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1.	Ness-Jensen, Eivind, et al. (author) All-cause and cancer-specific mortality in GORD in a population-based cohort study (the HUNT study) 2018 In: Gut. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0017-5749 .- 1468-3288. Journal article (peer-reviewed)abstract OBJECTIVE: Gastro-oesophageal reflux is a public health concern which could have associated oesophageal complications, including adenocarcinoma, and possibly also head-and-neck and lung cancers. The aim of this study was to test the hypothesis that reflux increases all-cause and cancer-specific mortalities in an unselected cohort. DESIGN: The Nord-Trondelag health study (HUNT), a Norwegian population-based cohort study, was used to identify individuals with and without reflux in 1995-1997 and 2006-2008, with follow-up until 2014. All-cause mortality and cancer-specific mortality were assessed from the Norwegian Cause of Death Registry and Cancer Registry. Multivariable Cox regression was used to calculate HRs with 95% CIs for mortality with adjustments for potential confounders. RESULTS: We included 4758 participants with severe reflux symptoms and 51 381 participants without reflux symptoms, contributing 60 323 and 747 239 person-years at risk, respectively. Severe reflux was not associated with all-cause mortality, overall cancer-specific mortality or mortality in cancer of the head-and-neck or lung. However, for men with severe reflux a sixfold increase in oesophageal adenocarcinoma-specific mortality was found (HR 6.09, 95% CI 2.33 to 15.93) and the mortality rate was 0.27 per 1000 person-years. For women, the corresponding mortality was not significantly increased (HR 3.68, 95% CI 0.88 to 15.27) and the mortality rate was 0.05 per 1000 person-years. CONCLUSIONS: Individuals with severe reflux symptoms do not seem to have increased all-cause mortality or overall cancer-specific mortality. Although the absolute risk is small, individuals with severe reflux symptoms have a clearly increased oesophageal adenocarcinoma-specific mortality.
2.	Hallan, Andreas, et al. (author) Risk factors on the development of new-onset gastroesophageal reflux symptoms : a population-based prospective cohort study : the HUNT study 2015 In: The American Journal of Gastroenterology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0002-9270 .- 1572-0241. Journal article (peer-reviewed)abstract OBJECTIVES: Gastroesophageal reflux disease (GERD) is a highly prevalent disorder. This study assessed the risk factors of new-onset gastroesophageal reflux symptoms (GERS). METHODS: The study was based on the HUNT study, a prospective population-based cohort study conducted in 1995-1997 and 2006-2009 in Nord-Trondelag County, Norway. All inhabitants from 20 years of age were invited. Risk factors of new-onset heartburn or acid regurgitation were examined using logistic regression, providing odds ratios (OR) and 95% confidence intervals (CI). RESULTS: A total of 29,610 individuals were included (61% response rate). Participants reporting no GERS at baseline and severe GERS at follow-up (new-onset GERS; n=510) were compared with participants reporting no complaints at both times (n=14,406). Increasing age (OR 1.01 per year, 95% CI 1.00-1.02) was positively associated, whereas male sex (OR 0.81, 95% CI 0.66-0.98) and higher education (OR 0.69, 95% CI 0.56-0.86) were negatively associated with new-onset GERS. Gain in body mass index (BMI) was dose-dependently associated with new-onset GERS (OR 1.30 per unit increase in BMI, 95% CI 1.25-1.35), irrespective of baseline BMI. Previous and current tobacco smoking were associated with new-onset GERS (OR 1.37, 95% CI 1.07-1.76 and OR 1.29, 95% CI 1.00-1.67, respectively). Tobacco smoking cessation was associated with new-onset GERS among those with gain in BMI upon quitting (OR 2.03, 95% CI 1.31-3.16, with >3.5 BMI units increase). CONCLUSIONS: New-onset GERS were associated with increasing age, female sex, lower education, gain in BMI, and ever tobacco smoking. Tobacco smoking cessation was associated with new-onset GERS among those who gained weight upon quitting.
3.	Holmberg, Dag, et al. (author) Incidence and Mortality in Upper Gastrointestinal Cancer After Negative Endoscopy for Gastroesophageal Reflux Disease 2022 In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 162:2, s. 431-438.e4 Journal article (peer-reviewed)abstract BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is associated with an increased risk of cancer of the upper gastrointestinal tract. This study aimed to assess whether and to what extent a negative upper endoscopy in patients with GERD is associated with decreased incidence and mortality in upper gastrointestinal cancer (ie, esophageal, gastric, or duodenal cancer).METHODS: We conducted a population-based cohort study of all patients with newly diagnosed GERD between July 1, 1979 and December 31, 2018 in Denmark, Finland, Norway, and Sweden. The exposure, negative upper endoscopy, was examined as a time-varying exposure, where participants contributed unexposed person-time from GERD diagnosis until screened and exposed person-time from the negative upper endoscopy. The incidence and mortality in upper gastrointestinal cancer were assessed using parametric flexible models, providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs).RESULTS: Among 1,062,740 patients with GERD (median age 58 years; 52% were women) followed for a mean of 7.0 person-years, 5324 (0.5%) developed upper gastrointestinal cancer and 4465 (0.4%) died from such cancer. Patients who had a negative upper endoscopy had a 55% decreased risk of upper gastrointestinal cancer compared with those who did not undergo endoscopy (HR, 0.45; 95% CI, 0.43-0.48), a decrease that was more pronounced during more recent years (HR, 0.34; 95% CI, 0.30-0.38 from 2008 onward), and was otherwise stable across sex and age groups. The corresponding reduction in upper gastrointestinal mortality among patients with upper endoscopy was 61% (adjusted HR, 0.39; 95% CI, 0.37-0.42). The risk reduction after a negative upper endoscopy in incidence and mortality lasted for 5 and at least 10 years, respectively.CONCLUSIONS: Negative upper endoscopy is associated with strong and long-lasting decreases in incidence and mortality in upper gastrointestinal cancer in patients with GERD.
4.	Holmberg, Dag, et al. (author) Non-erosive gastro-oesophageal reflux disease and incidence of oesophageal adenocarcinoma in three Nordic countries : population based cohort study 2023 In: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 382, s. e076017- Journal article (peer-reviewed)abstract Objective To assess the incidence rate of oesophageal adenocarcinoma among patients with non-erosive gastro-oesophageal reflux disease compared with the general population.Design Population based cohort study.Setting All patients in hospital and specialised outpatient healthcare in Denmark, Finland, and Sweden from 1 January 1987 to 31 December 2019.Participants 486 556 adults (>18 years) who underwent endoscopy were eligible for inclusion: 285 811 patients were included in the non-erosive gastro-oesophageal reflux disease cohort and 200 745 patients in the validation cohort with erosive gastro-oesophageal reflux disease.Exposures Non-erosive gastro-oesophageal reflux disease was defined by an absence of oesophagitis and any other oesophageal diagnosis at endoscopy. Erosive gastro-oesophageal reflux disease was examined for comparison reasons and was defined by the presence of oesophagitis at endoscopy.Main outcome measures The incidence rate of oesophageal adenocarcinoma was assessed for up to 31 years of follow-up. Standardised incidence ratios with 95% confidence intervals were calculated by dividing the observed number of oesophageal adenocarcinomas in each of the gastro-oesophageal reflux disease cohorts by the expected number, derived from the general populations in Denmark, Finland, and Sweden of the corresponding age, sex, and calendar period.Results Among 285 811 patients with non-erosive gastro-oesophageal reflux disease, 228 developed oesophageal adenocarcinomas during 2 081 051 person-years of follow-up. The incidence rate of oesophageal adenocarcinoma in patients with non-erosive gastro-oesophageal reflux disease was 11.0/100 000 person-years. The incidence was similar to that of the general population (standardised incidence ratio 1.04 (95% confidence interval 0.91 to 1.18)), and did not increase with longer follow-up (1.07 (0.65 to 1.65) for 15-31 years of follow-up). For validity reasons, we also analysed people with erosive oesophagitis at endoscopy (200 745 patients, 1 750 249 person-years, and 542 oesophageal adenocarcinomas, corresponding to an incidence rate of 31.0/100 000 person-years) showing an increased overall standardised incidence ratio of oesophageal adenocarcinoma (2.36 (2.17 to 2.57)), which became more pronounced with longer follow-up.Conclusions Patients with non-erosive gastro-oesophageal reflux disease seem to have a similar incidence of oesophageal adenocarcinoma as the general population. This finding suggests that endoscopically confirmed non-erosive gastro-oesophageal reflux disease does not require additional endoscopic monitoring for oesophageal adenocarcinoma.
5.	Kauppila, Joonas H., et al. (author) Risk Factors for Suicide After Bariatric Surgery in a Population-based Nationwide Study in Five Nordic Countries 2022 In: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 275:2, s. E410-E414 Journal article (peer-reviewed)abstract Objective:To identify risk factors for suicide after bariatric surgery.Summary background data:Bariatric surgery reduces obesity-related mortality. However, it is for unclear reasons is associated with an increased risk of suicide.Methods:This population-based cohort study included patients having undergone bariatric surgery in 1982 to 2012 in any of the 5 Nordic countries, with follow-up through 2012. Eleven potential risk factors of suicide (sex, age, comorbidity, surgery type, surgical approach, calendar year of surgery, history of depression or anxiety, psychosis, schizophrenia, mania, or bipolar disorder, personality disorder, substance use, and number of previously documented psychiatric diagnoses) were analyzed using Cox regression.Results:Of 49,977 bariatric surgery patients, 98 (0.2%) committed suicide during follow-up. Women had a decreased risk of suicide compared to men (hazard ratio [HR] = 0.48, 95% confidence interval [CI] 0.33-0.77), although age and comorbidity did not influence this risk. Compared to gastric bypass, other types of bariatric surgery had lower risk of suicide (HR = 0.44, 95%CI 0.27-0.99). There was no difference in suicide risk between laparoscopic and open surgical approach. A history of depression or anxiety (HR = 6.87, 95%CI 3.97-11.90); mania, bipolar disorder, psychosis, or schizophrenia (HR = 2.70, 95%CI 1.14-6.37); and substance use (HR = 2.28, 95%CI 1.08-4.80), increased the risk of suicide. More of the above psychiatric diagnoses increased the risk of suicide (HR = 22.59, 95%CI 12.96-39.38 for ≥2 compared to 0 diagnoses).Conclusions:Although the risk of suicide is low, psychiatric disorders, male sex, and gastric bypass procedure seem to increase the risk of suicide after bariatric surgery, indicating a role for tailored preoperative psychiatric evaluation and postoperative surveillance.
6.	Lie, Tina Malene, et al. (author) Snus and risk of gastroesophageal reflux : a population-based case-control study : the HUNT study 2017 In: Scandinavian Journal of Gastroenterology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0036-5521 .- 1502-7708. Journal article (peer-reviewed)abstract Objective: Tobacco smoking is a risk factor for gastroesophageal reflux, but whether other tobacco products increase the risk is unclear. The aim of this study was to investigate if snus increases the risk of gastroesophageal reflux symptoms (GERS). Material and Methods: The study was based on the third Nord-Trøndelag health study (HUNT3), a population-based study of all adult residents in Nord-Trøndelag County, Norway, performed in 2006−2009. The association between self-reported severe heartburn/regurgitation and snus use was assessed by logistic regression. Results: Compared to never snus users, daily snus users had a reduced risk of GERS (OR 0.77, 95% CI 0.64−0.93), while previous snus users and those using <2 boxes of snus/month had an increased risk (OR 1.20, 95% CI 1.00−1.46 and 1.41, 95% CI 1.02−1.96, respectively). There was no association between age when starting using snus and GERS. Snus users who started using snus to quit or cut down on cigarette smoking, who started using both snus and cigarettes or cigarettes alone had an increased risk of GERS. Snus users <30 years of age had an increased risk of GERS (OR 1.49, 95% CI 1.02−2.16), while those aged between 50−60 and 60−70 years had a reduced risk (OR 0.67, 95% CI 0.49−0.93 and 0.51, 95% CI 0.28−0.94, respectively). Conclusions: Daily snus users had a reduced risk of GERS. However, previous snus users and subgroups of snus users had an increased risk of GERS indicating reverse causality, such that snus use could increase the risk of GERS.
7.	Lin, Yulan, et al. (author) Metabolic syndrome and esophageal and gastric cancer 2015 In: Cancer Causes and Control. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0957-5243 .- 1573-7225. Journal article (peer-reviewed)abstract BACKGROUND: The role of the metabolic syndrome in the etiology of esophageal and gastric cancer is unclear. METHODS: This was a large nationwide cohort study based on data from 11 prospective population-based cohorts in Norway with long-term follow-up, the Cohort of Norway (CONOR) and the third Nord-Trondelag Health Study (HUNT3). The metabolic syndrome was assessed by objective anthropometric and metabolic biochemical measures and was defined by the presence of at least three of the following five factors: increased waist circumference, elevated triglycerides, low high-density lipoprotein cholesterol, hypertension and high glucose. Newly diagnosed cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma and gastric adenocarcinoma were identified from the Norwegian Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models with adjustment for potential confounders. RESULT: Among 192,903 participants followed up for an average of 10.6 years, 62 developed esophageal adenocarcinoma, 64 had esophageal squamous-cell carcinoma and 373 had gastric adenocarcinoma. The metabolic syndrome was significantly associated with an increased risk of gastric adenocarcinoma (HR 1.44, 95% CI 1.14-1.82), but not associated with esophageal adenocarcinoma (HR 1.32, 95% CI 0.77-2.26) or esophageal squamous-cell carcinoma (HR 1.08, 95% CI 0.64-1.83). Increased waist circumference was associated with an increased HR of esophageal adenocarcinoma (HR 2.48, 95% CI 1.27-4.85). No significant association was found between any single component of the metabolic syndrome and risk of esophageal squamous-cell carcinoma. High waist circumference (HR 1.71, 95% CI 1.05-2.80), hypertension (HR 2.41, 95% CI 1.44-4.03) and non-fasting glucose (HR 1.74, 95% CI 1.18-2.56) were also related to an increased risk of gastric adenocarcinoma in women, but not in men. CONCLUSION: Metabolic syndrome was associated with an increased risk of gastric adenocarcinoma in women. Of the individual components of the metabolic syndrome, high waist circumference was positively associated with risk of esophageal adenocarcinoma. Positive associations were also observed for women between high waist circumference, hypertension, high non-fasting glucose and risk of gastric adenocarcinoma. However, further evidence is warranted due to the limited number of cases and the inability to effectively identify gastric cardia adenocarcinoma.
8.	Lu, Yunxia, et al. (author) Anthropometry-based obesity phenotypes and risk of colorectal adenocarcinoma : a large prospective cohort study in Norway 2016 In: Epidemiology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1044-3983. ; 27:3, s. 423-432 Journal article (peer-reviewed)abstract BACKGROUND: It is unclear whether obesity phenotypes measured by different anthropometric indices are associated with a risk of colorectal adenocarcinoma by anatomical location. METHODS: We compiled harmonized population-based cohort studies (Cohort of Norway, CONOR) with 143,477 participants that were conducted between 1994 and 2010. General, abdominal, and gluteofemoral obesity were assessed by body mass index (BMI, kg/m(2)), waist circumference (cm), and hip circumference (cm). Other measures examined were waist to hip ratio, waist to height ratio, and body adiposity index. We performed Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of obesity relative to a risk of colorectal adenocarcinoma. RESULTS: In total, 2,044 incident cases of colorectal adenocarcinoma were identified. We observed a positive association between waist circumference (high versus low) and adenocarcinoma in the proximal colon (HR = 1.9, 95% CI = 1.5, 2.5) and distal colon (HR = 1.7, 95% CI = 1.3, 2.3) when adjusted for BMI. The association with waist circumference was especially strong in men. BMI was not associated with adenocarcinoma in the colon or rectum after adjusting for waist circumference. We found no association between hip circumference and colorectal adenocarcinoma. When adjusted for BMI plus waist circumference, body adiposity index was negatively associated with adenocarcinoma in the proximal or distal colon. CONCLUSION: Abdominal obesity, but not general or gluteofemoral obesity, was associated with an increased risk of adenocarcinoma in the proximal and the distal colon, especially in men. Muscularity may be negatively associated with risk of colon adenocarcinoma.
9.	Lu, Yunxia, et al. (author) Metabolic predispositions and increased risk of colorectal adenocarcinoma by anatomical locations : a large population-based cohort study in Norway 2015 In: American Journal of Epidemiology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0002-9262 .- 1476-6256. Journal article (peer-reviewed)abstract Whether different definitions of metabolic syndrome (MetS) are differently associated with colorectal adenocarcinoma (CA) by anatomical location is unclear. A population-based cohort study, the Cohort of Norway (CONOR) Study, was conducted in Norway from 1995 to 2010. Anthropometric measurements, blood samples, and lifestyle data were collected at recruitment. CAs were identified through linkage to the Norwegian Cancer Register. A composite index of MetS as defined by the International Diabetes Federation (IDF) or/and the National Cholesterol Education Program's Adult Treatment Panel III (ATP III) and single components of MetS, including anthropometric factors, blood pressure, lipids, triglycerides, and glucose, were analyzed. Cox proportional hazards regression was performed to estimate hazard ratios and 95% confidence intervals. Significant associations between single MetS components and CA, except for reduced high-density lipoprotein cholesterol and nonfasting glucose levels, were observed. MetS defined by 2 criteria separately showed a similar association with CA in general, and MetS defined by both the IDF and ATP III showed consistent results. Stronger associations were observed in the proximal colon among men (IDF: hazard ratio (HR) = 1.51, 95% confidence interval (CI): 1.24, 1.84; ATP III: HR = 1.40, 95% CI: 1.15, 1.70) and in the rectum among women (IDF: HR = 1.42, 95% CI: 1.07, 1.89; ATP III: HR = 1.43, 95% CI: 1.08, 1.90).
10.	Maret-Ouda, John, et al. (author) Aspiration pneumonia after antireflux surgery among neurologically impaired children with GERD 2020 In: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 55:11, s. 2408-2412 Journal article (peer-reviewed)abstract BACKGROUND AND OBJECTIVE: Aspiration pneumonia is a common and serious complication to gastroesophageal reflux disease (GERD) among neurologically impaired children. Medication of GERD does not effectively prevent aspiration pneumonia, and whether antireflux surgery with fundoplication is better in this respect is uncertain. The objective was to determine whether fundoplication prevents aspiration pneumonia among children with neurological impairment and GERD.METHODS: This was a population-based cohort study from Denmark, Finland, Norway and Sweden, consisting of neurologically impaired children with GERD who underwent fundoplication. The risk of aspiration pneumonia before fundoplication (preoperative person-time) was compared with the risk after surgery (postoperative person-time). Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs). Except for confounding adjusted for by means of the "crossover like" design, the HRs were adjusted for age, sex, year of entry and respiratory diseases.RESULTS: Among 578 patients (median age 3.5 years), the preoperative person-time was 956 years and the postoperative person-time was 3324 years. Fundoplication was associated with 56% decreased overall HR of aspiration pneumonia (HR 0.44, 95% CI 0.27-0.72), and the HRs decreased over time after surgery. The risk of other types of pneumonia than aspiration pneumonia was not clearly decreased after fundoplication (HR 0.79, 95% CI 0.59-1.08). The 30-day mortality rate was 0.7% and the complication rate was 3.6%.CONCLUSIONS: Antireflux surgery decreases, but does not eliminate, the risk of aspiration pneumonia among neurologically impaired children with GERD. Fundoplication may be a treatment option when aspiration pneumonia is a recurrent problem in these children.TYPE OF STUDY: Cohort study.LEVEL OF EVIDENCE: Prognosis study-level I.
11.	Markar, Sheraz, et al. (author) Hospital Volume of Antireflux Surgery in Relation to Endoscopic and Surgical Re-interventions 2020 In: Annals of Surgery. - : Wolters Kluwer. - 0003-4932 .- 1528-1140. ; 274:6, s. 1138-1143 Journal article (peer-reviewed)abstract Objective: To test the hypothesis that higher hospital volume decreases endoscopic and surgical re-intervention rates after antireflux surgery.Background: Antireflux surgery for gastro-esophageal reflux disease is followed by varying rates of re-interventions. Whether hospital volume influences re-intervention rates is uncertain.Methods: This population-based cohort study used nationwide data from Denmark, Finland, and Sweden for patients having undergone primary antireflux surgery. Hospitals were divided into tertiles based upon annual volume, that is, 3 equal-sized groups. The outcomes were 30-day surgical re-intervention, endoscopic re-intervention, and secondary antireflux surgery. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) for risk of the first outcome occurrence. Incidence rate ratios were calculated to count all outcome occurrences. All risk estimates were adjusted for age, sex, comorbidity, type of antireflux surgery, year of surgery, and country.Results: Among 33,060 patients and a median follow-up of 12 years after antireflux surgery, the frequencies of 30-day re-intervention, endoscopic re-intervention, and secondary antireflux surgery were 1.2%, 4.6%, and 7.0%, respectively. When comparing the highest with the lowest tertiles, higher hospital volume did not decrease HRs of 30-day re-intervention (adjusted HR = 1.14, 95% CI 0.73-1.77), endoscopic re-intervention (HR = 1.21, 95% CI 0.96-1.51), or secondary antireflux surgery (HR = 1.28, 95% CI 1.05-1.54), but rather increased point estimates. The incidence rate ratios showed similar patterns.Conclusions: Higher hospital volume of primary antireflux surgery may not decrease risk of endoscopic or surgical re-intervention, suggesting that centralization will not decrease rates of postoperative complications or recurrence of gastro-esophageal reflux disease.
12.	Ness-Jensen, Eivind, et al. (author) Changes in prevalence, incidence and spontaneous loss of gastro-oesophagealreflux symptoms : a prospective population-based cohort study, the HUNT study 2012 In: Gut. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0017-5749 .- 1468-3288. Journal article (peer-reviewed)abstract OBJECTIVE: Changes in the occurrence of gastro-oesophageal reflux symptoms (GORS) in the population remain uncertain. This study aimed to determine the prevalence changes, the incidence and the spontaneous loss of GORS. DESIGN: This population-based cohort study was conducted within the Nord-Trondelag Health Study (the HUNT study), a longitudinal series of population-based health surveys in Nord-Trondelag County, Norway. The study base encompassed all adult residents in the county, and the participants reported the degree of GORS during the previous 12 months. The number of participants included were 58,869 (64% response rate) in 1995-7 and 44,997 (49%) in 2006-9. Of these, 29,610 persons (61%) were prospectively followed up for an average of 11 years. RESULTS: Between 1995-7 and 2006-9, the prevalence of any, severe and at least weekly GORS increased by 30% (from 31.4% to 40.9%), 24% (from 5.4% to 6.7%) and 47% (from 11.6% to 17.1%), respectively. The average annual incidence of any and severe GORS was 3.07% and 0.23%, respectively. In women, but not men, the incidence of GORS increased with increasing age. The average annual spontaneous loss (not due to antireflux medication) of any and severe GORS was 2.32% and 1.22%, respectively. The spontaneous loss of GORS decreased with increasing age. CONCLUSION: Between 1995-7 and 2006-9 the prevalence of GORS increased substantially. At least weekly GORS increased by 47%. The average annual incidence of severe GORS was 0.23%, and the corresponding spontaneous loss was 1.22%. The incidence and spontaneous loss of GORS were influenced by sex and age.
13.	Ness-Jensen, Eivind, et al. (author) Lifestyle intervention in gastroesophageal reflux disease 2016 In: Clinical Gastroenterology and Hepatology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1542-3565. ; 14:2, s. 175- Journal article (peer-reviewed)abstract BACKGROUND & AIMS: Gastroesophageal reflux disease (GERD) affects up to 30% of adults in Western populations and is increasing in prevalence. GERD is associated with lifestyle factors, particularly obesity and tobacco smoking, which also threatens the patient's general health. GERD carries the risk of several adverse outcomes and there is widespread use of potent acid-inhibitors, which are associated with long-term adverse effects. The aim of this systematic review was to assess the role of lifestyle intervention in the treatment of GERD. METHODS: Literature searches were performed in PubMed (from 1946), EMBASE (from 1980), and the Cochrane Library (no start date) to October 1, 2014. Meta-analyses, systematic reviews, randomized clinical trials (RCTs), and prospective observational studies were included. RESULTS: Weight loss was followed by decreased time with esophageal acid exposure in 2 RCTs (from 5.6% to 3.7% and from 8.0% to 5.5%), and reduced reflux symptoms in prospective observational studies. Tobacco smoking cessation reduced reflux symptoms in normal-weight individuals in a large prospective cohort study (odds ratio, 5.67). In RCTs, late evening meals increased time with supine acid exposure compared with early meals (5.2% point change), and head-of-the-bed elevation decreased time with supine acid exposure compared with a flat position (from 21% to 15%). CONCLUSIONS: Weight loss and tobacco smoking cessation should be recommended to GERD patients who are obese and smoke, respectively. Avoiding late evening meals and head-of-the-bed elevation is effective in nocturnal GERD.
14.	Ness-Jensen, Eivind, et al. (author) Tobacco smoking, alcohol consumption and gastro-oesophageal reflux disease 2017 In: Best Practice and Research: Clinical Gastroenterology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1521-6918 .- 1532-1916. Journal article (peer-reviewed)abstract Gastro-oesophageal reflux disease (GORD) develops when reflux of gastric content causes troublesome symptoms or complications. The main symptoms are heartburn and acid regurgitation and complications include oesophagitis, strictures, Barrett's oesophagus and oesophageal adenocarcinoma. In addition to hereditary influence, GORD is associated with lifestyle factors, mainly obesity. Tobacco smoking is regarded as an aetiological factor of GORD, while alcohol consumption is considered a triggering factor of reflux episodes and not a causal factor. Yet, both tobacco smoking and alcohol consumption can reduce the lower oesophageal sphincter pressure, facilitating reflux. In addition, tobacco smoking reduces the production of saliva rich in bicarbonate, which is important for buffering and clearance of acid in the oesophagus. Alcohol also has a direct noxious effect on the oesophageal mucosa, which predisposes to acidic injury. Tobacco smoking cessation reduces the risk of GORD symptoms and avoidance of alcohol is encouraged in individuals where alcohol consumption triggers reflux.
15.	Ness-Jensen, Eivind, et al. (author) Tobacco smoking cessation and improved gastroesophageal reflux : a prospective population-based cohort study : the HUNT study 2014 In: The American Journal of Gastroenterology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0002-9270 .- 1572-0241. Journal article (peer-reviewed)abstract Objective: Tobacco smoking increases the risk of gastroesophageal reflux symptoms (GERS), but whether tobacco smoking cessation improves GERS is unclear. The aim of this study was to clarify if tobacco smoking cessation improves GERS. Design: The study was based on the Nord-Trøndelag health study (the HUNT study), a prospective population-based cohort study conducted from 1995-1997 to 2006-2009 in Nord-Trøndelag County, Norway. All residents of the county from 20 years of age were invited. The study included 29,610 individuals (61% response rate) who reported whether they had heartburn or acid regurgitation. The association between tobacco smoking cessation and improvement in GERS was assessed by logistic regression, providing odds ratios (ORs) with 95% confidence intervals (CIs). The analyses were stratified by antireflux medication, and the results were adjusted for sex, age, body mass index (BMI), alcohol consumption, education, and physical exercise. Subgroup analyses were also stratified by BMI. Results: Among individuals using antireflux medication at least weekly, cessation of daily tobacco smoking was associated with improvement in GERS from severe to no or minor complaints (adjusted OR 1.78, 95% CI 1.07 to 2.97), compared with persistent daily smoking. This association was present among individuals within the normal range of BMI (OR 5.67, 95% CI 1.36 to 23.64), but not among overweight individuals. There was no association between tobacco smoking cessation and GERS status among individuals with minor GERS or individuals using antireflux medication less than weekly. Conclusion: Tobacco smoking cessation was associated with improvement in severe GERS only in individuals of normal BMI using antireflux medication at least weekly, but not in other individual with GERS.
16.	Ness-Jensen, Eivind, et al. (author) Weight loss and reduction in gastroesophageal reflux : a prospective population-based cohort study : the HUNT study 2013 In: The American Journal of Gastroenterology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0002-9270 .- 1572-0241. Journal article (peer-reviewed)abstract OBJECTIVES: High body mass index (BMI) is an established risk factor of gastroesophageal reflux symptoms (GERS). The aim of this study was to clarify if weight loss reduces GERS. METHODS: The study was part of the Nord-Trondelag health study (the HUNT study), a prospective population-based cohort study conducted in Nord-Trondelag County, Norway. All residents of the county from 20 years of age were invited. In 1995-1997 (HUNT 2) and 2006-2009 (HUNT 3), 58,869 and 44,997 individuals, respectively, responded to a questionnaire on heartburn and acid regurgitation. Among these, 29,610 individuals (61% response rate) participated at both times and were included in the present study. The association between weight loss and reduction of GERS was calculated using logistic regression. The analyses were stratified by antireflux medication and the results adjusted for sex, age, cigarette smoking, alcohol consumption, education, and physical exercise. RESULTS: Weight loss was dose-dependently associated with a reduction of GERS and an increased treatment success with antireflux medication. Among individuals with >3.5 units decrease in BMI, the adjusted odds ratio (OR) of loss of any (minor or severe) GERS was 1.98 (95% confidence interval (CI) 1.45-2.72) when using no or less than weekly antireflux medication, and 3.95 (95% CI 2.03-7.65) when using at least weekly antireflux medication. The corresponding ORs of loss of severe GERS was 0.90 (95% CI 0.32-2.55) and 3.11 (95% CI 1.13-8.58). CONCLUSIONS: Weight loss was dose-dependently associated with both a reduction of GERS and an increased treatment success with antireflux medication in the general population.
17.	Talabani, Aras Jamal, et al. (author) Risk factors of admission for acute colonic diverticulitis in a population-based cohort study : the HUNT Study, Norway 2016 In: World Journal of Gastroenterology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 2219-2840 .- 1007-9327. Journal article (peer-reviewed)abstract AIM: To assess risk factors of hospital admission for acute colonic diverticulitis. METHODS: The study was conducted as part of the second wave of the population-based North Trondelag Health Study (HUNT2), performed in North Trondelag County, Norway, 1995 to 1997. The study consisted of 42570 participants (65.1% from HUNT2) who were followed up from 1998 to 2012. Of these, 22436 (52.7%) were females. The cases were defined as those 358 participants admitted with acute colonic diverticulitis during follow-up. The remaining participants were used as controls. Univariable and multivariable Cox regression analyses was used for each sex separately after multiple imputation to calculate HR. RESULTS: Multivariable Cox regression analyses showed that increasing age increased the risk of admission for acute colonic diverticulitis: Comparing with ages < 50 years, females with age 50-70 years had HR = 3.42, P < 0.001 and age > 70 years, HR = 6.19, P < 0.001. In males the corresponding values were HR = 1.85, P = 0.004 and 2.56, P < 0.001. In patients with obesity (body mass index ≥ 30) the HR = 2.06, P < 0.001 in females and HR = 2.58, P < 0.001 in males. In females, present (HR = 2.11, P < 0.001) or previous (HR = 1.65, P = 0.007) cigarette smoking increased the risk of admission. In males, breathlessness (HR = 2.57, P < 0.001) and living in rural areas (HR = 1.74, P = 0.007) increased the risk. Level of education, physical activity, constipation and type of bread eaten showed no association with admission for acute colonic diverticulitis. CONCLUSION: The risk of hospital admission for acute colonic diverticulitis increased with increasing age, in obese individuals, in ever cigarette smoking females and in males living in rural areas.
18.	Talseth, Arne, et al. (author) Quality of life and psychological and gastrointestinal symptoms after cholecystectomy : a population-based cohort study 2017 In: BMJ Open Gastroenterology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 2054-4774. Journal article (peer-reviewed)abstract OBJECTIVE: The study aims to examine gastrointestinal symptoms, quality of life and the risk of psychological symptoms after cholecystectomy. DESIGN: This is a prospective population-based cohort study based on the Nord-Trondelag Health Study (HUNT) Norway. HUNT is a repeated health survey of the county population and includes a wide range of health-related items. In the present study, all 3 HUNT surveys were included, performed between 1984 and 2008. Selected items were scores on quality of life, the Hospital Anxiety and Depression Scale (HADS) and selected gastrointestinal symptoms. Participants who underwent cholecystectomy for gallstone disease between 1 January 1990 and until 1 year before attending HUNT3 were compared with the remaining non-operated cohort. Associations between cholecystectomy and the postoperative scores and symptoms were assessed by multivariable regression models. RESULTS: Participants in HUNT1, HUNT2 and HUNT3 were 77 212 (89.4% of those invited), 65 237 (69.5%) and 50 807 (54.1%), respectively. In the study period, 931 participants were operated with cholecystectomy. Cholecystectomy was associated with an increased risk of diarrhoea and stomach pain postoperatively. In addition, cholecystectomy was associated with an increased risk of nausea postoperatively in men. We found no associations between cholecystectomy and quality of life, symptoms of anxiety and depression, constipation, heartburn, or acid regurgitation following surgery. CONCLUSIONS: In this large population-based cohort study, cholecystectomy was associated with postoperative diarrhoea and stomach pain. Cholecystectomy for gallstone colic was associated with nausea in men. There were no associations between quality of life, symptoms of anxiety and depression, constipation, heartburn, or acid regurgitation.
19.	Talseth, Arne, et al. (author) Risk factors of having cholecystectomy for gallstone disease in a prospective population-based cohort study 2016 In: British Journal of Surgery. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0007-1323 .- 1365-2168. Journal article (peer-reviewed)abstract BACKGROUND: The relationship between different lifestyle factors and the risk of needing cholecystectomy for gallstone disease is not clear. This study aimed to assess the association between anthropometric, lifestyle and sociodemographic risk factors and the subsequent risk of requiring cholecystectomy for gallstone disease during long-term follow-up in a defined population cohort. METHODS: Data from a large population-based cohort study performed from 1995 to 1997 were used (the second Norwegian Nord-Trondelag health study, HUNT2). Following HUNT2, from 1998 to 2011, all patients operated on for gallstone disease with cholecystectomy at the two hospitals in the county, Levanger Hospital and Namsos Hospital, were identified. A Cox proportional hazards model was used for multivariable risk analysis. RESULTS: The HUNT2 cohort included 65 237 individuals (69.5 per cent response rate), aged 20-99 years. During a median follow-up of 15.3 (range 0.6-16.4) years, 1162 cholecystectomies were performed. In multivariable analysis, overweight individuals (body mass index (BMI) 25.0-29.9 kg/m(2) ) had a 58 per cent increased risk of cholecystectomy compared with individuals with normal weight (BMI less than 25.0 kg/m(2) ). Obese individuals (BMI 30 kg/m(2) or above) had a twofold increased risk. Increasing waist circumference independently increased the risk of cholecystectomy. In women, current hormone replacement therapy (HRT) increased the risk, whereas hard physical activity and higher educational level were associated with reduced risk of cholecystectomy. CONCLUSION: High BMI and waist circumference increased the risk of having cholecystectomy for both sexes. In women, the risk was increased by HRT, and decreased by hard physical activity and higher educational level.
20.	van Duijnhoven, Fraenzel J. B., et al. (author) Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations 2018 In: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 142:6, s. 1189-1201 Journal article (peer-reviewed)abstract Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-TrOndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n=626; HUNT2 n=112; median follow-up=6.9 years) were matched to 738 controls. Vitamin D [25(OH)D-2 and 25(OH)D-3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of 25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend=0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend=0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.
21.	Wang, Qiao-Li, et al. (author) Association between metformin use and risk of esophageal squamous cell carcinoma in a population-based cohort study 2020 In: The American Journal of Gastroenterology. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0002-9270 .- 1572-0241. Journal article (peer-reviewed)abstract Objectives: Esophageal cancer is a highly fatal malignant neoplasm, with two etiologically different histological types. A large prospective study is expected to elucidate the specific risk of the 90% subtype of esophageal cancer, esophageal squamous cell carcinoma, with metformin therapy. This study aims to determine the association between metformin use and incident esophageal squamous cell carcinoma risk. Methods: This was a nationwide population-based prospective cohort study conducted in Sweden in 2005-2015. Among 8.4 million participants identified in the cohort, 411,603 (5%) were metformin users. The users were compared with 10 times as many frequency-matched non-users of metformin (n=4,116,030) by age and sex. Metformin use was treated as a time-varying variate and multivariable cause-specific proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for esophageal squamous cell carcinoma, adjusted for age, sex, calendar year, residence area, tobacco smoking, alcohol overconsumption, and use of non-steroidal anti-inflammatory drugs or statins. Results: The incidence rates of esophageal squamous cell carcinoma were 3.5 per 100,000 person-years among the metformin users and 5.3 per 100,000 person-years in the non-users. Metformin users overall were at a decreased risk of esophageal squamous cell carcinoma compared with non-users (HR 0.68, 95% CI 0.54-0.85). The decrease in risk was more pronounced in new metformin users (HR 0.44, 95% CI 0.28-0.64) and participants aged 60-69 years (HR 0.45, 95% CI 0.31-0.66). Conclusions: Metformin use decreases the risk of developing esophageal squamous cell carcinoma.
22.	Yanes, Manar, et al. (author) Laryngeal and Pharyngeal Squamous Cell Carcinoma After Antireflux Surgery in the 5 Nordic Countries 2022 In: Annals of Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 0003-4932 .- 1528-1140. ; 276:2, s. E79-E85 Journal article (peer-reviewed)abstract Objective: The aim of this study was to clarify whether antireflux surgery prevents laryngeal and pharyngeal squamous cell carcinoma.Summary Background Data: Gastroesophageal reflux disease (GERD) seems to increase the risk of laryngeal and pharyngeal squamous cell carcinoma.Methods: All-Nordic (Denmark, Finland, Iceland, Norway, and Sweden) population-based cohort study of adults with documented GERD in 1980 to 2014. First, cancer risk after antireflux surgery was compared to the expected risk in the corresponding background population by calculating standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). Second, cancer risk among antireflux surgery patients was compared to nonoperated GERD patients using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs, adjusted for sex, age, calendar period, and diagnoses related to tobacco smoking, obesity, and alcohol overconsumption.Results: Among 814,230 GERD patients, 47,016 (5.8%) underwent antireflux surgery. The overall SIRs and HRs of the combined outcome laryngeal or pharyngeal squamous cell carcinoma (n=39) were decreased after antireflux surgery [SIR=0.62 (95% CI 0.44-0.85) and HR=0.55 (95% CI 0.38-0.80)]. The point estimates were further decreased >10 years after antireflux surgery [SIR=0.48 (95% CI 0.26-0.80) and HR=0.47 (95% CI 0.26-0.85)]. The risk estimates of laryngeal squamous cell carcinoma were particularly decreased >10 years after antireflux surgery [SIR=0.28 (95% CI 0.08-0.72) and HR=0.23 (95% CI 0.08-0.69)], whereas no such decrease over time after surgery was found for pharyngeal squamous cell carcinoma. Analyses of patients with severe GERD (reflux esophagitis or Barrett esophagus) showed similar results.Conclusion: Antireflux surgery may decrease the risk of laryngeal squamous cell carcinoma and possibly also of pharyngeal squamous cell carcinoma.
23.	Yanes, Manar, et al. (author) Mortality, Reoperation, and Hospital Stay Within 90 Days of Primary and Secondary Antireflux Surgery in a Population-Based Multinational Study. 2021 In: Gastroenterology. - : Elsevier. - 0016-5085 .- 1528-0012. ; 160:7, s. 2283-2290 Journal article (peer-reviewed)abstract BACKGROUND & AIMS: Absolute rates and risk factors of short-term outcomes after antireflux surgery remain largely unknown. We aimed to clarify absolute risks and risk factors for poor 90-day outcomes of primary laparoscopic and secondary antireflux surgery.METHODS: This population-based cohort study included patients who had primary laparoscopic or secondary antireflux surgery in the 5 Nordic countries in 2000-2018. In addition to absolute rates, we analyzed age, sex, comorbidity, hospital volume, and calendar period in relation to all-cause 90-day mortality (main outcome), 90-day reoperation, and prolonged hospital stay (≥2 days over median stay). Multivariable logistic regression provided odds ratios (ORs) with 95% confidence intervals (95% CI), adjusted for confounders.RESULTS: Among 26,193 patients who underwent primary laparoscopic antireflux surgery, postoperative 90-day mortality and 90-day reoperation rates were 0.13% (n = 35) and 3.0% (n = 750), respectively. The corresponding rates after secondary antireflux surgery (n = 1 618) were 0.19% (n = 3) and 6.2% (n = 94). Higher age (56-80 years vs 18-42 years: OR, 2.66; 95% CI 1.03-6.85) and comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 6.25; 95% CI 2.42-16.14) increased risk of 90-day mortality after primary surgery, and higher hospital volume suggested a decreased risk (highest vs lowest tertile: OR, 0.58; 95% CI, 0.22-1.57). Comorbidity increased the risk of 90-day reoperation. Higher age and comorbidity increased risk of prolonged hospital stay after both primary and secondary surgery. Higher annual hospital volume decreased the risk of prolonged hospital stay after primary surgery (highest vs lowest tertile: OR, 0.74; 95% CI, 0.67-0.80).CONCLUSION: These findings suggest that laparoscopic antireflux surgery has an overall favorable safety profile in the treatment of gastroesophageal reflux disease, particularly in younger patients without severe comorbidity who undergo surgery at high-volume centers.

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