Treatment of Newly Diagnosed Gastroesophageal Reflux Disease in a National Population-based Cohort
Conditions: Gastroesophageal Reflux
Sponsor: University of Southern Denmark

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Title 
Treatment of Newly Diagnosed Gastroesophageal Reflux Disease in a National Population-based Cohort 
Aim  
To compare rate of surgery with medical treatment in patients with newly diagnosed gastro-esophageal 
reflux disease in a nationwide population based cohort over 15 years. 
Background 
Episodic reflux of gastric contests to the esophagus is physiological but is considered gastroesophageal 
reflux disease (GERD) when accompanied by bothersome symptoms, typically heartburn, regurgitation or 
retrosternal pain. Extra-esophageal symptoms such as asthma, laryngitis and chronic cough may also occur 
(1). GERD is a complex and multifaceted disease (2, 3), affecting 10-20% of the Western population (4) and 
has been shown to significantly reduce the quality of life (5). Worldwide, the prevalence of GERD has been 
increasing (6–8). Treatment of GERD consists of anti-secretory drugs, mainly proton pump inhibitors (PPI), 
or anti-reflux surgery. Laparoscopic anti-reflux surgery is considered standard of care in surgical treatment 
of gastro-esophageal reflux disease (9) and with careful patient selection based on thorough preoperative 
workup (10), symptom control and patient satisfaction are high compared to medical therapy. This has 
previously been demonstrated in metaanalysis (11, 12). 
From 1990-2000 the utilization of anti-reflux surgery in the USA rose to 16.7 procedures per 100.000 
inhabitants with a concomitant rise in the use of the transabdominal laparoscopic approach. This resulted 
in a decline of perioperative mortality and morbidity (13, 14). The rate of anti-reflux surgery dropped to 6.1 
procedures per 100.000 inhabitants in 2010, men the patients were now older with significantly higher 
levels of comorbidity. Despite this, length of stay, morbidity and mortality was reduced even further. The 
laparoscopic approach is used in 80% of American procedures and the rate has not changed during the last 
ten years. It is unknown whether Denmark follows the same trends, as the popularity of anti-reflux surgery 
has been somewhat limited and the surgical setup is different with significantly fewer centers. In a Danish 
study, investigating the rate of reoperative anti-reflux surgery from 1997-2005, the rate of primary surgery 
was 5.2 per 100.000 inhabitants with a reoperation rate of 5% (15), however no data has been presented 
after 2005, and no Danish study has focused on treatment of newly diagnosed patients suffering from 
reflux disease.  
As such, it is currently unknown how many patients each year are given the diagnosis GERD after upper 
endoscopy in Denmark and what treatment they receive. It is also unknown how the utilization of medical 
and surgical treatment has developed in this group of patients.  
Methods 
The study is a register-based cohort study with data from Danish national health registries (The National 
Patient Registry, The Danish National Prescription Register and The Civic Registry). The study period is 
2000-2015.  
The study population consists of all adult Danish patients diagnosed with GERD and GERD-related diagnosis 
identified with ICD-10 codes DK20.9B, DK21.0-21.9B & DK22.7 using The National Patient Registry).To 

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validate GERD-diagnosis, upper endoscopy must have been performed no more than three months before 
time of diagnosis for the patient to be included.  Endoscopy must have been performed during the study 
period 2000-2015. 
Patients with GERD and GERD-related diagnosis up to four years before upper endoscopy are excluded 
from the study as are patients with any diagnosis of cancer of the gastrointestinal tract 4 years prior to 
upper endoscopy to the end of follow-up.  
Age, sex and Charlson Comorbidity Index at date of primary upper endoscopy are derived from the National 
Patient Registry. From the same source, any anti-reflux surgery (Nomesco:  KJBC00, KJBC01, KJBC02, 
KJBW96, KJBW97) performed within two years of inclusion are identified.  
From The National Prescription Register, data on medical treatment with any antacid and anti-secretory 
treatment (ATC: MA02B) are identified from 4 years before inclusion to 2 years after. Data on anti-
thrombotic drugs and non-steroid anti-inflammatory drugs (ATC: MB01A & MM01A) are also retrieved for 
the same period to adjust for possible preventive therapy with anti-secretory drugs.  From the Civic 
Register, data on mortality in the follow-up period are retrieved. 
Statistical analysis 
Data will be analyzed using STATA15. Descriptive analysis of age, sex, Charlson Comorbidity Index, mortality 
and rate of anti-thrombotic treatment comparing patients treated pharmacologically (in defined daily 
dosages per year) or surgically (any anti-reflux procedure) for reflux disease using Student’s t-test, Chi2-test 
and Mann-Whitney-U test.  
Logistic and multinominal regression will be performed with treatment type (pharmacological, surgical or 
none) as primary outcome and age, sex, Charlson Comorbidity Index, pharmacological anti-reflux treatment 
prior to diagnosis, antithrombotic treatment and year of diagnosis as independent variables.  
Secondary analysis will be performed using Cox-regression investigating time to initiation of any treatment 
with age, sex, Charlson Comorbidity Index, pharmacological anti-reflux treatment prior to diagnosis, 
antithrombotic treatment and year of diagnosis as independent variables. Change in treatment rates over 
time will also be investigated using national Danish census data and Poisson regression.  
Sensitivity analysis excluded patients with anti-thrombotic treatment will be performed.  
Funding and Ethical considerations 
The study is part of a ph.d. thesis and is funded by The Region of Southern Denmark, The University of 
Southern Denmark, The Department of Surgery, Kolding Hospital  and The Research Council at Little Belt 
Hospital.  
The study requires no informed consent in Danish law as the study is register-based. However, permission 
from The Danish Data Protection Agency and The Danish Health Data Agency will be obtained before the 
study is commenced.  
None of the involved parties have financial interests or conflicts of interest pertaining to this study.  

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