Reviews on Recent Clinical Trials - Volume 15, Issue 1, 2020

Background: According to European legislation, a clinical trial is a research involving patients, which also includes a research end-product. The main objective of the clinical trial is to prove that the research product, i.e. a proposed medication or treatment, is effective and safe for patients. The implementation, development, and operation of a patient database, which will function as a matrix of samples with the appropriate parameterization, may provide appropriate tools to generate samples for clinical trials. Aims: The aim of the present work is to review the literature with respect to the up-to-date progress on the development of databases for clinical trials and patient recruitment using free and open-source software in the field of endocrinology. Methods: An electronic literature search was conducted by the authors from 1984 to June 2019. Original articles and systematic reviews selected, and the titles and abstracts of papers screened to determine whether they met the eligibility criteria, and full texts of the selected articles were retrieved. Results: The present review has indicated that the electronic health records are related with both the patient recruitment and the decision support systems in the domain of endocrinology. The free and open-source software provides integrated solutions concerning electronic health records, patient recruitment, and the decision support systems. Conclusion: The patient recruitment relates closely to the electronic health record. There is maturity at the academic and research level, which may lead to good practices for the deployment of the electronic health record in selecting the right patients for clinical trials.

Background: Biofilm is a fundamental component in the pathogenesis of infections related to the use of the central venous catheter (CVC,) which can represent an important health issue in everyday practice of nursing and medical staff. Objective: The objective of the following review is to analyze the components of biofilm and their role in catheter-related infection determinism in an evidencebased nursing perspective in such a way as to give health professionals useful suggestions in the prevention and management of these complications. Methods: The following databases were consulted for the bibliographic search: Medline, Scopus, Science Direct. Biofilm can be the cause of CVC extraction and can lead to serious haematogenic infectious complications that can increase the morbidity and mortality of affected patients. Results: Updated pathophysiologic knowledge of biofilm formation and appropriate diagnostic methodology are pivotal in understanding and detecting CVC-related infections. Lock therapy appears to be a useful, preventive, and therapeutic aid in the management of CVCrelated infections. New therapies attempting to stop bacterial adhesion on the materials used could represent new frontiers for the prevention of CVC-related infections. Conclusion: The correct evidence-based nursing methods, based on the use of guidelines, provides the opportunity to minimize the risks of infection through the implementation of a series of preventive measures both during the CVC positioning phase and in the subsequent phase, for example, during device management which is performed by medical and nursing staff.

Objective: To discuss the potential risks and their mitigation strategies in the post-conduct phase of the trial. Background: Risk management is very important for the clinical trial (CT) to ensure that the trial delivers its desired outcome(s) in terms of achieving protocol objective and regulatory compliance. Methodology: Experienced members of the clinical operation team of a pharmaceutical major underwent a series of sessions to identify risks associated with the post-conduct phase of CT and developed mitigation strategies based on own experiences and guidance documents. The risks were categorized into major, minor and critical risks. Results: In the post-conduct phase of a clinical trial, critical risk identified were; failure to communicate to the stakeholder about premature termination of the trial, mismatch of statistical analysis results and protocol objective/ regulatory requirement, clinical study report (CSR) noncompliant with regulatory requirements or delay in CSR preparation. Safety checks suggested to mitigate these risks including the development of related checklist or shell of relevant documents and its review by clinical development, quality assurance (QA) and regulatory affairs (RA) team prior to finalization. Additionally, six major and five minor risk areas were identified and safety checks were suggested. Conclusion: Sponsors must act proactively to ensure a systematic approach to conduct various post conduct trial activities and the plans to mitigate the risks that could affect the quality and outcome of the clinical trial. Future Perspective: A close coordination with all stakeholders for timely anticipation of risks and execution of mitigation strategies are required for successful CT outcomes.

Background: Prostate cancer (PCa) is the sixth primary cause of cancer death. However, conflicts are present about the efficacy and safety of Non-steroidal anti-androgens (NSAA) for its treatment. The aim of this study was to assess the efficacy and safety of NSAAs versus any comparator for the treatment of advanced or metastatic PCa (mPCa). Methods: MEDLINE and the Cochrane Library were searched. References of included studies and clinicaltrials.gov were also searched for relevant studies. Only English language studies after 1990 were considered for review. Randomized controlled trials (RCTs) examining the efficacy and safety of NSAAs as compared with any other comparator including surgery or chemotherapy in mPCa patients were included. The outcomes include efficacy, safety and the tolerability of the treatment. The Cochrane Risk of Bias Assessment Tool was used for quality assessment. Two authors were independently involved in the selection, extraction and quality assessment of included studies and disagreements were resolved by discussion or by consulting a third reviewer. Results: Fifty-eight out of 1307 non-duplicate RCTs with 29154 patients were considered for the review. NSAA showed significantly better progression-free survival [PFS] (Hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.46-0.78; P=0.0001), time to distant metastasis or death [TTD] (HR, 0.80; 95% CI 0.73-0.91; P<0.0001), objective response (Odds ratio [OR], 1.64; 95% CI 1.06-2.54; P=0.03) and clinical benefits (OR, 1.33; 95% CI 1.08-1.63; P=0.006) as compared to the control group. There was no significant difference observed between the groups in terms of overall survival (HR, 0.95; 95%CI, 0.87-1.03; P=0.18) and time to progression (HR, 0.93; 95% CI 0.77-1.11; P=0.43). Treatment-related adverse events were more with the NSAA group, but the discontinuation due to lack of efficacy reason was 43% significantly lesser than the control group in patients with mPCa. Rest of the outcomes were appeared to be non-significant. Conclusion: Treatment with NSAA was appeared to be better efficacious with respect to PFS, TTD, and response rate with considerable adverse events when compared to the control group in patients with metastatic PCa.

Background: In recent years, attention of the scientific community has been drawn to the study of the role of homocysteine in the pathology of diseases in general and the respiratory system in particular. Violations of the synthesis and disposal of homocysteine are the cause of its excessive accumulation in the body, which subsequently leads to damage to all organs and systems. Methods: We conducted this study on 64 white non-linear rats of 6-8 and 24-26 months old rats, which were divided into two control and experimental groups during the experiment. The study of ultrastructural changes in the lungs of rats was performed using an electron microscope. Results: The results of the conducted study show that all the animals of the experimental group, corresponding to 32 (50%) cases, possess conspicuous morphological changes in the structure of the lungs. The specific features of mature animals were the narrowing of the alveolar space of the part of the alveoli and the increase in the number of macrophages in them. Partial desquamation of capillary endothelial lining and a slight increase of collagen fibers in interalveolar membranes were observed compared to control animals. A characteristic feature for older animals was the growth of connective tissue, predominantly collagen fibers, which led to pneumosclerosis. The thickening of the aerogemic barrier was also detected, and the endothelial lining was intermittent or desquamated. Conclusion: Mature animals of the experimental group were characterized by activation of inflammatory processes, oxidative stress, due to increased production of macrophages and, as a consequence, the launch of the humorous link of immunity, while in old rats were determined by fibrosis, disorders of the trophic and gas metabolism, as well as damage to the endothelium part of lungs.

Background: Although previous research has shown that internalizing and externalizing behavior problems often co-occur, the relationship between the developmental trajectories of these two types of behavior problems is understudied. The co-occurring evolutions of developmental trajectories of two behaviors has two components: 1) the correlation between the slopes of two behavior profiles (termed the association of the evolutions); and 2) the marginal correlation of two development trajectory profiles, which is the development of correlation between internalizing and externalizing behavior over time (termed the evolution of the association). The association of the evolutions and the evolution of the association have not been fully explored in the context of the development of internalizing and externalizing behavior problems among kindergarteners in the United States. Methods: The random-effects approach for joint modeling of multivariate longitudinal profiles was used to evaluate the co-development and its temporal pattern of internalizing and externalizing behavior problems on a nationally representative sample of 9791 kindergarteners from the Early Childhood Longitudinal Study-Kindergarten Class of 1998-99 (ECLS-K). Results: There was a moderate positive association between the evolutions of the two behavior problems with correlation coefficient of 0.319. The evolution of association between the two behaviors was increasing over time with the correlation coefficient from 0.195 at the Fall of kindergarten to 0.291 by the time of fifth grade in general. Race and age groups act differently on the evolution of association. The associations were getting stronger for the Asian group and older groups than their peer groups. Conclusion: This investigation of the association of evolutions and the evolution of association between the internalizing and externalizing behaviors show that the two problem behaviors reciprocally reinforce each other and lead to increases in the other in a moderate strength and the strength is increasing over time.

Introduction: Controlling of secondary traumatic brain injuries (TBI) is necessary due to its salient effect on the improvement of patients with TBI and the final outcomes within early hours of trauma onset. This study aims to investigate the effect of intravenous tranexamic acid (TAX) administration on decreased hemorrhage during surgery. Methods: This double-blind, randomized, and placebo-controlled trial was conducted on patients referring to the emergency department (ED) with IPH due to brain contusion within 8 h of injury onset. The patients were evaluated by receiving TXA and 0.9% normal saline as a placebo. The following evaluation and estimations were performed: intracranial hemorrhage volume after surgery using brain CT-scan; hemoglobin (Hb) volume before, immediately after, and six hours after surgery; and the severity of TBI based on Glasgow Coma Score (GCS). Results: 40 patients with 55.02 ± 18.64 years old diagnosed with a contusion and intraparenchymal hemorrhage. Although the (Mean ± SD) hemorrhage during surgery in patients receiving TXA (784.21 ± 304.162) was lower than the placebo group (805.26 ± 300.876), no significant difference was observed between two groups (P=0.83). The (Mean ± SD) Hb volume reduction immediately during surgery (0.07 ± 0.001 and 0.23 ± 0.02) and six hours after surgery (0.04 ± 0.008 and 0.12 ± 0.006) was also lower in TXA group but had no significant difference (P = 0.89 and P = 0.97, respectively). Conclusion: Using TXA may reduce the hemorrhage in patients with TBI, but this effect, as in this study, was not statistically significant and it is suggested that a clinical trial with a larger population is employed for further investigation.

Objective: The present study was conducted to investigate the effect of intradermal administration of sterile water compared to intravenous morphine on patients with renal colic. Methods: This double-blind, randomized clinical trial study was conducted in 2017 to compare the therapeutic effects of intradermal sterile water with those of intravenous morphine on patients with renal colic presenting to the emergency departments (ED) of Imam Khomeini and Golestan Hospitals in Ahvaz, Iran. The first group received 0.5 ml of intradermal sterile water, and the second group 0.1mg/kg of intravenous morphine plus 0.5 ml of intradermal sterile water in the most painful area or the center of the painful area in the flank. The pain severity was measured using a visual analogue scale (VAS), and the medication side-effects were recorded at the beginning of the study and minutes 15, 30,45 and 60. Results: A total of 94 patients were studied in two groups. The mean severity of pain was 2.97 ± 1.51 in the sterile water group and 2.34 ± 1.89 in the morphine group at minute 30 (P=0.042), 2.58 ± 1.43 in the sterile water group and 1 ± 1.23 in the morphine group at minute 45 (P<0.001), and 1.89 ± 1.7 in the sterile water group and 0.52 ± 0.79 in the morphine group at minute 60 (P<0.001). Conclusion: Morphine reduces pain faster and more effectively than intradermal sterile water; nevertheless, treatment with intradermal sterile water can be used as an appropriate surrogate or adjunct therapy for pain control, particularly in special patients or in case of medication scarcity.