Left ventricular ejection fraction: time to revise the metric?

In this paper, we highlight the prevalent misconception among patients regarding the normal value of left ventricular ejection fraction in cardiac function assessment. This misconception arises from the proportion dominance effect, wherein individuals tend to judge based on proportions rather than absolute values. We explain how this misunderstanding impacts patient demoralization and medical adherence, leading to worse clinical outcomes. To address this, the concept of "Left Ventricular Ejection Fraction - Proportion of Normal" is introduced, which adjusts left ventricular ejection fraction to a patient-specific normal range. This patient-centric approach aims to enhance comprehension, engagement, and adherence by conveying accurate information through the lens of proportions, thereby potentially improving clinical outcomes.

Usefulness of the PRECISE-DAPT score at differentiating between ticagrelor and prasugrel for dual antiplatelet therapy initiation.

As a part of dual antiplatelet therapy (DAPT), prasugrel or ticagrelor is prescribed along with aspirin to patients of acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We aimed to assess if the PRECISE-DAPT score, which provides prediction of bleeding during DAPT, could be used to choose between prasugrel and ticagrelor for DAPT initiation. 181 patients out of which 71 received prasugrel and 110 received ticagrelor were enrolled in this prospective cohort study. PRECISE-DAPT score was calculated for everyone and was used to dichotomize patients into two subgroups (score <25 and ≥25). After balancing potential confounders in baseline characteristics of the subgroups using propensity scores, comparison of a composite outcome of 4-point major adverse cardiovascular events (4P-MACE) (i.e., cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization due to stent thrombosis) and bleeding (any type as defined by the Bleeding Academic Research Consortium) within 1-year post-PCI was performed among the subgroups using Cox proportional hazards regression. Prasugrel was associated with lower and comparatively higher 4P-MACE events in subgroups with score ≥25 (HR: 0.17; 95% CI, 0.04-0.77) and score <25 (HR: 3.58; 95% CI, 0.62-20.70) respectively. For bleeding outcome, prasugrel trended towards more clinical benefit for scores ≥25 (HR: 0.44; 95% CI, 0.10-1.93) than <25 (HR: 0.93; 95% CI, 0.13-6.58). Therefore, prasugrel was associated with better clinical effectiveness and trended towards a lower bleeding risk compared to ticagrelor within 1-year post-PCI for those with a high PRECISE-DAPT score (≥25). This finding requires validation through larger studies.

Prasugrel Versus Ticagrelor in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: a Systematic Review and Meta-analysis of Randomized Trials.

PURPOSE: Dual antiplatelet therapy (DAPT) with aspirin and ticagrelor or prasugrel is the mainstay of treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We aimed to systematically perform a head-to-head comparison of ticagrelor vs prasugrel in terms of efficacy and safety. METHODS: We searched PubMed/Medline, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) for relevant published randomized controlled trials (RCTs). The primary outcome was adverse cardiovascular events and secondary outcome was bleeding events. A random-effects meta-analysis was used to obtain the pooled estimate of each outcome. RESULTS: Nine RCTs with a total number of 6990 patients (3550 treated with prasugrel and 3481 treated with ticagrelor) were included. No significant difference between prasugrel and ticagrelor was observed in terms of mortality (OR 0.86, 95% CI 0.66 to 1.13, P = 0.28), major adverse cardiovascular events (MACEs) (OR 0.85, 95% CI 0.70 to 1.03, P = 0.10), non-fatal myocardial infarction (OR 0.78, 95% CI 0.57 to 1.06, P = 0.11), stroke (OR 1.02, 95% CI 0.60 to 1.72, P = 0.95), stent thrombosis (OR 0.76, 95% CI 0.47 to 1.21, P = 0.25), thrombolysis in myocardial infarction (TIMI) defined major (OR 0.94, 95% CI 0.19 to 4.67, P = 0.94), minor (OR 0.35, 95% CI 0.08 to 1.62, P = 0.18) and minimal (OR 0.48, 95% CI 0.19 to 1.18, P = 0.11) bleeding and Bleeding Academic Research Consortium (BARC) defined bleeding (OR 1.06, 95% CI 0.82 to 1.36, P = 0.68). CONCLUSION: In patients with ACS undergoing PCI, both prasugrel and ticagrelor were associated with similar cardiovascular outcomes and adverse bleeding events.

Medication adherence, recall periods and factors affecting it: A community-based assessment on patients with chronic diseases in urban slums.

OBJECTIVE: To evaluate medication adherence, the effect of recall periods on self-reported adherence and factors influencing medication adherence among patients of chronic diseases, such as hypertension and diabetes, particularly in the community. METHODS: A cross-sectional cohort study was conducted among individuals with hypertension and/or diabetes coming as outpatients in community camps organised in a cluster of urban slums. Responses towards questions regarding self-reported quantitative and qualitative adherence for one week and one month along with information on pill burden, socio-demographic and other factors were recorded using a mobile application. RESULTS: Among 379 participants living in urban slum communities, who were prescribed anti-hypertensive or oral anti-diabetic medications previously, mean medication adherence over previous one week was 67.99% (standard deviation (SD) ± 38.32) and 6.87 (SD ± 3.62) on a ten-point numeric scale. The medication adherence for one month showed a strong significantly positive correlation with that of 1 week for both percentage-based (r = +0.910, 95% CI = 0.864 to 0.950, P < .0001) and Likert (ρ = +0.836, 95% CI = 0.803 to 0.863, P < .0001) scales. Age (r = 0.219, 95% CI = 0.120 to 0.313, P = .043) and pill burden (r = -0.231, 95% CI = -0.145 to -0.322, P < .0001) were found to significantly affect medication adherence. The odds of random blood sugar reduction were found to be significant (OR 1.98, 95% CI = 1.30 to 3.00, P = .001) with adequate adherence. A linear regression equation was developed to predict medication adherence percentage for a patient which was found to have 61.8% predictive power using multilayer perceptron modelling. CONCLUSION: Overall, medication adherence was sub-optimal. Adherence assessments can be reliably performed using either one week or one month recall periods. With further refinement and validation, the regression equation could prove to be a useful tool for physicians.

Comparison of Glycated Hemoglobin (HbA1c) Values Estimated by High-Performance Liquid Chromatography and Spectrophotometry: A Pilot Study.

Background Invasive blood sample collection followed by high-performance liquid chromatography (HPLC) based analysis is the gold standard for estimating glycated hemoglobin level or HbA1c currently. Spectrophotometry could be an alternative that holds the potential to be translated into a portable, non-invasive device for glycated hemoglobin level estimation. This study compares HbA1c values obtained from HPLC and spectrophotometry. Methods Venous blood samples were collected from both diabetic and non-diabetic participants in a cross-sectional study. The samples were subjected to both HPLC and spectrophotometry-based estimation of HbA1c%. The results obtained were compared, and the relationship between the two estimations were assessed. Results About 15 diabetic and non-diabetic individuals participated in the study and 28 samples were included in the final analysis. The Pearson's correlation coefficient was 0.65 (95% CI, 0.37-0.82), indicating that there was a strong positive association. This was further supported by the findings from linear regression analysis with a p-value of <0.001. Conclusions The positive correlation between the HPLC and spectrophotometric values supports the hypothesis that spectrophotometry could be an alternative to conventional HPLC for the measurement of HbA1c. This needs to be further validated through larger, well-powered studies.

Comparative effectiveness and safety of prasugrel and ticagrelor in patients of acute coronary syndrome undergoing percutaneous transluminal coronary angioplasty: A propensity score-matched analysis.

Evidence on comparative effectiveness and safety of prasugrel and ticagrelor post-percutaneous transluminal coronary angioplasty is scarce in Indian population. In a 1:1 propensity score-matched cohort with 71 individuals in each group, the incidence of a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization was not significantly different in prasugrel and ticagrelor group (7.04% vs 9.86%; absolute difference, 2.8%; HR, 0.65; 95% CI, 0.21-2.1; p = 0.49). There was no significant difference in bleeding (5.63% vs 9.86%; absolute difference, -4.20%; 95% CI, -13.0%-4.5%) and dyspnea (7.04% vs 12.7%; absolute difference, -5.60%; 95% CI, -15.4%-4.1%).

Retatrutide: a triple incretin receptor agonist for obesity management.

INTRODUCTION: Obesity treatment is evolving rapidly with the emergence of agents targeting incretin receptors. Retatrutide, a triple agonist of these receptors, shows promise in obesity management. AREAS COVERED: Retatrutide, in phase-2 trials, exhibited significant reductions in glycated hemoglobin (HbA1c) and dose-dependent weight loss in individuals with type 2 diabetes mellitus (T2DM). In non-T2DM individuals, it produced substantial weight loss and improved glucose levels, albeit with gastrointestinal side effects. The role of glucagon receptor agonism in the management of heart failure and its potential impact on eating patterns have also been covered in this article. EXPERT OPINION: Although the reductions in HbA1c and dose-dependent weight loss among individuals with T2DM were significantly more for higher doses of retatrutide, it needs to be observed that the active comparator was dulaglutide, which is not approved for the treatment of obesity, at a dose of 1.5 mg, which is much lower than the highest approved dose of 4.5 mg. Dose-dependent increase in heart rate and incidents of mild to moderate cardiac arrythmias raise cardiovascular safety concerns and signify that carrying out long-term cardiovascular outcome trials (CVOTs) will be critical. In addition, retatrutide's potential in heart failure management is intriguing given the series of positive findings of semaglutide on cardiovascular outcomes.

Comprehensive Pharmacist-led Transitions-of-care Medication Management around Hospital Discharge Adds Modest Cost Relative to Usual Care: Time-and-Motion Cost Analysis.

Optimal medication management is important during hospitalization and at discharge because post-discharge adverse drug events (ADEs) are common, often preventable, and contribute to patient harms, healthcare utilization, and costs. Conduct a cost analysis of a comprehensive pharmacist-led transitions-of-care medication management intervention for older adults during and after hospital discharge. Twelve intervention components addressed medication reconciliation, medication review, and medication adherence. Trained, experienced pharmacists delivered the intervention to older adults with chronic comorbidities at 2 large U.S. academic centers. To quantify and categorize time spent on the intervention, we conducted a time-and-motion analysis of study pharmacists over 36 sequential workdays (14 519 min) involving 117 patients. For 40 patients' hospitalizations, we observed all intervention activities. We used the median minutes spent and pharmacist wages nationally to calculate cost per hospitalization (2020 U.S. dollars) from the hospital perspective, relative to usual care. Pharmacists spent a median of 66.9 min per hospitalization (interquartile range 46.1-90.1), equating to $101 ($86 to $116 in sensitivity analyses). In unadjusted analyses, study site was associated with time spent (medians 111 and 51.8 min) while patient primary language, discharge disposition, number of outpatient medications, and patient age were not. In this cost analysis, comprehensive medication management around discharge cost about $101 per hospitalization, with variation across sites. This cost is at least an order of magnitude less than published costs associated with ADEs, hospital readmissions, or other interventions designed to reduce readmissions. Work is ongoing to assess the current intervention's effectiveness.

How to choose and interpret a statistical test? An update for budding researchers.

Postgraduate medical students are often not able to select and interpret the findings of statistical tests during their thesis or research projects. To go ahead with selection of tests to be performed, researchers need to determine the objectives of study, types of variables, analysis and the study design, number of groups and data sets, and the types of distribution. In this review, we summarize and explain various statistical tests to help postgraduate medical students to select the most appropriate techniques for their thesis and dissertation.

Famotidine Repurposing for Novel Corona Virus Disease of 2019: A Systematic Review.

BACKGROUND: COVID-19 caused by SARS-CoV-2 was declared as a global pandemic by the WHO. Famotidine is a histamine-2 (H2) receptor antagonist which blocks the H2 receptors in the parietal cells, decreasing gastric acid secretion. Our review aims to study all the available scientific evidence on famotidine research outcomes systematically to introspect its clinical efficacy and probable mechanisms and clinical efficacy against SARS-CoV-2. METHODOLOGY: An electronic search of PubMed, Scopus and Google Scholar was performed using MeSH terms "SARS CoV-2" OR "COVID-19" AND"FAMOTIDINE". Relevant informationwas extracted from studies reporting the efficacy of famotidine in COVID-19. RESULTS: We found a total of 32 studies, out of which only 14 were relevant and were included in our review.Molecular computational studies showed that famotidine selectively acts on viral replication proteases papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro). Additionally, it acts via inverse-agonism on the H2 receptors present in neutrophils and eosinophils which leads to inhibition of cytokine release. Clinical study findings have pointed toward significant improvements in COVID-19 patient-reported symptoms in non-hospitalized patients and reduction in intubation or death in critically ill patients associated with the usage of famotidine. However,in one of the studies,famotidine has failed to show any significant benefit in reducing mortality due to COVID-19. CONCLUSION: Famotidine has the potential to answer the ongoing global challenge owing to its selective action on viral replication. Additionally, clinical findings in COVID-19 patients support its efficacy to reduce clinical symptoms of COVID-19.We suggest that further optimally powered randomized clinical trials should be carried out to come up with definitive conclusions.

Carbovigilance: curtailing the global pharmaceutical carbon footprint.

Cutting emissions from the pharmaceutical industry is essential to curtailing the carbon footprint of healthcare globally. It is high time that the industry owned up to its carbon emission and took measures to curb back. In this study, we show how many of the leading global pharmaceutical firms have been able to reduce their carbon footprint while being profitable, indicating that modifications to reduce emissions would not pose a financial burden. We have come up with a 'modified emission intensity' index and a new term 'carbovigilance' in an attempt to bring this aspect of the pharmaceutical companies to light, while also encouraging them to work towards making positive contributions to a greener and healthier earth.

Can species distribution models and molecular tools help unravel disjunct distribution of Rhododendron arboreum?

The apparent absence of Himalayan low-elevation taxa in the central Indian region and resumption of their distribution in the high elevation of Western Ghats has puzzled biogeographers for several decades. Many theories have been proposed to explain this but attempts remain futile owing to insufficient empirical support. Here, we have employed a montane tree species, Rhododendron arboreum to investigate this pattern by integrating past ecological niche modelling with molecular signatures. Reconstruction of paleo-ecological niche from interglacial to Last Glacial Maxima (LGM) portrayed a gradual depletion of vegetation cover with extreme impoverishment in the Holocene. A similar pattern was also reflected from genetic signatures; population history revealed a very recent split between the Himalayas and Western Ghats in the late Quaternary. A few other tree species exhibiting the same disjunction demonstrated a similar modification of paleo-ecological niche from last interglacial. The study clearly indicated that the populations in the Western Ghats to be a relictual remnants of a once continuous distribution of R. arboreum.

COVID-19 and thrombotic complications-the role of anticoagulants, antiplatelets and thrombolytics.

Coronavirus disease 2019 (COVID-19) is a global pandemic the world is dealing with currently. Clinical evidences suggest that the patients are predisposed to both venous and arterial thrombotic complications. This is because of severe inflammatory responses, injury to endothelium and activation of platelets leading to increased coagulation. Additionally, individuals who are already receiving antithrombotic drug therapy for various cardiovascular diseases and complications might contract the disease in which case, attention should be given to the choice and duration of the therapy besides close monitoring of biochemical blood parameters. Herein, we review the incidences of thrombotic complications and their outcomes in COVID-19 patients as reported till date, while understanding the prophylactic and therapeutic roles of anticoagulants, antiplatelets and thrombolytics in the management of this severe viral respiratory illness.

The Potential Therapeutic Role of Proton Pump Inhibitors in COVID-19: Hypotheses Based on Existing Evidences.

Although the major therapeutic uses of the proton pump inhibitors are in gastric-acid related diseases, evidences are suggestive of a pleiotropic nature of the compounds. We comment on the probable pathways and cellular machineries via which proton pump inhibitors could show beneficial therapeutic effects against SARS-CoV-2 based on the existing evidences. Proton pump inhibitors have shown antiviral potencies in various in vivo and in vitro studies. Some of the major possible ways through which they can act against SARS-CoV-2 are by exerting anti-inflammatory and anti-fibrotic effects, via vacuolar ATPase pumps leading to raised endolysosomal pH and by targeting endosomal complexes. The current pandemic has put forward a challenge to find treatment options. Although the potential roles of proton pump inhibitors against SARS-CoV-2 have been discussed in recent publications, the clinical evidences for their real-world effectiveness do not point towards a beneficial effect clearly yet. We suggest that although proton pump inhibitors should strongly be considered as potential therapeutic options for COVID-19, larger studies in the form of randomized controlled trials would be required to arrive at a definite conclusion.

Understanding the molecular-pharmaceutical basis of sartan recalls focusing on valsartan.

Angiotensin receptor blockers (ARBs) or the 'sartans' are widely used for the management of hypertension and heart failure. There have been a series of recent incidents where drug formulations containing different ARBs as active pharmaceutical ingredients have been recalled by various pharmaceutical firms. This article addresses valsartan as well as other sartan recalls besides discussing the recent recalls of ranitidine and metformin, giving insights into the molecular-pharmaceutical basis of the recalls. A thorough literature search of PubMed/Medline and Google Scholar databases was performed to identify all relevant articles and information published up to 29th April 2020 using Medical Subject Headings (MeSH terms) and Boolean operators. We also searched for relevant information on the web using web-browsers and reference lists from original research papers and review articles. The main impurity found was N-nitrosodimethylamine (NDMA) which was thought to be formed due to a change in the manufacturing process of valsartan. Besides, other impurities such N-nitrosodiethylamine (NDEA) and N-nitroso-N-methyl-4-aminobutyric acid (NMBA) were found in batches of other sartans, such as losartan and irbesartan. All of these are carcinogens and harmful if consumed at a level beyond a certain acceptable daily limit. Ranitidine, and more recent metformin recalls, have also been linked with valsartan in view of the presence of NDMA, the same impurity. Safety of ARBs is a major concern among healthcare professionals after the recalls of valsartan in the recent years. Periodic quality assessment of the manufacturing process and the drugs is key to ensure safe, effective and high-quality drugs for the global population. Additionally, practising physicians need to be vigilant in reporting adverse events in their patients receiving treatments.

A Cost Variation Analysis of Drugs Available in the Indian Market for the Management of Thromboembolic Disorders.

Introduction Cardiovascular diseases (CVDs) have become one of the major causes of mortality among the Indian population. The costs of anticoagulant, antiplatelet, and fibrinolytic drugs that are used to treat various thromboembolic disorders and used as prophylactics for individuals at high risk of CVDs vary widely in the Indian pharmaceutical market. The aim of this study was to evaluate the cost variation of different brands of drug formulations and to compare the branded prices of the formulations with their corresponding generic and ceiling prices. Materials and methods This study followed an analytical method. Costs of various drugs were obtained from the October - December 2019 edition of the Current Index of Medical Specialities (CIMS) and December 2019 edition of the Monthly Index of Medical Specialities (MIMS) India. Cost ratio and percentage variation in cost per tablet/capsule/injection of different drugs available in the Indian market and manufactured by different pharmaceutical companies were calculated. Comparison of the branded prices with generic and ceiling prices was also performed for different drugs by using information available from official websites. Results Percentage variation in cost among the commonly prescribed drugs for the management of thromboembolic disorders was found to be highest for prasugrel 10 mg tablet (1,408.44%) while it was lowest for fondaparinux 2.5 mg / 0.5 ml injection (20%). Among the commonly prescribed drugs that are under Drugs Prices Control Order (DPCO) price control, streptokinase 1.5 MIU injection had the highest cost variation (132.02%) while enoxaparin 60 mg / 0.6 ml injection had the lowest (4.99%). Among some of the important formulations under the Jan Aushadhi scheme (JAS), acenocoumarol 2 mg tablet had the highest cost variation (680.09%) and cilostazol 50 mg tablet had the lowest (55.46%). Conclusions Wide differences exist in the costs of various anticoagulants, antiplatelets, and fibrinolytics available in the Indian market. The prescribing physician should be aware of theses variations and prescribe medicines accordingly, keeping in mind the financial status of the patients.

Tigecycline-Induced Severe Hypoglycemia in a Non-Diabetic Individual: A Case Report and Brief Review of Tigecycline-Induced Severe Hypoglycemia.

BACKGROUND Tigecycline is a broad-spectrum antibiotic belonging to the glycylcycline class. Hypoglycemia is a rare adverse effect associated with its use. We report a case of multiple episodes of severe hypoglycemia in a non-diabetic patient on treatment with tigecycline for cellulitis following snake bite. CASE REPORT A 45-years-old male was admitted with cellulitis of left leg due to snake bite with sepsis, acute kidney injury, and disseminated intravascular coagulation. A transtracheal aspirate culture showed infection with Klebsiella pneumoniae, and parenteral tigecycline was started based on the drug-sensitivity testing results. Multiple severe hypoglycemic episodes occurred, with persistently low blood glucose levels in the subsequent days. Tigecycline was stopped at the physician's discretion due to completion of the recommended course of treatment. The blood glucose levels continued to remain either below or on the lower end of the normal range before it started rising gradually. Tigecycline was again started based on another drug-sensitivity testing. A total of 4 episodes of hypoglycemia occurred over the next 2 days, and tigecycline was stopped prematurely. The patient's condition gradually improved with no more hypoglycemic episodes, and he was finally discharged. CONCLUSIONS We report a non-diabetic patient of cellulitis following snake bite who suffered from tigecycline-induced severe hypoglycemic episodes that persisted for a prolonged period of time. After a thorough search of the published literature, we could not find such a case of severe and sustained hypoglycemia due to tigecycline in an individual without diabetes and not on any hypoglycemic agent.

Risperidone-induced Somnambulism: A Case Report and Brief Review of Literature.

Atypical antipsychotic drugs have been recommended as the first-line agents in the treatment of schizophrenia. They are usually not associated with extrapyramidal symptoms and hyperprolactinemia. There is no previously reported case on somnambulism associated with risperidone intake. We report a case of risperidone-induced somnambulism in a schizophrenic patient. Somnambulism occurred while the patient was on a dose of 3 mg of risperidone per day. The dose was reduced to 2 mg per day along with the addition of clonazepam 0.5 mg daily at night. No further episode of somnambulism was reported after this. This case suggests the association of risperidone with occurrence of somnambulism. Further evidence to strengthen the causality of this needs to be gathered. This calls for prompt pharmacovigilance reporting of adverse drug events associated especially with antipsychotics.

Organoids: An invaluable tool in pharmacology.

Advances in stem cell cultures and human-induced pluripotent stem cells have inculcated interests in a rapidly evolving concept - "organoids." These are three-dimensional (3D) structures mimicking some of the phenomena of the real organs at anatomical, multicellular, and functional levels in vitro. Organoids have been proven to be better than two-dimensional cell culture in replicating the functionality, architectural, and geometrical features of tissues in vivo. Recent advancements have led to the generation of models for organ development and disease, finding applications in the drug discovery, screening of novel compounds, and personalized medicine. Since organoids follow the same natural pathway as the normal tissue or pathology, they can be used to study the expression of various genotypes and phenotypic variations across different species. In the light of these advancements, organoids are now being merged with bioengineering to come up with even better and reliable models to predict the disease progression and effectiveness of precision medicines, few of its important applications. This article discusses the various aspects of this emerging concept along with its uses, both in the present times and near future, with a special focus on pharmacological applications.