This meta-analysis evaluated clinical outcomes of patients with acute coronary syndrome undergoing percutaneous coronary interventions and treated with bivalirudin vs heparin. It analyzed data from 7 randomized controlled trials involving 30,088 patients. The analysis found that compared to heparin, bivalirudin was associated with a lower risk of major bleeding, net clinical outcomes, and major adverse cardiac events at 7 days. At 30 days, bivalirudin continued to be associated with a lower risk of major bleeding and net clinical outcomes, but there was no difference in major adverse cardiac events. This meta-analysis provides further support that bivalirudin provides improvements in outcomes with a reduction in bleeding complications compared to hepar
Implication of preoperative glycosylated hemoglobin level on short term outco...Dr.Debmalya Saha
ABSTRACT
Background: Diabetes mellitus is one of the significant risk factors for adverse outcomes after coronary artery bypass surgery. The glycosylated haemoglobin i.e. HbA1c is a reliable diagnostic test to know the long-term glycemic status. The objective of the study is to investigate the implication of preoperative HbA1c level on short term outcomes after coronary artery bypass grafting (CABG).
Method: Total 218 patients were studied, and the data were collected retrospectively. Patients are distributed into group 1 with HbA1c≤7 (good glycemic control) and group 2 with HbA1c>7 (poor glycemic control). The parameters studied for short term outcomes were revision due to bleeding, duration of mechanical ventilation, cerebrovascular accident (CVA), atrial fibrillation (AF), renal failure requiring dialysis, infective complications like sternal and leg wound infection, mediastinitis, pneumonia, urinary tract infection (UTI), sepsis; length of ICU stay and in-hospital mortality.
Result: In comparison to group 1, patients of group 2 showed statistically significant more morbidity in view of short-term outcomes in this study.
Conclusion: HbA1c>7 is associated with statistically significant adverse short-term outcomes after CABG.
Quantitative Statistical Analysis Work Sample From StatsworkStats Statswork
Quantitative Data Collection perhaps the most widely used method for primary data collection. A variety of different collection methods of research, including mail surveys and face to face interviews.
Implication of preoperative glycosylated hemoglobin level on short term outco...Dr.Debmalya Saha
ABSTRACT
Background: Diabetes mellitus is one of the significant risk factors for adverse outcomes after coronary artery bypass surgery. The glycosylated haemoglobin i.e. HbA1c is a reliable diagnostic test to know the long-term glycemic status. The objective of the study is to investigate the implication of preoperative HbA1c level on short term outcomes after coronary artery bypass grafting (CABG).
Method: Total 218 patients were studied, and the data were collected retrospectively. Patients are distributed into group 1 with HbA1c≤7 (good glycemic control) and group 2 with HbA1c>7 (poor glycemic control). The parameters studied for short term outcomes were revision due to bleeding, duration of mechanical ventilation, cerebrovascular accident (CVA), atrial fibrillation (AF), renal failure requiring dialysis, infective complications like sternal and leg wound infection, mediastinitis, pneumonia, urinary tract infection (UTI), sepsis; length of ICU stay and in-hospital mortality.
Result: In comparison to group 1, patients of group 2 showed statistically significant more morbidity in view of short-term outcomes in this study.
Conclusion: HbA1c>7 is associated with statistically significant adverse short-term outcomes after CABG.
Quantitative Statistical Analysis Work Sample From StatsworkStats Statswork
Quantitative Data Collection perhaps the most widely used method for primary data collection. A variety of different collection methods of research, including mail surveys and face to face interviews.
Transplantation of Autologous Bone Marrow- Derived Stromal Cells in Type 2 Di...CrimsonpublishersITERM
Type 2 Diabetes is a debilitating metabolic disorder which is also the seventh leading cause of death worldwide. Current therapeutic regimes to date have failed to achieve significant long-term glycemic control even with intensive insulin therapy as revealed by deregulated Hb1Ac and C-peptides levels. In the current study, we have evaluated the effect of regenerative cellular therapy for functional recovery from Diabetic pathophysiology. 10 patients with a median age of 51 years were selected for the study and subjected to bone marrow isolation. These samples were processed under sterile conditions for the enrichment of mononuclear cells (BM MNCs) from bone marrow. After strict quality control and characterization of cells, 2 x 106 cells/kg of BM MNCs were infused back into the patient through the anterior pancreaticoduodenal artery. We performed an evaluation of clinical parameters like Body Mass Index, Fasting Plasma Glucose, Fasting Plasma Insulin, HbA1c and C-peptide levels, and followed up the patients for 12 months. Our study showed a reduction in insulin dependency by ≥ 50%.
Study of Endothelial Dysfunction in Type 2 Diabetes Mellitusiosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Aims: Dried Blood Spot (DBS) sampling is a frequently used method to obtain Haemoglobin A1C (HbA1c) in clinical studies of freeliving populations. Under controlled conditions, DBS sampling is a valid and robust alternative to traditional Whole Blood (WB) sampling. The objective of this analysis was to investigate the impact of storage conditions on the validity of HbA1c assessed from DBS collected in free-living and to develop a method to correct for this type of error.
Utilizing the ORS in a Community Mental Health Clinic (student outcomes etc) ...Scott Miller
Outcomes of students and professionals were compared. Study found students equally effective or better than experienced therapists when students used the measures. Students who used the measures faithfully to guide practice had significantly better outcomes
Transplantation of Autologous Bone Marrow- Derived Stromal Cells in Type 2 Di...CrimsonpublishersITERM
Type 2 Diabetes is a debilitating metabolic disorder which is also the seventh leading cause of death worldwide. Current therapeutic regimes to date have failed to achieve significant long-term glycemic control even with intensive insulin therapy as revealed by deregulated Hb1Ac and C-peptides levels. In the current study, we have evaluated the effect of regenerative cellular therapy for functional recovery from Diabetic pathophysiology. 10 patients with a median age of 51 years were selected for the study and subjected to bone marrow isolation. These samples were processed under sterile conditions for the enrichment of mononuclear cells (BM MNCs) from bone marrow. After strict quality control and characterization of cells, 2 x 106 cells/kg of BM MNCs were infused back into the patient through the anterior pancreaticoduodenal artery. We performed an evaluation of clinical parameters like Body Mass Index, Fasting Plasma Glucose, Fasting Plasma Insulin, HbA1c and C-peptide levels, and followed up the patients for 12 months. Our study showed a reduction in insulin dependency by ≥ 50%.
Study of Endothelial Dysfunction in Type 2 Diabetes Mellitusiosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Aims: Dried Blood Spot (DBS) sampling is a frequently used method to obtain Haemoglobin A1C (HbA1c) in clinical studies of freeliving populations. Under controlled conditions, DBS sampling is a valid and robust alternative to traditional Whole Blood (WB) sampling. The objective of this analysis was to investigate the impact of storage conditions on the validity of HbA1c assessed from DBS collected in free-living and to develop a method to correct for this type of error.
Utilizing the ORS in a Community Mental Health Clinic (student outcomes etc) ...Scott Miller
Outcomes of students and professionals were compared. Study found students equally effective or better than experienced therapists when students used the measures. Students who used the measures faithfully to guide practice had significantly better outcomes
Bioequivalence and Average Bioequivalence (ABE)
Main concerns with ABE
Design and limitations of ABE studies
Individual and Population Bioequivalence (IBE and PBE)
Metrics
Design and sample size of replicate studies for IBE and PBE
Conduct and analysis
Example
Issues
Background: One of the commonest complications of poorly controlled Type 2 diabetes mellitus (T2DM) is Diabetic nephropathy (DN), which occurs in 30-40% of DM cases. It is important to identify the high-risk group who are likely to develop DN with the modifiable and non-modifiable risk factors. This study had the objectives to estimate and correlate the levels of the urine albumin creatinine ratio (UACR) with age, anthropometric measures, glycaemic control markers, lipids, and renal function. To estimate each variable as independent and multivariate risk factors.
Materials and Methods: It was an observational and cross-sectional study conducted in a tertiary care center in Eastern India. Totally, 221 consecutive ambulatory T2DM subjects were recruited after obtaining their written consent.
Results: The diabetics were classified as having diabetic nephropathy by the urine albumin creatinine ratio (ACR) of >30 mg/gm. 53.4% of our study group had DN. There was a significant risk associated with PPBS with p=0.043 (<0.05), serum creatinine with p=0.032 (<0.05), and urine albumin with p=0.0001 (<0.001). In the multivariate regression analysis of all these variables, there was a highly significant likelihood ratio for predicting DN with p=0.0001 (<0.001) with a predictive value of 74.5% in females and 75% in males.
Conclusion: The additive factors contributed by the risk factors in the prediction of DN will benefit the DM in the prevention of DN.
Keywords: diabetic nephropathy, risk factors, diabetic kidney disease, Asian Indian
The study to measure the level of serum annexin V in patients with renal hype...inventionjournals
ABSTRACT : Renovascular hypertension reflects the causal relation between anatomically evident arterial occlusive disease and elevated blood pressure. The coexistence of renal arterial vascular disease and hypertension roughly defines this type of nonessential hypertension. The aim of this study was to measure the level of serum Anti-Annexin V antibodies in patients with renal hypertension. Methods. This study was conducted on 115 patients, diagnosed with renal hypertension and hypertension. Informed consents were obtained from the patients and the study was approved by the Kharkiv National Medical University ethics committee. Ten healthy age and sex matched volunteers were included as a control group. All patients and controls were subjected to the following full history taking and thorough clinical examination. Routine laboratory testing included a complete blood count, and erythrocyte sedimentation rate (ESR) and kidney function tests (blood urea nitrogen and serum creatinine). Immunological tests for antinuclear antibody (ANA) and anticentromere antibodies (ACA) was performed by the indirect immunofluorescence technique. AntiScl-70 (anti-topoisomerase antibodies) and anticardiolipin antibodies (ACA: IgG and IgM) were tested using the ELISA technique. The anti-annexin V antibodies titre used the ZYMUTEST anti-Annexin IgG ELISA kit. [Hyphen-BioMed, France.]: to measure the IgG isotype of auto-antibodies to annexin V in human serum. Results. Anti-annexin V antibodies were present in 75% of patients (mean 83.46 ± 22.44 AU/mL) vs. 0% in the controls (mean 3.94 ± 4.5 AU/mL). Comparison between patients and controls as regards levels of anti-annexin V showed a highly significant difference (P < 0.001). Furthermore, correlation of anti-annexin V titres with the disease activity score in the patient group showed a statistically significant positive correlation (r = 0.51, P < 0.05).In addition, the anti-annexin V antibody titres in this study showed a highly significant positive correlation with ACL antibodies (r = 0.74, P < 0.001). Patients with antiphospholipid syndrome (APS) have been known to have a higher frequency of anti-annexin V antibodies, and thrombotic events have been reported more frequently in patients with positive anti-annexin V antibodies. Furthermore, inhibition of annexin V binding to negatively charged phospholipids may be an additional pathogenic mechanism of APS.
Efficiency of Use of Dietary Supplement Arteroprotect® In Prevention of Cardi...inventionjournals
Cardiovascular diseases are the leading cause of death in most developed countries and in many developing countries. The main cause of cardiovascular disease in 95% cases is supposed to be atherosclerosis, and the symptoms occur when the process is already at an advanced stage of disease. Present study was conducted to examine an efficiency of ARTEROprotect® (by Abela Pharm, Serbia) in prevention of cardiovascular diseases. The study was conducted by 76 doctors in primary health centers throughout the Republic of Serbia as a prospective clinical study of two groups of subjects. The study group included 4031 subjects (1785 males and 2246 females) who were taking ARTEROprotect® , while the control group consisted of 2564 subjects (1135 males and 1428 females) who were not taking it. Based on the results, dietary supplement ARTEROprotect® , used alone, could contribute to lowering levels of cholesterol, triglycerides, LDL-cholesterol; in combination with a statin it can achieve the target value of LDL- and HDL-cholesterol.
A primary Percutaneous Coronary Intervention (PCI) Primary PCI continues to be the optimal reperfusion therapy in
patients with ST elevation myocardial infarction however, in areas where PCI centers are not readily available, a pharmaco-invasive strategy has been proposed. This study investigated the safety, efficacy and cost effective analysis of a pharmaco-invasive strategy compared with primary (PCI) strategy for ST-Segment Elevation Myocardial Infarction (STEMI) in Gaza.
Methods: We ran domized 145 patients presenting within 2 hours of symptom onset of acute ST elevation myocardial infarction to primary PCI or for pharmaco-invasive PCI 2-24 hours after streptokinase, except in the event of failed reperfusion, in which case, emergency angiography was recommended. The primary endpoint a composite of death, shock and congestive heart failure at 30 days. Secondary end points: total bleeding and failed streptokinase required emergent PCI. Tertiary end points: cost effective analysis.
Root cause Analysis (RCA) & Corrective and Preventive action (CAPA) in MRCT d...Bhaswat Chakraborty
This presentation describes Identification & differentiation of Protocol deviation & violation; Different methods of RCA & best suitable method for Multiregional Clinical Trial; CAPA management and CAPA application to other trial sites/CRO/SMO/ Country that is involved in same trial (Strategic Management and application of CAPA in MRCT)
This presentation gives effective solutions to outliers issue in bioequivalence trials. It described what would be acceptable to Regulatory agencies as well as some new approaches.
Equivalence approches for complex generics DIA 11 april 2019 Bhaswat Chakraborty
This is a workshop that i gave a few days ago on bioequivalence of complex generics like peptides, polymers, liposomes, colloids, ophthamic and topical produtcts.
Clinical trials that are needed for efficacy & safety evidence of Medical devices include feasibility (pilot) and Pivotal trials. An extended battery of preclinical trials are also needed for high risk devices.
Writing Science papers for for publication requires something more thatn creativity. Target journals, content organization, wrting style, elegance and referencing are equally important.
Multidisc review of NDAs and BLAs nipicon 2018 Dr. ChakrabortyBhaswat Chakraborty
NDAS and BLAs cannot be authoritatively reviewed these days until experts from different disciplines act together like a team. This presentation give some foundational points and an illustrative example in that regard.
Teaching by stories, anecdotes and historical facts sept 25 2018Bhaswat Chakraborty
Many difficult principles in science and humanities can be taught best by a story (of its discovery), by an anecdote or some historical facts about them.
Orientation and Adaptation for Post-Graduate Pharmacy ProgramsBhaswat Chakraborty
PG Pharmacy programs are more focused and professionally oriented than the undergraduate counterpart. Many soft skills are required along with the curricular competence for excellence at the PG level.
Scientific integrity calls for some basic originality. Plagiarism can destroy this original creativity and ideation. This presentation defines plagiarism (stealing from others' works) and some of the creative and systematic remedies.
Best Practices to Risk Based Data Integrity at Data Integrity Conference, Lon...Bhaswat Chakraborty
Data integrity can be implemented using several approaches. One of the most effective ways to implement DI is a risk based approach. The speaker elaborates this.
There are several dimensions in Pharmaceutical ethics -- Practice-, research- and community oriented. This presentation mainly deals with Clinical research oriented Ethics.
Young pharmaceutical scientists are and can get involved in all aspects of new drug discovery and development. They have to be appropriately qualified, trained and experienced though,
This presentation mainly deals with clinical development of biosimilar products. It also gives enough on non-clinical development so that the audience is well oriented.
High variability in PK can be a characteristic of certain drug products which require different from ordinary strategies and study designs for establishing bioequivalence.
High variability in PK can be a characteristic of certain drug products which require different from ordinary strategies and study designs for establishing bioequivalence.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
1. Page53
International Journal of Biotechnology and Pharmacy Research, Vol. 2 Issue 2[2011]53-58
Corresponding Author:Dr. Bhaswat S. Chakraborty Sr. Vice President, Research and Development
Cadila Pharmaceuticals Limited,: Ahmedabad, Gujarat, India.
Email: drb.chakraborty@cadilapharma.co.in
Phone: +91-2714-220312
Received: 05 Jan 2011;Accepted:27 Jan 2011; Online:15Feb 2011
Review
Clinical Outcome of Patients of Acute Coronary Syndrome at 7 and 30
days Undergoing Percutaneous Coronary Interventions and Treated
with Bivalirudin and Heparin
Kumar A1, Kachhadiya R2, Chakraborty BS 1*
1Cadila Pharmaceuticals Ltd, Ahmedabad, Gujarat, India,
2Department of Pharmacology, Faculty of Pharmacy, NIRMA University, Ahmedabad, Gujarat
India.
Abstract
Background:Recent data suggest that Bivalirudin provides ischemic protection superior to Heparin,and comparable
to Heparin plus glycoprotein IIb/IIIa inhibitors, with significantly fewer bleeding complications. Whetherthis advan-
tage persists in large population has not beenfully defined.
Objective: This study systematically evaluates clinical outcomes of treatment with Bivalirudinvs Heparin in patients
of acute coronary syndrome undergoing Percutaneous coronary interventions (PCI).
Methods: We analyzed prospective, randomized controlled trials via electronic searches that have reported clinical
outcomes at 7 and 30 days. The outcomes were major bleeding, net clinical outcomes and Major Adverse Cardiac
Events – MACE. Data from individual trials were combined by a meta analysis method of Mantel-Haenszelcalculate a
relative risk (RR) and 95% confidence interval (95%CI) across the studies.Theheterogeneity across the trials was as-
sessed through χ2 statistic, I2 andvisual inspection of the forest plots.
Results: This meta-analysis involved a total of 30,088 patients (Bivalirudin, n=15,105; Heparin, n=14,983). Compared
with Heparin, Bivalirudin was associated with a lower risk of major bleeding (RR 0.38; 95%CI 0.29-0.48 at 7 days and
RR 0.67;95%CI 0.60-0.75 at 30 days), net clinical outcomes (RR 0.56; 95%CI 0.47-0.66 at 7 days and RR 0.89; 95%CI 0.83-
0.96 at 30 days) and MACE (RR 0.78; 95%CI 0.63-0.96 at 7 days). There was no significant difference in case of MACE
at 30 days (RR 1.02; 95%CI 0.93-1.11). Heterogeneity was observed across the trials that reported major bleeding
(χ2=14.71, 5 df, p=0.01, I2=66%) at 30 days, but not at 7 days for reported major bleeding, and also for net clinical out-
comes and MACE both at 7 days and 30 days.
Conclusion: This analysis further supports that Bivalirudin provides significantimprovement in net clinical outcomes
and MACE with a significant reduction of bleedingcomplications.
Key WordsMajor bleeding, Net clinical outcomes, MACE, Bivalirudin, Heparin
Introduction
Bivalirudin is most widely used
direct thrombin inhibitor all over
the world, which reduce the risk
of major adverse cardiac events
(MACE) and major bleeding as
reported in various clinical stu-
dies. Besides its property to dissolve the fibrin bound thrombin, Bivalirudin also
shows predictable linear pharmacokinetics and avoidance of (Heparin induced)
thrombocytopenia. Early trials of Bivalirudin as an anticoagulant suggested sim-
ilar endpoints as those of Heparin with GP IIb/IIIa inhibitors with lower rates of
major bleeding. Our aim was to detect a clinically meaningful difference in out-
2. Page54
comes by performing a meta-
analysis of most available pub-
lished clinical studies of Bivaliru-
din in acute cardiac syndromes
(ACS).
Materials and Methods
To the best of our knowledge, this
meta-analysis includes all the
currently completed randomized
published trials that have com-
pared different outcomes with
Bivalirudin vs. Heparin in pa-
tients of ACS who underwent
PCI. This analysis used the end
points of death, post procedural
myocardial infarction (MI), ur-
gent revascularization, and bleed-
ing as defined within each clinical
trial. Specifically, three outcomes
at 7 and 30 days, e.g. Major bleed-
ing, Net Clinical Outcomes
(Death, MI, Revascularization
and Major bleed) and Major Ad-
verse cardiac events (MACE)
were considered for comparison.
Search strategies included an
electronic search of bibliographic
databases (PubMed, Medline and
Science Direct), specific journals
(Journal of Invasive cardiology,
New England Journal of Medi-
cine, Circulation, American Heart
Journal, American Journal of
Cardiology, Journal of American
Medical Association, Journal of
the American College of Cardiol-
ogy), and review of bibliography
from eligible trials and use of the
“See Related Articles” links.
As mentioned, the outcomes were
the combined incidence of death
from any cause, myocardial in-
farction, or urgent target-vessel
revascularization (MACE) and
major bleeding. This triple end
point (MACE) was aimed at as-
sessing the risk of ischemic com-
plications. Net clinical outcome
was intended to measure the risk
of both ischemic (MACE) and
bleeding complications and was
the basis for determining the net
clinical benefit. Myocardial in-
farction (MI) was defined as the
development of pathologic Q
waves (≥30 msec in duration and
≥0.1 mV in depth) in two or more
contiguous electrocardiographic
leads or an elevation of creatine kinase MB isoenzyme levels (or total creatine
kinase if measures of creatine kinase MB were not available) to at least two times
the upper limit of the normal range. Urgent revascularization was defined as
severe myocardial infarction requiring immediate surgery or PCI. The definition
of major bleeding was intracranial, intraocular, or retroperitoneal haemorrhage;
clinically overt blood loss resulting in a decrease in haemoglobin of more than 3
g per deciliter; any decrease in haemoglobin of more than 4 g per decilitre; or
transfusion of 2 or more units of packed red cells or whole blood.
Two authors (AK and RK) separately reviewed literature search to identify stud-
ies that are randomized controlled trials evaluating outcomes at 7 and 30 days
with Bivalirudinvs Heparin in patients of acute coronary syndrome undergoing
percutaneous coronary interventions (PCI). Any disagreement in the rejection
process was first handled between them. When this could not be done, a third
independent reviewer's opinion was sought. Studies published in languages
other than English and studies with outcome reported on other than 7 or 30 days
were excluded.
Statistical Analysis
Meta-analysis (i.e, statistical pooled results) for major bleeding, MACE and Net
Clinical outcome was performed using the Mantel-Haenszel method. All three
outcomes were analyzed as dichotomous variables using fixed-effect model to
calculate a weighted estimate (risk ratio) and 95% confidence interval (CI) across
the studies. The heterogeneity across the trials was assessed through a χ2 statis-
tic, degree of freedom (P value of 0.10 was used to determine statistical signifi-
cance), I2 and visual inspection of the forest plots. I2 value represents the per-
centage of the total variation across trials due to heterogeneity rather than
chance (I2 value <25% is low and >75% is high). All analyses were done using
RevMan 5 (Cochrane Collaboration).
Results
The literature search identified 2 studies (BAT and CAHET D1+D2) that re-
ported outcomes at 7 days and 5 (ACUITY PCI, HORIZONE AMI, ISAR REACT
3, REPLACE 1 and REPLACE 2) studies that reported outcomes at 30 days, in-
volving a total of 30,088 patients (Bivalirudin, n = 15 105; Heparin, n = 14 983),
met our inclusion criteria. Detail flow chart for inclusion of studies is shown in
Figure 1. Out of these 30,088 patients, 4520 patients (Bivalirudin, n = 2305; Hepa-
rin, n = 2215) of 2 trials that reported outcomes at 7 days and 25568 patients (Bi-
valirudin, n = 12800; Heparin, n = 12768) of 5 trials that reported outcomes at 30
days were included in this Meta analysis. All the included studies characteristics
are mentioned in Table 1. ACUITY PCI study was divided into 2 subpart; ACU-
ITY PCI 1 (Bivalirudin + GPIIb/IIIa inhibitor) and ACUITY PCI 2 (Bivalirudin
alone) in comparison of Heparin plus GP IIb/IIIa inhibitor. All the seven in-
cluded trials had reported required outcomes e.g. major bleeding, net clinical
outcomes (death, MI, revascularization and major bleed) and MACE.
Major bleeding was reported in all the 7 identified studies as shown in Figure 2.
Statistically significant difference was observed for major bleeding with a RR of
0.38 (95% CI 0.29 to 0.48) at 7 days (Figure 2A) and RR of 0.67 (95% CI 0.60 to
0.75) at 30 days (Figure 2B) indicates low incidence of bleeding with Bivalirudin.
There was no heterogeneity across the trials that reported Major bleeding at 7
days (χ2=0.39, 1 df, p=0.53, I2 =0%) but observed across the trials that reported
major bleeding at 30 days (χ2=14.71, 5 df, p=0.01, I2 =66%).
Figure 3 shows the net clinical outcomes at 7 days (Figure 3A) and at 30 days
(Figure 3B). Net clinical outcomes were significantly lower in Bivalirudin group
with RR of of 0.56 (95% CI 0.47 to 0.66) at 7 days and RR of 0.89 (95% CI 0.83 to
0.96) at 30 days. Heterogeneity was not observed across the trials that reported
net clinical outcomes at 7 days (χ2=2.37, 1 df, p=0.12, I2 =58%) and at 30 days
(χ2=3.63, 5 df, p=0.60, I2 =0%) as well.
Analyzed results of ischemic triplet (MACE), as shown in Figure 4, revealed sta-
tistically significant difference observed at 7 days with RR of 0.78 (95% CI 0.63 to
3. Page55
0.96) but not at 30 days with RR
of 1.02 (95% CI 0.93 to 1.11). No
significant heterogeneity was ob-
served across the trials that re-
ported MACE either at 7 days
(χ2=1.47, 1 df, p=0.22, I2 =32%) or
at 30 days (χ2=5.24, 5 df, p=0.39, I2
=05%).
Discussion
More than 1.4 million persons are admitted to hospitals in the United States
every year with acute coronary syndromes (e.g., unstable angina or myocardial
infarction without ST-segment elevation).[8]In India, an estimated 2 million pa-
tients are currently suffering from coronary heart diseases also making it the
country with highest acute syndromes in the world.[9] The thrombotic
tions in patients of acute coronary syndrome (ACS) undergoingpercutaneous
coronary interventions are related to activation of the intrinsic coagulation
tem and to platelet aggregation. During coronary interventions, Heparin has
been the primary choice for anticoagulation since its inception.[10] Aspirin,
dogrel – a platelet glycoprotein IIb/IIIa inhibitor, and an antithrombotic agent
are also recommended for patients for whom an invasive strategy is chosen.[11-13]
4. Page56Unfractionated Heparin has been
the standard of adjunctive anti-
thrombin therapy during percu-
taneous coronary intervention
(PCI) for more than 25 years. Yet
Heparin is subject to important
intrinsic limitations, including
unpredictable pharmacokinetics,
inhibition by plasma proteins,
and the potential to activate
platelets.[14-17] Considerable re-
ductions in periprocedural com-
plications have been achieved
with administration of glycopro-
tein IIb/IIIa (GpIIb/IIIa) antago-
nists in addition to Heparin.[18]
These potent platelet inhibitors
are not used universally because
of cost and increased bleeding risk. Most of the anticoagulants are not capable to
dissolve the fibrin bound thrombin. Such thrombin usually activates platelets
through thromboxen A2 independent mechanism which can not be blocked by
aspirin or any other anticoagulants except direct thrombin inhibitors (DTI). One
of the best available DTI, with well established safety and efficacy in various in-
dication of ACS is Bivalirudin.
This meta analysis of 7 trials reveals a lower risk of major bleeding with Bivali-
rudin in comparison to Heparin in patients of ACS undergoing PCI. Statistically
significant improvement is suggested with Bivalirudin treatment in net clinical
outcomes at both 7 and 30 days. The ischemic events (MACE) are higher in He-
parin group at 7 days but at 30 days there is no significant difference between
the two groups. All 7 trials included in the meta analysis consisted of homoge-
neous population as there is no significant heterogeneity found between Hepa-
rin and Bivalirudin groups except in the case of major bleeding at 30 days and
that is because of diference in doses and GP IIb/IIIa inhibitor use among the 5
trials.
This meta-analysis shows a significant reduction in both ischemic events as well
as major bleeding, contrastingameta-analysis performed by Kong and his col-
5. Page57
leagues[19] which included 6 trials
with 5674 patients. [20, 21-23, 24] The
latter showed thatBivalirudinre-
duces the incidence of ischemic
heart disease at least to the same
degree as does UFH (Unfractio-
nated Heparin) but with statisti-
cally significant reduction inma-
jor bleeding (P < .001). Another meta-analysis performed by Singh et al.25 has
reported similar results to ours but they pooled data from trials that reported
outcomes at different time period ranging from 48 hours to 6 months. We have
combined the data from the trials that reported outcomes specifically at 7 days
and 30 days separately which is more logical. The combination of both safety
and efficacy measures is not ideal, hence we reported safety (major bleeding and
ischemic event and net clinical outcomes) separately from the efficacy measures.
Conclusion
This meta-analysis finds that
Bivalirudin is associated with
lower incidences of net clinical
outcomes as well as bleeding at 7
days and 30 days relative to those
of Heparin. Furthermore,
Bivalirudin treatment showed a
lower risk of ischemic event
(MACE) at 7 days than that of
Heparin but at 30 days there was
no significant difference between
Heparin and Bivalirudin treated
groups.
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