Extent of use of artificial intelligence & machine learning protocols in cancer diagnosis: A scoping review.

Background & objectives: Artificial intelligence (AI) and machine learning (ML) have shown promising results in cancer diagnosis in validation tests involving retrospective patient databases. This study was aimed to explore the extent of actual use of AI/ML protocols for diagnosing cancer in prospective settings. Methods: PubMed was searched for studies reporting usage of AI/ML protocols for cancer diagnosis in prospective (clinical trial/real world) setting with the AI/ML diagnosis aiding clinical decision-making, from inception till May 17, 2021. Data pertaining to the cancer, patients and the AI/ML protocol were extracted. Comparison of AI/ML protocol diagnosis with human diagnosis was recorded. Through a post hoc analysis, data from studies describing validation of various AI/ML protocols were extracted. Results: Only 18/960 initial hits (1.88%) utilized AI/ML protocols for diagnostic decision-making. Most protocols used artificial neural network and deep learning. AI/ML protocols were utilized for cancer screening, pre-operative diagnosis and staging and intra-operative diagnosis of surgical specimens. The reference standard for 17/18 studies was histology. AI/ML protocols were used to diagnose cancers of the colorectum, skin, uterine cervix, oral cavity, ovaries, prostate, lungs and brain. AI/ML protocols were found to improve human diagnosis, and had either similar or better performance than the human diagnosis, especially made by the less experienced clinician. Validation of AI/ML protocols was described by 223 studies of which only four studies were from India. Also there was a huge variation in the number of items used for validation. Interpretation & conclusions: The findings of this review suggest that a meaningful translation from the validation of AI/ML protocols to their actual usage in cancer diagnosis is lacking. Development of regulatory framework specific for AI/ML usage in healthcare is essential.

Nature and mechanism of immune boosting by Ayurvedic medicine: A systematic review of randomized controlled trials.

BACKGROUND: Many Ayurvedic preparations are claimed to have immune-boosting properties, as suggested in various published randomized clinical trials (RCTs). AIM: To compile evidence on the nature and mechanism of immune system enhancement by Ayurvedic preparations in healthy and sick individuals. METHODS: After prospectively registering study protocol with PROSPERO, we searched PubMed, DOAJ, Google Scholar, three dedicated Ayurveda research portals, two specialty Ayurveda journals, and reference lists for relevant records published until February 6, 2021 using appropriate search strategies. Baseline features and data pertaining to the nature and mechanism of immune system function were extracted from all eligible records. Methodological quality was assessed using the Cochrane RoB-2 tool. RESULTS: Of 12554 articles screened, 19 studies reporting 20 RCTs (17 parallel group design, three crossover design) with 1661 unique patients were included; 11/19 studies had Indian first authors. Healthy population was included in nine studies, of which one study included pregnant women and two included pediatric population; remaining studies included patients with different health conditions, including one study with coronavirus disease 2019 patients. A total of 21 Ayurvedic interventions were studied, out of which five were composite mixtures. The predominant route of administration was oral; dose and frequency of administration of the intervention varied across the studies. The results reported with five RCTs exploring five Ayurvedic interventions were incomplete, ambiguous, or confusing. Of the remaining 16 interventions, indirect evidence of immune enhancement was reported with four interventions, while lack of the same was reported with two interventions. Enhancement of T helper cells and natural killer cells was reported with three and four interventions, respectively, while the pooled results did not clearly point toward enhancement of other components of the immune system, including cytotoxic T cells, B lymphocytes, immunoglobulins, cytokines, complement components, leucocyte counts, and other components. Nine of the 20 RCTs had a high risk of bias, and the remaining 11 RCTs had some concerns according to RoB-2. CONCLUSION: Various Ayurvedic preparations appear to enhance the immune system, particularly via enhancements in natural killer cells and T helper cells.

Safety and Efficacy of Ivermectin and Doxycycline Monotherapy and in Combination in the Treatment of COVID-19: A Scoping Review.

INTRODUCTION AND OBJECTIVE: Ivermectin (IVM) and doxycycline (DOXY) have demonstrated in-vitro activity against SARS-CoV-2, and have a reasonable safety profile. The objective of this systematic review was to explore the evidence in the literature on the safety and efficacy of their use as monotherapy and combination therapy in COVID-19 management. METHODS: After prospectively registering the study protocol with the Open Science Framework, we searched PubMed, Google Scholar, clinicaltrials.gov, various pre-print servers and reference lists for relevant records published until 16 February, 2021 using appropriate search strategies. Baseline features and data pertaining to efficacy and safety outcomes were extracted separately for IVM monotherapy, DOXY monotherapy, and IVM + DOXY combination therapy. Methodological quality was assessed based on the study design. RESULTS: Out of 200 articles screened, 19 studies (six retrospective cohort studies, seven randomised controlled trials, five non-randomised trials, one case series) with 8754 unique patients with multiple stages of COVID-19 were included; four were pre-prints and one was an unpublished clinicaltrials.gov document. The comparator was standard care and 'hydroxychloroquine + azithromycin' in seven and three studies respectively, and two studies were placebo controlled; six studies did not have a comparator. IVM monotherapy, DOXY monotherapy and IVM + DOXY were explored in eight, five and five studies, respectively; one study compared IVM monotherapy and IVM + DOXY with placebo. While all studies described efficacy, the safety profile was described in only six studies. Efficacy outcomes were mixed with some studies concluding in favour of the intervention and some studies displaying no significant benefit; barring one study that described 9/183 patients with erosive esophagitis and non-ulcer dyspepsia with IVM + DOXY (without causality assessment details), there were no new safety signals of concern with any of the three interventions considered. The quality of studies varied widely, with five studies having a 'good' methodological quality. CONCLUSIONS: Evidence is not sufficiently strong to either promote or refute the efficacy of IVM, DOXY, or their combination in COVID-19 management. SYSTEMATIC REVIEW PROTOCOL REGISTRATION DETAILS: Open Science Framework: https://osf.io/n7r2j .

Importance of Evidence-Based Health Insurance Reimbursement and Health Technology Assessment for Achieving Universal Health Coverage and Improved Access to Health in India.

OBJECTIVE: To review the importance of evidence-based methods in health insurance reimbursement for achieving universal health coverage in India. METHODS: A narrative literature review was performed. RESULTS: The out-of-pocket (OOP) healthcare expenditure in India is among the highest in the world. This situation is despite the implementation of numerous government health schemes and the availability of a large number of health insurance programs, both public and private. Compromised quality of care in many public healthcare facilities is a major factor driving the average Indian citizen to increasingly depend upon private healthcare facilities, further escalating OOP spending. The low awareness and poor uptake of insurance policies among Indians is one of the biggest challenges in the implementation of universal health coverage (UHC) in India. The catastrophic burden of high OOP expenses on individual households could be reduced by taking steps to enhance health insurance uptake, which can be in turn achieved by strengthening the healthcare reimbursement system in India. CONCLUSIONS: The application of the principles of evidence-based healthcare for reimbursement requires the systematic assessment of all health technologies, which is already being done in developed countries. The enactment of health schemes such as Ayushman Bharat-Pradhan Mantri Jan Arogya Yojana and setting up of Health Technology Assessment in India are steps toward reducing OOP expenditure and achieving UHC in India. We review the importance and challenges of evidence-based reimbursement and health technology assessment toward achieving UHC in India.

A Critical Overview of Systematic Reviews of Chemotherapy for Advanced and Locally Advanced Pancreatic Cancer using both AMSTAR2 and ROBIS as Quality Assessment Tools.

BACKGROUND: We performed a critical overview of published systematic reviews (SRs) of chemotherapy for advanced and locally advanced pancreatic cancer, and evaluated their quality using AMSTAR2 and ROBIS tools. MATERIALS AND METHODS: PubMed and Cochrane Central Library were searched for SRs on 13th June 2020. SRs with meta-analysis which included only randomized controlled trials and that had assessed chemotherapy as one of the treatment arms were included. The outcome measures, which were looked into, were progression-free survival (PFS), overall survival (OS), and adverse events (AEs) of grade 3 or above. Two reviewers independently assessed all the SRs with both ROBIS and AMSTAR2. RESULTS: Out of the 1,879 identified records, 26 SRs were included for the overview. Most SRs had concluded that gemcitabine-based combination regimes, prolonged OS and PFS, but increased the incidence of grade 3-4 toxicities when compared to gemcitabine monotherapy, but survival benefits were not consistent when gemcitabine was combined with molecular targeted agents. As per ROBIS, 24/26 SRs had 'high' risk of bias, with only 1/26 SR having 'low' risk of bias. As per AMSTAR2, 25/26 SRs had 'critically low', and 1/26 SR had 'low' confidence in the results. The study which scored 'low risk of bias' in ROBIS scored 'low confidence in results' in AMSTAR2. The inter- rater reliability for scoring the overall confidence in the SRs with AMSTAR2 and the overall domain in ROBIS was substantial; ROBIS: kappa=0.785, SEM=0.207, p<0.001; AMSTAR2: kappa= 0.649, SEM=0.323, p<0.001. CONCLUSION: Gemcitabine-based combination regimens can prolong OS and PFS but also worsen AEs when compared to gemcitabine monotherapy. The included SRs have an overall low methodological quality and high risk of bias as per AMSTAR2 and ROBIS respectively.

Real world safety of bevacizumab in cancer patients: A systematic literature review of case reports.

BACKGROUND: Real-world safety of bevacizumab in cancer patients is limited. OBJECTIVE: To review the adverse drug reactions (ADRs) due to bevacizumab in cancer patients, in published case reports. METHODS: PubMed was searched; case reports of patients with any type of cancer, administered with bevacizumab (monotherapy/combination) and reported ADRs were included. Causality of ADRs was presented as reported in individual papers. ADRs were classified using the information in the USFDA-approved prescribing information (PI) of bevacizumab as 'Serious', 'Common', and 'Post-marketing surveillance' ADRs; ADRs not mentioned in the bevacizumab PI were termed as 'Non-label ADRs'. RESULTS: A total of 130 published papers comprising 154 cases from 22 different countries were included. Most papers (102/130; 78.46%) had moderate methodological quality. Age range of patients was 9-77 years. Off-label use of bevacizumab was found in 34/154 cases (22.08%). Ninety-six unique ADRs were found among 154 ADRs; most reported ADRs affected circulatory, digestive, and respiratory systems (33, 32, and 26 cases respectively). Most commonly reported ADRs were posterior leukoencephalopathy, fistulae, and gastrointestinal perforation (17, 17, and 16 cases respectively). Twenty-eight unique non-label ADRs (29.17%) were found. CONCLUSION: Bevacizumab is associated with more ADRs in the real world among cancer patients than those reported during clinical trials.

Efficacy and Safety of EGFR Inhibitors in the Treatment of EGFRPositive NSCLC Patients: A Meta-Analysis.

BACKGROUND: We compared the response rates, survival rates, and safety profile of epidermal growth factor receptor (EGFR) inhibitors with non-targeted chemotherapy and older EGFR inhibitors when used to treat advanced non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials, and clinicaltrial.- gov for randomized controlled trials published until 11-Feb-2020. Treatment outcomes were compared between EGFR inhibitor and pooled comparator; a subgroup analysis compared outcomes between EGFR inhibitor and non-targeted chemotherapy, and between newer and older EGFR inhibitors. RESULTS: Twenty-one studies with 4,250 unique patients were included. Significantly higher objective response rate (ORR) (odds ratio (OR) 2.28; 95% CI 2.00-2.61), higher disease control rate (DCR) (OR 2.3; 95% CI 1.88-3.06), and longer progression-free survival (PFS) (Hazard ratio (HR) 0.56; 95% CI 0.52-0.60) were observed in the EGFR inhibitor group compared to the pooled comparator group. Subgroup analysis revealed that the ORR, DCR, and PFS were significantly higher with EGFR inhibitors than non-targeted chemotherapy, and only PFS (and not ORR and DCR) was significantly longer with newer EGFR inhibitors than the older EGFR inhibitors. Overall survival (OS) was not significantly different between EGFR inhibitors and pooled comparator (HR 0.91; 95% CI 0.83-1.00) as well as in either of the subgroup analyses. Adverse events ≥ grade 3 and treatment discontinuation were significantly higher with non-targeted chemotherapy compared to the EGFR inhibitors. CONCLUSION: The benefits of prolongation of ORR, DCR, and PFS might not imply significantly improved OS after therapy with EGFR inhibitors when compared with non-targeted chemotherapy or older EGFR inhibitors.

Hydroxychloroquine and Remdesivir in COVID-19: A critical analysis of recent events.

The world is going through an unprecedented medical emergency with no effective remedy for the SARS-CoV2 virus causing Covid-19. Two drugs used for other indications in the past, hydroxychloroquine (HCQ) and remdesivir (RDV), are sought to be repurposed to treat Covid-19. Both these drugs have received emergency use authorisation by the US Food and Drug Administration. In this review, we critically analyse the identification of and subsequent events concerning these two drugs as potential treatment options for Covid-19, and conclude by raising some ethical issues that require serious thought from the global scientific community concerned with using these two drugs against Covid-19.

Key Words: Covid-19, hydroxychloroquine, remdesivir, USFDA, emergency use authorisation

.

Real world evidence: An Indian perspective.

Randomized controlled trials (RCTs) are the gold standard for measuring the safety and efficacy of drugs. However, they are being challenged by payers and health care providers since they are looking for real world evidence (RWE) to validate whether the new intervention provides similar safety and efficacy as reported in RCT data. RWE uses real world data (RWD) to generate insight, foresight, and explorative findings on diseases, products, and patient populations. There are varied sources of RWD such as administrative data, large pragmatic trials, registries, electronic health records, and health surveys. RWE approaches are increasingly becoming the normal practice in developed countries to bring a product to the healthcare market and to ensure its significance in clinical practice. The Indian healthcare sector is growing at a brisk pace and is grasping up with the principles of health economics and outcome research, thereby exhibiting the value of real-world insights in healthcare decision. India has taken a step toward RWE by developing a framework to assist health care providers in harmonizing RWD for economic, clinical, and humanistic outcome.

Can Health Technology Assessment (HTA) provide a solution to tackle the increasing health-care expenditure in India?

The private health-care system in India is effective but expensive. Due to the absence of a comprehensive and well-penetrated insurance scheme that caters to the majority of the Indian population, most of the private health care consultations are out-of-pocket (OOP), and this is pushing many people to poverty. In this article, we describe the concept of health technology assessment (HTA), and review its possible role in improving the health-care system in India. We additionally comment on its present status and possible role of its implementation in the Indian context.

Effects of slow breathing exercise on cardiovascular functions, pulmonary functions & galvanic skin resistance in healthy human volunteers - a pilot study.

BACKGROUND & OBJECTIVES: Regular practice of slow breathing has been shown to improve cardiovascular and respiratory functions and to decrease the effects of stress. This pilot study was planned to evaluate the short term effects of pranayama on cardiovascular functions, pulmonary functions and galvanic skin resistance (GSR) which mirrors sympathetic tone, and to evaluate the changes that appear within a short span of one week following slow breathing techniques. METHODS: Eleven normal healthy volunteers were randomized into Pranayama group (n=6) and a non-Pranayama control group (n=5); the pranayama volunteers were trained in pranayama, the technique being Anuloma-Viloma pranayama with Kumbhak. All the 11 volunteers were made to sit in similar environment for two sessions of 20 min each for seven days, while the pranayama volunteers performed slow breathing under supervision, the control group relaxed without conscious control on breathing. Pulse, GSR, blood pressure (BP) and pulmonary function tests (PFT) were measured before and after the 7-day programme in all the volunteers. RESULTS: While no significant changes were observed in BP and PFT, an overall reduction in pulse rate was observed in all the eleven volunteers; this reduction might have resulted from the relaxation and the environment. Statistically significant changes were observed in the Pranayama group volunteers in the GSR values during standing phases indicating that regular practice of Pranayama causes a reduction in the sympathetic tone within a period as short as 7 days. INTERPRETATION & CONCLUSIONS: Beneficial effects of pranayama started appearing within a week of regular practice, and the first change appeared to be a reduction in sympathetic tone.