Risk of Scrotal Hydroceles After Nephrectomy For Kidney Cancer

This population-based study will use provincial health administrative data to examine the risk of hospital admission for hydrocelectomy among males who underwent nephrectomy for kidney cancer, compared with males from the general population with similar baseline health characteristics, who did not undergo nephrectomy. We will use health administrative data from Ontario, Canada, to identify males who underwent nephrectomy for kidney cancer between 1992 and 2024. Four surgical cohorts will be constructed based on procedure type and surgical approach: laparoscopic total nephrectomy, open total nephrectomy, laparoscopic partial nephrectomy, and open partial nephrectomy. A propensity score will be calculated based on sociodemographic characteristics, comorbidities, and health care utilization. For each surgical cohort, patients will be matched to non-nephrectomy male controls (1:4) based on propensity score, age, index date, and modified Charlson Score (excluding cancer). The primary analysis will compare patients undergoing laparoscopic total nephrectomy and laparoscopic partial nephrectomy with matched non-nephrectomy controls from the general population. The primary outcome is hospital admission for hydrocelectomy. Secondary outcomes include diagnosis of hydrocele with receipt of a scrotal ultrasound, and receipt of a scrotal ultrasound. Additional analyses will compare surgical approaches.

Study Overview

• Status: Completed
• Conditions: Laparoscopic Nephrectomy; Nephrectomy; Hydrocele; Hydrocelectomy; Hydrocele of Tunica Vaginalis; Kidney Cancers
• Intervention / Treatment: Procedure: Laparoscopic nephrectomy for kidney cancer; Procedure: Open nephrectomy for kidney cancer

Detailed Description

*Background*

Previous reports among male living kidney donors have documented postoperative testicular pain and/or scrotal swelling on the side of nephrectomy. Many affected donors were subsequently diagnosed with hydroceles and required surgical intervention (hydrocelectomy). However, existing studies were generally small, had limited follow-up, and lacked appropriate comparison groups.

To address these limitations, a large population-based study of living kidney donors was conducted. Male donors who underwent laparoscopic donor nephrectomy had a substantially higher incidence of scrotal surgery than matched nondonors: 7.8% of donors (70/898) underwent scrotal surgery compared with 0.2% of nondonors (19/8,980), corresponding to 8.3 versus 0.2 events per 1,000 person-years. The hazard ratio was 38.8 (95% CI, 22.1-67.9; P < 0.001), and the 20-year cumulative incidence was 13.8% in donors versus 0.7% in nondonors.

In exploratory secondary analyses, additional surgical cohorts were examined to determine whether similar patterns were observed following other kidney or retroperitoneal procedures. Compared with the general nonsurgical population, patients undergoing nephrectomy for reasons other than donation also appeared to have higher rates of subsequent scrotal surgery. Among those undergoing partial nephrectomy, incidence rates were 1.1 events per 1,000 person-years after laparoscopic procedures and 0.8 events per 1,000 person-years after open procedures. Among those undergoing total nephrectomy, incidence rates were 2.9 and 1.5 events per 1,000 person-years following laparoscopic and open procedures, respectively.

Although these analyses were descriptive and unadjusted for confounding, the findings raise the possibility that aspects of nephrectomy surgery, particularly laparoscopic approaches, may contribute to hydrocele formation. The reasons for this potential difference between laparoscopic and open approaches remain unclear. One proposed mechanism is disruption of lymphatic drainage or venous outflow along the gonadal vessels during retroperitoneal surgery. Because nephrectomy involves mobilization of the kidney and surrounding structures, it may affect scrotal lymphatic or venous drainage. However, the long-term risk of hydrocele formation and repair after nephrectomy performed for kidney cancer has not been well characterized.

Primary Objective: To evaluate whether males who underwent laparoscopic nephrectomy (partial or complete) for kidney cancer have a higher risk of hospital admission for hydrocelectomy compared with males with similar indicators of baseline health selected from the general population.

*Study Setting and Data Sources*

This study will be conducted at ICES (ices.on.ca). ICES is an independent, non-profit research institute with legal authority under Ontario's health information privacy legislation to collect and analyze health care and demographic data without individual consent for the purposes of health system evaluation and improvement. Data use for this project is authorized under Section 45 of Ontario's Personal Health Information Protection Act (PHIPA), which does not require Research Ethics Board approval.

Data from multiple linked databases will be used to identify the cohort, establish baseline characteristics, and define outcomes. These databases include Ontario's Registered Persons Database (RPDB), the Ontario Health Insurance Plan (OHIP), and the Canadian Institute for Health Information's (CIHI) Discharge Abstract Database (DAD), National Ambulatory Care Reporting System (NACRS), and Same Day Surgery (SDS).

Given the nature of the data sources, minimal missingness is expected across study variables. This retrospective cohort study will rely entirely on existing administrative health data available at ICES. To promote research transparency and reproducibility, this study protocol will be registered on ClinicalTrials.gov prior to initiating outcome analyses.

*Study Population*

Male patients undergoing nephrectomy will be identified using hospitalization records in CIHI-DAD and SDS between 1992 and 2024. Only the first nephrectomy occurring during the study period will be examined. Four nephrectomy cohorts will be constructed based on procedure type and surgical approach:

1. Laparoscopic total nephrectomy
2. Open total nephrectomy
3. Laparoscopic partial nephrectomy
4. Open partial nephrectomy

A fifth cohort of non-nephrectomy controls will be selected from the general male population.

*Baseline Characteristics and Matching*

Baseline variables will be assessed at the index date, defined as the date of nephrectomy surgery for exposed patients. For general population comparators who did not undergo nephrectomy, an index date will be randomly assigned based on the distribution of nephrectomy index dates (drawn from the surgical cohort being compared).

Baseline characteristics will be summarized using descriptive statistics and standardized differences. To reduce confounding, 1:4 propensity score matching will be performed, pairing each nephrectomy patient with up to four controls using greedy nearest-neighbour matching without replacement. Matches will be restricted using a caliper width equal to 0.2 of the standard deviation of the logit of the propensity score. Matching variables will include the propensity score, age, index date, and modified Charlson Comorbidity Score (excluding cancer). Post-matching balance between groups will be assessed using standardized mean differences.

*Outcomes*

The primary outcome is hospital admission and receipt of surgery for hydrocele excision (hydrocelectomy). To ensure accurate outcome ascertainment, evidence of both a hospital-based procedural code (CCI codes: 1QH87LA, 1QH87LB, 1QH52HA, 1QH52LA, 1QH80LA, 1QG52HA, 1QG52LA; CCP codes: 731, 730, 7391, 7339) and a surgeon fee-for-service code (OHIP fee codes: S611, S630) is required, with each recorded in separate healthcare databases within 30 days of one another. The date of hospital admission will be recorded as the outcome date.

Observation time will be censored at death, emigration, or the maximum follow-up date (March 31, 2025). Secondary outcomes include receipt of a scrotal ultrasound and diagnosis of hydrocele with a scrotal ultrasound in administrative health records.

*Statistical Analysis*

Five cohorts will be defined: laparoscopic total nephrectomy, open total nephrectomy, laparoscopic partial nephrectomy, open partial nephrectomy, and non-nephrectomy controls. For all nephrectomy patients, the index date will be the date of surgery. For controls, index dates will be assigned by bootstrapping from the distribution of nephrectomy index dates (from the surgical cohort being compared).

The primary analysis will compare each laparoscopic nephrectomy cohort with matched non-nephrectomy controls.

1. Laparoscopic total nephrectomy vs. matched non-nephrectomy controls
2. Laparoscopic partial nephrectomy vs. matched non-nephrectomy controls

Incidence rates (per 1,000 person-years), rate differences, and hazard ratios (HRs) will be calculated using Cox proportional hazards models with robust variance estimation to account for matching. If the proportional hazards assumption is violated, stratified log-rank tests will be used, and restricted mean survival times will be estimated at 20 years. Cumulative incidence will be estimated using Aalen-Johansen methods to account for the competing risk of death and will be reported at 1, 5, 10, 15, 20, and 25 years. Subgroup analyses will stratify results by age (<39, 40 to 59, 60 to 79, 80+), cohort entry year (1992-2002, 2003-2013, 2014-2024), and modified Charlson score (0, 1 to 2, 3+) (cancer removed from score).

*Additional Analyses*

In additional analyses, the primary analysis will be repeated, comparing different surgical cohorts. These comparisons include:

Total nephrectomy:

i) laparoscopic total nephrectomy vs. open total nephrectomy, ii) open total nephrectomy vs. matched non-nephrectomy controls, and iii) laparoscopic total nephrectomy only vs laparoscopic total nephrectomy with ureterectomy.

Partial nephrectomy:

i) laparoscopic partial nephrectomy vs. open partial nephrectomy and ii) open partial nephrectomy vs. matched non-nephrectomy controls.

For comparisons of surgical approaches (open vs. laparoscopic) or the effect of ureterectomy, inverse probability of treatment weighting (IPTW) using propensity scores will be applied to balance baseline characteristics between groups. Weighted analyses will estimate the effect of the exposure (surgical approach or ureterectomy) on outcomes, targeting the average treatment effect in the treated (ATT). All estimates will be reported with 95% confidence intervals. Hierarchical testing will be applied, with significance testing stopping after the first non-significant result (α = 0.05 per test); all remaining estimates will be presented without p-values.

• Study Type: Observational
• Enrollment (Actual): 40000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Male residents of Ontario, Canada identified through provincial administrative health databases who underwent nephrectomy for kidney cancer between July 1, 1992 and March 31, 2024, along with matched non-nephrectomy controls from the general population.

Description

*Laparoscopic total nephrectomy*

Inclusion criteria

Male individuals who underwent laparoscopic complete/total nephrectomy between July 1, 1992, and March 31, 2024, with a most responsible diagnosis of malignant kidney, renal pelvis, or ureter cancer at the time of nephrectomy. The index date is defined as the date of the first laparoscopic total nephrectomy during the study period.

Exclusion criteria

• Individuals with data record errors (e.g., missing or invalid age, sex, or date of birth), who are less than 0 years of age or greater than 105 years of age, with a death record on or before their cohort entry, or have a date of last contact <4 months after cohort entry (to restrict to permanent residents of the province).
• Prior partial nephrectomy at any time in the lookback.
• Prior total nephrectomy before the start of accrual (before July 1, 1992).
• Individuals who underwent conversion from laparoscopic to open nephrectomy during the same surgical episode.
• Individuals with no recorded primary care visit in the year prior to the index date.
• History of scrotal or male genital conditions or procedures prior to the index date, including hydrocele, hydrocelectomy, scrotal ultrasound, scrotal or testicular malignancy, or other scrotal/genital procedures.

*Laparoscopic partial nephrectomy*

Inclusion criteria

Male individuals who underwent laparoscopic partial nephrectomy between July 1, 1992 and March 31, 2024, with a most responsible diagnosis of malignant kidney, renal pelvis, or ureter cancer at the time of nephrectomy. The index date is defined as the date of the first laparoscopic partial nephrectomy during the study period.

Exclusion criteria

• Individuals with data record errors (e.g., missing or invalid age, sex, or date of birth), who are less than 0 years of age or greater than 105 years of age, with a death record on or before their cohort entry, or have a date of last contact <4 months after cohort entry (to restrict to permanent residents of the province).
• Prior total nephrectomy at any time in the lookback.
• Any nephrectomy before the start of accrual (before July 1, 1992).
• Individuals who underwent conversion from laparoscopic to open nephrectomy during the same surgical episode.
• Individuals with no recorded primary care visit in the year prior to the index date.
• History of scrotal or male genital conditions or procedures prior to the index date, including hydrocele, hydrocelectomy, scrotal ultrasound, scrotal or testicular malignancy, or other scrotal/genital procedures.

*Open total nephrectomy*

Inclusion criteria

Male individuals who underwent open complete/total nephrectomy between July 1, 1992 and March 31, 2024, with a most responsible diagnosis of malignant kidney, renal pelvis, or ureter cancer at the time of nephrectomy. The index date is defined as the date of the first open total nephrectomy during the study period.

Exclusion criteria

• Individuals with data record errors (e.g., missing or invalid age, sex, or date of birth), who are less than 0 years of age or greater than 105 years of age, with a death record on or before their cohort entry, or have a date of last contact <4 months after cohort entry (to restrict to permanent residents of the province).
• Prior partial nephrectomy at any time in the lookback.
• Prior total nephrectomy before the start of accrual (before July 1, 1992).
• Individuals who underwent conversion from laparoscopic to open nephrectomy during the same surgical episode.
• Individuals with no recorded primary care visit in the year prior to the index date.
• History of scrotal or male genital conditions or procedures prior to the index date, including hydrocele, hydrocelectomy, scrotal ultrasound, scrotal or testicular malignancy, or other scrotal/genital procedures.

*Open partial nephrectomy*

Inclusion criteria

Male individuals who underwent open partial nephrectomy between July 1, 1992 and March 31, 2024, with a most responsible diagnosis of malignant kidney, renal pelvis, or ureter cancer at the time of nephrectomy. The index date is defined as the date of the first open partial nephrectomy during the study period.

Exclusion criteria

• Individuals with data record errors (e.g., missing or invalid age, sex, or date of birth), who are less than 0 years of age or greater than 105 years of age, with a death record on or before their cohort entry, or have a date of last contact <4 months after cohort entry (to restrict to permanent residents of the province).
• Prior total nephrectomy at any time in the lookback.
• Any nephrectomy before the start of accrual (before July 1, 1992).
• Individuals who underwent conversion from laparoscopic to open nephrectomy during the same surgical episode.
• Individuals with no recorded primary care visit in the year prior to the index date.
• History of scrotal or male genital conditions or procedures prior to the index date, including hydrocele, hydrocelectomy, scrotal ultrasound, scrotal or testicular malignancy, or other scrotal/genital procedures.

*Non-Nephrectomy Control Cohort*

Inclusion criteria

The control cohort will consist of male individuals identified in RPDB. Index dates will be randomly assigned by bootstrapping dates from the appropriate nephrectomy group, such that each control is assigned an actual nephrectomy index date randomly sampled with replacement from that group. Controls will be carefully screened to ensure that none are included in the nephrectomy cohort being compared.

Exclusion criteria

• Individuals with data record errors (e.g., missing or invalid age, sex, or date of birth), who are less than 0 years of age or greater than 105 years of age, with a death record on or before their cohort entry, or have a date of last contact <4 months after cohort entry (to restrict to permanent residents of the province).
• Any nephrectomy (partial or total).
• Individuals with no recorded primary care visit in the year prior to the index date.
• History of scrotal or male genital conditions or procedures prior to the index date, including hydrocele, hydrocelectomy, scrotal ultrasound, scrotal or testicular malignancy, or other scrotal/genital procedures.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Laparoscopic total nephrectomy; Males who underwent laparoscopic total nephrectomy for kidney cancer between July 1, 1992 and March 31, 2024. Surgeon-fee-for-service code (OHIP fee code: E792, S413, S416, with no evidence of E766, E767, E768, S424, S420) and a hospital-based procedural code (CCI: 1PC89DA, 1PC91DA; CCP: 674, 6741, 6742, 6744).	Procedure: Laparoscopic nephrectomy for kidney cancer; Receipt of a laparoscopic (total or partial) nephrectomy for kidney cancer
Laparoscopic partial nephrectomy; Males who underwent laparoscopic partial nephrectomy for kidney cancer between July 1, 1992 and March 31, 2024. Surgeon-fee-for-service code (OHIP fee code: S411, S423) and a hospital-based procedural code (CCI: 1PC87DA; CCP: 673).	Procedure: Laparoscopic nephrectomy for kidney cancer; Receipt of a laparoscopic (total or partial) nephrectomy for kidney cancer
Open total nephrectomy; Males who underwent open total nephrectomy for kidney cancer between July 1, 1992 and March 31, 2024. Surgeon-fee-for-service code (OHIP fee code: S413, S415, S416, with no evidence of E792, E766, E767, E768, S424, S420) and a hospital-based procedural code (CCI: 1PC89LB, 1PC89PF, 1PC89QF, 1PC91LB, 1PC91PF, 1PC91QF; CCP: 674, 6741, 6742, 6744).	Procedure: Open nephrectomy for kidney cancer; Receipt of an open (total or partial) nephrectomy for kidney cancer
Open partial nephrectomy; Males who underwent open partial nephrectomy for kidney cancer between July 1, 1992 and March 31, 2024. Surgeon-fee-for-service code (OHIP fee code: S411, S423) and a hospital-based procedural code (CCI: 1PC87LA, 1PC87LAXXE, 1PC87LAXXG, 1PC87NQ; CCP: 673).	Procedure: Open nephrectomy for kidney cancer; Receipt of an open (total or partial) nephrectomy for kidney cancer
Non-nephrectomy controls; Males from the general Ontario population who did not undergo any nephrectomy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hydrocelectomy	A hospital-based procedural code (CCI code: 1QH87LA, 1QH87LB, 1QH52HA, 1QH52LA, 1QH80LA, 1QG52HA, 1QG52LA; CCP code: 731, 730, 7391, 7339) and a surgeon-fee-for-service code (OHIP fee code: S611, S630) within 30 days.	Follow-up period (index date to outcome, emigration, or maximum follow-up date [March 31, 2025]).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hydrocele diagnosis	A hospital-based diagnosis code (ICD-9 code: 6030, 6031, 6038, 6039; ICD-10-CA code: N43, N430, N431, N432, N433, P835) and an OHIP claims diagnostic code (OHIP diagnostic code: 603) and a scrotal ultrasound within 6 months, including the date of the ultrasound (OHIP fee code: J183).	Follow-up period (index date to outcome, emigration, or maximum follow-up date [March 31, 2025]).
Scrotal ultrasound	Scrotal ultrasound receipt (OHIP fee code: J183).	Follow-up period (index date to outcome, emigration, or maximum follow-up date [March 31, 2025]).

Collaborators and Investigators

• Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Publications and helpful links

General Publications

• Garg AX, McArthur E, Sontrop JM, Boudville N, Connaughton DM, Cuerden MS, Feldman LS, Lam NN, Lentine KL, Nguan C, Parikh CR, Segev DL, Sener A, Smith G, Wang C, Weir MA, Yohanna S, Young A, Naylor KL. Risk for Scrotal Surgery After Laparoscopic Donor Nephrectomy : A Population-Based Cohort Study. Ann Intern Med. 2026 Jan;179(1):23-31. doi: 10.7326/ANNALS-25-02257. Epub 2025 Nov 11.
• Gjertson CK, Sundaram CP. Testicular pain following laparoscopic renal surgery. J Urol. 2008 Nov;180(5):2037-40; discussion 2040-1. doi: 10.1016/j.juro.2008.07.045. Epub 2008 Sep 18.
• Choi SW, Moon HW, Kim KS, Choi YS, Cho HJ. Testicular Pain Following Laparoscopic Donor Nephrectomy: An Underreported Complication. J Endourol. 2024 Dec;38(12):1340-1345. doi: 10.1089/end.2024.0454. Epub 2024 Sep 16.
• Garg AX, Feldman LS, Sontrop JM, Cuerden MS, Arnold JB, Boudville N, Karpinski M, Klarenbach S, Knoll G, Lok CE, McArthur E, Miller M, Monroy-Cuadros M, Naylor KL, Prasad GVR, Storsley L, Nguan C. Testicular Pain After Living Kidney Donation: Results From a Multicenter Cohort Study. Can J Kidney Health Dis. 2025 Mar 29;12:20543581251324610. doi: 10.1177/20543581251324610. eCollection 2025.
• Shirodkar SP, Gorin MA, Sageshima J, Bird VG, Martinez JM, Zarak A, Guerra G, Chen L, Burke GW, Ciancio G. Technical modification for laparoscopic donor nephrectomy to minimize testicular pain: a complication with significant morbidity. Am J Transplant. 2011 May;11(5):1031-4. doi: 10.1111/j.1600-6143.2011.03495.x.
• Sureka SK, Srivastava A, Agarwal S, Srivastava A, An S, Singh S, Mittal V, Patidar N, Kapoor R, Ansari MS. Prevention of Orchialgia After Left-Sided Laparoscopic Donor Nephrectomy-A Prospective Study. J Endourol. 2015 Jun;29(6):696-9. doi: 10.1089/end.2014.0645. Epub 2015 Jan 28.
• El Hennawy HM, Al Faifi AS, Al Atta E, Safar O, Thamer S, El Nazer W, Kamal AI, Abdelaziz AA, Kawasmeh SA, Mirza N, Zaitoun MF, Al-Alsheikh K, Shalkamy O, Mahedy A. Post-Laparoendoscopic Single-Site Donor Nephrectomy Ipsilateral Testicular Pain, Does Operative Technique Matter? A Single Center Experience and Review of Literature. Minim Invasive Surg. 2022 Mar 23;2022:3292048. doi: 10.1155/2022/3292048. eCollection 2022.
• Pinar U, Pettenati C, Hurel S, Pietak M, Dariane C, Audenet F, Legendre C, Rozenberg A, Mejean A, Timsit MO. Persistent orchialgia after laparoscopic living-donor nephrectomy: an underestimated complication requiring information adjustment. World J Urol. 2021 Feb;39(2):621-627. doi: 10.1007/s00345-020-03228-6. Epub 2020 May 3.
• Schoephoerster J, Matas A, Jackson S, Pruett TL, Finger E, Kandaswamy R, Dunn T, Kirchner V, Anderson JK, Humphreville V. Orchialgia After Living Donor Nephrectomy: An Underreported Entity. Transplant Direct. 2022 Oct 24;8(11):e1383. doi: 10.1097/TXD.0000000000001383. eCollection 2022 Nov.
• Srivastava A, Kapoor R, Srivastava A, Ansari MS, Singh M, Kapoor R. Orchialgia after laproscopic renal surgery: a common problem with questionable etiology. Are there any predictors? World J Urol. 2013 Oct;31(5):1153-7. doi: 10.1007/s00345-012-0864-7. Epub 2012 Apr 15.
• Chin EH, Hazzan D, Herron DM, Gaetano JN, Ames SA, Bromberg JS, Edye M. Laparoscopic donor nephrectomy: intraoperative safety, immediate morbidity, and delayed complications with 500 cases. Surg Endosc. 2007 Apr;21(4):521-6. doi: 10.1007/s00464-006-9021-y. Epub 2006 Dec 16.
• Jalali M, Rahmani S, Joyce AD, Cartledge JJ, Lewis MH, Ahmad N. Laparoscopic donor nephrectomy: an increasingly common cause for testicular pain and swelling. Ann R Coll Surg Engl. 2012 Sep;94(6):407-10. doi: 10.1308/003588412X13171221592177.
• Kim FJ, Pinto P, Su LM, Jarrett TW, Rattner LE, Montgomery R, Kavoussi LR. Ipsilateral orchialgia after laparoscopic donor nephrectomy. J Endourol. 2003 Aug;17(6):405-9. doi: 10.1089/089277903767923209.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 1992
• Primary Completion (Actual): March 31, 2024
• Study Completion (Actual): March 31, 2025

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: kidney cancer; nephrectomy; laparoscopic; hydrocele; hydrocelectomy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Gonadal Disorders; Urologic Neoplasms; Testicular Diseases; Kidney Neoplasms; Testicular Hydrocele
• Other Study ID Numbers: 2026 0906 626 002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The dataset from this study is held securely in coded form at ICES. While legal data sharing agreements between ICES and data providers (e.g., healthcare organizations and government) prohibit ICES from making the dataset publicly available, access may be granted to those who meet pre-specified criteria for confidential access, available at www.ices.on.ca/DAS (email: das@ices.on.ca). The full dataset creation plan and underlying analytic code are available from the authors upon request, understanding that the computer programs may rely upon coding templates or macros that are unique to ICES and are therefore either inaccessible or may require modification.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No