| 1. |
- Engstrom, Arvid, et al.
(författare)
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Association of glucagon-like peptide-1 receptor agonists with serious liver events among patients with type 2 diabetes: A Scandinavian cohort study
- 2023
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Ingår i: HEPATOLOGY. - 0270-9139 .- 1527-3350. ; 79:6, s. 1401-1411
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims:Clinical trials suggest that glucagon-like peptide-1 (GLP-1) receptor agonists may have beneficial effects on NAFLD, but the impact on hard hepatic end points is unknown. We assessed the association between the use of GLP-1 receptor agonists and the risk of serious liver events in routine clinical practice. Approach and Results:Cohort study using data from nationwide registers in Sweden, Denmark, and Norway, 2007-2020, including 91,479 initiators of GLP-1 receptor agonists and 244,004 initiators of the active comparator, dipeptidyl peptidase-4 inhibitors, without a history of chronic liver disease other than NAFLD/NASH. The primary outcome was serious liver events: a composite of incident compensated and decompensated cirrhosis and HCC. Secondary outcomes were the individual components of the primary outcome. Cox regression was used to estimate HRs, using propensity score weighting to control for confounding. Users of GLP-1 receptor agonists had 608 serious liver events (adjusted incidence rate: 16.9 events per 10,000 person-years), compared with 1770 events among users of dipeptidyl peptidase-4 inhibitors (19.2 events per 10,000 person-years). The adjusted HR was 0.85 (95% CI: 0.75 to 0.97), and the rate difference was -2.1 (-4.4 to 0.1) events per 10,000 person-years. In secondary outcome analyses, the adjusted HR was 0.85 (0.75 to 0.97) for compensated and decompensated cirrhosis and 1.05 (0.80 to 1.39) for HCC. Conclusions:The use of GLP-1 receptor agonists was associated with a significantly reduced risk of serious liver events, driven by a reduction of compensated and decompensated cirrhosis.
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| 2. |
- Pasternak, Bjorn, et al.
(författare)
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Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study
- 2024
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Ingår i: BMJ-BRITISH MEDICAL JOURNAL. - 0959-535X .- 1756-1833. ; 385
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate whether use of glucagon-like peptide 1 (GLP1) receptor agonists is associated with increased risk of thyroid cancer. DESIGN Scandinavian cohort study. SETTING Denmark, Norway, and Sweden, 2007-21. PARTICIPANTS Patients who started GLP1 receptor agonist treatment were compared with patients who started dipeptidyl peptidase 4 (DPP4) inhibitor treatment, and in an additional analysis, patients who started sodiumglucose cotransporter 2 (SGLT2) inhibitor treatment. MAIN OUTCOME MEASURES Thyroid cancer identified from nationwide cancer registers. An active -comparator new user study design was used to minimise risks of confounding and time related biases from using real world studies of drug effects. Cox regression was used to estimate hazard ratios, controlling for potential confounders with propensity score weighting. RESULTS The mean follow-up time was 3.9 years (standard deviation 3.5 years) in the GLP1 receptor agonist group and 5.4 years (standard deviation 3.5 years) in the DPP4 inhibitor group. 76 of 145 410 patients (incidence rate 1.33 events per 10 000 person years) treated with GLP1 receptor agonists and 184 of 291 667 patients (incidence rate 1.46 events per 10 000 person years) treated with DPP4 inhibitors developed thyroid cancer. GLP1 receptor agonist use was not associated with increased risk of thyroid cancer (hazard ratio 0.93, 95% confidence interval 0.66 to 1.31; rate difference -0.13, 95% confidence interval -0.61 to 0.36 events per 10 000 person years). The hazard ratio for medullary thyroid cancer was 1.19 (0.37 to 3.86). In the additional analysis comparing the GLP1 receptor agonist group with the SGLT2 inhibitor group, the hazard ratio for thyroid cancer was 1.16 (0.65 to 2.05). CONCLUSIONS In this large cohort study using nationwide data from three countries, GLP1 receptor agonist use was not associated with a substantially increased risk of thyroid cancer over a mean follow-up of 3.9 years. In the main analysis comparing GLP1 receptor agonists with DPP4 inhibitors, the upper limit of the confidence interval was consistent with no more than a 31% increase in relative risk.
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| 3. |
- Ueda, Peter, et al.
(författare)
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Use of DPP4 Inhibitors and GLP-1 Receptor Agonists and Risk of Intestinal Obstruction: Scandinavian Cohort Study
- 2023
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Ingår i: Clinical Gastroenterology and Hepatology. - 1542-3565 .- 1542-7714.
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Concerns have been raised that the incretin-based diabetes drugs dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists may increase the risk of intestinal obstruction. We aimed to assess the association between use of DPP4 inhibitors and GLP-1 receptor agonists and the risk of intestinal obstruction. Methods: Using data from nationwide registers in Sweden, Denmark, and Norway, 2013–2021, we conducted 2 cohort studies, one for DPP4 inhibitors and one for GLP-1 receptor agonists, to investigate the risk of intestinal obstruction as compared with an active comparator drug class (sodium-glucose co-transporter 2 [SGLT2] inhibitors). Results: Among 19,0321 new users of DPP4 inhibitors (median (interquartile range [IQR]) follow-up time, 1.3 [0.6–2.6] years) and 139,315 new users of SGLT2 inhibitors (median [IQR] follow-up time, 0.8 [0.4–1.7] years), 919 intestinal obstruction events occurred. Use of DPP4 inhibitors, as compared with SGLT2 inhibitors, was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate, 2.0 vs 1.8 per 1000 person-years; hazard ratio, 1.13; 95% confidence interval, 0.96–1.34). Among 121,254 new users of GLP-1 receptor agonists (median [standard deviation] follow-up time, 0.9 [0.4–1.9] years) and 185,027 new users of SGLT2 inhibitors (median [IQR] follow-up time, 0.8 [0.4–1.8] years), 557 intestinal obstruction events occurred. Use of GLP-1 receptor agonists was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate, 1.3 vs 1.6 per 1000 person-years; hazard ratio, 0.83; 95% confidence interval, 0.69–1.01). Conclusions: In this analysis of nationwide data from 3 countries, previous safety signals indicating an increased risk of intestinal obstruction with use of DPP4 inhibitors and GLP-1 receptor agonists were not confirmed.
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| 4. |
- von Zur-Mühlen, Bengt, et al.
(författare)
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Healthcare Resource Use, Cost, and Sick Leave Following Kidney Transplantation in Sweden : A Population-Based, 5-Year, Retrospective Study of Outcomes: COIN
- 2018
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Ingår i: Annals of Transplantation. - 1425-9524 .- 2329-0358. ; 23, s. 852-866
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Tidskriftsartikel (refereegranskat)abstract
- Background: Improved understanding of the impact of kidney transplantation on healthcare resource use/costs and loss of productivity could aid decision making about funding allocation and resources needed for the treatment of chronic kidney disease in stage 5.Material/Methods: This was a retrospective study utilizing data from Swedish national health registers of patients undergoing kidney transplantation. Primary outcomes were renal disease-related healthcare resource utilization and costs during the 5 years after transplantation. Secondary outcomes included total costs and loss of productivity. Regression analysis identified factors that influenced resource use, costs, and loss of productivity.Results: During the first year after transplantation, patients (N=3120) spent a mean of 25.7 days in hospital and made 21.6 outpatient visits; mean renal disease-related total cost was & euro;66,014. During the next 4 years, resource use was approximately 70% (outpatient) to 80% (inpatient) lower, and costs were 75% lower. Before transplantation, 62.8% were on long-term sick leave, compared with 47.4% 2 years later. Higher resource use and costs were associated with age <10 years, female sex, graft from a deceased donor, prior hemodialysis, receipt of a previous transplant, and presence of comorbidities. Higher levels of sick leave were associated with female sex, history of hemodialysis, and type 1 diabetes. Overall 5-year graft survival was 86.7% (95% CI 85.3-88.2%).Conclusions: After the first year following transplantation, resource use and related costs decreased, remaining stable for the next 4 years. Demographic and clinical factors, including age <10 years, female sex, and type 1 diabetes were associated with higher costs and resource use.
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| 5. |
- Wang, Yun-Han, et al.
(författare)
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Association Between Proton Pump Inhibitor Use and Risk of Asthma in Children
- 2021
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Ingår i: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 175:4, s. 394-403
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The use of proton pump inhibitors (PPIs) in children has increased substantially in recent years, concurrently with emerging concerns that these drugs may increase the risk of asthma. Whether PPI use in the broad pediatric population is associated with increased risk of asthma is not known.OBJECTIVE: To investigate the association between PPI use and risk of asthma in children.DESIGN, SETTING, AND PARTICIPANTS: This nationwide cohort study collected registry data in Sweden from January 1, 2007, to December 31, 2016. Children and adolescents 17 years or younger were matched by age and propensity score into 80 870 pairs of those who initiated PPI use and those who did not. Data were analyzed from February 1 to September 1, 2020.EXPOSURES: Initiation of PPI use.MAIN OUTCOMES AND MEASURES: The primary analysis examined the risk of incident asthma with a median follow-up to 3.0 (interquartile range, 2.1-3.0) years. Cox proportional hazards regression was used to estimate hazard ratios (HRs).RESULTS: Among the 80 870 pairs (63.0% girls; mean [SD] age, 12.9 [4.8] years), those who initiated PPI use had a higher incidence rate of asthma (21.8 events per 1000 person-years) compared with noninitiators (14.0 events per 1000 person-years), with an HR of 1.57 (95% CI, 1.49-1.64). The risk of asthma was significantly increased across all age groups and was highest for infants and toddlers with an HR of 1.83 (95% CI, 1.65-2.03) in the group younger than 6 months and 1.91(95% CI, 1.65-2.22) in the group 6 months to younger than 2 years (P < .001for interaction). The HRs for individual PPIs were 1.64 (95% CI, 1.50-1.79) for esomeprazole, 1.49 (95% CI, 1.25-1.78) for lansoprazole. 1.43 (95% CI, 1.35-1.51) for omeprazole, and 2.33 (95% CI, 1.30-4.18) for pantoprazole. In analyses of the timing of asthma onset after PPI initiation, the HRs were 1.62 (95% Cl. 1.42-1.85) for 0 to 90 days, 1.73 (95% CI, 1.52-1.98) for 91to 180 days. and 1.53 (95% CI, 1.45-1.62) for 181days to end of follow-up. The association was consistent through all sensitivity analyses, including high-dimensional propensity score matching (HR, 1.48; 95% CI, 1.41-1.55).CONCLUSIONS AND RELEVANCE: In this cohort study, initiation of PPI use compared with nonuse was associated with an increased risk of asthma in children. Proton pump inhibitors should be prescribed to children only when clearly indicated, weighing the potential benefit against potential harm.
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| 6. |
- Wang, Yun-Han, et al.
(författare)
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Association Between Proton Pump Inhibitor Use and Risk of Fracture in Children
- 2020
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Ingår i: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 29, s. 452-452
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Tidskriftsartikel (refereegranskat)abstract
- This study of a Swedish national registry cohort assesses the association between proton pump inhibitor use and risk of fracture in children.Question: Is proton pump inhibitor (PPI) use associated with increased risk of fracture in children?Findings: This pediatric cohort compared 115933 patients who initiated PPI use with 115933 matched individuals who did not initiate use and found that PPI use was associated with an 11% increased risk of fracture, a significant difference.Meaning: These data suggest that PPI use is associated with a small increased risk of fracture in children; the findings inform safety considerations when these drugs are prescribed to pediatric patients.Importance: Proton pump inhibitor (PPI) use has been linked to increased risk of fracture in adults. Despite a trend in prescription of PPIs in children, there is scarce evidence regarding this safety concern in pediatric patients.Objective: To evaluate the association between PPI use and risk of fracture in children.Design: This nationwide register-based cohort study included data from Sweden from July 2006 to December 2016. Children younger than 18 years who initiated PPI use were matched on propensity score and age with those who did not initiate PPI use.Exposure: Initiation of PPI use.Main Outcomes and Measures: Cox regression was adopted to estimate hazard ratios (HRs) for a first fracture of any type and 5 subtypes of fracture, with follow-up for up to 5 years. To address potential residual confounding, high-dimensional propensity score matching and a direct comparison with histamine-2 receptor antagonists were performed.Results: There were a total of 115933 pairs of children included. During a mean (SD) of 2.2 (1.6) years of follow-up, 5354 and 4568 cases of any fracture occurred among those who initiated PPIs vs those who did not, respectively (20.2 vs 18.3 events per 1000 person-years; hazard ratio [HR], 1.11 [95% CI, 1.06-1.15]). Use of PPIs was associated with increased risk of upper-limb fracture (HR, 1.08 [95% CI, 1.03-1.13]), lower-limb fracture (HR, 1.19 [95% CI, 1.10-1.29]), and other fractures (HR, 1.51 [95% CI, 1.16-1.97]) but not head fracture (HR, 0.93 [95% CI, 0.76-1.13]) or spine fracture (HR, 1.31 [95% CI, 0.95-1.81]). The HRs for fracture according to cumulative duration of PPI use were 1.08 (95% CI, 1.03-1.13) for 30 days or less, 1.14 (95% CI, 1.09-1.20) for 31 to 364 days, and 1.34 (95% CI, 1.13-1.58) for 365 days or more. The association was consistent in most sensitivity analyses, including high-dimensional propensity score matching (HR, 1.10 [95% CI, 1.06-1.15]), although the analysis of PPI vs histamine-2 receptor antagonist did not reach statistical significance (HR, 1.06 [95% CI, 0.97-1.15]).Conclusions and Relevance: In this large pediatric cohort, PPI use was associated with a small but significant increased risk of any fracture. Risk of fracture should be taken into account when weighing the benefits and risks of PPI treatment in children.
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| 7. |
- Wang, Yun-Han, et al.
(författare)
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Association between proton pump inhibitor use and risk of fracture in children
- 2020
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Ingår i: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 29:Suppl. 3, s. 452-452
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Proton pump inhibitor (PPI) use has been linked to increased risk of fracture in adults. Despite an increasing trend in prescription of PPIs in children, there is scarce evidence regarding this safety concern in pediatric patients.Objectives: To evaluate the association between PPI use and risk of fracture in children.Methods: We conducted a nationwide register-based cohort study of children aged <18 years in Sweden between July, 2006 to December, 2016. The analyzed cohort included 115,933 pairs of PPI initiators and non-initiators matched on propensity score and age. Cox regression was used to estimate hazard ratios (HRs) for a first fracture of any type and 5 subtypes of fracture with follow-up up to 5 years. To address potential residual confounding, high-dimensional propensity score-matching and a direct comparison with histamine-2-receptorant agonists (H2RA) were performed.Results: During mean 2.2 (standard deviation 1.6) years of follow-up, 5,354 and 4,568 cases of any fracture occurred among PPI initiators and non-initiators, respectively (20.2 versus 18.3 events per 1000 person-years; HR, 1.11; 95%CI, 1.06-1.15). PPI was associated with increased risk of upper limb fracture (HR, 1.08; 95%CI, 1.03-1.13), lower limb fracture (HR, 1.19; 95%CI, 1.10-1.29), other fracture (HR, 1.51; 95%CI, 1.16-1.97) but not head fracture (HR, 0.93; 95%CI, 0.76-1.13) and spine fracture (HR, 1.31; 95%CI, 0.95-1.81). The HRs for fracture according to cumulative duration of PPI use were 1.08 (95%CI, 1.03-1.13) for ≤30 days, 1.14 (95% CI, 1.09-1.20) for31-364 days and 1.34 (95% CI, 1.13-1.58) ≥365 days. The association was consistent in most sensitivity analyses, including high-dimensional propensity score-matching (HR, 1.10; 95% CI, 1.06-1.15), although the analysis of PPI vs H2RA did not reach statistical significance (HR,1.06; 95%CI, 0.97-1.15).Conclusions: In this large pediatric cohort, PPI use was associated with a small but statistically significant increased risk of any fracture. Risk of fracture should be taken into account when weighing the benefits and risks of PPI treatment in children.
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| 8. |
- Wang, Yun-Han, et al.
(författare)
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Association between proton pump inhibitor use and risk of pneumonia in children : nationwide self-controlled case series study in Sweden
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the association between use of proton pump inhibitors (PPIs) and risk of pneumonia in children.Design: Nationwide register-based self-controlled case series study.Setting: Sweden, July 2006 to December 2016.Participants: Children aged <18 years who were treated with PPIs and had a hospitalisation or hospital emergency care visit for pneumonia within 1 year before and 2 years after PPI initiation.Main outcomes and measures: The primary analysis examined the risk of pneumonia during the risk period (ongoing PPI treatment), the pre-exposure period (<= 30 days preceding PPI treatment) and the postexposure period (days 1-365 after PPI discontinuation), comparing to the unexposed period. Conditional Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% CIs.Results: A total of 2356 cases of pneumonia were included. Compared with the unexposed period, the risk of pneumonia was significantly increased during ongoing PPI treatment, with an adjusted IRR of 1.40 (95% CI 1.21 to 1.62). The risk of pneumonia was also increased in the pre-exposure period (adjusted IRR, 1.80, 95% CI 1.51 to 2.13), but not in the postexposure period (adjusted IRR 0.98, 95% CI 0.89 to 1.08). Dividing the risk period by time since treatment initiation, the increased risk of pneumonia was highest in the first 30 days (adjusted IRR 1.63, 95% CI 1.35 to 1.97), remained during days 31-90 (adjusted IRR 1.32, 95% CI 1.04 to 1.69), but waned in days >= 91 (IRR 1.06, 95% CI 0.79 to 1.41).Conclusions and relevance: An increased risk of pneumonia was observed both immediately before and immediately after PPI initiation. This pattern of association can likely be explained by an underlying risk of pneumonia due to factors transiently present at the time around PPI initiation. Thus, our findings do not support a causal relationship between PPI use and risk of pneumonia.
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| 9. |
- Wang, Yun-Han, et al.
(författare)
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Proton pump inhibitor use and risk of depression and anxiety in children : nationwide cohort study
- 2022
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Ingår i: Clinical and Translational Science. - : John Wiley & Sons. - 1752-8054 .- 1752-8062. ; 15:5, s. 1112-1122
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Tidskriftsartikel (refereegranskat)abstract
- Although some data have linked proton pump inhibitor (PPI) use to risk of depression and anxiety, there are no studies investigating this safety issue in children. This study investigated the association between PPI use and risk of depression and anxiety in children. We conducted a nationwide register-based cohort study in Sweden, July 1, 2007, to December 31, 2016. Following matching on age and propensity score, we included 29,320 pairs of PPI initiators and noninitiators among children aged 7-17 years old. The primary analysis examined the risk of incident depression and anxiety, a composite outcome defined as a diagnosis of depression, anxiety, or a prescription for an antidepressant. Children who initiated PPI use had higher hazards for risk of depression and anxiety compared with noninitiators (hazard ratios [HRs], 2.61; 95% confidence interval [CI], 2.32-2.94). In analyses of the timing of depression and anxiety onset after PPI initiation, the HRs were 3.71 (95% CI, 2.17-6.34) for 1-30 days, 3.47 (95% CI, 2.33-5.18) for 31-90 days, 2.71 (2.04-3.60) for 91-180 days, 2.52 (2.00-3.16) for 181-365 days, and 2.34 (1.94-2.82) for 366-730 days. Significant associations were observed across all age groups. The magnitude of the association increased with longer duration of PPI use (p for trend < 0.0001). The association was consistent through all sensitivity analyses, including high-dimensional propensity score matching (HR, 2.31, 95% CI, 2.05-2.61). PPI use was associated with increased risk of depression and anxiety in children. Further investigation is warranted to confirm or refute this potential association.
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| 10. |
- Wintzell, Viktor, et al.
(författare)
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Association between azathioprine use and risk of acute pancreatitis in pediatric inflammatory bowel disease : A nationwide Swedish cohort study
- 2018
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Ingår i: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 27:Suppl. 2, s. 196-196
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Studies have shown an association between use of azathioprine and acute pancreatitis in adult inflammatory bowel disease. However, whether there is an association among pediatric patients isnot known.Objectives: To investigate if there is an association between use of azathioprine and the risk of acute pancreatitis in pediatric inflammatory bowel disease (pIBD) patients.Methods: We conducted a nationwide Swedish cohort study based on health care register data, 2006‐2014. From a cohort of all pediatric patients (<18 years) with IBD (n = 4631), we included 1477 episodes of new azathioprine use and 1477 episodes of no use in propensity score‐matched (1:1 ratio) analyses. The propensity score included patient characteristics, comorbidities, previous treatment, indicators of disease severity and health care utilization. Incident cases of acute pancreatitis occurring in the primary risk period of 90 days following treatment initiation were identified through outpatient and inpatient hospital records. A sensitivity analysis was restricted to inpatient cases alone. A secondary risk period of 91‐365 days following treatment initiation was also assessed. Cox proportional hazards models were used to estimate hazard ratios (HRs).Results: Among azathioprine‐exposed, mean age was 14.3 (SD 3.2) years, 56.5% were male, and 56.1% had Crohn's disease and 43.9% had ulcerative colitis or IBD‐unclassified. During the first 90 days following azathioprine initiation, 23 patients (1.6%) experienced acute pancreatitis compared with 5 patients (0.3%) in the no use group; corresponding incidence rates were 65 and 16 per 1000 person‐years. The risk was significantly higher in patients with azathioprine use, HR = 4.21 (95% CI 1.60‐11.08). The HR was similar when only considering acute pancreatitis events in inpatient care (4.82 [1.65‐14.03]) and there was no increased risk during the period 91‐365 days following treatment initiation (0.36 [0.03‐4.01]).Conclusions: Use of azathioprine was associated with an increased risk of acute pancreatitis in pIBD during the first 90 days of use but not later. The finding suggests that the risk of acute pancreatitis needs to be considered when deciding on optimal treatment strategy in pIBD. Additional analyses also including nationwide Danish data are ongoing and will be presented at the conference.
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