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Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) generally have a high symptom burden and poor health-related quality of life, often requiring recurring systemic corticosteroid use and repeated sinus surgery. Dupilumab is a fully human monoclonal antibody that inhibits signalling of interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation, and has been approved for use in atopic dermatitis and asthma. In these two studies, we aimed to assess efficacy and safety of dupilumab in patients with CRSwNP despite previous treatment with systemic corticosteroids, surgery, or both. LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52 were two multinational, multicentre, randomised, double-blind, placebo-controlled, parallel-group studies assessing dupilumab added to standard of care in adults with severe CRSwNP. SINUS-24 was done in 67 centres in 13 countries, and SINUS-52 was done in 117 centres in 14 countries. Eligible patients were 18 years or older with bilateral CRSwNP and symptoms despite intranasal corticosteroid use, receiving systemic corticosteroids in the preceding 2 years, or having had sinonasal surgery. Patients in SINUS-24 were randomly assigned (1:1) to subcutaneous dupilumab 300 mg or placebo every 2 weeks for 24 weeks. Patients in SINUS-52 were randomly assigned (1:1:1) to dupilumab 300 mg every 2 weeks for 52 weeks, dupilumab every 2 weeks for 24 weeks and then every 4 weeks for the remaining 28 weeks, or placebo every 2 weeks for 52 weeks. All patients were randomly assigned centrally with a permuted block randomisation schedule. Randomisation was stratified by asthma or non-steroidal anti-inflammatory drug-exacerbated respiratory disease status at screening, previous surgery at screening, and country. Patients with or without comorbid asthma were included. Coprimary endpoints were changes from baseline to week 24 in nasal polyp score (NPS), nasal congestion or obstruction, and sinus Lund-Mackay CT scores (a coprimary endpoint in Japan), done in an intention-to-treat population. Safety was assessed in a pooled population of both dupilumab groups in SINUS-52 up to week 24 and the dupilumab group in SINUS-24 and the placebo groups in both studies until week 24. The trials are complete and registered at ClinicalTrials.gov, NCT02912468 and NCT02898454. Between Dec 5, 2016, and Aug 3, 2017, 276 patients were enrolled in SINUS-24, with 143 in the dupilumab group and 133 in the placebo group receiving at least one study drug dose. Between Nov 28, 2016, and Aug 28, 2017, 448 patients were enrolled in SINUS-52, with 150 receiving at least one dose of dupilumab every 2 weeks, 145 receiving at least one dose of dupilumab every 2 weeks for 24 weeks and every 4 weeks until week 52, and 153 receiving at least one dose of placebo. Dupilumab significantly improved the coprimary endpoints in both studies. At 24 weeks, least squares mean difference in NPS of dupilumab treatment versus placebo was −2·06 (95% CI −2·43 to −1·69; p<0·0001) in SINUS-24 and −1·80 (−2·10 to −1·51; p<0·0001) in SINUS-52; difference in nasal congestion or obstruction score was −0·89 (−1·07 to −0·71; p<0·0001) in SINUS-24 and −0·87 (−1·03 to −0·71; p<0·0001) in SINUS-52; and difference in Lund-Mackay CT scores was −7·44 (−8·35 to −6·53; p<0·0001) in SINUS-24 and −5·13 (−5·80 to −4·46; p<0·0001) in SINUS-52. The most common adverse events (nasopharyngitis, worsening of nasal polyps and asthma, headache, epistaxis, and injection-site erythema) were more frequent with placebo. In adult patients with severe CRSwNP, dupilumab reduced polyp size, sinus opacification, and severity of symptoms and was well tolerated. These results support the benefits of adding dupilumab to daily standard of care for patients with severe CRSwNP who otherwise have few therapeutic options. Sanofi and Regeneron Pharmaceuticals.

Seminal fluid hypersensitivity usually is characterized by postcoital vulvovaginal itching, swelling, redness, with or without systemic signs and symptoms. Efforts to manage this condition have either met with poor patient acceptance or have not been uniformly successful. We describe a 23-year-old atopic woman with documented IgE-mediated local and cutaneous hypersensitivity to SF. Using a controlled, single-blind challenge method, pretreatment with intravaginal 4% cromolyn sodium in a water-based cream completely blocked both local and cutaneous immediate hypersensitivity reactions to SF in this highly sensitive patient. We believe this may represent an alternative and more desirable method of preventive management in such patients.

This chapter reviews food additives that have been associated with both acute and chronic urticaria, angioedema, and anaphylaxis. The molecular mechanism of reactions, study design, relevant skin testing, additive challenge design, and the use of elimination diets are also reviewed.

To the Editor: There have been numerous reports of adverse reactions to nifedipine, including transient hypotension, tremors, muscle cramps, and dizziness. 1 However, none to date has included tetany. Our recent experience with nifedipine presents a possible new adverse reaction. A 73-year-old woman was admitted to the cardiac care unit with a preliminary diagnosis of unstable angina. On the second hospital day, her usual nifedipine dose of 10 mg three times a day was increased to 30 mg three times a day. Two hours later, the patient became dizzy, diaphoretic, and bradycardiac and experienced tetanic contractions and near syncope; blood pressure . . .

Current evidence suggests that controlling antibiotic resistance requires the monitoring of both susceptibility trends and antimicrobial usage within specific patient-care areas of the hospital. To assess the differences between antimicrobial usage-versus-susceptibility relationships found in the hospital and those relationships found in specific patient-care areas, susceptibility and antimicrobial usage data collected over a 5-year period (1992-1996) at the Medical University of South Carolina were analyzed. For each area, the relationship between drug use and susceptibility was analyzed for 8 gram-negative organisms with respect to 19 different agents and for 3 staphylococci with respect to 10 agents with use of simple linear regression. The relationships found in the hospital had a poorer overall agreement with the relationships found in the intensive care units (ICUs; <20%) than they did with the relationships found in the non-ICUs (∼65%). Surveillance should include both susceptibility and drug usage patterns in individual areas within an institution.

Evaluation of antimicrobial usage vs. susceptibility relationships typically involves single agents. However, susceptibility profiles may be affected by multiple drugs. From 1992 through 1996, we studied relationships between drug usage and the susceptibility (only susceptibility rates of ⩾70%) of Acinetobacter anitratus (baumannii), Enterobacter aerogenes, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Serratia marcescens to 22 agents. Linear regression was used to assess usage of each agent vs. susceptibility to it and to all agents. Only relationships with a coefficient of determination of ⩾0.5 and a negative slope were evaluated and classified as increasing drug use and decreasing susceptibility (↑D, ↓%S) or decreasing drug use and increasing susceptibility (↓D, ↑%S). The mean numbers (range) of drugs associated with a change in susceptibility were 1.7 (0–14) and 0.6 (0–7), respectively, for ↑D, ↓%S and ↓D, ↑%S relationships. Multiple antimicrobials are associated with susceptibility to other drugs; thus, surveillance of these relationships should not be limited to single drugs.