Immunogenicity, clinical efficacy and safety of additional second COVID-19 booster vaccines against Omicron and its subvariants: A systematic review.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 is a new variant of concern (VOC) and an emerging subvariant that exhibits heightened infectivity, transmissibility, and immune evasion, escalating the incidence of moderate to severe coronavirus disease 2019 (COVID-19). It resists monoclonal antibodies and diminishes vaccine efficacy. Notably, new sublineages have outpaced earlier predominant sublineages. Although the primary vaccination series and initial boosters were robust against previous VOCs, their efficacy waned against Omicron and its subvariants. In this systematic review, we assessed real-world evidence on the immunogenicity, clinical efficacy, and safety of a second booster or fourth COVID-19 vaccine dose against the Omicron VOC and its subvariants. A comprehensive literature search was conducted in Medline/PubMed, Google Scholar, bioRxiv, and medRxiv, and relevant studies published between 2022 and 30 May 2023 were reviewed. We found a total of 40 relevant articles focusing on a second booster dose for COVID-19, including clinical trials and observational studies, involving 3,972,856 patients. The results consistently revealed that an additional second booster dose restored and prolonged waning immunity, activating both humoral and cellular responses against Omicron and its subvariants. A second booster treatment correlated with enduring protection against COVID-19, notably preventing substantial symptomatic disease and mortality associated with severe Omicron infection. Both monovalent messenger RNA (mRNA) and nonmRNA vaccines demonstrated similar efficacy and safety, with bivalent mRNA vaccines exhibiting broader protection against emerging subvariants of Omicron. The safety profiles of second booster were favourable with only mild systemic and local symptoms reported in some recipients. In conclusion, this systematic review underscores the additional COVID-19 vaccine boosters, particularly with bivalent or multivalent mRNA vaccines, for countering the highly infectious emerging subvariants of Omicron.

A review of real-world evidence on preemptive pharmacogenomic testing for preventing adverse drug reactions: a reality for future health care.

Adverse drug reactions (ADRs) are a significant public health concern and a leading cause of hospitalization; they are estimated to be the fourth leading cause of death and increasing healthcare costs worldwide. Carrying a genetic variant could alter the efficacy and increase the risk of ADRs associated with a drug in a target population for commonly prescribed drugs. The use of pre-emptive pharmacogenetic/omic (PGx) testing can improve drug therapeutic efficacy, safety, and compliance by guiding the selection of drugs and/or dosages. In the present narrative review, we examined the current evidence of pre-emptive PGx testing-based treatment for the prevention of ADRs incidence and hospitalization or emergency department visits due to serious ADRs, thus improving patient safety. We then shared our perspective on the importance of preemptive PGx testing in clinical practice for the safe use of medicines and decreasing healthcare costs.

Glucagon-like peptide-1 receptor agonists in adolescents with overweight or obesity with or without type 2 diabetes multimorbidity-a systematic review and network meta-analysis.

AIM: To synthesize the evidence on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adolescents with overweight or obesity. MATERIALS AND METHODS: For this systematic review and network meta-analysis, we searched five databases and registries until 2 March 2024 for eligible randomized controlled trials (RCTs). The primary outcome was weight change. We did a pairwise meta-analysis to compare GLP-1RAs and placebo, followed by a drug-wise network meta-analysis (NMA) to compare GLP-1RAs against each other. RESULTS: We screened 770 records to include 12 RCTs with 883 participants. The evidence suggests that GLP-1RAs reduced weight (mean difference -4.21 kg, 95% confidence interval [CI] -7.08 to -1.35) and body mass index (BMI; mean difference -2.11 kg/m2, 95% CI -3.60 to -0.62). The evidence on waist circumference, body fat percentage and adverse events (AEs) was very uncertain. The results remained consistent with subgroup analyses for coexisting type 2 diabetes. Longer therapy duration led to a greater reduction in weight and BMI. In the NMA, semaglutide led to the greatest weight reduction, followed by exenatide, liraglutide and lixisenatide. CONCLUSIONS: The evidence suggests that GLP-1RAs reduce most weight-related outcomes in adolescents, with semaglutide being the most efficacious. There is uncertain evidence on body fat and serious AEs, probably due to fewer studies and low incidence, respectively. Larger RCTs with head-to-head comparisons, pragmatic design, adiposity-related outcomes, and economic evaluation can further guide the use and choice of GLP-1RAs.

A meta-analysis and mapping of global mpox infection among children and adolescents.

Monkeypox (mpox) is a significant health concern affecting children and adolescents globally. This systematic review and meta-analysis aims to synthesise the available evidence on the proportion of children and adolescents affected by the mpox virus. A comprehensive search was conducted in seven electronic databases (PubMed, Scopus, Web of Science, EMBASE, ProQuest, EBSCOHost, and Cochrane) to identify the original reports on mpox cases in children and adolescents till 15 January 2023. Descriptive reports on probable or laboratory-confirmed mpox in children and adolescents (0-17 years old) were considered eligible. Studies not providing separate data for the above age group and case-control studies were excluded. The primary outcome was pooled proportion of mpox cases among children and adolescents. Proportion meta-analysis and heterogeneity between studies were determined using a restricted maximum likelihood estimator, and a random-effects model was fitted to the data. Sensitivity analysis and subgroup analysis were also conducted. A drapery plot was also provided as a complementary figure to the forest plot. The protocol was prospectively registered with PROSPERO (CRD42023392475). A total of 440 studies were identified, of which 37 were included in the review and 25 in the meta-analysis (62,701 participants with 3306 children and adolescents). The pooled proportion of children and adolescents was 0.46 (95% CI: 0.30-0.63, I2 :100%). The proportion of children and adolescents was significantly lower (p < 0.001) in the ongoing pandemic 0.04 (95% CI: 0.00-0.32) than before 2022 0.62 (95% CI: 0.49-0.74). The meta-regression showed that the higher the study's sample size, the lower the proportion of children among the mpox cases. Both overall and subgroup heterogeneity were high. Adolescents and children below 5 years are commonly affected by the ongoing pandemic. In conclusion, the high proportion of children affected by the mpox virus highlights the need for increased research and targeted interventions to prevent and control the spread of the virus in this population.

Role of CD4+ T Cells in Parkinson's Disease.

Parkinson's disease (PD) is a progressive condition that affects both the central nervous system and other body parts that are controlled by the nervous system. PD is characterized by brain dopaminergic neurons loss and, at present, there are only symptomatic treatments available to alleviate the effects of the disease. With extensive research, new insights have led to defining PD as a multi-system disorder with immune dysfunction playing a dominant part in the disease pathogenesis as well as its progression. Neuroinflammation in PD leads to neurodegeneration, which is, in turn, regulated by the peripheral adaptive immunity, with CD4+ T cells being a significant player. Patients with PD have diverse CD4+ T cell phenotypes and functional profiles. These phenotypes vary, from being proinflammatory (Th1 and Th17) to anti-inflammatory (Th2 and Tregs). This report focuses on reviewing the expression of CD4+ T cells in PD and its role in the prognosis and treatment of PD.

A systematic review to identify novel clinical characteristics of monkeypox virus infection and therapeutic and preventive strategies to combat the virus.

Since May 2022, there has been a global increase in the number of Mpox virus (MPXV) cases in countries that were previously considered non-endemic. In July 2022, the World Health Organization (WHO) declared this outbreak a public health emergency of international concern. The objective of this systematic review is to examine the novel clinical features of Mpox and to assess the available treatment options for managing the disease in patients who are afflicted with it. We conducted a systematic search in several databases, including PubMed, Google Scholar, Cochrane Library, and the grey literature, from May 2022 to February 2023. We identified 21 eligible studies, which included 18,275 Mpox cases, for final qualitative analysis. The majority of cases were reported in men who have sex with men (MSM) and immunocompromised individuals with HIV (36.1%). The median incubation period was 7 days (IQR: 3-21). The novel clinical manifestations include severe skin lesions on the palms, oral and anogenital regions, as well as proctitis, penile edema, tonsillitis, ocular disease, myalgia, lethargy, and sore throat, without any preceding prodromal symptoms or systemic illness. In addition, fully asymptomatic cases were documented, and various complications, including encephalomyelitis and angina, were noted. Clinicians must be familiar with these novel clinical characteristics, as they can aid in testing and tracing such patients, as well as asymptomatic high-risk populations such as heterosexuals and MSM. In addition to supportive care, currently, there are several effective prophylactic and treatment strategies available to combat Mpox, including the vaccines ACAM2000 and MVA-BN7, as well as the immunoglobulin VIGIV and the antivirals tecovirimat, brincidofovir, and cidofovir against severe Mpox infection.

Current evidence on efficacy of COVID-19 booster dose vaccination against the Omicron variant: A systematic review.

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic, which affected around 45 million confirmed cases of COVID-19, including more than 6 million deaths. However, on November 24, 2021, the World Health Organization announced a new severe acute respiratory syndrome coronavirus 2 variant designated as the B.1.1.529, a variant of concern (VOC), and the variant has been named as "Omicron." Available preliminary evidence suggests that, as compared with previous VOCs, it has an increased risk of infectivity. Studies have shown that protection from various vaccines effectiveness against hospitalization and death from severe COVID-19 disease is decreasing slowly after a two-dose schedule of COVID-19 vaccines. In response to experiencing a new COVID-19 variant and ongoing resurgence of cases, the importance of COVID-19 vaccine booster dose and durability of the effect of the third dose of vaccine against COVID-19 Omicron variant is controversial yet. To address this, we conducted a systematic literature survey on effectiveness of the third or booster dose of COVID-19 vaccine against the Omicron variant. We have performed a systematic search in PubMed (Medline), Google Scholar, and MedRXiv database, from inception to January 2022 using the MeSH terms and keywords "Corona Virus Disease-2019 OR COVID-19 AND Omicron AND COVID-19 Booster Vaccine." We have identified a total of 27 published studies. We have reviewed all the eligible available studies on the effectiveness of the COVID-19 vaccine booster shots against the Omicron variant. This review may be helpful in accelerating the COVID-19 booster dose vaccination.

Liquid biopsy for precision diagnostics and therapeutics.

Liquid biopsy (LB) has emerged as a highly promising and non-invasive diagnostic approach, particularly in the field of oncology, and has garnered interest in various medical disciplines. This technique involves the examination of biomolecules released into physiological fluids, such as urine samples, blood, and cerebrospinal fluid (CSF). The analysed biomolecules included circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), cell-free DNA (cfDNA), exosomes, and other cell-free components. In contrast to conventional tissue biopsies, LB provides minimally invasive diagnostics, offering invaluable insights into tumor characteristics, treatment response, and early disease detection. This Review explores the contemporary landscape of technologies and clinical applications in the realm of LB, with a particular emphasis on the isolation and analysis of ctDNA and/or cfDNA. Various methodologies have been employed, including droplet digital polymerase chain reaction (DDP), BEAMing (beads, emulsion, amplification, and magnetics), TAm-Seq (tagged-amplicon deep sequencing), CAPP-Seq (cancer personalized profiling by deep sequencing), WGBS-Seq (whole genome bisulfite sequencing), WES (whole exome sequencing), and WGS (whole-genome sequencing). Additionally, CTCs have been successfully isolated through biomarker-based cell capture, employing both positive and negative enrichment strategies based on diverse biophysical and other inherent properties. This approach also addresses challenges and limitations associated with liquid biopsy techniques, such as sensitivity, specificity, standardization and interpretability of findings. This review seeks to identify the current technologies used in liquid biopsy samples, emphasizing their significance in identifying tumor markers for cancer detection, prognosis, and treatment outcome monitoring.

Advancing cancer theranostics through biomimetics: A comprehensive review.

Nanotheranostics, especially those employing biomimetic approaches, are of substantial interest for molecular imaging and cancer therapy. The incorporation of diagnostics and therapeutics, known as cancer theranostics, represents a promising strategy in modern oncology. Biomimetics, inspired by nature, offers a multidisciplinary avenue with potential in advancing cancer theranostics. This review comprehensively analyses recent progress in biomimetics-based cancer theranostics, emphasizing its role in overcoming current treatment challenges, with a focus on breast, prostate, and skin cancers. Biomimetic approaches have been explored to address multidrug resistance (MDR), emphasizing their role in immunotherapy and photothermal therapy. The specific areas covered include biomimetic drug delivery systems bypassing MDR mechanisms, biomimetic platforms for immune checkpoint blockade, immune cell modulation, and photothermal tumor ablation. Pretargeting techniques enhancing radiotherapeutic agent uptake are discussed, along with a comprehensive review of clinical trials of global nanotheranostics. This review delves into biomimetic materials, nanotechnology, and bioinspired strategies for cancer imaging, diagnosis, and targeted drug delivery. These include imaging probes, contrast agents, and biosensors for enhanced specificity and sensitivity. Biomimetic strategies for targeted drug delivery involve the design of nanoparticles, liposomes, and hydrogels for site-specific delivery and improved therapeutic efficacy. Overall, this current review provides valuable information for investigators, clinicians, and biomedical engineers, offering insights into the latest biomimetics applications in cancer theranostics. Leveraging biomimetics aims to revolutionize cancer diagnosis, treatment, and patient outcomes.

Recent Insights into the Neurobiology of Alzheimer's Disease and Advanced Treatment Strategies.

In recent years, significant advancements have been made in understanding Alzheimer's disease from both neurobiological and clinical perspectives. Exploring the complex systems underlying AD has unveiled insights that could potentially revolutionize therapeutic approaches. Recent investigations have highlighted intricate interactions among genetic, molecular, and environmental factors in AD. Optimism arises from neurobiological advancements and diverse treatment options, potentially slowing or halting disease progression. Amyloid-beta plaques and tau protein tangles crucially influence AD onset and progression. Emerging treatments involve diverse strategies, such as approaches targeting multiple pathways involved in AD pathogenesis, such as inflammation, oxidative stress, and synaptic dysfunction pathways. Clinical trials using humanized monoclonal antibodies, focusing on immunotherapies eliminating amyloid-beta, have shown promise. Nonpharmacological interventions such as light therapy, electrical stimulation, cognitive training, physical activity, and dietary changes have drawn attention for their potential to slow cognitive aging and enhance brain health. Precision medicine, which involves tailoring therapies to individual genetic and molecular profiles, has gained traction. Ongoing research and interdisciplinary collaboration are expected to yield more effective treatments.

Association and Mechanisms of Proton Pump Inhibitors Use with Type-2Diabetes Mellitus Incidence in Adults: A Systemic Review andMeta-Analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are an extensively prescribed class of anti-ulcer drugs. This systematic review aimed to investigate the association between PPI use and the risk of new-onset diabetes mellitus or type 2 diabetes (T2DM) incidence. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, Cochrane Library, and ClinicalTrials.gov using the search terms "proton pump inhibitor," "proton pump inhibitors," "PPIs," "diabetes mellitus," and "type 2 diabetes" from inception to February 2023. Statistical analyses were performed using the "Review Manager 5.4" version, and a statistically highly significant P-value <0.05 was set. RESULTS: This systematic review identified 12 studies (8 cohort, 1 RCT, and 3 case-control) with a total of 12, 64, 816 population, and the median age ranged from ≥18 yrs to ≤ 75 yrs. The pooled relative risk (RR) observations of a random-effects meta-analysis model showed that chronic exposure to PPI use has a significant association with T2DM risk incidence (RR, 2.44; 95% confidence interval, 1.31-4.54; I2 = 99%, P < 0.00001). The systematic review findings of the three case-control studies also supported an association of dose-dependent and chronic use of PPIs with an incidence of T2DM among chronic users. CONCLUSION: The systematic review concludes that chronic PPI exposure increases the risk of T2DM incidence. The authors recommend the shortest possible duration of PPI use and not prescribing PPIs to high-risk prediabetics and those without a compelling indication for PPI use. Regular education to patients regarding adverse reactions with prolonged use may decrease the risk of adverse effects associated with PPIs. The authors suggest that gut dysbiosis, hypergastrinemia, hypomagnesemia, decreased pancreatic secretions and IGF-1 levels, and PXR activation associated with chronic acid suppression among chronic PPI users and the potency of PPIs might explain the association between abnormal glucose metabolism and T2DM incidence. Finally, the authors recommend further randomized controlled trials to investigate the association between PPIs and the risk of new-onset T2DM incidence.

Health care associated infections, antimicrobial resistance and outcomes in patients admitted to intensive care unit, India: A five-Year retrospective cohort study.

Background: The present study was conducted to study the prevalence of HAIs in a newly established MICU, common microorganisms causing HAIs and their antibiotic-sensitivity profile, and antimicrobial utilization and mortality rate. Methods: The present retrospective cohort study was carried out at AIIMS, Bhopal (2015-2019). The prevalence of HAIs was determined; sites of HAIs and common causative microorganisms were identified, and their antibiotic-sensitivity profiles were studied. The group of patients with HAIs was matched with a control group drawn from the pool of patients without HAIs; this matching was done with respect to age, gender, and clinical diagnosis. Antimicrobial utilization, Period of ICU stay, comorbidities and patient mortality rates in the two groups were analyzed. The clinical criteria by the CDC- National Nosocomial Infections Surveillance to diagnose HAIs. Results: A total of 281 ICU patients' records were analyzed. The mean age was 47.21 ± 19.07 years. Of these 89 were found to have developed ICU-acquired HAIs (Prevalance:32%). Bloodstream infections (33%) and respiratory tract infections (30.68%), catheter-associated urinary tract infections (25.56%), and surgical site infections (6.76%) were the commonest. The most frequently isolated microorganism causing HAIs was K. pneumonia (18%), A. baumannii (14%) and E. coli (12%), 31% isolates of which were multidrug resistant. The average length of ICU stay was high in patients with HAIs (13.85 vs 8.2 days). The most common co-morbidity was type 2 diabetes mellitus (42.86%). Prolonged ICU stays [OR 1.13, (95% CI; 0.04-0.10)] and the presence of HAIs [OR 1.18(95%CI; (0.03-0.15)] were associated with an increased risk of mortality. Conclusions: An increased prevalence of HAIs essentially bloodstream infections and respiratory infections with MDR organisms to antimicrobials in the watch group is highly considerable. Acquisition of HAIs with MDR organisms and increased length of hospital stay are considerable risk factors for increased mortality in ICU-admitted patients. Regular antimicrobial stewardship activities and revising existing hospital infection control policies accordingly may reduce HAIs.

Anti-arthritic efficacy of Bombax ceiba ethanolic extract in a murine model for rheumatoid arthritis using in vivo, in vitro and radiological analysis.

Rheumatoid arthritis (RA) is a multisystem autoimmune disease that causes discomfort, synovial membrane inflammation, peripheral joint inflammation, morning stiffness, articular tissue loss, and restricted joint movement. In the present study, we aim to explore the anti-arthritic efficacy of Bombax ceiba ethanolic extract in a Freund's Complete Adjuvant-induced arthritis, in murine model. The hot soxhlet method was used to extract dried aerial components of Bombax ceiba using an ethyl alcohol: water (70:30) ratio. Bombax ceiba ethanolic extract at two doses of 200 and 400 mg/kg was investigated in Wistar rats against Freund's full adjuvant-induced chronic immunological arthritis. Anti-arthritis efficacy was studied utilising morphological research (paw volume, paw diameter, and body weight). On the 28th day, the animals were sacrificed, and haematological parameters, pro-inflammatory cytokines (TNF-alpha, IL-6), cell culture, histological and radiological analysis were performed. BCEE inhibited paw oedema significantly (P 0.05) at a dose of 40mg/Kg, which was corroborated by paw volume and diameter, as well as haematological parameters, in Freund's complete adjuvant-induced arthritis model. The BCEE also significantly reduced pro-inflammatory cytokine levels and the histopathological changes caused by Freund's full adjuvant model. BCEE preserves synovial membranes by enhancing health and has shown a significant anti-arthritic activity. Thus, data confirms the traditional usage of Bombax ceiba for arthritis.

Epidemiology, clinical presentation and treatment outcomes in patients with COVID-19 in an ambulatory setting: a cross sectional study during the massive SARS-CoV-2 wave in India.

The COVID-19 pandemic, caused by SARS-CoV-2, has profoundly affected developing countries like India. This retrospective cross-sectional analysis investigated epidemiological, clinical characteristics, treatment strategies, and outcomes for hospitalized COVID-19 patients during the Massive SARS-CoV-2 Wave in India. Among 233 patients, the median age was 47.33 years, mostly male. Hospital stays averaged 8.4 days. Common symptoms include fever (88.41%), dry cough (56.2%), myalgia (44.20%), and shortness of breath (22.8%). The most common comorbidities were diabetes mellitus (52%) and hypertension (47.2%). Elevated biomarkers include D-dimer (24.4%), CRP (32.1%), ferritin (26.60%), and others. Prescription analysis revealed that antibiotics (42.6%), Antivirals (37%), anthelmintics (20.30%), vitamins and nutritional supplements (20.71%) and glucocorticoids (12.8%) were the most commonly prescribed. Oxygen therapy was needed by 19.31% of patients in the moderate and severe categories within 24 hours of admission. The mortality rate was 8.58%. The surge led to increased hospitalizations and mortality, particularly among young adults. Diabetes and hypertension were correlated with mortality. Irregular use of drugs lacking evidence, like antibiotics and anthelmintics, vitamins and nutritional supplements, was observed in COVID-19 management. This study underscores the impact of the pandemic in India and highlights the need for evidence-based treatments.

Prevalence of overweight and obesity and their effect on COVID-19 severity and hospitalization among younger than 50 years versus older than 50 years population: A systematic review and meta-analysis.

Cohort studies have shown that both overweight and obesity have their impact by increasing hospitalization with COVID-19. We conducted a systematic literature search in PubMed, Google Scholar, and MedRxiv databases following the PRISMA guidelines. Statistical analyses were performed using STATA software version 16 MP (Stata Corp, College Station, TX, USA) and Med Calc software version 22.009(Med Calc software Ltd, Ostend, Belgium). The primary outcome was to measure the prevalence of overweight and obesity and their impact on the risk of hospitalization among COVID-19 patients under and above 50 years of age. In total, 184 studies involving 2,365,377 patients were included. The prevalence of overweight was highest among those younger than 50 years of age over those older than 50 years of age, (26.33% vs. 30.46%), but there was no difference in obesity (36.30% vs. 36.02%). Overall, the pooled prevalence of overweight and obesity among hospitalized COVID-19 patients was 31.0% and 36.26%, respectively. Compared with normal weight, the odds of hospitalization with overweight (odds ratio [OR] 2.186, 95% confidence interval [CI] [1.19, 3.99], p < 0.01) and obesity (OR 3.069, 95% CI [1.67, 5.61], p < 0.001) in those younger than 50 years and obesity (OR 3.977, 95% CI [2.75, 5.73], p < 0.001) in the older than 50 years age group were significantly high. The increased prevalence of overweight and obesity among the under 50 years age group and obesity among the older than 50 years age group significantly increased the rate of COVID-19 infections, severity and hospitalization.

Clinical virology and effect of Covid-19 vaccination and monoclonal antibodies against highly infectious SARS- CoV-2 omicron sub variant BF.7 (BA.5.2.1.7): A systematic review.

Over time, the SARS-CoV-2 virus has acquired several genetic mutations, particularly on the receptor-binding domain (RBD) spike glycoprotein. The Omicron variant is highly infectious, with enhanced immune escape activity, and has given rise to various sub-lineages due to mutations. However, there has been a sudden increase in COVID-19 reports of the Omicron subvariant BF.7 (BA.2.75.2), which has the highest number of reported cases, accounting for 76.2% of all cases worldwide. Hence, the present systematic review aimed to understand the viral mutations and factors associated with the increase in the reports of COVID-19 cases and to assess the effectiveness of vaccines and mAbs against the novel Omicron variant BF.7. The R346T mutation on the spike glycoprotein RBD might be associated with increased infection rates, severity, and resistance to vaccines and mAbs. Booster doses of COVID-19 vaccination with bivalent mRNA booster vaccine shots are effective in curtailing infections and decreasing the severity and mortality by enhancing the neutralizing antibodies (Abs) against the emerging Omicron subvariants of SARS-CoV-2, including BF.7 and future VOCs.

Global prevalence and effect of comorbidities and smoking status on severity and mortality of COVID-19 in association with age and gender: a systematic review, meta-analysis and meta-regression.

A COVID-19 patient often presents with multiple comorbidities and is associated with adverse outcomes. A comprehensive assessment of the prevalence of comorbidities in patients with COVID-19 is essential. This study aimed to assess the prevalence of comorbidities, severity and mortality with regard to geographic region, age, gender and smoking status in patients with COVID-19. A systematic review and multistage meta-analyses were reported using PRISMA guidelines. PubMed/MEDLINE, SCOPUS, Google Scholar and EMBASE were searched from January 2020 to October 2022. Cross-sectional studies, cohort studies, case series studies, and case-control studies on comorbidities reporting among the COVID-19 populations that were published in English were included. The pooled prevalence of various medical conditions in COVID-19 patients was calculated based on regional population size weights. Stratified analyses were performed to understand the variations in the medical conditions based on age, gender, and geographic region. A total of 190 studies comprising 105 million COVID-19 patients were included. Statistical analyses were performed using STATA software, version 16 MP (StataCorp, College Station, TX). Meta-analysis of proportion was performed to obtain pooled values of the prevalence of medical comorbidities: hypertension (39%, 95% CI 36-42, n = 170 studies), obesity (27%, 95% CI 25-30%, n = 169 studies), diabetes (27%, 95% CI 25-30%, n = 175), and asthma (8%, 95% CI 7-9%, n = 112). Moreover, the prevalence of hospitalization was 35% (95% CI 29-41%, n = 61), intensive care admissions 17% (95% CI 14-21, n = 106), and mortality 18% (95% CI 16-21%, n = 145). The prevalence of hypertension was highest in Europe at 44% (95% CI 39-47%, n = 68), obesity and diabetes at 30% (95% CI, 26-34, n = 79) and 27% (95%CI, 24-30, n = 80) in North America, and asthma in Europe at 9% (95% CI 8-11, n = 41). Obesity was high among the ≥ 50 years (30%, n = 112) age group, diabetes among Men (26%, n = 124) and observational studies reported higher mortality than case-control studies (19% vs. 14%). Random effects meta-regression found a significant association between age and diabetes (p < 0.001), hypertension (p < 0.001), asthma (p < 0.05), ICU admission (p < 0.05) and mortality (p < 0.001). Overall, a higher global prevalence of hypertension (39%) and a lower prevalence of asthma (8%), and 18% of mortality were found in patients with COVID-19. Hence, geographical regions with respective chronic medical comorbidities should accelerate regular booster dose vaccination, preferably to those patients with chronic comorbidities, to prevent and lower the severity and mortality of COVID-19 disease with novel SARS-CoV-2 variants of concern (VOC).

Rationality, Efficacy, Tolerability of Empagliflozin Plus Linagliptin Combination for the Management of Type 2 Diabetes Mellitus: A Systematic Review of Randomized Controlled Trials and Observational Studies.

BACKGROUND: Treatment of diabetes mellitus includes more than one drug of different groups, which may lead to a high pill burden and non-adherence to drugs. We have aimed to systematically analyze the clinical efficacy, safety, and pharmacoeconomic cost-effectiveness of the fixed-dose combination of empagliflozin plus a linagliptin in Type-2 Diabetes mellitus (T2DM) patients. METHODS: A literature search of PubMed/MEDLINE, SCOPUS, Google Scholar, and EMBASE was performed using the MeSH terms and/or keywords"((Single-pill combination) OR ((Fixeddose combination) OR (Combination therapy)) AND (Empagliflozin add on-to Linagliptin) OR (Empagliflozin combined with Linagliptin) OR ((Combination of Empagliflozin and Linagliptin)" from the inception to February 2021. RESULTS: Search results were found in a total of 13 clinical studies. After removing duplicates and studies not according to inclusion criteria, a total of eight clinical studies (Randomized controlled trials: 7; Observational cohort studies: 1) were included (n=7491). A significant reduction in the primary endpoint, the mean changes in baseline HbA1c at the end of 24 weeks and/or 52 weeks was found in the empagliflozin plus a linagliptin combination group in all included studies. In addition, significant efficacy was seen in decreasing the secondary endpoints such as the mean change in the fasting plasma glucose, systolic and diastolic blood pressure (DBP), and body weight with fewer adverse events than the adverse effects with either drug alone. CONCLUSION: After reviewing findings from the available clinical studies of the combination of empagliflozin plus linagliptin, we conclude that the combination is effective, safe, tolerable, and rationale cost effective compared to placebo and either drug alone for the management of T2DM in patients with inadequate glycemic control with metformin alone, patients with intolerance to metformin, increased baseline HbA1c, patients with overweight or obesity and diabetic hypertensive, CHF, atherosclerotic cardiovascular disease, and renal dysfunction patients. Future randomized controlled trials in a larger number of T2DM patients with or without CHF and renal failure patients are recommended.

Anti-inflammatory and arthritic activity of zaltoprofen compared to piroxicam in murine models.

Zaltoprofen, a unique propionic acid group of NSAIDs, works by blocking the enhancing effects of bradykinin along with the COX-2 enzyme. Therefore, it is of interest to evaluate the acute and chronic anti-inflammatory (arthritic) potential of zaltoprofen versus piroxicam in Murine models. A total of 48 Wister rats (200-250 g) of either sex (24 in each model) were used in the present study. The anti-inflammatory and arthritic potential of zaltoprofen was evaluated and compared by Carrageenan-induced acute inflammation and formalin-induced chronic inflammation. There was a significant inhibition of paw volume (P<0.001) on different time scales with two different doses of the test compound (Zaltoprofen 10 & 20 mg/kg) in the acute inflammation model compared to the negative control (NaCl 10 ml/kg). However, in the chronic inflammation model, zaltoprofen 10 mg/kg and 20 mg/kg doses of the test compound showed a significant reduction in chronic inflammation, comparable to the negative control (NaCl 10 ml/kg), although the potency was lower than the positive control (piroxicam 10 mg/kg) (P 0.05). Thus, zaltoprofen shows significant anti-inflammatory and arthritic effects in both acute and chronic models by inhibiting various inflammatory mediators.

Assessment of WHO core drug use indicators at a tertiary care Institute of National importance in India.

Rational prescribing of medicines is an important aspect of drug prescribing which helps in safe and efficacious and cost-effective drug treatment for patients. WHO Prescription indicators are intended to evaluate the services provided to the population concerning the rational use of medicines. The study aims to study prescription practices and rational use of medicines in the department of Internal medicine, using WHO prescribing indicators in a tertiary care teaching institute of national importance. A total of 50 prescriptions were digitally photographed and analysed for prescription practices and rational drug use, using standard WHO core prescribing indicators. A total of 301 drugs with multiple and diverse diagnoses were used. Statistical analysis was done using SPSS 22 version. The average number of drugs per prescription was 3.48%. It was found that only 13.79% of prescriptions have generic names, whereas 27.58% of patient encounters had at least one drug from the National List of Essential Medicine, 6.8% of prescriptions have antibiotics and 0.7% of prescriptions were injections. The number of prescriptions with fixed drug combinations was 27.55%. Indicators such as percentage of the National List of Essential Medicine, fixed drug combinations and prescribing with a generic name are used. Hence, we will suggest regular prescription audit practices and conducting CMEs and training workshops for clinicians for the rational use of medicines in all healthcare settings to succeed in the rational use of medicine.