A Review on Repurposed Drugs and Vaccine Trials for Combating SARS CoV-2.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19), emerged in Wuhan, China in December 2019 and then spread worldwide rapidly. The records from World Health Organisation (WHO), Centres of Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) backup the fact that no medications have proven to be completely effective for prevention or treatment of SARS-CoV-2. The clinical trials are underway for many repurposed, investigational drugs and vaccine candidates. BioNTech and Pfizer Inc, Moderna, Gamaleya institute and University of Oxford (collaboration with AstraZeneca) announced positive results in the Phase 3 interim analyses of vaccine trials in November 2020. Twelve countries have approved Pfizer- BioNTech COVID-19 vaccine for emergency use, as of December 2020. OBJECTIVE: The objective was to summarize the repurposed/investigational drugs, their mechanism of action, and rationale for their use in COVID-19 treatment. The article also aimed to summarize the vaccine trials that are currently undergoing across the globe. METHODS: In order to find the content for review, studies defining COVID-19 chronology, repurposed drugs along with their mode of action and potential vaccine trials were studied and summarized. RESULTS AND CONCLUSION: The article summarizes potential therapeutic candidates (repurposed and investigational agents) for SARS-CoV-2, their possible mechanism of action and discussion related to their involvement in recent clinical trials. Innovative vaccine platform technologies are also highlighted that are recently being used in the vaccine production pipeline.

Performance of Long-Term CT and PET/CT Surveillance for Detection of Distant Recurrence in Patients with Resected Stage IIIA-D Melanoma.

BACKGROUND: Follow-up for patients with resected stage IIIA-D melanoma may include computed tomography (CT) or positron emission tomography (PET)/CT imaging to identify distant metastases. The aim of this study was to evaluate the test performance over follow-up time, of structured 6- and 12-monthly follow-up imaging schedules in these patients. METHODS: We conducted a retrospective analysis of consecutive resected stage IIIA-D melanoma patients from Melanoma Institute Australia (2000-2017). Patients were followed until a confirmed diagnosis of distant metastasis, end of follow-up schedule, or death. Test accuracy was evaluated by cross-classifying the results of the test against a composite reference standard of histopathology, cytology, radiologic imaging, and/or clinical follow-up, and then quantified longitudinally using logistic regression models with random effects. RESULTS: In total, 1373 imaging tests were performed among 332 patients. Distant metastases were detected in 110 (33%) patients during a median follow-up of 61 months (interquartile range 38-86), and first detected by imaging in 86 (78%) patients. 152 (68%) patients had at least one false-positive result. Sensitivity of the schedule over 5 years was 79% [95% confidence interval (CI) 70-86%] and specificity was 88% (95% CI 86-90%). There was no evidence of a significant difference in test performance over follow-up time or by American Joint Committee on Cancer (AJCC) substage. The positive predictive value ranged between 33 and 48% over follow-up time, reflecting a ratio of 1:2 false-positives per true-positive finding. CONCLUSIONS: Regular 6- or 12-monthly surveillance imaging using CT or PET/CT has reasonable and consistent sensitivity and specificity over 5-year follow-up for resected stage IIIA-D melanoma patients. These data are useful when discussing the risks and benefits of long-term follow-up.

A Review on Rheumatoid Arthritis Interventions and Current Developments.

Rheumatoid arthritis is a chronic autoimmune disorder characterized by inflammation, swelling, and joint destruction primarily affecting the peripheral joints. In recent years, RA has become an alarming concern affecting more than 1.5% of the population worldwide. The majority of the drugs in clinical trials for rheumatoid arthritis are immunomodulatory. The development of novel drugs for RA is impending and scientists are exploring new strategies through various innovative approaches for RA drug development. Treat-to-target and window of opportunity hypothesis are the new approaches that are used to treat, improve outcomes, and prevent long-term use of ineffective therapy, respectively. Novel therapeutic agents (e.g. GM-CSF inhibitors, Matrix metalloproteinase inhibitors) and delivery systems (e.g., Liposomes, Superparamagnetic iron oxide nano particles (SPIONs)) are under investigation for more target based therapy with reduced side effects and toxicity. The new drug discovery and repositioning of previously FDA-approved drugs are also being considered for chronic inflammatory disorder. The review encompasses a vast array of information, including genetics, etiology, clinical symptoms, current treatment, and newer therapeutics approaches, focused on the development of RA interventions. The introduction of the bioinformatics-based approach in RA has also been significantly discussed in the review. This review provides a general understanding of the challenges and uncertainties in the treatment of RA and summarizes the evolving scenario as well as innovative approaches taken into consideration for drug development in rheumatoid arthritis.

Cost-effectiveness analysis of PET/CT surveillance imaging to detect systemic recurrence in resected stage III melanoma: study protocol.

INTRODUCTION: In the new era of effective systemic therapies for advanced melanoma, early detection of lower volume recurrent disease using surveillance imaging can improve survival. However, intensive imaging follow-up strategies are likely to increase costs to health systems and may pose risks to patients. The objective of this study is to estimate from the Australian health system perspective the cost-effectiveness of four follow-up strategies in resected stage III melanoma over a 5-year period following surgical treatment with curative intent. METHODS AND ANALYSIS: A decision-analytic model will be built to estimate the costs and benefits of (1) 12 monthly, (2) 6 monthly, (3) 3-4 monthly positron emission tomography/CT imaging for 5 years, compared with (4) no imaging follow-up. The model will be populated with probabilities of disease recurrence, test performance measures using data from >1000 consecutive resected stage III melanoma patients from Melanoma Institute Australia diagnosed between 2000 and 2017. Healthcare resource use, including surveillance imaging, doctor's visits, subsequent tests and procedures to investigate suspicious findings, will be quantified from detailed patient records and valued using Australian reference pricing. Economic outcomes include cost per new distant melanoma recurrence detected and cost per diagnostic error avoided, for no imaging compared with the other strategies.Deterministic sensitivity analyses will examine the robustness of model results. ETHICS AND DISSEMINATION: This study was approved by the Sydney Local Health District, Sydney Local Health District Ethics Review Committee (RPAH Zone), AU/1/830638 and the Australian Institute of Health and Welfare (EO2019-1-454). The results of this study will be published in peer-reviewed medical and health economics journals and will inform melanoma management guidelines.

Cost-Effectiveness of a Psycho-Educational Intervention Targeting Fear of Cancer Recurrence in People Treated for Early-Stage Melanoma.

OBJECTIVE: This study aimed to evaluate the cost effectiveness of a newly developed psycho-educational intervention to reduce fear of cancer recurrence (FCR) in early-stage melanoma patients. METHODS: A within-trial cost-effectiveness and cost-utility analysis was conducted from the Australian health system perspective using data from linked Medicare records. Outcomes included FCR, measured with the severity subscale of the FCR Inventory; quality-adjusted life years (QALYs) measured using the preference-based instrument, Assessment of Quality of Life-8 Dimensions (AQoL-8D) and 12-month survival. An incremental cost-effectiveness ratio (ICER) was calculated for two economic outcomes: (1) cost per additional case of 'high' FCR avoided and (2) cost per QALY gained. Means and 95% CIs around the ICER were generated from non-parametric bootstrapping with 1000 replications. RESULTS: A total of 151 trial participants were included in the economic evaluation. The mean cost of the psycho-educational intervention was AU$1614 per participant, including intervention development costs. The ICER per case of high FCR avoided was AU$12,903. The cost-effectiveness acceptability curve demonstrated a 78% probability of the intervention being cost effective relative to the control at a threshold of AU$50,000 per extra person avoiding FCR. The ICER per QALY gained was AU$116,126 and the probability of the intervention being cost effective for this outcome was 36% at a willingness to pay of AU$50,000 per QALY. CONCLUSION: The psycho-educational intervention reduced FCR at 12 months for people at high risk of developing another melanoma and may represent good value for money. For the QALY outcome, the psycho-educational intervention is unlikely to be cost effective at standard government willingness-to-pay levels. The trial was prospectively registered in the Australian and New Zealand Clinical Trials Registry (CTRN12613000304730).

False-Positive Results and Incidental Findings with Annual CT or PET/CT Surveillance in Asymptomatic Patients with Resected Stage III Melanoma.

OBJECTIVE: The aim of this study was to quantify false-positive and incidental findings from annual surveillance imaging in asymptomatic, American Joint Committee on Cancer stage III melanoma patients. METHODS: This was a cohort study of patients treated at Melanoma Institute Australia (2000-2015) with baseline computed tomography (CT) or positron emission tomography (PET)/CT imaging and at least two annual surveillance scans. False-positives were defined as findings suspicious for melanoma recurrence that were not melanoma, confirmed by histopathology, subsequent imaging, or clinical follow-up, while incidental findings were defined as non-melanoma-related findings requiring further action. Outcomes of incidental findings were classified as 'benign' if they resolved spontaneously or were not seriously harmful; 'malignant' if a second malignancy was identified; or 'other' if potentially harmful. RESULTS: Among 154 patients, 1022 scans were performed (154 baseline staging, 868 surveillance) during a median follow-up of 85 months (interquartile range 56-112); 57 patients (37%) developed a recurrence. For baseline and surveillance imaging, 124 false-positive results and incidental findings were identified in 81 patients (53%). The frequency of these findings was 5-14% per year, and an additional 181 tests, procedures, and referrals were initiated to investigate these findings. The diagnosis was benign in 109 findings of 124 findings (88%). Fifteen patients with a benign finding underwent an unnecessary invasive procedure. Surveillance imaging identified distant metastases in 20 patients (13%). CONCLUSION: False-positive results and incidental findings occur in at least half of all patients undergoing annual surveillance imaging, and the additional healthcare use is substantial. These findings persist over time. Clinicians need to be aware of these risks and discuss them with patients, alongside the expected benefits of surveillance imaging.