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Excess Anion Gap

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41. Evotaz - atazanavir / cobicistat

abnormality MAA Marketing Authorization Application NMR Nuclear Magnetic Resonance P-gp P-glycoprotein PI protease inhibitor PK pharmacokinetic(s) Ph. Eur. European Pharmacopoeia OATP organic anion transporting polypeptide QD once daily RNA ribonucleic acid RTV ritonavir SAE serious adverse event SCE Summary of Clinical Efficacy SCS Summary of Clinical Safety SD standard deviation SmPC Summary of Product Characteristics TDF tenofovir TVD Truvada UGT UDP glucuronosyltransferase 1 ULN upper limit of normal

2015 European Medicines Agency - EPARs

42. Ebymect - dapagliflozin / metformin

associated with hypoxia. Diagnosis The risk of lactic acidosis must be considered in the event of non-specific signs such as muscle cramps with digestive disorders, abdominal pain and severe asthenia. Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain and hypothermia followed by coma. Diagnostic laboratory findings are decreased blood pH, plasma lactate levels above 5 mmol/L, and an increased anion gap and lactate/pyruvate ratio. If metabolic acidosis is suspected, treatment (...) of prompt treatment), metabolic complication that can occur due to accumulation of metformin, a component of this medical product. Reported cases of lactic acidosis in patients on metformin have occurred primarily in diabetic patients with significant renal failure. The incidence of lactic acidosis can and should be reduced by also assessing other associated risk factors such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any conditions

2015 European Medicines Agency - EPARs

43. Ravicti - glycerol phenylbutyrate

in the diet, removal of excess ammonia via waste nitrogen scavenging drugs (e.g., NaPBA) and replacement of certain urea cycle intermediates (Table 2 below). Only a minority of UCD patients are diagnosed based on newborn screening (i.e., argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL) and arginase (ARG) deficiency subtypes), and most UCD patients are therefore diagnosed after presenting with symptoms of hyperammonaemia. Because even severe (e.g., seizures, cerebral oedema (...) the pharmacological nature of GPB and its metabolites this is acceptable. Safety pharmacology programme A range of GLP safety pharmacology studies has been performed with GPB using both in vitro and in vivo models. The organ systems evaluated include the CNS, cardiovascular system and respiratory system (Table 2.3.1). Cardiovascular system: An in vitro hERG study was completed using concentrations of PBA (pro-drug) and PAA (active constituent) well in excess of peak plasma exposures observed in clinical studies

2015 European Medicines Agency - EPARs

44. Lynparza - olaparib

Next generation sequencing NHEJ Non-homologous end joining OATP Organic anion-transporting protein OCT Organic cation-transporter ORR Objective response rate OS Overall survival PARP Polyadenosine 5’diphosphoribose polymerase PBMC Peripheral blood mononuclear cells PCR Polymerase chain reaction PD Pharmacodynamic PFS Progression-free survival PFS2 Time from start of randomisation to second progression or death PK Pharmacokinetics PLD Pegylated liposomal doxorubicin PR Partial response PSR Platinum (...) . The discriminatory power of the dissolution method has been investigated. The proposed dissolution method for routine quality control has shown to be discriminant for active substance particle size and for drug loading. However, the method is not sensitive enough to discriminate the different polymorphic forms. Nevertheless, the overall control strategy was considered appropriate to compensate for this gap, a specific NIR method being in place for the monitoring of the polymorphic form in routine. The primary

2015 European Medicines Agency - EPARs

45. Acid-base assessment of post-parturient German Holstein dairy cows from jugular venous blood and urine: A comparison of the strong ion approach and traditional blood gas analysis. Full Text available with Trip Pro

. For this, we sampled blood from the jugular vein and urine from 145 German Holstein cows within 1 to 76 days post-partum. In blood, the metabolic parameters non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHB), as well as numerous parameters of the acid-base status were measured. The traditional approach, based on bicarbonate concentration, base excess (BE) and anion gap (AG), was compared to the strong ion approach variables, e.g. acid total (Atot), measured strong ion difference (SIDm), strong (...) ion gap (SIG), and unmeasured anions (XA), respectively. Results of both approaches were set against the outcome of urine analysis, i.e. the NABE, base-acid ratio and pH of urine, in a cluster analysis, which provided 7 moderately stable clusters. Evaluating and interpreting these 7 clusters offered novel insights into the pathophysiology of the acid-base equilibrium in fresh post-partum dairy cows. Especially in case of subclinical acid-base disorders, the parameters of the strong ion difference

2019 PLoS ONE

46. Point-of-care blood tests during home visits by out-of-hours primary care clinicians; a mixed methods evaluation of a service improvement. Full Text available with Trip Pro

were obtained for patient interviews.Out-of-hours primary care.All patients requiring home visits from the service during the implementation period.The i-STAT POC blood test platform was introduced to two bases providing home visits for a period of 8 months. Venous blood samples were used and two cartridges were available. The CHEM8 cartridge measures sodium, potassium, chloride, total carbon dioxide (TCO2), anion gap, ionised calcium, glucose, urea, creatinine, haematocrit and haemoglobin. The CG4 (...) cartridge measures lactate, pH, PaO2 and PCO2, TCO2, bicarbonate, base excess and oxygen saturation.The proportion of home visits where tests were taken, the clinical contexts of those tests, the extent to which clinicians felt the tests had influenced their decisions, time taken to perform the test and problems encountered. Clinician and patient experiences of using POC tests.i-STAT POC tests were infrequently used, with successful tests taken at just 47 contacts over 8 months of implementation

2020 BMJ open

47. Review article: Ketoacidosis in the emergency department. (Abstract)

after initial resolution. Checkpoint inhibitors may present with fulminant diabetic ketoacidosis in individuals with previously normal glucose tolerance. Ketoacidosis may also occur as a result of starvation and alcohol excess, as well as a number of rare causes. Other causes of metabolic acidosis with both high and normal anion gap need to be considered in the differential diagnosis of ketoacidosis. Diabetic ketoacidosis may also present with biochemical changes suggestive of myocardial ischaemia

2020 Emergency medicine Australasia

48. ABCD position statement on the risk of diabetic ketoacidosis with the use of sodium-glucose cotransporter-2 inhibitors

are usually higher than 11 mmol/L but can be lower and, therefore, in a person known to have diabetes the diagnosis of diabetic ketoacidosis should always be considered even if blood glucose levels are normal. 38 This is particularly relevant in patients taking SGLT-2 inhibitors. Diagnosis of DKA in patients taking SGLT-2 inhibitors 2,37 Arterial pH Less than 7.3 Blood ketones Above 3 mmol/L Anion gap Above 10 Bicarbonate Less than 15 mmol/L Clinical Deteriorating level of consciousness in severe cases (...) Further management Once DKA is confirmed, ABCD advises to stop the SGLT-2 inhibitor immediately and treat ketoacidosis with existing Trust or JBDS protocol. 37 The focus of treatment is to correct pH, bicarbonate and the anion gap. A variable rate intravenous insulin infusion (VRIII) with dextrose and Date of preparation 18.11.2016 potassium rather than a fixed rate insulin infusion may be needed to avoid hypoglycaemia and hypokalaemia. Despite stopping an SGLT-2 inhibitor the associated increase

2016 Association of British Clinical Diabetologists

49. Mitochondrial Function, Biology, and Role in Disease Full Text available with Trip Pro

disruption of frataxin, cyclophilin D, and components of the ETC result in either basal or excessive pressure-overload–induced cardiac dysfunction and are associated with reduced NAD + -NADH ratio and increased mitochondrial protein acetylation. , , In primary cardiomyocytes, frataxin and complex I disruption of the acetylome are corrected in parallel with improvement in mitochondrial function after Sirt3 induction. , Although incompletely characterized, these data support the concept that control (...) to the acetylation of specific targets within a pathway compared with the global functioning of the canonical pathway in response to acetylation. This is most vividly illustrated where FAO is increased in the presence of excess fat and mitochondrial protein acetylation, , in contrast to studies that have shown direct deacetylation of lysine residues on FAO enzymes resulting in activation of enzyme activity. , The mechanisms underpinning these effects and whether this might be a result of tissue-distinct

2016 American Heart Association

50. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection

NMA network meta-analysis OAT organic anion transporter OR odds ratio ORF open reading frame PCR polymerase chain reaction PEG-IFN pegylated interferon PI protease inhibitor PICO population, intervention, comparison, outcomes PICOT population, intervention, comparison, outcomes, time PWID people who inject drugs RNA ribonucleic acid RCT randomized controlled trial RR relative risk RUP reuse prevention SAGE (WHO) Strategic Advisory Group of Experts SIGN Safe Injection Global Network SIP sharp (...) , oesophageal varices and bleeding, hepatic encephalopathy, sepsis and renal failure Hepatocellular carcinoma (HCC) Primary cancer of the liver arising in hepatocytes NATURAL HISTORY OF HBV INFECTIONxvi Hepatitis B surface antigen (HBsAg) HBV envelope protein and excess coat particles detectable in the blood in acute and chronic hepatitis B infection Hepatitis B core antigen (HBcAg) HBV core protein. The core protein is coated with HBsAg and therefore not found free in serum Hepatitis B e antigen (HBeAg

2015 World Health Organisation Guidelines

52. Trulicity - dulaglutide

-go-related gene HILIC Hydrophilic Interaction liquid chromatography HPAEC High pH Anion-Exchange Chromatography HR Hazard ratio HR Heart rate i.v. Intravenous ICH International conference on harmonization IDF International Diabetes Federation IFU Instructions for use IgG Immunoglobulin IgG4 Immunoglobulin G4 INR max Maximum international normalized ratio response IPC In-Process Control IPS In-Process Specification ITT Intent to treat IVGTT Intravenous glucose tolerance test K i affinity constant

2014 European Medicines Agency - EPARs

54. Management of Substance Use Disorder

. Alcohol Use Disorder Stabilization and Withdrawal 58 c. Opioid Use Disorder Stabilization and Withdrawal 60 d. Sedative Hypnotic Use Disorder Stabilization and Withdrawal 62 VII. Knowledge Gaps and Recommended Research 63 A. Determination of Treatment Setting 63 B. Pharmacotherapy 63 a. Opioid Use Disorder 63 b. Stimulant Use Disorder 63 C. Psychosocial Interventions 64 a. Substance Use Disorders 64 b. Opioid Use Disorder 64 D. Follow-up 64 E. Stabilization and Withdrawal 64 F. Telehealth 64 Appendix (...) % of Americans over age 18 have a non-tobacco SUD, and about one in every four Americans will develop a non-tobacco SUD over the course of a lifetime.[3,4] According to the Centers for Disease Control and Prevention (CDC), excessive alcohol use costs the United States (U.S.) over $223.5 billion annually.[5] According to the U.S. Department of Justice, the estimated cost of illicit drug use in the U.S. was more than $193 billion (in 2007).[6] This reflects direct and indirect public costs related to crime

2015 VA/DoD Clinical Practice Guidelines

55. Treatment of Hypertension in Patients With Coronary Artery Disease Full Text available with Trip Pro

evidence, to develop recommendations that will be appropriate for both BP reduction and the management of CAD in its various manifestations. When data are meager or lacking, the writing group has proposed consensus recommendations and has highlighted opportunities for well-designed prospective clinical trials to fill knowledge gaps. All of the discussion and recommendations refer to adults. The writing committee has not addressed hypertension or IHD in the pediatric age group. In addition (...) Hg) accounted for nearly 60% of all excess IHD, overall cardiovascular disease (CVD), or all-cause mortality. Epidemiological data show that lower BP levels are associated with lower disease risks, suggesting that future coronary events can be prevented by reducing BP. Elevated BP represents a substantial population-attributable risk for men and women, both black and white. , 1.1.1. Effects of Treatment The risk of CVD in the patient with hypertension has been shown to be greatly reduced

2015 American Heart Association

57. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection

NMA network meta-analysis OAT organic anion transporter OR odds ratio ORF open reading frame PCR polymerase chain reaction PEG-IFN pegylated interferon PI protease inhibitor PICO population, intervention, comparison, outcomes PICOT population, intervention, comparison, outcomes, time PWID people who inject drugs RNA ribonucleic acid RCT randomized controlled trial RR relative risk RUP reuse prevention SAGE (WHO) Strategic Advisory Group of Experts SIGN Safe Injection Global Network SIP sharp (...) , oesophageal varices and bleeding, hepatic encephalopathy, sepsis and renal failure Hepatocellular carcinoma (HCC) Primary cancer of the liver arising in hepatocytes NATURAL HISTORY OF HBV INFECTIONxvi Hepatitis B surface antigen (HBsAg) HBV envelope protein and excess coat particles detectable in the blood in acute and chronic hepatitis B infection Hepatitis B core antigen (HBcAg) HBV core protein. The core protein is coated with HBsAg and therefore not found free in serum Hepatitis B e antigen (HBeAg

2015 World Health Organisation HIV Guidelines

58. Intravenous infusion of magnesium sulfate and its effect on horses with trigeminal-mediated headshaking. Full Text available with Trip Pro

+ , Mg2+ , total magnesium (tMg), glucose, and lactate were measured; strong ion difference (SID) and anion gap (AG) were calculated for each time point.Blood variables including pH, Na+ , Cl- , K+ , SID, AG, lactate, Ca2+ , tMg, and Mg2+ had significant changes with MSS as compared to DS treatment. Glucose, SBE, and HCO3- did not have significant changes. A 29% reduction in head-shaking rate occurred after MSS treatment but no change occurred after DS treatment.Administration of MSS IV increased (...) magnesium sulfate infusion.Six geldings with trigeminal-mediated headshaking.Prospective randomized crossover study. Horses were controlled for diet and infused IV with 5% dextrose solution (DS; control solution at 2 mL/kg body weight [BW]) and MgSO4 50% solution (MSS at 40 mg/kg BW). Head-shaking behavior was recorded at times T0 (baseline, before infusion) and T15, T30, T60, and T120 minutes post-infusion. Venous blood variables such as pH, HCO3- , standard base excess (SBE), Na+ , Cl- , K+ , Ca2

2019 Journal of Veterinary Internal Medicine

59. Diabetes, Pre-Diabetes and Cardiovascular Diseases

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3050 5.3 Risk engines developed for people with diabetes . . . . . .3050 5.4 Risk assessment based on biomarkers and imaging . . . . .3050 5.5 Gaps in knowledge . . . . . . . . . . . . . . . . . . . . . . . . .3050 5.6 Recommendations for cardiovascular risk assessment in diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3051 6. Prevention of cardiovascular disease in patients with diabetes .3051 6.1 Lifestyle (...) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3051 6.1.1. Diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3051 6.1.2. Physical activity . . . . . . . . . . . . . . . . . . . . . . . .3052 6.1.3. Smoking . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3052 6.1.4. Gaps in knowledge . . . . . . . . . . . . . . . . . . . . . .3052 6.1.5. Recommendations on life style modi?cations in diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3052 6.2 Glucose control

2013 European Society of Cardiology

60. A young man with back spasms

potassium. Despite that concern, this ECG is diagnostic of hypokalemia. Labs showed: Na 133 mmol/L K 2.6 mmol/L Cl 61 mmol/L Bicarbonate 60 mmol/L BUN 75 mg/dL Creatinine 7.75 mg/dL (baseline 2.5) Anion Gap 18 mmol/L Calcium 10.6 mg/dL Phos 3.0 mg/dL Mg 2.3 mg/dL ABG (hours later during admission) showed: pH 7.49 pCO2 66 mm Hg HCO3 49 mEq/L BE 25.5 mEq/L This shows a chronic metabolic alkalosis with respiratory compensation. These disorders are clearly not acute because the bicarb has had time (...) greater than the normal SID of 38 (resulting from normal values of Na = 140 and Cl = 102). An elevated SID is an independent variable causing alkalosis because there is a relative excess of positive strong ions compared to the normal milieu (relatively more Na+ than Cl-). As biologic physical processes are beholden to the principle of maintaining electrical neutrality, the body fills the relative void of negative ions with the single negative ion to which it has unlimited supply (dependent variable

2018 Dr Smith's ECG Blog

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