This study evaluated differences in estimated glomerular filtration rate (GFR) and antimicrobial dosing recommendations when using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation versus the Cockcroft-Gault equation in patients with chronic kidney disease. The CKD-EPI equation estimated higher average GFRs compared to the Cockcroft-Gault equation. There was a 15-25% discordance rate in antimicrobial dosing recommendations between the two equations. While the equations showed statistically significant differences, the clinical significance of these differences in patient outcomes is uncertain. Clinical judgment should be used when making renal dosage adjustments of antimicrobials.
1) A double-blind clinical trial was conducted over 6 months to determine if a cysteine-rich protein supplement (IMN1207) had any positive or negative effects on clinical outcomes in lung cancer patients undergoing chemotherapy or radiotherapy compared to a casein protein supplement.
2) 35 lung cancer patients completed the study. Those receiving the cysteine-rich protein had a mean weight gain of 2.5% while those receiving casein lost 2.6% weight on average. Secondary outcomes like survival, muscle strength, and quality of life also improved more in the cysteine-rich protein group.
3) The cysteine-rich protein appeared to reverse weight loss and improve some measures of health more
Modeling Algorithm of Estimation Of Renal Function by the Cockcroft and M...hiij
The purpose of this study was to determine the concordance between two equations used for estimating
glomerular filtration rate, in order to verify the possibility to be used interchangeably in the clinical
practice. The two equations are of Cockcroft & Gault (CG) (1976) formula and MDRD (modification of
Diet in Renal Disease) (1999) formula, these two models allow the assessment of glomerular filtration rate
(GFR) by calculating creatinine clearance (CLCR).To make a comparison between these two formulas
different models were examined for Subjects with normal renal function, Patients with renal impairment,
Diabetic patients, Age and sex, finally lean and obese patients by modeling two algorithms with the two
functions. Results show that the formula of Cockcroft & Gault remains the method of choice for estimating
renal function in clinical practice.
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
Hybrid Genetic Algorithm for Optimization of Food Composition on Hypertensive...IJECEIAES
The healthy food with attention of salt degree is one of the efforts for healthy living of hypertensive patient. The effort is important for reducing the probability of hypertension change to be dangerous disease. In this study, the food composition is build with attention nutrition amount, salt degree, and minimum cost. The proposed method is hybrid method of Genetic Algorithm (GA) and Variable Neighborhood Search (VNS). The three scenarios of hybrid GA-VNS types had been developed in this study. Although hybrid GA and VNS take more time than pure GA or pure VNS but the proposed method give better quality of solution. VNS successfully help GA avoids premature convergence and improves better solution. The shortcomings on GA in local exploitation and premature convergence is solved by VNS, whereas the shortcoming on VNS that less capability in global exploration can be solved by use GA that has advantage in global exploration.
This study investigated the role of neuronal apoptosis in volumetric changes of the hippocampus in diabetes mellitus type 1 rats. The key findings were:
1. The volume of the dentate gyrus and CA3 region was reduced in diabetic and vitamin C-treated rats compared to controls, indicating volume reduction can occur independently of neuronal loss.
2. The number of apoptotic neurons in the dentate gyrus and CA3 was significantly higher in diabetic rats compared to other groups, showing neuronal apoptosis is increased by diabetes.
3. A response index using the ratio of dentate gyrus to CA3 volumes and neuronal densities provided a predictive model, with the curves meeting at a critical point of 0
Can treating metabolic acidosis of ckd slow decline in eGFR?Adeel Rafi Ahmed
The UBI study was a multicenter RCT that investigated whether treating metabolic acidosis in patients with CKD stages 3-5 using oral sodium bicarbonate could preserve kidney function compared to standard care. The study found that sodium bicarbonate treatment was associated with a lower rate of CKD progression, lower risk of doubling of serum creatinine, lower risk of starting renal replacement therapy, and lower risk of all-cause mortality compared to standard care. Treatment with sodium bicarbonate was also found to be safe with no adverse effects on blood pressure or fluid volume status. The results provide support for actively managing metabolic acidosis in CKD to help prevent disease progression.
Autologous steam cells infusion (ASCI) in COPD patients: impact on quality of...Dra. Mônica Lapa
Methods
Were recruited from the pulmonology ambulatory 20 grade 3 COPD (GOLD 2017) in a 12-month follow-up (Figure 1) and study was approved by the Institutional Review Board. Inclusion aged between 40 to 70 years undergoing optimized treatment for COPD with grade 2 or 3 that is, they were all using beta-2 long-action agonists associated with long-acting anticholinergic and inhaled corticosteroids; a forced expiratory volume in the first second (FEV1) of 30-50%, they have quitted tobacco use for at least six months and could be submitted to the pulmonary rehabilitation program. Exclusion: absence of emphysema on chest tomography; infection or history of infectious disease for less than 3 months; previous history of coronary artery disease; presence of pulmonary hypertension; use of home oxygen therapy; advanced hepatic or renal insufficiency; detection of immunosuppressive or infectious diseases; and presence of known neoplasms.
Association between polymorphisms of the DNA repair gene (OGG1) in Iraqi pati...iosrjce
IOSR Journal of Pharmacy and Biological Sciences(IOSR-JPBS) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of Pharmacy and Biological Science. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Pharmacy and Biological Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
1) A double-blind clinical trial was conducted over 6 months to determine if a cysteine-rich protein supplement (IMN1207) had any positive or negative effects on clinical outcomes in lung cancer patients undergoing chemotherapy or radiotherapy compared to a casein protein supplement.
2) 35 lung cancer patients completed the study. Those receiving the cysteine-rich protein had a mean weight gain of 2.5% while those receiving casein lost 2.6% weight on average. Secondary outcomes like survival, muscle strength, and quality of life also improved more in the cysteine-rich protein group.
3) The cysteine-rich protein appeared to reverse weight loss and improve some measures of health more
Modeling Algorithm of Estimation Of Renal Function by the Cockcroft and M...hiij
The purpose of this study was to determine the concordance between two equations used for estimating
glomerular filtration rate, in order to verify the possibility to be used interchangeably in the clinical
practice. The two equations are of Cockcroft & Gault (CG) (1976) formula and MDRD (modification of
Diet in Renal Disease) (1999) formula, these two models allow the assessment of glomerular filtration rate
(GFR) by calculating creatinine clearance (CLCR).To make a comparison between these two formulas
different models were examined for Subjects with normal renal function, Patients with renal impairment,
Diabetic patients, Age and sex, finally lean and obese patients by modeling two algorithms with the two
functions. Results show that the formula of Cockcroft & Gault remains the method of choice for estimating
renal function in clinical practice.
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
Hybrid Genetic Algorithm for Optimization of Food Composition on Hypertensive...IJECEIAES
The healthy food with attention of salt degree is one of the efforts for healthy living of hypertensive patient. The effort is important for reducing the probability of hypertension change to be dangerous disease. In this study, the food composition is build with attention nutrition amount, salt degree, and minimum cost. The proposed method is hybrid method of Genetic Algorithm (GA) and Variable Neighborhood Search (VNS). The three scenarios of hybrid GA-VNS types had been developed in this study. Although hybrid GA and VNS take more time than pure GA or pure VNS but the proposed method give better quality of solution. VNS successfully help GA avoids premature convergence and improves better solution. The shortcomings on GA in local exploitation and premature convergence is solved by VNS, whereas the shortcoming on VNS that less capability in global exploration can be solved by use GA that has advantage in global exploration.
This study investigated the role of neuronal apoptosis in volumetric changes of the hippocampus in diabetes mellitus type 1 rats. The key findings were:
1. The volume of the dentate gyrus and CA3 region was reduced in diabetic and vitamin C-treated rats compared to controls, indicating volume reduction can occur independently of neuronal loss.
2. The number of apoptotic neurons in the dentate gyrus and CA3 was significantly higher in diabetic rats compared to other groups, showing neuronal apoptosis is increased by diabetes.
3. A response index using the ratio of dentate gyrus to CA3 volumes and neuronal densities provided a predictive model, with the curves meeting at a critical point of 0
Can treating metabolic acidosis of ckd slow decline in eGFR?Adeel Rafi Ahmed
The UBI study was a multicenter RCT that investigated whether treating metabolic acidosis in patients with CKD stages 3-5 using oral sodium bicarbonate could preserve kidney function compared to standard care. The study found that sodium bicarbonate treatment was associated with a lower rate of CKD progression, lower risk of doubling of serum creatinine, lower risk of starting renal replacement therapy, and lower risk of all-cause mortality compared to standard care. Treatment with sodium bicarbonate was also found to be safe with no adverse effects on blood pressure or fluid volume status. The results provide support for actively managing metabolic acidosis in CKD to help prevent disease progression.
Autologous steam cells infusion (ASCI) in COPD patients: impact on quality of...Dra. Mônica Lapa
Methods
Were recruited from the pulmonology ambulatory 20 grade 3 COPD (GOLD 2017) in a 12-month follow-up (Figure 1) and study was approved by the Institutional Review Board. Inclusion aged between 40 to 70 years undergoing optimized treatment for COPD with grade 2 or 3 that is, they were all using beta-2 long-action agonists associated with long-acting anticholinergic and inhaled corticosteroids; a forced expiratory volume in the first second (FEV1) of 30-50%, they have quitted tobacco use for at least six months and could be submitted to the pulmonary rehabilitation program. Exclusion: absence of emphysema on chest tomography; infection or history of infectious disease for less than 3 months; previous history of coronary artery disease; presence of pulmonary hypertension; use of home oxygen therapy; advanced hepatic or renal insufficiency; detection of immunosuppressive or infectious diseases; and presence of known neoplasms.
Association between polymorphisms of the DNA repair gene (OGG1) in Iraqi pati...iosrjce
IOSR Journal of Pharmacy and Biological Sciences(IOSR-JPBS) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of Pharmacy and Biological Science. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Pharmacy and Biological Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Quality of Life, Clinical Effectiveness and Satisfaction in Patient with Beta...Sunil Vadithya
Quality of Life, Clinical Effectiveness and Satisfaction in Patient with Beta Thalassemia Major and Sickel Cell Anemia Receiver Deferasirox Chelation Therapy
The Fabrication of Drug Enfused Microparticles for Drug Delivery PurposesAnurag Ojha
This document describes research into developing biodegradable microparticle implants for long-term delivery of the pain medication celecoxib to manage osteoarthritis pain. Five copolymers of varying compositions were used to fabricate drug-loaded microparticles. In vitro drug release studies found that altering the polymer matrix hydrophobicity affected release patterns, with more hydrophobic matrices releasing drug more slowly over 60 days. The microparticles have the potential to provide over 6 months of therapeutic drug levels for osteoarthritis pain management.
1) ADMA levels are significantly elevated in patients with severe sepsis compared to healthy controls and correlate with severity of organ failure and mortality.
2) Higher ADMA levels on day 1 are associated with need for inotropic support and higher levels on day 7 correlate with increased mortality.
3) While CRP and ADMA both increase in sepsis, only ADMA levels correlate with severity of organ dysfunction.
CompAct Renal 2012-2014 - Top 10 Articlespa21vifor
This document provides a summary of 10 articles from the CompAct Renal platform that discuss various topics related to the treatment of hyperphosphatemia and CKD-MBD. The articles cover subjects like the association between phosphate binder use and lower mortality, insights into optimal hyperphosphatemia treatment, causes of non-adherence to treatment regimens, the relationship between high pill burden and disease burden, challenges of implementing renal diets, and novel research on FGF-23 and potential treatment strategies. The document is a compilation of CompAct's most read articles from the past two years on issues surrounding hyperphosphatemia management and CKD-MBD.
1. The study assessed the reliability and linearity of the Arf6 G-LISA assay, which quantifies activated Arf6 protein levels.
2. A linear regression analysis found the assay to be highly linear from 0-15ng of recombinant Arf6 protein, explaining 98% of variance.
3. A multiple regression model found that the absorbance signal correlated significantly with the amount of Arf6 protein, primary antibody dilution, and secondary antibody dilution used. The model explained 96% of variance in assay results.
Clinical Usefulness of a New Equation for Estimating Body Fat
(Utilidad clínica de una nueva ecuación para estimar la grasa corporal)
Javier Gómez-Ambrosi, PHD1,2⇓, Camilo Silva, MD2,3, Victoria Catalán, PHD1,2, Amaia Rodríguez, PHD1,2, Juan Carlos Galofré, MD, PHD3, Javier Escalada, MD, PHD2,3, Victor Valentí, MD, PHD2, Fernando Rotellar, MD, PHD2, Sonia Romero, MSC2,3, Beatriz Ramírez, MSC1,2, Javier Salvador, MD, PHD2,3 and Gema Frühbeck, MD, PHD1,2,3
Corresponding author: Javier Gómez-Ambrosi, jagomez@unav.es.
Diabetes Care 2012 Feb; 35(2): 383-388. https://doi.org/10.2337/dc11-1334
This document describes a label-free quantitative proteomics method using liquid chromatography coupled to mass spectrometry (LC/MS). The method relies on comparing changes in peptide signal responses and retention times (accurate mass retention time or AMRT components) between control and experimental samples to determine relative protein abundance changes. The method was tested by spiking increasing amounts of standard proteins into human serum samples and observing a linear relationship between signal response and protein concentration. The quantitative proteomics strategy provides a simple LC/MS-based method for comparing protein profiles between samples without using stable isotope labeling.
Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyeliti...degarden
This document discusses mitochondrial dysfunction and its role in the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). It presents the results of biochemical testing on neutrophils from 138 ME/CFS patients and 53 healthy controls. All patients showed measurable mitochondrial dysfunction correlated with illness severity. Patients divided into two groups based on how cellular metabolism compensates for the dysfunction. The testing provides a diagnostic tool for ME/CFS, though mitochondrial dysfunction is also seen in other illnesses.
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%.
This study compared the effects of two treatment regimens for type 2 diabetes: dual therapy of metformin and glimepiride (Group A) versus triple therapy of metformin, glimepiride, and voglibose (Group B). Both regimens led to significant decreases in BMI, fasting blood glucose, post-prandial blood glucose, and HbA1c after 3 months of treatment. However, the triple therapy was more effective at lowering post-prandial glucose and had protective effects on kidney function. The results suggest that adding voglibose to metformin and glimepiride dual therapy provides better glucose control and management of diabetes.
Population-Based Pharmacokinetic Modeling of Vancomycin in Children with Rena...Mawaya Tanaka
This study compared vancomycin clearance and dosing in children with normal versus impaired renal function. The researchers conducted population-based pharmacokinetic modeling and Monte Carlo simulations using vancomycin concentration and dosing data from 126 children, matched into 63 pairs based on age, weight and renal function. The results showed that vancomycin clearance was significantly lower in children with renal impairment compared to those with normal function. A dosing regimen of 45 mg/kg/day achieved the target AUC/MIC ratio of ≥400 in 80% of children with renal impairment, compared to 60 mg/kg/day needed in children with normal renal function. The study provides guidance on appropriate vancomycin dosing for children based
This article discusses a study of 124 patients with differentiated thyroid cancer who underwent dosimetric evaluation to determine the optimal radioactive iodine dose for treatment. Dosimetry calculations were performed using MIRD methodology to estimate radiation doses to bone marrow, lungs, and tumor metastases. The goal was to determine the maximum safe dose that would deliver less than 3 Gy to bone marrow or 30 Gy to lungs, while aiming to deliver over 100 Gy to metastases for a curative intent. No patients experienced permanent bone marrow suppression when doses were under 3 Gy. The largest administered dose was 38.5 GBq (1,040 mCi) based on bone marrow dose limitations. Dosimetry-guided treatment allows administration of the maximum possible
The biomarker of choice in association of dyslipidemia with osteoporosis: A c...SriramNagarajan17
This case study describes a 55-year-old male patient who presented with pain in his lower limb and was diagnosed with both dyslipidemia and osteoporosis based on his medical history and laboratory tests. He had a family history of metabolic diseases and consumed excessive alcohol. His dyslipidemia was diagnosed based on genetic predisposition and lipid profile showing low HDL and high LDL levels. His osteoporosis was diagnosed a year and a half later when he fractured his femur during a walk and was found to have low bone mineral density. The conclusion is that low HDL and high LDL levels in the lipid profile are the biomarker of choice for associating dyslipidemia with osteoporosis as these
This document summarizes a drug use evaluation (DUE) of daptomycin from June to October 2014. Data was collected from 21 patients on daptomycin, but 10 patients were excluded for reasons such as duplication, not completing therapy, or having an actual body weight less than 130% of ideal body weight. The remaining 10 patients were included in the analysis. Most patients were dosed using adjusted body weight and had indications of MRSA infections or reactions to vancomycin. Adverse reactions occurred in 2 patients. Outcomes included resolution of infection in 5 patients, discontinuation due to adverse reactions in 2 patients, and discontinuation due to lack of efficacy in 3 patients. The study had a small sample size making it
This study developed and validated a multivariate logistic regression equation to screen for undiagnosed diabetes using readily available clinical data. The equation incorporated age, sex, BMI, time since eating, and random blood glucose. When applied to the derivation and validation datasets, the equation had sensitivities of 65% and 62%, specificities of 96%, and positive predictive values of 67% and 63%. The equation performed better than recommended static blood glucose cut-off points in identifying undiagnosed diabetes cases and had fewer false positives. The study concludes the equation improves diabetes screening over current methods and can easily be implemented using a handheld calculator.
This document summarizes recent advances in treatment approaches for genetic disorders. It discusses enzyme replacement therapy, which has proven effective for lysosomal storage disorders like Gaucher's disease and Hurler syndrome. It also reviews enzyme enhancement therapy, hematopoietic stem cell transplantation, organ transplantation, gene therapy, and hormonal therapies. The document indicates that while many treatment options now exist, high costs remain a major barrier, and there is still no cure for most genetic disorders.
This document describes a study that used liquid chromatography-mass spectrometry (LC-MS) to analyze serum metabolomic profiles of patients with esophageal squamous cell carcinoma (ESCC) compared to healthy controls. The analysis identified 652 molecular features that were significantly dysregulated in ESCC patients. Phosphatidylcholines were found to be a major class of dysregulated metabolites, suggesting perturbation of phosphocholine metabolism in ESCC. Targeted MS/MS analysis in positive and negative modes was able to characterize the structure of seven metabolites. The findings illustrate how metabolomic analysis using LC-MS can help characterize molecular alterations associated with ESCC.
International Journal of Computational Engineering Research(IJCER) is an intentional online Journal in English monthly publishing journal. This Journal publish original research work that contributes significantly to further the scientific knowledge in engineering and Technology.
A neural-network-approach-in-predicting-the-blood-glucose-level-for-diabetic-...Cemal Ardil
The document describes a proposed neural network approach for predicting blood glucose levels in diabetic patients. It combines principal component analysis and wavelet neural network modeling. The proposed system makes separate predictions for morning, afternoon, evening and night intervals using data from one patient over 77 days. Comparisons with other neural network models using the same dataset show improved prediction accuracy, indicating the effectiveness of the proposed approach.
Evaluation of the Impact of Biofield Treatment on Physical and Thermal Proper...wilhelm mendel
In the present study, the influence of biofield treatment on physical and thermal properties of Casein Enzyme Hydrolysate (CEH) and Casein Yeast Peptone (CYP) were investigated. The control and treated samples were characterized by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), Thermo Gravimetric Analysis (TGA), particle size and surface area analysis. The FTIR results revealed that biofield treatment has caused reduction of amide group (amide-I and amide-II) stretching vibration peak that is associated with strong intermolecular hydrogen bonding in treated CEH as compared to control. However, no significant changes were observed in FTIR spectrum of treated CYP. The TGA analysis of treated CEH showed a substantial improvement in thermal stability which was confirmed by increase in maximum thermal decomposition temperature (217°C) as compared to control (209°C). Similarly, the treated CYP also showed enhanced thermal stability as compared to control. DSC showed increase in melting temperature of treated CYP as compared to control. However the melting peak was absent in DSC of treated CEH which was probably due to rigid chain of the protein. The surface area of treated CEH was increased by 83% as compared to control. However, a decrease (7.3%) in surface area was observed in treated CYP. The particle size analysis of treated CEH showed a significant increase in average particle size (d50) and d99 value (maximum particle size below which 99% of particles are present) as compared to control sample. Similarly, the treated CYP also showed a substantial increase in d50 and d99 values which was probably due to the agglomeration of the particles which led to formation of bigger microparticles. The result showed that the biofield treated CEH and CYP could be used as a matrix for pharmaceutical applications.
Drug dosage adjustment using renal estimation equations. A review of the lite...Greenberg, Eric
This article reviews the accuracy and clinical use of the Cockcroft-Gault and abbreviated Modification of Diet in Renal Disease equations for estimating glomerular filtration rate and adjusting drug dosing in patients with chronic kidney disease. It discusses factors that can affect the accuracy of the equations like patient age, gender, weight, and ethnicity. While the abbreviated MDRD equation has advantages over Cockcroft-Gault like less bias and greater precision, more research is still needed before recommending its widespread use in adjusting medication doses due to limitations in certain patient populations. The article concludes an updated review of literature regarding using these equations for individualized drug dosing.
This document discusses a study comparing the implications of using the CKD-EPI equation versus the MDRD equation to estimate GFR and diagnose chronic kidney disease (CKD) in a large healthcare system. The study found:
1) The number of patients identified with CKD stages 3-5 decreased by 10% when using the CKD-EPI equation compared to the MDRD equation.
2) Changes in CKD identification varied by patient characteristics, with a 35% decrease in patients under 60 years old and a 10% increase in patients over 90 years old.
3) Only 14% of patients identified with CKD based on either equation also had a related ICD-9 diagnosis
Quality of Life, Clinical Effectiveness and Satisfaction in Patient with Beta...Sunil Vadithya
Quality of Life, Clinical Effectiveness and Satisfaction in Patient with Beta Thalassemia Major and Sickel Cell Anemia Receiver Deferasirox Chelation Therapy
The Fabrication of Drug Enfused Microparticles for Drug Delivery PurposesAnurag Ojha
This document describes research into developing biodegradable microparticle implants for long-term delivery of the pain medication celecoxib to manage osteoarthritis pain. Five copolymers of varying compositions were used to fabricate drug-loaded microparticles. In vitro drug release studies found that altering the polymer matrix hydrophobicity affected release patterns, with more hydrophobic matrices releasing drug more slowly over 60 days. The microparticles have the potential to provide over 6 months of therapeutic drug levels for osteoarthritis pain management.
1) ADMA levels are significantly elevated in patients with severe sepsis compared to healthy controls and correlate with severity of organ failure and mortality.
2) Higher ADMA levels on day 1 are associated with need for inotropic support and higher levels on day 7 correlate with increased mortality.
3) While CRP and ADMA both increase in sepsis, only ADMA levels correlate with severity of organ dysfunction.
CompAct Renal 2012-2014 - Top 10 Articlespa21vifor
This document provides a summary of 10 articles from the CompAct Renal platform that discuss various topics related to the treatment of hyperphosphatemia and CKD-MBD. The articles cover subjects like the association between phosphate binder use and lower mortality, insights into optimal hyperphosphatemia treatment, causes of non-adherence to treatment regimens, the relationship between high pill burden and disease burden, challenges of implementing renal diets, and novel research on FGF-23 and potential treatment strategies. The document is a compilation of CompAct's most read articles from the past two years on issues surrounding hyperphosphatemia management and CKD-MBD.
1. The study assessed the reliability and linearity of the Arf6 G-LISA assay, which quantifies activated Arf6 protein levels.
2. A linear regression analysis found the assay to be highly linear from 0-15ng of recombinant Arf6 protein, explaining 98% of variance.
3. A multiple regression model found that the absorbance signal correlated significantly with the amount of Arf6 protein, primary antibody dilution, and secondary antibody dilution used. The model explained 96% of variance in assay results.
Clinical Usefulness of a New Equation for Estimating Body Fat
(Utilidad clínica de una nueva ecuación para estimar la grasa corporal)
Javier Gómez-Ambrosi, PHD1,2⇓, Camilo Silva, MD2,3, Victoria Catalán, PHD1,2, Amaia Rodríguez, PHD1,2, Juan Carlos Galofré, MD, PHD3, Javier Escalada, MD, PHD2,3, Victor Valentí, MD, PHD2, Fernando Rotellar, MD, PHD2, Sonia Romero, MSC2,3, Beatriz Ramírez, MSC1,2, Javier Salvador, MD, PHD2,3 and Gema Frühbeck, MD, PHD1,2,3
Corresponding author: Javier Gómez-Ambrosi, jagomez@unav.es.
Diabetes Care 2012 Feb; 35(2): 383-388. https://doi.org/10.2337/dc11-1334
This document describes a label-free quantitative proteomics method using liquid chromatography coupled to mass spectrometry (LC/MS). The method relies on comparing changes in peptide signal responses and retention times (accurate mass retention time or AMRT components) between control and experimental samples to determine relative protein abundance changes. The method was tested by spiking increasing amounts of standard proteins into human serum samples and observing a linear relationship between signal response and protein concentration. The quantitative proteomics strategy provides a simple LC/MS-based method for comparing protein profiles between samples without using stable isotope labeling.
Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyeliti...degarden
This document discusses mitochondrial dysfunction and its role in the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). It presents the results of biochemical testing on neutrophils from 138 ME/CFS patients and 53 healthy controls. All patients showed measurable mitochondrial dysfunction correlated with illness severity. Patients divided into two groups based on how cellular metabolism compensates for the dysfunction. The testing provides a diagnostic tool for ME/CFS, though mitochondrial dysfunction is also seen in other illnesses.
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%.
This study compared the effects of two treatment regimens for type 2 diabetes: dual therapy of metformin and glimepiride (Group A) versus triple therapy of metformin, glimepiride, and voglibose (Group B). Both regimens led to significant decreases in BMI, fasting blood glucose, post-prandial blood glucose, and HbA1c after 3 months of treatment. However, the triple therapy was more effective at lowering post-prandial glucose and had protective effects on kidney function. The results suggest that adding voglibose to metformin and glimepiride dual therapy provides better glucose control and management of diabetes.
Population-Based Pharmacokinetic Modeling of Vancomycin in Children with Rena...Mawaya Tanaka
This study compared vancomycin clearance and dosing in children with normal versus impaired renal function. The researchers conducted population-based pharmacokinetic modeling and Monte Carlo simulations using vancomycin concentration and dosing data from 126 children, matched into 63 pairs based on age, weight and renal function. The results showed that vancomycin clearance was significantly lower in children with renal impairment compared to those with normal function. A dosing regimen of 45 mg/kg/day achieved the target AUC/MIC ratio of ≥400 in 80% of children with renal impairment, compared to 60 mg/kg/day needed in children with normal renal function. The study provides guidance on appropriate vancomycin dosing for children based
This article discusses a study of 124 patients with differentiated thyroid cancer who underwent dosimetric evaluation to determine the optimal radioactive iodine dose for treatment. Dosimetry calculations were performed using MIRD methodology to estimate radiation doses to bone marrow, lungs, and tumor metastases. The goal was to determine the maximum safe dose that would deliver less than 3 Gy to bone marrow or 30 Gy to lungs, while aiming to deliver over 100 Gy to metastases for a curative intent. No patients experienced permanent bone marrow suppression when doses were under 3 Gy. The largest administered dose was 38.5 GBq (1,040 mCi) based on bone marrow dose limitations. Dosimetry-guided treatment allows administration of the maximum possible
The biomarker of choice in association of dyslipidemia with osteoporosis: A c...SriramNagarajan17
This case study describes a 55-year-old male patient who presented with pain in his lower limb and was diagnosed with both dyslipidemia and osteoporosis based on his medical history and laboratory tests. He had a family history of metabolic diseases and consumed excessive alcohol. His dyslipidemia was diagnosed based on genetic predisposition and lipid profile showing low HDL and high LDL levels. His osteoporosis was diagnosed a year and a half later when he fractured his femur during a walk and was found to have low bone mineral density. The conclusion is that low HDL and high LDL levels in the lipid profile are the biomarker of choice for associating dyslipidemia with osteoporosis as these
This document summarizes a drug use evaluation (DUE) of daptomycin from June to October 2014. Data was collected from 21 patients on daptomycin, but 10 patients were excluded for reasons such as duplication, not completing therapy, or having an actual body weight less than 130% of ideal body weight. The remaining 10 patients were included in the analysis. Most patients were dosed using adjusted body weight and had indications of MRSA infections or reactions to vancomycin. Adverse reactions occurred in 2 patients. Outcomes included resolution of infection in 5 patients, discontinuation due to adverse reactions in 2 patients, and discontinuation due to lack of efficacy in 3 patients. The study had a small sample size making it
This study developed and validated a multivariate logistic regression equation to screen for undiagnosed diabetes using readily available clinical data. The equation incorporated age, sex, BMI, time since eating, and random blood glucose. When applied to the derivation and validation datasets, the equation had sensitivities of 65% and 62%, specificities of 96%, and positive predictive values of 67% and 63%. The equation performed better than recommended static blood glucose cut-off points in identifying undiagnosed diabetes cases and had fewer false positives. The study concludes the equation improves diabetes screening over current methods and can easily be implemented using a handheld calculator.
This document summarizes recent advances in treatment approaches for genetic disorders. It discusses enzyme replacement therapy, which has proven effective for lysosomal storage disorders like Gaucher's disease and Hurler syndrome. It also reviews enzyme enhancement therapy, hematopoietic stem cell transplantation, organ transplantation, gene therapy, and hormonal therapies. The document indicates that while many treatment options now exist, high costs remain a major barrier, and there is still no cure for most genetic disorders.
This document describes a study that used liquid chromatography-mass spectrometry (LC-MS) to analyze serum metabolomic profiles of patients with esophageal squamous cell carcinoma (ESCC) compared to healthy controls. The analysis identified 652 molecular features that were significantly dysregulated in ESCC patients. Phosphatidylcholines were found to be a major class of dysregulated metabolites, suggesting perturbation of phosphocholine metabolism in ESCC. Targeted MS/MS analysis in positive and negative modes was able to characterize the structure of seven metabolites. The findings illustrate how metabolomic analysis using LC-MS can help characterize molecular alterations associated with ESCC.
International Journal of Computational Engineering Research(IJCER) is an intentional online Journal in English monthly publishing journal. This Journal publish original research work that contributes significantly to further the scientific knowledge in engineering and Technology.
A neural-network-approach-in-predicting-the-blood-glucose-level-for-diabetic-...Cemal Ardil
The document describes a proposed neural network approach for predicting blood glucose levels in diabetic patients. It combines principal component analysis and wavelet neural network modeling. The proposed system makes separate predictions for morning, afternoon, evening and night intervals using data from one patient over 77 days. Comparisons with other neural network models using the same dataset show improved prediction accuracy, indicating the effectiveness of the proposed approach.
Evaluation of the Impact of Biofield Treatment on Physical and Thermal Proper...wilhelm mendel
In the present study, the influence of biofield treatment on physical and thermal properties of Casein Enzyme Hydrolysate (CEH) and Casein Yeast Peptone (CYP) were investigated. The control and treated samples were characterized by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), Thermo Gravimetric Analysis (TGA), particle size and surface area analysis. The FTIR results revealed that biofield treatment has caused reduction of amide group (amide-I and amide-II) stretching vibration peak that is associated with strong intermolecular hydrogen bonding in treated CEH as compared to control. However, no significant changes were observed in FTIR spectrum of treated CYP. The TGA analysis of treated CEH showed a substantial improvement in thermal stability which was confirmed by increase in maximum thermal decomposition temperature (217°C) as compared to control (209°C). Similarly, the treated CYP also showed enhanced thermal stability as compared to control. DSC showed increase in melting temperature of treated CYP as compared to control. However the melting peak was absent in DSC of treated CEH which was probably due to rigid chain of the protein. The surface area of treated CEH was increased by 83% as compared to control. However, a decrease (7.3%) in surface area was observed in treated CYP. The particle size analysis of treated CEH showed a significant increase in average particle size (d50) and d99 value (maximum particle size below which 99% of particles are present) as compared to control sample. Similarly, the treated CYP also showed a substantial increase in d50 and d99 values which was probably due to the agglomeration of the particles which led to formation of bigger microparticles. The result showed that the biofield treated CEH and CYP could be used as a matrix for pharmaceutical applications.
Drug dosage adjustment using renal estimation equations. A review of the lite...Greenberg, Eric
This article reviews the accuracy and clinical use of the Cockcroft-Gault and abbreviated Modification of Diet in Renal Disease equations for estimating glomerular filtration rate and adjusting drug dosing in patients with chronic kidney disease. It discusses factors that can affect the accuracy of the equations like patient age, gender, weight, and ethnicity. While the abbreviated MDRD equation has advantages over Cockcroft-Gault like less bias and greater precision, more research is still needed before recommending its widespread use in adjusting medication doses due to limitations in certain patient populations. The article concludes an updated review of literature regarding using these equations for individualized drug dosing.
This document discusses a study comparing the implications of using the CKD-EPI equation versus the MDRD equation to estimate GFR and diagnose chronic kidney disease (CKD) in a large healthcare system. The study found:
1) The number of patients identified with CKD stages 3-5 decreased by 10% when using the CKD-EPI equation compared to the MDRD equation.
2) Changes in CKD identification varied by patient characteristics, with a 35% decrease in patients under 60 years old and a 10% increase in patients over 90 years old.
3) Only 14% of patients identified with CKD based on either equation also had a related ICD-9 diagnosis
Creatinine clearance: When Does It Matter?PASaskatchewan
This document provides information on estimating kidney function and adjusting drug dosing in patients with chronic kidney disease (CKD). It describes the differences between creatinine clearance (CrCl), estimated glomerular filtration rate (eGFR), and their respective formulas (Cockcroft-Gault and MDRD/CKD-EPI). While both CrCl and eGFR can be used to estimate kidney function and guide drug dosing, CrCl may be preferred in the elderly and for drugs with a narrow therapeutic index. The document reviews drug classes that commonly require dosage adjustments in CKD and provides an example case of adjusting anticoagulation therapy in a patient with CKD.
This document discusses antibiotic dosing during renal failure. It explains the importance of dose adjustments with renal impairment due to decreased drug elimination. It compares methods to calculate glomerular filtration rate (GFR) and creatinine clearance, such as the Modification of Diet in Renal Disease (MDRD) and Cockroft-Gault equations. It also describes different types of dialysis and considerations for dosing antibiotics in patients receiving dialysis or continuous renal replacement therapy.
1. The publication of new UK guidelines for Chronic Kidney Disease in 2005 led to changes in how renal impairment is classified and estimated glomerular filtration rate (eGFR) is now routinely reported.
2. While eGFR provides a quick assessment of kidney function, it should not be used to calculate drug dosages because it is standardized to a body surface area of 1.73m2 and can over or under estimate renal function in individuals.
3. The Cockcroft-Gault equation, which estimates creatinine clearance based on creatinine levels, age, gender and weight, is preferable for calculating drug dosages in patients with renal impairment.
Correlation of Serum Creatinine Based Calculation of Glomerular Filtration Ra...ijtsrd
INTRODUCTION GFR is best index of kidney function in health and disease and accurate values are needed for optimal decision making in clinical settings. Estimated GFR eGFR based on serum creatinine is first line test of kidney function. CG formula is creatinine based equation and widely applied. Tc99m DTPA Diethylene Triamine Penta Acetic acid is the most commonly used radiopharmaceutical for GFR studies. The Gate method has been most common in the routine setting. AIM AND OBJECTIVES To study correlation of serum creatinine based calculation of GFR with measured ratio isotope GFR in healthy individuals and CKD patients. To assess the accuracy of GFR as calculated by CG GFR formulae using serum creatinine against measured RI GFR Tc 99m DTPA . METHODS This study observational study, which is done in department of medicine and department of nuclear medicine at Army Hospital RandR, Delhi Cantt in CKD and healthy individuals. Our study includes a total of 100 subjects with varying renal functions which includes 50 healthy individual and 50 CKD patients. RESULTS In this study it has been observed that in healthy group CG GFR has weak correlation with DTPA GFR r = 0.104 with p 0.471 . Lt Col (Dr.) Rahul Soni | Dr. Jayita Debnath "Correlation of Serum Creatinine Based Calculation of Glomerular Filtration Rate with Measured Radio Isotope Glomerular Filtration Rate in Healthy Individuals and Chronic Kidney Disease Patients" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-2 , February 2021, URL: https://www.ijtsrd.com/papers/ijtsrd38443.pdf Paper Url: https://www.ijtsrd.com/medicine/other/38443/correlation-of-serum-creatinine-based-calculation-of-glomerular-filtration-rate-with-measured-radio-isotope-glomerular-filtration-rate-in-healthy-individuals-and-chronic-kidney-disease-patients/lt-col-dr-rahul-soni
Optimizing Protocol Design and Enhancing Patient Enrollment Case Study Covance
An emerging biopharmaceutical company was considering development of a pharmacologic agent for treatment of patients with diabetic kidney disease (DKD).
In this presentation i have tried to explain in brief about nomograms and their applications, the general approach to individualise doage regimen by using pharmacokinetic data
This document discusses drug dosing considerations in patients with chronic kidney disease. It provides guidelines for estimating glomerular filtration rate (GFR) using creatinine-based equations like CKD-EPI and Cockcroft-Gault to guide drug dosing. For drugs that are renally cleared, doses may need to be reduced as kidney function declines. Drugs are classified by their fraction excreted unchanged to determine dosing adjustments needed. Examples of common drug classes like antihypertensives, hypoglycemics, and antimicrobials are outlined with dosing recommendations based on a patient's GFR and kidney function stage. Measuring drug levels can help optimize therapeutic regimens in patients with chronic kidney
Establishment and analysis of a disease risk prediction model for chronic kid...KrishMendapara1
This study developed and evaluated a chronic kidney disease (CKD) risk prediction model using gene expression data and random forest algorithms. The researchers:
1. Identified differentially expressed genes (DEGs) from multiple kidney tissue datasets and used enrichment analysis to examine biological processes and pathways associated with CKD.
2. Employed Lasso regression and random forest with recursive feature elimination to select six key genes (DUSP1, GADD45B, IFI44L, IFI30, ATF3, and LYZ) that distinguish CKD from healthy samples.
3. Created a random forest model using the six genes and evaluated its performance on validation datasets, achieving an AUC of 0.
Extrapolation of preclinical data to clinical data.pptxVincyDinakaran
EXTRAPOLATION OF PRECLINICAL DATA TO CLINICAL DATA
EXTRAPOLATION
It is the prediction of effects in humans from effects in animals using pharmacokinetics and pharmacodynamics studies.
Extrapolation of drug dose or pharmacokinetic parameter to a species of interest is called scaling.
Scaling is of two types:
ISOMETRIC SCALING – dose for one species is applied to all
ALLOMETRIC SCALING – correlating mass of an organism with physiological parameters
ALLOMETRIC SCALING
It was a technique developed to explain the observed relationship between organ size and body weight of mammals.
Allometric scaling of pharmacokinetic data typically focus on interspecies relationship between clearance and volume of distribution of unbound drug and species body weight. These are then extrapolated to humans.
DISADVANTAGES
Purely empirical.
Cannot give any idea about the mechanism of action.
PBPK (Physiology based pharmacokinetic) modelling
It make use of data such as prediction of clearance and tissue distribution from in- vitro and in-silico data.
It is useful in predicting plasma and tissue concentration time profiles.
Also useful in addressing issues in pharmacokinetics (eg: saturable metabolism) and inter-species differences in nature, expression levels and dissipation of pharmacological effects.
NEW METHODS OF PREDICTING PHARMACOKINETICS
Methods for predicting human volume of distribution
Methods for predicting human clearance
Methods for predicting human t ½
Methods for predicting human oral bioavailability
Methods for predicting human volume of distribution
● Average fraction unbound in tissue method
● Proportionality
● Allometry without protein binding
● Allometry corrected for protein binding
a. Average fraction unbound in tissue
Uses experimentally determined value for volume of distribution and plasma protein binding for each species , along with standard values for extracellular fluid volumes , plasma volumes and calculate the fraction unbound in tissues in animal species
Fut = Vr Fu
[VDss – Vp (Fu Ve)] – [(1-Fu)(Re/i)Vp]
Avg Fut of different species is calculated and averaged.
Average will be equal to human Fut
Experimentally determine human Fu
VD(human prediction)= Vp+ [Fu(human) x Ve] + {[1-Fu(human) ]x (Re/i)x Vp} +Vr {Fu(human) / Fut(avg) }
b. Proportionality Method
Proportionality could be setup between the fraction of drug in plasma in dog and the human and the volume of distribution in these 2 species.
The assumption was that the tissue binding of drug is similar in dogs and humans and that physiological parameters such as extracellular fluid volumes are similar between the 2 species.
VD (human prediction) = Fu(human). VD(dog)
Fu(dog)
Fu – fraction of unbound drug in the plasma of dog and human
VD(dog) –volume of distribution at steady state in dog
The IFCC Working Group on Standardization of HbA1c has achieved the following in their efforts to standardize HbA1c measurement globally:
1. Established a reference measurement procedure using purified calibrators and HPLC or capillary electrophoresis.
2. Developed a network of reference laboratories worldwide to implement the reference system.
3. Begun work on traceability to the IFCC reference system, though full implementation is on hold pending further studies relating HbA1c to average blood glucose levels.
The position of the IFCC Working Group is that the name HbA1c should continue to be used in clinical practice, measurement units should be reported as mmol/mol
This slides contains 3 sections:
a. measurement of renal dysfuntion in cirrhosis
b. Evolution of hepatorenal syndrome
c. treatment of hepatorenal Syndrome
1) Recent studies have suggested that lower levels of weekly solute clearance through peritoneal dialysis are adequate, challenging previous guidelines recommending higher targets.
2) The ADEMEX and Hong Kong trials found no difference in patient survival between higher and lower dialysis dose groups, suggesting a minimum delivered weekly Kt/V of 1.7 may be sufficient.
3) The 2006 KDOQI guidelines established a minimum delivered weekly Kt/V target of 1.7 based on these studies, lower than the previous target of 2.1. Maintaining solute clearance above this minimum is recommended to optimize patient outcomes and longevity on peritoneal dialysis.
Predicting volume of distribution for drug compounds using decision treesNithyakalyani Chinnaiah
This document provides an overview of a student's MSc dissertation project that aims to improve the prediction of volume of distribution (VD) for drug compounds using a two-stage classification-regression approach. The student conducted literature research on previous methods for predicting VD and proposes using a novel method that first classifies compounds into categories based on their VD values, then predicts a numeric VD value using regression models built specifically for each class. The document outlines the student's motivations and contributions, and provides background information on VD, molecular descriptors, classification and regression techniques like random forest that will be used. It also summarizes relevant prior work and previews the methodology that will be evaluated in the dissertation.
This document describes a study that aimed to determine if there is a relationship between insulin levels in the blood and various chemical and demographic variables using data from the National Health and Nutrition Examination Survey. The researchers analyzed relationships between insulin levels and urinary levels of iodine, creatinine, perchlorate, nitrate, and thiocyanate as well as demographic factors including gender, age, and household income. Initial models showed violations of assumptions that were addressed through data transformations, resulting in a log-transformed linear model that better fit the data.
Definition and staging criteria of acute kidney injury in adults up todateCamilaEscobar83
The document discusses the definition and staging criteria for acute kidney injury (AKI) in adults. It describes the Kidney Disease Improving Global Outcomes (KDIGO) criteria as the preferred definition, which defines AKI based on changes in serum creatinine and urine output over specific time periods. AKI is staged from 1 to 3 based on the degree of increase in creatinine or decrease in urine output. The limitations of the criteria are that they do not distinguish etiologies, the use of urine output alone is not well validated, and determining baseline creatinine can be challenging in some patients.
This document summarizes research aimed at developing new inhibitors of the glycogen phosphorylase (GP) enzyme for potential treatment of type 2 diabetes. Computational models were developed to predict the activity of 21 test ligands as GP inhibitors. The models suggested ligands S1, S2, and S21 may be potent nanomolar inhibitors of GP, among the best known. These promising ligands will now be synthesized and experimentally tested for their ability to inhibit GP.
This document describes a research project on developing a closed-loop system to control blood glucose levels in type 1 diabetic patients. It presents the aims and objectives, which include simulating a type 1 diabetic patient model, controlling the model using Internal Model Control, and testing the stability of the closed-loop system. A literature review discusses previous works that used various control methods like model predictive control and fuzzy logic control. The methodology describes linearizing the diabetic patient model, modeling the system in Simulink, designing IMC, PID and LQG controllers, and testing stability. Results show the internal model controller maintained blood glucose levels and was stable based on analysis plots and the Bode stability criterion. The conclusion recommends the IMC strategy for
ABSTRACT- Introduction: Importance of measurement of glycated hemoglobin (HbA1c) has been recommended for
the diagnosis of diabetes and pre-diabetes. However, various epidemiological studies conducted different parts of the
universe have shown significant discordance between HbA1c and glucose-based tests. Glycated hemoglobin (HbA1c) is
assumed to be the gold standard for monitoring glycemic control in patients with diabetes mellitus disorder. The Glycated
hemoglobin (HbA1c) assay provided an accurate, precise measure of chronic glycemic levels, and associates with the risk
of diabetes complications.
Materials and Methods: This is a cross sectional prospective study. A total of 868 individuals attended to the medicine
outpatient clinic at Lord Buddha Koshi Medical College, Saharsa, Bihar between Jan 2016 to Dec 2016 were selected for
the study after screening a large cohort visited OPD. The results of FPG, OGTT, and HbA1c for 868 individual were
analyzed as well as all grouped as diabetic patients, glucose intolerant (pre-diabetes) patients, and non-diabetic patients
according to new ADA criteria for the diagnosis of diabetes.
Results: Diagnostic sensitivity of all diabetic criteria were 80.33% for A1c; 75% for OGTT and only 41.87% for FPG
respectively.
Conclusion: The proposed A1c diagnostic criteria have greater diagnostic than FPG and 2-h OGTT regarding a diagnosis
of diabetes mellitus disorder.
Key-words- Glycated Hemoglobin, Fasting Plasma Glucose, Oral glucose tolerances test (OGTT), Diabetes Mellitus,
and Pre- diabetes
Similar to Evaluation of the chronic kidney disease epidemiology 2010 (20)
El documento describe las acciones tomadas por el servicio farmacéutico de un hospital para prevenir errores de medicación a través de la implementación de sistemas de dosis unitaria y listos para usar. Esto incluyó la preparación centralizada de medicamentos comúnmente usados en UCI para garantizar su seguridad y calidad, así como la documentación de procesos y procedimientos. La implementación redujo errores, costos y riesgos para los pacientes.
1) The study assessed the prevalence of and risk factors for acute kidney injury (AKI) in 114 patients treated with intravenous polymyxin B for at least 3 days.
2) AKI developed in 22% of patients. Risk factors for AKI included abnormal baseline serum creatinine, use of vasoactive drugs, and infections located in the abdomen, blood, or catheter.
3) Patients who developed AKI had a strikingly higher mortality rate of 92% compared to 53% in patients without AKI.
This document reviews the pharmacokinetic considerations for antimicrobial therapy in patients receiving renal replacement therapy. It discusses the principles of drug removal during renal replacement therapies like hemodialysis and hemofiltration. Hemodialysis removes drugs mainly by diffusion while hemofiltration removes drugs by convection. The efficiency of drug removal depends on characteristics of the drug and renal replacement therapy device. Hydrophilic antimicrobials with high renal clearance may require increased dosing with renal replacement therapy, while lipophilic drugs with low renal clearance may require no dose adjustment. Therapeutic drug monitoring can help optimize drug exposure during renal replacement therapy.
Ultimo concenso para monitorizacion de vancomicinaeduardo de avila
The document summarizes guidelines from infectious disease societies for therapeutic monitoring of vancomycin treatment. It provides recommendations for dosing, monitoring, and targeting trough serum concentrations of vancomycin based on a review of existing evidence. The guidelines recommend initial doses based on actual body weight and subsequent adjustments based on serum concentrations to achieve target concentrations. Trough serum concentrations are recommended for monitoring effectiveness, with concentrations of 15-20 mg/L suggested to optimize outcomes for serious infections while avoiding resistance. Monitoring is advised for certain high-risk patients.
This research report compares the pharmacodynamics of intermittent and prolonged infusions of piperacillin/tazobactam using Monte Carlo simulations and pharmacokinetic data from hospitalized patients. The authors found that prolonged infusion regimens of 3.375 g or more every 8 hours achieved excellent target attainment against common gram-negative pathogens like E. coli and Enterobacteriaceae with MICs up to 16 μg/mL, using lower daily doses than standard intermittent regimens. However, none of the regimens tested provided optimal coverage against Pseudomonas aeruginosa and Klebsiella pneumoniae.
El documento discute el ajuste de dosis de antibióticos en pacientes con insuficiencia renal u hepática. La insuficiencia renal requiere reducir la dosis en 30% para cada nivel de daño renal. La insuficiencia hepática no tiene una regla general, se debe usar la información específica de cada antibiótico. La hemodiálisis elimina antibióticos con bajo peso molecular o volumen de distribución, por lo que la dosis debe administrarse después de la sesión. Técnicas de depuración más intensivas pueden eliminar antib
Comparing outcomes of meropenem administration strategies 2010eduardo de avila
This document systematically reviews evidence comparing traditional and alternative dosing strategies for meropenem. Sixteen studies were reviewed, including 13 pharmacokinetic/dynamic assessments, 5 clinical evaluations, and 3 economic appraisals. Studies suggest alternative dosing strategies like prolonged or continuous infusion may increase achieving pharmacodynamic targets compared to traditional dosing. However, evidence linking these strategies to improved clinical outcomes is lacking. Smaller, more frequent doses appear to provide similar clinical outcomes and pharmacodynamic target attainment as traditional dosing, with potential cost savings. Overall, alternative dosing strategies seem to provide comparable outcomes to traditional dosing, but evidence is limited and largely based on healthy subjects. Larger clinical trials are needed.
Este documento proporciona guías para ajustar las dosis de varios fármacos comúnmente utilizados en pacientes con insuficiencia renal. Incluye tablas con las dosis usuales de los fármacos, y cómo deben ajustarse las dosis en función del aclaramiento de creatinina del paciente. También incluye nomogramas para calcular las dosis y los intervalos de dosificación de aminoglucósidos y vancomicina en pacientes con insuficiencia renal.
it describes the bony anatomy including the femoral head , acetabulum, labrum . also discusses the capsule , ligaments . muscle that act on the hip joint and the range of motion are outlined. factors affecting hip joint stability and weight transmission through the joint are summarized.
This presentation includes basic of PCOS their pathology and treatment and also Ayurveda correlation of PCOS and Ayurvedic line of treatment mentioned in classics.
This presentation was provided by Steph Pollock of The American Psychological Association’s Journals Program, and Damita Snow, of The American Society of Civil Engineers (ASCE), for the initial session of NISO's 2024 Training Series "DEIA in the Scholarly Landscape." Session One: 'Setting Expectations: a DEIA Primer,' was held June 6, 2024.
This slide is special for master students (MIBS & MIFB) in UUM. Also useful for readers who are interested in the topic of contemporary Islamic banking.
How to Setup Warehouse & Location in Odoo 17 InventoryCeline George
In this slide, we'll explore how to set up warehouses and locations in Odoo 17 Inventory. This will help us manage our stock effectively, track inventory levels, and streamline warehouse operations.
Executive Directors Chat Leveraging AI for Diversity, Equity, and InclusionTechSoup
Let’s explore the intersection of technology and equity in the final session of our DEI series. Discover how AI tools, like ChatGPT, can be used to support and enhance your nonprofit's DEI initiatives. Participants will gain insights into practical AI applications and get tips for leveraging technology to advance their DEI goals.
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Main Java[All of the Base Concepts}.docxadhitya5119
This is part 1 of my Java Learning Journey. This Contains Custom methods, classes, constructors, packages, multithreading , try- catch block, finally block and more.
Walmart Business+ and Spark Good for Nonprofits.pdfTechSoup
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Answers about how you can do more with Walmart!"
Evaluation of the chronic kidney disease epidemiology 2010
1. Infectious Diseases
Evaluation of the Chronic Kidney Disease Epidemiology
Collaboration Equation for Dosing Antimicrobials
Kurt A Wargo and Thomas M English
lomerular filtration rate (GFR) is
G the most accurate measure of one
of the major functions of the kidneys
BACKGROUND: Since the derivation of the Modification of Diet in Renal Disease
(MDRD) equation for estimating glomerular filtration rate (GFR), investigators
(clearance), though difficult and costly to determined that it cannot be used for drug dosing. In 2009, the Chronic Kidney
directly measure.1 Clinically, estimation of Disease Epidemiology Collaboration (CKD-EPI) derived an equation that was
more accurate than the MDRD estimation of GFR. Therefore, questions exist
GFR using the Modification of Diet in Re-
about which method should be preferred in making dosage adjustments for
nal Disease (MDRD) equation allows renally eliminated antimicrobials.
practitioners to stage chronic kidney dis- OBJECTIVE: To determine whether a difference exists when making antimicrobial
ease.2 When making estimations of kidney dosage adjustments in patients with CKD based on estimation of GFR using the
function at the bedside, for the purpose of CKD-EPI and Cockcroft-Gault equations.
drug dosing, practitioners utilize the Cock- METHODS: A database of 409 patients with CKD admitted to a tertiary care facility
croft-Gault equation.3 This equation esti- was used. GFR was calculated using both the CKD-EPI equation(s) and the
mates creatinine clearance (CrCl) and is Cockcroft-Gault equation and compared using correlation and Bland-Altman
recommended by the Food and Drug Ad- methodology. Dosage discordance rates of antimicrobials were determined.
ministration (FDA) for use by pharmaceu- RESULTS: Average GFRs for all patients using the Cockcroft-Gault and CKD-EPI
equations were 34.8 ± 12 mL/min and 39.9 ± 13 mL/min, respectively (5.09 [95% CI
tical companies when specific renal dos-
4.60 to 5.59]; p < 0.001). The correlation coefficient between the 2 estimations was
age adjustments are required.4 Since the high (r = 0.91). The Bland-Altman plot yielded limits of agreement of 15.3 and –5.1;
derivation of the MDRD equation and the thus, the CKD-EPI estimation may range from 5.1 mL/min below to 15.3 mL/min
finding that it was a more accurate predic- above the Cockcroft-Gault estimation for 95% of the cases. A discordance rate of
tor of renal function than the Cockcroft- 15–25% existed among the recommended dosing adjustments of the selected
Gault equation estimate, questions have antimicrobials when comparing the Cockcroft-Gault and CKD-EPI estimations.
existed with regard to its use for the pur- CONCLUSIONS: Though this study did not determine which equation should be
selected to dose adjust antimicrobials, it demonstrated statistically significant
pose of making drug dosage adjustments.2
differences between the Cockcroft-Gault and CKD-EPI equations. The clinical
To complicate matters, in 2009 a new set significance of these differences is uncertain in the absence of data assessing
of equations for the measurement of GFR, clinical outcomes that result from the use of the discordant doses. Clinical
derived from the Chronic Kidney Disease judgment should be employed when making renal dosage adjustments of
Epidemiology Collaboration (CKD -EPI) antimicrobials.
study, were found to provide a statistically KEY WORDS: antimicrobials, chronic kidney disease, CKD-EPI, Cockcroft-Gault,
more accurate estimation of GFR than the dosing, MDRD.
MDRD equation.5 Unfortunately, because Ann Pharmacother 2010;44:439-46.
Published Online, 17 Feb 2010, theannals.com, DOI 10.1345/aph.1M602
Author information provided at end of text.
theannals.com The Annals of Pharmacotherapy I 2010 March, Volume 44 I 439
2. KA Wargo and TM English
these equations estimate GFR and not CrCl, questions still proved observational analysis conducted at an 881-bed ter-
exist as to which method to use when estimating renal func- tiary care facility. A search engine was used to identify pa-
tion for the purposes of drug dosing in patients with CKD. tients admitted with a SCr of 1.3–3 mg/dL. Patients were in-
Differences exist between the CKD -EPI, MDRD, and cluded in the analysis if they were identified as having CKD
Cockcroft-Gault estimations of kidney function.2,3,5 One dif- by physician documentation and were classified as CKD
ference between the equations is that the 6-variable MDRD stages 3 (GFR 30–59 mL/min), 4 (15–29 mL/min), or 5
equation takes into account 3 biochemical markers, serum (<15 mL/min), using the MDRD equations. Excluded pa-
creatinine (SCr), serum albumin, and blood urea nitrogen tients were those with acute renal dysfunction, defined as an
(BUN), along with age, race, and sex. On the other hand, 8 elevation in SCr of 0.5 mg/dL from baseline, or from physi-
CKD -EPI equations exist, which take into account race, sex, cian documentation, end-stage renal disease on dialysis,
and SCr. The Cockcroft-Gault equation, on the other hand, is CKD stages 1 or 2, and those who were of a race other
dependent only on weight and SCr (Table 1). than white or African American.
One of the major responsibilities of pharmacists in- Estimation of GFR was performed using the CKD -EPI
volves making drug dosing adjustments based on estima- equations and MDRD equations normalized to body sur-
tions of renal clearance of medications. Therefore, it is in- face area (BSA) in order to determine the patient-specific
creasingly important that an equation that accurately esti- GFR in milliliters/minute.8 The Cockcroft-Gault estima-
mates this clearance is utilized when providing the most tion of renal function was used as the comparator equation,
optimal drug dosing recommendations. While both the in which the lower of actual or ideal body weight (IBW)
CKD -EPI and MDRD equations appear to more accurate- was used. For patients whose actual body weight exceeded
ly estimate GFR than does the Cockcroft-Gault equation, their IBW by greater than 30%, an adjusted weight was
they have not been validated for the purposes of making used in the calculation. Adjusted body weight was deter-
drug dosage adjustments. Numerous research studies have mined by the equation [(actual body weight – IBW) ≥ 0.4]
indicated that significant differences exist when comparing
+ IBW. Dosing discordance rates between the Cockcroft-
Cockcroft-Gault and MDRD equations for estimating re-
Gault and CKD -EPI equations were determined based on
nal function for the purposes of making dosage adjust-
the manufacturers’ renal dosing recommendations of 8
ments; however, this is the first study to compare the
common antimicrobials (Table 2).7,9 These antimicrobials
Cockcroft-Gault and CKD -EPI equations for this intent.6
were selected because the manufacturers’ recommenda-
tions for dosage adjustment in renal dysfunction were
Methods based on the Cockcroft-Gault equation.
The methods for this study have been previously de-
scribed.7 In short, this was an institutional review board–ap- STATISTICAL ANALYSIS
Data were compiled in Microsoft Access
(Microsoft Corp., Redmond, WA) and statisti-
cal testing was completed using SPSS soft-
Table 1. CKD-EPI Equations5
ware.10 Using the single proportion sample
Serum size measurement, a total of 247 patients were
Creatinine
Race and Sex (mg/dL) Equation needed to detect a 20% discordance rate with a
Black 95% confidence interval. Comparison of con-
female ≤0.7 GFR = 166 × (SCr/0.7)0.329 × (0.993)Age tinuous variables was performed by using
>0.7 GFR = 166 × (SCr/0.7)1.209 × (0.993)Age paired t-test and dichotomous variables were
male ≤0.9 GFR = 163 × (SCr/0.9)0.411 × (0.993)Age compared using the χ2 test, as appropriate.
>0.9 GFR = 163 × (SCr/0.9)1.209 × (0.993)Age Linear regression was incorporated to evaluate
White or other correlations between continuous variables, as
female ≤0.7 GFR = 144 × (SCr/0.7)0.329 × (0.993)Age appropriate. The Bland-Altman method was
>0.7 GFR = 144 × (SCr/0.7)1.209 × (0.993)Age used to assess agreement between the CKD -
male ≤0.9 GFR = 141 × (SCr/0.9)0.411 × (0.993)Age
EPI and Cockcroft-Gault estimations of renal
>0.9 GFR = 141 × (SCr/0.9)1.209 × (0.993)Age
function.11,12 χ2 Analysis was used to detect a
Single Equation GFR = 141 × min(SCr/k,1)α × max(SCr/k,1)–1.209 × 0.993Age
× [1.018 if female] × [1.159 if black], where α = –0.329 for difference in dosing discordance data. Level of
females and –0.411 for males; k = 0.7 for females and significance was set as p < 0.05. Data are pre-
0.9 for males; max = maximum of SCr/k or 1; and min =
minimum of SCr/k or 1.
sented as means (range) for continuous vari-
ables and as a number for dichotomous vari-
CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; GFR = ables, and 95% confidence intervals are report-
glomerular filtration rate; SCr = serum creatinine.
ed as appropriate.
440 I The Annals of Pharmacotherapy I 2010 March, Volume 44 theannals.com
3. Evaluation of Equation for Dosing Antimicrobials
Results equation was 39.9 ± 13 mL/min (Table 4). The absolute
mean difference between the 2 estimations was 5.10 ± 3.61
A total of 409 patients were eligible for evaluation in mL/min (95% CI 4.60 to 5.59; p < 0.001). Compared with
this analysis, as previously described.7 The mean ± SD age our previous data, the absolute mean difference in GFR,
of the cohort was 73.4 ± 12.5 years (Table 3). Patients using the MDRD and CKD -EPI equations, was 0.3 ± 0.22
were evenly distributed based on their sex, with the excep- mL/min (95% CI –0.14 to 0.76; p = 0.180).
tion of SCr, which was higher in males than in females (p A correlation coefficient was determined for the rela-
< 0.01). There was a preponderance of whites (81%) in the tionship of between calculated GFR using the CKD -EPI
cohort studied. Mean weight was 80 ± 23 kg, BSA was and Cockcroft-Gault equations among the patients evaluat-
1.90 ± 0.26 m2, BUN was 35 ± 16 mg/dL, SCr was 1.75 ± ed. Excellent correlation existed among all patients (r =
0.5 mg/dL. Among the cohort of patients sampled, 46% 0.91); however, the line of unity demonstrated that CKD -
weighed within 30% of their IBW, 36% exceeded their EPI estimations were consistently higher than Cockcroft-
IBW by greater than 30%, and another 18% weighed less Gault estimations of GFR (Figure 1). When comparing the
than their IBW. 2 estimates of GFR using the method described by Bland-
When estimating renal function, the average CrCl, using Altman, the difference in values was plotted against the
the Cockcroft-Gault equation, for all patients was 34.8 ± mean for the 2 methods in order to determine the variabili-
12 mL/min, whereas the average GFR using the CKD -EPI ty between them.10,11 The limits of agreement were 15.3
and –5.1; thus the CKD -EPI estimation may be 15.3
mL/min above or 5.1 mL/min below the Cockcroft-Gault
estimation for 95% of the cases (Figure 2). For the upper
Table 2. Manufacturer-Recommended Renal Dosing for limit of agreement, the confidence interval was 14.4 to
Selected Antimicrobials7,9 16.2 mL/min and for the lower limit, the confidence inter-
FDA-Recommended val was –6.0 to – 4.7 mL/min.
Antimicrobial CrCl (mL/min) to Adjust Dosage Antimicrobial dosage discordance rates were calculated
Cefazolin 10–30 to evaluate the difference between the estimations of renal
<10 function (Figure 3). It was determined that an overall dis-
Cefepime 30–60
11–29
cordant rate of 15–25% existed between the recommended
<11 dosing adjustments of the selected antimicrobials when
Daptomycin <30 comparing the Cockcroft-Gault and CKD -EPI estima-
Levofloxacin 20–49 tions. This discordant rate was lower than in our previous
10–19
study comparing the Cockcroft-Gault and MDRD estima-
Meropenem 26–50
10–25 tions, which found a difference of 20–36%.7 When com-
<10 paring the CKD -EPI and MDRD estimations, a 7–12%
Piperacillin/tazobactam 20–40 discordant rate was present. For the comparison of Cock-
<20
croft-Gault and CKD -EPI estimations, the majority
Trimethoprim/sulfamethoxazole 15–30
(88–96%) of discordance occurred when the manufacturer
CrCl = creatinine clearance; FDA = Food and Drug Administration. recommended a dosage adjustment; however, the dosage
adjustment was deemed unnecessary, accord-
ing to estimation by the CKD -EPI equation.
Table 3. Demographics7
Discussion
Female Male
Parameter (n = 208) (n = 201)
One well-recognized component of clinical
Age, y, mean (range) 75 (31–102) 72 (33–94) pharmacy involves renal dose adjustment of
African American, n 45 33 pharmacotherapy, when deemed appropriate.
SCr, mg/dL (mean ± SD) 1.66 ± 0.43 1.85 ± 0.55a The Pharmacy and Therapeutics committee at
BUN, mg/dL (mean ± SD) 34.6 ± 16.6 35.4 ± 15.2
our institution has approved the right of clini-
Actual weight, kg, mean (range) 77 (32–160) 83 (44–177)
cal pharmacists to dose-adjust medications
Ideal weight, kg, mean (range) 55 (43–84) 73 (55–94)
based on FDA-approved manufacturer recom-
Height, inches, mean (range) 64 (50–75) 70 (63–79)
Actual weight >130% of ideal weight, n 104 41a
mendations. This dosing modification may be
Actual weight <ideal weight, n 26 46a
done by pharmacists without prior approval
from the physician. Therefore, having an accu-
BUN = blood urea nitrogen; SCr = serum creatinine. rate estimation of renal function is of the ut-
a
p < 0.05.
most importance and has much clinical rele-
theannals.com The Annals of Pharmacotherapy I 2010 March, Volume 44 I 441
4. KA Wargo and TM English
vance. Ideally, clinical data such as urine output, nutrition- age adjustments to be statistically greater with the MDRD
al status, trends in SCr, and severity of illness would play a equation compared with the Cockcroft-Gault equation us-
more significant role in the decision by clinical pharma- ing actual body weight and the Cockcroft-Gault equation
cists to adjust doses as needed for renal function than the using IBW (88%, 85%, 82%; p < 0.001). The results of
estimates provided by equations. In reality, though, the use this large-scale study further validate the authors’ original
of equations to estimate renal function play a bigger role in 1999 findings that the MDRD equation is more accurate
this decision. Therefore, there is a strong need for estima- than Cockcroft-Gault estimations.2 Further, the authors
tions of renal function to be as accurate as possible and in suggest that, when the MDRD equation is normalized to
accordance with the method used by pharmaceutical com- BSA, it may be used for the purposes of drug dosing. Un-
panies in the development of renal dosing guidelines. fortunately, because of current FDA mandates, it is unrea-
In order to facilitate this process, and in accordance with sonable for the pharmaceutical industry to review all of
the Levey and colleagues2 data that demonstrated that their dosage recommendations based on the more accurate
MDRD estimations were more accurate than Cockcroft- MDRD, and now CKD -EPI equations. Further, with an
Gault estimations, our institution reports the 4-variable absolute difference in concordance of 3% between the
MDRD GFR in the routine chemistry panel of all patients. MDRD and Cockcroft-Gault estimation, it can be argued
However, there is a lack of literature to date that has evalu- that clinical significance does not differ between the 2.
ated the clinical utility of the MDRD or CKD -EPI equa- Therefore, continued use of the Cockcroft-Gault estima-
tions for making dosage adjustments of renally eliminated tion of renal function is rational.
medications. Further, considering that the FDA continues The findings of the present analysis demonstrate the ex-
to require that the pharmaceutical industry make dosage istence of a statistically significant difference when com-
adjustment recommendations based on the Cockcroft- paring the CKD -EPI and Cockcroft-Gault estimations of
Gault equation, it makes it difficult to advocate the use of renal function. Even though a strong correlation existed
MDRD or CKD -EPI. Finally, no equation gives an accu- when evaluating our entire cohort of patients, the Bland-
rate estimate of renal function in patients with fluctuating Altman method for assessing agreement demonstrated a
SCr concentrations; therefore, decisions to dose-adjust wide variation between the 2 estimations. Interestingly,
medications should not be made based on the results of a this variation was smaller than in our previous study com-
calculation of GFR at 1 moment in time. paring the Cockcroft-Gault and MDRD equations, 20.6
The existing literature comparing Cockcroft-Gault and and –9.8, though estimation of GFR was still higher with
MDRD estimations of kidney function demonstrates a sig- both of these equations compared with the Cockcroft-
nificant discordance between the 2 estimations.5 Since our Gault estimation.7 Additionally, based on the method cho-
original comparison, published in 2005, others have veri- sen to estimate GFR, antimicrobials in this analysis would
fied the discordance that exists between the 2 estima- still have been dosed differently 15–25% of the time, albeit
tions.5,13,14 In 2009, Levey and colleagues attempted to re- lower than our previous results comparing the MDRD and
solve the question of discordance between the MDRD and Cockcroft-Gault equations (20 –36%).7 These data imply
Cockcroft-Gault estimations by comparing their estima- that the CKD -EPI estimation is closer to the Cockcroft-
tions with a directly measured GFR (using iothalamate Gault estimation of renal function than is the MDRD.
clearance) in over 5500 patients.5 In their study, they found However, the possibility of clinically important differences
concordance rates with manufacturer-recommended dos- between the Cockcroft-Gault and CKD -EPI equations ex-
Table 4. Mean Difference in Cockcroft-Gault, CKD-EPI, and MDRD Equationsa,7
Cockcroft-Gault CKD-EPI GFR MDRD
GFR (mL/min), (mL/min), (mL/min),
Characteristic Mean ± SD Mean ± SD Mean ± SD p Valueb
Overall (n = 409) 34.8 ± 12.0 39.9 ± 12.5 40.2 ± 12.2 <0.001
Female (n = 208) 30.3 ± 10.9 34.5 ± 10.6 34.9 ± 10.3 <0.001
Male (n = 201) 39.5 ± 11.3 45.5 ± 11.9 45.7 ± 11.5 <0.001
White (n = 331) 35.4 ± 12.0 39.8 ± 12.4 40.0 ± 12.0 <0.001
African American (n = 78) 32.3 ± 11.7 40.2 ± 13.2 40.8 ± 13.1 <0.001
CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; GFR = glomerular filtration rate; MDRD = Modification of Diet in Renal Disease.
a
Based on demographics.
b
Statistical significance existed when comparing Cockcroft-Gault with both the CKD-EPI and the MDRD equations; no significant differences were
observed when comparing CKD-EPI and MDRD.
442 I The Annals of Pharmacotherapy I 2010 March, Volume 44 theannals.com
5. Evaluation of Equation for Dosing Antimicrobials
ist and merit further consideration, considering that 1 in 4 when the CKD -EPI estimation was used, leading to the
patients would have received a different dose of medica- potential for adverse reactions such as seizures, arrhyth-
tion based on equation selected. mias, renal failure, gastrointestinal symptoms, and neuro-
As stated previously, the majority of discordance existed muscular hypersensitivity. Although the potential for such
when the manufacturer recommended a dosage adjustment adverse reactions is quite low and may not bear clinical
according to the Cockcroft-Gault estimation, yet that par- significance, the variation between the 2 estimations was
ticular level of dosage adjustment was unnecessary accord- so great (15.3 to –5.1 mL/min), a clinically significant dif-
ing to GFR estimation by the CKD -EPI equation. Accord- ference may be implied. However, without actually admin-
ing to this rationale, in patients with discordant dosage rec- istering antimicrobials to the patients, directly measuring
ommendations, 88–96% would have been overdosed GFR, comparing that measurement to our estimations, and
Figure 1. Comparison of CKD-EPI and Cockcroft-Gault estimations of renal function for the study population using correlation (N = 409). The line of
unity demonstrates that CKD-EPI estimations of GFR are consistently higher than Cockcroft-Gault estimations in our population. CG = Cockcroft-Gault;
CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; GFR = glomerular filtration rate.
Figure 2. Comparison of CKD-EPI and Cockcroft-Gault estimations of renal function for the study population using Bland-Altman plot (N = 409). The
limits of agreement demonstrate that CKD-EPI estimations of GFR are 15.3 mL/min above to 5.1 mL/min below Cockcroft-Gault estimations in 95% of
cases. CG = Cockcroft-Gault; CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; GFR = glomerular filtration rate.
theannals.com The Annals of Pharmacotherapy I 2010 March, Volume 44 I 443
6. KA Wargo and TM English
assessing outcomes, clinical significance can only be im- analysis and the Levey and colleagues study.5 Of note, the
plied from this analysis. cohort of patients in the CKD -EPI study exhibited a mean
Interestingly, the discordance between MDRD and age of 47 ± 15 (internal validation set) and 50 ± 15 years
CKD -EPI dosing recommendations was quite small, rang- (external validation set), whereas our analysis consisted of
ing from 7% to 17%, indicating that little difference would a significantly older population, mean of 73.4 ± 12.5 years.
exist when making dosing recommendations based on ei- However, results from a study by Cirillo and colleagues
ther the CKD -EPI or MDRD equations. This, however, is suggests this difference may not be significant, as they
not entirely surprising given the data presented in the Lev- found the MDRD equation to be a more accurate predictor
ey and colleagues study,5 as well as the data from this of GFR than the Cockcroft-Gault equation in older pa-
study compared with our previous study.7 tients.16
This analysis contains various limitations, based on a A final limitation of this analysis lies within our method
series of assumptions. Measurement of actual GFR was of selecting patients. While we were able to recruit more than
not conducted on patients. Instead, we relied on the data a sufficient number of patients to power this analysis, we did
presented in the Levey and colleagues CKD -EPI study not include patients with SCr less than 1.3 mg/dL with sub-
to establish that GFR can be accurately estimated, using stantially decreased renal function or patients with SCr
their equation.5 Thus, the major limitation of this analy- greater than 3 mg/dL yet not on dialysis. Therefore, all of the
sis is associated with the comparison of 2 estimated val- possible patients with stages 3–5 CKD were not captured.
ues. Furthermore, drug concentration monitoring was Taking into consideration the data from the present
not performed during this analysis due to a lack of re- study, along with previously reported information, we
sources. agree with the comments by Stevens and colleagues when
Because the CKD -EPI equation was chosen as the com- they stated, “It is time to move beyond the focus on differ-
parator estimator of renal function, it becomes important to ences among equations and towards a focus on using the
control for patient demographic differences between this most accurate clinical data to improve the care of our pa-
Figure 3. Antimicrobial dosage discordance rate when comparing the MDRD and CKD-EPI estimations of GFR with the manufacturer-recommended
dosage adjustment using the Cockcroft-Gault estimation.7 CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; GFR = glomerular filtra-
tion rate; MDRD = Modification of Diet in Renal Disease; Pip/Tazo = piperacillin/tazobactam; Trim/Sulfa = trimethoprim/sulfamethoxazole.
Black bars = MDRD vs CKD-EPI.
White bars = Cockcroft-Gault vs CKD-EPI.
Dotted bars = Cockcroft-Gault vs MDRD.
444 I The Annals of Pharmacotherapy I 2010 March, Volume 44 theannals.com
7. Evaluation of Equation for Dosing Antimicrobials
tients.”17 The question should not be which equation we 13. Gill J, Malyuk R, Djurdjev O, Levin A. Use of GFR equations to adjust
drug doses in an elderly multi-ethnic group—a cautionary tale. Nephrol
use to dose-adjust antimicrobials but rather, “Is this the
Dial Transplant 2007;22:2894-9. DOI 10.1093/ndt/gfm289
only tool we need to use?”18 In our opinion, assessment of 14. Golik MV, Lawrence KR. Comparison of dosing recommendations for
clinical information of our patients should be the lone fac- antimicrobial drugs based on two methods for assessing kidney function:
tor when deciding to dose-adjust medications. Cockcroft-Gault and Modification of Diet in Renal Disease. Pharma-
cotherapy 2008;28:1125-32. DOI 10.1592/phco.28.9.1125
Results from previous studies have raised questions in 15. Stevens LA, Nolin TD, Richardson MM, et al. Comparison of drug dos-
the minds of clinicians as to whether the MDRD equation, ing recommendations based on measured GFR and kidney function esti-
and now the CKD -EPI equation, should be the preferred mating equations. Am J Kidney Dis 2009;54:33- 42.
DOI 10.1053/j.ajkd.2009.03.008
method to estimate renal function, in order to make critical
16. Cirillo M, Anastasio P, De Santo NG. Relationship of gender, age, and
decisions about medication dosing. Though the results of body mass index to errors in predicted kidney function. Nephrol Dial
this study show that the CKD -EPI equation is closer than Transplant 2005;20:1791-8. DOI 10.1093/ndt/gfh962
the MDRD equation to the Cockcroft-Gault estimations, 17. Stevens LA, Nolin T, Levey AS. In reply to ‘Estimated GFR for drug
dosing: a bedside formula,’ ‘Drug dose adjustments in patients with re-
statistically and potentially clinically significant differ- nal impairment,’ ‘Use of the MDRD study equation for drug dosing,’
ences still exist. It is our opinion that differences between and ‘Estimated GFR vs creatinine clearance for drug dosing.’ Am J Kid-
estimations of renal function will always exist and, ulti- ney Dis 2009;54:985-6. DOI 10.1053/j.ajkd.2009.08.017
mately, when faced with the decision to adjust dosages, 18. Wargo KA. Clinical judgment: to dose adjust antimicrobials or not. Phar-
macotherapy 2008;28:281e-3e.
clinical judgment should prevail.
Kurt A Wargo PharmD BCPS, Associate Clinical Professor, Harri-
son School of Pharmacy, Auburn University, Auburn, AL
Evaluación de la Ecuación del Chronic Kidney Disease
Thomas M English PhD, University of Alabama at Birmingham;
Huntsville Regional Medical Campus, Huntsville, AL Epidemiology Collaboration para Ajustes en Dosis de Agentes
Reprints: Dr. Wargo, 301 Governors Dr. SW, Suite 385C1, Antimicrobiales
Huntsville, AL, fax 256/551-4567, wargoka@auburn.edu. KA Wargo y TM English
Financial disclosure: None reported Ann Pharmacother 2010;44:439- 46.
References EXTRACTO
TRASFONDO: Estudios realizados han determinado que la ecuación
1. Slikensen JR, Kasiske BL. Laboratory assessment of kidney disease:
derivada del estudio de Modificación de Dieta en la Enfermedad Renal
clearance, urinalysis, and kidney biopsy. In: Brenner BM, Levine SA,
(MDRD) para estimar la tasa de filtración glomerular (GFR) no puede
eds. Brenner & Rector’s: the kidney. 7th ed. Philadelphia, PA: WB Saun- ser utilizada para realizar ajustes en dosis en pacientes renales. En el año
ders, 2004:1107-19. 2009, el Chronic Kidney Disease Epidemiology Collaboration (CKD -
2. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more ac- EPI) derivó una ecuación más precisa que la ecuación MDRD para
curate method to estimate glomerular filtration rate from serum creati- estimar la GFR. No está claro cuál método debe utilizarse para realizar
nine: a new prediction equation. Modification of Diet in Renal Disease ajustes en dosis de agentes antimicrobiales que son eliminados renalmente.
Study Group. Ann Intern Med 1999;130:461-70. OBJETIVO: Determinar si existe diferencia al realizar ajustes en dosis de
3. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum agentes antimicrobiales en pacientes con enfermedad crónica del riñón
creatinine. Nephron 1976;16:31- 41. (CKD) cuando se estima la GFR utilizando las ecuaciones CKD -EPI y
4. Food and Drug Administration. Guidance for industry: pharmacokinetics Cockroft-Gault (CG)
in patients with impaired renal function—study design, data analysis, MÉTODOS: Se realizó un análisis de observación de 409 pacientes con
and impact on dosing and labeling. Rockville, MD: US Department of CKD admitidos a una facilidad de cuidado terciario. Se estimó la GFR
Health and Human Services, May 1998. utilizando la ecuación de CKD -EPI y se comparó con el estimado de
5. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate GFR calculado con la ecuación de CG utilizando análisis de correlación
glomerular filtration rate. Ann Intern Med 2009;150:604-12. y el método Bland-Altman. Se determinó la diferencia en dosis de los
agentes antimicrobiales seleccionados al utilizar los valores de GFR
6. Greenberg E, Saad N, Abraham T, Balmir E. Drug dosage adjustment
calculados.
using renal estimation equations: a review of the literature. Hosp Pharm
RESULTADOS: La GFR promedio de los pacientes se calculó en 34.8 ± 12
2009;44:577-83.
mL/min al utilizar la ecuación CG y 39.9 ± 13 mL/min al utilizar la
7. Wargo KA, Eiland EH III, Hamm W, English TM, Phillippe HM. Com-
ecuación CKD -EPI (5.09; 95% CI 4.60 y 5.59, p < 0.001). El coeficiente
parison of the Modification of Diet in Renal Disease and Cockcroft- de correlación entre ambos estimados fue alto (r = 0.91). Los límites de
Gault equations for antimicrobial dosage adjustments. Ann Pharma- concordancia en la gráfica Bland-Altman fueron 15.3 y –5.1. El estimado
cother 2006;40:1248-53. DOI 10.1345/aph.1G635 de GFR calculado con la ecuación de CKD -EPI pudiera estar entre 5.1
8. DuBois D, DuBois E. A formula to estimate the approximate surface mL/min por debajo y 15.3 mL/min por encima del estimado con la
area if height and weight be known. Arch Intern Med 1916;17:863-71. ecuación CG en el 95% de los casos. Se observó una diferencia de 15 a
9. Lacy CF, Armstrong LL, Goldman MP, Lance LL. Drug information 25% en los ajustes de dosis recomendados de los agentes antimicrobiales.
handbook. 13th ed. Hudson, OH: Lexi-Comp, Inc., 2005. CONCLUSIONES: Este estudio demostró diferencias significativas en los
10. SPSS for Windows, Rel. 15.0.0., 2006. Chicago, IL: SPSS Inc. ajustes en dosis de agentes antimicrobiales al utilizar las ecuaciones
11. Bland JM, Altman DG. Statistical methods for assessing agreement be- CKD -EPI y CG. Se desconoce el significado clínico de estas diferencias
tween two methods of clinical measurement. Lancet 1986;1:307-10. ante la ausencia de datos que evalúen los resultados clínicos asociados
con la diferencia de las dosis calculadas. Se debe utilizar el juicio clínico
12. Bland JM, Altman DG. Applying the right statistics: analyses of mea-
al hacer ajustes en dosis de agentes antimicrobiales.
surement studies. Ultrasound Obstet Gynecol 2003;22:85-93.
DOI 10.1002/uog.122 Traducido por Astrid J García-Ortiz
theannals.com The Annals of Pharmacotherapy I 2010 March, Volume 44 I 445
8. KA Wargo and TM English
L’Evaluation d’Une Nouvelle Equation pour Estimer le Taux de hospitalier de soins tertiaires. Le TFG était calculé par les 2 équations à
Filtration Glomérulaire en Présence d’Insuffisance Rénale l’étude et les résultats évalués par des analyses de corrélation et une
analyse comparative de Bland-Altman. Le taux de discordance des
KA Wargo et TM English recommandations des ajustements posologiques dérivés de ces différents
Ann Pharmacother 2010;44:439- 46. estimés du TFG était finalement déterminé.
RÉSULTATS: Les valeurs moyennes de TFG étaient de 34.8 ± 12 mL/min
et de 39.9 ± 13 mL/min pour les formules CG et CKD -EPI, respective-
RÉSUMÉ ment (différence moyenne absolue 5.1; intervalle de confiance de 95%
INTRODUCTION: Plusieurs recherches démontrent que l’équation MDRD 4.6 – 5.59, p < 0.001). Une très bonne corrélation entre les 2 estimés a
(modification de la diète en présence de maladie rénale-Modification of été notée (r = 0.91). Selon les limites d’entente déterminées par l’analyse de
Diet in Renal Disease) pour évaluer le taux de filtration glomérulaire Bland-Altman, les estimés du TFG obtenus avec la formule CKD -EPI
(TFG) ne peut être utilisée pour guider les ajustements posologiques de pouvaient être, dans 95% des cas, inférieurs de 5.1 mL/min et supérieurs
différents médicaments. En 2009, le groupe d’épidémiologie sur de 15.3 mL/min par rapport aux valeurs obtenues par l’équation CG. Un
l’insuffisance rénale chronique (CKD -EPI) a proposé une méthode plus taux de discordance pouvait varier entre 15 et 25% au niveau des
précise que l’équation MDRD pour l’estimation du TFG. Ce nouvel différentes recommandations d’ajustements posologiques basées sur les
outil n’a toutefois pas été évalué dans un contexte d’estimation de la estimations de la fonction rénale à l’étude.
fonction rénale et de recommandation pharmacothérapeutique. CONCLUSIONS: Cette étude a démontré une différence statistiquement
OBJECTIF: L’objectif de cette étude est de déterminer s’il existe une significative entre les estimés du TFG obtenus par la formule CG et
différence entre les recommandations d’ajustements posologiques des l’équation CKD -EPI. La significative clinique d’une telle différence
antibiotiques en présence d’insuffisance rénale, lorsque ces demeure toutefois à être précisée. Un jugement clinique est donc nécessaire
recommandations sont basées sur l’estimation du TFG dérivé de la lors d’ajustements posologiques d’antimicrobiens pour un patient chez
formule Cockcroft-Gault (CG) et de l’équation CKD -EPI. qui l’estimation de la fonction rénale se fait par différentes méthodes.
MÉTHODOLOGIE: Il s’agit d’une étude rétrospective ayant évalué le Traduit par Sylvie Robert
dossier de 409 patients insuffisants rénaux admis dans un centre
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