Daily Respiratory Research Analysis

BACKGROUND: Electronic letters have demonstrated effectiveness in improving vaccination uptake among patients with chronic diseases, but the effects of serial implementation over consecutive influenza seasons are unknown. METHODS: In a nationwide randomized implementation trial, conducted during the 2024-2025 influenza season, that included all Danish citizens 18-64 years of age who were eligible for free-of-charge influenza vaccination because of a chronic condition, we randomly assigned participants in a 2.45:1:1:1:1:1:1 ratio to usual care (no letter) or to one of six different behaviorally informed electronic letter strategies. All data were sourced from nationwide Danish health registries. The primary end point was receipt of an influenza vaccine on or before January 1, 2025, analyzed through seven coprimary comparisons (all intervention groups pooled vs. usual care, and each intervention group vs. usual care). RESULTS: We randomly assigned 308,978 Danish citizens 18-64 years of age; 164,100 (53.1%) were female; the median age was 52.1 years (interquartile range, 39.7-59.2). Compared with usual care, influenza vaccination rates were higher among those receiving any intervention letter (36.5% vs. 24.1%; difference, 12.4 percentage points [99.29% confidence interval [CI], 11.9-12.9]; P<0.001). Significant increases in influenza vaccination were observed with each letter type compared with usual care. Among the six different electronic letter strategies, the largest effect size was observed with a repeated cardiovascular-focused letter (39.1% vs. 24.1%; difference, 15.0 percentage points [99.29% CI, 14.2 to 15.7]; P<0.001). There was no apparent difference in the effect size of letters compared with usual care across major subgroups, including among those who had also received a similar letter during the preceding influenza season. CONCLUSIONS: Electronically delivered, letter-based nudges significantly increased influenza vaccination among 18-to-64-year-old individuals with chronic diseases compared with usual care, when delivered during a second consecutive season. The largest effect size was with a strategy where a letter focused on the potential cardiovascular benefits of influenza vaccination was sent twice. (ClinicalTrials.gov number, NCT06600490.).

BACKGROUND: Radiation-induced lung injury is a major dose-limiting toxicity in thoracic radiotherapy. Pirfenidone, an oral antifibrotic drug that is often used to treat idiopathic pulmonary fibrosis, could offer therapeutic benefits for patients with radiation-induced lung injury. We evaluated the efficacy and safety of pirfenidone in patients with grade 2 or grade 3 radiation-induced lung injury. METHODS: This multicentre, open-label, randomised, phase 2 clinical trial enrolled patients with grade 2 or grade 3 radiation-induced lung injury diagnosed according to Common Terminology Criteria for Adverse Events version 5.0 from ten medical centres across China. Eligible patients were aged 18-75 years with an Eastern Cooperative Oncology Group performance status of 0-2 and had grade 2 or grade 3 radiation-induced lung injury. Patients were randomly assigned (1:1) using a computer-generated random number table to receive either pirfenidone plus glucocorticoids or glucocorticoids alone. Pirfenidone was given orally three times daily at doses of 200 mg in week 1, 300 mg in week 2, and 400 mg in weeks 3-24. Glucocorticoids were administered concurrently at the equivalent dose of prednisone 40 mg/day, divided into two oral doses, and maintained for 2 weeks, followed by a tapering schedule of 10 mg every 2 weeks over a period of 6 to 8 weeks. The control group received glucocorticoids only. The primary endpoint, evaluated in the modified intention-to-treat population, was the change in the percentage of carbon monoxide diffusing capacity (DLCO%) from baseline to week 24. Safety was assessed in all participants who received at least one dose of treatment. The trial is registered with ClinicalTrials.gov, NCT03902509, and has completed enrolment. FINDINGS: Between Nov 29, 2021, and Dec 4, 2023, 134 patients were enrolled and randomly assigned, with 67 patients in each group study group. 105 (78%) of 134 patients were male and 29 (22%) were female. The median follow-up was 9·2 months (IQR 6·3-16·0). At week 24, the pirfenidone group showed an 8·0% improvement from baseline in DLCO%, whereas the control group showed a 2·4% reduction (least squares mean difference 10·4%, 95% CI 4·3-16·5; p=0·0010). The most common grade 3 or worse adverse events included pneumonia (four [6%] of 67 patients in the pirfenidone group vs eight [12%] of 67 patients in the control group), and rash (two [3%] of 67 patients in the pirfenidone group vs none in the control group). Serious adverse events occurred in 12 (18%) of 67 patients in the pirfenidone group and 11 (16%) of 67 patients in the control group. There were no treatment related deaths. INTERPRETATION: Pirfenidone in combination with glucocorticoids provides a potential therapeutic strategy for grade 2 or grade 3 radiation-induced lung injury, addressing the unmet clinical need for effective antifibrotic therapy in patients receiving thoracic radiotherapy. Further investigation is needed to validate these findings in patients with worse radiation-induced lung injury than was studied here. FUNDING: Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Key R&D Program of China, National Natural Science Foundation of China, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center.

BACKGROUND: The high-dose inactivated influenza vaccine (HD-IIV) has demonstrated superior protection against a range of hospitalization endpoints versus standard-dose inactivated influenza vaccine (SD-IIV), but its effectiveness against specific cardiovascular (CV) outcomes and in those with pre-existing CV disease (CVD) is not well elucidated. METHODS: In a prespecified secondary analysis of the FLUNITY-HD individual-level pooled dataset integrating two methodologically harmonized pragmatic, individually randomized trials conducted in Denmark and Spain, we investigated the relative vaccine effectiveness (rVE) of HD-IIV vs. SD-IIV against severe CV outcomes and according to pre-existing CVD among adults aged ≥65 years. Data were primarily obtained from routine healthcare databases, with follow-up from 14 days post-vaccination to May 31 the following year. RESULTS: The pooled dataset encompassed 466,320 individually randomized participants, of whom 107,700 (23.1%) had a history of CVD. HD-IIV reduced the incidence of hospitalization for influenza or pneumonia, cardio-respiratory disease, laboratory-confirmed influenza, and any cause compared with SD-IIV, irrespective of the presence or absence of pre-existing CVD (p CONCLUSIONS: In a prespecified pooled analysis of 466,320 individually randomized older adults, HD-IIV reduced the incidence of a wide range of severe CV and respiratory outcomes compared with SD-IIV, with consistent findings regardless of prior history of CVD. Among CV outcomes, the protective effect of HD-IIV vs. SD-IIV was particularly pronounced against hospitalization for heart failure.