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Excess Anion Gap

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21. Primary postpartum haemorrhage

, ALP, GGT, LD, calcium, phosphate, magnesium, anion gap, osmolality, urea/creatinine ratio, globulin, albumin- corrected calcium, eGFR (patients over 18 years). Critical bleeding Major haemorrhage that is life threatening and likely to result in the need for massive transfusion. 1 Massive transfusion In adults, massive transfusion may be defined as a transfusion of half of one blood volume in four hours, or more than one blood volume in 24 hours (adult blood volume is approximately 70 mL/kg). 1 (...) · Fibrinogen concentrate or cryoprecipitae to maintain fibrinogen > 2.5 g/L · FFP 2 units MHP PACK 2 · RBC 4 units · Fibrinogen concentrate or cryoprecipitate to maintain fibrogen > 2.5 g/L · FFP 2 units · Platelets 1 adult dose · If ionised calcium 35° C · pH > 7.2 · Base excess minus 6 to positive 6 · Lactate 1.1 mmol/L · Platelets > 50 x 10 9 /L · PT/aPPT 2.5 g/L Optimise · Oxygenation · Cardiac output · Tissue perfusion · Temperature (actively warm woman and fluid) · Metabolic state Monitor (30?60

2019 Queensland Health

22. BSPED Interim Guideline for the Management of Children and Young People under the age of 18 years with Diabetic Ketoacidosis

. It needs differentiating from ongoing ketosis. For example: If following intravenous fluids the patient remains acidotic with Sodium = 142 and Chloride = 126 then the component of the apparent base excess attributable to the chloride is calculated as: Base excess due to Chloride = (Sodium – Chloride) – 32 = (142 - 126) – 32 = ( 16 ) – 32 = - 16 Anion gap = Sodium – (Chloride + Bicarbonate) Base excess due to Chloride = (Sodium – Chloride) – 32 (ISPAD formula) Albumin A low serum albumin can also (...) to monitor than corrected sodium and that management should aim to ensure that the effective osmolality remains stable during treatment of DKA. Please discuss with the consultant on call. Effective osmolality = 2 x Sodium + Glucose Corrected sodium (mmol/L) = measured sodium + (glucose – 5.6) 3.5 Anion gap If the clinical picture is not improving consideration should be given to calculating the anion gap The anion gap is typically 20-30 mmol/l in a patient with ketoacidosis. However an anion gap >35 mmol

2020 British Society for Paediatric Endocrinology and Diabetes

23. Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada

and healthcare outcomes of Canadians living with diabetes. A primary purpose is to address clinical care gaps that exist, i.e. discrepan- cies between evidence-based knowledge and day-to-day clinical practice.Theguidelinesalsosummarizekeyresearch?ndingsand makeclinicaldecisionsmoretransparent.Theyaremeanttoreduce inappropriatevariationinpractice,promotee?cientuseof health- careresources,empowerpeoplelivingwithdiabetes,identifygaps inknowledge,prioritizeresearchactivities,informpublicpolicy,and support

2018 Diabetes Canada

24. Trientine tetrahydrochloride (Cuprior) - Hepatolenticular Degeneration

mediates the binding of copper molecules to apoceruloplasmin in hepatocytes, forming ceruloplasmin, which can then safely transport the bound copper to its intended sites. In addition, the ATP7B protein serves to transport excess copper from hepatocytes into the bile for subsequent excretion, thus permitting safe elimination of excess copper. Such copper transport systems are required as, although copper is essential for cellular function, free copper is toxic and causes cell damage. Normal dietary (...) The dose is usually between 225 mg and 600 mg per day (1½ to 4 tablets) in 2 to 4 divided doses. Children aged controls, no effect of TETA Hayashi et al. 2005 **SSBs: single-strand breaks, LEC: Long-Evans Cinnamon, O 2 - -:superoxide anion The pharmacology studies sourced from published literature demonstrate proof of concept that TETA 4HCl can decrease copper levels in the liver and increase urinary excretion of copper in rats administered exogenous copper. Furthermore, in vivo models of WD in which

2017 European Medicines Agency - EPARs

25. Spotlight: A case of Metformin Associated Lactic Acidosis

in the presence of CKD, can produce an unusually high anion gap. Patients may also have marked leukocytosis with bandemia. 2. How does severe acidemia lead to acute kidney injury? Traditionally, metabolic acidosis is thought to be a consequence of kidney failure. However, in situations like MALA, acidemia itself can be the culprit of acute kidney injury. Broadly speaking, severe acidemia damages multiple organ systems with neurological, skin, cardiac, renal, gastrointestinal, and hematological manifestations (...) acidosis. Thus, any patient with type II diabetes on metformin presenting with a markedly elevated metabolic anion gap and a high lactate level should be strongly considered for MALA. Regardless of the etiology of acidosis, severe acidemia adversely affects multiple organ systems and impairs response to native and exogenous catecholamines, which need to be kept in consideration during treatment. Current treatment for MALA centers on supportive measures for patients in respiratory distress or shock

2018 Clinical Correlations

27. Cardiopulmonary Resuscitation in Infants and Children With Cardiac Disease (Full text)

for resuscitation of infants and chil- dren with structurally normal hearts. The most recent guidelines update, published in 2015, 3,4 focused on the quality of cardiopulmonary resuscitation (CPR), with an emphasis on minimizing interruptions in chest compres- sions, providing adequate rate and depth of compres- sions, and avoiding excessive ventilation. 3–5 Although this emphasis is also recommended in infants and chil- dren with heart disease, there are additional important considerations. This scientific (...) , along with gaps in knowledge that highlight future directions for research relevant to the pediatric cardiac population. The contributors to this scientific statement were selected on the basis of their expertise in disciplines re- lated to the management of children with congenital and acquired heart disease. The writing group for this statement was selected and organized according to the conflict-of-interest management policy of the AHA. The writing group performed MEDLINE database searches

2018 American Heart Association PubMed abstract

28. CRACKCast Episode 185 – Alcohol Related Disease

or undetectable at presentation in patients with alcoholic ketoacidosis. In addition, such patients may have hypoglycemia or hyperglycemia, hypokalemia, hypophosphatemia, hypomagnesemia, an elevated serum osmolal gap, and mixed acid-base disorders. Diagnosis of AKA: Suspicion or clinical history and a low glucose level (90% with a glucose <13 mmol/L) Elevated anion gap Ketonuria (*) or ketonemia (serum beta-hydroxybutyrate much superior) Keep that ddx broad! Don’t forget other life threats: diabetic (...) items on excess consumption from the Alcohol Use Disorders Identification Test (AUDIT). The questions, below, have been validated primarily in male veterans but studies demonstrating validity in primary care and other populations are beginning to appear. The AUDIT-C is briefer than the original test, but still requires scoring. How often do you have a drink containing alcohol? How many drinks containing alcohol do you have on a typical day when you are drinking? How often do you have six or more

2018 CandiEM

29. Physiologic Predictors of Severe Injury: Systematic Review

Highway Traffic Safety Administration requested this report from the EPC Program at AHRQ to support revision of the Field Triage Guidelines. AHRQ assigned this report to the Pacific Northwest Evidence-based Practice Center (Contract No. 290-2015-00009-I). The reports and assessments provide organizations with comprehensive, evidence-based information on common medical conditions and new health care technologies and strategies. They also identify research gaps in the selected scientific area, identify (...) was for the Glasgow Coma Scale, age, and arterial pressure (GAP) combination measure (AUROC, 0.96; estimate based on emergency department data). All of the measures had low sensitivities and comparatively high specificities (e.g., sensitivities ranging from 13% to 74% and specificities ranging from 62% to 96% for out- of-hospital pooled estimates). Conclusions. Physiologic measures usable in triaging trauma patients have been evaluated in multiple studies; however, their predictive utilities are moderate and far

2018 Effective Health Care Program (AHRQ)

30. Metformin Use in Patients with Historical Contraindications or Precautions

, observational studies will also be useful in comparing metformin to newer diabetes agents in these populations. Additional studies focusing specifically on cohorts with eGFR 30-45 mL/min/1.73m 2 or even 45mg/dl (5.0mEq/L), decreased blood pH, and electrolyte disturbances with an increased anion gap. It may result from lactate overproduction because of inadequate tissue oxygen delivery or without overt tissue hypoperfusion. The LA type classifications are explained in Table 1. Table 1. Lactic Acidosis Type (...) discouraged use of metformin in many individuals with relatively normal kidney function. Therefore, the kidney function cutoff was revised to an eGFR of 45 mL/min/1.73m 2 if renal function is monitored every 3 months to 6 months, but still contraindicated if eGFR is 45mg/dl or 5.0mEq/L, decreased blood pH, and electrolyte disturbances with an increased anion gap. Metformin-associated LA is defined as meeting the definition for LA plus either (a) elevated metformin level or (b) investigator judgment

2017 Veterans Affairs Evidence-based Synthesis Program Reports

31. i STAT CG4+ and CHEM8+ cartridges for point-of-care testing in the emergency department

dioxide and total carbon dioxide. The CHEM8+ cartridge measures sodium, potassium, chloride, total carbon dioxide, anion gap, ionised calcium, glucose, urea nitrogen, creatinine, lactate, haematocrit and haemoglobin. The i-STAT cartridges are single-use and each cartridge requires 2 to 3 drops of blood. Cost and resource use Cost and resource use The CG4+ cartridge costs £12.49 per test, excluding VAT. The CHEM8+ cartridge costs £19.54 per test, excluding VAT. The i-STAT analyser costs £5191 (...) and haematology tests: sodium potassium chloride urea nitrogen/urea glucose creatinine ionised calcium total carbon dioxide (TCO 2 ) anion gap (calculated) haematocrit haemoglobin (calculated). Detailed information on the cartridges and tests is available on the manufacturer's website, including their intended use, methods and performance data on the tests. T o use a test cartridge, the operator and patient information is entered into the i-STAT analyser using the keypad. Two or 3 drops of blood (between 65

2015 National Institute for Health and Clinical Excellence - Advice

32. Interventions Targeting Sensory Challenges in Children with Autism Spectrum Disorder - An Update

in individuals with autism spectrum disorders. Neuropsychiatr Dis Treat. 2011;7:27-30. doi: 10.2147/ndt.s10327. PMID: 21326652.X-1, X-2 715. Lanovaz MJ, Sladeczek IE, Rapp JT. Effects of music on vocal stereotypy in children with autism. J Appl Behav Anal. 2011 Fall;44(3):647-51. doi: 10.1901/jaba.2011.44-647. PMID: 21941398.X-3, X-4 716. Larson HJ, Cooper LZ, Eskola J, et al. Addressing the vaccine confidence gap. Lancet. 2011 Aug 6;378(9790):526-35. doi: 10.1016/s0140-6736(11)60678-8. PMID: 21664679.X-1

2017 Effective Health Care Program (AHRQ)

33. CRACKCast E126 – Diabetes Mellitus and Disorders of Glucose Homeostasis

patient, with profound electrolyte imbalance. Let’s emphasize the key points here: Insulin deficiency Hyperglycemia Dehydration and electrolyte imbalance Anion-gap metabolic acidosis [2] List 6 potential triggers for DKA DKA most commonly occurs in patients with type 1 diabetes and is associated with inadequate administration of insulin, infection, or myocardial infarction. DKA can also occur in type 2 diabetics and may be associated with any type of stress, such as sepsis or GI bleeding (...) . The pathogenesis of prediabetes is thought to be related to insulin resistance. NOTE: Type 1 diabetes results from a chronic autoimmune process that usually exists in a preclinical state for years. The classic manifestations of type 1—hyperglycemia and ketosis—occur late in the course of the disease, and are an overt sign of beta cell destruction. [1] Define diabetic ketoacidosis (DKA) DKA is a syndrome in which insulin deficiency and glucagon excess combine to produce a hyperglycemic, dehydrated, acidotic

2017 CandiEM

34. Practical Management of Hyperglycaemic Hyperosmolar State (HHS) in children

be confirmed through laboratory investigation. The ISPAD clinical practice consensus guideline criteria for diagnostic features of HHS include: ? Plasma glucose concentration >33.3 mmol/L ? Venous pH > 7.25; arterial pH > 7.30 ? Serum bicarbonate >15 mmol/L ? Small ketonuria, absent to mild ketonaemia ? *Effective serum osmolality > 320 mOsm/kg ? Altered consciousness (e.g., obtundation, combativeness, seizures) ? Anion Gap may be variable # *Serum osmolality = 2 x serum sodium + serum glucose + serum urea (...) (all in mmol/L) # Anion gap = (+) – (Cl- + HCO3-) There may be overlap between HHS and DKA, making management challenging. Mild acidosis can be present in HHS due to lactic acidosis resulting from severe dehydration. There may also 5 Version 2, July 2017 Review 2020 Authors: SM Ng, JA Edge, AE Timmis ssociation of Children’s Diabetes Clinicians Clinicians be extreme hyperglycaemia in DKA resulting in hyperosmolality, particularly if high glucose drinks were used by patients to quench thirst

2018 British Society for Paediatric Endocrinology and Diabetes

35. Diagnosis and Management of Noncardiac Complications in Adults With Congenital Heart Disease: A Scientific Statement From the American Heart Association (Full text)

be as high as 16% and carries clinical consequences such as increased incident thromboem- bolic complications. 52 In addition, cyanotic patients may develop secondary renal tubular acidosis with subse- quent normal anion gap metabolic acidosis. 53 Management Assessment of kidney function may be accomplished through standard methods of calculating GFR, relying on serum creatinine, age, sex, and race. Normal kidney function is defined as = 90 mL·min -1 ·1.73 m -2 . Because of the high prevalence of renal (...) mentioned, pneumonia is the most common noncardiac cause of death in adults with CHD, which is likely re- lated to associated genetic disorders, associated immune compromise, or congenital abnormalities of the lung. 15 The other infection that stands out in adults with CHD is peritonitis, although no specific correlative or pathogenic findings have been documented. In the report from the CONCOR registry (Congenital Corvitia) of patients with CHD in the Netherlands, excess mortality was found in patients

2017 American Heart Association PubMed abstract

37. Ongentys (opicapone) - Parkinson?s disease

activity to Opicapone was only shown for serine/threonine phosphatase (PP2A), tyrosine kinase ZAP70 and Mitochondrial Translocator Protein (TSPO) at a concentration of 4.13 µg/ml (IC 50 = 7.18 – 18.54 µg/ml). For the metabolite BIA 9-1103, this was shown to have potential to inhibit TSPO and phosphodiesterase (PDE5A1) activity at a concentration of 5.72 µg/ml (IC 50 = 3.6 µg/ml). It is noted that these levels are in excess to levels expected in human exposure (Cmax of 1.55 µg/ml), so these findings (...) levels. Opicapone inhibited hERG current with an IC 50 of 388.9 µM. BIA 9-1079 had an IC 50 121.1 µM in the hERG assay. Both levels of compound that may lead to inhibition are well in excess of anticipated clinical exposure. No obvious concerns are raised in terms of safety pharmacology for Opicapone and the major animal metabolite, BIA 9-1079. Assessment report EMA/343011/2016 Page 16/140 Following CHMP advice given, further characterisation of the major human metabolite, BIA 9-1103 was requested

2016 European Medicines Agency - EPARs

38. Zavicefta (ceftazidime / avibactam) - infections

MITT Modified intention to treat mMITT Microbiologically modified intention to treat MRIB Moderate renal impairment at baseline MS MTZ Mass Spectrometry Metronidazole NLT NMR NP Not less than Nuclear Magnetic Resonance Nosocomial Pneumonia OAT Organic anion transporter PACMP PAR PCS Post-approval change management protocol Proven Acceptable Range Potentially clinically significant Ph. Eur. PTA European Pharmacopoeia Probability of PK/PD target attainment QbD QTPP q8h, q12h, q24h, q48h Quality (...) . These changes improved the operability and processing and also the quality of the avibactam sodium produced. Development of the control strategy for the manufacture of avibactam sodium has used a science and risk based approach Assessment report EMA/CHMP/377887/2016 Page 15/120 • Critical Quality Attributes (CQAs) for avibactam sodium were determined, following the principles defined in ICH Q11. • A risk-based approach was used to identify knowledge gaps and risks to the CQAs for avibactam sodium

2016 European Medicines Agency - EPARs

39. 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

40. 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

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