Lin 2000.

Methods	This was a prospective, double‐blind, RCT. Setting Departments of Emergency Medicine and Medicine, Saint Vincent's Hospital & Medical Center of New York and New York Medical College, New York, NY, US Date of study May 1998 and April 1999 Duration of study 2 hours
Participants	Inclusion criteria of the trial Adults (> 18 years) with acute allergic syndromes, i.e. acute urticaria, acute angioedema, acute unexplained stridor (loud wheezing), acute pruritic rash Present for < 12 hours from the time of alleged allergen exposure Due to ingested food; ingested, inhaled, or injected drug; or after contact with latex Exclusion criteria of the trial Pregnancy Randomised 100 participants were randomised: 21 men and 27 women in the ranitidine and diphenhydramine group, and 15 men and 28 women in the diphenhydramine group. Age The median age in the ranitidine and diphenhydramine group was 32.3 years (ranging from 19.6 to 79.4) and 31.7 years (ranging from 21.3 to 74.4) in the diphenhydramine group. Baseline data The median duration of symptoms was 1 hour in the ranitidine and diphenhydramine group and 2 hours in the diphenhydramine group. Stridor, tongue swelling, or laryngoedema affected 5 participants in each group. Antihistamines were taken by 10 participants in the preceding 36 hours of the study (by 4 in the ranitidine and diphenhydramine group and 6 diphenhydramine group). Withdrawals/dropouts There were 9 withdrawals/dropouts after randomisation: 1 participant was inadvertently studied twice and 8 were lost prior to administration.
Interventions	Intervention A: 50 mg diphenhydramine and 50 mg ranitidine (H1 + H2) intravenously (48) Control intervention B: 50 mg diphenhydramine and normal saline solution (H1) intravenously (43) Supplemental medications, e.g. epinephrine, corticosteroids, bronchodilators and additional doses of antihistamines, were "administered at the discretion of the study physicians".
Outcomes	Assessments were at baseline and 1 hour and 2 hours relative to the experimental treatment. Primary outcomes of the trial 1) Investigator‐assessed resolution of urticaria (check‐off cartoon of body areas) and angioedema at 2 hours Secondary outcomes of the trial 1) Heart rate, blood pressure, and respiratory rates 2) Side‐effects 3) Symptoms (none, mild, moderate, and severe)
Notes	Only data on participants with acute urticaria (29 in the ranitidine and diphenhydramine group and 24 in the diphenhydramine group) were included.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (page 463): "Recruited patients were randomly assigned to treatment...on the basis of a random number assignment list." Comment: This was probably done.
Allocation concealment (selection bias)	Low risk	Quote (page 463): "Recruited patients were randomly assigned to treatment...Each treatment designation was placed in a sealed opaque envelope stored in a locked cabinet." Comment: A form of central allocation was probably done.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (page 463): "A staff member uninvolved with the patient's care then drew into a syringe either 50 mg of ranitidine solution or an equal volume of normal saline solution on the basis of a random number assignment list. Immediately after an intravenous injection of 50 mg of diphenhydramine was given, the unmarked syringe containing either saline solution or ranitidine was then given to the study physician, who was unaware of its contents." Comment: The report provides sufficient detail about the measures used to blind study participants and personnel from knowledge of which intervention a participant received, to permit a clear judgement. We judged this as at a low risk of bias.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (page 463): "A staff member uninvolved with the patient's care then drew into a syringe either 50 mg of ranitidine solution or an equal volume of normal saline solution on the basis of a random number assignment list. Immediately after an intravenous injection of 50 mg of diphenhydramine was given, the unmarked syringe containing either saline solution or ranitidine was then given to the study physician, who was unaware of its contents." Comment: The outcomes were investigator‐assessed. We judged that the intended blinding of participants and key personnel was probably effective and unlikely to introduce bias into the outcome assessment.
Incomplete outcome data (attrition bias) All outcomes	Low risk	9/100 were not included in the analysis (1 was inadvertently studied twice, and 8 withdrew after the study medication had been obtained, but before administration). Another 9 were reclassified, but included on the basis of an intention‐to‐treat (ITT) analysis. Comment: 9 dropouts were equally balanced between the 2 groups. We judged this as at a low risk of bias.
Selective reporting (reporting bias)	Low risk	The protocol for the study was not available, but the prespecified outcomes and those mentioned in the methods section appear to have been reported. Comment: We judged this as at a low risk of bias.
Other bias	Unclear risk	10 participants took antihistamines (4 in the ranitidine and diphenhydramine group and 6 in the diphenhydramine group) < 36 hours prior to the study. There was no declaration of potential conflicts of interest or funding support. Comment: There was insufficient information to permit a clear judgement of the risk of bias.