Phenotype Algorithm Pseudo Code

Herpes Zoster

Phenotype Algorithm Pseudo Code

Group Health and University of Washington

March 7, 2013

Contacts:
David Carrell (, 206-287-2705)
Eric Baldwin ()

BACKGROUND

Herpes zoster, also known as zoster or shingles, is caused by a virus called varicella zoster virus (VZV). Initial infection with the virus causes chickenpox. After chickenpox resolves the virus continues to reside in certain nerve cells. It may remain latent for many years. It may re-activate any time, up to years later, and cause shingles. Shingles is a painful skin rash. How the virus remains latent in the body is not well understood. For additional information see Wikipedia (http://en.wikipedia.org/wiki/Herpes_zoster).

ALGORITHM and COVARIATES

This algorithm and covariates require the following types of information:

·  Patient demographics

·  Enrollment/encounter history

·  Diagnosis codes (ICD)

·  Procedure codes (CPT and/or ICD)

·  Medications

·  Nursing home admissions

Some covariates are ever/never measures and others are repeated measures requiring associated dates.

CASES

Cases are identified by first applying inclusion criteria, then excluding from this set any subjects meeting any of the exclusion criteria. Inclusion criteria include a minimum enrollment history to increase the probability that a subject’s status with respect to herpes zoster infection is known by the health care system. This is especially important for controls, but the criterion is applied to cases as well to enhance comparability across the two groups. An index date is required for each case.

Case inclusion criteria:

Potential cases must meet all of the following inclusion criteria:

I-1 Is at least 40 years of age at time of assessment.

I-2 Has at least one diagnosis code for herpes zoster (ICD 053.xx) or varicella zoster (ICD 052.xx) on or after the 40th birthday.

I-2-a Exclude from any such diagnosis codes those occurring on the same calendar date as a herpes vaccination. This reduces the chance of false positives caused when a zoster/varicella diagnosis code is recorded for an encounter where an uninfected person with no history of infection receives a zoster vaccination. Group Health used CPT procedures codes to identify vaccinations (defined in section COVARIATES, below). You may use additional site-specific information to identify vaccinations as appropriate for your site.

I-3 Has ≥5 years of continuous enrollment (or encounter) history since age 35.

Note: Implementations of “continuous enrollment” may vary by institution. Continuous enrollment is defined at Group Health as a period of enrollment in a Group Health-administered insurance or integrated health care plan for at least 5 years, allowing interruptions or gaps in coverage of up to three months. Gaps of this size are allowed because they typically represent administrative data inconsistencies rather than actual interruptions in access to care.

Sites may implement continuous enrollment in whatever manner they deem to be consistent with continuous enrollment, including use of more granular rules. For example, Mayo Clinic’s continuous enrollment rules incorporate patient age and gender into the calculation. This is sensible because younger men receiving regular care at Mayo Clinic tend to have fewer encounters than women of the same age or older men.

Case exclusion criteria:

Exclude from the set of potential cases subjects with any of the following:

E-1 Has diagnosis codes on 2+ separate calendar days for HIV infection (ICD 042.xx–044.xx).

E-2 Has any diagnosis codes for cancer of the blood or bone marrow (ICD 200.xx–208.xx) during the 365-day period prior to the index date (index date is defined below).

Note: Optionally, ICD diagnosis data may be supplemented with diagnosis data available locally from cancer registries, such as the Surveillance Epidemiology and End Results (SEER) registry.

E-3 Has any cancer chemotherapy infusion (see Appendix A) during the 180-day period prior to the index date (index date is defined below)..

Index date for cases:

The index date for cases is provided as subject age in years (expressed as real number with at least two significant digits to the right of the decimal point; see data dictionary) at the subject’s index date. The index date is defined as the date of the first valid herpes zoster or varicella zoster diagnosis on or after the subject’s 40th birthday.

CONTROLS

Controls are identified by first applying inclusion criteria, then excluding from this set any subjects who meet any of several exclusion criteria. Index dates are not defined for controls.

Controls inclusion criteria:

Potential controls must meet all of the following inclusion criteria:

I-1 Is at least 40 years of age at time of assessment.

I-2 Has ≥5 years of continuous enrollment/contact since age 35.

Note: “Continuous enrollment/contact” is implemented in an integrated group practice (HMO) setting as a period of continuous enrollment ignoring gaps of up to 90 days (which tend to reflect administrative data lags rather than actual interruptions in access to care). In fee-for-service or non-integrated care settings, continuous enrollment is implemented as consecutive 18-month periods with at least one encounter per period. Encounters may be rolled up to the calendar date for purposes of establishing encounters during an 18-month period.

Controls exclusion criteria:

Exclude from the set of potential controls subjects with any of the following:

E-1 Has diagnosis codes on ≥2 separate calendar days for HIV infection (ICD: 042.xx–044.xx).

E-2 Has any diagnosis codes ever for herpes zoster (ICD: 053.xx) or varicella zoster (ICD: 052.xx).

No index date for controls:

There is no index date for controls.

COVARIATES

Covariates are collected in the same manner for both cases and controls, except as noted below. Some covariates are captured as repeated measures (as noted). Detailed definitions of all variables, including covariates, are provided in the data dictionary (an Excel file).

Note: Many of these covariates are also used for the clostridium difficile (c-diff) phenotype.

1.  Demographics

·  Self-reported sex

·  Self-reported ancestry (race and ethnicity)

·  Calendar year of birth (4-digit)

2.  BMI (repeated measurements rolled up to calendar date)

·  BMI

·  Age in years (as real number) at BMI measurement

·  Optionally, weight component of BMI

·  Optionally, height component of BMI

3.  Nursing home admissions

·  Ever admitted to a nursing home (yes/no)

·  Age in years (as real number) of earliest admission to a nursing home

·  Age in years (as real number) of latest admission to a nursing home

4.  Vaccinations for herpes zoster

·  Ever vaccinated (yes/no; CPT codes: 90396, 90736)

·  Age in years (as real number) at earliest vaccination

·  Age in years (as real number) at latest vaccination

5.  Herpes simplex (HSV1 or HSV2) infections

·  Ever infected with herpes simplex (ICD: 054.0–054.3)

·  Age in years (as real number) at earliest herpes simplex infection

·  Age in years (as real number) at latest herpes simplex infection

6.  Antiviral medications at strengths for treating herpes zoster

·  Ever exposed to zoster-strength antiviral medications (yes/no; see Appendix B)

·  Age in years (as real number) at earliest zoster-strength antiviral medications

·  Age in years (as real number) at latest zoster-strength antiviral medications

7.  Transplant medications

·  Ever exposed to transplant medications (yes/no; see Appendix C)

·  Age in years (as real number) at earliest transplant medication

·  Age in years (as real number) at latest transplant medication

·  Cases only: Exposed any time from the earliest know patient contact through index date + 7days (yes/no)

8.  Steroid medications

·  Ever exposed to transplant medications (yes/no; see Appendix D)

·  Age in years (as real number) at earliest transplant medication

·  Age in years (as real number) at latest transplant medication

·  Cases only: Exposed between 21 days prior to index date through 7 days after index date (yes/no)

9.  Anti tumor necrosis factor (Anti-TNF) medications

·  Ever exposed to transplant medications (yes/no; see Appendix E)

·  Age in years (as real number) at earliest transplant medication

·  Age in years (as real number) at latest transplant medication

·  Cases only: Exposed between 21 days prior to index date through 7 days after index date (yes/no)

10. Cancer of the blood or bone marrow (repeated measurements rolled up to calendar date)

·  Blood or bone marrow cancer diagnosis code (ICD: 200.xx–208.xx)

·  Age in years (as real number) at date of diagnosis

11. Chemotherapy (repeated measurements rolled up to calendar date)

·  Defined as above in Case Exclusion Criterion E-3 and as below in Appendix A.

·  Age in years (as real number) on date of chemotherapy procedure (calculated as [procedure date minus birth date]/365.25).

FLOW DIAGRAM

This is a schematic representation of the phenotype definition logic described above.

APPENDIX A

Procedure Codes for Cancer Chemotherapy

Procedure codes for identifying administration of cancer chemotherapies are drawn from the following sources.

·  International Classification of Diseases (ICD)

·  National Uniform Billing Committee Official UB-04 Data Specifications (UB-04)

·  Medicare G-Codes (G)

·  Current Procedural Terminology (CPT)

·  Healthcare Common Procedure Coding System (CPT_HCPCS)

Note that the chemotherapeutic infusion codes listed in Table A below are sufficient to capture cancer chemotherapy events. Chemotheraputic agents (captured, e.g., by CPT J-codes) provide additional information about the medication being infused, but because some medications are indicated for non-cancer treatments, a code for a therapeutic agent alone is insufficient to identify cancer chemotherapy. We thus rely exclusively on the infusion code to capture the events of interest.

Table A: Cancer Chemotherapy Infusion Codes /
Source / Code / Brief Description /
ICD / 00.10 / Implant chemo agent
UB-04 / 331 / Rad therapeutic chemo in
UB-04 / 332 / Rad therapeutic chemo or
UB-04 / 335 / Rad therapeutic chemo iv
G / 4621B / 10 quart chemotherapy wa
CPT / 61517 / Implt brain chemotx add-on code
CPT / 96400 / Chemotherapy, sc/im che
CPT / 96401 / Chemo, anti-neopl, sq/im
CPT / 96402 / Chemo hormon antineopl s
CPT / 96405 / Chemo intralesional, up
CPT / 96406 / Chemo intralesional over
CPT / 96408 / Chemotherapy, push techn
CPT / 96409 / Chemo, iv push, sngl dru
CPT / 96410 / Chemotherapy,infusion me
CPT / 96411 / Chemo, iv push, addl dru
CPT / 96412 / Chemo, infuse method add
CPT / 96413 / Chemo, iv infusion, 1 hr
CPT / 96414 / Chemo, infuse method add
CPT / 96415 / Chemo, iv infusion, addl
CPT / 96416 / Chemo prolong infuse w/p
CPT / 96417 / Chemo iv infus each addl
CPT / 96420 / Chemo, ia, push tecnique
CPT / 96422 / Chemo ia infusion up to
CPT / 96423 / Chemo ia infuse each add
CPT / 96425 / Chemotherapy,infusion me
CPT / 96440 / Chemotherapy, intracavit
CPT / 96445 / Chemotherapy, intracavit
CPT / 96450 / Chemotherapy, into cns
CPT / 96500 / Chemo injection chemo
CPT / 96501 / Chemo injection chemo
CPT / 96504 / Chemo injection chemo
CPT / 96505 / Chemo injection chemo
CPT / 96508 / Chemo injection chemo
CPT / 96509 / Chemo injection chemo
CPT / 96510 / Chemo injection chemo
CPT / 96511 / Chemo injection chemo
CPT / 96512 / Chemo injection chemo
CPT / 96524 / Chemo injection chemo
CPT / 96526 / Chemo injection chemo
CPT / 96535 / Chemo injection chemo
CPT / 96538 / Chemo injection chemo
CPT / 96540 / Chemo injection chemo
CPT / 96542 / Chemotherapy injection
CPT / 96545 / Provide chemotherapy age
CPT / 96549 / Chemotherapy, unspecifie
CPT / 96910 / Photochemotherapy with u
CPT / 96912 / Photochemotherapy with u
CPT / 96913 / Photochemotherapy, uv-a
ICD / 99.25 / Inject/infusion of cancer chemo
CPT / 99555 / Home infuse, chemotherap
CPT_HCPCS / C8953 / Chemotx adm, IV push
CPT_HCPCS / C8954 / Chemotx adm, IV inf up to 1h
CPT_HCPCS / C8955 / Chemotx adm, IV inf, addl hr
CPT_HCPCS / G0355 / Chemo adminisrate subcut/IM
CPT_HCPCS / G0359 / Chemotherapy IV one hr initi
CPT_HCPCS / G0360 / Each additional hr 1-8 hrs
CPT_HCPCS / G0361 / Prolong chemo infuse>8hrs pu
CPT_HCPCS / G8371 / Chemother not rec stg3 colon
CPT_HCPCS / G8372 / Chemother rec stg3 colon ca
CPT_HCPCS / G8373 / Chemo plan documen prior che
CPT_HCPCS / G8374 / Chemo plan not doc prior che
CPT_HCPCS / G9021 / Chemo assess nausea vomit L1
CPT_HCPCS / G9022 / Chemo assess nausea vomit L2
CPT_HCPCS / G9023 / Chemo assess nausea vomit L3
CPT_HCPCS / G9024 / Chemo assess nausea vomit L4
CPT_HCPCS / G9025 / Chemo assessment pain level1
CPT_HCPCS / G9026 / Chemo assessment pain level2
CPT_HCPCS / G9027 / Chemo assessment pain level3
CPT_HCPCS / G9028 / Chemo assessment pain level4
CPT_HCPCS / G9029 / Chemo assess for fatigue L1
CPT_HCPCS / G9030 / Chemo assess for fatigue L2
CPT_HCPCS / G9031 / Chemo assess for fatigue L3
CPT_HCPCS / G9032 / Chemo assess for fatigue L4
CPT_HCPCS / Q0081 / Infusion ther other than che
CPT_HCPCS / Q0083 / Chemo by other than infusion
CPT_HCPCS / Q0084 / Chemotherapy by infusion
CPT_HCPCS / Q0085 / Chemo by both infusion and o
CPT_HCPCS / S5019 / Chemotherapy admin supplies
CPT_HCPCS / S5020 / Chemotherapy admin supplies
CPT_HCPCS / S9329 / HIT chemo per diem
CPT_HCPCS / S9330 / HIT cont chem diem
CPT_HCPCS / S9331 / HIT intermit chemo diem

APPENDIX B

Antiviral Medications

Antiviral medications are collected as covariates for this phenotype. Qualifying medications are listed in Table B. These antiviral medications are sometimes used to treat herpes zoster (which we want to capture) and sometimes used to treat other conditions (which we want to ignore). We use a minimum dosage rule to determine when a medication is most likely being used to treat herpes zoster. Our rule requires that the total dose prescribed over a 28-day period exceed the minimum specified in Table B).

Note that minimum dose varies by medication.

Table B: Antiviral Medications /
Drug name / Route / Minimum total dose in any 28-day period /
Acyclovir / Oral / ≥ 24,000 mg
Famcyclovir / Oral / ≥ 10,500 mg
Valcyclovir / Oral / ≥ 21,000 mg

APPENDIX C

Transplant Medications

Tranaplant medications are collected as covariates for this phenotype. Qualifying medications are listed in the following table.