Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The gold standard program (GSP) for smoking cessation : a cohort study of its effectiveness among smokers with and without cancer

BACKGROUND: Smoking cessation treatment is an important prognostic factor for survival after a cancer diagnosis, especially for tobacco-related cancers. After being diagnosed with lung cancer, approximately 50% of patients continue smoking or frequently relapse after a quit attempt. Given the importance of smoking cessation treatment for cancer survivors, the objective was to compare the effectiveness of a 6-week intensive smoking cessation intervention, the Gold Standard Program (GSP), among cancer survivors compared with smokers without cancer. Second, we compared successful quitting among socioeconomically disadvantaged cancer survivors with that among nondisadvantaged cancer survivors.MATERIALS AND METHODS: This was a cohort study based on 38,345 smokers from the Danish Smoking Cessation Database (2006-2016). Linkage to the National Patient Register was used to identify cancer survivors undergoing the GSP after being diagnosed with cancer (except nonmelanoma skin cancer). Linkage to the Danish Civil Registration System was used to identify participants who died, went missing, or emigrated before the follow-up. Logistic regression models were applied to evaluate effectiveness.RESULTS AND CONCLUSION: Six percent (2438) of the included smokers were cancer survivors at the time they undertook the GSP. Their 6-month successful quitting showed no difference compared to that of smokers without cancer, neither before nor after adjustment; 35% versus 37% in crude rates and an aOR of 1.13 (95% CI: 0.97-1.32). Likewise, the results for disadvantaged compared to nondisadvantaged cancer survivors were not significantly different (32% versus 33% and an adjusted aOR of 0.87 (95% CI 0.69-1.11)). Overall, an intensive smoking cessation program seems effective in helping both people without cancer and cancer survivors become successful quitters

The Danish lung cancer registry: A nationwide validation study

BACKGROUND: This study evaluates the validity of the information in the Danish Lung Cancer Registry (DLCR). Since 2000, the DLCR has been a tool for monitoring interventions and outcome of all Danish lung cancer patients with the intent to streamline and improve treatment and survival. The DLCR receives information from the Danish Patient Registries in addition to clinical information from the treating physicians. In the year 2022, more than 50 papers have been published using DLCR as a data source. However, the DLCR has not previously been validated.METHODS: A random sample of 1000 patients diagnosed with non-small cell lung cancer from 2014 to 2016 and recorded in the DLCR were included for validation. Medical records were reviewed and were considered as the "gold standard" to which data listed in the DLCR were compared.RESULTS: Information was retrieved from medical charts for all patients. Agreement on stage at diagnosis was 90.1 % (95 % CI 88.0-91.9) and on date of diagnoses was 93.8 (95 % CI 92.1-93.2). Agreement on smoking status in pack years (+/- 10 pack years) was 91.2 % (95 % CI 88.6-93.2). The positive predictive value of treatment intent was 87.4 (95 % CI 85.1-89.6).CONCLUSION: The data in the DLCR are complete, detailed and accurate. The comparison of data from the DLCR with the medical records revealed overall high validity of the data in the registry.</p