Chloroquine Induced Oxidative Stress in Male Albino Mice: RCT

Many drugs have been found to induce oxidative stress. Oxidative stress is responsible for a large number of diseases. Chloroquine is one of the drugs, which can induce oxidative stress, when it is given at higher dose. Purpose: To find the effect of chloroquine as stress inducer on albino mice. Study Design: Randomized clinical trial. Methodology: Sixty male albino mice were taken into this randomized controlled study. Those were divided into two groups of 30 each. Group A was the control group while group B mice were given single oral dose of 970 mg/kg of body weight of chloroquine on 9th day of experiment. Terminal intracardiac blood sample was obtained on 17th day of experiment. Statistical analysis: SPSS version 23 was used for data analysis. Results: When results of group B were compared with those of group A, there was highly significant (p= 0.000) rise in serum malondialdehyde level and highly significant (p= 0.000) decrease in serum glutathione peroxidase level. Conclusion: It was concluded that Chloroquine induces oxidative stress when it is given at the dose of 970 mg/kg of body weight in mice. Keywords: Chloroquine, Oxidative Stress and Malondialdehyde.

Master Protocols for Precision Medicine in Oncology: Overcoming Methodology of Randomized Clinical Trials

Randomized clinical trials are considered the milestones of clinical research in oncology, and guided the development and approval of new compounds so far. In the last few years, however, molecular and genomic profiling led to a change of paradigm in therapeutic algorithms of many cancer types, with the spread of different biomarker-driven therapies (or targeted therapies). This scenario of “personalized medicine” revolutionized therapeutic strategies and the methodology of the supporting clinical research. New clinical trial designs are emerging to answer to the unmet clinical needs related to the development of these targeted therapies, overcoming the “classical” structure of randomized studies. Innovative trial designs able to evaluate more than one treatment in the same group of patients or many groups of patients with the same treatment (or both) are emerging as a possible future standard in clinical trial methodology. These are identified as “master protocols”, and include umbrella, basket and platform trials. In this review, we described the main characteristics of these new trial designs, focusing on the opportunities and limitations of their use in the era of personalized medicine.

Chloroquine Induced Hepatotoxicity in Male Albino Mice: RCT

Many drugs have been found to induce hepatotoxicity and acute liver failure. Chloroquine is one of those drugs, which can induce hepatotoxicity when it is given at higher dose Purpose: To find the effect of chloroquine on liver function tests (LFTs) Study Design: Randomized clinical trial Methodology: Sixty male albino mice were taken into this randomized controlled study. Those were divided into two groups of 30 each. Group A was the control group while group B mice were given single oral dose of 970 mg/kg of body weight of chloroquine on 9th day of experiment. Terminal intracardiac blood sample was obtained on 17th day of experiment Statistical analysis: SPSS version 23 was used for data analysis Results: When results of group B were compared with those of group A, they depicted highly significant (p=0.000) rise in serum ALP. Serum albumin decreased significantly (p= 0.007). Serum AST increased significantly (p=0.005). Serum ALT, however, did not rise significantly (p=0.285) in group B. Similarly, serum total proteins did not decrease significantly ( p=0.530) in group B Conclusion: It was concluded that chloroquine induced mild hepatotoxicity in male albino mice when a single oral dose of 970 mg/kg of body weight of it is given Key Words: Chloroquine, Hepatotoxicity and Alkaline Phosphatase.

The role of machine learning in clinical research: transforming the future of evidence generation

Background Interest in the application of machine learning (ML) to the design, conduct, and analysis of clinical trials has grown, but the evidence base for such applications has not been surveyed. This manuscript reviews the proceedings of a multi-stakeholder conference to discuss the current and future state of ML for clinical research. Key areas of clinical trial methodology in which ML holds particular promise and priority areas for further investigation are presented alongside a narrative review of evidence supporting the use of ML across the clinical trial spectrum. Results Conference attendees included stakeholders, such as biomedical and ML researchers, representatives from the US Food and Drug Administration (FDA), artificial intelligence technology and data analytics companies, non-profit organizations, patient advocacy groups, and pharmaceutical companies. ML contributions to clinical research were highlighted in the pre-trial phase, cohort selection and participant management, and data collection and analysis. A particular focus was paid to the operational and philosophical barriers to ML in clinical research. Peer-reviewed evidence was noted to be lacking in several areas. Conclusions ML holds great promise for improving the efficiency and quality of clinical research, but substantial barriers remain, the surmounting of which will require addressing significant gaps in evidence.

REPORT-PFP: a consensus from the International Patellofemoral Research Network to improve REPORTing of quantitative PatelloFemoral Pain studies

Patellofemoral pain is a common and often debilitating musculoskeletal condition. Clinical translation and evidence synthesis of patellofemoral pain research are compromised by heterogenous and often inadequately reported study details. This consensus statement and associated checklist provides standards for REPORTing of quantitative PatelloFemoral Pain (REPORT-PFP) research to enhance clinical translation and evidence synthesis, and support clinician engagement with research and data collection. A three-stage Delphi process was initiated at the 2015 International Patellofemoral Research Network (iPFRN) retreat. An initial e-Delphi activity (n=24) generated topics and items, which were refined at the 2017 iPFRN retreat, and voted on prior to and following the 2019 iPFRN retreat (n=51 current and past retreat participants). Voting criteria included ‘strongly recommended’ (essential), ‘recommended’ (encouraged) and uncertain/unsure. An item was included in the checklist if ≥70% respondents voted ‘recommended’. Items receiving ≥70% votes for ‘strongly recommended’ were labelled as such. The final REPORT-PFP checklist includes 31 items (11 strongly recommended, 20 recommended), covering (i) demographics (n=2,4); (ii) baseline symptoms and previous treatments (n=3,7); (iii) outcome measures (2,4); (iv) outcomes measure description (n=1,2); (v) clinical trial methodology (0,3) and (vi) reporting study results (n=3,0). The REPORT-PFP checklist is ready to be used by researchers and clinicians. Strong stakeholder engagement from clinical academics during development means consistent application by the international patellofemoral pain research community is likely. Checklist adherence will improve research accessibility for clinicians and enhance future evidence synthesis.

Bringing Advances in Elder Abuse Research Methodology and Theory to Evaluation of Interventions

The elder abuse field needs high-quality intervention research to assess the best strategies to combat the problem, but few such studies exist. Significant advances have been made in elder abuse research methodology, measurement, justice theory, and other relevant areas, which may remedy this gap. Particular advances include the use of elder abuse severity measures and goal attainment scaling, and the application of restorative justice theory to intervention. Elder abuse research also may benefit from advances in biomedical clinical trial methodology, including characterizing and following up with subjects excluded from trials or those who drop out, estimating numbers needed to treat to assess cost-effectiveness, and a priori stopping rules for when an intervention proves quickly beneficial or harmful. In this article, we argue these advances can and should inform elder abuse intervention research, propose a theoretical framework to guide such efforts, and demonstrate how this framework can inform practice, using elder abuse multidisciplinary teams and nursing home shelters as examples.

Intelligent Virtual Reality Therapy Systems for Motor and Cognitive Rehabilitation: A Survey based on Clinical Trial Studies

Rehabilitation is the process related to the recovery, maintenance or improvement of physical mental and / or cognitive skills necessary to carry out daily activities. Virtual reality therapy, virtual reality (VR) immersion therapy, simulation therapy or virtual reality exposure therapy is an intervention method of using virtual reality technology for psychological or occupational therapy. The possibility of simulating situations necessary for the treatment, controlling variables and reducing the patient’s exposure to risks are popular factors for this tool. Many studies indicate that therapy with the aid of virtual reality brings great benefits to the patient. In this article, we present, through a review of 117 articles, the feasibility of applying VR in treatments with clinical trial methodology, identifying through the "Patient, Intervention, Comparison and Outcomes" the characteristics, population, treatment time, forms of comparison and if the results obtained are effective. The characteristics identified during the process show that virtual reality applied to therapies can be used without negative interference in the treatment. In addition, the results show that VR in rehabilitation treatments are motivating and show better results than traditional treatments.

Knowledge and Perception Regarding Clinical Trials Among Dental Students-A Questionnaire Based Study

Clinical trials play an important role in improvement of quality on healthcare practice. Good clinical practice is a backbone of conductance of trials. A lack of knowledge may translate to a negative perception towards clinical trials. The study aims to evaluate the awareness of clinical trials among undergraduate dental students in a private dental institute. We have quantified the knowledge and perception of clinical trials by a structured validated questionnaire. The questionnaire was administered to dental students from first year undergraduate to third year Postgraduate. The percentage of questions answered were calculated and tabulated in the excel sheet. Data were analysed using SPSS statistical software and the chi-square test was done. P valve was set as 0.05 as a level of significance. From statistical analysis, postgraduate students (59.2%) had better knowledge than undergraduate students (40.8%). Around (46.7%) had been involved in clinical trial training. Within the limitations of current study, students pursuing postgraduate had a better knowledge of clinical trial methodology than compared to undergraduate students.

Global Trials, Local Bodies: Negotiating Difference and Sameness in Indian For-profit Clinical Trials

Global clinical trials depend on a range of standards in order for research results to be comparable. As standardization is more than a mere technical exercise, tensions can arise when things are not uniform. This paper uses empirical data from interviews with principal investigators as well as Clinical Research Organization and pharmaceutical industry representatives working in India’s clinical trial industry to critically examine the ways Indian researchers navigate quests for standardization. It turns the analytical lens to the often obfuscated work of standardization aiming to transcend the biological and cultural specificity of research participants and research sites. Drawing on the concept of local biologies, it illustrates that the universal body presumed by clinical trial methodology is, in fact, a specifically Euro-American one: Indian participants not only need to be made globally comparable but also aligned with the drugs’ future consumers. Focusing on the tensions between biomedicine’s postulation of bodily universality and trial participants’ local biologies, this paper advances recent interventions problematizing the structural violence undergirding global clinical trials. It also contributes to the literature on local biologies in its discussion of how these are negotiated in Indian for-profit clinical trials.

Vaccination against Japanese encephalitis with IC51: systematic review on immunogenicity, duration of protection and safety

Japanese encephalitis is a disease caused by a flavivirus which is transmitted by mosquitos in endemic countries. Considering the potentially severe outcomes of the disease, vaccination is recommended for those at risk of exposure. During recent years, IC51 (IXIARO®, JESPECT®, JEVAL®) has increasingly been used to protect travellers from Europe and the USA. However, no systematic review exists that summarizes the currently available evidence on the immunogenicity and safety of this vaccine. We conducted a systematic review on the immunogenicity and safety of IC51, using the databases PubMed, MEDLINE, EMBASE and ClinicalTrials.gov (search date: 31 August 2019). Data extracted from included studies were grouped by outcomes and stratified by population and setting. Risk of bias (ROB) was assessed using the RoB 2 tool for randomized controlled trials (RCTs) and ROBINS-I for non-randomized studies. Due to high heterogeneity, meta-analysis was not performed. A total of 32 studies from 16 countries met the inclusion criteria (15 RCTs, 17 non-randomized studies). ROB was serious or high in the majority of studies. Seroprotection rates ranged from 93 to 100% in adults (seven studies) and from 91 to 100% in children (four studies). In the study involving adults aged 64 years and older, seroprotection was 65% with higher rates in persons who were previously vaccinated against tick-borne encephalitis virus. Safety was investigated in 27 studies. Rates of serious adverse events were below 5% in all age groups, with the majority not being causally related to the vaccine. IC51 is a safe vaccine with good seroprotective abilities in persons aged >2 months to <64 years. The body of evidence, however, is weakened by a large amount of heterogeneity in study and clinical trial methodology. Further well-designed RCTs with special risk groups are needed.