Neonatal outcomes in women with Multiple Sclerosis - Influence of disease activity: A Danish nationwide cohort study.

BACKGROUND: Maternal Multiple Sclerosis (MS) has been associated with an increased risk of adverse birth outcomes. We hypothesized that active disease during conception and pregnancy plays an important role in this context, which this study aims to address. METHODS: We used the Danish registers to conduct a nationwide cohort study. Information on maternal disease activity during pregnancy was retrieved using proxies from the linked registers (hospitalization, magnetic resonance imaging of the brain, and use of systemic corticosteroids during pregnancy). Neonates, exposed in utero to maternal disease activity constituted the exposed cohort and the unexposed cohort constituted neonates without in utero exposure to maternal disease activity. The examined outcomes were preterm birth, small for gestational age, low 5-minute Apgar score, and major congenital anomalies. In logistic regression models we estimated the odds ratios (OR) with adjustment for confounders such as maternal age, comorbidities, parity, smoking, calendar year of birth, and disease-modifying treatment. RESULTS: Among the study population of 2492 children of mothers with MS we identified 273 (11 %) neonates exposed to maternal disease activity during pregnancy, and 2219 (89 %) neonates without exposure to disease activity. The adjusted odds ratios (aOR) for preterm birth, small for gestational age, low 5-minute Apgar score, and major congenital anomalies among children born to women with disease activity during pregnancy were 0.92 (95 % confidence interval (95 % CI) 0.53-1.60), aOR 1.19 (95 % CI 0.62-2.26), aOR 2.57 (95 % CI 0.93-7.15) and aOR 0.93 (95 % CI 0.48-1.83), respectively. CONCLUSIONS: Women with MS having disease activity during pregnancy did not have a statistically significantly increased risk of adverse neonatal outcomes compared to women with MS without disease activity, which is overall reassuring results. We believe, that this will be useful knowledge for patients and clinicians in planning a pregnancy and preparing a birth plan.

Effects of Demographic and Socio-Economic Factors on Investigation Time of Lung Cancer Patients in Denmark: A Retrospective Cohort Study.

Background: Lung cancer is one of the most common cancer types worldwide. The significance of the individual socio-economic position on the delay in lung cancer diagnosis has not been properly investigated. The purpose of this nationwide population-based study is to examine the association between position and the length of the primary investigation for lung cancer. Materials and Methods: This register study was based on all lung cancer patients in Denmark who were diagnosed in 2012 to 2017, in total 28,431 patients. We used a multivariate logistic regression model and multivariate zero-inflated negative binomial model to estimate the effect of education level, family income, difficulty of transport, and cohabitation status on the length of the primary investigation. Results: We found that the patients' income, difficulty of transport, and cohabitation status were associated with the length of the primary investigation. The chance of carrying out the investigation process within 24 days is higher for patients with a high income (adjusted OR = 0.86 with 95% CI (0.81; 0.91)), lower for patients with troublesome transport (adjusted OR = 0.67 with 95% CI (0.61; 0.72)), and lower for patients living alone (adjusted OR = 0.93 with 95% CI (0.88; 0.99)). Conclusion: Several socio-economic factors are associated with the length of the primary lung cancer investigation. To ensure that all patients receive the most appropriate health care and to avoid extra investigation time, clinicians may pay extra attention to patients who are less fortunate due to low income, troublesome transport to the hospital, or living alone.

A population-based nationwide study on total colectomy for ulcerative colitis and risk of ten prevalent inflammatory or autoimmune diseases.

BACKGROUND: There is growing evidence to support a role of the gut microbiome in the development of chronic inflammatory and autoimmune disease (IAD). We used total colectomy (TC) for ulcerative colitis (UC) as a model for a significant disruption in gut microbiome to explore an association with subsequent risk of IAD. METHODS: We identified all patients with UC and no diagnosis of IAD prior to their UC diagnosis in Denmark from 1988 to 2015. Patients were followed from the date of UC to a diagnosis of IAD, death or end of follow-up, whichever occurred first. We used Cox regression to estimate hazard ratios (HRs) of IAD associated with TC, adjusting for age, sex, Charlson Comorbidity Index, and calendar year of UC diagnosis. RESULTS: 30,507 patients with UC (3,155 with TC and 27,352 without) were identified from the Danish National Patient Registry. During 43,266 person-years of follow-up, 2733 patients were diagnosed with an IAD. The risk of any IAD was higher for patients with TC compared to patients without (adjusted HR [aHR] 1.39 (95% CI: 1.24-1.57)). When the analyses were adjusted for exposure to antibiotics, immunomodulatory medicine and biologics (covering 2005-2018), the risk of IAD was still higher for patients with total colectomy (aHR = 1.41 (95% CI: 1.09;1.83)). Disease-specific analyses were weakened by a low number of outcomes. CONCLUSIONS: The risk of IAD was higher for patients who underwent TC for UC compared to patients who did not.KEY MESSAGESWhat is already known?o The gut microbiome plays an important role in host immune homeostasis, and changes in gut bacterial diversity and composition may change the individual's risk of inflammatory and autoimmune disease (IAD).What is new here?o Patients with ulcerative colitis who undergo total colectomy have a higher risk of being diagnosed with IAD, compared to patients with ulcerative colitis who do not undergo total colectomy.How can this study help patient care?o Future research can help uncover the mechanisms responsible for the higher risk of certain IADs after total colectomy. If the microbiome plays a role, modifying the gut microbiome could prove a viable therapeutic strategy to reduce the risk of developing IADs.

In this nationwide Danish cohort study of all Danish UC patients diagnosed in the period from 1988 to 2015, the risk of being diagnosed with inflammatory and autoimmune disease is higher for patients who underwent total colectomy compared to UC patients without total colectomy.

Cardiovascular diseases in elderly survivors of diffuse large B-cell lymphoma: a Danish population-based cohort study.

Diffuse large B-cell lymphoma is an aggressive disease occurring primarily in elderly patients. Despite high curative rates with doxorubicin-containing treatment, some elderly patients receive less intensive treatments, mainly due to advanced age, comorbidities, and concerns of cardiotoxicity from doxorubicin-containing regimens. We analyzed 1009 patients aged 75 years or older and 10,090 age- and sex-matched comparisons. We aimed to evaluate long-term cardiovascular side effects in elderly patients treated with doxorubicin. Approximately, 64% of patients received doxorubicin-containing treatment. These patients had a persistently increased risk of new-onset heart failure with a hazard ratio of 1.5 and 1.7 when conditioning on survival without heart failure to 6 and 24 months, respectively. Moreover, we observed an increased risk of venous thromboembolism during the first six months following the lymphoma diagnosis. On the contrary, no difference in risk of developing ischemic heart disease or stroke following doxorubicin-containing treatment was observed.

Use of Drugs with Anticholinergic Properties at Hospital Admission Associated with Mortality in Older Patients: A Danish Nationwide Register-Based Cohort Study.

BACKGROUND: Use of drugs with anticholinergic properties (DAP) has a negative impact on older people. OBJECTIVE: Our aim was to examine the association between DAP at hospital admission and mortality in older patients. PATIENTS AND METHODS: We performed a nationwide population-based cohort study including patients aged ≥ 65 years admitted to Danish geriatric medicine departments during 2005-2014. National health registers were used to link with individual-level data. Patients were followed to emigration, death, or study termination (31 December 2015). DAP was defined as medications included in the anticholinergic cognitive burden (ACB) scale, which assigns each DAP a score between 1 and 3. The individual ACB score was calculated and the number of DAP counted. We used Cox proportional-hazard regressions to estimate the crude and adjusted hazard ratios adjusting for age, activities of daily living, marital status, index admission period, BMI, and prior hospitalizations (model 1), and additionally Charlson Comorbidity Index (model 2). RESULTS: We included 74,589 patients aged (median [IQR]) 83 (77-88) years. Use of one or more DAP (62.5%) was associated with increased mortality compared with those with no use (p < 0.001). In the fully adjusted model 2, compared with no use, higher mortality risks (HR [95% CI]) were seen with ACB score of 2 and number of DAP ≥ 5 for 30-day (1.46 [1.32-1.61] and 1.46 [1.09-1.95]), 1-year (1.34 [1.28-1.41] and 1.48 [1.29-1.70]), and overall mortality (1.27 [1.23-1.31] and 1.44 [1.31-1.59]), respectively. CONCLUSIONS: Use of DAP at hospital admission is associated with short- and long-term mortality in geriatric patients. Deprescribing studies are warranted to study whether the impact on mortality can be attenuated.

Association of Body Mass Index With All-Cause Mortality in Acutely Hospitalized Older Patients.

OBJECTIVES: The aim was to examine the relationship between body mass index (BMI) and mortality in older hospitalized patients taking activities of daily living (ADLs) into account. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Nationwide population-based study of all patients aged ≥65 years admitted to Danish geriatric medical departments during 2005 to 2014 and included in the National Danish Geriatric Database. METHODS: Patients were followed until death, emigration, or study termination (December 31, 2015). Primary outcome was all-cause mortality. BMI and ADLs were routinely assessed on admission and linked at an individual level to the Danish national health registers. Kaplan-Meier analysis was used to estimate crude survival according to each BMI subcategory and Cox regression to examine the association with mortality adjusting for age, comorbidity, polypharmacy, ADLs, marital status, prior hospitalizations, and admission year. RESULTS: In total, 74,589 patients (63% women) were included aged [mean (SD)] 82.5 (7.5) years with BMI [mean (SD)] of 23.9 (5.1) kg/m2. During follow-up 51,188 died. Follow-up time was 191,972 person-years. Unadjusted and adjusted hazard ratio (HR) for overall, 30-day, and 1-year mortality decreased significantly with increasing BMI. In women, the highest adjusted HR (95% confidence interval) for overall mortality was seen for underweight patients (BMI <16) 1.83 (1.72-1.95) and the lowest for obesity grade II patients (BMI = 35.0-39.9) 0.66 (0.60-0.73) when using normal weight (BMI = 18.5-24.9) as reference. In men, the HR for BMI <16 and BMI = 35.0-39.9 were 1.98 (1.76-2.23) and 0.56 (0.49-0.65), respectively. CONCLUSIONS AND IMPLICATIONS: In hospitalized older patients, association between mortality and BMI did not show a U-shaped or J-shaped curve after adjustment of multiple confounders, including ADLs. Instead, mortality was highest in patients with low BMI and decreased with increasing BMI before leveling off in the obese range. Our study highlights the need for a debate and reassessment of what should be the ideal BMI in this vulnerable patient group.

The risk of chronic diseases and congenital malformations during childhood and adolescence after in utero exposure to thiopurines.

BACKGROUND: Women with autoimmune diseases, particularly inflammatory bowel disease (IBD), often need to continue immunomodulatory therapies during pregnancy. While the evidence of birth and short-term outcomes in children exposed in utero to these medicines is reassuring, long-term safety data are lacking. AIM: To assess any association between in utero exposure to thiopurines and diagnoses of chronic diseases (type 1 diabetes, coeliac disease, thyroid disease, rheumatoid arthritis, IBD and asthma) and congenital malformations during childhood and adolescence. METHODS: This nationwide cohort study was based on information using Danish registers and comprised all live-born children from 1995 to 2015 (N = 1 308 778). Children exposed in utero to thiopurines were followed for a median of 8.9 years (25%-75% percentiles 5.5-12.4 years); children not exposed were followed for 13.9 years (25%-75% percentiles 8.7-19.0 years). Analyses were adjusted for a number of confounders including the type of maternal underlying disease. RESULTS: A total of 1047 children had been exposed to thiopurines in utero; 96 developed a chronic disease and 126 were diagnosed with congenital malformations during follow-up. The adjusted hazard ratio for rheumatoid arthritis was 0.78 (95% CI 0.35-1.73); for IBD, it was 1.45 (95% CI 0.64-3.27); for asthma 0.94 (95% CI 0.73-1.21), and for congenital malformations, it was 0.95 (95% CI 0.78-1.15). For type 1 diabetes, coeliac disease, thyroid disease and ulcerative colitis, we had insufficient data to perform adjusted analysis. CONCLUSION: We found no increased risk of seven common chronic diseases or congenital malformations during childhood and adolescence after gestational exposure to thiopurines.

Activities of daily living at hospital admission associated with mortality in geriatric patients with dementia: a Danish nationwide population-based cohort study.

PURPOSE: Determining life expectancy in patients with dementia are challenging. We aimed at studying the association between basic activities of daily living as measured by the Barthel Index at hospital admission and mortality among older patients with dementia. METHODS: All patients aged ≥ 65 years with diagnosed dementia in the population-based National Danish Geriatric Database from 2005 to 2014 were included and followed until death, emigration, or study termination (31.12.2015). Data on Barthel Index (BI) were used to assess ADL. Patients were categorized into four predefined standard BI subcategories according to the national Danish version of the statistical classification of diseases [BI = 0-24 (very low ADL), BI = 25-49 (low ADL), BI = 50-79 (moderate reduced ADL), and BI = 80-100 (independent ADL)]. Association with mortality was assessed using multivariable Cox regression analysis adjusting for age, marital status, Charlson Comorbidity Index, BMI, prior hospitalizations, year of admission and polypharmacy. RESULTS: In total, 6550 patients (women 62%) were included, median (IQR) age 84 (79-88) years and BI 37 (13-63). Mortality increased significantly with decreasing BI in both the crude and multivariable analysis. In subcategories BI = (80-100) and BI = (0-24), survival time (median (95%)) was 3.6 (3.4-3.9) years and 0.8 (0.7-0.9) years, respectively. Also, in patients with BI = (0-24), the overall mortality risk (HR (95% CI)) was 2.5 (2.2-2.8), 30-day risk 11.8 (5.8-23.9), and 1-year risk 4.4 (3.6-5.5) when using BI = (80-100) as reference. CONCLUSION: Barthel Index is independently associated with all-cause mortality among older patients with dementia admitted to hospital. BI may be a helpful tool for clinicians when discussing treatment and care strategies with patients and their families.

Activities of daily living at hospital admission and estimated survival time of older patients.

BACKGROUND: Predicting expected survival time in acutely hospitalised older patients is a clinical challenge. OBJECTIVE: To examine if activities of daily living (ADL) assessed by Barthel-Index-100 (Barthel-Index) at hospital admission adds useful information to clinicians on expected survival time in older patients. METHODS: A nationwide population-based cohort study was used. All patients aged ≥65 years in the National Danish Geriatric Database from 2005 to 2014 were followed up until death, emigration or study termination (31 December 2015). Individual data were linked to national health registers. Barthel-Index was categorised into five-point subcategories with a separate category of Barthel-Index = 0. Kaplan-Meier analysis was used to assess crude survival proportions (95% CI) and Cox regression to examine association of Barthel-Index and mortality adjusting for age, Charlson comorbidity index, medication use, BMI, marital status, prior hospitalisations and admission year. RESULTS: In total, 74,589 patients (63% women) aged (mean (SD)) 82.5(7.5) years with Barthel-Index (median (IQR)) 54(29-77) were included. In patients with Barthel-Index = 100-96 crude survival was 0.96(0.95-0.97) after 90-days, 0.88(0.87-0.89) after 1-year, and 0.79(0.78-0.80) after 2-years. Corresponding survival in patients with Barthel-Index = 0 was 0.49(0.47-0.51), 0.35(0.34-0.37) and 0.26(0.24-0.27). Decreasing Barthel-Index was associated with increasing mortality in the multivariable analysis. In women with Barthel-Index = 0, the mortality risk (HR (95% CI)) was 14.74(11.33-19.18) after 90-days, 8.40(7.13-9.90) after 1-year and 6.22(5.47-7.07) after 2-years using Barthel-Index = 100-96 as reference. In men, the corresponding risks were 11.36(8.81-14.66), 6.22(5.29-7.31) and 5.22(4.56-5.98). CONCLUSIONS: ADL measured by Barthel-Index provides useful, easily accessible and independent information to clinicians on expected survival time in patients admitted to a geriatric department.

Association between number of medications and mortality in geriatric inpatients: a Danish nationwide register-based cohort study.

PURPOSE: To explore the association between the number of medications and mortality in geriatric inpatients taking activities of daily living and comorbidities into account. METHODS: A nationwide population-based cohort study was performed including all patients aged ≥ 65 years admitted to geriatric departments in Denmark during 2005-2014. The outcome of interest was mortality. Activities of daily living using Barthel Index (BI) were measured at admission. National health registers were used to link data on an individual level extracting data on medications, and hospital diseases. Patients were followed to the end of study (31/12/2015), death, or emigration, which ever occurred first. Kaplan-Meier survival curves were used to estimate crude survival proportions. Univariable and multivariable analyses were performed using Cox regression. The multivariable analysis were adjusted for age, marital status, period of hospital admission, BMI, and BI (model 1), and additionally either number of diseases (model 2) or Charlson comorbidity index (model 3). RESULTS: We included 74,603 patients (62.8% women), with a median age of 83 (interquartile range [IQR] 77-88) years. Patients used a median of 6 (IQR 4-9) medications. Increasing number of medications was associated with increased overall, 30-day, and 1-year mortality in all three multivariable models for both men and women. For each extra medication, the mortality increased by 3% in women and 4% in men in the fully adjusted model. CONCLUSION: Increasing number of medications was associated with mortality in this nationwide cohort of geriatric inpatients. Our findings highlight the importance of polypharmacy in older patients with comorbidities.

Incidence of community-onset extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae infections: an 11-year population-based study in Denmark.

Background: Data elucidating trends of community-onset extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae infections remain sparse in low prevalence areas. We conducted a population-based study to determine the incidence, temporal trends and co-resistance of community-onset ESBL infections.Methods: We identified all recorded episodes of E. coli and K. pneumoniae bacteraemia and urinary tract infections in adult patients (>15 years) in the North Denmark Region between 2007-2017. Using population-based registries, we obtained information on demographics and place of acquisition, and investigated the standardized incidence rates and temporal trends of community-onset ESBL infections and the associated patterns of co-resistance.Results: A total of 3741 episodes of community-onset ESBL E. coli or K. pneumoniae infections were observed during the study period, with the annual standardized incidence rate increasing from 7.5 to 105 per 100,000 person-years between 2007-2017. The increase was conveyed primarily by a rise in E. coli urinary tract infections shifting from being mainly healthcare-associated to community-acquired. ESBL-producing isolates increased from 0.5 to 4.0% with considerable co-resistance.Conclusion: The proportion of E. coli and K. pneumoniae isolates producing ESBL have increased considerably in the North Denmark Region. The increasing incidence and frequent co-resistance should raise awareness among physicians responsible for empirical antibiotic treatment.