Good Clinical Practice Guidelines Research Articles

Protocol for a randomised, double-blinded, controlled trial of youth with childhood-onset obesity treated with semaglutide 2.4 mg/week: the RESETTLE trial

IntroductionChildhood-onset obesity poses significant health risks, including early-onset type 2 diabetes, cardiovascular disease, and reduced quality of life. Hospital-based non-pharmacological obesity care can reduce childhood obesity, but 25% of children do not respond. Therefore, this study investigates the effect of the glucagon-like peptide-1 receptor agonist, semaglutide, as an add-on to hospital-based obesity care in youth who still have obesity following hospital-based obesity care as children. Furthermore, biomedical and psychosocial factors linked to treatment response will be investigated, alongside an exercise-based strategy to prevent weight regain and maintain a healthy body composition after semaglutide treatment.Methods and analysisThis is an investigator-initiated, randomised, placebo-controlled, double-blind trial. We will enrol expectedly 180–270 young adults aged 18–28 years based on their previous response to a paediatric obesity management programme and their current body mass index (BMI). Participants are categorised into four groups: low treatment response (BMI SD score (SDS) reduction <0.10; BMI ≥30 kg/m2); medium treatment response (BMI SDS reduction >0.25; BMI ≥30 kg/m2); high treatment response (BMI SDS reduction >0.50; BMI <30 kg/m2) and a population-based reference group with normal weight development in childhood. Participants with BMI ≥30 kg/m2are randomised 2:1 to subcutaneous injections of semaglutide 2.4 mg/week or placebo as an add-on to hospital-based obesity care for 68 weeks. The primary outcome is the change in BMI from randomisation to the end of treatment with semaglutide compared with placebo. Secondary endpoints are changes in weight and body composition.Ethics and disseminationThe trial has been approved by the Danish Medicines Agency and the Ethical Committee of the Capital Region of Denmark (H-20039422). The trial will be conducted in accordance with the Declaration of Helsinki and follow the guidelines for Good Clinical Practice. Results will be presented at international scientific conferences and published in peer-reviewed scientific journals.Trial registration numberEudraCT 2019-002274-31.

Optimal timing of recombinant herpes zoster virus vaccination for a JAK inhibitor treatment in rheumatoid arthritis: a multicentre, open-label, randomised comparative study (STOP-HZ study): study protocol

IntroductionJanus kinase (JAK) inhibitors are an important therapeutic option in the treatment of rheumatoid arthritis, but increase the risk of developing herpes zoster. Although a dry recombinant zoster vaccine (RZV) that can be used under immunosuppressive conditions has recently been developed, its optimal use and appropriate timing in patients scheduled to start JAK inhibitors is still unclear. The present study is designed to clarify the appropriate timing of JAK inhibitor initiation to measure varicella zoster virus (VZV)-specific IgG titers and VZV-specific T cell response in patients with rheumatoid arthritis who start tofacitinib at the first RZV vaccination or at the second one.Methods and analysisSTOP HZ (Effectiveness andSafeTyOfProphylactic RecombinantHerpesZoster Virus Vaccination for Rheumatoid Arthritis Patients with Tofacitinib Treatment) study is a multicentre, open-label, randomised, comparative study in patients with rheumatoid arthritis who are scheduled to start tofacitinib. This study enrols 60 study subjects in 12 sites. Enrolled subjects receive RZV two times on day 1 and week 8 and initiate tofacitinib 5 mg two times a day at the time of their first RZV (day 1, group A) or second RZV (week 8, group B) based on randomisation. The random assignment is performed centrally in a 1:1 ratio. Patients in Group B continue the same treatment until the start of tofacitinib treatment. Primary endpoint is VZV-specific IgG antibody titers at week 12 compared with those at baseline in each group. Secondary endpoints include comparison of VZV-specific IgG antibody between the groups, changes in disease activity of rheumatoid arthritis, VZV-specific T cell response and adverse events.Ethics and disseminationThe study has been approved by the Certified Review Board of Keio (No. 2022008), and conforms to the Declaration of Helsinki and good clinical practice guidelines. Written informed consent is obtained from participants prior to enrolment. The results of this study are planned to be submitted for publishment in relevant peer-review journals.Trial registration numberjRCTs031230329.

Efficacy of High Flow Nasal Cannula in the Treatment of Patients with COVID-19 with Acute Respiratory Distress Syndrome: Results of Single Centre Study in Vietnam.

Most hospitalized patients required invasive or non-invasive ventilation and High Flow Nasal Cannula (HFNC). Therefore, this study was conducted to describe the characteristics of patients with severe Coronavirus Disease-2019 (COVID-19) treated by HFNC and its effectiveness for reducing the rate of intubated-mechanical ventilation in the Intensive Care Unit (ICU) of Phu Chanh COVID-19 Department-Binh Duong General Hospital. It was a cross-sectional and descriptive study. All severe patients with COVID-19 with acute respiratory failure eligible for the study were included. Patient characteristics, clinical symptoms, laboratory results, and treatment methods were collected for analysis; parameters and data related to HFNC treatment and follow-up were analysed. 80 patients, aged of 49.7 ± 16.6years, were treated with HFNC at admission in ICU. 14 patients had type 2 diabetes (17.5%), 3 patients had chronic respiratory disease (3.8%), 19 patients had high blood pressure (23.8%), and 5 patients with other comorbidities (7.4%). The majority of patients with severe COVID-19 had typical symptoms of COVID-19 such as shortness of breath (97.5%), intensive tired (81.3%), cough (73.7%), anosmia (48.3%), ageusia (41.3%), and fever (26.3%). The results of arterial blood gases demonstrated severe hypoxia under optimal conventional oxygen therapy (PaO2 = 52.5 ± 17.4mmHg). Respiratory rate, SpO2, PaO2 were significantly improved after using HFNC at 1st day, 3rd day and 7th day (P < 0.05; P < 0.05; P < 0.01; respectively). Receiver operating characteristics (ROC) index was significantly increased after treating with HFNC vs before HFNC treatment (4.79 ± 1.86, 5.53 ± 2.39, and 7.41 ± 4.24 vs 2.97 ± 0.39; P < 0.05, P < 0.05 and P < 0.01, respectively). 54 (67.5%) patients were success with HFNC treatment and 26 (32.5%) patients with HFNC failure needed to treat with Continuous Positive Airway Pressure (CPAP) (13 patients; 50%) or intubated ventilation (13 patients; 50%). HFNC therapy could be considered as a useful and effective alternative treatment for patients with acute respiratory failure. HFNC might help to delay the intubated ventilation for patients with respiratory failure and to minimise the risk of invasive ventilation complications and mortality. However, it is crucial to closely monitor the evolution of patient's respiratory status and responsiveness of HFNC treatment to avoid unintended delay of intubation-mechanical ventilation. An independent ethics committee approved the study (The Ethics Committee of Binh Duong General Hospital; No. HDDD-BVDK BINH DUONG 9.2021), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.

Anticoagulation Therapy Timing in patients with Atrial Fibrillation after Acute and Chronic Subdural Haematoma (ATTAACH): a pilot randomised controlled trial

IntroductionSubdural haematomas (SDHs), acute or chronic, are common neurosurgical diagnoses. These problems can occur among patients requiring direct oral anticoagulation (DOAC) for atrial fibrillation. There are currently no guidelines regarding...

Predicting mucosal inflammation in IBD patients using patient-reported symptom scores and a faecal calprotectin home test: protocol for a multicentre prospective validation study

IntroductionCrohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) with a relapsing-remitting nature. With adequate non-invasive prediction of mucosal inflammation, endoscopies can be prevented and treatment optimised earlier...

Improve Mental Health (Improve-MH) in refugee families using a culturally adapted, general practitioner-delivered psychotherapeutic intervention combined with Triple P Online parenting programme: study protocol of a multicentre randomised controlled trial

IntroductionGermany and the European Union have experienced successive waves of refugees since 2014, resulting in over 1.6 million arrivals, including families with young children. These vulnerable populations often face xenophobia,...

Knowledge and Practices Related to Research Misconduct among Healthcare Researchers in India: Cross-Sectional Study

ABSTRACT Introduction: Practices known to harm the integrity of scientific and medical research during planning, conduct, documentation, and reporting are termed as research misconduct. It is an unfortunate, prevalent reality of the research world. In the present study, we tried to assess the knowledge about research misconduct, its determinants, observed practices of research misconduct among healthcare practitioners, level of satisfaction with the order of authorship in one’s published manuscript, and their views for action to be taken against those involved in research misconduct in our institution. Materials and Methods: This cross-sectional study recruited eligible participants (Faculty Members and Senior Residents of Medical, Dental, and Nursing Professionals) through one-to-one interviews and web-based platforms. Data analysis was conducted by using Statistical Package for the Social Sciences 23(SPSS-23). Result: Of the 356 participants, around 60% had complete knowledge about research misconduct, and 74.2% had observed research misconduct in their workplace at some point in time. There was no association between correct knowledge about research misconduct and the type of healthcare researchers, awareness of the International Committee of Journal of Medical Ethics (ICJME), and training on good clinical practices. 54.8% of the participants considered those involved in research misconduct should not be permitted to be co-guide and guide of students. Conclusion: Training of healthcare researchers on publication ethics and good clinical practice guidelines seems to improve knowledge about research misconduct. Further, stringent action should be taken against those who conduct research misconduct.

Effect of Tiotropium on eye findings in the treatment of chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) is a persistent, chronic inflammatory disease of the lungs. Tiotropium, used in the treatment of COPD, is a muscarinic receptor antagonist that provides long-acting bronchodilation. Our study aimed to investigate the effects of Tiotropium on anterior chamber parameters.MethodsThe study was conducted as an observational cross-sectional and prospectively between October 2023 and April 2024. Patients were examined in three groups: Group 1 consisted of untreated COPD patients; Group 2 consisted of healthy volunteers similar age and gender, and Group 3 included COPD patients receiving Tiotropium 18 mcg via HandiHaler. Anterior chamber parameters, intraocular pressure values, and photopic-mesopic pupil diameters were measured at the initial visit for Group 1 and Group 2 patients, and at the third month of treatment for Group 3 patients.ResultsThirty-six patients were included in each group in the study. No significant differences were observed in ocular findings between the patient and control groups. In COPD patients receiving Tiotropium, narrowing of angle parameters, an increase in photopic-mesopic pupil diameters, and intraocular pressure were observed at the third month of treatment.ConclusionThis study is the first research that investigate the effects of Tiotropium on anterior chamber parameters, pupil diameters, and intraocular pressure in COPD treatment. In conclusion, patients with COPD receiving Tiotropium therapy for three months showed narrowing in angle parameters, an increase in intraocular pressure, and photopic-mesopic pupil diameter; however, no patients developed drug-induced acute angle closure glaucoma.Trial registrationAn independent ethics committee approved the study (Giresun EAH KEAK 2023/180 and 9.10.2023/02) which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice. The study was conducted as prospectively, observational case–control. The Clinical Trial Number obtained for the study is NCT06525051 and was taken on 2024–07-29.

Serum immunoglobulin levels in group E of chronic obstructive pulmonary disease: insights for clinical management and immunoglobulin therapy strategies

ObjectiveThe study aimed to characterize serum immunoglobulin (Ig) concentrations and their relationship with clinical and paraclinical features in patients with COPD group E in the stable stage. Additionally, the study focused on evaluating the relationship between serum Ig levels and the risk of exacerbations over the next 12 months, thereby clarifying the role of serum Ig deficiency in affecting the future risk for these patients.MethodsA prospective observational study assessed IgG, IgA, IgM, and IgE levels in 67 COPD patients and 30 healthy controls at Military Hospital 103 from October 2017 to August 2020. Primary outcomes included Ig isotype levels in COPD patients, with secondary outcomes exploring differences compared to controls and associations with clinical variables.ResultsCOPD patients showed significantly lower IgG concentrations and higher IgA levels than controls. IgM and IgE levels did not differ significantly. Subgroup analysis revealed notable decreases in IgG1 and IgG3 concentrations, with 10.4% of patients exhibiting reduced IgG levels and 0.3% diagnosed with common variable immunodeficiency. No significant associations were found between Ig levels and exacerbation risk or clinical variables.ConclusionsSerum IgG and IgM concentrations were significantly reduced in COPD patients compared to normal individuals, with IgG1 and IgG3 concentrations notably low. Serum IgA levels were significantly higher in COPD patients compared with normal controls. However, no significant association was found between Ig concentrations, particularly serum IgG deficiency and its subclasses, with the frequency and risk of exacerbations during 12 months of longitudinal follow-up. Caution is warranted in the use of immunoglobulin therapy in the treatment of COPD patients.Trial registrationAn independent ethics committee approved the study (Ethics Committee of Military Hospital 103 (No. 57/2014/VMMU-IRB), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.

Qualitative Analysis of Inquiries Received by FDA Regarding Conduct of Clinical Trials during the Covid-19 Public Health Emergency

BackgroundThis report describes the U.S. Food and Drug Administration (FDA) experience in establishing a dedicated mailbox, and in publishing related guidance, to address concerns among interested parties regarding the conduct of clinical trials during the COVID-19 public health emergency (PHE).MethodsSix hundred and thirty-four mailbox inquiries were received from March 2020 through February 2022. Qualitative methods were used to provide a structured description of, and identify common themes among, these inquiries.ResultsMost inquiries came from U.S.-based interested parties, including sponsors, industry trade associations, academic institutions, hospitals, clinics, research sites, trial participants, and individual persons. Approximately one-fifth of questions were related directly to COVID-19 (e.g., proposals for treatment); other inquiries were related to conduct of routine trial-related activities, and concerns were often focused on maintaining compliance with good clinical practice. In March 2020, FDA published a guidance titled Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency; the document was subsequently revised eight times based in part on issues raised in mailbox inquiries.ConclusionsThe dedicated mailbox enabled expedited communication among invested parties during the COVID-19 PHE; FDA also provided updates of the aforementioned guidance. These efforts supported the continuance of ongoing trials and the initiation of new trials during the PHE in accordance with good clinical practice guidelines, thereby helping to ensure the safety of trial participants while maintaining the quality of trial data. By soliciting and responding to trial-related inquiries and addressing corresponding needs and concerns, FDA improved transparency and communication.

Assessing the Decision-Making Capabilities of Artificial Intelligence Platforms as Institutional Review Board Members.

Background: Institutional review boards (IRBs) face delays in reviewing research proposals, underscoring the need for optimized standard operating procedures (SOPs). This study assesses the abilities of three artificial intelligence (AI) platforms to address IRB challenges and draft essential SOPs. Methods: An observational study was conducted using three AI platforms in 10 case studies reflecting IRB functions, focusing on creating SOPs. The accuracy of the AI outputs was assessed against good clinical practice (GCP) guidelines. Results: The AI tools identified GCP issues, offered guidance on GCP violations, detected conflicts of interest and SOP deficiencies, recognized vulnerable populations, and suggested expedited review criteria. They also drafted SOPs with some differences. Conclusion: AI platforms could aid IRB decision-making and improve review efficiency. However, human oversight remains critical for ensuring the accuracy of AI-generated solutions.

A phase 1/2 study of EG-70 (detalimogene voraplasmid) intravesical monotherapy for patients with BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ.

TPS4626 Background: High-risk non-muscle-invasive bladder cancer (NMIBC) is treated with adjuvant intravesical Bacille Calmette-Guérin (BCG). However, approximately 50% of patients experience recurrence and/or progression after BCG treatment and are considered unresponsive. EG-70 (detalimogene voraplasmid) is an investigational drug product that was specifically engineered for intravesical administration to elicit local stimulation of anti-tumor immune responses in the bladder and drive durable efficacy in patients with BCG-unresponsive NMIBC, while mitigating the risk of systemic toxicities from immune stimulation. The phase 1 (dose-escalation) part of the first-in-human LEGEND (NCT04752722) phase 1/2, open-label, multicenter study of EG-70 in patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) is complete: intravesical instillation of EG-70 was well tolerated with an overall complete response (CR) rate of 73%; and the recommended phase 2 dose (RP2D) was identified. Here we describe the ongoing phase 2 part of the study, which opened to enrollment in May 2023. Methods: Patient eligibility criteria: age ≥18 years; ECOG PS 0−2; BCG-unresponsive NMIBC with CIS, with or without resected coexisting papillary tumors, ineligible for, or have elected not to undergo, cystectomy; satisfactory bladder function with ability to retain study drug for ≥60 minutes. Prior checkpoint inhibitor treatment is allowed if completed within 30 days before study entry. Patients are treated with EG-70 at the RP2D (800 µg in 50 mL) by intravesical administration on weeks 1, 2, 5, and 6 of a 12-week cycle, for 4 cycles in one of two cohorts: BCG-unresponsive (Cohort 1); BCG-naïve or BCG-incompletely treated (Cohort 2). Patients in either cohort who exhibit stable disease (SD) or CR at week 12 will continue treatment until week 24; patients with progressive disease (PD) will discontinue treatment. Patients who experience or maintain CR at week 24 will receive additional cycles every 12 weeks until week 48; patients with SD or PD at week 24 will discontinue treatment. Patients with PD at any time after week 24 will discontinue treatment. Phase 2 primary objective: evaluate efficacy (CR rate at week 48) and safety of EG-70. Secondary objectives: evaluate progression-free survival, CR rate at 12, 24, 36 and 48 weeks, and duration of response. The study is being conducted in accordance with the International Conference on Harmonisation Good Clinical Practice guidelines and with the principles of the Declaration of Helsinki. All patients provide written informed consent. The ongoing, registration-enabling phase 2 portion of the LEGEND study is anticipated to recruit approximately 100 patients from sites in North America, Europe, and the Asia-Pacific region. Clinical trial information: NCT04752722 .

Disease characteristics, effectiveness, and safety of vestronidase alfa for the treatment of patients with mucopolysaccharidosis VII in a novel, longitudinal, multicenter disease monitoring program

BackgroundMucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of β-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII.MethodsThis disease monitoring program (DMP) is an ongoing, multicenter observational study collecting standardized real-world data from patients with MPS VII (N ≈ 50 planned) treated with vestronidase alfa or any other management approach. Data are monitored and recorded in compliance with Good Clinical Practice guidelines and planned interim analyses of captured data are performed annually. Here we summarize the safety and efficacy outcomes as of 17 November 2022.ResultsAs of the data cutoff date, 35 patients were enrolled: 28 in the Treated Group and seven in the Untreated Group. Mean (SD) age at MPS VII diagnosis was 4.5 (4.0) years (range, 0.0 to 12.4 years), and mean (SD) age at DMP enrollment was 13.9 (11.1) years (range, 1.5 to 50.2 years). Ten patients (29%) had a history of nonimmune hydrops fetalis. In the 23 patients who initiated treatment prior to DMP enrollment, substantial changes in mean excretion from initial baseline to DMP enrollment were observed for the three urinary glycosaminoglycans (uGAGs): dermatan sulfate (DS), -84%; chondroitin sulfate (CS), -55%; heparan sulfate (HS), -42%. Also in this group, mean reduction from initial baseline to months 6, 12, and 24 were maintained for uGAG DS (-84%, -87%, -89%, respectively), CS (-70%, -71%, -76%, respectively), and HS (+ 3%, -32%, and − 41%, respectively). All adverse events (AEs) were consistent with the known vestronidase alfa safety profile. No patients discontinued vestronidase alfa. One patient died.ConclusionsTo date, the DMP has collected invaluable MPS VII disease characteristic data. The benefit-risk profile of vestronidase alfa remains unchanged and favorable for its use in the treatment of pediatric and adult patients with MPS VII. Reductions in DS and CS uGAG demonstrate effectiveness of vestronidase alfa to Month 24. Enrollment is ongoing.

A Brief Review on Good Clinical Practice and its Training Methods

Abstract The field of clinical research continues to advance, and for ethical conduct of research, researchers need to have a strong foundation in good clinical practice (GCP). GCP guidelines are internationally recognized standards that govern the conduct of clinical trials, ensuring the protection of human subjects and the generation of reliable data. However, novice researchers or postgraduate medical students who would delve into research activities may face difficulty getting avenues for GCP training. Hence, in this brief review article, we discuss the significance of GCP in the field of clinical research with a glimpse of its history, development, and key principles. We provide a list of online courses, benefits, and disadvantages of those courses, and a list of organizations that conduct GCP workshops or continued medical education programs in India.

Recommendations for the Clinical Development of Medicinal Products for Non-specific Influenza Chemoprophylaxis

INTRODUCTION. The evolution of the influenza virus has led to a gradual decrease in the effectiveness of current antivirals. Better methods of prevention, detection, control, and treatment of influenza are needed, including more effective vaccines and antivirals. At the moment, the Russian Federation and the Eurasian Economic Union lack documents regulating the conduct of clinical trials of medicinal products for influenza prevention and require that guidelines should be developed for the matter.AIM. The authors aimed to analyse the main regulatory approaches to preclinical and clinical development programmes for medicinal products for influenza prevention in the Russian Federation, the Eurasian Economic Union (EAEU), the European Union, and the United States of America.DISCUSSION. This review substantiates the importance of non-specific influenza chemoprophylaxis in reducing the risk of adverse outcomes of the disease. The authors analysed the main stages of preclinical development of medicinal products for influenza prevention and the potential contribution of preclinical studies to the planning of clinical trials. When developing preclinical and clinical programmes for medicinal products for influenza prevention, it is necessary, first of all, to take into account the requirements of the national good clinical practice guidelines and the EAEU guidelines for clinical trials in general. This article pays particular attention to the clinical trial designs used internationally, the possible options for their implementation, the characteristics of study populations, the formation of study groups, and the selection of primary and secondary endpoints.CONCLUSIONS. The article proposes approaches to planning and conducting clinical trials of medicinal products for the prevention of influenza, taking into account the specifics of legal norms and clinical traditions of Russian practice. These recommendations will ensure high-quality data on the effectiveness and safety of investigational medicinal products and accelerate the introduction of new effective medicinal products for influenza prevention into medical practice.

Home-based Intervention with Semaglutide Treatment of Neuroleptic-Related Prediabetes (HISTORI): protocol describing a prospective, randomised, placebo controlled and double-blinded multicentre trial

IntroductionSubjects with schizophrenia have a 2–3 fold higher mortality rate than the general population and a reduced life expectancy of 10–20 years. Approximately one-third of this excess mortality has been...

임상시험연구 교과기반 학습성과 평가

Objectives The purpose of this study is to evaluate the awareness of ethical perspective and clinical research coordinator's roles in an entry-level clinical trial research course based on the course-embedded assessment tied with the program learning outcomes of the bachelor's degree among nursing students.&#x0D; Methods Three professional clinical coordinators affiliated with Korea National Enterprise for Clinical Trials (KoNECT) and two nursing professors developed the course based on Good Clinical Practice guidelines in clinical trials. Eighty-three nursing students enrolled and completed this course. Three evaluation criteria were rated in the course-embedded assessment: Completion of the course by getting certificate from the KoNECT(70%), attendance (10%), reflection journal report (20%). Additionally, learners responded two surveys on the satisfaction with education and awareness of ethical roles in clinical trial research. Data were analyzed using the SPSS 23.0 program. The difference in ethical awareness of clinical trial research according to general characteristics was analyzed using t-test and ANOVA with Scheffé's multiple comparison. Importance-Performance analysis(IPA) and thematic analysis were used for ethical perspective and the clinical research coordinator's roles.&#x0D; Results All students completed the clinical trial research course by getting the KoNECT certificates, and 94% of students reported that they were satisfied with the course. IPA analysis showed that nursing students recognized all the ethical roles of clinical trial research nurses as more important and more performing. Thematic analysis exhibited that the roles of CRC had four main themes: expertise and responsibility as clinical trial specialists, decision-making based on ethical principles, sufficient education and explanation for the voluntary participation of subjects, and the convergent capability underlying clinical trial research.&#x0D; Conclusions Based on these findings, the entry-level clinical trial research course was useful for developing awareness of ethical roles and CRC's roles, and provided a new opportunity to map out nursing students' career path.&#x0D;

Impact of intraosseous regional administration of tranexamic acid in total knee arthroplasty on perioperative blood loss: a protocol for a randomised controlled trial

IntroductionTotal knee arthroplasty (TKA) is a common surgical intervention to treat joint diseases. However, TKA is associated with significant blood loss. Tranexamic acid (TXA) has been used to reduce perioperative...

Predicting mortality risk in hospitalized COVID-19 patients: an early model utilizing clinical symptoms

BackgroundDespite global efforts to control the COVID-19 pandemic, the emergence of new viral strains continues to pose a significant threat. Accurate patient stratification, optimized resource allocation, and appropriate treatment are crucial in managing COVID-19 cases. To address this, a simple and accurate prognostic tool capable of rapidly identifying individuals at high risk of mortality is urgently needed. Early prognosis facilitates predicting treatment outcomes and enables effective patient management. The aim of this study was to develop an early predictive model for assessing mortality risk in hospitalized COVID-19 patients, utilizing baseline clinical factors.MethodsWe conducted a descriptive cross-sectional study involving a cohort of 375 COVID-19 patients admitted and treated at the COVID-19 Patient Treatment Center in Military Hospital 175 from October 2021 to December 2022.ResultsAmong the 375 patients, 246 and 129 patients were categorized into the survival and mortality groups, respectively. Our findings revealed six clinical factors that demonstrated independent predictive value for mortality in COVID-19 patients. These factors included age greater than 50 years, presence of multiple underlying diseases, dyspnea, acute confusion, saturation of peripheral oxygen below 94%, and oxygen demand exceeding 5 L per minute. We integrated these factors to develop the Military Hospital 175 scale (MH175), a prognostic scale demonstrating significant discriminatory ability with an area under the curve (AUC) of 0.87. The optimal cutoff value for predicting mortality risk using the MH175 score was determined to be ≥ 3 points, resulting in a sensitivity of 96.1%, specificity of 63.4%, positive predictive value of 58%, and negative predictive value of 96.9%.ConclusionsThe MH175 scale demonstrated a robust predictive capacity for assessing mortality risk in patients with COVID-19. Implementation of the MH175 scale in clinical settings can aid in patient stratification and facilitate the application of appropriate treatment strategies, ultimately reducing the risk of death. Therefore, the utilization of the MH175 scale holds significant potential to improve clinical outcomes in COVID-19 patients.Trial registrationAn independent ethics committee approved the study (Research Ethics Committee of Military Hospital 175 (No. 3598GCN-HDDD; date: October 8, 2021), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.

Pragmatic Adaptive Trial for Respiratory Infection in Children (PATRIC) Clinical Registry protocol

IntroductionAcute respiratory infections (ARI) are the most common cause of paediatric hospitalisation. There is an urgent need to address ongoing critical knowledge gaps in ARI management. The Pragmatic Adaptive Trial...