Bisoprolol

We evaluated drug use periods produced by different methods by expert opinion of two independent reviewers (HT and MK), both having expertise in clinical pharmacy. We evaluated warfarin (Anatomical Therapeutic Chemical code [ATC] B01AA03), bisoprolol (C07AB07), simvastatin (C10AA01), risperidone (N05AX08) and mirtazapine (N06AX11) purchases. The drug use periods were calculated with 13 different methods: time windows 90, 180, 360 days (WIN_90 … WIN_360); 1 DDD per day and grace periods 30, 90, 180 days (DDD_1_30 … DDD_1_180); 1 DDD and 50% proportional grace period which corresponds to 2/3 DDDs per day dose, and the grace period was included in the last purchase (DDD_066_0); 1 tablet per day and grace periods 0, 30, 90, 180 days (TAB_1_0 … TAB_1_180); 1 tablet per day with 50% proportional grace period, which corresponds to 2/3 tablets per day dose, and the grace period was included in the last purchase (TAB_066_0 in tables,) and PRE2DUP. When calculating whether the purchased amount was enough to last to the next purchase with different methods, time spent in hospital between two purchases was removed from the refill time as patients do not use their own drugs during hospital stays. Grace periods were not included in the duration of the last purchase of each drug use period (except for 50% proportional grace models).
Methods were evaluated in two separate sets: one including DDD and time window methods and PRE2DUP, and another including tablet methods with PRE2DUP. These sets included different examples (100 randomly selected purchases for each of the five drugs) because only histories having tablet information (only tablet formulations) for all purchases could be used when evaluating tablet methods. Reviewers reviewed all purchases of the person for that drug during the follow-up to decide correct formation of drug use period containing this selected purchase (when drug use period started and what purchases should be joined together). The information extracted from purchases were purchase dates, number of packages and which package was purchased, amount of DDDs purchased and days in hospital between this and the following purchase if next purchase existed. The evaluation was based on reviewer’s experience on drug use and purchasing patterns. We randomized and blinded the order of the methods for each evaluation (person and drug) to avoid bias. The evaluation included two steps;
In this study, “correctness” refers to whether drug use periods included correct purchases and whether the estimated duration was correct according to expert-opinion based evaluation. We categorized expert-opinion based correctness of drug use periods into five groups:
The main correctness measure in our study was percentage of completely correct solutions according to expert-opinion. The evaluation was based on reviewer’s experience on drug purchasing patterns and thus, no fixed dose assumptions were used in the evaluation.
Inter-rater reliability was calculated with Cohen’s Kappa. Statistics were calculated with R 3.01 (www.R-project.org). Methods were implemented with dBase 9 (dBase LLC, Binghampton, NY).

Patients were recruited from University Hospital Coventry and Warwickshire (UHCW), an 1100 bed tertiary UK hospital in the West Midlands, UK. The COVID-19 positive, symptomatic group were patients that were admitted based on respiratory symptoms and were then found to be COVID-19 positive based on a PCR test. Asymptomatic patients were identified through regular SARS-CoV-2 screening in accordance with the national guidelines at the time. COVID-19 negative patients (control arm) were identified from patients entering hospital for surgery associated with non-infectious conditions (for example, a prostate biopsy). These patients received a SARS-CoV-2 PCR test prior to admission to the hospital. The patients were reviewed for eligibility, consented to enter the study and were given a patient information leaflet. A letter detailing recruitment was then sent to their general practitioner. Demographic data collected included the age, gender, nationality, smoker status, medications they were currently prescribed and SARS-CoV-2 vaccination status of the patient. The most common medications the participants were prescribed were paracetamol, bisoprolol, omeprazole, AdCal D3, a statin, metformin, amlodipine, ramipril and sertraline. These drugs were seen in all the groups. In total, 85 patients were recruited into the study. Table 1 provides the demographic breakdown of the patient groups.

The use of BBs was identified according to the self-reported prescription medications questionnaire (https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/questionnaires.aspx?BeginYear=2005). Non-selective BBs included propranolol, carvedilol, nadolol, sotalol, pindolol, labetalol, penbutolol and timolol. Selective BBs included nebivolol, metoprolol, atenolol, bisoprolol, acebutolol, and betaxolol. The duration of the use of BBs was also obtained from the questionnaire, which was divided into four quartiles as follows: First quartile, ≤2 years; second quartile, 2-4 years; third quartile, 4-6 years; fourth quartile, >6 years). The long-term use of BBs in participants was defined as a BB treatment duration of >6 years.