Evaluation of ivabradine plus beta-blocker versus beta-blocker alone in addition to standard care in reducing hospitalization and major adverse cardiovascular event in patients with chronic heart failure: a prospective observational study in tertiary care hospital in central India.

BACKGROUND: In recent years, there has been an increase in cases of heart failure, ultimately leading to an increase in hospitalization for heart failure (HF) and cardiovascular mortality. The aim of our study was to evaluate ivabradine combined with beta-blocker versus beta-blocker alone in addition to standard care for chronic heart failure, followed for a period of 6 months for the rate of hospitalization and major adverse cardiovascular event (MACE) in patients with reduced left ventricular ejection fraction (LVEF < 35%). RESULTS: A total of 64 patients were included in this observational study with 30 patients in the ivabradine + beta-blocker (IVA + BB) group and 34 in the beta-blocker (BB) group. The median (IQR) age of the study sample was 57 (50-62) and 58.5 (55-67) in IVA + BB and BB groups, respectively, with LVEF < 35%. The incidence of the primary endpoint of composite MACE (MI, stroke, death, worsening of HF) was 5 in both groups. The mean heart rate was significantly decreased (p < 0.001) at 3-month and 6-month follow-up from baseline in the ivabradine + beta-blocker group as compared to the beta-blocker group alone, while it significantly increased in the beta-blocker group at 3 months (p < 0.01) and also at sixth months (p < 0.05). Parameters such as the New York Heart Association (NYHA) class and the Minnesota Living with Heart Failure questionnaire (MLWHFQ) were also assessed but did not show significant change. CONCLUSION: Overall, observations from the study results show that IVA + BB seems to be overall well tolerated in the study sample, with a somewhat smaller decrease in hospitalization and a delay in MACE events in the sample population enrolled in a tertiary care hospital in India. Further exploration in a larger sample is required concerning the Indian population.

Evaluating the Efficacy and Safety of Tirzepatide on Glycaemic and Non-glycaemic Outcomes in Diabetes: A Systematic Review of Meta-Analyses.

Tirzepatide is a novel once-a-week dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, recently approved for type 2 diabetes mellitus (T2DM) and obesity. A systematic review of the literature published in multiple meta-analyses on Tirzepatide with emphasis on its effect on glycaemic and non-glycaemic parameters was conducted. We systematically searched the electronic databases PubMed and Google Scholar up to August 2023 for meta-analyses that compared Tirzepatide with placebo or active antihyperglycaemic drugs in subjects with T2DM. Various parameters for efficacy and safety, with their point estimates and confidence intervals, such as glycated haemoglobin (HbA1c), fasting serum glucose (FSG), body weight, lipid, and cardiovascular outcomes were assessed. Six meta-analyses fulfilled the pre-specified criteria and were included in the study. In all the studies, Tirzepatide treatment at different doses resulted in a significant reduction in HbA1c and FSG levels along with a significant reduction in weight compared with active control and placebo groups. Tirzepatide significantly reduced levels of triglycerides and increased high-density lipoprotein (HDL) cholesterol, whether used as monotherapy or add-on therapy. The studies suggested the cardiovascular safety of Tirzepatide as there was no increase in major adverse cardiovascular events (MACE). The drug shows lesser hypoglycemia but predominant gastrointestinal adverse effects such as nausea, vomiting, and diarrhoea. In conclusion, Tirzepatide shows superior glycaemic control and weight loss in patients with T2DM with beneficial effects on lipids, without an increased risk of hypoglycemia and cardiovascular events.

Molnupiravir in COVID-19: A Scoping Review.

BACKGROUND: COVID-19, first detected in Wuhan, China, has evolved into a lifethreatening pandemic spread across six continents, with the global case count being more than 243 million, and mortality over 4.95 million, along with causing significant morbidity. It has initiated an era of research on repurposed drugs such as hydroxychloroquine, lopinavir/ritonavir, corticosteroids, remedesivir, ivermectin, alongside selective antivirals to treat or prevent COVID- 19. Molnupiravir is an orally available emerging antiviral drug considered highly promising for COVID-19. METHODS AND RESULTS: We have performed a scoping review for the use of molnupiravir against SARS-CoV-2 and COVID-19. It acts by inhibiting RNA-dependent RNA polymerase (RdRp), and exhibits broad-spectrum antiviral activity. Preclinical studies have evaluated the therapeutic efficacy as well as prophylactic activity of molnupiravir against SARS CoV-2 in various animal models that include ferrets, hamsters, mice, immunodeficient mice implanted with human lung tissue and cell cultures, in various doses ranging from 5-300 mg/kg, and results have been encouraging. Initial evidence of safety and efficacy from early phase clinical studies has been encouraging too, and recent results from a large phase 3 global trial have shown significant benefits among symptomatic outpatients. Other late-phase clinical trials are still underway with the aim of establishing molnulpiravir as a therapeutic option for COVID-19, particularly for non-hospitalized patients. CONCLUSION AND RELEVANCE: On the basis of the limited evidence available as of now, molnupiravir could prove to be a promising oral therapy, worthy of further exploration of its utility for both treatment and prevention of COVID-19 in humans. Elaborate clinical evaluation is further warranted to confirm whether the results are replicable to the clinical scenario among outpatients to reduce the chance of progression to more severe disease.

Citrulline: pharmacological perspectives and its role as an emerging biomarker in future.

L-Citrulline is a naturally occurring non-essential amino acid, an intermediate in urea cycle and conditionally essential in intestinal pathology. It is a potent hydroxyl radical scavenger and much more effective precursor of arginine and nitric oxide (NO) than arginine itself so exploited in therapeutics. Plasma citrulline concentration is used by clinicians to assess functional enterocyte mass in various chronic and acute small bowel pathologies like short bowel syndrome that has become an indication in clinical practice. Its supplementation is likely to be used in conditions like erectile dysfunction, sickle cell anemia, short bowel syndrome (to restore nitrogen balance), hyperlipidemia, cancer chemotherapy, hypercholestremia, in hyperoxic lung damage, urea cycle disorders, Alzheimers disease, multi-infarct dementia and as an immunomodulator. Its emerging role as a biomarker in intestinal pathology and early diagnosis of Rheumatoid arthritis has spread considerable interest. Antibody detection to Anti-cyclic citrullinated peptide (ACCP) antibodies can be recommended for early detection of RA decreasing joint damage and deformity, because these are detected well before the onset of disease manifestations of RA. The test is highly specific than RF (Rheumatoid factor), with moderate sensitivity, but much useful in differentiating RA from other disorders. Further studies and exploration is required in these areas.

Novel actions of progesterone: what we know today and what will be the scenario in the future?

OBJECTIVES: This article is aimed to review the novel actions of progesterone, which otherwise is considered as a female reproductive hormone. The article focuses on its important physiological actions in males too and gives an overview of its novel perspectives in disorders of central and peripheral nervous system. KEY FINDINGS: Progesterone may have a potential benefit in treatment of traumatic brain injury, various neurological disorders and male related diseases like benign prostatic hypertrophy (BPH), prostate cancer and osteoporosis. Norethisterone (NETA), a progesterone derivative, decreases bone mineral loss in male castrated mice suggesting its role in osteoporosis. In the future, progesterone may find use as a male contraceptive too, but still needs confirmatory trials for safety, tolerability and acceptability. Megestrol acetate, a progesterone derivative is preferred in prostatic cancer. Further, it may find utility in nicotine addiction, traumatic brain injury (recently entered Phase III trial) and Alzheimer's disease, diabetic neuropathy and crush injuries. Studies also suggest role of progesterone in stroke, for which further clinical trials are needed. The non genomic actions of progesterone may be in part responsible for these novel actions. SUMMARY: Although progesterone has shown promising role in various non-hormonal benefits, further clinical studies are needed to prove its usefulness in conditions like stroke, traumatic brain injury, neuropathy and crush injury. In male related illnesses like BPH and prostatic Ca, it may prove a boon in near future. New era of hormonal male contraception may be initiated by use of progesterone along with testosterone.

Effects of calcium, strontium, and barium on isolated phrenic nerve-diaphragm preparation of rat and their interactions with diltiazem and nifedipine.

Calcium (Ca2+), strontium (Sr2+), and barium (Ba2+) are expected to exert similar chemical and pharmacological effects. The effects of barium, strontium and calcium were studied on the contractions of rat phrenic nerve-diaphragm preparations, following electrical stimulation and their interactions with nifedipine (nif) and diltiazem (DZM) were also studied. Low doses of strontium chloride (SrCl2), barium chloride (BaCl2) and calcium chloride (CaCl2) were able to increase the force of contraction of the rat diaphragm when actively stimulated. Diltiazem inhibited the stimulant effects of Sr2+, Ba2+, and Ca2+. On the other hand, nifedipine blocked the effects of Sr2+ and Ca2+ but potentiated the effects of Ba2+. Strontium, barium, and calcium restored the contractility of the muscle following electrical stimulation when the tissue was in biological fluid absolutely depleted of calcium. These findings suggest that Sr2+ and Ba2+ may be able to substitute Ca2+ in the rat diaphragm for its contractions and nifedipine and diltiazem may follow different mechanisms of actions or channels in their blocking effects.