A Comprehensive Literature Review on Managing Systemic Lupus Erythematosus: Addressing Cardiovascular Disease Risk in Females and Its Autoimmune Disease Associations.

This review aimed to evaluate the mechanism of premature cardiovascular disease (CVD) in systemic lupus erythematosus (SLE) patients, particularly in the female population, and emphasize the need for early management interventions; explore the association between SLE and two autoimmune diseases, myasthenia gravis (MG) and antiphospholipid antibody syndrome (APS), and their management strategies; and evaluate the effectiveness of pharmacological and non-pharmacological interventions in managing SLE, focusing on premenopausal females, females of childbearing age, and pregnant patients. We conducted a comprehensive literature review to achieve these objectives using various databases, including PubMed, Google Scholar, and Cochrane. The collected data were analyzed and synthesized to provide an evidence-based overview of SLE, its management strategies as an independent disease, and some disease associations. The treatment should be focused on remission, preventing organ damage, and improving the overall quality of life (QOL). Extensive emphasis should also be focused on diagnosing SLE and concurrent underlying secondary diseases timely and managing them appropriately.

Effect of Music Tempo on Pattern Reversal Visual Evoked Potential in Young Adults-Multisensory Stochastic Resonance: A Pilot Study.

Stochastic resonance (SR) is a phenomenon in which an intermediate level of noise enhances the response of a weak input signal. This phenomenon is experimentally used for rehabilitation and treatment of visuomotor disorders associated with low amplitude and higher latency P100 VEPs. We presupposed that shortly it will be possible to develop and design new devices that enable multisensory SR in the audio-visual modality for human sensorimotor enhancement and rehabilitation purposes. This study was newer in which the auditory noise was used in the form of song of different tempos and their amplitude and latency of P100 PRVEP (pattern reversal visual evoked potential) was compared. Whether the different tempos song may affects the PRVEP. This study was conducted on 57 healthy volunteers in AIIMS Bhopal. The subjects were placed in front of a computer displaying a checkerboard 8x8 size. Electrodes were pasted on their scalp. The average latencies and amplitudes of the PRVEP were recorded at resting, then with the stimulus of acoustic noise in the form of low and high tempo song. The PRVEP were recorded for each event. We found that low- and high-tempo songs do not affect the latency component of PRVEP, while it significantly affects amplitude. Music therapy can help with vision rehabilitation, especially in patients with low amplitude PRVEP. A more significant number of samples for further study in this field in multisensory SR with visual evoked potentials (VEP) are necessary. We can also conclude that a sound-free environment is essential during VEP recording.

Subjective and Objective Assessment of Effect of Allergic Rhinitis on Voice in Indian Patients.

To perform a subjective and objective assessment of vocal complaints in patients of allergic rhinitis (AR) using voice handicap index and video-stroboscopy respectively and find the association of their parameters with severity of the disease. Cross-sectional-observational study design. Outpatient department of Otorhinolaryngology of a tertiary centre. Seventy-five adult patients diagnosed with AR and classified according to 'Allergic Rhinitis and its Impact on Asthma' guidelines were compared with same number of normal subjects as controls, with the same age and sex, to ensure uniformity. Both the groups were asked to fill a self-answered questionnaire called Voice Handicap Index (VHI) and underwent laryngeal examination with Video-Stroboscopy (VS). The mean VHI score of the AR group (29.45 ± 32.11) was significantly higher (p < 0.05) than that of controls (12.07 ± 16.62). VS parameters including amplitude, supraglottic activity, vocal edge and phase closure also showed significant difference between cases and controls (p < 0.05). VHI scores increased, but the VS findings did not change significantly with the severity of the disease. AR patients show subjective and objective derangements of voice quality. VHI scores show increase, while VS parameters do not change with the severity of AR.

Applications of Nanotechnology in Forest Management.

Relatively a new branch of technology, Nanotechnology has been found effective and applicable in various scientific disciplines. Its effectiveness has attracted many researchers to use it for solving various issues related to the natural resource management. Lots of studies have been carried out so far and published related to the applications of nanotechnology in climate science, forestry, agro-ecosystem, medical science and industrial sectors. Solving climate change issues in forestry sector, development of new nanomaterials for the management of forests from risks like drought, flood, salinity, fire, invasion, pathogen etc., water resource management in forest system, increasing energy efficiency of forests, improved forest produce, applications in forest based paper industries and other potential domains and its application has been reviewed in this paper along with some of frequently used nanomaterials, generally used or have potential to be used. Some industries currently using this technology are also enlisted. It was concluded that the nanotechnology has significant scope in the field of forestry as an enabling technology yet the future directions and requirements of applying nanotechnology in forestry sector are still in budding stage especially in India and may be applied at large scale by facilitating technical and legal institutions, large R&D grants and research collaborations.

Using machine learning to develop a novel COVID-19 Vulnerability Index (C19VI).

COVID-19 is now one of the most leading causes of death in the United States (US). Systemic health, social and economic disparities have put the minorities and economically poor communities at a higher risk than others. There is an immediate requirement to develop a reliable measure of county-level vulnerabilities that can capture the heterogeneity of vulnerable communities. This study reports a COVID-19 Vulnerability Index (C19VI) for identifying and mapping vulnerable counties. We proposed a Random Forest machine learning-based vulnerability model using CDC's sociodemographic and COVID-19-specific themes. An innovative 'COVID-19 Impact Assessment' algorithm was also developed for evaluating severity of the pandemic and to train the vulnerability model. Developed C19VI was statistically validated and compared with the CDC COVID-19 Community Vulnerability Index (CCVI). Finally, using C19VI and the census data, we explored racial inequalities and economic disparities in COVID-19 health outcomes. Our index indicates that 575 counties (45 million people) fall into the 'very high' vulnerability class, 765 counties (66 million people) in the 'high' vulnerability class, and 1435 counties (204 million people) in the 'moderate' or 'low' vulnerability class. Only 367 counties (20 million people) were found as 'very low' vulnerable areas. Furthermore, C19VI reveals that 524 counties with a racial minority population higher than 13% and 420 counties with poverty higher than 20% are in the 'very high' or 'high' vulnerability classes. The C19VI aims at helping public health officials and disaster management agencies to develop effective mitigation strategies especially for the disproportionately impacted communities.

Computational insights of phytochemical-driven disruption of RNA-dependent RNA polymerase-mediated replication of coronavirus: a strategic treatment plan against coronavirus disease 2019.

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised global health concerns. RNA-dependent RNA polymerase (RdRp) is the prime component of viral replication/proliferation machinery and is considered to be a potential drug target against SARS-CoV-2. The present study investigated the anti-RdRp activity of phytochemicals against SARS-CoV-2 infection. Virtual ligand screening was carried out to determine the potent compounds against RdRp. Molecular docking and an MD Simulation study were employed to evaluate the spatial affinity of selected phytochemicals for the active sites of RdRp. Structural stability of target compounds was determined using root mean square deviation computational analysis and drug-like abilities were investigated using ADMET. Bond distances between ligand and receptor were marked to predict the strength of interaction. Aloe, azadirachtin, columbin, cirsilineol, nimbiol, nimbocinol and sage exhibited the highest binding affinities and interacted with active sites of RdRp, surpassing the ability of chloroquine, lamivudine, favipiravir and remdesivir to target the same. All the natural metabolites exhibited stable conformation during MD Simulation of 101 ns at 310 K. Kinetic, potential and electrostatic energy were observed to be least in the case of natural metabolites in comparison with synthetic analogues. Deviations and fluctuations were observed to be structurally least in target phytochemicals. Physiochemical and biological properties of these compounds further validated their drug-like properties. Non-bonded distance was found to be short enough to form hydrogen bonding or hydrophobic interactions, which revealed that these target compounds can strongly bind with RdRp. The study found potential phytochemicals to disrupt the replication domain of SARS-CoV-2 by hindering RdRp. We therefore anticipate that the current findings could be considered as valuable for the development of an efficient preventive/therapeutic expedient against COVID-19.

A comparative evaluation of iliac crest bone graft with and without injectable and advanced platelet rich fibrin in secondary alveolar bone grafting for cleft alveolus in unilateral cleft lip and palate patients: A randomized prospective study.

PURPOSE: Platelet rich fibrin enhances bone healing and results in better graft intake and helps in faster periodontal healing. In this study we have used a combination of two newly developed forms of platelet rich fibrin: injectable and advanced along with iliac bone graft for secondary alveolar bone grafting and compared it with cases in which only iliac bone graft was used. METHODS: 30 patients with alveolar cleft, with age group of ≥7 years, having complete unilateral cleft alveolus were included and divided into 2 groups of 15 patients each randomly. In Group A, secondary alveolar bone grafting was done using iliac bone graft along with injectable and advanced palate rich fibrin and in Group B, secondary alveolar bone grafting was done only with iliac bone graft. Success of the treatment was assessed using radiographic and clinical methods which included: The bone resorption of the interalveolar septum height of the teeth adjacent to the cleft, evaluated as per Bergland classification, assessment of periodontal status of the teeth adjacent to cleft alveolus. RESULTS: After 3 months and 6 months postoperatively: study group had better overall scores as per Bergland criteria. Periodontal status improved in both groups but was more in study group compared to control group. For both evaluations the data was clinically favorable in the study group. CONCLUSION: On preliminary investigations it shows that combination of injectable and advanced platelet rich fibrin seems to enhance bone formation in alveolar clefts when admixed with autologous cancellous bone harvested from the iliac crest than using iliac bone graft alone. It also reduces the chances of bone resorption and show higher percentage of bone volume. Secondary alveolar grafting improves periodontal health around the cleft alveolus.

The role of dietary polyphenols in inflammatory bowel disease: A possible clue on the molecular mechanisms involved in the prevention of immune and inflammatory reactions.

Inflammatory bowel disease (IBD) is one of the major complications of the gastrointestinal tract, characterized by chronic inflammation, which disturbs the quality of life of the affected individuals. Genetic predisposition, immune, inflammatory, and enzyme-mediated signaling cascades are the primary mechanisms involved in the pathogenesis of the disease. Currently, the treatment strategy involves the maintenance of remission and induction of inflammation by anti-inflammatory agents and immune suppressants. Polyphenol-containing diets, including fruits and vegetables of regular use, possess anti-inflammatory, and antioxidant potential through the inhibition of major contributing pathways to IBD. This review discusses the role of these dietary polyphenols in downregulating the major signaling cascades in IBD. Our review encourages the development of nutritional strategies to improve the efficiency of current therapies for IBD and reduce the risks of side effects associated with conventional therapy. PRACTICAL APPLICATIONS: At present, almost every third person in society is under stress and having chronic disorders like diabetes, arthritis, allergy, cardiovascular disease, IBD, etc. This insists on the direct/indirect role of changes in the lifestyle for such deterioration in society. This review would emphasize the medicinal value of polyphenols present in fruits and vegetables for chronic inflammatory disorders. This concept portrays the food components which have the potential to promote health, improve general well-being, and reduce the risk of IBD. We propose to add fruits with bioactive polyphenols in the regular diet to help in preventing the immune-mediated intestinal chronic inflammatory syndrome and reduce the risks of colorectal cancer development.

Early thrombolysis is associated with decreased operative mortality in postinfarction ventricular septal rupture.

BACKGROUND: Post myocardial infarction ventricular septal rupture (PMI-VSR) is a dreaded mechanical complication of acute coronary syndromes. Given that surgical mortality approaches 50%, it is pragmatic that the risk factors for mortality and outcomes after surgical correction of PMI- VSR are carefully scrutinized. METHODS: We performed a single-center, retrospective cohort study of 35 patients presenting for surgical closure of post myocardial infarction ventricular septal rupture over six years. We reviewed patient characteristics, clinical, echocardiographic, angiographic and perioperative risk factors which may affect mortality after surgical repair of PMIVSR and 30 day and one year mortality rates of these patients. Univariate and multivariate logistic and cox proportional hazard regression analysis was used to identify predictors of operative and overall mortality. Long term survival was presented with Kaplan-Meier Survival Curve. RESULTS: Sixteen patients (46%) were in cardiogenic shock. Concomitant coronary artery bypass grafting (CABG) was done in 22 patients (63%) but did not influence survival. Preoperative thrombolysis was done in 12 patients (34%) out of which 10 (53%) survived Operative mortality was 46% and one-year mortality was 49%. Multivariate analysis identified preoperative thrombolysis: Hazards ratio, 0.12; 95% CI, 0.02-0.61; p value of 0.01, as significant independent predictor of survival in PMIVSR cohort. CONCLUSIONS: Preoperative thrombolysis is associated with decreased odds of operative and overall mortality after surgical repair in PMIVSR patients.

Elemental formula associated hypophosphataemic rickets.

OBJECTIVES: Hypophosphataemic rickets (HR) is usually secondary to renal phosphate wasting but may occur secondary to reduced intake or absorption of phosphate. We describe a series of cases of HR associated with the use of Neocate®, an amino-acid based formula (AAF). METHODS: A retrospective review of cases with HR associated with AAF use presenting to centres across the United Kingdom. RESULTS: 10 cases were identified, over a 9 month period, all associated with Neocate® use. The age at presentation was 5 months to 3 years. The majority (8/10) were born prematurely. Gastro oesophageal reflux disease (6/10) was the most frequent indication for AAF use. Radiologically apparent rickets was observed after a median of 8 months (range 3-15 months) of exclusive Neocate® feed. The majority (7/10) were diagnosed on the basis of incidental findings on radiographs: rickets (6/10) or fracture with osteopenia (5/10). All patients had typical biochemical features of HR with low serum phosphate, high alkaline phosphatase, normal serum calcium and 25 hydroxyvitamin D. However, in all cases the tubular reabsorption of phosphate (TRP) was ≥96%. Phosphate supplementation resulted in normalisation of serum phosphate within 1-16 weeks, and levels remained normal only after Neocate® cessation. In patients with sufficient follow up duration (4/10), normalisation of phosphate and radiological healing of rickets was noted after 6 months (range: 6-8 months) following discontinuation of Neocate®. CONCLUSION: The presence of a normal TRP and resolution of hypophosphataemia and rickets following discontinuation of Neocate® indicates this is a reversible cause likely mediated by poor phosphate absorption. Close biochemical surveillance is recommended for children on Neocate®, especially in those with gastrointestinal co-morbidities, with consideration of a change in feed or phosphate supplementation in affected children.

Flow cytometric osmotic fragility test and eosin-5'-maleimide dye-binding tests are better than conventional osmotic fragility tests for the diagnosis of hereditary spherocytosis.

INTRODUCTION: Hereditary spherocytosis (HS) is the most common inherited hemolytic anemia with heterogeneous clinico-laboratory manifestations. We evaluated the flow-cytometric tests: eosin-5'-maleimide (EMA) and flow-cytometric osmotic fragility test (FOFT) and the conventional osmotic fragility tests (OFT) for the diagnosis of hereditary spherocytosis (HS). METHODS: One hundred two suspected HS patients underwent EMA, FOFT, incubated OFT (IOFT), and room temperature OFT (RT-OFT). In addition, 10 cases of immune hemolytic anemia (IHA) were included, and performance of the above 4 tests was evaluated. For EMA and FOFT, 5 normal controls were assessed together with the patients and cutoffs were calculated using receiver-operator-characteristics curve (ROC) analysis. RESULTS: The best cutoff for %EMA decrease was 12.5%, and for FOFT, %residual red cells (%RRC) was 25.6%. The sensitivity and specificity of RT-OFT was 62.06% and 86.3%, respectively, while that of IOFT was 79.31% and 87.67%, respectively. Both flow cytometric tests performed better. Sensitivity and specificity of EMA was 86.2% and 93.9% respectively, and that of FOFT was 96.6% and 98.63%, respectively. The combination of the FOFT with IOFT or EMA dye-binding test yields a sensitivity of 100%, but with EMA, it had a higher specificity. Hb/MCHC was a predictor of the severity of the disease while %EMA decrease and %RRC did not correlate with severity of the disease. CONCLUSION: Flow-cytometric osmotic fragility test is the best possible single test followed by EMA for diagnosis of HS. A combination of FOFT and EMA can correctly diagnose 100% patients. These tests are likely to replace conventional OFTs in future.

Anesthesia in pregnancy with heart disease.

Management of pregnant women with heart disease remains challenging due to the advancement of innovations in cardiac surgery and correction of complex cardiac anomalies, and more recently, with the successful performance of heart transplants, cardiac diseases are not only likely to coexist with pregnancy, but will also increase in frequency over the years to come. In developing countries with a higher prevalence of rheumatic fever, cardiac disease may complicate as many as 5.9% of pregnancies with a high incidence of maternal death. Since many of these deaths occur during or immediately following parturition, heart disease is of special importance to the anesthesiologist. This importance arises from the fact that drugs used for preventing or relieving pain during labor and delivery exert a major influence - for better or for worse - on the prognosis of the mother and newborn. Properly administered anesthesia and analgesia can contribute to the reduction of maternal and neonatal mortality and morbidity.

The effect of increased chewing strokes on the DeMeester score.

Saliva is known to be protective for esophageal mucosa. Increased chewing strokes result in a quantitative and qualitative enhancement of saliva. Reduction in the amount of saliva produced results in an increased incidence of gastroesophageal reflux disease (GERD), which can be objectively measured by the DeMeester score. The impact of increased chewing strokes on the DeMeester score remains largely unknown, thus this study aimed to find out their impact on the value of the DeMeester score and its individual components.The effect of increased chewing strokes on the DeMeester score was investigated in 12 subjects (5 male and 7 female) who were diagnosed with GERD. All subjects underwent a 48-hour pH monitoring using the Bravo® pH capsule. All the patients chewed their food 20 times more on Day 2 as compared to Day 1. The data were analyzed for change in the DeMeester score and its individual components in 2 days.In patients with GERD (DeMeester score > 14.72 on Day 1), the number of long refluxes (>5 minutes) on Day 2 (mean = 3.2, SD = 2.3) was significantly lower than on Day 1 (mean = 6.4, SD = 2.7); Z = -2.032, p = 0.04. Though, the DeMeester score and its other individual parameters decreased on Day 2, they were not statistically significant.In patients with GERD, increased chewing strokes lead to a decrease in the number of long reflux episodes. Though there is a decrease in the DeMeester score and its other individual components, larger randomized controlled studies are required to reach statistical significance.

Utilizing PBPK Modeling to Evaluate the Potential of a Significant Drug-Drug Interaction Between Clopidogrel and Dasabuvir: A Scientific Perspective.

Dasabuvir, a component of VIEKIRA PAK, is a substrate of CYP2C8 enzymes. Prescribing information for VIEKIRA PAK contraindicates gemfibrozil, a strong CYP2C8 inhibitor, because coadministration significantly increases dasabuvir exposures, which may increase the risk of QT prolongation. Clopidogrel may increase dasabuvir exposures primarily due to CYP2C8 inhibition by clopidogrel-acyl-ß-D-glucuronide. This commentary outlines the US Food and Drug Administration (FDA) interdisciplinary review team's scientific perspective to address the potential for a significant drug-drug interaction (DDI) between clopidogrel and VIEKIRA PAK.

Delirium after cardiac surgery: A pilot study from a single tertiary referral center.

BACKGROUND: Advances in cardiac surgery has shifted paradigm of management to perioperative psychological illnesses. Delirium is a state of altered consciousness with easy distraction of thoughts. The pathophysiology of this complication is not clear, but identification of risk factors is important for positive postoperative outcomes. The goal of the present study was to prospectively identify the incidence, motoric subtypes, and risk factors associated with development of delirium in cardiac surgical patients admitted to postoperative cardiac intensive care, using a validated delirium monitoring instrument. MATERIALS AND METHODS: This is a prospective, observational study. This study included 120 patients of age 18-80 years, admitted to undergo cardiac surgery after applying inclusion and exclusion criteria. Specific preoperative, intraoperative, and postoperative data for possible risk factors were obtained. Once in a day, assessment of delirium was done. Continuous variables were measured as mean ± standard deviation, whereas categorical variables were described as proportions. Differences between groups were analyzed using Student's t-test, Mann-Whitney U-test, or Chi-square test. Variables with a P < 0.1 were then used to develop a predictive model using stepwise logistic regression with bootstrapping. RESULTS: Delirium was seen in 17.5% patients. The majority of cases were of hypoactive delirium type (85.72%). Multiple risk factors were found to be associated with delirium, and when logistic regression with bootstrapping applied to these risk factors, five independent variables were detected. History of hypertension (relative risk [RR] =6.7857, P = 0.0003), carotid artery disease (RR = 4.5000, P < 0.0001) in the form of stroke or hemorrhage, noninvasive ventilation (NIV) use (RR = 5.0446, P < 0.0001), Intensive Care Unit (ICU) stay more than 10 days (RR = 3.1630, P = 0.0021), and poor postoperative pain control (RR = 2.4958, P = 0.0063) was associated with postcardiac surgical delirium. CONCLUSIONS: Patients who developed delirium had systemic disease in the form of hypertension and cerebrovascular disease. Delirium was seen in patients who had higher postoperative pain scores, longer ICU stay, and NIV use. This study can be used to develop a predictive tool for diagnosing postcardiac surgical delirium.

Comparative Effect of Levosimendan and Milrinone in Cardiac Surgery Patients With Pulmonary Hypertension and Left Ventricular Dysfunction.

OBJECTIVE: To compare the effects of levosimendan with milrinone in cardiac surgical patients with pulmonary hypertension and left ventricular dysfunction. DESIGN: A prospective, randomized study. SETTING: Tertiary care teaching hospital. PARTICIPANTS: The study included patients with valvular heart disease and pulmonary artery hypertension undergoing valve surgery. INTERVENTIONS: Forty patients were allocated randomly to receive either milrinone, 50 µg/kg bolus followed by infusion at a rate of 0.5 µg/kg/min (group 1), or levosimendan, 10 µg/kg bolus followed by infusion at a rate of 0.1 µg/kg/min (group 2) for 24 hours after surgery. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters were measured using a pulmonary artery catheter, and biventricular functions were assessed using echocardiography. Mean pulmonary artery pressures and the pulmonary vascular resistance index were comparable between the 2 groups at several time points in the intensive care unit. Biventricular function was comparable between both groups. Postcardiopulmonary bypass right ventricular systolic and diastolic functions decreased in both groups compared with baseline, whereas 6 hours postbypass left ventricular ejection fraction improved in patients with stenotic valvular lesions. Levosimendan use was associated with higher heart rate, increased cardiac index, decreased systemic vascular resistance index, and increased requirement of norepinephrine infusion compared with milrinone. CONCLUSIONS: The results of this study demonstrated that levosimendan was not clinically better than milrinone. Levosimendan therapy resulted in a greater increase in heart rate, decrease in systemic vascular resistance, and a greater need for norepinephrine than in patients who received milrinone.

Invasive floating macrophytes reduce greenhouse gas emissions from a small tropical lake.

Floating macrophytes, including water hyacinth (Eichhornia crassipes), are dominant invasive organisms in tropical aquatic systems, and they may play an important role in modifying the gas exchange between water and the atmosphere. However, these systems are underrepresented in global datasets of greenhouse gas (GHG) emissions. This study investigated the carbon (C) turnover and GHG emissions from a small (0.6 km(2)) water-harvesting lake in South India and analysed the effect of floating macrophytes on these emissions. We measured carbon dioxide (CO2) and methane (CH4) emissions with gas chambers in the field as well as water C mineralization rates and physicochemical variables in both the open water and in water within stands of water hyacinths. The CO2 and CH4 emissions from areas covered by water hyacinths were reduced by 57% compared with that of open water. However, the C mineralization rates were not significantly different in the water between the two areas. We conclude that the increased invasion of water hyacinths and other floating macrophytes has the potential to change GHG emissions, a process that might be relevant in regional C budgets.

Association of CYP2C19, CYP3A5 and GPIIb/IIIa gene polymorphisms with Aspirin and Clopidogrel Resistance in a cohort of Indian patients with Coronary Artery Disease.

INTRODUCTION: Dual antiplatelet therapy with clopidogrel and aspirin is the current standard of care in the management of patients with coronary artery disease (CAD) and acute coronary syndrome (ACS). The variability in response to these antiplatelet agents may be due to the underlying genetic diversity. This study was designed to determine the resistance to aspirin and clopidogrel in Indian patients and to look for correlation, if any, with selected polymorphisms. METHODS: Platelet function testing by light transmission aggregometry was performed on 72 patients with CAD/ACS who were stable on dual antiplatelet therapy (clopidogrel 75 mg OD and aspirin 150 mg OD) along with 72 controls. Aspirin resistance was considered as mean platelet aggregation ≥ 70% with 10 µm ADP and ≥ 20% with 0.75 mm arachidonic acid. Clopidogrel resistance was defined as <10% decrease from the baseline in platelet aggregation in response to ADP 10 µm and semi-response as <30% decrease from the baseline. Polymorphisms CYP2C19*2, *3, CYP3A5*3 and PLA1/A2 were genotyped. RESULTS: We found 51.4% patients with inadequate response to clopidogrel (1.4% resistant and 50% semi-responders) and 5.5% patients semi-responders to aspirin, none being completely resistant. The genotype and allele frequencies of CYP2C19*2 and PLA1/A2 gene polymorphisms were significantly different between clopidogrel semi-responders and responders. Carriers of CYP2C19*2 and CYP3A5*3 showed diminished inhibition of platelet aggregation. No significant correlation was found between coronary events, type of coronary intervention with clopidogrel nonresponsiveness. CONCLUSION: Unlike aspirin, a high proportion of partial responders to clopidogrel were identified. In an interim analysis on 72 Indian patients, a significant association was found between CYP2C19*2 and PLA1/A2 in clopidogrel semi-responders.

Direct-acting antiviral drugs for the treatment of chronic hepatitis C virus infection: Interferon free is now.

Chronic hepatitis C (CHC) is a global, serious, and life-threatening disease. Virologic response at 12 weeks post-treatment (SVR12) signifies a durable virologic response and is currently the primary efficacy endpoint used in registrational trials. This change led to more rapid clinical development and earlier approvals of highly effective and well-tolerated therapies, facilitating access to those in need. Hepatitis C virus (HCV) infection is a therapeutic area where mathematical modeling has proven helpful in understanding the drug mechanism and characterizing viral kinetics to inform therapy decisions. The availability of direct-acting antivirals (DAAs) provides various treatment options for HIV/HCV coinfected patients, but the complexity of predicting and managing drug-drug interactions presents a unique challenge. Real-world experience or noninterventional studies can provide insight regarding the safety and use of therapeutics that may not be readily available from traditional clinical trials. This article provides a brief overview of the development of promising drugs for the treatment of CHC.

Preinduction hemodynamic fluctuations in renal transplant recipients--comparison of two combined anesthesia regimens.

An ideal anesthetic technique for a renal allograft recipient must ensure hemodynamic stability, enhance graft reperfusion, and provide good postoperative pain relief. Hence, a combined general and epidural anesthesia is preferred. In our clinical practice, it has been observed that in chronically ill end-stage renal disease (ESRD) patients, a bolus injection of epidural local anesthetics invariably necessitated the use of vasopressor agents. Such hemodynamic fluctuations may not be favorable for the graft. A prospective, randomized, double-blind study was conducted on 50 ESRD adults, 18-55 years, scheduled for elective live related kidney transplantation. The patients randomly received either epidural fentanyl (50 µg) and normal saline (10 mL) or epidural fentanyl (50 µg) and bupivacaine (0.5%; 10 mL) followed by standardized general anesthesia. Perioperative hemodynamics and vasopressor requirements were compared with both regimens. Early graft function was assessed by the onset of diuresis after declamping, serial creatinine values, glomerular filtration rate, and 24-hour urine output estimation. In the preoperative period, statistically significant reduction in the mean arterial pressure and the cardiac index occurred in 60% of the patients receiving epidural bupivacaine boluses. These hypotensive episodes required a therapeutic intervention prior to general anesthesia, that is, intravenous mephenteramine (3-6 mg; 9.60±2.32 mg) and crystalloid infusion (189.28±21.29 mL). Intraoperative hemodynamic parameters, surgical blood loss, and transplanted kidney function were comparable between the groups. We concluded that the use of regional anesthetics needed to administered cautiously in renal transplant recipients to maintain hemodynamic parameters.