevalent health challenge that is particularly challenging to treat in elderly patients. Although lifestyle guidance and laxative therapy often yield positive outcomes, patients occasionally...

Pneumonectomy for severe post-tuberculosis bronchiectasis: A successful of case report and review of the long-term outcome.

Limited clinical intervention studies highlight the absence of evidence-based international guidelines for effectively managing post-tuberculosis lung disease, emphasizing bronchiectasis. The aim of this study was to describe a case of left pneumonectomy for severe post-tuberculosis cystic bronchiectasis and to provide a review of the post-surgical mortality rate, complications, survival rate, and the patient's quality of life following the pneumonectomy procedure. A 36-year-old Indonesian male smoker presented with worsening breathing difficulties and fever. The patient had a history of pulmonary tuberculosis six years ago and reported negative tuberculosis tests after completing TB treatment. However, lung function of the patient progressively declined over the years. Bronchoscopy, chest X-ray, and high-resolution computerized tomography (CT) scan revealed infected cystic bronchiectasis and identified a prominent left lung collapse with calcification in the left pleura. The patient underwent left pneumonectomy through left posterolateral thoracotomy under general anesthesia. The patient was discharged after seven post-operative days with no eventful course. No further complications were found after a one-year post-surgery follow-up, and the patient returned to normal activities, improved fitness, and was fitter in daily life. Based on the literature review, post-surgical mortality rates of pneumonectomy are acceptable, with bronchopleural fistula, cardiac arrest, and thoracic hemorrhage being common causes. Yet, the chances of a complete cure are high. Complications can occur in approximately one-third of patients, including arrhythmia, pulmonary infection, fever, and wound infections. The overall 5-year survival rate following pneumonectomy is generally favorable. Regarding the quality of life, pneumonectomy can have mixed effects. While it could improve symptoms and quality of life, it may impair the quality of life for certain patients, particularly elderly patients and those with lower preoperative quality of life. Although the post-surgical mortality rate, complications, and long-term survival rates of pneumonectomy are generally satisfactory, the expectation of improved post-surgical quality of life should be discussed with the patient prior to surgery.

The Associations of Vitamin D with Ovarian Reserve Markers and Depression: A Narrative Literature Review.

Since the identification of vitamin D receptors in both the female reproductive tract and the central nervous system, further data have shown that vitamin D is involved in the processes of reproductive and mental health. This paper reviews current research on the associations of vitamin D with ovarian reserve markers and depression and discusses the potential role of vitamin D in their relationships. There have been numerous studies reporting that vitamin D was significantly related to ovarian reserve markers and depression in basic or clinical research, but some observational and interventional clinical studies have shown inconsistent results. Nevertheless, recent meta-analyses of interventional studies have provided promising results showing that vitamin D supplementation significantly improves ovarian reserve metrics, especially in a subgroup of women with normal or diminished ovarian reserve, and decreases depressive symptoms and risk. The demonstration of an association of vitamin D with both ovarian reserve and depression could suggest that vitamin D may be another important key in explaining female reproductive depression. Larger-scale studies in standardized settings will be needed in order to gain further insight into the role of vitamin D in female reproduction and depression.