Concomitant disease

The GAD-7 questionnaire is a one-dimensional self-administered scale designed to assess the presence of the symptoms of Generalized Anxiety Disorder (GAD), as listed in the DSM-IV. The contents of the questionnaire were selected by the original authors from a larger list of symptoms. Since the Spanish version has inherited these contents, its content validity is justified by the original version. Since the objective was to obtain an instrument as similar to the original as possible, extraction of additional contents was considered inappropriate. The methodology currently recommended for adaptation of psychometric instruments was used [23 (link),24 ]; assumptions of the Classical Test Theory were also used [25 ]. The total GAD-7 score is calculated by simple addition of the answers to each item. Scores for all 7 items range from 0 (Not at all) and 3 (Nearly every day). Therefore, the total score ranges from 0 and 21. According to the original authors [22 (link)], the total score may be categorized into four severity groups: minimal (0-4), mild (5-9), moderate (10-14) and serious (14-20)[22 (link)].
The process of cultural adaptation of the questionnaire started with duplicate translations of the English original into Spanish by two separate English-speaking native translators. Both translations were reviewed by an Expert Panel consisting of 4 clinicians (including a psychiatrist), 1 expert in clinical research, and 2 methodologists specialized in measurement tasks. Both translations were then merged into a single reconciled version, which was subject to a content validity process by interrater agreement estimation. A panel of 8 specialists in psychiatric disorders was selected for this purpose. These specialists independently assessed whether each item did or did not properly measure GAD (objective concept) and whether it could or could not measure depression (distractor concept). The index of item-objective congruence was computed from the specialists' ratings [26 ]. This index has a value of 1 in the event of perfect congruence in assigning the item to one domain, and a valued of -1 when such congruence is lacking.
After content validity assessment, a pilot test was conducted on a reduced sample of patients and control subjects to assess understandability and feasibility of the translation in real subjects. Completion time was also estimated. As the questionnaire will be used in the future to identify possible GAD cases, a subsample of healthy subjects was included to further assess understandability. The reconciled version was administered to the pilot sample together with a brief additional questionnaire to ascertain the help needed to complete the questionnaire, the difficulties encountered, and sociodemographic variables. In view of the results obtained in the pilot test, the questionnaire header was modified to emphasize the frequency of symptom onset; the anchors of the response categories were also modified. The final version was translated back into English by two separate translators and sent to the original authors for conceptual equivalence assessment.
Once piloted, the final version was included in a Case Report Form (CRF) for administration to the scaling and validation sample subjects in order to determine the psychometric properties of the final version. The CRF included information on disease diagnosis, sociodemographic variables, disease treatment variables and concomitant diseases, several concurrent questionnaires of patient-reported measures, and information on the number of visits to primary care and specialist physicians.

Information from patients’ electronic health records regarding co-morbidities, medical history, and intercurrent disease is registered at baseline and throughout the course of the trial.

Height and weight were assessed in all patients the day prior to surgery to mitigate potential measurement and temporal biases. BMI was calculated by dividing the weight in kilograms by the square of their height in meters (kg/m2). The duration of GD was defined as the number of years between the date of initial diagnosis and the date of surgery. Disease status was assessed using the serum thyroid function test (TFT), including thyroid stimulating hormone (TSH), triiodothyronine (T3), free thyroxine (T4), and TR-Ab levels before surgery, either as outpatients or after hospital admission. Pathology reports were used to review the final results after surgery.
Patients with GD received treatment based on the 2016 American Thyroid Association (ATA) guidelines for hyperthyroidism (1 (link)). Patients with concomitant thyroid cancer were managed according to the 2015 ATA management guidelines for differentiated thyroid cancer (37 (link)). After the thyroidectomy, all patients discontinued antithyroid drugs and started taking L-T4 at a daily dosage suitable for their body weight (1.6 μg/kg). Patients with concomitant thyroid cancer were closely monitored every 3–6 months during the first year and then annually thereafter. Thyroid ultrasonography was conducted annually for patients with cancer.