| 1. |
- Blomstrand, Peter, et al.
(författare)
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Left ventricular diastolic function, assessed by echocardiography and tissue Doppler imaging, is a strong predictor of cardiovascular events, superior to global left ventricular longitudinal strain, in patients with type 2 diabetes
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16:9, s. 1000-1007
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of the study was to determine whether left ventricular systolic function, in terms of global left ventricular longitudinal strain (GLS), and diastolic function, expressed as the ratio between early diastolic transmitral flow and mitral annular motion velocities (E/e'), can predict cardiovascular events in patients with diabetes mellitus type 2.Methods and results: We prospectively investigated 406 consecutive patients, aged 55-65 years, with diabetes mellitus, who participated in the CARDIPP study. Echocardiography, pulse pressure (pp), and glycosylated haemoglobin (HbA1c) were analysed. Twelve cases of myocardial infarction and seven cases of stroke were identified during the follow-up period of 67 +/- 17 months. Univariate Cox regression analysis showed that E/e' was a strong predictor of cardiovascular events (hazards ratio 1.12; 95% confidence interval 1.06-1.18, P < 0.001). E/e' was prospectively associated with cardiovascular events independent of age, sex, GLS, left ventricular ejection fraction (LVEF), pp, and HbA1c in multivariate analysis. Receiver operating characteristic curves showed that E/e' and HbA1c were the strongest predictors for cardiovascular events, both having an area under the curve (AUC) of 0.71 followed by LVEF with an AUC of 0.65 and GLS of 0.61. In a Kaplan-Meyer analysis, the cumulative probability of an event during the follow-up period was 8.6% for patients with an E/e' ratio >15 compared with 2.6% for patients with E/e' <= 15, P = 0.011.Conclusion: In middle-aged patients with type 2 diabetes, E/e' is a strong predictor of myocardial infarction and stroke, comparable with HbA1c and superior to GLS and LVEF.
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| 2. |
- Brusselaers, Nele, et al.
(författare)
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Menopausal hormone therapy and the risk of esophageal and gastric cancer
- 2017
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- A protective effect of female sex hormones has been suggested to explain the male predominance in esophageal and gastric adenocarcinoma, but evidence is lacking. We aimed to test whether menopausal hormone therapy (MHT) decreases the risk of these tumors. For comparison, esophageal squamous cell carcinoma was also assessed. This population-based matched cohort study included all women who had ever used systemic MHT in Sweden in 2005-2012. A comparison cohort of non-users of MHT was matched to the MHT-users regarding age, parity, thrombotic events, hysterectomy, diabetes, obesity, smoking-related diseases, and alcohol-related diseases. Individuals with any previous cancer were excluded. Data on MHT use, cancer, comorbidity, and mortality were collected from well-established Swedish nationwide registers. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using conditional logistic regression. Different MHT regimens and age groups were compared in sub-group analyses. We identified 290,186 ever-users and 870,165 non-users of MHT. Ever-users had decreased ORs of esophageal adenocarcinoma (OR=0.62, 95% CI 0.45-0.85, n=46), gastric adenocarcinoma (OR=0.61, 95% CI 0.50-0.74, n=123), and esophageal squamous cell carcinoma (OR=0.57, 95% CI 0.39-0.83, n=33). The ORs were decreased for both estrogen-only MHT and estrogen and progestin combined MHT, and in all age groups. The lowest OR was found for esophageal adenocarcinoma in MHT-users younger than 60 years (OR=0.20, 95% CI 0.06-0.65). Our study suggests that MHT-users are at a decreased risk of esophageal and gastric adenocarcinoma, and also of esophageal squamous cell carcinoma. The mechanisms behind these associations remain to be elucidated.
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| 3. |
- Emilsson, Louise, 1982-, et al.
(författare)
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Mortality in small bowel cancers and adenomas : A nationwide, population-based matched cohort study
- 2023
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Ingår i: Cancer Epidemiology. - : Elsevier. - 1877-7821 .- 1877-783X. ; 85
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Tidskriftsartikel (refereegranskat)abstract
- Background: Small bowel adenocarcinoma (SBA), neuroendocrine tumors (NET) and gastrointestinal stromal tumors (GIST) are neoplastic lesions of the small bowel while small bowel adenomas are precursors of SBA.Aim: To examine mortality in patients diagnosed with SBA, small bowel adenomas, NET and GIST.Methods: We performed a population-based matched cohort study encompassing all individuals with SBA (n = 2289), adenomas (n = 3700), NET (n = 1884) and GIST (n = 509) in the small bowel diagnosed at any of Sweden's 28 pathology departments between 2000 and 2016 (the "ESPRESSO study"). Each case was matched by sex, age, calendar year and county of residence to up to 5 comparators from the general population. Through Cox regression we estimated hazard ratios (HRs) and 95% confidence intervals (95%CIs) for death and cause-specific death adjusting for education.Results: During follow-up until December 31, 2017, 1836 (80%) deaths occurred in SBA patients, 1615 (44%) in adenoma, 866 (46%) in NET and 162 (32%) in GIST patients. This corresponded to incidence rates of 295, 74, 80 and 62/1000 person-years respectively and adjusted HRs of 7.60 (95%CI=6.95-8.31), 2.21 (2.07-2.36), 2.74 (2.50-3.01) and 2.33 (1.90-2.87). Adjustment for education had a substantial impact on the HR for death in SBA but not for other neoplasias. The predominant cause of excess death was cancer in all groups.Conclusion: This study confirms earlier findings of increased death rates in patients with SBA and NET in a modern study population. We also demonstrate a more than 2-fold increased risk of death in both GIST and the SBA precursor adenoma.
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| 4. |
- Holmberg, Dag, et al.
(författare)
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Incidence and Mortality in Upper Gastrointestinal Cancer After Negative Endoscopy for Gastroesophageal Reflux Disease
- 2022
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 162:2, s. 431-438.e4
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Tidskriftsartikel (refereegranskat)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.
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| 5. |
- Holmberg, Dag, et al.
(författare)
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Non-erosive gastro-oesophageal reflux disease and incidence of oesophageal adenocarcinoma in three Nordic countries : population based cohort study
- 2023
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Ingår i: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 382, s. e076017-
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Tidskriftsartikel (refereegranskat)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.
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| 6. |
- Maret-Ouda, John, et al.
(författare)
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Antireflux surgery and risk of esophageal adenocarcinoma : a systematic review and meta-analysis
- 2016
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Ingår i: Annals of Surgery. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0003-4932. ; 263:2, s. 251-257
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the preventive effect of antireflux surgery against esophageal adenocarcinoma (EAC), compared to medical treatment of gastroesophageal reflux disease (GERD) and to the background population. Background: GERD is causally associated with EAC. Effective symptomatic treatment can be achieved with medication and antireflux surgery, yet the possible preventive effect on EAC development remains unclear. Methods: This systematic review identified 10 studies comparing EAC risk following antireflux surgery with non-operated GERD patients, including 7 studies of patients with Barrett’s esophagus; and 2 studies comparing EAC risk after antireflux surgery to the background population. A fixed-effects Poisson meta-analysis was conducted to calculate pooled incidence rate ratios (IRR) and 95% confidence intervals (CI). Results: The pooled IRR in patients following antireflux surgery was 0.76 (95% CI 0.42-1.39) compared to medically treated GERD patients. In patients with Barrett’s esophagus, the corresponding IRR was 0.46 (95% CI 0.20-1.08), and 0.26 (95% CI 0.09-0.79) when restricted to publications after 2000. There was no difference in EAC risk between antireflux surgery and medical treatment in GERD patients without known Barrett’s esophagus (IRR 0.98, 95% CI 0.72-1.33). The EAC risk remained elevated in patients following antireflux surgery compared to the background population (IRR 10.78, 95% CI 8.48-13.71). While the clinical heterogeneity of the included studies was high, the statistical heterogeneity was low. Conclusions: Antireflux surgery may prevent EAC better than medical therapy in patients with Barrett’s esophagus. The EAC risk following antireflux surgery does not seem to revert to that of the background population.
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| 7. |
- Maret-Ouda, John, et al.
(författare)
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Appendectomy and future risk of microscopic colitis : a population-based case-control study in Sweden
- 2023
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 21:2, s. 467-475.e2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Microscopic colitis (MC) is an inflammatory bowel disease and a common cause of chronic diarrhea. Appendectomy has been suggested to have immunomodulating effects in the colon, influencing the risk of gastrointestinal disease. The relationship between appendectomy and MC has only been sparsely studied.METHODS: This was a case-control study based on the nationwide ESPRESSO cohort, consisting of histopathological examinations in Sweden, linked to national registers. Patients with MC were matched to population controls by age, sex, calendar year of biopsy and county of residence. Data on antecedent appendectomy and comorbidities were retrieved from the Patient Register. Unconditional logistic regression models were conducted presenting odds ratios (ORs) and 95% confidence intervals (Cl) adjusted for country of birth and matching factors. Further sub-analyses were made based on MC subtypes (lymphocytic colitis [LC] and collagenous colitis [CC]), follow-up time post appendectomy and severity of appendicitis.RESULTS: The study included 14,520 cases of MC and 69,491 controls, among these 7.6% (n=1,103) and 5.1% (n=3,510), respectively, had a previous appendectomy ≥1 year prior to MC/matching date. Patients with a previous appendectomy had an increased risk of MC in total (OR 1.50, 95% CI 1.40-1.61); and per subtype CC (OR 1.67, 95% CI 1.48-1.88), LC (OR 1.42, 95% CI 1.30-1.55). The risk remained elevated throughout follow-up, and the highest risk was observed in non-complicated appendicitis.CONCLUSIONS: This nationwide case-control study found a modestly increased risk of developing MC following appendectomy.
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| 8. |
- Maret-Ouda, John, et al.
(författare)
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Aspiration pneumonia after antireflux surgery among neurologically impaired children with GERD
- 2020
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 55:11, s. 2408-2412
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Tidskriftsartikel (refereegranskat)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.
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| 9. |
- Maret-Ouda, John, et al.
(författare)
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Association between laparoscopic antireflux surgery and recurrence of gastroesophageal reflux
- 2017
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Ingår i: Journal of the American Medical Association. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0098-7484 .- 1538-3598.
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Cohort studies, mainly based on questionnaires and interviews, have reported high rates of reflux recurrence after antireflux surgery, which may have contributed to a decline in its use. Reflux recurrence after laparoscopic antireflux surgery has not been assessed in a long-term population-based study of unselected patients. OBJECTIVES: To determine the risk of reflux recurrence after laparoscopic antireflux surgery and to identify risk factors for recurrence. DESIGN AND SETTING: Nationwide population-based retrospective cohort study in Sweden between January 1, 2005, and December 31, 2014, based on all Swedish health care and including 2655 patients who underwent laparoscopic antireflux surgery according to the Swedish Patient Registry. Their records were linked to the Swedish Causes of Death Registry and Prescribed Drug Registry. EXPOSURES: Primary laparoscopic antireflux surgery due to gastroesophageal reflux disease in adults (>18 years). MAIN OUTCOMES AND MEASURES: The outcomewas recurrence of reflux, defined as use of antireflux medication (proton pump inhibitors or histamine2 receptor antagonists for >6 months) or secondary antireflux surgery. Multivariable Cox regression was used to assess risk factors for reflux recurrence. RESULTS: Among all 2655 patients who underwent antireflux surgery (median age, 51.0 years; interquartile range, 40.0-61.0 years; 1354 men [51.0%]) and were followed up for a median of 5.6 years, 470 patients (17.7%) had reflux recurrence; 393 (83.6%) received long-term antireflux medication and 77 (16.4%) underwent secondary antireflux surgery. Risk factors for reflux recurrence included female sex (hazard ratio [HR], 1.57 [95%CI, 1.29-1.90]; 286 of 1301 women [22.0%] and 184 of 1354 men [13.6%] had recurrence of reflux), older age (HR, 1.41 [95%CI, 1.10-1.81] for age 61 years compared with 45 years; recurrence among 156 of 715 patients and 133 of 989 patients, respectively), and comorbidity (HR, 1.36 [95%CI, 1.13-1.65] for Charlson comorbidity index score 1 compared with 0; recurrence among 180 of 804 patients and 290 of 1851 patients, respectively). Hospital volume of antireflux surgery was not associated with risk of reflux recurrence (HR, 1.09 [95%CI, 0.77-1.53] for hospital volume 24 surgeries compared with 76 surgeries; recurrence among 38 of 266 patients [14.3%] and 271 of 1526 patients [17.8%], respectively). CONCLUSIONS AND RELEVANCE: Among patients who underwent primary laparoscopic antireflux surgery, 17.7%experienced recurrent gastroesophageal reflux requiring long-term medication use or secondary antireflux surgery. Risk factors for recurrence were older age, female sex, and comorbidity. Laparoscopic antireflux surgery was associated with a relatively high rate of recurrent gastroesophageal reflux disease requiring treatment, diminishing some of the benefits of the operation.
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| 10. |
- Maret-Ouda, John
(författare)
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Clinical and oncopreventive outcomes of antireflux surgery
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gastro-oesophageal reflux disease (GORD), with heartburn and acid regurgitation as main symptoms, is a common disease with increasing prevalence. GORD is associated with oesophageal adenocarcinoma, a cancer with demanding treatment and yet poor prognosis. GORD is typically managed with pharmacological treatment, mainly using proton pump inhibitors, or through laparoscopic antireflux surgery. The aim of this thesis was to evaluate outcomes of antireflux surgery, i.e. safety, effectiveness and prevention of oesophageal adenocarcinoma. Study I and II were nationwide Swedish cohort studies based on data from the Patient Registry, Causes of Death Registry, Registry of the Total Population (in study I only), and the Swedish Prescribed Drug Registry (in study II only). Study I assessed safety aspects with focus on the risk of mortality, reoperation and prolonged hospital stay among patients of working age who underwent primary laparoscopic antireflux surgery for GORD. In addition, it provided descriptive data regarding trends and comorbidities among patients who had undergone such surgery. The study found low risks of mortality (0.08%) and reoperation (0.4%) within 90 days of surgery. Patients of female sex, and older age and with more comorbidities had an increased risk of prolonged hospital stay. Generally, the number of patients who underwent antireflux surgery in Sweden decreased substantially during the period, while the proportion with severe comorbidities among the operated patients increased over time. Study II assessed the risk of recurrence of reflux symptoms following primary laparoscopic antireflux surgery for GORD, using reoperation or prescribed medications against reflux (exceeding six months of treatment) as the measures of this outcome. The reflux recurrence rate was 17.7% during the median follow-up of 5.6 years, and the majority of patients (83.6%) had medical treatment. Female sex, older age, and comorbidity were associated with an increased reflux recurrence, but hospital volume was not. Study III was a systematic review and meta-analysis assessing if oesophageal adenocarcinoma can be prevented by antireflux surgery. No clear differences in risk were found when comparing surgery with medication, and the risk of oesophageal adenocarcinoma remained elevated following antireflux surgery compared to the general background population. Study IV was a Nordic cohort study, based on nationwide registries from Denmark, Finland, Iceland, Norway, and Sweden, including patients with GORD. The risk of oesophageal adenocarcinoma was initially high, but decreased over time both following antireflux surgery and presumed medical therapy to a risk in line with that of the general background population after 15 years. The risk of oesophageal adenocarcinoma was similar when directly comparing medical and surgical therapy. In conclusion, laparoscopic antireflux surgery can be considered a safe and effective treatment option of GORD which is potentially underused in clinical practice, especially among young and otherwise healthy individuals who might otherwise need lifelong medical treatment. Effective treatment of GORD seems to reduce the risk of oesophageal adenocarcinoma.
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| 11. |
- Maret-Ouda, John, et al.
(författare)
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Cohort profile : the Nordic antireflux surgery cohort (NordASCo)
- 2017
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Ingår i: BMJ Open. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 2044-6055.
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To describe a newly created all-Nordic cohort of patients with gastro-oesophageal reflux disease (GORD), entitled the Nordic Antireflux Surgery Cohort (NordASCo), which will be used to compare participants having undergone antireflux surgery with those who have not regarding risk of cancers, other diseases and mortality. PARTICIPANTS: Included were individuals with a GORD diagnosis recorded in any of the nationwide patient registries in the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) in 1964-2014 (with various start and end years in different countries). Data regarding cancer, other diseases and mortality were retrieved from the nationwide registries for cancer, patients and causes of death, respectively. FINDINGS TO DATE: The NordASCo includes 945 153 individuals with a diagnosis of GORD. Of these, 48 433 (5.1%) have undergone primary antireflux surgery. Median age at primary antireflux surgery ranged from 47 to 52 years in the different countries. The coding practices of GORD seem to have differed between the Nordic countries. FUTURE PLANS: The NordASCo will initially be used to analyse the risk of developing known or potential GORD-related cancers, that is, tumours of the oesophagus, stomach, larynx, pharynx and lung, and to evaluate the mortality in the short-term and long-term perspectives. Additionally, the cohort will be used to evaluate the risk of non-malignant respiratory conditions that might be caused by aspiration of gastric contents.
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| 12. |
- Maret-Ouda, John, et al.
(författare)
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Esophageal adenocarcinoma after obesity surgery in a population-based cohort study
- 2015
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Ingår i: Surgery for Obesity and Related Diseases. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1550-7289. ; 13:1, s. 28-34
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is strongly associated with esophageal adenocarcinoma (EAC), yet whether weight loss reduces the risk of EAC is unclear. Objectives: To test the hypothesis that the risk of EAC decreases following weight reduction achieved by obesity surgery. Setting: Nationwide register-based cohort study. Methods: This study included a majority of individuals who underwent obesity surgery in Sweden in 1980-2012. The incidence of EAC following obesity surgery was compared to the incidence in the corresponding background population of Sweden by means of calculation of standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). The risk of EAC after obesity surgery was also compared with the risk in non-operated obese individuals by means of multivariable Cox regression, providing hazard ratios (HRs) with 95% CIs, adjusted for potential confounders. Results: Among 34,437 study participants undergoing obesity surgery and 239,775 person- 15" years of follow-up, 8 cases of EAC occurred (SIR 1.6, 95% CI 0.7-3.2). No clear trend of decreased SIRs was seen in relation to increased follow-up time after surgery. The SIR of EACs (n=53) among 123,695 non-operated obese individuals (673,238 person-years) was increased to a similar extent as in the obesity surgery cohort (SIR=1.9, 95% CI 1.4-2.5). Cox regression showed no difference in risk of EAC between operated and non-operated participants (adjusted HR=0.9, 95% CI 0.4-1.9). Conclusions: The risk of EAC might not decrease following obesity surgery, but even larger studies with longer follow-up are needed to establish this association.
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| 13. |
- Maret-Ouda, John, et al.
(författare)
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Gastroesophageal Reflux Disease : A Review.
- 2020
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Ingår i: Journal of the American Medical Association (JAMA). - CHICAGO USA : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 324:24, s. 2536-2547
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Gastroesophageal reflux disease (GERD) is defined by recurrent and troublesome heartburn and regurgitation or GERD-specific complications and affects approximately 20% of the adult population in high-income countries.Observations: GERD can influence patients' health-related quality of life and is associated with an increased risk of esophagitis, esophageal strictures, Barrett esophagus, and esophageal adenocarcinoma. Obesity, tobacco smoking, and genetic predisposition increase the risk of developing GERD. Typical GERD symptoms are often sufficient to determine the diagnosis, but less common symptoms and signs, such as dysphagia and chronic cough, may occur. Patients with typical GERD symptoms can be medicated empirically with a proton pump inhibitor (PPI). Among patients who do not respond to such treatment or if the diagnosis is unclear, endoscopy, esophageal manometry, and esophageal pH monitoring are recommended. Patients with GERD symptoms combined with warning symptoms of malignancy (eg, dysphagia, weight loss, bleeding) and those with other main risk factors for esophageal adenocarcinoma, such as older age, male sex, and obesity, should undergo endoscopy. Lifestyle changes, medication, and surgery are the main treatment options for GERD. Weight loss and smoking cessation are often useful. Medication with a PPI is the most common treatment, and after initial full-dose therapy, which usually is omeprazole 20 mg once daily, the aim is to use the lowest effective dose. Observational studies have suggested several adverse effects after long-term PPI, but these findings need to be confirmed before influencing clinical decision making. Surgery with laparoscopic fundoplication is an invasive treatment alternative in select patients after thorough and objective assessments, particularly if they are young and healthy. Endoscopic and less invasive surgical techniques are emerging, which may reduce the use of long-term PPI and fundoplication, but the long-term safety and efficacy remain to be scientifically established.Conclusions and Relevance: The clinical management of GERD influences the lives of many individuals and is responsible for substantial consumption of health care and societal resources. Treatments include lifestyle modification, PPI medication, and laparoscopic fundoplication. New endoscopic and less invasive surgical procedures are evolving. PPI use remains the dominant treatment, but long-term therapy requires follow-up and reevaluation for potential adverse effects.
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| 14. |
- Maret-Ouda, John, et al.
(författare)
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Mortality from laparoscopic antireflux surgery in a nationwide cohort of the working-age population
- 2016
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Ingår i: British Journal of Surgery. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0007-1323 .- 1365-2168.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Effective treatment of severe gastro-oesophageal reflux disease is available through medication or surgery. Postoperative risks have contributed to decreased use of antireflux surgery. We aimed to assess short-term mortality following primary laparoscopic fundoplication. Method: Population-based nationwide Swedish cohort study including all Swedish hospitals performing laparoscopic fundoplication, between 1997 and 2013. All patients aged 18-65 years with gastro-oesophageal reflux disease who underwent primary laparoscopic fundoplication during the study period were included. Main outcome was absolute all-cause and surgery-related 90-day and 30-day mortality. Secondary outcomes were reoperation and length of hospital stay. Logistic regression was used to calculate odds ratios with 95% confidence intervals of reoperation within 90 days and prolonged hospital stay (>4 days). Results: Of 8947 included patients, 5306 (59.3%) were men, and 551 (6.2%) had a significant comorbidity (Charlson comorbidity score >0). Median age at surgery was 48 years, and median hospital stay was 2 days. Annual rate of laparoscopic fundoplication decreased from 15.3 to 2.4 cases per 100 000 inhabitants during the study period, while the proportion of patients with comorbidity increased more than 2-fold. All-cause 90- and 30-day mortality were 0.08% (n=7) and 0.03% (n=3), respectively. Only 1 death (0.01%) was directly surgery-related. 90-day reoperation rate was 0.4% (n=39). Comorbidity and higher age entailed increased risk for prolonged hospital stay, but not for reoperation. Conclusion: This population-based study revealed a remarkably low 90-day mortality and reoperation rate following laparoscopic, results which might influence clinical decision-making in the treatment of severe gastro-oesophageal reflux disease.
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| 15. |
- Maret-Ouda, John, et al.
(författare)
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Nordic registry-based cohort studies : possibilities and pitfalls when combining Nordic registry data
- 2017
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Ingår i: Scandinavian Journal of Public Health. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1403-4948 .- 1651-1905.
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Tidskriftsartikel (refereegranskat)abstract
- Aims: All five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) have nationwide registries with similar data structure and validity, as well as personal identity numbers enabling linkage between registries. These resources provide opportunities for medical research that is based on large registry-based cohort studies with long and complete follow-up. This review describes practical aspects, opportunities, and challenges encountered when setting up all-Nordic registry-based cohort studies. Methods: Relevant articles describing registries often used for medical research in the Nordic countries were retrieved. Further, our experiences of conducting this type of study, including planning, acquiring permissions, data retrieval, and data cleaning and handling, and the possibilities and challenges we have encountered, are described. Results: Combining data from the Nordic countries makes it possible to create large and powerful cohorts. The main challenges include obtaining all permissions within each country, usually in the local language, and to retrieve the data. These challenges emphasise the importance of having experienced collaborators within each country. Following the acquisition of data, data management requires the understanding of differences between the variables to be used in the various countries. A concern is the long time required between initiation and completion. Conclusions: Nationwide Nordic registries can be combined into cohorts with high validity and statistical power, but the considerable expertise, workload, and time required to complete such cohorts should not be underestimated.
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| 16. |
- Maret-Ouda, John, et al.
(författare)
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Objectively confirmed gastroesophageal reflux disease and risk of atrial fibrillation : a population-based cohort study in Sweden
- 2022
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Ingår i: European Journal of Gastroenterology and Hepathology. - : Ovid Technologies (Wolters Kluwer Health). - 0954-691X .- 1473-5687. ; 34:11, s. 1116-1120
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study aimed to determine the risk of atrial fibrillation in patients with objectively confirmed GERD. Methods This was a nationwide population-based cohort study between 2005 and 2018, including the majority (n = 8 421 115) of all Swedish adult residents (>= 18 years). Within this cohort, the exposed group were all individuals with a diagnosis of esophagitis or Barrett's esophagus, and the unexposed group was made up of five times as many individuals without any GERD, matched by age, sex, and calendar year. The outcome was the first diagnosis of atrial fibrillation. Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for confounders. Results Among 118 013 individuals with esophagitis or Barrett's esophagus and 590 065 without GERD, 7042 (6.0%) and 40 962 (6.9%) developed atrial fibrillation, respectively. The risk of atrial fibrillation among patients with GERD was 13% increased within the first year of diagnosis (HR, 1.13; 95% CI, 1.06-1.20), but was not increased after that. Among individuals aged less than 60 years, the HR of atrial fibrillation was 55% increased within the first year of diagnosis (HR, 1.55; 95% CI, 1.27-1.88), and this association remained increased after the first year (HR, 1.14; 95% CI, 1.06-1.22). No association was found in older participants (>= 60 years). Results were similar in men and women. Conclusion This large population-based cohort study indicates that objectively determined GERD increases the risk of atrial fibrillation shortly after diagnosis in men and women younger than 60 years.
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| 17. |
- Maret-Ouda, John, et al.
(författare)
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Opportunities for preventing esophageal adenocarcinoma
- 2016
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Ingår i: Cancer Prevention Research. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1940-6207. ; 9:11, s. 828-834
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Tidskriftsartikel (refereegranskat)abstract
- Esophageal adenocarcinoma is rapidly increasing in incidence in many Western societies, requires demanding treatment and is associated with a poor prognosis, therefore preventive measures are highly warranted. To assess the opportunities for prevention, we reviewed the available literature and identified seven main potentially preventive targets. Preventive effects were found based on medium level observational evidence following treatment of gastroesophageal reflux disease (both using medication and surgery) and tobacco smoking cessation, which should be clinically recommended among exposed patients. Non-steroidal anti-inflammatory drugs appears to prevent esophageal adenocarcinoma, and the limited existing data also indicates a protective effect of medication with statins or hormone replacement therapy in women, but current evidence is insufficient to guide clinical decision-making regarding these drugs. The evidence is presently insufficient to assess the potentially preventive role of weight loss. Whether avoidance of eradication of Helicobacter pylori prevents esophageal adenocarcinoma is not studied, but there is no evidence that such eradication increases symptoms of gastro- esophageal reflux or prevalence of erosive esophagitis. The introduction of preventive actions should be tailored towards high-risk individuals, i.e. older men with obesity and gastroesophageal reflux disease and individuals with Barrett’s esophagus rather than the population at large.
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| 18. |
- Maret-Ouda, John, et al.
(författare)
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Proton pump inhibitor use and risk of pneumonia : a self-controlled case series study
- 2023
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Ingår i: Journal of gastroenterology. - : Springer. - 0944-1174 .- 1435-5922. ; 58, s. 734-740
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent research indicates that use of proton pump inhibitors (PPIs) is associated with pneumonia, but existing evidence is inconclusive because of methodological issues. This study aimed to answer whether PPI-use increases risk of pneumonia while taking the methodological concerns of previous research into account.Methods: This population-based and nationwide Swedish study conducted in 2005-2019 used a self-controlled case series design. Data came from national registries for medications, diagnoses, and mortality. Conditional fixed-effect Poisson regression provided incidence rate ratios (IRR) with 95% confidence intervals (CI) for pneumonia comparing PPI-exposed periods with unexposed periods in the same individuals, thus controlling for confounding. Analyses were stratified by PPI-treatment duration, sex, age, and smoking-related diseases. Use of histamine type-2 receptor antagonists (used for the same indications as PPIs) and risk of pneumonia was analysed for assessing the validity and specificity of the results for PPI-therapy and pneumonia.Results: Among 519,152 patients with at least one pneumonia episode during the study period, 307,709 periods of PPI-treatment occurred. PPI-use was followed by an overall 73% increased risk of pneumonia (IRR 1.73, 95% CI 1.71-1.75). The IRRs were increased across strata of PPI-treatment duration, sex, age, and smoking-related disease status. No such strong association was found between histamine type-2 receptor antagonist use and risk of pneumonia (IRR 1.08, 95% CI 1.02-1.14).Conclusions: PPI-use seems to be associated with an increased risk of pneumonia. This finding highlights a need for caution in using PPIs in individuals with a history of pneumonia.
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| 19. |
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| 20. |
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| 21. |
- Maret-Ouda, John, et al.
(författare)
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The risk of mortality following secondary fundoplication in a population-based cohort study
- 2016
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Ingår i: The American Journal of Surgery. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0002-9610 .- 1879-1883.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mortality following laparoscopic fundoplication has been found to be negligible. However, some patients require secondary fundoplication, and the risk of mortality following such procedure is scarcely studied. METHODS: This nationwide Swedish population-based cohort study included all patients undergoing secondary fundoplication following primary laparoscopic fundoplication in 1997 to 2013, regardless of indication. Primary outcome was mortality within 90 days of surgery, and secondary outcome was postoperative length of hospital stay. RESULTS: A total of 9,765 patients underwent primary laparoscopic fundoplication, 540 (5.5%) patients underwent secondary fundoplication. About 382 (70.7%) were conducted laparoscopically, and 158 (29.3%) were conducted with an open technique. No deaths occurred within 90 days of the secondary fundoplication. Median length of stay was longer following secondary fundoplication (4.8 days, interquartile range 1.0 to 5.0 days), compared to primary laparoscopic fundoplication (2.5 days, interquartile range 1.0 to 3.0 days). CONCLUSIONS: This population-based cohort study indicates that secondary fundoplication following primary laparoscopic fundoplication is a safe procedure. The longer hospital stay following secondary fundoplication compared to primary laparoscopic fundoplication is likely explained by the higher rate of open surgical approach.
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| 22. |
- Maret-Ouda, John, et al.
(författare)
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What is the most effective treatment for severe gastro-oesophageal reflux disease?
- 2015
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Ingår i: BMJ. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0959-8138 .- 1756-1833.
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Tidskriftsartikel (refereegranskat)abstract
- This is one of a series of occasional articles that highlight areas of practice where management lacks convincing supporting evidence. The series adviser is David Tovey, editor in chief, the Cochrane Library.
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| 23. |
- Markar, Sheraz, et al.
(författare)
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Hospital Volume of Antireflux Surgery in Relation to Endoscopic and Surgical Re-interventions
- 2020
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Ingår i: Annals of Surgery. - : Wolters Kluwer. - 0003-4932 .- 1528-1140. ; 274:6, s. 1138-1143
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Tidskriftsartikel (refereegranskat)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.
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| 24. |
- Selin, Daniel, et al.
(författare)
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Cohort profile : the swedish pancreatitis cohort (SwePan)
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The Swedish Pancreatitis Cohort (SwePan) was designed to study long-term outcomes following an episode of acute pancreatitis. It can also be used to study various risk factors for developing acute pancreatitis.PARTICIPANTS: The SwePan is a register-based nationwide matched cohort. It includes all Swedish cases of acute pancreatitis during 1990-2019. It contains 95 632 individuals with acute pancreatitis and 952 783 pancreatitis-free individuals matched on sex, age and municipality of residence. Follow-up was censored at death, emigration or end of study (31 December 2019). The dataset includes comprehensive information based on several registries, and includes diagnoses, prescribed medications and socioeconomic factors both prior to inclusion and during follow-up.FINDINGS TO DATE: During the study period, the number of cases of acute pancreatitis in Sweden has more than doubled from 1977 cases in 1990 to 4264 cases in 2019. The median age of first episode of acute pancreatitis has increased from 58 years (IQR 44-73 years) in 1990 to 64 years (IQR 49-76 years) in 2019. Cases with acute pancreatitis were generally less healthy compared with the pancreatitis-free individuals (Charlson Comorbidity Index of 0 in 59.2% and 71.4%, respectively).FUTURE PLANS: SwePan will be used to determine the incidence of acute pancreatitis in Sweden over time and assess long-term all-cause and cause-specific mortality after an episode of acute pancreatitis. Some examples of additional planned studies are (1) assessment of long-term risk of diabetes and (2) risk of malignancy in adjacent organs following acute pancreatitis and (3) assessment of risk factors for development of acute pancreatitis including various drugs.
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| 25. |
- Selin, Daniel, et al.
(författare)
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Exploring the association between acute pancreatitis and biliary tract cancer : a large-scale population-based matched cohort study
- 2024
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Ingår i: United European Gastroenterology journal. - : John Wiley & Sons. - 2050-6406 .- 2050-6414.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Biliary tract cancer (BTC) often goes undetected until its advanced stages, resulting in a poor prognosis. Given the anatomical closeness of the gallbladder and bile ducts to the pancreas, the inflammatory processes triggered by acute pancreatitis might increase the risk of BTC.Objective: To assess the association between acute pancreatitis and the risk of BTC.Methods: Using the Swedish Pancreatitis Cohort (SwePan), we compared the BTC risk in patients with a first-time episode of acute pancreatitis during 1990–2018 to a 1:10 matched pancreatitis-free control group. Multivariable Cox regression models, stratified by follow-up duration, were used to calculate hazard ratios (HRs), adjusting for socioeconomic factors, alcohol use, and comorbidities.Results: BTC developed in 0.94% of 85,027 acute pancreatitis patients and in 0.23% of 814,993 controls. The BTC risk notably increased within 3 months of hospital discharge (HR 82.63; 95% CI: 63.07–108.26) and remained elevated beyond 10 years of follow-up (HR 1.82; 95% CI: 1.35–2.47). However, the long-term risk of BTC subtypes did not increase with anatomical proximity to the pancreas, with a null association for gallbladder and extrahepatic tumors. Importantly, patients with acute pancreatitis had a higher occurrence of early-stage BTC within 2 years of hospital discharge than controls (13.0 vs. 3.6%; p-value <0.01).Conclusion: Our nationwide study found an elevated BTC risk in acute pancreatitis patients; however, the risk estimates for BTC subtypes were inconsistent, thereby questioning the causality of the association. Importantly, the amplified detection of early-stage BTC within 2 years after a diagnosis of acute pancreatitis underscores the necessity for proactive BTC surveillance in these patients.
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