Association between the use of Proton Pump Inhibitors and Histamine-2 Receptor Antagonists and the risk of gastric cancer in Norway

Background: The use of proton pump inhibitors (PPIs) on prescription has increased over the last decade in Norway. PPIs are an important medication in the treatment of acid related disorders such as peptic ulcer disease, gastroesophageal reflux disease and Helicobacter Pylori (H. Pylori) infection. However, many previous studies have raised concern about the potential risk of gastric cancer following the use of PPIs. In this registry-based study we will investigate the association between use of PPI and Histamine-2 receptor antagonist (H2RA) and the risk of gastric cancer in Norway. Methods: This population-based nested case-control study comprises all primary gastric cancer cases in Norway diagnosed between 2007 and 2015 at an age of 18-85 and registered in the Cancer Registry of Norway. Ten cancer free controls were matched to each case on birth year, sex and index date (date of diagnosis). PPI and H2RA drug exposure were retrieved from the Norwegian Prescription Database and modelled as binary use, long-term use, cumulative use and in an active comparator design. Moreover, we used a stratified cox regression adjusted for H. Pylori, residency, education, comorbidity and other drug use to assess the link between PPI and H2RA use and the risk of gastric cancer. Results: Among 33 847 individuals in this study, we found an increased risk of gastric cancer among PPI users (HR=1.25, 95% Cl 1.13-1.37) and long-term PPI users (HR=1.18, 95% Cl 1.03-1.36) in Norway. There was also a significant impact on gastric cancer among PPI users living in Northern Norway (HR=1.43, 95% Cl 1.27-1.61). However, the dose-response relationship for PPI and the corresponding results for H2RA were not associated with an increased risk of gastric cancer. Conclusion: The association found between PPI use and the increased risk of gastric cancer was most likely due to confounding by indication like H. Pylori infection and other unobserved confounders. Observational studies adjusted for all relevant confounders and larger clinical studies with a longer follow-up are needed to establish or rule out a causal relationship between PPI use and gastric cancer risk in the future

Association Of Diurnal Temperature Range With Pediatric Influenza Hospitalization Rates In The United States, 2009 – 2019

Introduction: Climate change may have a negative impact on respiratory illnesses, such as influenza. Diurnal temperature range (DTR), an indicator of climate change, is the difference between the maximum and minimum temperature within a day or a week. As the climate warms, global DTR decreases, though there might be regions where DTR increases instead. Previous literature conducted in non-U.S. regions found both positive and negative associations between DTR and influenza infections. A group especially vulnerable to the effects of DTR are children less than 5 years of age due to their less-developed thermoregulation capability. This study thus aimed to explore the association of DTR with pediatric influenza hospitalization rates in different U.S. states from 2009 to 2019 to further understand this relationship. Methods: Utilizing weekly influenza hospitalization rates from the Center for Disease Control and Prevention (CDC)’s FluSurv-NET surveillance system and meteorological data from the National Oceanic and Atmospheric Administration (NOAA), we employed a distributed non-linear lag model and a generalized additive model using a quasi-Poisson distribution to examine the complex non-linear relationship between the two variables, adjusting for relative humidity, mean temperature, and precipitation. Results: New York’s Albany and Rochester, Michigan, and California exhibited positive associations between DTR and pediatric influenza hospitalization rate (relative risk at maximum DTR was 3.06 (95% confidence interval (CI): 1.532 – 5.893), 1.97 (95% CI: 1.018 –3.812), 2.07 (95% CI: 1.185 – 3.601), and 1.69 (95% CI: 1.054 – 2.707), respectively). Additionally, there was a respective 1,403% (p = 0.007), 475% (p = 0.045), 569% (p = 0.011), and 344% (p=0.030) change in hospitalization rate for every 1°C increase in DTR. Conclusions: Our results can be used to inform the development of an early warning system that can alert the potential impact of a significant increase in DTRs. With regard to climate change, if global DTR decreases as the climate warms, then our results suggest that hospitalization rates will decrease as well, though in regions where DTR increases, hospitalization rates might increase. Further research on the relationship between temperature variability and respiratory infections that utilizes more granular data and that considers other important meteorological factors, influenza strain type, and vaccination history is needed