Publications by authors named "Søren Lophaven"

20 Publications

  • Page 1 of 1

Surgery, cancer and mortality among patients with ulcerative colitis diagnosed 1962-1987 and followed until 2017 in a Danish population-based inception cohort.

Aliment Pharmacol Ther 2021 Oct 29. Epub 2021 Oct 29.

Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.

Background: Long-term data on the natural disease course of unselected patients with ulcerative colitis (UC) are limited.

Aims: To determine the long-term course and prognosis of UC, including patients' risks of surgery, cancer and mortality, in a population-based cohort followed for over 50 years METHODS: All incident patients with UC diagnosed between 1962 and 1987 in Copenhagen County, Denmark were included in a population-based cohort. We extracted information about IBD-related surgeries, cancers and mortality from patient files from 1962 to 1987, and from the Danish National Patient Registry, Cancer Registry, and Register of Causes of Death during 1988-2017. Patients were matched with up to 50 individuals from the general population.

Results: We followed 1161 patients for a median of 34 years (range: 0.1-56.0). Median age at diagnosis was 33 years (range: 2-88). The cumulative probability of colectomy 10, 20, 30, 40 and 50 years after diagnosis was 22% (95% CI: 20%-25%), 27% (95% CI: 25%-30%), 31% (95% CI: 28%-34%), 34% (95% CI: 31%-37%), and 40% (95% CI: 36%-44%), respectively. The risk of small intestinal, colon, rectal and anal cancer was higher than among controls, as was cancer of the skin, pancreas and thyroid. All-cause mortality was lower than controls (adjusted RR: 0.90, 95% CI: 0.82-0.99).

Conclusion: In this population-based cohort of UC patients diagnosed between 1962 and 1987, 40% underwent colectomy within 50 years of diagnosis. Physicians need to be aware that UC patients are at increased risk of intestinal and extra-intestinal cancers. However, UC patients' risk of mortality is comparable to that of the background population.
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http://dx.doi.org/10.1111/apt.16677DOI Listing
October 2021

The clinical course of Crohn's disease in a Danish population-based inception cohort with more than 50 years of follow-up, 1962-2017.

Aliment Pharmacol Ther 2021 Sep 20. Epub 2021 Sep 20.

Department of Gastroenterology, North Zealand Hospital, University of Copenhagen, Copenhagen, Denmark.

Background: Few population-based studies have investigated the long-term prognosis of Crohn's disease (CD).

Aim: To determine the long-term natural disease course of CD with regard to surgery, cancer and mortality in a population-based cohort followed for more than 50 years.

Methods: All patients diagnosed with CD from 1962 to 1987 in Copenhagen County, Denmark were included in a population-based cohort. Information about surgeries, cancers and mortality was collected from patient files from 1962 to 1987 and from the Danish National Patient Registry, Cancer Registry, and from the Register of Causes of Death, 1987-2017. Patients were matched with individuals from the general population.

Results: A total of 373 patients were followed for a median of 33 years (range: 0-56 years). The cumulative probability of surgery 10, 20, 30, 40 and 50 years after diagnosis was 62% (CI 95%: 57%-67%), 71% (CI 95%: 66%-75%), 72% (CI 95%: 67%-76%), 74% (CI 95%: 69%-79%) and 74% (CI 95%: 69%-79%), respectively. A total of 142 patients (54%) were operated upon at least twice: 69 (26%) needing two surgeries and 73 (28%) needing three or more. Patients with CD were found to be at increased risk of intestinal (small bowel, rectum and anus) and extra-intestinal (respiratory organs and skin) cancer. All-cause mortality among CD patients was higher than among controls (RR: 1.22, CI 95%: 1.04-1.43), whereas mortality due to gastrointestinal cancer was not.

Conclusion: After 50 years of follow-up, 75% CD patients had undergone surgery, with most needing repeat surgery. The risk of intestinal and extra-intestinal cancers, as well as mortality, was higher among CD patients than the background population.
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http://dx.doi.org/10.1111/apt.16615DOI Listing
September 2021

Microscopic colitis in Denmark: regional variations in risk factors and frequency of endoscopic procedures.

J Crohns Colitis 2021 Jul 7. Epub 2021 Jul 7.

Department of Gastroenterology, North Zealand University Hospital, Capital Region, Denmark.

Objective: Microscopic colitis (MC), encompassing collagenous colitis (CC) and lymphocytic colitis (LC), is an increasingly prevalent gastrointestinal disease with an unknown aetiology. Previous research has reported significant differences in the incidence of MC within Denmark, with the lowest incidence found in the most populated region (Capital Region of Denmark). Our aim was to elucidate the causes of these regional differences.

Design: All incident MC patients (n=14,302) with a recorded diagnosis of CC (n=8,437) or LC (n=5,865) entered in The Danish Pathology Register between 2001 and 2016 were matched to 10 reference individuals (n=142,481). Information regarding drug exposure, including proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs), statins and nonsteroidal anti-inflammatory drugs (NSAIDs), were retrieved from The Danish National Prescription Registry. Information regarding endoscopy rate, smoking related diseases and immune-mediated inflammatory diseases were acquired from The Danish National Patient Registry.

Results: Smoking, immune-mediated inflammatory diseases, exposure to PPIs, SSRIs statins and NSAIDs were significantly associated with MC in all Danish regions. The association between drug exposure and MC was weakest in the Capital Region of Denmark with an Odds Ratio of 1.8 (95% confidence interval (CI): 1.61-2.01). The relative risk of undergoing a colonoscopy with biopsy was significantly increased in sex and age-matched controls in all regions compared to controls from the Capital Region of Denmark, with the greatest risk found in the Region of Southern Denmark, 1.37 (95%CI: 1.26-1.50).

Conclusions: The cause of the regional differences in MC incidence in Denmark seems to be multifactorial, including variations in disease awareness and distribution of risk factors.
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http://dx.doi.org/10.1093/ecco-jcc/jjab119DOI Listing
July 2021

Cancer incidence in Thyborøn-Harboøre, Denmark: a cohort study from an industrially contaminated site.

Sci Rep 2021 06 21;11(1):13006. Epub 2021 Jun 21.

Omicron, Løvparken 21, 4000, Roskilde, Denmark.

In a fishing community Thyborøn-Harboøre on the Danish West coast, a chemical factory polluted air, sea, and ground with > 100 xenobiotic compounds. We investigated cancer incidence in the community. A historical cohort was identified from the Central Population Register and followed for cancer incidence in the Danish Cancer Register including inhabitants from 1968-1970 at height of pollution, and newcomers in 1990-2006 after pollution control. Two fishing communities without pollution, Holmsland and Hanstholm, were referent cohorts. We calculated rate ratios (RR) and 95% confidence intervals (CI). In 1968-1970, 4914 persons lived in Thyborøn-Harboøre, and 9537 persons in Holmsland-Hanstholm. Thyborøn-Harboøre had a statistically significant excess cancer incidence compared with Holmsland-Hanstholm; RR 1.20 (95% CI 1.11-1.29) deriving from kidney and bladder cancer; stomach and lung cancer in men, and colorectal cancer in women. In 1990-2006, 2933 persons came to live in Thyborøn-Harboøre. Their cancer incidence was the same as for newcomers to Holmsland-Hanstholm; RR 1.07 (95% CI 0.88-1.30). Persons in Thyborøn-Harboøre at height of chemical pollution had a cancer risk 20% above persons living in non-polluted fishing communities with a pattern unlikely to be attributable to life style. The study suggested that chemical pollution may have affected cancer risk.
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http://dx.doi.org/10.1038/s41598-021-92446-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217208PMC
June 2021

Insights into the early use of oral semaglutide in routine clinical practice: The IGNITE study.

Diabetes Obes Metab 2021 09 16;23(9):2177-2182. Epub 2021 Jun 16.

Department of Internal Medicine/Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Oral semaglutide is the first oral glucagon-like peptide-1 receptor agonist for the treatment of type 2 diabetes, and showed significant benefits in glycaemic control and weight reduction versus active comparators in the PIONEER phase 3a randomized controlled trial programme. In this retrospective study, we present early data on the use of oral semaglutide in clinical practice, from the US IBM Explorys electronic health record database. In 782 patients prescribed oral semaglutide, 54.5% were women, and the mean age (SD) was 57.8 years (11.3); 66.0% of patients received their prescription from a primary care practitioner. Although prescribing information recommends increasing the dose to 7 mg after 30 days, 37.0% of patients received a prescription only for the initial 3 mg dose. Mean body mass index was 36.2 kg/m (7.6); mean HbA1c was 8.4% (1.8%). Mean HbA1c change from baseline to approximately 6 months after oral semaglutide initiation was -0.9% (95% CI: -1.1%; -0.6%), with greater reductions in patients with higher baseline HbA1c. These data indicate prevalent early adoption of oral semaglutide in primary care, show real-world improvements in glycaemic control, and identify potential treatment gaps.
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http://dx.doi.org/10.1111/dom.14453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453868PMC
September 2021

Does Lolland-Falster make people sick, or do sick people move to Lolland-Falster? An example of selective migration and mortality in Denmark, 1968-2017.

Soc Sci Med 2021 05 3;277:113893. Epub 2021 Apr 3.

Centre for Epidemiological Research, Nykøbing Falster Hospital, University of Copenhagen, Nykøbing Falster, Denmark.

Introduction: Lolland-Falster is a rural area in south-eastern Denmark that scores unfavourable in health surveys and has the lowest life expectancy in the country. To determine the origin of poor health in Lolland-Falster, we investigated impact on mortality of long-term population movements.

Methods: We used data from the Danish Central Population Register 1968-2017 to track movements in and out of Lolland-Falster. This enabled us to calculate mortality based on tenure of residence. Poisson regression adjusted for sex, 5-year age-groups, and calendar year; separately for men and women; and ages <30, 30-64 and ≥ 65 years; was reported as mortality rate ratios (MRR) with 95% confidence intervals (95% CI).

Results: Until 1988, mortality in Lolland-Falster was fairly similar to that in the rest of Denmark. Hereafter, mortality rates drifted apart. In 2008-2017, MRR of the total Lolland-Falster population was 1.21 (95% CI: 1.19-1.23). In each 10-year calendar period, people recently in-migrating constituted about one fourth of the population. MRRs of the in-migrating population increased over time from 1.17 (95% CI: 1.08-1.26) in 1968-1977, to 1.82 (95% CI: 1.75-1.89) in 2008-2017. Persons aged 30-64 constituted the largest in-migrating group and had highest excess mortality, MRR 2.34 (95% CI: 2.19-2.50) in 2008-2017.

Conclusion: Long-term selective in-migration of vulnerable persons was behind the gradual build-up of the currently high mortality in Lolland-Falster compared to the rest of Denmark. In particular, people of working age in-migrating to Lolland-Falster contributed to this disparity.
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http://dx.doi.org/10.1016/j.socscimed.2021.113893DOI Listing
May 2021

Outcomes in GLP-1 RA-Experienced Patients Switching to Once-Weekly Semaglutide in a Real-World Setting: The Retrospective, Observational EXPERT Study.

Diabetes Ther 2021 Mar 17;12(3):879-896. Epub 2021 Feb 17.

College of Osteopathic Medicine, Touro University California, Vallejo, CA, USA.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective for glycaemic control and weight loss in patients with type 2 diabetes (T2D). In this retrospective, observational study, we analysed glycated haemoglobin (HbA1c) and weight following switching to semaglutide from any other GLP-1 RA, using US electronic health records and prescription data.

Methods: Adults (≥ 18 years old) with T2D required at least one prescription for injectable semaglutide at index date (treatment switch), at least one prescription for any other GLP-1 RA in the previous 365 days, a baseline HbA1c and/or weight measurement in the 90 days pre-index and a follow-up measurement at 180 and 365 days post-index. HbA1c and weight cohorts were analysed separately using an ANCOVA model. Sensitivity analyses were conducted in patients with at least two prescriptions for pre-switch GLP-1 RA. A secondary analysis compared subgroups receiving different GLP-1 RAs pre-switch.

Results: Patients with HbA1c (n = 710) and weight (n = 921) data had similar baseline characteristics. Significant reductions in HbA1c at 6 months (0.7%; 95% confidence interval [CI] - 0.8, - 0.6) were sustained at 12 months. Weight reductions were significant at 6 months (- 2.1 kg; 95% CI - 2.6, - 1.6) and greater at 12 months (- 2.8 kg; 95% CI - 3.9, - 1.8). These patterns were consistent with the two-prescription sensitivity analysis and independent of the pre-switch GLP-1 RA.

Conclusion: Switching to injectable semaglutide from any other GLP-1 RA was associated with significant improvements in glycaemic control and weight. Our findings support decision-making in clinical practice in patients with an indication to switch between GLP-1 RAs.
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http://dx.doi.org/10.1007/s13300-021-01010-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947062PMC
March 2021

Disease Activity Patterns, Mortality, and Colorectal Cancer Risk in Microscopic Colitis: A Danish Nationwide Cohort Study, 2001 to 2016.

J Crohns Colitis 2021 Apr;15(4):594-602

Department of Gastroenterology, North Zealand University Hospital, Capital Region, Denmark.

Background And Aims: The disease course of microscopic colitis [MC], encompassing collagenous colitis [CC] and lymphocytic colitis [LC], is not well known. In a Danish nationwide cohort, we evaluated the disease activity patterns as well as the risk of colorectal cancer [CRC] and mortality based on disease severity.

Methods: All incident MC patients [n = 14 302] with a recorded diagnosis of CC [n = 8437] or LC [n = 5865] in the Danish Pathology Register, entered between 2001 and 2016, were matched to 10 reference individuals [n = 142 481]. Incident cases of CRC after the index date were captured from the Danish Cancer Registry. Mortality data were ascertained from the Danish Registry of Causes of Death, and information about treatment was obtained from the Danish National Prescription Registry. The risk of CRC and mortality analyses were investigated by Cox regression and Kaplan-Meier estimates.

Results: We identified a self-limiting or transient disease course in 70.6% of LC patients and in 59.9% of CC patients, p <0.001. Less than 5% of MC patients experienced a budesonide-refractory disease course and were treated with immunomodulators or biologic treatment. A total of 2926 [20.5%] MC patients and 24 632 [17.3%] reference individuals died during the study period. MC patients with a severe disease had a relative risk [RR] of mortality of 1.41 (95% confidence interval [CI]: 1.32-1.50) compared with reference individuals. Only 90 MC patients were diagnosed with CRC during follow-up, corresponding to an RR of 0.48 [95% CI: 0.39-0.60].

Conclusions: A majority of MC patients experience an indolent disease course with a lower risk of developing CRC compared with the background population.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa207DOI Listing
April 2021

Incidence and prevalence of microscopic colitis between 2001 and 2016: A Danish nationwide cohort study.

J Crohns Colitis 2020 Jun 5. Epub 2020 Jun 5.

Department of Gastroenterology, North Zealand University Hospital, Capital Region, Denmark.

Background: Epidemiological studies suggest an increasing global incidence of microscopic colitis, including collagenous colitis and lymphocytic colitis.

Aims: To investigate the incidence and prevalence of microscopic colitis in Denmark.

Methods: In a nationwide cohort study, we included all incident patients with a recorded diagnosis of collagenous colitis or lymphocytic colitis in the Danish Pathology Register between 2001 and 2016.

Results: A total of 14,302 microscopic colitis patients - 8,437 (59%) with collagenous and 5,865 (41%) with lymphocytic colitis - were identified during the study period. The prevalence in December 2016 was estimated to be 197.9 cases per 100,000 inhabitants. Microscopic colitis was more prevalent among females (n=10,127 (71%)), with a mean annual incidence of 28.8, compared to 12.3 per 100,000 person-years among males. The overall mean incidence during the study period was 20.7 per 100,000 person-years. Mean age at time of diagnosis was 65 (SD:14) for microscopic colitis, 67 (SD:13) for collagenous colitis and 63 (SD:15) for lymphocytic colitis. The overall incidence increased significantly from 2.3 cases in 2001 to 24.3 cases per 100,000 person-years in 2016. However, the highest observed incidence of microscopic colitis was 32.3 cases per 100,000 person-years in 2011. Large regional differences were found, with the highest incidence observed in the least populated region.

Conclusions: The incidence of microscopic colitis in Denmark has increased 10-fold during the last 15 years and has now surpassed that of Crohn's disease and ulcerative colitis. However, incidence has stabilised since 2012, suggesting that a plateau has been reached.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa108DOI Listing
June 2020

High incidence of dementia in Faroese-born female residents in Denmark.

Alzheimers Dement (N Y) 2020 27;6(1):e12022. Epub 2020 Apr 27.

Nykøbing Falster Hospital University of Copenhagen Copenhagen Denmark.

Introduction: To assess whether the incidence of dementia among immigrants in Denmark from the Faroe Islands is similar to that of the inhabitants of their new country.

Methods: Data on Faroese-born immigrants in Denmark were retrieved from the Danish Central Population Register. Incident dementia cases were identified from the Danish National Patient Register. Standardized incidence ratios (SIRs) were used to compare the dementia incidence in immigrants with the general Danish population.

Results: Female, first-generation Faroese immigrants had double the risk of dementia compared with Danes (SIR 2.1, 95% confidence interval [CI] 1.8-2.5); the excess risk prevailed even beyond 10 years in Denmark, and it affected all sub-types of dementia. In male immigrants, only a modest, statistically non-significant excess risk was seen (SIR 1.2, 95% CI 0.9-1.6).

Discussion: The observation of an excess risk of dementia in women only but not in men of Faroese origin living in Denmark underscores the complexity of the etiology of dementia.
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http://dx.doi.org/10.1002/trc2.12022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185209PMC
April 2020

Long-Term Exposure to Road Traffic Noise and Incidence of Diabetes in the Danish Nurse Cohort.

Environ Health Perspect 2019 05;127(5):57006

Section of Environmental Health, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

Background: Evidence on the association between road traffic noise and diabetes risk is sparse and inconsistent with respect to how confounding by air pollution was treated.

Objectives: In this study, we aimed to examine whether long-term exposure to road traffic noise over 25 years is associated with incidence of diabetes, independent of air pollution.

Methods: A total of 28,731 female nurses from the Danish Nurse cohort ([Formula: see text] at recruitment in 1993 or 1999) were linked to the Danish National Diabetes Register with information on incidence of diabetes from 1995 until 2013. The annual mean weighted levels of 24-h average road traffic noise ([Formula: see text]) at nurses' residences from 1970 until 2013 were estimated with the Nord2000 method and annual mean levels of particulate matter (PM) with diameter [Formula: see text] and [Formula: see text] ([Formula: see text] and [Formula: see text]), nitrogen dioxide ([Formula: see text]), and nitrogen oxide ([Formula: see text]) with the Danish AirGIS modeling system. Cox proportional hazards regression models were used to examine the association between residential [Formula: see text] in four different exposure windows (1-, 5-, 10-, and 25-years) and the incidence of diabetes, adjusted for lifestyle factors and air pollutants.

Results: Of 23,762 nurses free of diabetes at the cohort baseline, 1,158 developed diabetes during a mean follow-up of 15.2 years. We found weak positive associations between 5-y mean exposure to [Formula: see text] (per [Formula: see text] increase) and diabetes incidence in a crude model [hazard ratio (HR): 1.07; 95% confidence interval (CI): 0.99, 1.12], which attenuated in a model adjusted for lifestyle factors (HR:1.04; 95% CI: 0.97, 1.12), and reached unity after additional adjustment for [Formula: see text] (HR: 0.99; 0.91, 1.08). In analyses by level of urbanization, we found a positive association between noise and diabetes in urban areas (HR:1.27; 95% CI: 0.98, 1.63) that was unchanged after adjusting for [Formula: see text] (HR: 1.25; 95% CI: 0.97, 1.62), but we found no apparent association in provincial (HR: 1.02; 95% CI: 0.88, 1.18) or rural areas (HR: 0.97; 95% CI: 0.87, 1.08).

Conclusion: In the nationwide cohort of Danish nurses 44 years of age and older, we found no association between long-term exposure to road traffic noise and diabetes incidence after adjustment for [Formula: see text] but found suggestive evidence of an association limited to urban areas. https://doi.org/10.1289/EHP4389.
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http://dx.doi.org/10.1289/EHP4389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791549PMC
May 2019

Inflammatory bowel disease and Parkinson's disease.

Gut 2020 05 10;69(5):970. Epub 2019 May 10.

Statistics and Programming, Larix A/S, Herlev, Denmark.

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http://dx.doi.org/10.1136/gutjnl-2019-318958DOI Listing
May 2020

What does migration between the faroe islands and denmark tell us about the etiology of Parkinson's disease?

Mov Disord 2019 06 9;34(6):922-923. Epub 2019 Apr 9.

Department of Occupational Medicine and Public Health, The Faroese Hospital System, Tórshavn, Faroe Islands.

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http://dx.doi.org/10.1002/mds.27692DOI Listing
June 2019

Long-term exposure to road traffic noise and incidence of breast cancer: a cohort study.

Breast Cancer Res 2018 10 5;20(1):119. Epub 2018 Oct 5.

Nykøbing F Hospital, University of Copenhagen, Ejegodvej 63, 4800, Nykøbing F, Denmark.

Background: Exposure to road traffic noise was associated with increased risk of estrogen receptor (ER)-negative (ER-) breast cancer in a previous cohort study, but not with overall or ER-positive (ER+) breast cancer, or breast cancer prognosis. We examined the association between long-term exposure to road traffic noise and incidence of breast cancer, overall and by ER and progesterone receptor (PR) status.

Methods: We used the data from a nationwide Danish Nurse Cohort on 22,466 female nurses (age > 44 years) who at recruitment in 1993 or 1999 reported information on breast cancer risk factors. We obtained data on the incidence of breast cancer from the Danish Cancer Registry, and on breast cancer subtypes by ER and PR status from the Danish Breast Cancer Cooperative Group, up to 31 December 2012. Road traffic noise levels at the nurses' residences were estimated by the Nord2000 method between 1970 and 2013 as annual means of a weighted 24 h average (L) at the most exposed facade. We used time-varying Cox regression to analyze the associations between the 24-year, 10-year, and 1-year mean of L and breast cancer, separately for total breast cancer and by ER and PR status.

Results: Of the 22,466 women, 1193 developed breast cancer in total during 353,775 person-years of follow up, of whom 611 had complete information on ER and PR status. For each 10 dB increase in 24-year mean noise levels at their residence, we found a statistically significant 10% (hazard ratio and 95% confidence interval 1.10; 1.00-1.20) increase in total breast cancer incidence and a 17% (1.17; 1.02-1.33) increase in analyses based on 611 breast cancer cases with complete ER and PR information. We found positive, statistically significant association between noise levels and ER+ (1.23; 1.06-1.43, N = 494) but not ER- (0.93; 0.70-1.25, N = 117) breast cancers, and a stronger association between noise levels and PR+ (1.21; 1.02-1.42, N = 393) than between noise levels and PR- (1.10; 0.89-1.37, N = 218) breast cancers. Association between noise and ER+ breast cancer was statistically significantly stronger in nurses working night shifts (3.36; 1.48-7.63) than in those not working at night (1.21; 1.02-1.43) (p value for interaction = 0.05).

Conclusion: Long-term exposure to road traffic noise may increase risk of ER+ breast cancer.
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http://dx.doi.org/10.1186/s13058-018-1047-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173937PMC
October 2018

BMI at school age and incident asthma admissions in early adulthood: a prospective study of 310,211 children.

Clin Epidemiol 2018 25;10:605-612. Epub 2018 May 25.

Section of Metabolic Genetics and Section of Epidemiology, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.

Background: Excess body weight in adulthood is associated with risk for asthma admission (AA). Our aim was to investigate if this association also applies to the relation between body mass index (BMI) in childhood and AAs in early adulthood (age 20-45 years).

Methods: This was a prospective study of 310,211 schoolchildren (born 1930-1989) from the Copenhagen School Health Records Register. Height and weight were measured annually, and generated BMI -scores were categorized as low (lower quartile), normal (interquartile) and high (upper quartile). Associations between BMI at ages 7-13 and AA were estimated by Cox regressions, and presented as hazard ratios (HRs) and 95% confidence intervals (CI). Main outcome was incident hospital AAs (extracted from the Danish National Patient Register) in early adulthood.

Results: During 4,708,607 person-years of follow-up, 1,813 incident AAs were observed. Nonlinear associations were detected between childhood BMI and AAs. The risk of AA increased for females in the highest BMI category in childhood, with the highest HR of 1.3 (95% CI 1.16-1.55) at the age of 13 years. By contrast, males in the low BMI category had a higher risk of AA in early adulthood, with the highest HR of 1.24 (95% CI 1.03-1.51) at the age of 12 years. Females with an increase in BMI between ages 7 and 13 years had an increased risk of AA compared with females with stable BMI (HR 1.28, 95% CI 1.10-1.50).

Conclusion: The association between childhood BMI and AA in early adulthood is non-linear. High BMI increases the risk of AA in females, whereas low BMI increases the risk in males.
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http://dx.doi.org/10.2147/CLEP.S156310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973632PMC
May 2018

Impact of assumptions - the example of the Welch-analysis of mammography screening effectiveness.

Acta Oncol 2017 08 17;56(8):1131-1133. Epub 2017 Feb 17.

a Department of Public Health , University of Copenhagen , Copenhagen , Denmark.

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http://dx.doi.org/10.1080/0284186X.2017.1288921DOI Listing
August 2017

Benefit-to-harm ratio of the Danish breast cancer screening programme.

Int J Cancer 2017 08 10;141(3):512-518. Epub 2017 May 10.

Department of Public Health, University of Copenhagen, DK-1014, Copenhagen, Denmark.

The primary aim of breast cancer screening is to reduce breast cancer mortality, but screening also has negative side-effects as overdiagnosis. To evaluate a screening programme, both benefits and harms should be considered. Published estimates of the benefit-to-harm ratio, the number of breast cancer deaths prevented divided by the number of overdiagnosed breast cancer cases, varied considerably. The objective of the study was to estimate the benefit-to-harm ratio of breast cancer screening in Denmark. The numbers of breast cancer deaths prevented and overdiagnosed cases [invasive and ductal carcinoma in situ (DCIS)] were estimated per 1,000 women aged 50-79, using national published estimates for breast cancer mortality and overdiagnosis, and national incidence and mortality rates. Estimations were made for both invited and screened women. Among 1,000 women invited to screening from age 50 to age 69 and followed until age 79, we estimated that 5.4 breast cancer deaths would be prevented and 2.1 cases overdiagnosed, under the observed scenario in Denmark of a breast cancer mortality reduction of 23.4% and 2.3% of the breast cancer cases being overdiagnosed. The estimated benefit-to-harm ratio was 2.6 for invited women and 2.5 for screened women. Hence, 2-3 women would be prevented from dying from breast cancer for every woman overdiagnosed with invasive breast cancer or DCIS. The difference between the previous published ratios and 2.6 for Denmark is probably more a reflection of the accuracy of the underlying estimates than of the actual screening programmes. Therefore, benefit-to-harm ratios should be used cautiously.
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http://dx.doi.org/10.1002/ijc.30758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488203PMC
August 2017

Which Cognitive Domains are Improved by Treatment with Vortioxetine?

Int J Neuropsychopharmacol 2016 May 26;19(10). Epub 2016 May 26.

Background: These post hoc analyses evaluated vortioxetine efficacy on cognitive dysfunction in depression. Data were from a double-blind, randomized, fixed-dose, placebo-controlled, 8-week depression study in adults aged 18-65 years (n = 602) with DSM-IV-defined major depressive disorder (MDD). Subjects were randomized (1:1:1) to vortioxetine 10mg/day or 20mg/day or placebo.

Methods: Cognitive function was assessed at baseline, Week 1 (10mg/day only) and Week 8 using Digit Symbol Substitution Test (DSST) number of correct symbols, Rey Auditory Verbal Learning Test, Trail Making Test, Stroop test, Simple Reaction Time, and Choice Reaction Time tests. The cognition variables were standardized and used for constructing composite Z-scores for the cognitive domains of executive function, attention/speed of processing, and memory.

Results: At Week 1, vortioxetine 10mg/day separated from placebo for attention/speed of processing (standardized composite Z-score = 0.21; p = 0.0238) and DSST number of correct symbols (standardized effect size = 0.18; p = 0.0458) and for executive function (standardized composite Z-score = 0.20; p = 0.0274). At Week 8, vortioxetine 10mg/day and 20mg/day separated from placebo for executive function and attention/speed of processing, with standardized composite Z-scores ranging from 0.35 to 0.49 (all p < 0.01). Standardized composite Z-scores for memory were 0.31 ( p = 0.0036, 10mg/day) and 0.22 ( p = 0.0349, 20mg/day). Standardized effect sizes for DSST were 0.51 ( p < 0.0001, 10mg/day) and 0.52 ( p < 0.0001, 20mg/day). Results are limited by the post hoc nature of the analyses and the absence of an active reference in the original study.

Conclusions: Vortioxetine (10 and 20mg/day) had a multi-domain beneficial effect on cognitive performance, as evidenced by improvements in measures of executive function, attention/speed of processing, and memory. The effect on the DSST may be due to improvements in several cognitive skills.
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http://dx.doi.org/10.1093/ijnp/pyw054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5091828PMC
May 2016

A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults.

Int J Neuropsychopharmacol 2014 Oct 30;17(10):1557-67. Epub 2014 Apr 30.

H. Lundbeck A/S,Copenhagen,Denmark.

The efficacy of vortioxetine 10 and 20 mg/d vs. placebo on cognitive function and depression in adults with recurrent moderate-to-severe major depressive disorder (MDD) was evaluated. Patients (18-65 yr, N = 602) were randomized (1:1:1) to vortioxetine 10 or 20 mg/d or placebo for 8 wk in a double-blind multi-national study. Cognitive function was assessed with objective neuropsychological tests of executive function, processing speed, attention and learning and memory, and a subjective cognitive measure. The primary outcome measure was change from baseline to week 8 in a composite z-score comprising the Digit Symbol Substitution Test (DSST) and Rey Auditory Verbal Learning Test (RAVLT) scores. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). In the pre-defined primary efficacy analysis, both doses of vortioxetine were significantly better than placebo, with mean treatment differences vs. placebo of 0.36 (vortioxetine 10 mg, p < 0.0001) and 0.33 (vortioxetine 20 mg, p < 0.0001) on the composite cognition score. Significant improvement vs. placebo was observed for vortioxetine on most of the secondary objectives and subjective patient-reported cognitive measures. The differences to placebo in the MADRS total score at week 8 were -4.7 (10 mg: p < 0.0001) and -6.7 (20 mg: p < 0.0001). Path and subgroup analyses indicate that the beneficial effect of vortioxetine on cognition is largely a direct treatment effect. No safety concern emerged with vortioxetine. Vortioxetine significantly improved objective and subjective measures of cognitive function in adults with recurrent MDD and these effects were largely independent of its effect on improving depressive symptoms.
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http://dx.doi.org/10.1017/S1461145714000546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162519PMC
October 2014

Transdermal fentanyl matrix patches Matrifen and Durogesic DTrans are bioequivalent.

Eur J Pharm Biopharm 2010 Jun 10;75(2):225-31. Epub 2010 Feb 10.

Medical University/AKH, Department of Special Anaesthesia and Pain Therapy, Vienna, Austria.

Aim: The pharmacokinetic profiles of the two commercially available transdermal fentanyl patches Matrifen (100 microg/h) and Durogesic DTrans (100 microg/h), used to manage severe chronic pain, were compared regarding their systemic exposure, rate of absorption, and safety.

Methods: Transdermal matrix fentanyl patches [Matrifen or Durogesic DTrans (100 microg/h)] were applied for 72 h to 30 healthy male subjects in a randomized, four-period (two replicated treatment sequences), crossover study; 28 subjects completed the study. The pharmacokinetic parameters of fentanyl were determined for 144 h after application using plasma samples. Safety of the patches (adverse events) and performance (adhesion, skin irritation, residual fentanyl content in the patch) were evaluated.

Results: The plasma concentration-time curves of Matrifen (Test) and Durogesic DTrans (Reference) were similar. The geometric least square means of the Test/Reference ratio (90% confidence intervals [CI]) were within the range of 80-125%, demonstrating bioequivalence of Matrifen and Durogesic DTrans: AUC(0-tlast) 92.5 (CI 88.7-96.4), AUC(0-inf) 91.7 (CI 88.0-95.7), and C(max) 98.3 (CI 92.9-104.1). After 72 h application, Matrifen had a more efficient utilization of fentanyl (mean+/-SD 82.3+/-9.43%) than Durogesic DTrans (52.3+/-12.8%), with substantially lower residual fentanyl in patch after use. The pharmacokinetic parameters showed lower intra- and inter-subject variability for Matrifen than for Durogesic DTrans patch.

Conclusions: Despite different technologies, the transdermal fentanyl patches Matrifen and Durogesic DTrans are bioequivalent. Compared with Durogesic DTrans, the Matrifen patch had lower initial and lower residual fentanyl content, as well as lower intra- and inter-subject variability, allowing reproducible drug delivery and reliable analgesia.
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http://dx.doi.org/10.1016/j.ejpb.2010.02.005DOI Listing
June 2010
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