Impact of high-salt diet in health and diseases and its role in pursuit of cancer immunotherapy by modulating gut microbiome.

Cancer chemotherapy remains an area of concern, as many of the therapies are uncomfortable involving side effects and unpleasant experiences. These factors could further reduce patient's quality of life, and even endanger their life. Many therapeutic strategies have been tried to reduce the unpleasant side effects and increase the treatment effectiveness; however, none have shown to have promising effects. One of the main hindrances to cancer therapy is the escape strategies by tumor cells to the immune attack. Promoting inflammation in the tumor microenvironment is the cornerstone and key therapeutic target in cancer chemotherapy. High-salt diet (HSD) intake, though it has deleterious effects on human health by promoting chronic inflammation, is found to be advantageous in the tumor microenvironment. Studies identified HSD favors an increased abundance of Bifidobacterium species in the tumor environment due to gut barrier alteration, which, in turn, promotes inflammation and favors improved response to cancer chemotherapy. A review of the literature was carried out to find out the effects of an HSD on health and diseases, with special mention of its effect on cancer chemotherapy. Studies emphasized HSD would block the myeloid-derived suppressor cells which will enhance the tumor immunity. Exploration of the precise mechanism of simple HSD regime/ingestion of specific bacterial species as probiotics will be effective and essential to formulate the game-changing cancer chemotherapy. With the modern era of healthcare moving toward precision medicine where the physician can choose the treatment option suitable for the individual, HSD regime/ingestion of specific bacterial species can be considered.

Assessing the Efficacy of the ARMOR Tool-Based Deprescribing Intervention for Fall Risk Reduction in Older Patients Taking Fall Risk-Increasing Drugs (DeFRID Trial): Protocol for a Randomized Controlled Trial.

BACKGROUND: Falls in older patients can lead to serious health complications and increased health care costs. Fall risk-increasing drugs (FRIDs) are a group of drugs that may induce falls or increase the tendency to fall (ie, fall risk). Deprescribing is the process of withdrawal from an inappropriate medication, supervised by a health care professional, with the goal of managing polypharmacy and improving outcomes. OBJECTIVE: This study aims to assess the effectiveness of a deprescribing intervention based on the Assess, Review, Minimize, Optimize, and Reassess (ARMOR) tool in reducing the risk of falls in older patients and evaluate the cost-effectiveness of deprescribing FRIDs. METHODS: This is an open-label, parallel-group randomized controlled academic trial. Individuals aged 60-80 years who are currently taking 5 or more prescribed drugs, including at least 1 FRID, will be recruited. Demographic data, medical conditions, medication lists, orthostatic hypotension, and fall history details will be collected. Fall concern will be assessed using the Fall Efficacy Scale, and fall risk will be assessed by the Timed Up and Go test and Tinetti Performance-Oriented Mobility Assessment tool. In this study, all treating physicians will be randomized using a stratified randomization method based on seniority. Randomized physicians will do deprescribing with the ARMOR tool for patients on FRIDs. Participants will maintain diaries, and monthly phone follow-ups will be undertaken to monitor falls and adverse events. Physical assessments will be performed to evaluate fall risk every 3 months for a year. The rationality of prescription drugs will be evaluated using the World Health Organization's core indicators. RESULTS: The study received a grant from the Indian Council of Medical Research-Safe and Rational Use of Medicine in October 2023. The study is scheduled to commence in April 2024 and conclude by 2026. Efficacy will be measured by fall frequency and changes in fall risk scores. Cost-effectiveness analysis will also include the incremental cost-effectiveness ratio calculation. Adverse events related to deprescription will be recorded. CONCLUSIONS: This trial will provide essential insights into the efficacy of the ARMOR tool in reducing falls among the geriatric population who are taking FRIDs. Additionally, it will provide valuable information on the cost-effectiveness of deprescribing practices, offering significant implications for improving the well-being of older patients and optimizing health care resource allocation. The findings from this study will be pertinent for health care professionals, policy makers, and researchers focused on geriatric care and fall prevention strategies. TRIAL REGISTRATION: Clinical Trials Registry - India CTRI/2023/12/060516; https://ctri.nic.in/Clinicaltrials/pubview2.php. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55638.

Efficacy and Safety of Anti-SARS-CoV-2 Monoclonal Antibodies: An Updated Review.

Monoclonal antibodies (mAbs) had received emergency use authorization for mild-to-moderate coronavirus disease 2019 (COVID-19) or for prophylaxis against COVID-19, including casirivimab plus imdevimab (C+I), bamlanivimab plus etesevimab (B+E), tixagevimab plus cilgavimab (T+CG), and sotrovimab (S) and bebtelovimab (BEB). This systematic review was done to assess the efficacy and safety of the same. PubMed, Embase, Scopus, medRxiv, bioRxiv, and FDA fact sheets were searched for the studies published between January 2021 and May 2022, and appropriate search terms related to the mentioned mAbs were used for data collection. Review included original research including randomized clinical trials and observational studies published or preprints. Studies included in the review had compared with placebo or standard of care or no treatment or mAbs with each other and also of various doses. Data extraction was done and reviewed the same for both efficacy and safety. Total of 20 studies were included in this review. The rate of hospitalization within 30 days showed ∼2% in comparison to ∼7% with placebo. Significant reduction in viral load was more observed with combination mAbs. Combination therapy showed faster virological cure against the Gamma variant. With C + I as postexposure prophylaxis (PEP), 29.0% of asymptomatic participants developed symptomatic COVID-19. Pre-exposure prophylaxis with T+CG reduced the incidence of infection by 77%. Infusion-related reaction was the most common adverse event (AE). The neutralizing mAbs reduced hospitalization in mild-to-moderate patients with infusion-related reactions as common AE. The response was better in the seronegative patients. Most of these studies were conducted in unvaccinated individuals and against Alpha, Gamma, and Delta variants.

Efficacy and safety of Molnupiravir in COVID-19 patients: a systematic review.

BACKGROUND: Molnupiravir is an oral antiviral drug that received Emergency Use Authorization in three countries for the treatment of mild COVID-19. The aim of this systematic review was to find out the safety and efficacy of Molnupiravir in SARS-COV-2 infections. METHODS: The electronic databases such as PubMed, MedRxiv, BioRxiv, FDA, ClinicalTrials.Gov, ctri.nic.in and Google Scholar were searched for articles from January 2021 to March 2022 using the keywords such as "Molnupiravir", "COVID-19", "Oral antiviral pill", "MK-4482", "EIDD-280", "Efficacy" and "Safety". Details of published, unpublished with interim reports and ongoing studies of Molnupiravir in COVID-19 were retrieved, and a systematic review was performed. RESULTS: A total of 6 articles and 18 ongoing trials data were collected. Out of these, data from 4 published and 2 unpublished with interim reports were extracted. After review of these studies, it was observed that the daily dose of 1600 mg Molnupiravir for 5 days was safe and tolerable with nausea, diarrhea and headache as the common adverse effects. The results also showed significant decrease in time to viral clearance with 800 mg twice daily in mild patients and reduction in the risk of hospitalization or death by 50% in non-hospitalized COVID-19 patients. CONCLUSION: Evidence from clinical studies showed that Molnupiravir caused significant reduction in the risk of hospitalization or death in high-risk mild COVID-19 patients. Molnupiravir was also found to be well tolerated and safe without any major adverse events on short-term use. For confirmative use of this drug in mild-to-moderate COVID-19 disease, further studies are required in vaccinated COVID-19 patients and against emerging variants.

Inception of the Indian Digital Health Mission: Connecting the Dots.

The purpose of the National Digital Health Mission (or more precisely, the Ayushman Bharat Digital Mission) is to promote and facilitate the evolution of the National Digital Health Ecosystem in India. The Health Facility Registry, the Healthcare Professionals Registry, and the Unified Health Interface are the major components of the proposed system-which is intended to be a co-operative federated architecture with optimal interoperability provision coupled with authorized access.

Ivermectin in COVID-19 Management: What is the Current Evidence?

Ivermectin (IVM), an approved anthelminthic drug, has been reported to have antiviral, antibacterial, and anticancer activities. Antiviral activity is due to the inhibition of nuclear cargo importin (IMP) protein. The anti-SARS CoV-2 activity through in vitro study was first reported by an Australian team. Later, many studies were conducted, and most of the study results were available as non-peer-reviewed preprints. In this narrative review, literature on the clinical studies conducted with ivermectin from published articles, preprints, and unpublished evidence was collected until 13th June 2021. They are discussed based on the severity of COVID-19 disease. Out of the 23 peer-reviewed published articles, 13 studies were randomized controlled trials. The remaining were either prospective interventional, prospective observational, retrospective cohort, cross-sectional, or case series type of studies; additionally, there were 10 randomized controlled trials available as preprints. In most studies, ivermectin was used in combination with doxycycline, azithromycin, or other drugs. Some studies suggested that a higher dose or increased duration of ivermectin usage was required to achieve favorable effects. In this review, articles on the prophylactic role of ivermectin in COVID-19 are also discussed - wherein the results are more promising. Despite accumulating evidence suggesting the possible use of ivermectin, the final call to incorporate ivermectin in the management of COVID-19 is still inconclusive.

Dapagliflozin for heart failure: is it a class effect?

Dapagliflozin, an SGLT2 inhibitor used in the management of Type 2 diabetes mellitus, has been recently approved for the control of worsening cardiovascular events, including deaths and hospitalizations, in adults with heart failure with reduced ejection fraction. Previously, canagliflozin had a label change with regards to its additional usage in the reduction of risk of hospitalization for heart failure in patients with both Type 2 diabetes mellitus and diabetic nephropathy with albuminuria. On the other hand, the therapeutic application of empagliflozin and ertugliflozin in heart failure is yet to be delineated comprehensively. The beneficial effects of these SGLT2 inhibitors, dapagliflozin in particular, in heart failure are found to be independent of neither the glucose-lowering nor the SGLT2 inhibiting effects.

Effect of long-term acid suppression therapy with proton pump inhibitors or H2 receptor blockers on serum vitamin B12 levels in elderly population.

BACKGROUND: Long-term usage of acid suppression drugs like proton pump inhibitors (PPIs) or H2 receptor blockers in the elderly population has been found to result in vitamin B12 deficiency. However, the reports are equivocal. OBJECTIVE: To determine the serum vitamin B12 levels in elderly patients under chronic acid suppression therapy. METHODS: Patients aged above 60 years and on any of the PPIs or H2 blockers for at least 6 months were recruited. Out of 77 patients recruited, 60 patients were included for the final analysis. The serum vitamin B12 levels were measured using the AccuDiag™-Vitamin B12 ELISA system. RESULTS: Out of 60 patients, pantoprazole (40%) and omeprazole (37%) were the commonly prescribed acid-suppressing drugs. Nearly 50% of the patients on prolonged acid suppression therapy were either "deficient" (less than 200 pg/ml) or "insufficient" (200 to 300 pg/ml) in serum vitamin B12 levels. Neither the average serum vitamin B12 levels (p = 0.994) nor the vitamin B12 status (p = 0.226) varied significantly across the drug groups of pantoprazole, omeprazole, and ranitidine. CONCLUSIONS: Prolonged acid suppression therapy with PPIs or H2 blockers may result in serum vitamin B12 deficiency. However, there was no class (PPIs vs. H2 receptor blockers)- or drug (pantoprazole vs. omeprazole vs. ranitidine)-based differences found in the vitamin B12 deficiency caused.

Association of plasma docetaxel levels with ABCB1 gene polymorphisms and tumour response in locally advanced breast cancer patients of South India on neo-adjuvant chemotherapy.

BACKGROUND: Genetic factors could be attributed to the variability in docetaxel plasma levels and its subsequent therapeutic response. The objectives of this study were to assess the effect of ABCB1 gene polymorphisms [SNPs rs1045642 (C3435T) and rs1128503 (C1236T)] on docetaxel plasma levels and also to analyze the influence of docetaxel plasma levels on tumour response in the ethnically distinct South Indian population. METHODS: 104 locally advanced breast cancer (LABC) patients on docetaxel-based neo-adjuvant chemotherapy (NACT) were included. The plasma docetaxel levels were estimated using the validated reverse phase liquid chromatography with mass spectrometry (LC-MS/MS). DNA was extracted (phenol-chloroform extraction method) and the real-time PCR system using validated TaqMan® SNP genotyping assay method was used for genotyping. Tumour response was assessed by RECIST criteria based on the MRI images. RESULTS: Patients with "CT/TT" genotype of the SNP C1236T had a C0/Ct ratio of 1.6 times higher than those with "CC" genotype (13.5 ± 6.5 vs 8.3 ± 3.1, p = 0.002). Though not significant, patients with "CT/TT" genotype had greater initial plasma concentration (C0) and area under the plasma concentration-time curve (AUC0-t). Conversely, the SNP C3435T was not associated with the plasma docetaxel levels. Furthermore, the C0 and normalized C0 were found to be higher in tumour responders compared to non-responders (p < 0.05). CONCLUSIONS: The plasma levels of docetaxel were significantly influenced by the SNP C1236T of ABCB1 gene coding for the MDR1 transporter (P-glycoprotein). The plasma levels of docetaxel were also found to influence its therapeutic effect.

5G in healthcare: how fast will be the transformation?

The 5G technology, with its low latency, high speed, enhanced high-resolution bandwidth, superior reliability, and less energy consumption, is bound to transform telemedicine and the healthcare industry as a whole. This next-generation wireless networking technology has many far-reaching implications in both preventive and therapeutic care of the patients. Remote monitoring of patients is possible with wearables facilitated by robust sensors coupled to 5G network. Virtual patient consultation; augmented reality (AR) and virtual reality (VR)-based simulated surgeries; artificial intelligence (AI)-powered robotic surgeries; real-time maintenance of ambulances and other medical devices; and dynamic huge data repository are some of the other applications of 5G technology in the health sector.

Influence of ABCB1 C3435T and C1236T gene polymorphisms on tumour response to docetaxel-based neo-adjuvant chemotherapy in locally advanced breast cancer patients of South India.

WHAT IS KNOWN AND OBJECTIVE: Variable response to docetaxel-based neo-adjuvant chemotherapy (NACT) in breast cancer patients had been reported. Genetic polymorphisms in the ABCB1 gene coding for the efflux transporter MDR1 (P-glycoprotein, P-gp) could result in altered tumour response. Hence, this study was proposed to assess the effect of single nucleotide polymorphisms (SNPs) of ABCB1 gene on tumour response in locally advanced breast cancer patients (LABC) of South India who have a distinct genetic makeup. METHODS: Out of 162 LABC patients recruited, 129 patients were included for the final analysis. DNA was extracted by "phenol-chloroform extraction method" from the WBCs, and genotyping for SNPs rs1045642 (C3435T) and rs1128503 (C1236T) in ABCB1 gene was performed with real-time PCR system using validated TaqMan® SNP genotyping assay method. Tumour response was assessed by RECIST criteria based on the MRIs taken before and after completion of four cycles of docetaxel therapy. RESULTS AND DISCUSSION: A total of 102 (79.1%) patients were found to be responders and 27 (20.9%) patients were found to be non-responders to docetaxel therapy. Patients with "CT/TT" genotypes (response rate: 83.3%) of ABCB1 (C1236T) gene showed better tumour response than those with "CC" genotype (response rate: 16.6%) [OR = 2.94 (CI: 1.15-7.52); P = 0.03]. However, on performing binary logistic regression, neither the studied SNPs nor the non-genetic factors like age, BMI, postmenopausal status, laterality of the tumour, ER status, PR status and Her-2/neu status were found to be associated with tumour response to docetaxel (P > 0.05). WHAT IS NEW AND CONCLUSION: The tumour response to docetaxel was significantly influenced by the SNP C1236T of ABCB1 gene coding for the P-gp. However, when adjusted for other non-genetic factors, neither of the ABCB1 variants were found to be associated with tumour response to docetaxel-based NACT in LABC patients of South India.

Lack of effect of the SLC47A1 and SLC47A2 gene polymorphisms on the glycemic response to metformin in type 2 diabetes mellitus patients.

Background This work aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) in the SLC47A1 (922-158G>A; rs2289669) and SLC47A2 (-130G>A; rs12943590) genes on the relative change in HbA1c in type 2 diabetes mellitus (T2DM) patients of South India who are taking metformin as monotherapy. It also aims to study the effects of these SNPs on the dose requirement of metformin for glycemic control and the adverse effects of metformin. Methods Diabetes patients on metformin monotherapy were recruited based on the eligibility criteria (n=105). DNA was extracted and genotyping was performed with a real-time PCR system using TaqMan® SNP genotyping assay method. The HbA1c levels were measured using Bio-Rad D-10™ Hemoglobin Analyzer. Results After adjusting for multiple comparisons (Bonferroni correction) the difference found in the glycemic response between the "GG" genotype and "AG/AA" genotype groups of the SLC47A2 gene was not significant (p=0.027; which was greater than the critical value of 0.025). Patients with "GG" genotype showed a 5.5% decrease in HbA1c from baseline compared to those with the "AG/AA" genotype (0.1% increase). The SNP in the SLC47A1 gene also did not influence the glycemic response to metformin (p=0.079). The median dose requirements based on the genotypes of the rs12943590 variant (p=0.357) or rs2289669 variant (p=0.580) were not significantly different. Similarly, there was no significant difference in the occurrence of adverse effects across the genotypes in both the SLC47A1 (p=0.615) and SLC47A2 (p=0.309) genes. Conclusions The clinical response to metformin was not associated with the SNPs in the SLC47A1 and SLC47A2 genes coding for the multidrug and toxin extrusion protein (MATE) transporters. Furthermore, the studied SNPs had no influence on the dose requirement or adverse effects of metformin.

Cetirizine-Induced Fixed Drug Eruption.

Cetirizine, a piperazine-derivative second-generation antihistaminic, is used for a wide variety of disorders such as urticaria, eczema, and allergies. Adverse reactions due to this drug are usually rare, especially fixed drug eruption (FDE), a delayed cell-mediated hypersensitivity reaction, is scarce. Here, we report a case of cetirizine-induced FDE. A 34-year-old female developed hyperpigmented, itchy patches over both forearms, legs, feet, and right side of the chest after taking tablet cetirizine for dry cough with similar episode 2 years back on the same sites. The patient responded slowly with conservative treatment and the lesions disappeared after 10 days. She was advised to avoid the causative in near future. This case report highlighted FDE due to an antihistaminic which themselves will be prescribed to treat allergies.