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Abstract Objective Safe patient care can help reduce treatment costs, morbidity, and mortality. This study aimed to assess dentists’ perceptions of patient safety culture and related factors in the Eastern region of Saudi Arabia. Methods This cross-sectional study used a sample of 271 dental professionals working in private and public dental hospitals and clinics in the Eastern region of Saudi Arabia. The Safety Attitude Questionnaire (SAQ), a validated tool consisting of 36 items on a 5-point Likert scale, was used to assess dentists’ perceptions of patient safety culture. The score of SAQ ranges from 0 to 100 and a cut-off ≥ 75 is considered a positive attitude toward patient safety culture. Results There were 53.9% males and 46.1% females in the study with a mean age of 35.56 ± 6.87 years. Almost half of the participants (52%) attended a course on patient safety and 22.1% experienced medical error in the last month. The mean score of the SAQ of the sample was 65.14 ± 13.03 and the patient safety score was significantly related to the marital status (P = 0.041), attendance of patient safety course (P

SARS-CoV-2 spread rapidly across the globe, contributing to the death of millions of individuals from 2019 to 2023, and has continued to be a major cause of morbidity and mortality after the pandemic. At the start of the pandemic, no vaccines or anti-viral treatments were available to reduce the burden of disease associated with this virus, as it was a novel SARS coronavirus. Because of the tremendous need, the development of vaccines to protect against COVID-19 was critically important. The flexibility and ease of manufacture of nucleic acid–based vaccines, specifically mRNA-based products, allowed the accelerated development of COVID-19 vaccines. Although mRNA-based vaccines and therapeutics had been in clinical trials for over a decade, there were no licensed mRNA vaccines on the market at the start of the pandemic. The rapid development of mRNA-based COVID-19 vaccines reduced serious complications and death from the virus but also engendered significant public concerns, which continue now, years after emergency-use authorization and subsequent licensure of these vaccines. This article summarizes and addresses some of the safety concerns that continue to be expressed about these vaccines and their underlying technology. [ABSTRACT FROM AUTHOR]

Objective: Safe patient care can help reduce treatment costs, morbidity, and mortality. This study aimed to assess dentists' perceptions of patient safety culture and related factors in the Eastern region of Saudi Arabia. Methods: This cross-sectional study used a sample of 271 dental professionals working in private and public dental hospitals and clinics in the Eastern region of Saudi Arabia. The Safety Attitude Questionnaire (SAQ), a validated tool consisting of 36 items on a 5-point Likert scale, was used to assess dentists' perceptions of patient safety culture. The score of SAQ ranges from 0 to 100 and a cut-off ≥ 75 is considered a positive attitude toward patient safety culture. Results: There were 53.9% males and 46.1% females in the study with a mean age of 35.56 ± 6.87 years. Almost half of the participants (52%) attended a course on patient safety and 22.1% experienced medical error in the last month. The mean score of the SAQ of the sample was 65.14 ± 13.03 and the patient safety score was significantly related to the marital status (P = 0.041), attendance of patient safety course (P < 0.001), and experience of medical error (P = 0.008). The highest mean score (73.27 ± 20.11) was for the job satisfaction domain, followed by the safety climate domain (67.69 ± 16.68), and working conditions domain (66.51 ± 20.43). About one-quarter of the participants (22.5%) demonstrated positive attitudes toward patient safety culture. Multiple logistic regression analysis showed that dental professionals who attended a patient safety course were 4.64 times more likely to demonstrate positive attitudes toward patient safety than those who did not attend a course (P < 0.001). Conclusion: This study showed that patient safety culture was significantly related to the attendance of safety courses, marital status, and experiencing medical error. About one out of four dental professionals demonstrated a positive attitude towards patient safety culture which was significantly associated with the attendance of the safety course. [ABSTRACT FROM AUTHOR]

Since its first approval by the Food and Drug Administration in 1989 for strabismus, botulinum toxin indications of use have been widely expanded. Due to its anticholinergic properties, this toxin is currently approved in adult patients for the treatment of a wide range of neuromuscular, otolaryngologic, orthopedic, gastrointestinal, and urologic disorders. Approved pediatric indications of use include the treatment of blepharospasm associated with dystonia, strabismus, lower-limb spasticity, focal spasticity in patients with cerebral palsy, and neurogenic detrusor overactivity. Alongside these approved indications, botulinum toxin is extensively used off-label. Although several clinical studies have shown that botulinum toxin is effective and well-tolerated in children, uncertainties persist regarding its long-term effects on growth and appropriate dosing in this population. As such, further research is needed to better define the botulinum toxin risk–benefit profile and expand approved uses in pediatrics. This narrative review aimed to provide a broad overview of the evidence concerning the clinical effectiveness and safety of BoNT with respect to its principal authorized and non-authorized pediatric therapeutic indications, as well as to describe perspectives on its future use in children. [ABSTRACT FROM AUTHOR]

Existing Mechanical Insufflation-Exsufflation (MI-E) devices often overlook the impact of cough airflow pressure on mucus clearance, particularly lacking in control over airway pressure during the expiratory phase, which can lead to airway collapse and other types of airway damage. This study optimizes the design of cough assist system and explores the effectiveness of PID and adaptive control methods in regulating airway pressure. The adaptive control method compensates for hose pressure drop by online estimation of the ventilatory hose characteristics. It achieves precise tracking of target pressure and ensures the generation of peak flow rates effective for mucus clearance, even in the absence of known patient lung physiological states and unknown hose leakage parameters. Through a series of comparative experiments, this paper confirms the significant advantages of adaptive control in reducing oscillations and overshoot, capable of more stable and precise airway pressure adjustments. This improved control strategy not only enhances clinical safety but also significantly improves therapeutic outcomes and reduces the risk of complications. The findings indicate that the revamped cough assist system, employing an adaptive control strategy, can effectively prevent airway damage during assisted coughing, offering a safer and more effective sputum clearance solution for critically ill patients with expectoration disorders.

Abstract Background The burden of chronic conditions is growing in Australia with people in remote areas experiencing high rates of disease, especially kidney disease. Health care in remote areas of the Northern Territory (NT) is complicated by a mobile population, high staff turnover, poor communication between health services and complex comorbid health conditions requiring multidisciplinary care. Aim This paper aims to describe the collaborative process between research, government and non-government health services to develop an integrated clinical decision support system to improve patient care. Methods Building on established partnerships in the government and Aboriginal Community-Controlled Health Service (ACCHS) sectors, we developed a novel digital clinical decision support system for people at risk of developing kidney disease (due to hypertension, diabetes, cardiovascular disease) or with kidney disease. A cross-organisational and multidisciplinary Steering Committee has overseen the design, development and implementation stages. Further, the system’s design and functionality were strongly informed by experts (Clinical Reference Group and Technical Working Group), health service providers, and end-user feedback through a formative evaluation. Results We established data sharing agreements with 11 ACCHS to link patient level data with 56 government primary health services and six hospitals. Electronic Health Record (EHR) data, based on agreed criteria, is automatically and securely transferred from 15 existing EHR platforms. Through clinician-determined algorithms, the system assists clinicians to diagnose, monitor and provide guideline-based care for individuals, as well as service-level risk stratification and alerts for clinically significant events. Conclusion Disconnected health services and separate EHRs result in information gaps and a health and safety risk, particularly for patients who access multiple health services. However, barriers to clinical data sharing between health services still exist. In this first phase, we report how robust partnerships and effective governance processes can overcome these barriers to support clinical decision making and contribute to holistic care.

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Background: Oxygen therapy (OT) is a commonly prescribed essential medicine for people of all ages in the management of hypoxia. The adverse effects of inappropriate OT supplementation may be underestimated by health professionals and lead to poor health outcomes among hospitalised patients. Knowledge, attitude and practice (KAP) assessments of medical staff members to OT guidelines are essential to ensure optimal patient care. Aims: To perform a KAP assessment of OT administration among doctors and nurses employed at the national hospital of Fiji in 2021. Methods: Prospective cross‐sectional study design. KAP assessment was performed with an online questionnaire and clinical observation. Results: The study population (N = 116) consisted of doctors (20.7%) and nurses (79.3%) representing the acute medical, burns, cardiac care, intensive care, surgical and postanaesthetic recovery units. Overall, the proportion of participants who obtained a good score (>70%) was 87% for knowledge, 87.93% for attitudes and 84% for practice. Best knowledge scores were obtained for general OT indications (71%) and scenarios where immediate oxygen application is required (70%). Lowest knowledge scores were for OT contraindications (14%) and oxygen saturation for acute myocardial infarction (32%), asthma (36%) and healthy newborns (43%). The most positive attitudes were in response to the statement that OT guidelines are essential (96%). A total of 78 (80.4%) patients were being cared for with good OT practice. Conclusions: Good KAP scores were obtained for medical staff in Fiji regarding OT administration. Ongoing professional education activities should include updated training of OT contraindications and optimal oxygen saturation levels for special patient groups. [ABSTRACT FROM AUTHOR]

The objective of this systematic review of the literature is to compare a selection of currently utilized disposable and reusable laparoscopic medical devices in terms of safety (1st criteria), cost and carbon footprint. A search was carried out on electronic databases for articles published up until 6 May 2022. The eligible works were prospective (randomized or not) or retrospective clinical or medical-economic comparative studies having compared disposable scissors, trocars, and mechanical endoscopic staplers to the same instruments in reusable. Two different independent examiners extracted the relevant data. Among the 2882 articles found, 156 abstracts were retained for examination. After comprehensive analysis concerning the safety and effectiveness of the instruments, we included four articles. A study on trocars highlighted increased vascular complications with disposable instruments, and another study found more perioperative incidents with a hybrid stapler as opposed to a disposable stapler. As regards cost analysis, we included 11 studies, all of which showed significantly higher costs with disposable instruments. The results of the one study on carbon footprints showed that hybrid instruments leave four times less of a carbon footprint than disposable instruments. The literature on the theme remains extremely limited. Our review demonstrated that from a medical and economic standpoint, reusable medical instruments, particularly trocars, presented appreciable advantages. While there exist few data on the ecological impact, those that do exist are unmistakably favorable to reusable instruments. [ABSTRACT FROM AUTHOR]

Background: The burden of chronic conditions is growing in Australia with people in remote areas experiencing high rates of disease, especially kidney disease. Health care in remote areas of the Northern Territory (NT) is complicated by a mobile population, high staff turnover, poor communication between health services and complex comorbid health conditions requiring multidisciplinary care. Aim: This paper aims to describe the collaborative process between research, government and non-government health services to develop an integrated clinical decision support system to improve patient care. Methods: Building on established partnerships in the government and Aboriginal Community-Controlled Health Service (ACCHS) sectors, we developed a novel digital clinical decision support system for people at risk of developing kidney disease (due to hypertension, diabetes, cardiovascular disease) or with kidney disease. A cross-organisational and multidisciplinary Steering Committee has overseen the design, development and implementation stages. Further, the system's design and functionality were strongly informed by experts (Clinical Reference Group and Technical Working Group), health service providers, and end-user feedback through a formative evaluation. Results: We established data sharing agreements with 11 ACCHS to link patient level data with 56 government primary health services and six hospitals. Electronic Health Record (EHR) data, based on agreed criteria, is automatically and securely transferred from 15 existing EHR platforms. Through clinician-determined algorithms, the system assists clinicians to diagnose, monitor and provide guideline-based care for individuals, as well as service-level risk stratification and alerts for clinically significant events. Conclusion: Disconnected health services and separate EHRs result in information gaps and a health and safety risk, particularly for patients who access multiple health services. However, barriers to clinical data sharing between health services still exist. In this first phase, we report how robust partnerships and effective governance processes can overcome these barriers to support clinical decision making and contribute to holistic care. [ABSTRACT FROM AUTHOR]

Coronaviruses are the causative agents of several recent outbreaks, including the COVID-19 pandemic. One therapeutic approach is blocking viral binding to the host receptor. As binding largely depends on electrostatic interactions, we hypothesized possible inhibition of viral infection through application of electric fields, and tested the effectiveness of Tumor Treating Fields (TTFields), a clinically approved cancer treatment based on delivery of electric fields. In preclinical models, TTFields were found to inhibit coronavirus infection and replication, leading to lower viral secretion and higher cell survival, and to formation of progeny virions with lower infectivity, overall demonstrating antiviral activity. In a pilot clinical study (NCT04953234), TTFields therapy was safe for patients with severe COVID-19, also demonstrating preliminary effectiveness data, that correlated with higher device usage. [ABSTRACT FROM AUTHOR]

Salacia plants has been used as a traditional medicine for diabetes in India, Sri Lanka and South-eastern Asia. This extract is well-known for anti-a-glucosidase activity, delaying glucose absorption. The purpose of this clinical trial was to investigate the clinical safety of Salacia oblonga extract (trunk) formulation to healthy volunteers. A total of 16 volunteers who satisfied the inclusion criteria were enrolled in this study. Six tablets (Salacia oblonga trunk extract (SQE):30mg/tablet) of the test substance were to be taken orally each day, with administration three times daily before meal. The test meal intake period lasted for 12 weeks, and was followed by a 4 weeks test-meal withdrawal period. Flatus, constipation, diarrhea, upper abdominal pain were observed slightly and disappeared in withdrawal period in this study. These findings were considered to be adverse events to test meal, result from fermentation of undigested glucose by bacteria; however, they were reversible and mild in each case, accordingly were not considered issue for clinical safety. These reactions were considered to be related the inhibitory action of Salacia oblonga extract against absorption of glucoses from the gastrointestinal tract. This formulation was highly safe, and produced no reactions that might cause concern, reflecting results in clinical studies of other Salacia plant extracts. [ABSTRACT FROM AUTHOR]

Since its first approval by the Food and Drug Administration in 1989 for strabismus, botulinum toxin indications of use have been widely expanded. Due to its anticholinergic properties, this toxin is currently approved in adult patients for the treatment of a wide range of neuromuscular, otolaryngologic, orthopedic, gastrointestinal, and urologic disorders. Approved pediatric indications of use include the treatment of blepharospasm associated with dystonia, strabismus, lower-limb spasticity, focal spasticity in patients with cerebral palsy, and neurogenic detrusor overactivity. Alongside these approved indications, botulinum toxin is extensively used off-label. Although several clinical studies have shown that botulinum toxin is effective and well-tolerated in children, uncertainties persist regarding its long-term effects on growth and appropriate dosing in this population. As such, further research is needed to better define the botulinum toxin risk–benefit profile and expand approved uses in pediatrics. This narrative review aimed to provide a broad overview of the evidence concerning the clinical effectiveness and safety of BoNT with respect to its principal authorized and non-authorized pediatric therapeutic indications, as well as to describe perspectives on its future use in children.

Background: Withania somnifera (L.) Dunal, known as Ashwagandha, is an adaptogen with significant importance in Ayurveda for its potential health benefits in strength ('balavardhan') and muscle growth ('mamsavardhan'). Despite numerous studies on its efficacy, limited research is reported on its clinical safety and tolerability in healthy individuals. Objective: This research evaluated the tolerability and safety of standardized Withania somnifera root extract (WSE) capsules (AgeVel®/Witholytin®) at 1000 mg/day dose upon oral administration in healthy male participants. Method: A non-randomized, open-label, single-treatment clinical study included eighteen healthy male participants aged 18 to 60. The participants were administered a dose of 500 mg of the WSE capsules twice daily for four weeks. Each capsule contained not less than 7.50 mg of total withanolides. The study evaluated various indicators in a cohort of healthy participants throughout the trial, including vital signs, organ function tests, urine analysis, X-ray and ECG, cardiorespiratory endurance, body fat percentage, lean body weight, adverse events profile, and tolerability of the WSE capsules. Results: The participant's physical, hematological, and biochemical characteristics were normal, and no significant alterations or irregularities were observed in safety metrics like liver, kidney, and thyroid functions after administering AgeVel®/Witholytin®. Conclusion: This study found that healthy male participants could consume a standardized WSE at a daily dosage of 1000 mg for four weeks without any adverse effects. Future research should focus on long-term safety assessments in male and female participants.

Propolis is a natural resinous product collected from different parts of plants by bees and mixed with their salivary secretions. The occurrence of more than 180 different chemotypes has flavonoids, phenolic acids, esters, and phenolic aldehydes, as well as balsamic resins, beeswax, pollen, and essential and aromatic oils, among others. Its biological potential documented throughout the world justifies the need, from time to time, to organize reviews on the subject, with the intention of gathering and informing about the update on propolis. In this review (CRD42020212971), phytochemical advances, in vitro, in vivo, and clinical biological assays of pharmacological interest are showcased. The focus of this work is to present propolis clinical safety assays, antitumor, analgesic, antioxidant, anti‐inflammatory, and antimicrobial activities. This literature review highlights propolis' promising biological activity, as it also suggests that studies associating propolis with nanotechnology should be further explored for enhanced bioprocessing applications. [ABSTRACT FROM AUTHOR]

Coronaviruses are the causative agents of several recent outbreaks, including the COVID-19 pandemic. One therapeutic approach is blocking viral binding to the host receptor. As binding largely depends on electrostatic interactions, we hypothesized possible inhibition of viral infection through application of electric fields, and tested the effectiveness of Tumor Treating Fields (TTFields), a clinically approved cancer treatment based on delivery of electric fields. In preclinical models, TTFields were found to inhibit coronavirus infection and replication, leading to lower viral secretion and higher cell survival, and to formation of progeny virions with lower infectivity, overall demonstrating antiviral activity. In a pilot clinical study (NCT04953234), TTFields therapy was safe for patients with severe COVID-19, also demonstrating preliminary effectiveness data, that correlated with higher device usage.

ObjectiveThis qualitative study aimed to understand the clinical safety, efficacy, and receptiveness of using the female condom (FC) during anal intercourse among men who have sex with men (MSM).MethodsSubjects for this study were recruited from a two-group crossover trial among MSM in Shanghai. The trial consisted of two phases, each including the use of condoms (FC vs. male condom), questionnaires, and in-depth one-on-one interviews. The two phases were separated by a washout period of 4 weeks. The minimum sample size for this study was determined in accordance with the principle of “information saturation.” The qualitative data were organized and analyzed using ATLAS.ti version 7.ResultsA total of 26 participants from the MSM population were recruited for this study, with 10 assuming the insertive role (i.e., “1”), 8 assuming the receptive role (i.e., “0”), and 8 being versatile (i.e., “0.5”). Each participant completed the crossover trial comprising two phases. The cumulative usage of FCs and male condoms (MCs) amounted to 115 and 127 times, respectively. During the reported sexual encounters, no participants reported incidents of condom rupture, slippage, or other malfunctions. A few participants reported experiencing slight chafing pain, primarily put forward by “0” participants. Apart from those reports, no instances of bleeding, swelling, or allergic reactions were reported. The efficiency of FC in disease prevention, the sexual partner’s willingness to use FC, the freshness of FC, and positive sexual experiences were the main reasons for the consistent use of FC for anal sex. Discomfort and pain during sexual activity, the loose design and thick material of FCs, and difficulties in placing FCs were the major obstacles to FC use among MSM. The elements referring to the forehead exhibited varied in importance among “1,”, “0,” and “0.5” participants. Regarding the willingness to use the FC in the future anal intercourse, 61.54% of participants expressed a positive inclination, 23.08% were uncertain, and 15.38% stated that they would not. “A better sense of security during anal sex” was the main factor affecting willingness among “0” participants and “the sexual pleasure that the FC brought” among “1” participants. Improving the design and technology of FCs and increasing the frequency of use and practice might improve the use skills, which will favor the willingness to use FCs among the MSM population.ConclusionFCs received positive user feedback from study participants, but distinctions were found in individuals in different sexual roles. Large-scale quantitative studies are needed to evaluate the clinical safety of the FC and its effectiveness in preventing the transmission of STDs during anal intercourse.

A foundation for digitally enabling healthier living is the safe development and use of technology. The practice of digital health safety has emerged from patient harm attributed to failing technologies. The study aimed to investigate how to adopt and implement digital health safety guidelines at scale. Data was collected through an online survey, semi-structured interviews, focus groups, document review, and data mining of artefacts. The findings of this study capture the emerging practice from Australia in a way that offers insights into the problem of practice, patient safety practice, safety culture, and socio-technical factors. The research findings contribute to better understanding of the complexities of balancing digital innovation with patient safety. The four recommendations from the study and the provision of a logic model will support the audience to implement actions toward a safer digital health ecology. [ABSTRACT FROM AUTHOR]

Many cell types, including cancer cells, release tissue factor (TF)-exposing extracellular vesicles (EVs). It is unknown whether MSC-EVs pose a thromboembolism risk due to TF expression. Knowing that MSCs express TF and are procoagulant, we hypothesize that MSC-EVs also might. Here, we examined the expression of TF and the procoagulant activity of MSC-EVs and the impact of EV isolation methods and cell culture expansion on EV yield, characterization, and potential risk using a design of experiments methodology. MSC-EVs were found to express TF and have procoagulant activity. Thus, when MSC-derived EVs are employed as a therapeutic agent, one might consider TF, procoagulant activity, and thromboembolism risk and take steps to prevent them. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the safety of an injectable heparin-conjugated fibrin (HCF) hydrogel containing human synovium-derived mesenchymal stem cells (SDMSCs), TGF-β1, and BMP-4 after implantation into articular cartilage defect in patients with osteoarthritis (OA). The study included 15 OA patients with a mean age of 44.2±18.0 years. The median articular cartilage defect size was 4.9±2.0 cm. HCF hydrogel, containing SDMSCs and growth factors (TGF-β1 and BMP-4), was implanted into the cartilage defect using DUPLOJECT two-syringe device connected with the DUPLOTIP dual lumen cannula. Clinical and radiological outcomes were evaluated with VAS, WOMAC, KOOS, and MOCART. The clinical study results showed that implantation of HCF hydrogel with autologous SDMSCs, TGF-β1, and BMP-4 appeared to be safe and did not show severe adverse events in OA patients. The assessment of clinical outcomes after 6 months showed improvement in VAS, WOMAC, and KOOS scores in all patients. The MOCART evaluation demonstrated an enhancement of cartilage tissue repair in 73.3% of OA patients at 6 months after surgery. Thus, implantation of HCF hydrogel with SDMSCs, TGF-β1, and BMP-4 was safe and demonstrated signs of improvement in articular cartilage repair. The evaluation of the long-term safety and therapeutic efficacy of HCF hydrogel is required in a further clinical study using a larger number of OA patients.

Hassan Suliman Halawany,1 Nimmi Biju Abraham,2 Abid Hamoud Al-Badr,1 Khalifa S Al-Khalifa3 1Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia; 2School of Oral Health, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand; 3Department of Preventive Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaCorrespondence: Hassan Suliman Halawany, Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, P.O. Box 60169, Riyadh, 11545, Saudi Arabia, Tel +966 55 5415198, Email hhalawany@ksu.edu.saAim: To investigate dental students’ self-reported confidence in learning about various domains of patient safety during their clinical training years.Methods: The Health Professional Education in Patient Safety Survey (H-PEPSS) was distributed to the fourth- and fifth-year undergraduate students, interns and postgraduate dental students. The survey explores how the seven domains of the Canadian Patient Safety Institute Safety Competencies Framework and wider cases of patient safety issues are presented in dental education, as well as participants’ self-reported comfortability regarding revealing about patient safety issues. A comparison of the patient safety domains scores were assessed through learning scenarios (classroom and clinical), gender, level of study and type of institution.Results: Out of 409 participants, 359 undergraduate dental students and 131 postgraduate dental students responded to the survey. Irrespective of the groups, all dental students were most confident regarding their learning aspects about skills pertaining to clinical safety and effective communication and least confident in learning related to managing safety risks. All the patient safety factors irrespective of the scenario, scored above 75% and thus interpreted as good competence. Statistically significant differences were reported among the genders in the classroom scenario for learning about communicating effectively with the patients regarding patient safety issues (p < 0.05). Male dental students, undergraduates and those in the private institution were significantly less confident about recognizing and reporting to immediate risks in the clinical scenario compared to their respective counterparts (p < 0.05).Conclusion: Based on the results, the dental students are quite confident with regard to the learning aspects of clinical patient safety, nevertheless, their confidence in learning certain patient safety aspects warrants further improvement. This implies a need to address the impact of regular interventions, extra motivation and repeated mentoring in both the classroom and clinical scenarios on improving dental students’ confidence about patient safety.Keywords: patient safety, health care, clinical safety, dental students, postgraduates, questionnaire

Background An unmet medical need remains for an effective dengue tetravalent vaccine that can be administered irrespective of previous dengue exposure. TAK-003, a dengue tetravalent vaccine, has demonstrated efficacy in an ongoing phase 3 trial in children and adolescents living in dengue-endemic areas, with an acceptable safety profile in both dengue-naive and dengue-exposed individuals. Methods Safety findings are presented herein from an integrated analysis of data for healthy 4–60-year-olds from two phase 2 and three phase 3 double-blind, placebo-controlled clinical trials of TAK-003 (TAK-003, n = 14 627; placebo, n = 7167). Safety evaluation included analyses of postinjection reactogenicity, unsolicited adverse events (AEs), serious AEs (SAEs), and deaths. Subgroup analyses were performed by age group, baseline serostatus, and gender. Results The most common local and systemic AEs were injection site pain (43% for TAK-003 and 26% for placebo) and headache (34% and 30%, respectively). Injection site AEs were mostly mild and resolved within 1–3 days. Unsolicited AEs and AEs leading to discontinuation occurred with similar frequency across both groups, while SAEs were fewer for TAK-003 recipients (6% vs 8% for placebo). Four of the 5 vaccine-related SAEs (which included hypersensitivity, dengue fever, and dengue hemorrhagic fever) occurred in the placebo group. No deaths were considered vaccine-related. Subgroup analyses showed no differences in safety by baseline serostatus or by gender, albeit analysis by age indicated greater local reactogenicity rates for adolescents (46% for TAK-003 and 28% for placebo) and adults (56% and 19%, respectively) than for children (37% and 25%, respectively). Conclusions No important safety risks were identified, and TAK-003 was well tolerated irrespective of age, gender, or baseline dengue serostatus in recipients aged 4–60 years. [ABSTRACT FROM AUTHOR]

In the present study, we aimed to evaluate the efficacy and safety of biapenem in very elderly (≥ 85 years) patients. A retrospective study was conducted on very elderly patients who received biapenem for at least 72 h and had a complete medical record from January 2016 to December 2017. Baseline characteristics and laboratory test results were recorded and assessed. Finally, 275 unique patients with an average age of 88.5 ± 3.1 years were enrolled. Of these patients, 186 (67.6%) had successful treatment. Univariate analysis of various parameters showed that fever and BUN (serum urea nitrogen) elevation were associated with treatment failure. In contrast, other parameters showed no significant differences between the treatment success group and treatment failure group, which included primary underlying disease, monotherapy, prior use of antibiotics, alanine aminotransferase (ALT), aspartate aminotransferase (AST). Multivariate logistic regression analysis found that fever and BUN elevation were independent risk factors for treatment outcomes. BUN was elevated from 8.8 ± 5.6 to 9.9 ± 5.4 mmol/L after treatment (P = 0.007). Adverse drug reactions were observed in 10.9% (30/275) of patients, and all of these were mild or intermediate. The study suggested that biapenem was efficacious and safe in very elderly patients (≥ 85 years). [ABSTRACT FROM AUTHOR]

Context: Around 400,000 people currently live in care homes with increasing complexity of care needs and comorbidities. Despite this, there is a paucity of research that asks questions about how the care and clinical safety of this vulnerable population are managed. Objective: The aim of this research was to understand how registered care home managers approach clinical safety and what they feel helps or hinders them in this. Methods: The research took a Heideggerian interpretative phenomenological approach, embracing the closeness of the researcher to the participants and the subject matter to uncover rich and detailed findings. Five registered managers of care homes owned by one provider participated in semi-structured interviews between March and May 2020. Three of the interviews took place in the managers' care homes, and, due to coronavirus restrictions, two were undertaken via video conferencing software. Findings: Thematic analysis of the data generated unexpected findings demonstrating the significant impact on clinical safety in care homes caused not by the managers themselves, but by external forces, including regulation, shortcomings in the structure of the health and social care system in the UK and complex relationships between care homes and other agencies. Limitations: The strengths (e.g., in-depth data) and limitations (e.g., only including care homes in one area) of this phenomenological qualitative study are discussed. Implications: The findings led to recommendations that further research and reviews should be undertaken urgently to understand these factors in more detail. This would provide valuable guidance to inform system-wide reform to ensure better clinical safety for care home residents. [ABSTRACT FROM AUTHOR]

The study aimed to design a reliable and straightforward PBM method by implanting a medical scattering fiber above surgically exposed spinal cord in SCI patients. Moreover, the safety of this method was examined. Twelve patients with acute SCI (ASIA B) requiring posterior decompression were recruited. The medical scattering fiber was implanted above the spinal cord, and was continuously irradiated at 810 nm, 300 mW, 30 min/day, once per day for 7 days. The vital signs (temperature, blood pressure, respiratory rate, heart rate, and oxygen saturation), infection indicators (WBC, NEUT, hs-CRP, and PCT), photo-allergic reaction indicators (Eosinophil and Basophil), coagulation function indicators (PT, APTT, TT) and neurological stability indicators (ASIA sensory and motor scores) were recorded to evaluate the safety of PBM. Three months after surgery, 12 patients completed follow-up. In our study, direct PBM on SCI site did not cause clinically pathologic changes in vital signs of the patients. All patients had higher WBC, NEUT, and hs-CRP at day 3 during irradiation than those before surgery, and returned to normal at day 7. The changes in Eosinophil and Basophil that were closely associated with allergic reactions were within normal limits throughout the course of irradiation. The coagulation function (PT, APTT, and TT) of patients were also in the normal range. The ASIA sensory and motor scores of all patients had no changes throughout the irradiation process. However, in the follow-up, both ASIA sensory and motor scores of all patients had minor improvement than those in pre-irradiation, and 7 patients had adverse events, but they were not considered to be related to PBM. Our study might firstly employ direct PBM in the SCI by using scattered optical fibers. In a limited sample size, our study concluded that direct PBM at the site of SCI would not produce adverse effects within the appropriate irradiation parameters. The method is safe, feasible, and does not add additional trauma to the patient. Our preliminary study might provide a new methodology for the clinical PBM treatment of acute SCI. [ABSTRACT FROM AUTHOR]

Abstract Background In 2008, in the context of a complete computerisation of medical records, the Institut Català de la Salut (ICS, Catalan Health Institute) implemented a system in its electronic clinical workstation (ECW) to assist decision-making at the prescription level. This system is known as Self Audit, and it supports physicians in reviewing the medication of their patients. Self Audit provides lists of patients presenting medication-related problems (MRPs) that have potential for improvement, and provides therapeutic recommendations that are easy to apply from the system itself. The aim of this study was to analyse the main results derived from the use of Self Audit in primary care (PC) in Catalonia, and the effect of an incentive-based safety indicator on the results obtained. Methods A descriptive cross-sectional study was carried out to analyse variations in the MRPs detected by Self Audit during 2016, 2017, and 2018 in PC in Catalonia. The effect of a safety indicator on the results obtained was also studied. This safety indicator includes the most clinically relevant MRPs (i.e., therapeutic duplications, safety alerts from the Spanish Medicines Agency, and incidences of polymedication in patients over 65 years of age). Variation in the MRPs was measured using the differences between two evaluation points (initial and final). An MRP was considered resolved if the recommendation specified in the alert was followed. The prescriptions of 6411 PC doctors of the ICS who use the ECW and provide their services to 5.8 million Catalans through 288 PC teams were analysed. Results Analysis of the total safety-based MRPs detected by Self Audit gave overall resolutions from April to December of 9% (21,547) in 2016, 7% (15,924) in 2017, and 1% (2392) in 2018 out of the total number of MRPs recorded in April each year. Examination of the 3 types of MRPs with the highest clinical relevance that were linked to the safety indicator gave overall resolutions of 41% in 2016 (17,358), 20% in 2017 (7655), and 21% in 2018 (8135). Conclusions The ICS Self Audit tool assists in reducing the number of safety-based MRPs in a systematic manner, and yields superior results for the MRPs linked to a safety indicator included in the incentives of PC physicians.

Abstract Background In 2008, the Institut Català de la Salut (ICS, Catalan Health Institute) implemented a prescription decision support system in its electronic clinical workstation (ECW), which automatically generates online alerts for general practitioners when a possible medication-related problem (MRP) is detected. This tool is known as PREFASEG, and at the time of beginning a new treatment, it automatically assesses the suitability of the treatment for the individual patient. This analysis is based on ongoing treatments, demographic characteristics, existing pathologies, and patient biochemical variables. As a result of the assessment, therapeutic recommendations are provided. The objective of this study is to present the PREFASEG tool, analyse the main alerts that it generates, and determine the degree of alert acceptance. Methods A cross-sectional descriptive study was carried out to analyse the generation of MRP-related alerts detected by PREFASEG during 2016, 2017, and 2018 in primary care (PC) in Catalonia. The number of MRP alerts generated, the drugs involved, and the acceptance/rejection of the alerts were analysed. An alert was considered "accepted" when the medication that generated the alert was not prescribed, thereby following the recommendation given by the tool. The MRP alerts studied were therapeutic duplications, safety alerts issued by the Spanish Medicines Agency, and drugs not recommended for use in geriatrics. The prescriptions issued by 6411 ICS PC physicians who use the ECW and provide their services to 5.8 million Catalans through 288 PC teams were analysed. Results During the 3 years examined, 67.2 million new prescriptions were analysed, for which PREFASEG generated 4,379,866 alerts (1 for every 15 new treatments). A total of 1,222,159 alerts (28%) were accepted. Pharmacological interactions and therapeutic duplications were the most detected alerts, representing 40 and 30% of the total alerts, respectively. The main pharmacological groups involved in the safety alerts were nonsteroidal anti-inflammatory drugs and renin-angiotensin system inhibitors. Conclusions During the period analysed, 28% of the prescriptions wherein a toxicity-related PREFASEG alert was generated led to treatment modification, thereby helping to prevent the generation of potential safety MRPs. However, the tool should be further improved to increase alert acceptance and thereby improve patient safety.

The use of Poly (lactic acid) (PLA) as a slow-release vehicle for vaccines has attracted the attention of researchers, since its insertion improves the uptake of them, and reduces side effects or by stimulating recruited defense cells, assisting immunity without the need for booster vaccine doses. Seeking to develop new strategies for the administration of drugs and vaccines in aquaculture, we evaluated the biocompatibility and biodegradation of polymeric PLA devices and PLA plus vitamin E devices, implanted through subcutaneous (SC) and intraperitoneal (IP) routes in Nile tilapia. To carry out this study, 84 male tilapia (initial 243.82 ± 56.74 g; final 400.71 ± 100.54 g) were randomly distributed in 3 tanks (n = 28 fish per treatment/tank). The devices were prepared in two formulations: neat PLA (containing 100% PLA) and PLAVE (PLA plus vitamin E) implanted using a commercial AnimalTag® applicator, and non-implanted fish (control). Fish were sampled 15, 30, 60, and 120 days post-implantation (DPI). Blood analysis was used to access blood cells and blood smear for differential leucocytes count. Serum biochemistry to evaluated changes in serum proteins and glycemia. Histopathological investigation using hematoxylin-eosin (H&E) was used to assess polymer-tissue interaction. Histochemistry and immunohistochemistry was used to detection immune cells and phagocytes in capsule, and analyses of melanomacrophage centers (MMCs) to morphometric evaluation and percentage amount of melanin, hemosiderin and lipofucsin pigments. Histopathological study revealed an increase of capsular formation and inflammatory cell infiltration in PLAVE-implanted tilapia through SC route (15 DPI). Tilapia implanted with PLAVE and PLA (SC) presented mast cells and eosinophilic granular cells during 15, 30, and 60 DPI, with a decrease in these cells in the fibrous capsule around the polymer at 120 DPI. PLAVE implanted tilapia SC at 60 DPI showed significantly phagocytosis points than other groups. Phagocytic cells (F4/80+) were observed near to biopolymers in phagocytosis sites. Lipofuscin at 120 DPI in spleen melanomacrophage centers were significantly high in PLAVE implanted tilapias when compared to fish with PLA implants and control. The serum biochemical study of tilapia did not reveal changes in cytotoxicity and liver function in implanted fish. The absence of side effects in hematological and biochemical findings, including the absence of mortality after device implantation, proves its clinical safety. PLA implants in tilapia have demonstrated biocompatibility, biodegradation, clinical safety, and excellent evolution of foreign body inflammatory responses.

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The main objective is to evaluate clinical efficacy and safety of using calcipotriol–betamethasone compounding agent for psoriasis treatment through a systematic review and meta-analysis. We searched MEDLINE, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), and WanFang Data from inception till July 31, 2020. Efficacy was evaluated based on primary outcome indicators including skin lesion improvement and overall adverse reaction rate. Secondary outcome indicators included degree of life quality improvement, clinical effectiveness rate, and specific adverse reaction rates. RevMan5.3 was used to perform the meta-analysis. 22 studies finally met our inclusion criteria for the meta-analysis. The results indicated that for short-term treatment, a sequential therapy that uses calcipotriol betamethasone compounding agent and calcipotriol improves PASI score (MD = −0.94, 95% CI − 1.38 ~ − 0.49, P < 0.0001, I2 = 49%), comparing with using only calcipotriol. From a drug safety perspective, the difference in overall adverse reaction rate is not significant between the calcipotriol group and the sequential treatment group (RR = 0.50, 95% CI 0.22 ~ 1.14, P = 0.10, I2 = 33%). Calcipotriol betamethasone compounding agent may be more effective in plaque psoriasis treatment compared to use only calcipotriol, with no significant difference in adverse reaction rate between the two groups. Although the data were collected from 13 comparison groups, each group may not have sufficient data for a thorough and comprehensive analysis. Further research may be necessary for a more detailed evaluation of effectiveness of using calcipotriol betamethasone compounding agent for plaque psoriasis treatment. [ABSTRACT FROM AUTHOR]

Objective: Increasing complexity in healthcare systems necessitates effective handover. While a universal structure is often recommended, many frameworks do not include the patient. A systematic review was completed examining outcomes following handover that included patients or carers using a realist-orientated paradigm., Methods: The research group used Covidence™ software and followed PRISMA guidelines. A librarian-led search of Embase, Medline, PsycINFO and SCOPUS yielded 5,790 relevant studies for screening. Included studies reported on peer-reviewed studies that assessed qualitative or quantitative outcomes resulting from patient-centred handover. To assess quality, we used the McMaster Mixed Methods Appraisal Tool (MMAT). Patient-orientated and quantitative outcomes are reported descriptively. For qualitative outcomes, we employed a deductive analytical approach. Braun and Clarke's steps were followed to develop themes with group work used to clarify and discuss the various codes. Heterogenous reporting precluded meta-analysis., Results: Thirty studies were eligible (10 mixed methods; 11 quantitative; 9 qualitative) with variable quality and scope. Most studies related to nursing-led bedside handover and originated in Anglophone countries. Positive effects were reported for patient satisfaction, engagement, autonomy and effective information exchange. Providers reported a positive experience but also barriers to implementation, cognitive load and reducing compliance over time. There were contradicting findings for patient-orientated outcomes including falls risk. Publication bias may have led to under reporting of negative trials. There was limited reporting on physician-led handovers that included patients., Conclusions: Patient-centred handover was associated with self-reported benefits for patients and providers but potential advantages over conventional handover could be undermined by barriers such as time, implementation challenges and a perceived increase in staff workload., (© 2024 John Wiley & Sons Ltd.)

Existing Mechanical Insufflation-Exsufflation (MI-E) devices often overlook the impact of cough airflow pressure on mucus clearance, particularly lacking in control over airway pressure during the expiratory phase, which can lead to airway collapse and other types of airway damage. This study optimizes the design of cough assist system and explores the effectiveness of PID and adaptive control methods in regulating airway pressure. The adaptive control method compensates for hose pressure drop by online estimation of the ventilatory hose characteristics. It achieves precise tracking of target pressure and ensures the generation of peak flow rates effective for mucus clearance, even in the absence of known patient lung physiological states and unknown hose leakage parameters. Through a series of comparative experiments, this paper confirms the significant advantages of adaptive control in reducing oscillations and overshoot, capable of more stable and precise airway pressure adjustments. This improved control strategy not only enhances clinical safety but also significantly improves therapeutic outcomes and reduces the risk of complications. The findings indicate that the revamped cough assist system, employing an adaptive control strategy, can effectively prevent airway damage during assisted coughing, offering a safer and more effective sputum clearance solution for critically ill patients with expectoration disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu, Wang, Shen and Du.)

In regenerative medicine, ongoing advancements in cell culture techniques, including isolation, expansion, banking, and transport, are crucial for clinical success. Cryopreservation ensures off-the-freezer availability of living cells, enabling long-term storage and transport. Customizing cryopreservation techniques and cryoprotective agents (CPAs) for specific cell types is crucial for cell source quality, sustainability, safety, and therapeutic intervention efficiency. As regenerative medicine progresses, it becomes imperative that the scientific community and industry provide a comprehensive, cell-specific landscape of available and effective cryopreservation techniques, preventing trial-and-error approaches and unlocking the full potential of cell-based therapies. Open-sharing data could lead to safer, more efficient cell therapies and treatments. Two decades of dermal progenitor cell use for burn wound treatment and Good Manufacturing Practice-compliant technology transfers have highlighted the need for further cryopreservation optimization in manufacturing workflows. In this paper, we present experimental data assessing 5 different cryopreservation formulae for long-term storage of clinical-grade FE002 primary progenitor fibroblasts, emphasizing the crucial difference between DMSO-based and DMSO-free CPAs. Our findings suggest that CryoOx, a DMSO-free CPA, is a promising alternative yielding cell viability similar to that of established commercial CPAs. This research highlights the importance of secure, robust, and efficient cryopreservation techniques in cell banking for maximizing quality, ensuring patient safety, and advancing regenerative medicine., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This case study concerned clinical safety and behavioral-pharmacological intervention with an 18-year-old man who had autism spectrum disorder and high-frequency aggression toward care providers at a specialized school. A multicomponent behavior support plan included antecedent, differential reinforcement, environmental modification, and physical management procedures subsequently combined with psychotropic medication (aripiprazole). Clinical safety components emphasized comprehensive care provider training, continuous supervision, function-based treatment, and prevention-focused strategies. The behavioral-pharmacological intervention eliminated implementation of aggression-contingent physical restraint and was associated with increased transition compliance during the school day. Throughout the 7.5 months duration of the study, there were no injuries to the participant or other students and a single injury was sustained by one care provider. Intervention effects were long-standing, and care providers rated their training, implementation fidelity, and therapeutic outcome favorably. [ABSTRACT FROM AUTHOR]

Anemia is a common complication in patients with hemodialysis-dependent chronic kidney disease (HDD-CKD). Anemia is principally the result of erythropoietin deficiency, inflammation, and iron deficiency. High molecular weight iron oxide nanoparticles (IONP) are routinely administered intravenously to replace iron losses and, although effective, there are lingering concerns about possible safety issues. Ferric pyrophosphate citrate (FPC, Triferic, Triferic AVNU [Triferic and Triferic AVNU are the proprietary name for ferric pyrophosphate citrate. Triferic and Triferic AVNU are registered trademarks of Rockwell medical Inc.]) is a complex iron salt that donates iron directly to plasma transferrin. FPC is devoid of any carbohydrate moiety and is administered via the dialysate or intravenously during each hemodialysis session to replace iron and maintain hemoglobin. Controlled clinical trials of up to 48 weeks in duration have demonstrated the efficacy of regular administration of dialysate FPC for maintaining hemoglobin levels and iron balance in HDD-CKD patients. Clinical data also suggest that dialysate FPC may reduce the dose requirements for and use of erythropoiesis-stimulating agents and IONPs in HDD-CKD patients. Safety data from clinical studies and post-marketing surveillance show that FPC is well tolerated and not associated with an increased risk of infection, inflammation, iron overload, or serious hypersensitivity reactions. FPC represents an effective and well-tolerated choice for iron replacement and maintenance of hemoglobin in the long-term management of HDD-CKD patients. [ABSTRACT FROM AUTHOR]

Background: Warfarin is well known as a narrow therapeutic index that has prodigious variability in response which challenges dosing adjustment for the maintenance of therapeutic international normalized ratio. However, an appreciated population not on new oral anticoagulants may still need to be stabilized with warfarin dosing. Objective: The current study's main objective was to validate and compare two models of warfarin clinical algorithm models namely the Gage and the International Warfarin Pharmacogenetics Consortium (IWPC) with warfarin 5 mg fixed standard dosing strategy in a sample of Sudanese subjects. Method: We have conducted a cross-sectional study recruited from the out-patient clinic at a tertiary specialized heart center. We included subjects with unchanged warfarin dose (stabilized), and with therapeutic international normalized ratio. The predicted doses of warfarin in the two models were calculated by three different methods (accuracy, clinical practicality, and the clinical safety of the clinical algorithms). Main outcome measure: The primary outcomes were the measurements of the clinical (accuracy, practicality, and safety) in each of the two clinical algorithms models compared to warfarin 5 mg fixed standard dose strategy. Results: We have enrolled 71 Sudanese subjects with mean age (51.7 ± 14 years), of which (49, 69.0%) were females. There was no significant difference between the warfarin 5 mg fixed standard dose strategy and the predicted doses of the two clinical algorithm models (MAE 1.44, 1.45, and 1.49 mg/day [P =0.4]) respectively. In the clinical practicality, all of the three models had a high percent of subjects (95.0%, 51.9%, and 66.7%) in the ideal dose range in middle dose group (3-7 mg/ day) for warfarin 5 mg fixed standard dosing strategy, Gage, and IWPC clinical algorithm models respectively. However, a small percent of subjects was exhibited in the warfarin low dose group ≤ 3 mg/day (0.0%, 15.0%, and 10.0%) and warfarin high dose group ≥ 7 mg/day (0.0%, 33.3%, and 33.3%) for warfarin 5 mg fixed standard dosing strategy, Gage, and IWPC clinical algorithms respectively. In terms of clinical safety, the percent of subjects with severely over-prediction were 28.2%, 22.5%, and 22.5% for warfarin 5 mg fixed standard dosing, Gage, and IWPC, respectively. While the percent of severely under-prediction was 12.7%, 7.0%, and 5.6% for the warfarin 5 mg fixed standard dosing, Gage, and IWPC, respectively. Conclusion: The Gage and IWPC clinical algorithm models were accurate, more clinically practical, and clinically safe than warfarin 5 mg standard dosing in the study population. The cardiologist can use either models (Gage and IWPC) to stratify subjects for accurate, practical, and clinically safe warfarin dosing.. [ABSTRACT FROM AUTHOR]

Context Capsule of alkaloids from the leaf of Alstonia scholaris (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma. Objective To observe the clinical safety and tolerability of CALAS. Materials and methods Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects. Results Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group (p > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%). Discussion and conclusions CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies.

Abstract Background Total glucosides of paeony (TGP), an active compound extracted from the roots of Paeonia lactiflora Pallas, has been increasingly used as the adjunctive therapy for rheumatoid arthritis (RA) patients. Though TGP could mitigate the unanticipated adverse effects during the conventional treatment of RA, high-quality evidence-based meta-analysis data on this subject are still insufficient. The objective of this study is to evaluate the clinical safety of TGP adjuvant therapy in the RA treatment. Methods PubMed, EMBASE, Web of Science, China Network Knowledge Infrastructure (CNKI), SinoMed and WanFang Data were retrieved for randomized controlled trials (RCTs) and cohort study about TGP adjuvant therapy in patients with RA up to 28 January 2021. Literatures with eligibility criteria and information were screened and extracted by two researchers independently. The RevMan5.3 software was used for data analysis with effect estimates as risk ratio (RR) with 95% confidence interval (CI). Results A total of 39 studies involving 3680 RA participants were included. There were 8 comparisons: TGP plus methotrexate (MTX) therapy versus MTX therapy, TGP plus leflunomide (LEF) therapy versus LEF therapy, TGP plus MTX and LEF therapy versus MTX plus LEF therapy, TGP plus tripterygium glycosides (TG) therapy versus TG therapy, TGP plus meloxicam (MLX) therapy versus MLX therapy and TGP plus sulfasalazine (SSZ) therapy versus SSZ therapy, TGP plus iguratimod (IGU) therapy versus IGU therapy, TGP plus prednisone acetate tablets (PAT) therapy versus PAT therapy. The meta-analysis results showed that the occurrence of hepatic adverse effect (RR = 0.31, 95% CI = 0.23–0.41, P

Many cell types, including cancer cells, release tissue factor (TF)-exposing extracellular vesicles (EVs). It is unknown whether MSC-EVs pose a thromboembolism risk due to TF expression. Knowing that MSCs express TF and are procoagulant, we hypothesize that MSC-EVs also might. Here, we examined the expression of TF and the procoagulant activity of MSC-EVs and the impact of EV isolation methods and cell culture expansion on EV yield, characterization, and potential risk using a design of experiments methodology. MSC-EVs were found to express TF and have procoagulant activity. Thus, when MSC-derived EVs are employed as a therapeutic agent, one might consider TF, procoagulant activity, and thromboembolism risk and take steps to prevent them.

Background: In 2008, in the context of a complete computerisation of medical records, the Institut Català de la Salut (ICS, Catalan Health Institute) implemented a system in its electronic clinical workstation (ECW) to assist decision-making at the prescription level. This system is known as Self Audit, and it supports physicians in reviewing the medication of their patients. Self Audit provides lists of patients presenting medication-related problems (MRPs) that have potential for improvement, and provides therapeutic recommendations that are easy to apply from the system itself. The aim of this study was to analyse the main results derived from the use of Self Audit in primary care (PC) in Catalonia, and the effect of an incentive-based safety indicator on the results obtained.Methods: A descriptive cross-sectional study was carried out to analyse variations in the MRPs detected by Self Audit during 2016, 2017, and 2018 in PC in Catalonia. The effect of a safety indicator on the results obtained was also studied. This safety indicator includes the most clinically relevant MRPs (i.e., therapeutic duplications, safety alerts from the Spanish Medicines Agency, and incidences of polymedication in patients over 65 years of age). Variation in the MRPs was measured using the differences between two evaluation points (initial and final). An MRP was considered resolved if the recommendation specified in the alert was followed. The prescriptions of 6411 PC doctors of the ICS who use the ECW and provide their services to 5.8 million Catalans through 288 PC teams were analysed.Results: Analysis of the total safety-based MRPs detected by Self Audit gave overall resolutions from April to December of 9% (21,547) in 2016, 7% (15,924) in 2017, and 1% (2392) in 2018 out of the total number of MRPs recorded in April each year. Examination of the 3 types of MRPs with the highest clinical relevance that were linked to the safety indicator gave overall resolutions of 41% in 2016 (17,358), 20% in 2017 (7655), and 21% in 2018 (8135).Conclusions: The ICS Self Audit tool assists in reducing the number of safety-based MRPs in a systematic manner, and yields superior results for the MRPs linked to a safety indicator included in the incentives of PC physicians. [ABSTRACT FROM AUTHOR]

The therapeutic effect of CAR-T is often accompanied by sCRS, which is the main obstacle to the promotion of CAR-T therapy. The JAK1/2 inhibitor ruxolitinib has recently been confirmed as clinically effective in maintaining control over sCRS, however, its mechanism remains unclear. In this study, we firstly revealed that ruxolitinib significantly inhibited the proliferation of CAR-T cells without damaging viability, and induced an efficacy-favored differentiation phenotype. Second, ruxolitinib reduced the level of cytokine release not only from CAR-T cells, but also from other cells in the immune system. Third, the cytolytic activity of CAR-T cells was restored once the ruxolitinib was removed; however, the cytokines released from the CAR-T cells maintained an inhibited state to some degree. Finally, ruxolitinib significantly reduced the proliferation rate of CAR-T cells in vivo without affecting the therapeutic efficacy after withdrawal at the appropriate dose. We demonstrated pre-clinically that ruxolitinib interferes with both CAR-T cells and the other immune cells that play an important role in triggering sCRS reactions. This work provides useful and important scientific data for clinicians on the question of whether ruxolitinib has an effect on CAR-T cell function loss causing CAR-T treatment failure when applied in the treatment of sCRS, the answer to which is of great clinical significance. • Ruxolitinib inhibited CAR-T proliferation without damaging the viability. • Ruxolitinib reduced the cytokine level of the immune system. • Inhibition of CAR-T can be rapidly restored once the ruxolitinib was removed. • Ruxolitinib reduced CAR-T proliferation without affecting the therapeutic efficacy after withdrawal in vivo. [ABSTRACT FROM AUTHOR]

Background: In 2008, the Institut Català de la Salut (ICS, Catalan Health Institute) implemented a prescription decision support system in its electronic clinical workstation (ECW), which automatically generates online alerts for general practitioners when a possible medication-related problem (MRP) is detected. This tool is known as PREFASEG, and at the time of beginning a new treatment, it automatically assesses the suitability of the treatment for the individual patient. This analysis is based on ongoing treatments, demographic characteristics, existing pathologies, and patient biochemical variables. As a result of the assessment, therapeutic recommendations are provided. The objective of this study is to present the PREFASEG tool, analyse the main alerts that it generates, and determine the degree of alert acceptance.Methods: A cross-sectional descriptive study was carried out to analyse the generation of MRP-related alerts detected by PREFASEG during 2016, 2017, and 2018 in primary care (PC) in Catalonia. The number of MRP alerts generated, the drugs involved, and the acceptance/rejection of the alerts were analysed. An alert was considered "accepted" when the medication that generated the alert was not prescribed, thereby following the recommendation given by the tool. The MRP alerts studied were therapeutic duplications, safety alerts issued by the Spanish Medicines Agency, and drugs not recommended for use in geriatrics. The prescriptions issued by 6411 ICS PC physicians who use the ECW and provide their services to 5.8 million Catalans through 288 PC teams were analysed.Results: During the 3 years examined, 67.2 million new prescriptions were analysed, for which PREFASEG generated 4,379,866 alerts (1 for every 15 new treatments). A total of 1,222,159 alerts (28%) were accepted. Pharmacological interactions and therapeutic duplications were the most detected alerts, representing 40 and 30% of the total alerts, respectively. The main pharmacological groups involved in the safety alerts were nonsteroidal anti-inflammatory drugs and renin-angiotensin system inhibitors.Conclusions: During the period analysed, 28% of the prescriptions wherein a toxicity-related PREFASEG alert was generated led to treatment modification, thereby helping to prevent the generation of potential safety MRPs. However, the tool should be further improved to increase alert acceptance and thereby improve patient safety. [ABSTRACT FROM AUTHOR]

[Display omitted] Innovative technologies have been designed to improve efficacy and safety of chemical UV filters. Encapsulation can enhance efficacy and reduce transdermal permeation and systemic exposure. The aims of this work were (i) to determine the cutaneous biodistribution of avobenzone (AVO), oxybenzone (OXY), and octyl methoxycinnamate (OMC) incorporated in mesoporous silica SBA-15 and (ii) to perform preclinical (in vitro) and (iii) clinical safety studies to demonstrate their innocuity and to evaluate sun protection factor (SPF) in humans. Skin penetration studies showed that deposition of OXY and AVO in porcine and human skin after application of stick formulation with incorporated filters (stick incorporated filters) was significantly lower than from a marketed (non-encapsulated) stick. Cutaneous deposition and transdermal permeation of OXY in and across human skin were 3.8-and 13.4- fold lower, respectively, after application of stick entrapped filters. Biodistribution results showed that encapsulation in SBA-15 decreased AVO and OXY penetration reaching porcine and human dermis. Greater deposition (and permeation) of OXY in porcine skin than in human skin, pointed to the role of follicular transport. Stick incorporated filters had good biocompatibility in vivo and safety profiles, even under sun-exposed conditions. Entrapment of UV filters improved the SPF by 26% and produced the same SPF profile as a marketed stick. Overall, the results showed that SBA-15 enabled safety and efficacy of UV filters to be increased. [ABSTRACT FROM AUTHOR]

Capsule of alkaloids from the leaf of Alstonia scholaris (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma. To observe the clinical safety and tolerability of CALAS. Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects. Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group (p > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%). CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies. [ABSTRACT FROM AUTHOR]