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BICSTaR (BICtegravir Single Tablet Regimen) is an ongoing, observational cohort study assessing the virologic effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in treatment-experienced (TE) and treatment-naïve (TN) people with HIV across 14 countries over 24 months. We present 12-month outcomes from participants in the BICSTaR Japan cohort. Retrospective and prospective data were pooled from people with HIV aged ≥20 years receiving B/F/TAF within routine clinical care in Japan. Outcomes included virologic effectiveness (primary endpoint; HIV-1 RNA <50 copies/mL), CD4 count, CD4/CD8 ratio, drug-related adverse events (DRAEs), persistence, and patient-reported outcomes (prospective TN cohort only). Overall, 200 participants were enrolled and included in the 12-month analysis population (150 retrospective, 50 prospective; 116 TN and 84 TE). Most participants were male at birth (99%); median age was 34 years in TN and 45 years in TE participants. At 12 months, virologic effectiveness was high: 92% (90/98) of TN and 95% (72/76) of TE participants had HIV-1 RNA <50 copies/mL (missing = excluded analysis). Median (quartile [Q]1, Q3) CD4 cell count increased by +202.0 (126.0, 311.0) cells/μL in TN (p<0.001) and +11.0 (−60.0, 87.0) cells/μL in TE (p = 0.380) participants. Through 12 months, DRAEs were reported by 13% (25/200) of all participants (16% [18/116] TN, 8% [7/84] TE); diarrhea, weight gain, and headache were the most common. Most DRAEs were mild in severity and no severe DRAEs were reported. One TN participant (<1%; 1/116) and two TE participants (2%; 2/84) discontinued B/F/TAF due to DRAEs (macrocytic anemia, vertigo, diarrhea, and headache). Treatment persistence at 12 months exceeded 98% in both TN and TE participants. In prospective TN participants, improvements in bothersome symptom count and quality-of-life measures were observed. B/F/TAF demonstrated high levels of virologic effectiveness and tolerability in people with HIV treated as part of routine clinical care in Japan. [ABSTRACT FROM AUTHOR]

Background: Primary healthcare providers play a critical role in diagnosing and managing digestive disorders. Standardized clinical care guidelines have been developed, but with limited and inconsistent implementation. An evidence-based gastroenterology clinical care pathway (GUTLINK) has been proposed in one region of Canada; however, little is known in the medical literature about potential barriers to pathway implementation within primary care. We aimed to identify behavioral and environmental barriers and facilitators to implementation of evidence-based care pathways for undifferentiated lower gastrointestinal tract symptoms in primary care. Methods: One-on-one semi-structured interviews were conducted with primary healthcare providers between September 2021 and May 2022. Interview script development was guided by the COM-B framework. Interviews were transcribed and data were analyzed using an inductive thematic analysis approach. Results: A total of 15 primary healthcare provider interviews were conducted. Several key barriers to GUTLINK implementation were identified in all three domains of the COM-B framework. Key barriers included Capability (e.g., Physician Knowledge and Access to Allied Health), Opportunity (e.g., Access to diagnostic tools), and Motivation (e.g., Comfort with managing cases and optimism). Some of these barriers have not previously been identified in medical literature. Conclusions: Evidence-based clinical care pathways have the potential to support access to quality gastroenterology care, yet primary healthcare providers in this study identified several barriers to implementation. Potential solutions exist at the individual and clinic levels (e.g., greater education, improved provider-specialist communication), but must be supported with systems-level changes (e.g., increased funding for gastrointestinal care and e-Health platforms) to support pathway implementation and improve quality of care. [ABSTRACT FROM AUTHOR]

Background: Arthritis seriously affects people's quality of life, and there is an urgent clinical need to improve the efficacy of medications as well as to reduce the adverse effects induced by treatment. Combined colchicine therapy is gradually being embraced in clinical care, but the evidence remains insufficient. Methods: English databases were searched from the establishment to September 4, 2024. Eleven eligible Randomized controlled trials (RCTs) were included. The quality of the literature was assessed by the risk of bias tool in the Cochrane Handbook. Relative risk (RR) and Cohen's d (SMD) were used for categorical and continuous variables, respectively, at 95% confidence interval (CI), and Stata 17.0 software was used for statistical analysis. Sensitivity analyses were used to verify the stability of the analyzed results, and heterogeneity analyses were used to explore the sources of heterogeneity in the studies. Funnel plots and Egger's test were used to assess publication bias. Results: Eleven eligible RCTs were included in this study. Compared with conventional treatment, combined colchicine treatment improved patient's global assessment results (SMD = 1.24, 95% CI [0.01, 2.47], P = 0.05, I2 = 0]), stiffness (SMD = -0.81, 95% CI [-1.43, -0.19], P = 0.01, I2 = 63.91%]) and did not increase adverse effects (RR = 0.79, 95% CI [0.31, 1.27], P = 0.36, I2 = 0.00%). However, combined colchicine treatment did not improve visual analog scores (VAS) (SMD = -0.96, 95% CI [-2.85, 0.93], P = 0.13, I2 = 97.99%]), Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain (SMD = 0.01, 95% CI [-0.24, 0.27], P = 0.91, I2 = 0]), WOMAC function (SMD = -0.01, 95% CI [-0.36, 0.16], P = 0.44, I2 = 0]), Total WOMAC scale (SMD = -0.05, 95% CI [-0.33, 0.22], P = 0.70, I2 = 0]), physician 's global assessment (SMD = 0.36, 95% CI [-2.27, 3.00], P = 0.79, I2 = 97.04%]) and Modified Clinical Health Assessment Questionnaire (ModHAD) (SMD = -1.72, 95% CI [-4.90,1.45], P = 0.29, I2 = 99.11%]). Conclusion: Compared with colchicine alone, combination therapy improves patients' quality of life without increasing the incidence of adverse events. [ABSTRACT FROM AUTHOR]

Complex liver cancer is often difficult to expose or dissect, and the surgery is often challenging. 3D-printed models may realistically present 3D anatomical structure, which has certain value in planning and training of liver surgery. However, the existing 3D-printed models are all monolithic models, which are difficult to reuse and limited in clinical application. It is also rare to carry fluorescence to accurately present tumor lesions. Here we report reusable fluorescent assembled 3D-printed models to mimic minimally invasive resection of complex liver cancer. Based on the models, multiple copies of liver lesion structure assembled accessories can be printed for the same patient or different patients, ensuring the quantity and quality of simulated surgical training, and greatly reducing the cost of simulated surgical training. The addition of fluorescence is helpful in accurately presenting tumor lesions. The reusable fluorescent assembled 3D-printed models may mimic minimally invasive resection of complex liver cancer, demonstrating potential value in simulated surgery. [ABSTRACT FROM AUTHOR]

Background: Guidelines for the management of cardiac arrest play a crucial role in guiding clinical decisions and care. We examined the strength and quality of evidence underlying these recommendations in order to elucidate strengths and gaps in knowledge. Methods: Using the 2020 American Heart Association (AHA) Guidelines for Adult CPR, we subdivided all recommendations into advanced life support (ALS), basic life support (BLS), and recovery after cardiac arrest, as well as a more granular categorization by topic (i.e. the intervention or evaluation recommended). The Class of Recommendation (COR) and Level of Evidence (LOE) for each were reviewed. Additionally, we reviewed the 2023 guidelines to ensure the inclusion of the most recent updates. Results: We noted 254 recommendations, of which 181 were ALS, 69 were BLS, and 4 were recovery after resuscitation. In total, only 2 (1%) had the most robust evidence (LOE A), while 23% were at LOE B-NR (Non-Randomized), 15% at LOE B-R (Randomized), 50% at LOE C-LD (Limited Data), and 12% relied on expert opinion LOE C-EO (Expert Opinion). Despite the strength of ALS recommendations (Class 1, 2a, or 2b), none had LOE A. In BLS, no recommendations were supported by LOE A. For BLS, 7% of recommendations had LOE C (C-LD or C-EO). The evidence for specific BLS topics, such as airway management, was notably low. Among ALS topics, neurological prognostication had relatively stronger evidence. Conclusions: Only 26 out of the 81 COR 1 recommendations (32%) were supported by LOE A or B, indicating a strong discrepancy between the strength of recommendation and the underlying evidence in cardiac arrest guidelines. The findings underscore a pressing need for more rigorous research, particularly randomized trials. [ABSTRACT FROM AUTHOR]

The removal of subgingival deposits, especially calculus, plays a crucial role in basic periodontal therapy. However, manual detection methods affect accuracy owing to the operator's skill. To avoid this uncertainty, we have developed a calculus detection device named "Sensor probe" and evaluated its ability to detect calculus for future clinical applications. The Sensor probe consisted of a 635 nm-wavelength semiconductor laser and a 0.5 mm-diameter single-mode optical fiber. Initially, the performance of the device was evaluated using clinically obtained extracted teeth with calculus covered with a stainless-steel shielding plate with pinhole. Then, the effect of the optical fiber's end shape on calculus detection performance was analyzed. Lastly, the performance of the Sensor probe was compared to that of a conventional periodontal probe in terms of accuracy, sensitivity, and specificity for calculus detection using calculus-covered extracted teeth. The results indicated that Sensor probe detected dental calculus through the pinhole with a diameter of 300 μm or more when applied from a distance of 100 μm. The results analyzing the effect of the optical fiber's end shape on calculus detection performance showed that cutting the fiber end at an angle of 45° resulted in the most effective calculus detection. This may be because the laser light refracted on the cut surface and concentrated on the fiber side. Moreover, by comparing the performance of this device to a conventional periodontal probe revealed that the Sensor probe showed improved calculus detection accuracy in deeper periodontal pockets. This improvement was particularly significant in the apical third, where detection is typically difficult. In conclusion, a Sensor probe that uses an optical fiber with a 45° angled end may facilitate subgingival calculus detection. In future clinical applications, Sensor probes could lead to more accurate and efficient calculus removal, especially for deeper periodontal pockets. [ABSTRACT FROM AUTHOR]

Advancement of AI has opened new possibility for accurate diagnosis and prognosis using digital histopathology slides which not only saves hours of expert effort but also makes the estimation more standardized and accurate. However, preserving the AI model performance on the external sites is an extremely challenging problem in the histopathology domain which is primarily due to the difference in data acquisition and/or sampling bias. Although, AI models can also learn spurious correlation, they provide unequal performance across validation population. While it is crucial to detect and remove the bias from the AI model before the clinical application, the cause of the bias is often unknown. We proposed a Causal Survival model that can reduce the effect of unknown bias by leveraging the causal reasoning framework. We use the model to predict recurrence-free survival for the colorectal cancer patients using quantitative histopathology features from seven geographically distributed sites and achieve equalized performance compared to the baseline traditional Cox Proportional Hazards and DeepSurvival model. Through ablation study, we demonstrated benefit of novel addition of latent probability adjustment and auxiliary losses. Although detection of cause of unknown bias is unsolved, we proposed a causal debiasing solution to reduce the bias and improve the AI model generalizibility on the histopathology domain across sites. Open-source codebase for the model training can be accessed from https://github.com/ramon349/fair_survival.git [ABSTRACT FROM AUTHOR]

Background: There is growing interest in the use of biofeedback-augmented gait training in cerebral palsy (CP). Audiovisual, sensorimotor, and immersive biofeedback paradigms are commonly used to elicit short-term gait improvements; however, outcomes remain variable. Because biofeedback training requires that individuals have the capacity to both adapt their gait in response to feedback and retain improvements across sessions, changes in either capacity may affect outcomes. Yet, neither has been explored extensively in CP. Methods: In this study, we evaluated the extent to which adolescents with CP (7M/1F; 14 years (12.5,15.26)) could adapt gait and retain improvements across four, 20-minute sessions using combined audiovisual and sensorimotor biofeedback. Both systems were designed to target plantarflexor activity. Audiovisual biofeedback displayed real-time soleus activity and sensorimotor biofeedback was provided using a bilateral resistive ankle exoskeleton. We quantified the time-course of change in muscle activity within and across sessions and overground walking function before and after the four sessions. Results: All individuals were able to significantly increase soleus activity from baseline using multimodal biofeedback (p < 0.031) but demonstrated heterogeneous adaptation strategies. In-session soleus adaptation had a moderate positive correlation with short-term retention of the adapted gait patterns (0.40 ≤ ρ ≤ 0.81), but generally weak correlations with baseline walking function (GMFCS Level) and motor control complexity (ρ ≤ 0.43). The latter indicates that adaptation capacity may be a critical and unique metric underlying response to biofeedback. Notably, in-session gains did not correspond to significant improvements in overground walking function (p > 0.11). Conclusions: This work suggests that individuals with CP have the capacity to adapt their gait using biofeedback, but responses are highly variable. Characterizing the factors driving adaptation to biofeedback may be a promising avenue to understand the heterogeneity of existing biofeedback training outcomes and inform future system optimization for integration into clinical care. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has significantly impacted advanced practice nurses' practice and posed great challenges in patient care delivery. Purpose: The aim of this study was to investigate the impact of the COVID-19 pandemic on the practice of advanced practice nurses in mainland China and Hong Kong Special Administrative Region (SAR). Methods A cross-sectional descriptive survey was conducted March 2021 and January 2022. Advanced practice nurses were invited to participate in an online survey. The questionnaire described the socio-demographic characteristics, the impact of the COVID-19 pandemic on advanced nursing practice, patient outcomes, education needs about COVID-19, and the challenges, support, and concerns related to the advanced practice nurse practice during the pandemic. Wilcoxon signed-rank test or McNemar test were applied to measure the practice of APNs before and during the COVID-19 pandemic. Results: Respondents (N = 336) were from mainland China (n = 234) and Hong Kong SAR (n = 102). Participants reported increased practice-related workload during the pandemic. The proportions of advanced practice nurses focused on disease prevention (36.9%) and psychosocial well-being (15.5%) for patient-focused outcomes during the pandemic were higher compared to before the pandemic. Key challenges and concerns during the pandemic included heavy workloads and health concerns for themselves and their families. Despite difficulties, there were reports of positive changes since the outbreak including implementation of innovative measures to facilitate the advanced practice nursing and education about COVID-19. Conclusion: The study findings highlight that advanced practice nurses' work and responsibilities have changed in response to the pandemic. Providing education about COVID-19, innovative measures to facilitate advanced practice nursing, and understanding advanced practice nurses' concerns and challenges in providing patient care may inform future developments for improving their professional practice. [ABSTRACT FROM AUTHOR]

Background: Associations between intraoperative hypotension (IOH) and various postoperative outcomes were shown in retrospective trials using a variety of different definitions of IOH. This complicates the comparability of these trials and makes clinical application difficult. Information about the best performing definitions of IOH regarding 30-day mortality, hospital length of stay (hLOS), and postanesthesia care unit length of stay (PACU-LOS) is missing. Methods: A retrospective cohort trial was conducted using data from patients undergoing noncardiothoracic surgery. We split the obtained dataset into two subsets. First, we used one subset to choose the best fitting definitions of IOH for the outcomes 30-day mortality, hLOS, and PACU-LOS. The other subset was used to independently assess the performance of the chosen definitions of IOH. Results: The final cohort consisted of 65,454 patients. In the shaping subset, nearly all tested definitions of IOH showed associations with the three outcomes, where the risk of adverse outcomes often increased continuously with decreasing MAP. The best fitting definitions were relative time with a MAP (mean arterial pressure) of <80 mmHg for 30-day mortality, lowest MAP for one minute for hLOS, and lowest MAP for one cumulative minute for PACU-LOS. Testing these three definitions of IOH in the independent second subset confirmed the associations of IOH with 30-day mortality, hLOS, and PACU-LOS. Conclusions: Using a data-driven approach, we identified the best fitting definitions of IOH for 30-day mortality, hLOS, and PACU-LOS. Our results demonstrate the need for careful selection of IOH definitions. Clinical trial number: n/a, EC #2245/2020 [ABSTRACT FROM AUTHOR]

Objective: This systematic review and meta-analysis aimed to evaluate the prevalence of frailty and pre-frailty in older adults with diabetes; and to identify the risk factors associated with frailty in this population. Design: Systematic review and meta-analysis. Participants: 24,332 people aged 60 years and older with diabetes. Methods: Six databases were searched (PubMed, Embase, the Cochrane Library, Web of Science, China Knowledge Resource Integrated Database, and Chinese Biomedical Database) up to 15 January 2024. Random effects models were used in instances of significant heterogeneity. Subgroup analysis and meta-regression were conducted to identify the potential source of heterogeneity. The Agency for Healthcare Research and Quality (AHRQ) and the Newcastle-Ottawa Scale (NOS) were applied to assess the quality of included studies. Results: 3,195 abstracts were screened, and 39 full-text studies were included. In 39 studies with 24,332 older people with diabetes, the pooled prevalence of frailty among older adults with diabetes was 30.0% (95% CI: 23.6%-36.7%). Among the twenty-one studies involving 7,922 older people with diabetes, the pooled prevalence of pre-frailty was 45.1% (95% CI: 38.5%-51.8%). The following risk factors were associated with frailty among older adults with diabetes: older age (OR = 1.08, 95% CI: 1.04–1.13, p<0.05), high HbA1c (OR = 2.14, 95% CI: 1.30–3.50, p<0.001), and less exercise (OR = 3.11, 95% CI: 1.36–7.12, p<0.001). Conclusions: This suggests that clinical care providers should be vigilant in identifying frailty and risk factors of frailty while screening for and intervening in older adults with diabetes. However, there are not enough studies to identify comprehensive risk factors of frailty in older adults with diabetes. Trial registration: PROSPERO registration number:CRD42023470933. [ABSTRACT FROM AUTHOR]

Recent breakthroughs in medical AI have proven the effectiveness of deep learning in fetal echocardiography. However, the limited processing power of edge devices hinders real-time clinical application. We aim to pioneer the future of intelligent echocardiography equipment by enabling real-time recognition and tracking in fetal echocardiography, ultimately assisting medical professionals in their practice. Our study presents the YOLOv5s_emn (Extremely Mini Network) Series, a collection of resource-efficient algorithms for fetal echocardiography detection. Built on the YOLOv5s architecture, these models, through backbone substitution, pruning, and inference optimization, while maintaining high accuracy, the models achieve a significant reduction in size and number of parameters, amounting to only 5%-19% of YOLOv5s. Tested on the NVIDIA Jetson Nano, the YOLOv5s_emn Series demonstrated superior inference speed, being 52.8–125.0 milliseconds per frame(ms/f) faster than YOLOv5s, showcasing their potential for efficient real-time detection in embedded systems. [ABSTRACT FROM AUTHOR]

Introduction: The Fragility Index (FI) and the FI family are statistical tools that measure the robustness of randomized controlled trials (RCT) by examining how many patients would need a different outcome to change the statistical significance of the main results of a trial. These tools have recently gained popularity in assessing the robustness or fragility of clinical trials in many clinical areas and analyzing the strength of the trial outcomes underpinning guideline recommendations. However, it has not been applied to perioperative care Clinical Practice Guidelines (CPG). Objectives: This study aims to survey clinical practice guidelines in anesthesiology to determine the Fragility Index of RCTs supporting the recommendations, and to explore trial characteristics associated with fragility. Methods and analysis: A methodological survey will be conducted using the targeted population of RCT referenced in the recommendations of the CPG of the North American and European societies from 2012 to 2022. FI will be assessed for statistically significant and non-significant trial results. A Poisson regression analysis will be used to explore factors associated with fragility. Discussion: This methodological survey aims to estimate the Fragility Index of RCTs supporting perioperative care guidelines published by North American and European societies of anesthesiology between 2012 and 2022. The results of this study will inform the methodological quality of RCTs included in perioperative care guidelines and identify areas for improvement. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the efficacy and safety of berberine(BBR) plus 5-aminosalicylic acid (5-ASA) for treating ulcerative colitis (UC). Methods: A comprehensive search was conducted in electronic databases, including Medline/PubMed, Sinomed, Embase, CNKI, Wanfang, and VIP, through January 2024 to identify all randomized controlled trials (RCTs) that administered BBR conjunction in standard therapy(5-ASA) for to support the treatment of UC. The data were synthesized using a meta-analysis approach with RevMan 5.4.1. The primary endpoint was the clinical efficacy rate. In contrast, the secondary endpoints included the Baron score, disease activity index (DAI) score, symptom relief latency, inflammatory markers, immunological indicators, and adverse events. Results: In this analysis, 10 RCTs comprising 952 patients with UC were examined. BBR considerably improved the clinical efficacy rate (RR = 1.22, 95% CI [1.15, 1.30], P < 0.00001), attenuated the Baron score (SMD = -1.72, 95% CI [-2.30, -1.13], P < 0.00001) and reduced the DAI score (SMD = -2.93, 95% CI [-4.42, -1.43], P < 0.00001). Additionally, it ameliorated clinical symptoms (SMD = -2.74, 95% CI [-3.45, 2.02], P < 0.00001), diminished inflammatory responses (SMD = -1.59, 95% CI [-2.14, 1.04], P < 0.00001), and modulated immune reactions (SMD = 1.06,95% CI [0.24,1.87], P <0.00001). Nonetheless, the impact of BBR on reducing adverse reactions was not statistically significant (RR = 0.75, 95% CI [0.42, 1.33], P > 0.05). Conclusion: BBR demonstrates substantial efficacy in treating UC without causing severe adverse reactions and may serve as a viable complementary therapy. However, its clinical application warrants confirmation by additional high-quality, low-bias RCTs. [ABSTRACT FROM AUTHOR]

CD19-targeted chimeric antigen receptor (CAR) T cell therapies have driven a paradigm shift in the treatment of relapsed/refractory B-cell malignancies. However, >50% of CD19-CAR-T-treated patients experience progressive disease mainly due to antigen escape and low persistence. Clinical prognosis is heavily influenced by CAR-T cell function and systemic cytokine toxicities. Furthermore, it remains a challenge to efficiently, cost-effectively, and consistently manufacture clinically relevant numbers of virally engineered CAR-T cells. Using a highly efficient piggyBac transposon-based vector, Quantum pBac™ (qPB), we developed a virus-free cell-engineering system for development and production of multiplex CAR-T therapies. Here, we demonstrate in vitro and in vivo that consistent, robust and functional CD20/CD19 dual-targeted CAR-T stem cell memory (CAR-TSCM) cells can be efficiently produced for clinical application using qPB™. In particular, we showed that qPB™-manufactured CAR-T cells from cancer patients expanded efficiently, rapidly eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug. Therefore, the simplicity of manufacturing multiplex CAR-T cells using the qPB™ system has the potential to improve efficacy and broaden the accessibility of CAR-T therapies. [ABSTRACT FROM AUTHOR]

Rare cancers are defined by low incidence rates, and may lack evidence that supports uniform standards of care and relevant clinical guidelines. Rare cancers may represent up to 24% of all cancers, yet remain understudied and underappreciated in terms of their clinical and ultimately societal impact. The PLOS Rare Cancer Collection brings together a broad range of research endeavors that are being undertaken in rare cancers research ranging from basic biological evaluations to therapeutic drug development. This Overview presents a brief background to the Collection and highlights the contributions of included articles. [ABSTRACT FROM AUTHOR]

Low-Dose computer tomography (LDCT) is an ideal alternative to reduce radiation risk in clinical applications. Although supervised-deep-learning-based reconstruction methods have demonstrated superior performance compared to conventional model-driven reconstruction algorithms, they require collecting massive pairs of low-dose and norm-dose CT images for neural network training, which limits their practical application in LDCT imaging. In this paper, we propose an unsupervised and training data-free learning reconstruction method for LDCT imaging that avoids the requirement for training data. The proposed method is a post-processing technique that aims to enhance the initial low-quality reconstruction results, and it reconstructs the high-quality images by neural work training that minimizes the ℓ1-norm distance between the CT measurements and their corresponding simulated sinogram data, as well as the total variation (TV) value of the reconstructed image. Moreover, the proposed method does not require to set the weights for both the data fidelity term and the plenty term. Experimental results on the AAPM challenge data and LoDoPab-CT data demonstrate that the proposed method is able to effectively suppress the noise and preserve the tiny structures. Also, these results demonstrate the rapid convergence and low computational cost of the proposed method. The source code is available at https://github.com/linfengyu77/IRLDCT. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NGS) has been increasingly popular in genomics studies over the last decade and is now commonly used in clinical applications for precision diagnostics. Many disease areas typically involve different kinds of sample specimens, sample qualities and quantities. The quality of the DNA can range from intact, high molecular weight molecules to degraded, damaged and very short molecules. The differences in quality and quantity pose challenges for downstream molecular analyses. To overcome the challenge with the need of different molecular methods for different types of samples, we have developed a joint procedure for preparing enriched DNA libraries from high molecular weight DNA and DNA from formalin-fixed, paraffin-embedded tissue, fresh frozen tissue material, as well as cell-free DNA. [ABSTRACT FROM AUTHOR]

We introduce a new approach for automated guideline-based-care quality assessment, the bidirectional knowledge-based assessment of compliance (BiKBAC) method, and the DiscovErr system, which implements it. Our methodology compares the guideline's Asbru-based formal representation, including its intentions, with the longitudinal medical record, using a top-down and bottom-up approach. Partial matches are resolved using fuzzy temporal logic. The system was evaluated in the type 2 Diabetes management domain, comparing it to three expert clinicians, including two diabetes experts. The system and the experts commented on the management of 10 patients, randomly selected from 2,000 diabetes patients. On average, each record spanned 5.23 years; the data included 1,584 medical transactions. The system provided 279 comments. The experts made 181 different unique comments. The completeness (recall) of the system was 91% when the gold standard was comments made by at least two of the three experts, and 98%, compared to comments made by all three experts. The experts also assessed all of the 114 medication-therapy-related comments, and a random 35% of the 165 tests-and-monitoring-related comments. The system's correctness (precision) was 81%, compared to comments judged as correct by both diabetes experts, and 91%, compared to comments judged as correct by one diabetes expert and at least as partially correct by the other. 89% of the comments were judged as important by both diabetes experts, 8% were judged as important by one expert, and 3% were judged as less important by both experts. Adding the validated system comments to the experts' comments, the completeness scores of the experts were 75%, 60%, and 55%; the expert correctness scores were respectively 99%, 91%, and 88%. Thus, the system could be ranked first in completeness and second in correctness. We conclude that systems such as DiscovErr can effectively assess the quality of continuous guideline-based care. [ABSTRACT FROM AUTHOR]

Probabilistic hesitant fuzzy sets (PHFSs) are superior to hesitant fuzzy sets (HFSs) in avoiding the problem of preference information loss among decision makers (DMs). Owing to this benefit, PHFSs have been extensively investigated. In probabilistic hesitant fuzzy environments, the correlation coefficients have become a focal point of research. As research progresses, we discovered that there are still a few unresolved issues concerning the correlation coefficients of PHFSs. To overcome the limitations of existing correlation coefficients for PHFSs, we propose new correlation coefficients in this study. In addition, we present a multi-criteria group decision-making (MCGDM) method under unknown weights based on the newly proposed correlation coefficients. In addition, considering the limitations of DMs' propensity to use language variables for expression in the evaluation process, we propose a method for transforming the evaluation information of the DMs' linguistic variables into probabilistic hesitant fuzzy information in the newly proposed MCGDM method. To demonstrate the applicability of the proposed correlation coefficients and MCGDM method, we applied them to a comprehensive clinical evaluation of orphan drugs. Finally, the reliability, feasibility and efficacy of the newly proposed correlation coefficients and MCGDM method were validated. [ABSTRACT FROM AUTHOR]

Contrary to North America and Europe, the prevalence of hypertension is rising in West Africa. With a transition from whole foods to processed foods in Nigeria, diet plays a key driver of hypertension. To combat this, the national nutritional guidelines in Nigeria were implemented, but their translation into actionable tools for clinicians remains a challenge. Currently, there are no simple dietary assessment tools that are concise and suitable to be incorporated into clinical care without requiring extensive data analysis while still providing personalised dietary support to their patients. This study aims to deliver a clinically tested and validated short dietary assessment tool for clinicians, patients, and researchers across Nigeria to provide personalised dietary advice for patients with hypertension. The study will be conducted in two phases: Phase 1 (n = 75) will investigate the feasibility of the short FFQ and its agreement with 24-hour dietary recalls (3x) in a clinical setting in Nigeria. During the analysis of Phase 1 data, a scoring system will be developed based on the associations between individual food items in the FFQ and measures of hypertension. Phase 2 (n = 50) will assess the acceptability of the FFQ and validate the association between the FFQ score and hypertension. Expected outcomes: The development of a clinically tested and validated short food frequency questionnaire that will be ready to use by clinicians, patients, and researchers across Nigeria to support the prevention and management of hypertension. This study will contribute to knowledge on dietary assessment and hypertension prevention by developing a validated and acceptable FFQ, which will be valuable for clinicians and researchers for personalised dietary recommendations to combat hypertension in Nigeria. [ABSTRACT FROM AUTHOR]

Background: ChatGPT is a large language model designed to generate responses based on a contextual understanding of user queries and requests. This study utilised the entrance examination for the Master of Clinical Medicine in Traditional Chinese Medicine to assesses the reliability and practicality of ChatGPT within the domain of medical education. Methods: We selected 330 single and multiple-choice questions from the 2021 and 2022 Chinese Master of Clinical Medicine comprehensive examinations, which did not include any images or tables. To ensure the test's accuracy and authenticity, we preserved the original format of the query and alternative test texts, without any modifications or explanations. Results: Both ChatGPT3.5 and GPT-4 attained average scores surpassing the admission threshold. Noteworthy is that ChatGPT achieved the highest score in the Medical Humanities section, boasting a correct rate of 93.75%. However, it is worth noting that ChatGPT3.5 exhibited the lowest accuracy percentage of 37.5% in the Pathology division, while GPT-4 also displayed a relatively lower correctness percentage of 60.23% in the Biochemistry section. An analysis of sub-questions revealed that ChatGPT demonstrates superior performance in handling single-choice questions but performs poorly in multiple-choice questions. Conclusion: ChatGPT exhibits a degree of medical knowledge and the capacity to aid in diagnosing and treating diseases. Nevertheless, enhancements are warranted to address its accuracy and reliability limitations. Imperatively, rigorous evaluation and oversight must accompany its utilization, accompanied by proactive measures to surmount prevailing constraints. [ABSTRACT FROM AUTHOR]

This ex vivo study aimed to investigate surface roughness and substance loss after treatment with different professional cleaning methods and to determine whether subsequent polishing with a rubber cup and polishing paste is necessary. Samples (flat and natural surfaces) of human enamel and dentin were prepared (baseline) and treated with either a curette, air-polishing with erythritol, a rubber cup and polishing paste, or a combination thereof (treatment). Subsequently, all samples were immersed in an ultrasonic bath (ultrasonic) to remove residues from the treatment procedures. The surface roughness values sRa and sRz as well as tissue loss were measured profilometrically. Linear regression models were used to compare group differences (roughness and loss) considering the corresponding baseline value. The significance level was set at p<0.05. sRa increased significantly after treatment with curettes or air-polishing with erythritol in both enamel (p<0.001) and dentin (p<0.001) of flat samples. The same effect was observed for sRz in dentin (p<0.001) but not for enamel compared to negative control. Polishing with a rubber cup and paste alone had no significant effect on roughness values. When combined with other treatments, the effect of curette or air-polishing with erythritol dominated the effect. In enamel, none of the tested methods led to measurable tissue loss. In dentin, air-polishing with erythritol caused ≤50% tissue loss compared to the curette. Conclusively, for enamel, treatment effects on roughness were measurable but of limited clinical relevance. For dentin, air-polishing resulted in a smaller but insignificant roughness increase and less tissue loss compared to the curette. Polishing with a rubber cup and paste did not affect surface roughness. Regarding the clinical application, the use of air-polishing seems to be a less invasive procedure than using a curette; polishing with rubber cup and paste offers no advantage in terms of reducing roughness as a final procedure. [ABSTRACT FROM AUTHOR]

Due to the unnecessary immune responses induced by therapeutic antibodies in clinical applications, immunogenicity is an important factor to be considered in the development of antibody therapeutics. To a certain extent, there is a lag in using wet-lab experiments to test the immunogenicity in the development process of antibody therapeutics. Developing a computational method to predict the immunogenicity at once the antibody sequence is designed, is of great significance for the screening in the early stage and reducing the risk of antibody therapeutics development. In this study, a computational immunogenicity prediction method was proposed on the basis of AntiBERTy-based features of amino sequences in the antibody variable region. The AntiBERTy-based sequence features were first calculated using the AntiBERTy pre-trained model. Principal component analysis (PCA) was then applied to reduce the extracted feature to two dimensions to obtain the final features. AutoGluon was then used to train multiple machine learning models and the best one, the weighted ensemble model, was obtained through 5-fold cross-validation on the collected data. The data contains 199 commercial therapeutic antibodies, of which 177 samples were used for model training and 5-fold cross-validation, and the remaining 22 samples were used as an independent test dataset to evaluate the performance of the constructed model and compare it with other prediction methods. Test results show that the proposed method outperforms the comparison method with 0.7273 accuracy on the independent test dataset, which is 9.09% higher than the comparison method. The corresponding web server is available through the official website of GenScript Co., Ltd., https://www.genscript.com/tools/antibody-immunogenicity. [ABSTRACT FROM AUTHOR]

Quantifying neutralising capacity of circulating SARS-COV-2 antibodies is critical in evaluating protective humoral immune responses generated post-infection/post-vaccination. Here we describe a novel medium-throughput flow cytometry-based micro-neutralisation test to evaluate Neutralising Antibody (NAb) responses against live SARS-CoV-2 Wild Type and Variants of Concern (VOC) in convalescent/vaccinated populations. Flow Cytometry-Based Micro-Neutralisation Test (Micro-NT) was performed in 96-well plates using clinical isolates WT-B, WT-B.1.177.18 and/or VOCs Beta and Omicron. Plasma samples (All Ireland Infectious Diseases (AIID) Cohort) were serially diluted (8 points, half-log) from 1:20 and pre-incubated with SARS-CoV-2 (1h, 37°C). Virus-plasma mixture were added onto Vero E6 or Vero E6/TMPRSS2 cells for 18h. Percentage infected cells was analysed by automated flow cytometry following trypsinisation, fixation and SARS-CoV-2 Nucleoprotein intracellular staining. Half-maximal Neutralisation Titres (NT50) were determined using non-linear regression. Our assay was compared to Plaque Reduction Neutralisation Test (PRNT) and validated against the First WHO International Standard for anti-SARS-CoV-2 immunoglobulin. Both Micro-NT and PRNT achieved comparable NT50 values. Further validation showed adequate correlation with PRNT using a panel of secondary standards of clinical convalescent and vaccinated plasma samples. We found the assay to be reproducible through measuring both repeatability and intermediate precision. Screening 190 convalescent samples and 11 COVID-19 naive controls (AIID cohort) we demonstrated that Micro-NT has broad dynamic range differentiating NT50s <1/20 to >1/5000. We could also characterise immune-escape VOC Beta and Omicron BA.5, achieving fold-reductions in neutralising capacity similar to those published. Our flow cytometry-based Micro-NT is a robust and reliable assay to quantify NAb titres, and has been selected as an endpoint in clinical trials. [ABSTRACT FROM AUTHOR]

One hypothesis flowing from the network theory of psychopathology is that symptom network structure is associated with psychopathology severity and in turn, one may expect that individual network structure changes with the level of psychopathology severity. However, this expectation has rarely been addressed directly. This study aims to examine (1) the stability of individual contemporaneous symptom networks over a one-year period and (2) whether network stability is associated with a change in psychopathology. We used daily diary data of n = 66 individuals, located along the psychosis severity continuum, from two separate 90-day periods, one year apart (t = 180). Based on the newly developed Individual Network Invariance Test (INIT) to assess symptom-network stability, participants were divided into two groups with stable and unstable networks and we tested whether these groups differed in their absolute change in psychopathology severity. The majority of the sample (n = 51, 77.3%) showed a stable network over time while most individuals showed a decrease in psychopathological severity. We found no significant association between a change in psychopathology severity and individual network stability. Our results call for further critical evaluation of the association between networks and psychopathology to optimize the implementation of clinical applications based on current methods. [ABSTRACT FROM AUTHOR]

Background and aim: Hospitalization often leads to changes in patients' medicine which challenges a safe medication use after discharge. Medicine information helplines (MIHs) can be valuable for patients in overcoming these challenges. This study evaluates patient satisfaction with a newly established Danish hospital-based MIH for discharged patients. The MIH is operated by experienced pharmacists and a pharmacy technician, and the study explores how the service affects the patient's concerns and perception of safety in relation to their medication, followed by an assessment of the clinical impact of MIH on patient safety. Method: A randomized controlled study design was used in the present study. The study was registered at clinicaltrials.gov with the identification number NCT03829995. Participants were randomized 1:4 (50:200) into a control- and intervention group. Participants in the control group were offered standard care and those in the intervention group were offered access to the MIH. A telephone interview performed 2–4 weeks after discharge assessed patient satisfaction with the helpline and patient's feeling of safety in relation to medicine use (primary outcome). Data were analyzed using a Mann-Whitney U test. After case handling of each enquiry to the MIH, the cases were assessed with regard to medication-related problems (MRPs) and clinical impact of the MIH service was assessed (primary outcome). Results: A total of 250 participants were included in the study and 152 participated in the telephone interviews (33 control and 119 intervention). Thirty-seven questions were enquired by 26 participants to the MIH. Of these, 8 were requested before the telephone interviews and these patients all expressed a high satisfaction with the MIH (score 4.57 +/- 0.73 on a 5-point scale). Most patients offered access to the MIH expressed that it increased the sense of safety in relation to their medicines (79%). However, comparing the control- and intervention group with regard to patient concerns and feeling of safety in relation to medicine use no differences were found. Evaluation of the enquiries revealed at least one MRP per enquiry, and in most cases the advice given were assessed to have a high- or moderate clinical significance. Conclusion: The MIH was appreciated by the participants, indicating that the MIH could be a valuable service for discharged patients in improving the sense of safety in relation to medication and alleviating MRPs. Providing easy access for patients to medicine information may contribute to patient safe medicine use after discharge. [ABSTRACT FROM AUTHOR]

Background: Clinical collaboration between spine professionals in high-income countries (HICs) and low-and-middle-income countries (LMICs) may provide improvements in the accessibility, efficacy, and safety of global spine care. Currently, the scope and effectiveness of these collaborations remain unclear. In this review, we describe the literature on the current state of these partnerships to provide a framework for exploring future best practices. Methods: PubMed, Embase, and Cochrane Library were queried for articles on spine-based clinical partnerships between HICs and LMICs published between 2000 and March 10, 2023. This search yielded 1528 total publications. After systematic screening, nineteen articles were included in the final review. Results: All published partnerships involved direct clinical care and 13/19 included clinical training of local providers. Most of the published collaborations reviewed involved one of four major global outreach organizations with the majority of sites in Africa. Participants were primarily physicians and physicians-in-training. Only 5/19 studies reported needs assessments prior to starting their partnerships. Articles were split on evaluative focus, with some only evaluating clinical outcomes and some evaluating the nature of the partnership itself. Conclusions: Published studies on spine-focused clinical partnerships between HICs and LMICs remain scarce. Those that are published often do not report needs assessments and formal metrics to evaluate the efficacy of such partnerships. Toward improving the quality of spine care globally, we recommend an increase in the quality and quantity of published studies involving clinical collaborations between HICs and LICs, with careful attention to reporting early needs assessments and evaluation strategies. [ABSTRACT FROM AUTHOR]

An aneurysm is a pathological widening of a blood vessel. Aneurysms of the aorta are often asymptomatic until they rupture, killing approximately 10,000 Americans per year. Fortunately, rupture can be prevented through early detection and surgical repair. However, surgical risk outweighs rupture risk for small aortic aneurysms, necessitating a policy of surveillance. Understanding the growth rate of aneurysms is essential for determining appropriate surveillance windows. Further, identifying risk factors for fast growth can help identify potential interventions. However, studies in the literature have applied many different methods for defining the growth rate of abdominal aortic aneurysms. It is unclear which of these methods is most accurate and clinically meaningful, and whether these heterogeneous methodologies may have contributed to the varied results reported in the literature. To help future researchers best plan their studies and to help clinicians interpret existing studies, we compared five different models of aneurysmal growth rate. We examined their noise tolerance, temporal bias, predictive accuracy, and statistical power to detect risk factors. We found that hierarchical mixed effects models were more noise tolerant than traditional, unpooled models. We also found that linear models were sensitive to temporal bias, assigning lower growth rates to aneurysms that were detected earlier in their course. Our exponential mixed model was noise-tolerant, resistant to temporal bias, and detected the greatest number of clinical risk factors. We conclude that exponential mixed models may be optimal for large studies. Because our results suggest that choice of method can materially impact a study's findings, we recommend that future studies clearly state the method used and demonstrate its appropriateness. [ABSTRACT FROM AUTHOR]

Introduction: There has been global investment of new ways of working to support workforce pressures, including investment in clinical pharmacists working in primary care by the NHS in the England. Clinical pharmacists are well suited to support older adults who have multiple long-term conditions and are on multiple medications. It is important to establish an evidence base for the role of clinical pharmacists in supporting older adults in primary care, to inform strategic and research priorities. The aim of this scoping review is to identify, map and describe existing research and policy/guidance on the role of clinical pharmacists in primary care supporting older adults, and the models of care they provide. Methods and analysis: A scoping review guided by the Joanne Briggs Institute methodology for scoping reviews, using a three-step strategy. We will search Medline, CINAHL, Scopus, EMBASE, Web of Science, PSYCHInfo, and Cochrane for English language articles, from 2015 –present day. Grey literature will be searched using Grey Matters guidelines, the Index of Grey Literature and Alternative Sources and Resources, and Google keyword searching. References of all included sources will be hand searched to identify further resources. Using the Population, Concept and Context framework for inclusion and exclusion criteria, articles will be independently screened by two reviewers. The inclusion and exclusion criteria will be refined after we become familiar with the search results, following the iterative nature of a scoping review. Data will be extracted using a data extraction tool using Microsoft Excel and presented using a narrative synthesis approach. Ethics and dissemination: Ethical approval is not required for this review. Review findings will be disseminated in academic conferences and used to inform subsequent qualitative research. Findings will be published and shared with relevant local and national organisations. [ABSTRACT FROM AUTHOR]

Objective: Validate the performance characteristics of two analyte specific, laboratory developed tests (LDTs) for the quantification of SARS-CoV-2 subgenomic RNA (sgRNA) and viral load on the Hologic Panther Fusion® using the Open Access functionality. Methods: Custom-designed primers/probe sets targeting the SARS-CoV-2 Envelope gene (E) and subgenomic E were optimized. A 20-day performance validation following laboratory developed test requirements was conducted to assess assay precision, accuracy, analytical sensitivity/specificity, lower limit of detection and reportable range. Results: Quantitative SARS-CoV-2 sgRNA (LDT-Quant sgRNA) assay, which measures intermediates of replication, and viral load (LDT-Quant VLCoV) assay demonstrated acceptable performance. Both assays were linear with an R2 and slope equal to 0.99 and 1.00, respectively. Assay precision was evaluated between 4–6 Log10 with a maximum CV of 2.6% and 2.5% for LDT-Quant sgRNA and LDT-Quant VLCoV respectively. Using negative or positive SARS-CoV-2 human nasopharyngeal swab samples, both assays were accurate (kappa coefficient of 1.00 and 0.92). Common respiratory flora and other viral pathogens were not detected and did not interfere with the detection or quantification by either assay. Based on 95% detection, the assay LLODs were 729 and 1206 Copies/mL for the sgRNA and VL load LDTs, respectively. Conclusion: The LDT-Quant sgRNA and LDT-Quant VLCoV demonstrated good analytical performance. These assays could be further investigated as alternative monitoring assays for viral replication; and thus, medical management in clinical settings which could inform isolation/quarantine requirements. [ABSTRACT FROM AUTHOR]

Background: The largest nationally integrated health system in the United States, the Veterans Health Administration (VHA), has been undergoing a transformation toward a Whole Health (WH) System of Care. WH Clinical Care, a component of this system, includes holistically assessing the Veteran's life context, identifying what really matters to the Veteran, collaboratively setting and monitoring personal health and well-being goals, and equipping the Veteran with access to conventional and complementary and integrative health resources. Implementation of WH Clinical Care has been challenging. Understanding healthcare professionals' perspectives on the value of and barriers and facilitators to practicing WH Clinical Care holds relevance for not only VHA's efforts but also other health systems, in the U.S. and internationally, that are engaged in person-centered care implementation. Objectives: We sought to understand perspectives of healthcare professionals at VHA on providing WH Clinical Care to Veterans with COPD, as a lens to understand the broader issue of WH Clinical Care for Veterans living with complex chronic conditions. Design: We interviewed 25 healthcare professionals across disciplines and services at a VA Medical Center in 2020–2021, including primary care providers, pulmonologists, palliative care providers, and chaplains. Interview transcripts were analyzed using qualitative content analysis. Key results: Each element of WH Clinical Care raised complex questions and/or concerns, including: (1) the appropriate depth/breadth of inquiry in person-centered assessment; (2) the rationale for elicitation of what really matters; (3) the feasibility and appropriate division of labor in personal health goal setting and planning; and (4) challenges related to referring Veterans to a broad spectrum of supportive services. Conclusions: Efforts to promote person-centered care must account for healthcare professionals' existing comfort with its elements, advocate for a team-based approach, and continue to grapple with the conflicting structural conditions and organizational imperatives. [ABSTRACT FROM AUTHOR]

Background: The use of medications during pregnancy is a common event worldwide. Monitoring medicine prescriptions in clinical practice is a necessary step in assessing the impact of therapeutic choices in pregnant women as well as the adherence to clinical guidelines. The aim of this study was to provide prevalence data on medication use before, during and after pregnancy in the Italian population. Methods: A retrospective prevalence study using administrative healthcare databases was conducted. A cohort of 449,012 pregnant women (15–49 years) residing in eight Italian regions (59% of national population), who delivered in 2016–2018, were enrolled. The prevalence of medication use was estimated as the proportion (%) of pregnant women with any prescription. Results: About 73.1% of enrolled women received at least one drug prescription during pregnancy, 57.1% in pre-pregnancy and 59.3% in postpartum period. The prevalence of drug prescriptions increased with maternal age, especially during the 1st trimester of pregnancy. The most prescribed medicine was folic acid (34.6%), followed by progesterone (19%), both concentrated in 1st trimester of pregnancy (29.2% and 14.8%, respectively). Eight of the top 30 most prescribed medications were antibiotics, whose prevalence was higher during 2nd trimester of pregnancy in women ≥ 40 years (21.6%). An increase in prescriptions of anti-hypertensives, antidiabetics, thyroid hormone and heparin preparations was observed during pregnancy; on the contrary, a decrease was found for chronic therapies, such as anti-epileptics or lipid-modifying agents. Conclusions: This study represents the largest and most representative population-based study illustrating the medication prescription patterns before, during and after pregnancy in Italy. The observed prescriptive trends were comparable to those reported in other European countries. Given the limited information on medication use in Italian pregnant women, the performed analyses provide an updated overview of drug prescribing in this population, which can help to identify critical aspects in clinical practice and to improve the medical care of pregnant and childbearing women in Italy. [ABSTRACT FROM AUTHOR]

Objective: Numerous randomized controlled trials (RCTs) demonstrate the efficacy of cognitive behavioral therapy (CBT), metacognitive therapy (MCT), and methods to reduce intolerance of uncertainty (IU-CBT) in the treatment of generalized anxiety disorder (GAD). However, few studies have investigated these treatments under conditions of routine clinical care. The main objective of this study was to investigate the effectiveness of psychotherapy for GAD in an outpatient setting and to identify factors influencing treatment outcome. Methods: Fifty-nine GAD patients received naturalistic CBT (including MCT and IU-CBT) in an outpatient clinic and postgraduate training center for psychotherapy. Patients completed self-report questionnaires at the beginning and end of therapy regarding the main outcome worry as well as metacognitions, intolerance of uncertainty, depression, and general psychopathology. Results: Worry, negative metacognitions, intolerance of uncertainty, depression, and general psychopathology decreased significantly (p's <.001) with large effect sizes for all symptoms (d = 0.83–1.49). A reliable change in the main outcome worry was observed in 80% of patients, and recovery occurred in 23%. Higher worry scores at posttreatment were predicted by higher pretreatment scores, female sex, and less change in negative metacognitive beliefs during treatment. Conclusions: Naturalistic CBT for GAD appears to be effective in routine clinical care for worry as well as depressive symptoms, with particular benefits associated with altering negative metacognitions. However, a recovery rate of only 23% is lower than the rates reported in RCTs. Treatment needs to be improved, especially for patients with more severe GAD and for women. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the perceptions of third-year dental students regarding the application of ergonomic principles in the transition between preclinical and clinical training in Restorative Dentistry. Methods: We conducted a qualitative observational cross-sectional study. The sample consisted of forty-six third-year dental students at São Paulo State University (Unesp), School of Dentistry, Araraquara. Data was collected using an individual interview recorded on a digital voice recorder. A script containing questions related to the process of adaptation of students to clinical care with a view to ergonomic work posture was used. Data analysis was based on the quali-quantitative technique of Discourse of the Collective Subject (DCS), using Qualiquantisoft®. Results: Most students (97.80%) perceived the need for an adaptation period in the transition from the preclinic to the clinic regarding ergonomic posture requirements; a part of them (45.65%) claimed that they still could not adapt, primarily due to the difference between the laboratory and clinic in the workstation (50.00%). Some students suggested longer preclinical training in a clinical environment to facilitate this transition (21.74%). The dental stool (32.60%) and the dental chair (21.74%) were the external factors that contributed most to making this transition difficult. The difficulty of the restorative dentistry procedure (10.87%) also interfered with posture. Additionally, the most challenging ergonomic posture requirements in the transition period were maintaining 30 to 40 cm between the patient's mouth and operator's eyes (45.65%), positioning the patient in the dental chair correctly (15.22%), and working with the elbows close to the body (15.22%). Conclusion: Most students perceived the need for an adaptation period in the preclinical transition to the clinic, attributing difficulties to adopt the ergonomic posture requirements, to use the workstation and to perform the procedures on real patients. [ABSTRACT FROM AUTHOR]

Background: Since the emergence of the anti-PLA2R antibody (PLA2R-Ab) test, nephrology practice has not changed dramatically, with most nephrologists still relying on a kidney biopsy to diagnose membranous nephropathy. In this study, we examined the clinical accuracy of the anti-PLA2R antibody test using ELISA in routine clinical care. Methods: We conducted a retrospective analysis of PLA2R-Ab testing in 187 consecutive patients seen at a single UK centre between 2003 and 2020. We compared the kidney biopsy findings with the PLA2R-ab antibody test. Patients' demography, urine protein creatinine ratios, serum albumin, and treatment characteristics including supportive and immunosuppressive treatment were recorded. The clinical accuracy of the test (e.g. sensitivity and specificity, positive [PPV] and negative [NPV] predictive values) was calculated using the kidney biopsy findings as the diagnostic reference. Results: Mean levels of PLA2R-Ab titre in primary membranous nephropathy were 217RU/ml in comparison to 3RU/ml for both secondary membranous nephropathy and other diagnoses. Most patients with a positive PLA2R-Ab test had a confirmed renal biopsy diagnosis of primary membranous nephropathy with: PPV of 97.3%, sensitivity 75.5%, NPV was 79.8% and specificity was 97.8% at a cut-off threshold of >20 RU/ml. Conclusion: The anti-PLA2R antibody test is a highly specific test for diagnosing membranous nephropathy, and the test has the potential to allow for the diagnosis and treatment in up to 75% of PMN cases without the need for a renal biopsy. Nevertheless, patients with negative PLA2R-Ab tests will still require a biopsy to confirm their diagnosis. [ABSTRACT FROM AUTHOR]

Background: Patient and public involvement (PPI) has growing impact on the design of clinical care and research studies. There remains underreporting of formal PPI events including views related to using digital tools. This study aimed to assess the feasibility of hosting a hybrid PPI event to gather views on the use of digital tools in clinical care and research. Methods: A PPI focus day was held following local procedures and published recommendations related to advertisement, communication and delivery. Two exemplar projects were used as the basis for discussions and qualitative and quantitative data was collected. Results: 32 individuals expressed interest in the PPI day and 9 were selected to attend. 3 participated in person and 6 via an online video-calling platform. Selected written and verbal feedback was collected on two digitally themed projects and on the event itself. The overall quality and interactivity for the event was rated as 4/5 for those who attended in person and 4.5/5 and 4.8/5 respectively, for those who attended remotely. Conclusions: A hybrid PPI event is feasible and offers a flexible format to capture the views of patients. The overall enthusiasm for digital tools amongst patients in routine care and clinical research is high, though further work and standardised, systematic reporting of PPI events is required. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis is a chronic pruritic inflammatory skin disease commonly occurring in children. The objective of this study is to evaluate the treatment of pediatric atopic dermatitis with biologics, as they have displayed immense promising results in several recent clinical trials on atopic dermatitis (AD). Methods: We will conduct an extensive search for RCTs in several databases, including Embase, Cochrane Library, Web of Science, and PubMed, from the inception of the study till 15th May 2022. The primary outcomes will be the proportion of patients with EASI 75/90/100 after 12–16 weeks of treatment. The secondary outcomes will include the Numerical Rating Scale (NRS), Investigator Global Assessment (IGA)0–1, body surface area (BSA), Dermatology Life Quality Index (DLQI) scores, and incidence of adverse reactions. All studies will be screened by two independent researchers. They will assess the risk of bias in the included studies according to the RCTs bias risk evaluation tool in Cochrane System Review Manual 5.1.0. Meta-analysis will be performed using RevMan V.5.3.0 software. Results: The research results will provide a reference for the clinical application of biological agents in pediatric atopic dermatitis. Conclusion: We aim to evaluate the efficacy and safety of biologics in pediatric atopic dermatitis cases and provide evidence-based data for easy clinical application. PROSPERO registration number: CRD42022319052 (https://www.crd.york.ac.uk/PROSPERO/#joinuppage). [ABSTRACT FROM AUTHOR]

Following a huge global effort, the first World Health Organization (WHO)-endorsed catalogue of 17,356 variants in the Mycobacterium tuberculosis complex along with their classification as associated with resistance (interim), not associated with resistance (interim) or uncertain significance was made public In June 2021. This marks a critical step towards the application of next generation sequencing (NGS) data for clinical care. Unfortunately, the variant format used makes it difficult to look up variants when NGS data is generated by other bioinformatics pipelines. Furthermore, the large number of variants of uncertain significance in the catalogue hamper its useability in clinical practice. We successfully converted 98.3% of variants from the WHO catalogue format to the standardized HGVS format. We also created TBProfiler version 4.4.0 to automate the calling of all variants located in the tier 1 and 2 candidate resistance genes along with their classification when listed in the WHO catalogue. Using a representative sample of 339 clinical isolates from South Africa containing 691 variants in a tier 1 or 2 gene, TBProfiler classified 105 (15%) variants as conferring resistance, 72 (10%) as not conferring resistance and 514 (74%) as unclassified, with an average of 29 unclassified variants per isolate. Using a second cohort of 56 clinical isolates from a TB outbreak in Spain containing 21 variants in the tier 1 and 2 genes, TBProfiler classified 13 (61.9%) as unclassified, 7 (33.3%) as not conferring resistance, and a single variant (4.8%) classified as conferring resistance. Continued global efforts using standardized methods for genotyping, phenotyping and bioinformatic analyses will be essential to ensure that knowledge on genomic variants translates into improved patient care. [ABSTRACT FROM AUTHOR]

There is an increasing interest in the field of audiology and speech communication to measure the effort that it takes to listen in noisy environments, with obvious implications for populations suffering from hearing loss. Pupillometry offers one avenue to make progress in this enterprise but important methodological questions remain to be addressed before such tools can serve practical applications. Typically, cocktail-party situations may occur in less-than-ideal lighting conditions, e.g. a pub or a restaurant, and it is unclear how robust pupil dynamics are to luminance changes. In this study, we first used a well-known paradigm where sentences were presented at different signal-to-noise ratios (SNR), all conducive of good intelligibility. This enabled us to replicate findings, e.g. a larger and later peak pupil dilation (PPD) at adverse SNR, or when the sentences were misunderstood, and to investigate the dependency of the PPD on sentence duration. A second experiment reiterated two of the SNR levels, 0 and +14 dB, but measured at 0, 75, and 220 lux. The results showed that the impact of luminance on the SNR effect was non-monotonic (sub-optimal in darkness or in bright light), and as such, there is no trivial way to derive pupillary metrics that are robust to differences in background light, posing considerable constraints for applications of pupillometry in daily life. Our findings raise an under-examined but crucial issue when designing and understanding listening effort studies using pupillometry, and offer important insights to future clinical application of pupillometry across sites. [ABSTRACT FROM AUTHOR]

In this paper, we propose a partial randomized response technique to collect reliable sensitive data for estimation of population proportion in ranked set sampling (RSS) scheme using auxiliary information. The idea is to increase confidence and (or) co-operation of the respondents by providing them the option of both 'direct' and 'randomized' response for the inquired sensitive question. This option is quite logical because perception of sensitive (insensitive) inquiry can vary among respondents. The properties of the proposed method are discussed and compared with existing randomized response techniques. Cost analysis is also carried out to prove supremacy of the suggested method. Finally, an application to clinical trial on AIDS is included. [ABSTRACT FROM AUTHOR]

Ocular following eye movements have provided insights into how the visual system of humans and monkeys processes motion. Recently, it has been shown that they also reliably reveal stereoanomalies, and, thus, might have clinical applications. Their translation from research to clinical setting has however been hindered by their small size, which makes them difficult to record, and by a lack of data about their properties in sizable populations. Notably, they have so far only been recorded in adults. We recorded ocular following responses (OFRs)–defined as the change in eye position in the 80–160 ms time window following the motion onset of a large textured stimulus–in 14 school-age children (6 to 13 years old, 9 males and 5 females), under recording conditions that closely mimic a clinical setting. The OFRs were acquired non-invasively by a custom developed high-resolution video-oculography system, described in this study. With the developed system we were able to non-invasively detect OFRs in all children in short recording sessions. Across subjects, we observed a large variability in the magnitude of the movements (by a factor of 4); OFR magnitude was however not correlated with age. A power analysis indicates that even considerably smaller movements could be detected. We conclude that the ocular following system is well developed by age six, and OFRs can be recorded non-invasively in young children in a clinical setting. [ABSTRACT FROM AUTHOR]

Background: The association of head and cervical posture with malocclusion has been studied for many years. Despite extensively encouraging researches, no conclusive evidence has been reached for clinical application. Objective: To identify the question "Does head and cervical posture correlate to malocclusion?", a systematic review and meta-analysis based on the available studies were carried out (PROSPERO registration number: CRD42022319742). Methods: A search of PubMed, Embase, Cochrane Library, and the grey literature was performed without language restrictions. The study screening, data extraction, risk-of-bias evaluation and methodological quality assessment were performed by two independent investigators. When a disagreement arose, a third author was consulted. Results: 6 original cross-sectional studies involving 505 participants were included, which were of moderate methodological quality. NL/VER in Class Ⅱ group and NL/CVT in Class Ⅲ group showed significant differences compared to Class Ⅰ group, but no significant differences were observed in most of the variables like NSL/VER, OPT/CVT, OPT/HOR, CVT/HOR, NSL/OPT, NSL/CVT, NL/OPT in Class Ⅱ and Ⅲ groups. Conclusions: The results suggested that the current research evidence is not sound enough to prove the association of head and cervical posture with sagittal malocclusion. Better controlled design and a larger sample size are required for clarifying this question in future study. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to determine the association between hypothyroidism and overall and site-specific cancer in Spanish population. Methods: A cross-sectional study was performed using the population-based database BDCAP (Base de Datos Clínicos de Atención Primaria, primary care clinical database) to analyze the relative risk of cancer in Spanish population with hypothyroidism. Results: In a total of 2,414,165 patients diagnosed with hypothyroidism in BDCAP in 2019, the relative risk (OR) of cancer, compared to the non-hypothyroid population, was 1.73 (1.72–1.74) (P<0.0001). The higher risk was observed in both men (OR 2.15 [2.13–2.17]; P<0.0001) and women (OR 1.67 [1.636–1.68]; P<0.0001). However, hypothyroid persons aged 65 years or older had a reduced risk of cancer (OR 0.98 [0.97–0.98]; P<0.0001). In addition, hypothyroid patients aged 65 or over showed a decreased risk of cancers of the bladder, colorectal, gastric, pancreatic and prostate. Socioeconomic characteristics such as income level, municipality size, country of birth and employment situation had limited influence on the association between hypothyroidism and cancer. However, hypothyroid patients receiving replacement therapy exhibited higher cancer risk compared with patients without treatment (OR 1.30 [1.28–1.31]; P<0.0001). Conclusion: Spanish hypothyroid patients of both genders have a risk of overall cancer higher than that found in non-hypothyroid population. However, people over 65 years have a reduced risk of various malignancies. This peculiarity of hypothyroidism should be considered by the health authorities. [ABSTRACT FROM AUTHOR]

Background: Neurofilament light chain (NfL) in cerebrospinal fluid (CSF) is a biomarker of multiple sclerosis (MS). However, CSF sampling is invasive and has limited the clinical application. With the development of highly sensitive single-molecule assay, the accurate quantification of the very low NfL levels in blood become feasible. As evidence being accumulated, we performed a meta-analysis to evaluate the diagnostic and predictive value of blood NfL in MS patients. Methods: We performed literature search on PubMed, EMBASE, Web of Science and Cochrane Library from inception to May 31, 2022. The blood NfL differences between MS vs. controls, MS vs. clinically isolated syndrome (CIS), progressive MS (PMS) vs. relapsing-remitting MS (RRMS), and MS in relapse vs. MS in remission were estimated by standard mean difference (SMD) and corresponding 95% confidence interval (CI). Pooled hazard ratio (HR) and 95%CI were calculated to predict time to reach Expanded Disability Status Scale (EDSS) score≥4.0 and to relapse. Results: A total of 28 studies comprising 6545 MS patients and 2477 controls were eligible for meta-analysis of diagnosis value, and 5 studies with 4444 patients were synthesized in analysis of predictive value. Blood NfL levels were significantly higher in MS patients vs. age-matched controls (SMD = 0.64, 95%CI 0.44–0.85, P<0.001), vs. non-matched controls (SMD = 0.76, 95%CI 0.56–0.96, P<0.001) and vs. CIS patients (SMD = 0.30, 95%CI 0.18–0.42, P<0.001), in PMS vs. RRMS (SMD = 0.56, 95%CI 0.27–0.85, P<0.001), and in relapsed patients vs. remitted patients (SMD = 0.54, 95%CI 0.16–0.92, P = 0.005). Patients with high blood NfL levels had shorter time to reach EDSS score≥4.0 (HR = 2.36, 95%CI 1.32–4.21, P = 0.004) but similar time to relapse (HR = 1.32, 95%CI 0.90–1.93, P = 0.155) compared to those with low NfL levels. Conclusion: As far as we know, this is the first meta-analysis evaluating the diagnosis and predictive value of blood NfL in MS. The present study indicates blood NfL may be a useful biomarker in diagnosing MS, distinguishing MS subtypes and predicting disease worsening in the future. [ABSTRACT FROM AUTHOR]

Laboratory medicine plays a critical role in the modern healthcare system, and it is reported to influence 60–70% of clinical decision makings. The quantitative laboratory test results are interpreted by comparing to the Reference Intervals (RIs) and therefore the use of appropriate RIs is critical. Clinical laboratories in Bhutan have been randomly using RIs from textbooks and manufacturer's package inserts without even verifying their applicability and therefore lessening their contribution to clinical decision makings. To improve the healthcare service delivery in Bhutan, this study aims to establish routine clinical chemistry and haematological test RIs for healthy adults in the Bhutanese population. Out of 1150 (male, n = 570; female, n = 580) healthy Bhutanese adults listed for the study through a simple random sampling technique, 1002 (male, n = 405; female, n = 597) individuals were assessed and 815 (male, n = 372; female, n = 443) individuals were enrolled in the study. An adequate volume of venous blood was drawn from these participants with the use of standard phlebotomy technique for clinical chemistry and haematological analysis. The laboratory data were analysed with the use of statistical methods recommended by the International Federation of Clinical Chemistry and Laboratory Medicine and Clinical and Laboratory Standards Institute. After excluding the test results indicating underlying pathology and statistically detected outliers, a maximum of 775 (male, n = 346; female, n = 429) and 784 (male, n = 351; female, n = 433) individuals test values were eligible for clinical chemistry and haematology RIs establishment respectively. Statistically, there were no significant differences between age groups of same-sex for both test categories; however, significant differences between sex were observed for various test parameters in both test categories. Our RIs are generally comparable to other published literature. The established RIs are applicable to all the adult Bhutanese population; however, clinical laboratories should validate the transference of these RIs before using them for clinical purposes. [ABSTRACT FROM AUTHOR]

Swallowing is a complex process that involves precise coordination among oral and pharyngeal structures, which is essential to smooth transition of bolus and adequate airway protection. Tongue base retraction and hyolaryngeal excursion are two significant swallowing movements, and their related events can be examined using ultrasound imaging, which is physically and radioactively non-invasive. The present study aimed to 1) establish the temporal sequences and timing of swallowing events identified using ultrasound imaging, and 2) investigate the variability of the above temporal sequences and 3) investigate the effect of bolus type on the variability of temporal sequences in non-dysphagic individuals. Forty-one non-dysphagic young adults of both genders (19 males and 22 females) participated in the study. Ultrasound images were acquired mid-saggitally at their submental region during swallowing of boluses with different volume (i.e. 5mL or 10mL) and consistencies (i.e. IDDSI Levels 0 and 4). Timing and sequence of six events 1) displacement onset (TBOn), 2) maximum displacement (TBMax) and 3) displacement offset of tongue base retraction (TBOff); and, 4) displacement onset (HBOn), 5) maximum displacement (HBMax) and 6) displacement offset of the hyoid bone excursion (HBOff) were extracted from the ultrasound images. Out of the 161 swallows, 85.7% follow a general sequence of HBOn < TBOn < HBMax < TBMax < HBOff < TBOff. Percentage adherence to six anticipated paired-event sequences was studied. Results suggested the presence of individual variability as adherence ranged from 75.8% to 98.1% in four of the anticipated sequences, leaving only two sequences (HBOn < TBMax and TBMax < HBOff) obligatory (i.e. 100% adherence). For non-obligatory sequences, it was found that bolus type may have an effect on the level of adherence. Findings of the present study lay the groundwork for future studies on swallowing using ultrasound imaging and also the clinical application of ultrasonography. [ABSTRACT FROM AUTHOR]

The FDA's Accelerated Approval program (AA) is a regulatory program to expedite availability of products to treat serious or life-threatening illnesses that lack effective treatment alternatives. Ideally, all of the many stakeholders such as patients, physicians, regulators, and health technology assessment [HTA] agencies that are affected by AA should benefit from it. In practice, however, there is intense debate over whether evidence supporting AA is sufficient to meet the needs of the stakeholders who collectively bring an approved product into routine clinical care. As AAs have become more common, it becomes essential to be able to determine their impact objectively and reproducibly in a way that provides for consistent evaluation of therapeutic decision alternatives. We describe the basic features of an approach for evaluating AA impact that accommodates stakeholder-specific views about potential benefits, risks, and costs. The approach is based on a formal decision-analytic framework combining predictive distributions for therapeutic outcomes (efficacy and safety) based on statistical models that incorporate findings from AA trials with stakeholder assessments of various actions that might be taken. The framework described here provides a starting point for communicating the value of a treatment granted AA in the context of what is important to various stakeholders. [ABSTRACT FROM AUTHOR]

Continued waves, new variants, and limited vaccine deployment mean that SARS-CoV-2 tests remain vital to constrain the coronavirus disease 2019 (COVID-19) pandemic. Affordable, point-of-care (PoC) tests allow rapid screening in non-medical settings. Reverse-transcription loop-mediated isothermal amplification (RT-LAMP) is an appealing approach. A crucial step is to optimize testing in low/medium resource settings. Here, we optimized RT-LAMP for SARS-CoV-2 and human β-actin, and tested clinical samples in multiple countries. "TTTT" linker primers did not improve performance, and while guanidine hydrochloride, betaine and/or Igepal-CA-630 enhanced detection of synthetic RNA, only the latter two improved direct assays on nasopharygeal samples. With extracted clinical RNA, a 20 min RT-LAMP assay was essentially as sensitive as RT-PCR. With raw Canadian nasopharygeal samples, sensitivity was 100% (95% CI: 67.6% - 100%) for those with RT-qPCR Ct values ≤ 25, and 80% (95% CI: 58.4% - 91.9%) for those with 25 < Ct ≤ 27.2. Highly infectious, high titer cases were also detected in Colombian and Ecuadorian labs. We further demonstrate the utility of replacing thermocyclers with a portable PoC device (FluoroPLUM). These combined PoC molecular and hardware tools may help to limit community transmission of SARS-CoV-2. [ABSTRACT FROM AUTHOR]