Are paid tools worth the cost? A prospective cross-over study to find the right tool for plagiarism detection.

Background: The increasing pressure to publish research has led to a rise in plagiarism incidents, creating a need for effective plagiarism detection software. The importance of this study lies in the high cost variation amongst the available options for plagiarism detection. By uncovering the advantages of these low-cost or free alternatives, researchers could access the appropriate tools for plagiarism detection. This is the first study to compare four plagiarism detection tools and assess factors impacting their effectiveness in identifying plagiarism in AI-generated articles. Methodology: A prospective cross-over study was conducted with the primary objective to compare Overall Similarity Index(OSI) of four plagiarism detection software(iThenticate, Grammarly, Small SEO Tools, and DupliChecker) on AI-generated articles. ChatGPT was used to generate 100 articles, ten from each of ten general domains affecting various aspects of life. These were run through four software, recording the OSI. Flesch Reading Ease Score(FRES), Gunning Fog Index(GFI), and Flesch-Kincaid Grade Level(FKGL) were used to assess how factors, such as article length and language complexity, impact plagiarism detection. Results: The study found significant variation in OSI(p < 0.001) among the four software, with Grammarly having the highest mean rank(3.56) and Small SEO Tools having the lowest(1.67). Pairwise analyses revealed significant differences(p < 0.001) between all pairs except for Small SEO Tools-DupliChecker. Number of words showed a significant correlation with OSI for iThenticate(p < 0.05) but not for the other three. FRES had a positive correlation, and GFI had a negative correlation with OSI by DupliChecker. FKGL negatively correlated with OSI by Small SEO Tools and DupliChecker. Conclusion: Grammarly is unexpectedly most effective in detecting plagiarism in AI-generated articles compared to the other tools. This could be due to different softwares using diverse data sources. This highlights the potential for lower-cost plagiarism detection tools to be utilized by researchers.

Chimeric antigen receptor T cell: A cancer immunotherapy.

During present decade, targeted drug therapy has been the epitome for treatment of cancer. Drugs like Imatinib, a tyrosine kinase receptor inhibitor and Trastuzumab, an human epidermal growth factor receptor-2/neu inhibitor, has been developed and accepted widely for management of chronic myeloid leukaemia and breast cancer respectively. Recent development among the various immunotherapies is adoptive cell transfer (ACT). Research on development of various types of ACT immunotherapy is going on, but so far, Chimeric antigen receptors T cell therapy (CAR-T) has achieved the maximum advancement in terms of clinical development. CARs are the modified receptors that integrates specificity and responsiveness onto immune cells to enhance the recognition of cancer cells. For the CAR-T, the T cells are sequestered from a blood of a participant via apheresis. DNA of particular antigen is injected into harvested T cells to generate CARs on cell surface. Following surface manifestation of receptors, multiplication is carried out in enriched media followed by infusion into patient. After infusion, CAR-T cells targeted and exterminate the cancer cells. Initially, only two drugs targeting CD19 as genetically modified autologous immunotherapy has been approved in CAR-T therapy i.e., Tisagenlecleucel and Axicabtagene Ciloleucel, which are discussed in detail in current review. Recently two more drugs got approval i.e., brexucabtagene ciloleucel and lisocabtagene maraleucel, both are directed against CD19, similar to tisagenlecleucel. CAR-T cell therapy is approved for management of Acute Lymphoblastic Leukaemia, Chronic Lymphocytic Leukaemia and lymphoma. CAR-T cell persistence responsible for effectiveness and safety concerns are barriers for their wide application among patients. Growth factor receptors and cluster of differentiation are new drugs targets that are being explored as effective immunotherapy against cancers.

Impact of COVID-19 on Antimicrobial Resistance in Paediatric Population: a Narrative Review.

Purpose of Review: Irrational use of antimicrobials has been reported in paediatric population during the COVID-19 time period. This may lead to potential development of antimicrobial resistance and increased morbidity and mortality among this vulnerable population. The purpose of this review is to ascertain the impact of COVID-19 pandemic on antimicrobial resistance among paediatrics and the possible strategies to minimize the menace of antimicrobial resistance. Recent Findings: Recent findings indicate that the COVID-19 pandemic has direct as well as indirect impact on the development of antimicrobial resistance among paediatric population. Summary: This review article shows the impact of COVID-19 on the development of antimicrobial resistance and strategies to prevent it with special reference to antimicrobial stewardship programmes among paediatric population.

Efficacy and safety of vitamin D in tuberculosis patients: a systematic review and meta-analysis.

BACKGROUND: Evidence from the basic research and epidemiological studies indicates a beneficial effect of vitamin D in the treatment of tuberculosis (TB). However, the evidence from randomized controlled trials (RCTs) is inconsistent. OBJECTIVES: This systematic review and meta-analysis was performed to synthesize evidence regarding role of vitamin D versus placebo for the management of TB. MATERIALS AND METHODS: We searched PubMed and Cochrane Clinical Trial Registry for RCTs comparing vitamin D versus placebo for the treatment of TB. RCTs enrolling adult patients with TB receiving vitamin D in addition to standard treatment were included. Data were pooled using random effects model. The study was conducted according to PRISMA guidelines and protocol was registered with PROSPERO (CRD42016052841). RESULTS: Of 605 identified references, 12 RCTs were included. The overall risk of bias in included studies was low or unclear. There was no significant difference between vitamin D and placebo group for any outcomes of efficacy (time to culture conversion, time to smear conversion, rate of culture conversion, and rate of smear conversion) or safety (mortality, serious adverse events, and nonserious adverse events). CONCLUSION: Vitamin D administered with standard treatment has no beneficial effect in the TB patients as compared to the placebo.

Menace of antimicrobial resistance in LMICs: Current surveillance practices and control measures to tackle hostility.

Antimicrobial Resistance (AMR) is significant challenge humanity faces today, with many patients losing their lives every year due to AMR. It is more widespread and has shown a higher prevalence in low- and middle-income countries (LMICs) due to lack of awareness and other associated reasons. WHO has suggested some crucial guidelines and specific strategies such as antimicrobial stewardship programs taken at the institutional level to combat AMR. Creating awareness at the grassroots level can help to reduce the AMR and promote safe and effective use of antimicrobials. Control strategies in curbing AMR also comprise hygiene and sanitation as microbes travel from contaminated surroundings to the human body surface. As resistance to multiple drugs increases, vaccines can play a significant role in curbing the menace of AMR. This article summarizes the current surveillance practices and applied control measures to tackle the hostility in these countries with particular reference to the role of antimicrobial stewardship programs and the responsibilities of regulatory authorities in managing the situation.

Flashback and lessons learnt from history of pandemics before COVID-19.

With an increasing frequency of infectious disease outbreaks, the COVID-19 pandemic causing mortality around the world and the threat of similar future events looming large, mankind is faced with the herculean task of counteracting such threats with the best possible strategies and public health decisions. It is key that such decisions should be guided by previous examples of similar health emergencies. Here we review some of the significant infectious disease outbreaks, including epidemics and pandemics occurring worldwide in the past including their impact at population and global levels, unique challenges presented by each and the measures taken by authorities worldwide as well as the crucial lessons each epidemic or pandemic provided. This review highlights that throughout history measures such as contact tracing, quarantine and isolation have been incredibly effective in limiting an outbreak in its severity, thus ensuring accurate information flow to the public is as essential as limiting the spread of misinformation. With global populations rising, surveillance for emerging and re-emerging pathogens will play an immense role in preventing future epidemics or pandemics. And finally that even though for novel strains or pathogens, although vaccines are thought to be an irreplaceable defense, but their development and distribution in time to curb an epidemic has seldom been witnessed and remains an important challenge for the future. Hence, we conclude that looking at these past examples not only highlights the important knowledge gained for the strategies to devise, but also the mistakes that can be avoided in the way forward.

The Current Situation Regarding Long-Acting Insulin Analogues Including Biosimilars Among African, Asian, European, and South American Countries; Findings and Implications for the Future.

Background: Diabetes mellitus rates continue to rise, which coupled with increasing costs of associated complications has appreciably increased global expenditure in recent years. The risk of complications are enhanced by poor glycaemic control including hypoglycaemia. Long-acting insulin analogues were developed to reduce hypoglycaemia and improve adherence. Their considerably higher costs though have impacted their funding and use. Biosimilars can help reduce medicine costs. However, their introduction has been affected by a number of factors. These include the originator company dropping its price as well as promoting patented higher strength 300 IU/ml insulin glargine. There can also be concerns with different devices between the manufacturers. Objective: To assess current utilisation rates for insulins, especially long-acting insulin analogues, and the rationale for patterns seen, across multiple countries to inform strategies to enhance future utilisation of long-acting insulin analogue biosimilars to benefit all key stakeholders. Our approach: Multiple approaches including assessing the utilisation, expenditure and prices of insulins, including biosimilar insulin glargine, across multiple continents and countries. Results: There was considerable variation in the use of long-acting insulin analogues as a percentage of all insulins prescribed and dispensed across countries and continents. This ranged from limited use of long-acting insulin analogues among African countries compared to routine funding and use across Europe in view of their perceived benefits. Increasing use was also seen among Asian countries including Bangladesh and India for similar reasons. However, concerns with costs and value limited their use across Africa, Brazil and Pakistan. There was though limited use of biosimilar insulin glargine 100 IU/ml compared with other recent biosimilars especially among European countries and Korea. This was principally driven by small price differences in reality between the originator and biosimilars coupled with increasing use of the patented 300 IU/ml formulation. A number of activities were identified to enhance future biosimilar use. These included only reimbursing biosimilar long-acting insulin analogues, introducing prescribing targets and increasing competition among manufacturers including stimulating local production. Conclusions: There are concerns with the availability and use of insulin glargine biosimilars despite lower costs. This can be addressed by multiple activities.

Current utilization patterns for long-acting insulin analogues including biosimilars among selected Asian countries and the implications for the future.

INTRODUCTION: Prevalence rates for diabetes mellitus continue to rise, which, coupled with increasing costs of complications, has appreciably increased expenditure in recent years. Poor glycaemic control including hypoglycaemia enhances complication rates and associated morbidity, mortality and costs. Consequently, this needs to be addressed. Whilst the majority of patients with diabetes have type-2 diabetes, a considerable number of patients with diabetes require insulin to help control their diabetes. Long-acting insulin analogues were developed to reduce hypoglycaemia associated with insulin and help improve adherence, which can be a concern. However, their considerably higher costs have impacted on their funding and use, especially in countries with affordability issues. Biosimilars can help reduce the costs of long-acting insulin analogues thereby increasing available choices. However, the availability and use of long-acting insulin analogues can be affected by limited price reductions versus originators and limited demand-side initiatives to encourage their use. Consequently, we wanted to assess current utilisation rates for long-acting insulin analogues, especially biosimilars, and the rationale for patterns seen, across multiple Asian countries ranging from Japan (high-income) to Pakistan (lower-income) to inform future strategies. METHODOLOGY: Multiple approaches including assessing utilization and prices of insulins including biosimilars among six Asian countries and comparing the findings especially with other middle-income countries. RESULTS: Typically, there was increasing use of long-acting insulin analogues among the selected Asian countries. This was especially the case enhanced by biosimilars in Bangladesh, India, and Malaysia reflecting their perceived benefits. However, there was limited use in Pakistan due to issues of affordability similar to a number of African countries. The high use of biosimilars in Bangladesh, India and Malaysia was helped by issues of affordability and local production. The limited use of biosimilars in Japan and Korea reflects limited price reductions and demand-side initiatives similar to a number of European countries. CONCLUSIONS: Increasing use of long-acting insulin analogues across countries is welcomed, adding to the range of insulins available, which increasingly includes biosimilars. A number of activities are needed to enhance the use of long-acting insulin analogue biosimilars in Japan, Korea and Pakistan.

Opinion of primary care physicians regarding prescription of generic drugs: A Cross-sectional study.

BACKGROUND: Generics are low-cost alternatives of the existing approved branded drugs. The aim of this work was to study knowledge and perception about generic drugs among the doctors practicing in government and private healthcare sectors. METHODS: A cross-sectional study was conducted with a prevalidated questionnaire. Physicians working in government and private healthcare sectors were asked to fill the survey form after obtaining written informed consent. Descriptive analysis was used. RESULTS: Of 240, 11.6% of primary care physicians could identify all the correct statements regarding generic drugs and 57% physicians agreed or strongly agreed that doctors should prescribe only generic drugs. Substandard quality (24.4%) and less effectiveness (35.6%) of generics was cited major reason for low use. Majority (76.1%) believed that patients will accept substitution of branded with generics but 21% either did not or rarely inform patients regarding generics. Only 11.7% considered generics has low efficacy as compared to branded drugs but majority (57.4%) denied the interchangeability of generics. Majority were aware about the Jan Aushadhi scheme (79.3%) and Indian Medical Council Act (Professional conduct, Etiquette and Ethics) (76.8%). For personal use, 45.6% preferred generics. Around 44% agreed/strongly agreed for pharmacist's right to substitute branded drugs with generics but private practicing physicians opted against it. CONCLUSION: Knowledge and acceptance of generic drugs is still low amongst the doctors. Efforts need to be done increase the awareness and acceptability.

Adverse Events Reported From COVID-19 Vaccine Trials: A Systematic Review.

COVID-19 infection originated in Wuhan, China in December 2019 and crippled human health globally in no time. The public health emergency required urgent efforts to develop and test the efficacy and safety of vaccines to combat the COVID-19 pandemic. The emergency use approval has been granted to COVID-19 vaccines before the completion of conventional phases of clinical trials. However, there is no comprehensive review of safety data reported from the vaccine trials, which is critical information to inform the policies in order to improve uptake of COVID-19 vaccines and mitigate the risk aversion perceived due to the COVID-vaccine side effects. This study aims to systematically review and synthesize the evidence on the safety data from the published COVID-19 vaccine trials. This study followed PRISMA guidelines. We searched three major electronic databases (PubMed, Embase, and Google Scholar) for published studies between Dec 2019 and 2020. Eligible study designs were randomized trials and pre-and post-intervention evaluations. Descriptive findings of included studies were reported stratified by target population, setting, outcomes, and overall results. From PubMed, Embase, WHO database, and Google Scholar screened titles and abstracts, 11 studies were identified in this review. Most of the reactions reported were mild to moderate whereas a few with severe intensity. All reactions resolved within 3-4 days. The commonly reported local adverse events were pain at the site of injection, swelling, and redness. The systemic reactions included fever, fatigue, myalgia, and headache. Some trials also reported laboratory derangements  like decreased hemoglobin, increased bilirubin, altered SGOT and SGPT. None of these alterations were clinically manifested and were self-limiting. Few clinical trials reported serious adverse events, but they were unrelated to vaccination. This systematic review indicates that COVID-19 vaccines can be safe with no serious adverse events. However, long-term post-marketing surveillance data, particularly in high-risk vulnerable populations (elderly and those with co-morbidities, pregnant women, and children) is warranted to ensure the safety of COVID-19 vaccines.

Rapid review of suspected adverse drug events due to remdesivir in the WHO database; findings and implications.

Objectives: Remdesivir has shown promise in the management of patients with COVID-19 although recent studies have shown concerns with its effectiveness in practice. Despite this there is a need to document potential adverse drug events (ADEs) to guide future decisions as limited ADE data available before the COVID-19 pandemic. Methods: Interrogation of WHO VigiBase® from 2015 to 2020 coupled with published studies of ADEs in COVID-19 patients. The main outcome measures are the extent of ADEs broken down by factors including age, seriousness, region and organ. Results: A total 1086 ADEs were reported from the 439 individual case reports up to July 19, 2020, in the VigiBase®, reduced to 1004 once duplicates were excluded. Almost all ADEs concerned COVID-19 patients (92.5%), with an appreciable number from the Americas (67.7%). The majority of ADEs were from males > 45 years and were serious (82.5%). An increase in hepatic enzymes (32.1%), renal injury (14.4%), rise in creatinine levels (11.2%), and respiratory failure (6.4%) were the most frequently reported ADEs. Conclusions: Deterioration of liver and kidney function are frequently observed ADEs with remdesivir; consequently, patients should be monitored for these ADEs. The findings are in line with ADEs included in regulatory authority documents.

Household Transmission of COVID-19: A Cross-Sectional Study.

INTRODUCTION: The COVID-19 pandemic has brought the entire world to a standstill. The disease is rapidly transmitting in the community. Imposed lockdowns due to the COVID-19 pandemic have effectively delayed the transmission in the community but the transmissibility in households needs to be explored. The aim of this study was to estimate the household transmission of COVID-19 and assess the factors affecting transmission. PATIENTS AND METHODS: A cross-sectional study where the data were collected from a single isolation center, was conducted. Patients were contacted by phone. Information regarding number of COVID-19-positive cases in the family, their demographic details, along with number of rooms in their household was collected. RESULTS: A total of 369 families of COVID-19-positive patients were contacted. Nineteen families with a single member were excluded. Out of 350 families with a total 2126 members, 480 (22.5%) were COVID-19 positive. Mean age was 30.12 years (±14.39) and majority of them were males (68.9%). Majority of the cases (67.3%) were in the age group (19-49 years). Mean rooms per person were 0.51± 0.20 (0.14 to 1.50). Mild negative correlation was seen between number of positive COVID-19 cases and rooms per person (r= -0.138, p=0.008) while moderate negative correlation with number of family members and proportion of family members being COVID-19 positive (r= -0.542, p≤0.0001). CONCLUSION: One in four family members got infected with COVID-19, they were majority males and in the working age group. Negative correlation of positive cases with number of family members and mild negative correlation between rooms per person and proportion of family member affected indicates some other factors may be responsible for household transmission than these factors.

Favipiravir Use in COVID-19: Analysis of Suspected Adverse Drug Events Reported in the WHO Database.

BACKGROUND: COVID-19 caused by SARS-CoV-2 virus emerged as an unprecedented challenge to discover effective drugs for its prevention and cure. Hyperinflammation-induced lung damage is one of the poor prognostic indicators causing a higher rate of morbidity and mortality of COVID-19 patients. Favipiravir, an antiviral drug, is being used for COVID-19 treatment, and we currently have limited information regarding its efficacy and safety. Thus, the present study was undertaken to evaluate the adverse drug events (ADEs) reported in the WHO pharmacovigilance database. METHODS: This study analyzed all suspected ADEs related to favipiravir reported from 2015. The reports were analyzed based on age, gender, and seriousness of ADEs at the System Organ Classification (SOC) level and the individual Preferred Term (PT) level. RESULTS: This study is based on 194 ADEs reported from 93 patients. Most frequent ADEs suspected to be caused by the favipiravir included increased hepatic enzymes, nausea and vomiting, tachycardia, and diarrhea. Severe and fatal ADEs occurred more frequently in men and those over the age of 64 years. Blood and lymphatic disorders, cardiac disorders, hepatobiliary disorders, injury poisoning, and procedural complications were more common manifestations of severe ADEs. CONCLUSION: This study revealed that favipiravir appears to be a relatively safe drug. An undiscovered anti-inflammatory activity of favipiravir may explain the improvement in critically ill patients and reduce inflammatory markers. Currently, the data is based on very few patients. A more detailed assessment of the uncommon ADEs needs to be analyzed when more information will be available.

Opinion of patients seeking primary care regarding prescription of generic drugs: A cross-sectional study.

BACKGROUND: Generic drugs are low-cost alternatives to branded drugs. The government of India is encouraging physicians to prescribe the generics to decrease out-of-pocket expenditure of health care. Looking at India's low-prescription on generic drugs, it is crucial to analyze the factors responsible for it. A patient's unawareness may be an important factor; hence, it should be evaluated systematically. OBJECTIVES: This study was designed with the aim of assessing knowledge and perception of generics among patients visiting the outpatient department of primary care physicians at the Patan city of Gujarat. MATERIAL AND METHODS: A trained research associate visited the OPDs of various general practitioners to collect the data. A prevalidated questionnaire was administered to these patients. The data was analyzed with the help of statistical software. Descriptive statistics were used to analyze the data. RESULTS: Among 345 patients, only 33.6% reportedly heard about generics. Of these only a few patients (<13%) had used the generic drugs in past. The majority (>60%) believed that generics are safe. Those who were not willing to take generics reported efficacy as the major concern. Out of various factors that may affect knowledge of generic drugs, young age (OR = 5.3) and education (Primary (OR = 8.01), Secondary (OR = 6.19), and Higher secondary (OR = 3.07) were statistically significant. CONCLUSION: Awareness about the generic drugs was low among the patients visiting the primary care physician. The young age and primary and secondary education levels were significantly associated with the awareness regarding generics.

TGN-1412 and BIA-2474 Trials with Tragic End: Lessons Learnt To Make Clinical Trials Safer.

BACKGROUND: Globally, there have been tremendous efforts by regulatory authorities to make clinical trials safer by making stringent clinical trial regulations. Despite this, we witnessed several tragic events. TGN1412 and BIA 10-2474 phase I trials are infamous trails in which healthy volunteers either succumbed to severe adverse effects or faced irreversible impairments of the test drug. Such afflictions in clinical trials are not only turbulent to the image of pharmaceutical industry but it also conveys dispiriting message for clinical trial participants. OBJECTIVE: To make clinical trials safer for participants, some regulatory changes are warranted. METHODS: Some stipulated measures to improve safety of clinical trial participants include inclusion of patients instead of healthy volunteers in phase I clinical trials, all compounds which are used for first time in humans should be considered as high risk compounds, amendments in first in human clinical trial design to N of 1 randomized control trial in place of 6+2 design with the sequential dosing of subjects both within and between cohorts and the individual patient pharmacokinetic and pharmacodynamic data should be used to calculate sequential dosing. Besides these, there should be appropriate process for systematic risk assessment involving the use of statistical techniques to select pertinent risk factors with high predictive values of studies or sites that may be procumbent to non-compliance. CONCLUSION: Inclusion of above mentioned measures in clinical trials are bound to make them safer and may help in pacifying the insecurity that has emerged among humans to participate in clinical trials.