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Genome-Wide Study of Lipids

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eMERGE Northwestern University Lipids phenotype algorithm Below is a flowchart used to select patients and their lipid measures, specifically total cholesterol, HDL (high density lipoprotein), LDL (low density lipoprotein), and triglycerides, for a GWAS (Genome Wide Association Study) from an EMR (Electronic Medical Record). Lists of diagnoses, labs, and medications referred to in the flowchart can be found on the following pages. If you have questions regarding this algorithm, you may contact either: Jennifer A. Pacheco ([email protected]) Abel Kho ([email protected]) Laura Rasmussen-Torvik ([email protected]) Flowchart: All dates & med yes names anti-lipid Rx? Genotyped yes Cohort Get HRT Rx? yes earliest At least 1 Lipid dates yes panel? of possible Testosterone Earliest exclusions: Rx? yes exclusion yes dates Lipid panel Diabetes? yes results to study by date Hypo- or Hyper- yes thyroidism? yes Cancer? Page 1 of 6 Phenotype Specifications: Dates to extract for each exclusion are as follows, with diagnosis codes and medications to use listed at the end of the end of this appendix. Exclusion dates: Medications: earliest order or prescription date Diabetes, earliest of the following dates: o from the eMERGE Northwestern type 2 diabetes algorithm**: . earliest diagnosis date . earliest medication order or prescription date for: insulin, pramlintide (Symlin), or type 2 diabetes medication . earliest lab date where abnormal lab value as follows: random glucose > 200mg/dl, fasting glucose > 125 mg/dl, or hemoglobin A1c ≥ 6.0% (the cutoff used for controls) o earliest diagnosis date of any other diabetes diagnosis listed below Hypo- or Hyper-thyroidism, earliest of the following dates: o from the eMERGE Vanderbilt hypothyroidism algorithm**: . earliest hypothyroidism diagnosis date . earliest hypothyroidism (thyroid replacement) medication prescription date . earliest abnormal TSH or FT4 lab date o earliest diagnosis date of any other hypo- or hyper-thyroidism diagnosis listed below Cancer, earliest of the following dates: o earliest diagnosis date from diagnosis codes o earliest diagnosis date from cancer/tumor registry, if one exists **We are leveraging the existing validated phenotype algorithms for diabetes and hypothyroidism to identify patients that may have underlying pathologies affecting their lipid levels. However, we are relaxing the algorithms by only requiring one criterion to be satisfied, rather than two. This is to capture Type 1 diabetics and other forms of hypothyroidism that may affect lipid levels. Page 2 of 6 ICD-9 diagnosis codes: Diabetes: 250* Diabetes Type 1 and 2 357.2 Diabetic Neuropathy 362.01-362.02 Diabetic Retinopathy 583.81 Diabetic Nephropathy Hypothyroidism: 243* Congenital hypothyroidism 244* acquired hypothyroidism 245 thyroiditis 245.2 chronic lymphocytic thyroiditis 245.8 chronic thyroiditis NEC/NOS 245.9 thyroiditis NOS Hyperthyroidism: 242.00-242.33 242.90-242.93 Cancer: between 140* and 208* *any number of digits after the decimal point Page 3 of 6 Medications: Antilipemic medications: Statins, Niacins, Fibrates & combinations thereof: Atorvastatin, Simvastatin, Pravastatin, Lovastatin, Cerivastatin, Rosuvastatin, Fluvastatin, Pitavastatin Gemfibrozil/Fibrate, Fenofibrate, Cholestyramine Niacin/statin combinations Niacin, inc. generic names: 'INOSITOL/NIACIN','FOLIC Comment [JSA1]: If have dosing data, can ACID/NIACINAMIDE/CU/ZNOX', 'NIACINAMIDE' exclude on those on >=500mg/day Here is a comprehensive list of these meds by RxNorm ingredient level code, the list is derived from the following web page: http://www.mass.gov/?pageID=eohhs2terminal&L=6&L0=Home&L1=Provider&L2=Insurance+% 28including+MassHealth%29&L3=MassHealth&L4=MassHealth+Drug+List&L5=Therapeutic+Cl ass+Tables&sid=Eeohhs2&b=terminalcontent&f=masshealth_provider_pharmacy_therapeutic_t able_13&csid=Eeohhs2 rxcui tty str HMG-CoA Reductase Inhibitors 221072 IN Cerivastatin sodium 301542 IN rosuvastatin 36567 IN Simvastatin 41127 IN fluvastatin 42463 IN Pravastatin 6472 IN Lovastatin 83367 IN atorvastatin 861634 IN pitavastatin Nicotinic Acids 137732 IN chromium nicotinic acid complex 7393 IN Niacin 7405 IN Niacinamide Fibric Acids 1525 IN Bezafibrate 21149 IN ciprofibrate 24609 IN etofibrate 2594 IN Clofibrate 4719 IN Gemfibrozil 8703 IN Fenofibrate Bile Acid Sequestrants 141626 IN colesevelam 2447 IN Cholestyramine Resin 2685 IN Colestipol Cholesterol Absorption Inhibitors 341248 IN ezetimibe Miscellaneous 4301 IN Omega -3 Fatty Acids 484348 IN Omega-3 Acid Ethyl Esters (USP) Page 4 of 6 HRT (Hormone Replacement Therapy) , at least oral, implant, patch & other forms that are not creams/topical: Comment [JSA2]: This list of medications can be used or the list of medications by generic Conjugated estrogen ingredient below, whichever is easiest Look for the following brand names or: Optionally use NLP used by Marshfield in their HDL algorithm to find Conjugated Estrogen use: Earliest mention of the following Estrogen/Androgen drug use in clinical notes (regardless of age or gender) , CENESTIN, PREMARIN, PREMPHASE, Prempro , Enjuvia Excluded any records where topical or cream was indicated in the flanking text. Searched the flanking text in records where the drug name='ESTROGEN' for the following terms: post menopause, post menopause, postmenopausal, on estrogen, went off estrogen, stop estrogen, on unopposed estrogen, estrogen replacement, history of estrogen use, estrogen patch, estrogen usage, estrogen therapy, estrogen pill, unopposed estrogen use, chronic estrogen use. Kept records where drug name="ESTROGEN" and flanking text contained one of the above terms and there was no indicator of topical or cream in the flanking text. Conjugated Estrogen medications from RxNorm at ingredient level rxcui tty str Comment [JSA3]: RxNorm level = IN = 253166 IN estrogens, conjugated synthetic A Ingredient Comment [JSA4]: RxNorm ingredient name 4099 IN Estrogens, Conjugated (USP) 618365 IN estrogens, conjugated synthetic B Testosterone medications from RxNorm at ingredient level: rxcui tty str 10379 IN Testosterone 37855 IN testosterone 17-phenylpropionate 6904 IN Methyltestosterone Type 2 diabetes medications: Drug class Brand name Generic name Sulfonylureas acetohexamide Sulfonylureas Tolazamide Sulfonylureas Diabinese chlorpropamide Sulfonylureas Glucotrol glipizide Sulfonylureas Glucotrol XL glipizide Sulfonylureas Micronase glyburide Sulfonylureas Glynase glyburide Sulfonylureas Diabeta glyburide Sulfonylureas Amaryl glimepiride Meglitinides Prandin repaglinide Meglitinides Starlix nateglinide Biguanides Glucophage metformin Thiazoldinediones Avandia rosiglitazone Thiazoldinediones ACTOS pioglitazone Thiazoldinediones troglitazone Alpha-glucosidase inhibitors Precose acarbose Page 5 of 6 Alpha-glucosidase inhibitors Glyset miglitol DPPIV inhibitor Januvia sitagliptin Injectables Byetta exenatide Hypothyroidism medications (from Vanderbilt hypothyroidism algorithm for cases): Levothyroxine, synthroid, Levoxyl unithroid, armour thyroid, desiccated thyroid, cytomel, triostat, liothyronine, synthetic triiodothyronine, liotrix, thyrolar, T3* and T4* Page 6 of 6 .
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