This was a population-based cohort study using data extracted from the Leumit Health Services (LHS) electronic medical database. LHS is one of four Israeli health maintenance organisations. It has a countrywide presence and its membership during the study period consisted of 724 129 individuals, which constitutes about 7.4% of the Israeli population. The members come from all ethnic, religious and socioeconomic groups. All LHS members have uniform health insurance coverage and equitable access to healthcare services. The LHS database is continuously updated with information on demographics, medical visits, diagnoses, laboratory tests, hospitalisations, and medication prescriptions. It includes prescription records dating back to 1998, consisting of both refills and purchases for each patient. The validity of diagnoses in the database has been previously found to be high.14

This observational historical cohort study encompassed all LHS members aged 5–18 years between 1 January 2002 and 30 November 2022. The study group consisted of individuals with a confirmed diagnosis based on International Classification of Diseases, 9th Edition (ICD-9) criteria of ADHD (314.00–314.9). The control group consisted of randomly selected LHS members without ADHD, at a 2:1 ratio, individually matched for age (to a precision of quarter years), gender, socioeconomic status (SES; see details below), major sector (Arabs, Secular Jews, Ultra-Orthodox Jews), residence, year of first membership and cumulative years of LHS membership up to the index date.

SES classification was based on the Israeli Central Bureau of Statistics criteria, ranked from 1 (lowest) to 20 (highest); categories 1–3 indicated very low SES, 4–6 indicated low SES, 7–9 indicated medium SES, and 10–20 denoted medium-high SES.

The study group consisted of individuals with a confirmed diagnosis of ADHD (ADHD group) as described above. Diagnosis was based on Israeli Ministry of Health criteria, which adhere to international standards. Namely, the diagnosing physician must be a senior physician specialising in ADHD, such as a child or adult psychiatrist, child or adult neurologist or a paediatrician or family physician certified for ADHD diagnosis. Diagnoses were established according to the DSM-4-TR or DSM 5 criteria, depending on the year of diagnosis.3

Each individual in the ADHD group was randomly matched with two individuals from a control pool of LHS members without an ADHD diagnosis, matched on key demographic characteristics: year and quarter of birth, gender, major religious sector, SES, geographical region and years of LHS membership. Control group individuals were assigned the same index date as their corresponding ADHD cases to minimise potential confounding factors.

For each individual in the cohort, demographic and body mass index (BMI) data were extracted as recorded at the index date or, if unavailable, from the first measurement taken after the index date.

Additional medical parameters, including laboratory results, medication usage and specialist visits, were queried for the cohort. These data were collected for the 7 years following the index date. For laboratory tests with multiple results during the follow-up period, the median value was used. Medication usage was defined as at least one purchase of a drug within the relevant Anatomical Therapeutic Classification (ATC) during the follow-up period. The analysed ATC categories included D04AA (topical antihistamines), H02 (systemic corticosteroids), N03 (antiepileptics), N05 (psycholeptics), N06AB (selective serotonin reuptake inhibitors (SSRIs)), N06BA (centrally acting sympathomimetics), and R06 (systemic antihistamines).

Urticaria diagnoses included all urticarial diseases, according to ICD-9 codes 708, 708.0, 708.1, 708.2, 708.3, 708.5, 708.8, 708.9, 698.22. To identify the patients with SU, we used the following algorithm: one or more of the ICD-9 diagnoses codes 708.1, 708.8, 708.9, and absence of inducible urticaria diagnoses 708.0, 708.2, 708.3, 708.5 or 698.22.15 All SU patients were diagnosed and managed according to the joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA (2) LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) (EAACI/GA(2)LEN /EDF/WAO) guidelines.12