Algorithm for forming hospital care episodes by combining attendance contacts in the Danish National Patient Register: A methodological consensus-driven study.

BACKGROUND: Studying complete hospital care episodes from register data, for instance when assessing length of stay, discharges and readmissions, can cause methodological difficulties due to the lack of a contact linkage identifier. We aimed to develop an algorithm combining sequential attendance contacts in the Danish National Patient Register (DNPR) into hospital care episodes, spanning the entire duration and all contacts from hospital arrival to departure. METHODS: The algorithm was developed under the consensus of experts from research institutions across Denmark. It reads in second and third version DNPR data, deletes contacts without attendance, duplicates elective outpatient contacts corresponding to attendance dates and modifies contact types (e.g. repeated acute contacts), among others. Thereafter, sequential contacts within 4 h are marked as the same hospital care episode, consisting of one or more DNPR contact. We tested the algorithm in a data set of adults living in Denmark during 2013-2021 and compared different hourly cut-offs. RESULTS: For the demonstration, we included 120.2 m contacts from 5.7 m persons, combined into 105.9 m hospital care episodes. Of the hospital care episodes, 6.4% were acute inpatients, 8.3% were acute outpatients, 2.0% were elective inpatients and 83.3% were elective outpatients. Using 4 h as our recommendation, 3-h, 5-h and 6-h cut-offs for contact combining revealed only minor differences in the number of hospital care episodes (<0.4%), whereas 12-h (<1.7%) and 24-h cut-offs (<43.1%) had a larger impact. CONCLUSIONS: The algorithm automates data reading, modification and linkage of sequential attendance contacts. The algorithm can be initiated as a SAS macro and is available from an online repository.

Congenital malformations among offspring of women with type 1 diabetes who use insulin pumps: a prospective cohort study.

AIMS/HYPOTHESIS: Continuous subcutaneous insulin infusion by insulin pump is often superior in improving glycaemic control compared with conventional multiple daily insulin injection (MDI). However, whether pump treatment leads to improved pregnancy outcomes in terms of congenital malformations and perinatal death remains unknown. The present aim was to evaluate the risk of malformations and perinatal and neonatal death in pregnant women with type 1 diabetes treated with pump or MDI. METHODS: We performed a secondary analysis of a prospective multinational cohort of 2088 pregnant women with type 1 diabetes in a real-world setting who were treated by pump (n=750) or MDI (n=1338). ORs for offspring with congenital malformations or perinatal or neonatal death were calculated using crude data and by logistic regression on propensity score-matched data. RESULTS: At enrolment (gestational week 8; 95% CI 4, 14), pump users had a higher educational level (university degree: 37.3% vs 25.1%; p<0.001) and better glycaemic control (mean HbA1c: 51±10 mmol/mol [6.8±0.9%] vs 54±14 mmol/mol [7.1±1.3%], p<0.001) compared with MDI users. Moreover, a greater proportion of pump users had an HbA1c level below 75 mmol/mol (9%) (97.6% vs 91.9%, p<0.001), and more often reported taking folic acid supplementation (86.3% vs 74.8%; p<0.001) compared with MDI users. All clinically important potential confounders were balanced after propensity score matching, and HbA1c remained lower in pump users. The proportion of fetuses with at least one malformation was 13.5% in pump users vs 11.2% in MDI users (crude OR 1.23; 95% CI 0.94, 1.61; p=0.13; propensity score-matched (adjusted) OR 1.11; 95% CI 0.81, 1.52; p=0.52). The proportion of fetuses with at least one major malformation was 2.8% in pump users vs 3.1% in MDI users (crude OR 0.89; 95% CI 0.52, 1.51; p=0.66; adjusted OR 0.78; 95% CI 0.42, 1.45; p=0.43), and the proportions of fetuses carrying one or more minor malformations (but no major malformations) were 10.7% vs 8.1% (crude OR 1.36; 95% CI 1.00, 1.84; p=0.05; adjusted OR 1.23; 95% CI 0.87, 1.75; p=0.25). The proportions of perinatal and neonatal death were 1.6% vs 1.3% (crude OR 1.23; 95% CI 0.57, 2.67; p=0.59; adjusted OR 2.02; 95% CI 0.69, 5.93; p=0.20) and 0.3% vs 0.3% (n=2 vs n=4, p=not applicable), respectively. CONCLUSIONS/INTERPRETATIONS: Insulin pump treatment was not associated with a lower risk of congenital malformations, despite better glycaemic control in early pregnancy compared with MDI. Further studies exploring the efficacy and safety of pump treatment during pregnancy are needed.

Drug utilization of biologic therapy in Crohn's disease and ulcerative colitis: a population-based Danish cohort study 2015-2020.

OBJECTIVE: The aim of the study was to characterize the drug utilization and switch patterns of biological treatment of ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Using Danish national registries, this nationwide study included individuals diagnosed with UC or CD, bio-naïve at the initiation of treatment with infliximab, adalimumab, vedolizumab, golimumab, or ustekinumab in 2015-2020. Hazard ratios of discontinuing the first treatment or switching to another biological treatment were explored using Cox regression. RESULTS: Among 2995 UC patients and 3028 CD patients, infliximab was used as a first-line biologic treatment in 89% of UC patients and 85% of CD patients, followed by adalimumab with 6%, vedolizumab with 3%, and golimumab with 1% for UC, and adalimumab with 12%, vedolizumab with 2%, and ustekinumab with 0.4% for CD.When comparing adalimumab as the first treatment series to infliximab, there was a higher risk of treatment discontinuation (excluding switch) among UC patients (hazard ratio: 2.02 [95% confidence interval: 1.57; 2.60]) and CD patients (1.85 [1.52; 2.24]). When comparing vedolizumab to infliximab, there was a lower risk of discontinuation for UC patients (0.51 [0.29-0.89]), and for CD patients, although not significantly (0.58 [0.32-1.03]). We observed no significant difference in the risk of switching to another biologic treatment for any of the biologics. CONCLUSION: More than 85% of UC and CD patients initiating biologic therapy had infliximab as their first-line biologic treatment, in accordance with official treatment guidelines. Future studies should explore the higher incidence of treatment discontinuation of adalimumab as the first treatment series.Key summarySeveral biologic therapies are available in the treatment of ulcerative colitis and Crohn's disease.Clinical guidelines stipulate that infliximab should be the first-line biologic therapy.Drug utilization studies comparing biologic therapies head-to-head are sparse.In Denmark, during 2015-2020 infliximab remained the most widely used biologic treatment, with adalimumab being second.One in four patients experienced more than one biologic during the study period.The risk of discontinuation of biologic treatment (and not starting a new biologic) was higher for initiators of adalimumab.Clinical and social background factors available from the registers could not account for the observed risk difference in discontinuation.

PaCO2 trajectories in mechanically ventilated patients with COVID-19: A population-based cohort study.

OBJECTIVE: To identify PaCO2 trajectories and assess their associations with mortality in critically ill patients with coronavirus disease 2019 (COVID-19) during the first and second waves of the pandemic in Denmark. DESIGN: A population-based cohort study with retrospective data collection. PATIENTS: All COVID-19 patients were treated in eight intensive care units (ICUs) in the Capital Region of Copenhagen, Denmark, between March 1, 2020 and March 31, 2021. MEASUREMENTS: Data from the electronic health records were extracted, and latent class analyses were computed based on up to the first 3 weeks of mechanical ventilation to depict trajectories of PaCO2 levels. Multivariable Cox regression analyses were used to calculate adjusted hazard ratios (aHRs) for Simplified Acute Physiology Score 3, sex and age with 95% confidence intervals (CIs) for death according to PaCO2 trajectories. MAIN RESULTS: In latent class trajectory models, including 25,318 PaCO2 measurements from 244 patients, three PaCO2 latent class trajectories were identified: a low isocapnic (Class I; n = 130), a high isocapnic (Class II; n = 80), as well as a progressively hypercapnic (Class III; n = 34) trajectory. Mortality was higher in Class II [aHR: 2.16 {1.26-3.68}] and Class III [aHR: 2.97 {1.63-5.40}]) compared to Class I (reference). CONCLUSION: Latent class analysis of arterial blood gases in mechanically ventilated COVID-19 patients identified distinct PaCO2 trajectories, which were independently associated with mortality.

Shared and distinct factors underlying in-hospital mobility of older adults in Israel and Denmark (97/100).

BACKGROUND: Low in-hospital mobility is widely acknowledged as a major risk factor in acquiring hospital-associated disabilities. Various predictors of in-hospital low mobility have been suggested, among them older age, disabling admission diagnosis, poor cognitive and physical functioning, and pre-hospitalization mobility. However, the universalism of the phenomena is not well studied, as similar risk factors to low in-hospital mobility have not been tested. METHODS: The study was a secondary analysis of data on in-hospital mobility that investigated the relationship between in-hospital mobility and a set of similar risk factors in independently mobile prior to hospitalization older adults, hospitalized in acute care settings in Israel (N = 206) and Denmark (N = 113). In Israel, mobility was measured via ActiGraph GT9X and in Denmark by ActivPal3 for up to seven hospital days. RESULTS: Parallel multivariate analyses revealed that a higher level of community mobility prior to hospitalization and higher mobility ability status on admission were common predictors of a higher number of in-hospital steps, whereas the longer length of hospital stay was significantly correlated with a lower number of steps in both samples. The risk of malnutrition on admission was associated with a lower number of steps, but only in the Israeli sample. CONCLUSIONS: Despite different assessment methods, older adults' low in-hospital mobility has similar risk factors in Israel and Denmark. Pre-hospitalization and admission mobility ability are robust and constant risk factors across the two studies. This information can encourage the development of both international standard risk evaluations and tailored country-based approaches.

From expected to actual barriers and facilitators when implementing a new screening tool: A qualitative study applying the Theoretical Domains Framework.

AIM AND OBJECTIVES: To identify determinants for using a new screening tool to identify older patients eligible for targeted nurse-led intervention, as perceived by healthcare professionals implementing the tool, and to examine how these perceptions changed over time. DESIGN: A cross-sectoral longitudinal qualitative study based on semi-structured interviews with healthcare professionals in a Danish hospital and two collaborating municipalities. METHODS: In three focus groups, seven single interviews and a workshop, we examined the healthcare professionals' perceptions of and attitudes towards the new screening tool before, during and after the implementation. The Theoretical Domains Framework was used to identify the healthcare professionals' perception of barriers and facilitators, followed by content analysis. The results were further discussed using the COM-B system as an analytic framework. This qualitative study is reported according to the Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist. RESULTS: 'Professional role', 'Goals' and 'Environmental context' were the domains most talked about by the healthcare professionals across the three time points. The content analysis identified four determinants for using the new screening tool:Making time for the project, External motivation and management, Expectations and reality, and Professional identity. The healthcare professionals' perception of the determinants changed during the implementation, influencing their behaviour and, consequently, the implementation's sustainability. CONCLUSION: Perception of barriers and facilitators to the interventions were time- and context-sensitive. Beliefs and motivational factors changed during the project, which points out the importance of following implementation processes systematically to understand the outcome of an intervention. RELEVANCE FOR CLINICAL PRACTICE: Perceptions and attitudes towards a new initiative may change over time, emphasising the importance of following barriers and facilitators during the implementation of an intervention and working with an implementation plan that can be adapted along the way.

Trajectories of Infant Weight Gain from Birth to 12 Months and Adult-Onset Coronary Heart Disease.

OBJECTIVE: To investigate associations between infant weight gain trajectories and coronary heart disease (CHD). STUDY DESIGN: We followed 3645 Danish individuals born between 1959 and 1961 with information on weight at birth and at age 2 weeks and 1, 2, 3, 4, 6, or 12 months. Sex-specific weight trajectories were generated using latent class modeling. Cases of CHD (n = 279) were identified from national health registers. Hazard ratios (HRs) were estimated by Cox regression with sequential adjustment for sex, socioeconomic status, prepregnancy body mass index, maternal smoking, preterm birth, parity, and birth weight. RESULTS: We identified 5 trajectories of weight development in infancy in our cohort: very low-moderate increase (11.5% of the population), low-marked increase (13.9%), low-stable increase (32.4%), average-stable increase (29.8%), and high-moderate increase (12.4%). Compared with the average-stable increasing trajectory, having a very low-moderately increasing weight trajectory in infancy was associated with a higher frequency of adult CHD (HR, 1.56; 95% CI, 1.04-2.33). The higher frequency remained after adjustment for maternal factors but was slightly attenuated after additional adjustment for preterm birth and parity (HR, 1.41; 95% CI, 0.91-2.23) and disappeared after adjustment for birth weight (HR, 0.78; 95% CI, 0.44-1.37). The associations with CHD did not differ between the other trajectories and the average-stable increasing trajectory. CONCLUSIONS: Although a pattern of very low-moderate increasing weight during infancy was associated with a higher frequency of adult CHD, the association did not persist after adjustment for birth weight, highlighting the importance of prenatal exposures.

Variations in physical activity and sedentary behavior during and after hospitalization in acutely admitted older medical patients: a longitudinal study.

BACKGROUND: Inactivity is frequent among older patients during hospitalization. It is unknown how patients' daily activity pattern (diurnal profile) vary between hospitalization and after discharge. This study aims to describe and compare the distribution of physical activity and sedentary behavior in acutely hospitalized older patients during hospitalization and after discharge. METHODS: We included data on 80 patients (+65 years) admitted with acute medical illness from the STAND-Cph trial. Physical activity and sedentary behavior were measured as daily number of steps, uptime (walking/standing) and sedentary behavior (lying/sitting) with an activity monitor (activPAL3, PAL Technologies Ltd). The patients wore the monitor for three periods of one week: during hospitalization, after discharge, and four weeks after discharge. RESULTS: The patients' median age was 80 years [IQR: 75;88], 68% were female and the median De Morton Mobility Index (DEMMI) was 57 [IQR: 48;67]. The daily median uptime was 1.7 h [IQR: 1;2.8] during hospitalization, 4.0 h [IQR: 2.7;5.4] after discharge and 4.0 h [IQR: 2.8;5.8] four weeks after discharge. The daily median number of steps was 728 [IQR: 176;2089], 2207 [IQR: 1433;3148], and 2622 [IQR: 1714;3865], respectively, and median daily sedentary behavior was 21.4 h (IQR: 20.7;22.4), 19.5 h (IQR: 18.1;21.0) and 19.6 h (IQR: 18.0;20.8), respectively. During hospitalization, a small activity peak was observed between 9-11 AM without any notable variation after. At discharge and four weeks after discharge, a peak in physical activity was seen between 9-12 AM and at 5 PM. CONCLUSION: Older hospitalized patients spend most of their time being sedentary with their highest activity between 9-11 AM. Daily activity doubles after discharge with one extra peak in the afternoon. Daily routines might be disrupted, and older patients have the potential to be more physically active during hospitalization. Interventions that encourage physical activity during hospitalization are warranted.

Exposure to duloxetine during pregnancy and risk of congenital malformations and stillbirth: A nationwide cohort study in Denmark and Sweden.

BACKGROUND: The prevalence of depression and the exposure to antidepressants are high among women of reproductive age and during pregnancy. Duloxetine is a selective serotonin-norepinephrine reuptake inhibitor (SNRI) approved in the United States and Europe in 2004 for the treatment of depression. Fetal safety of duloxetine is not well established. The present study evaluates the association of exposure to duloxetine during pregnancy and the risk of major and minor congenital malformations and the risk of stillbirths. METHODS AND FINDINGS: A population-based observational study was conducted based on data from registers in Sweden and Denmark. All registered births and stillbirths in the medical birth registers between 2004 and 2016 were included. Malformation diagnoses were identified up to 1 year after birth. Logistic regression analyses were used. Potential confounding was addressed through multiple regression, propensity score (PS) matching, and sensitivity analyses. Confounder variables included sociodemographic information (income, education, age, year of birth, and country), comorbidity and comedication, previous psychiatric contacts, and birth-related information (smoking during pregnancy and previous spontaneous abortions and stillbirths). Duloxetine-exposed women were compared with 4 comparators: (1) duloxetine-nonexposed women; (2) selective serotonin reuptake inhibitor (SSRI)-exposed women; (3) venlafaxine-exposed women; and (4) women exposed to duloxetine prior to, but not during, pregnancy. Exposure was defined as redemption of a prescription during the first trimester and throughout pregnancy for the analyses of malformations and stillbirths, respectively. Outcomes were major and minor malformations and stillbirths gathered from the national patient registers. The cohorts consisted of more than 2 million births with 1,512 duloxetine-exposed pregnancies. No increased risk for major malformations, minor malformations, or stillbirth was found across comparison groups in adjusted and PS-matched analyses. Duloxetine-exposed versus duloxetine-nonexposed PS-matched analyses showed odds ratio (OR) 0.98 (95% confidence interval [CI] 0.74 to 1.30, p = 0.909) for major malformations, OR 1.09 (95% CI 0.82 to 1.45, p = 0.570) for minor malformation, and 1.18 (95% CI 0.43 to 3.19, p = 0.749) for stillbirths. For the individual malformation subtypes, some findings were statistically significant but were associated with large statistical uncertainty due to the extremely small number of events. The main limitations for the study were that the indication for duloxetine and a direct measurement of depression severity were not available to include as covariates. CONCLUSIONS: Based on this observational register-based nationwide study with data from Sweden and Denmark, no increased risk of major or minor congenital malformations or stillbirth was associated with exposure to duloxetine during pregnancy.

Number of traumatic brain injuries and temporal associations with depression: A register-based cohort study.

OBJECTIVE: To explore the association of the number of traumatic brain injuries (TBIs) and temporal associations with the subsequent risk of depression in the population. METHODS: National register-based cohort study on all individuals registered with TBI (ICD-10: S06, ICD-8: 85.0-85.5) from 1977 to 2015 in Denmark (n = 494,216) and a sex- and age-matched reference population (n = 499,505). The associations with the number of TBIs and time to depression (0-6, 7-12 and more than 12 months following TBI) were analyzed using Cox proportional hazard regression. RESULTS: During a follow-up of mean 14.5 (SD 11.3) years, a total of 27,873 (5.6%) individuals who had at least one TBI and 15,195 (3.0%) in the reference population were diagnosed with a depression. First-time TBI was associated with a higher risk of depression in both men (HR = 1.73 [95% CI:1.67-1.79]) and women (HR = 1.66 [95% CI:1.61-1.70]) after multiple adjustments for educational status and comorbidities including previous depression, and the association became stronger in a dose-response association with the number of TBIs (test for trend p < 0.01). The HRs for depression were highest the first 6 months after the TBI in both men (HR = 5.69 [95% CI:4.66-6.94]) and women (HR = 4.55 [95% CI:3.93-5.26]) and decreased gradually the following year but remained elevated from one year after TBI until end of follow-up independent of the number of TBIs (p < 0.01). The associations did not vary with age or calendar time. CONCLUSION: Traumatic brain injury is associated with a higher risk of depression, especially in the first months after TBI and the risk increases with the number of TBIs.

Symptoms and biomarkers associated with undiagnosed celiac seropositivity.

BACKGROUND: Studies have indicated that underdiagnosis and diagnostic delay are common in celiac disease. Therefore, it is important to increase our knowledge of what symptoms and biomarkers could identify undiagnosed cases of celiac disease. METHODS: We screened for celiac disease antibodies in stored blood samples from 16,776 participants in eight population-based studies examined during 1976-2012. Undiagnosed celiac seropositivity was defined as celiac disease antibody positivity (IgG-deamidated gliadin peptide above 10.0 U/mL and/or IgA-tissue transglutaminase (TTG) or IgG-TTG above 7.0 U/mL) without a known diagnosis of celiac disease in the National Patient Register. In all studies general health symptoms were recorded by participant-completed questionnaire, including self-perceived health, tiredness, headache and gastrointestinal symptoms. Furthermore, blood samples were drawn for analyses of biomarkers e.g. hemoglobin, blood glucose, cholesterol, liver parameters and vitamins. The participants with undiagnosed celiac seropositivity were matched by sex, age and study with four controls among the celiac disease antibody negative participants. RESULTS: We excluded, five participants with known celiac disease, resulting in a population of 16,771 participants. In this population 1% (169/16,771) had undiagnosed celiac seropositivity. There were no statistically significant differences in symptoms between cases and controls. Undiagnosed celiac seropositivity was associated with low blood cholesterol (< 5 mmol/L) and low hemoglobin (< 7.3 mmol/L for women and < 8.3 mmol/L for men). CONCLUSION: In this general population study, undiagnosed cases of celiac seropositivity did not have more symptoms than controls, confirming the diagnostic difficulties of celiac disease and the low prognostic value of symptoms for a diagnosis of celiac disease. Furthermore, decreased levels of cholesterol and/or hemoglobin in the blood were associated with undiagnosed celiac seropositivity.

Long-term Consequences of Undiagnosed Celiac Seropositivity.

INTRODUCTION: Diagnosed celiac disease (CD) is associated with lymphoproliferative malignancy and gastrointestinal cancer, but little is known about the long-term consequences of undiagnosed CD. We aimed to investigate long-term consequences of undiagnosed CD for mortality and incidence of cancer and other chronic diseases. METHODS: We screened biobank serum samples for immunoglobulin (Ig) A and IgG tissue transglutaminase (TTG) and IgG deamidated gliadin peptide in a study of 8 population-based cohort studies comprising 16,776 participants examined during 1976-2012 and followed with >99% complete follow-up in Danish nationwide registries until December 31, 2017, regarding vital status and incidence of diseases. Undiagnosed CD was defined as antibody positivity (IgA-TTG or IgG-TTG ≥ 7 U/mL and/or IgG deamidated gliadin peptide ≥ 10 U/mL) in individuals without a diagnosis of CD recorded in the National Patient Register. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox regression analyses with age as the underlying time scale. RESULTS: The prevalence of undiagnosed CD was 1.0% with no statistically significant increase over time. Undiagnosed CD was associated with increased risk of cancer overall (HR, 1.57; 95% CI, 1.16-2.11), gastrointestinal cancer (HR, 2.33; 95% CI, 1.35-4.04), cancer of the uterus (HR, 3.95; 95% CI, 1.46-10.69), breast cancer (HR, 1.98; 95% CI, 1.02-3.82), head and neck cancer (HR, 3.12; 95% CI, 1.15-8.43), and cardiovascular disease (HR, 1.37; 95% CI, 1.01-1.85). We found no statistically significant association between undiagnosed CD and mortality (HR, 1.19; 95% CI, 0.87-1.61). DISCUSSION: Undiagnosed CD was associated with increased risk of cardiovascular disease and cancer suggesting that untreated CD has serious long-term health consequences not only affecting the gastrointestinal tract (see Visual Abstract, Supplementary Digital Content, http://links.lww.com/AJG/B566).

Can we identify allergic rhinitis from administrative data: A validation study.

BACKGROUND: Important insights on, for example, prevalence, disease progression, and treatment of allergic rhinitis can be obtained from large-scale database studies if researchers are able to identify allergic individuals. We aimed to assess the validity of 13 different algorithms based on Danish nationwide prescription and/or hospital data to identify adults with allergic rhinitis. METHODS: Our primary gold standard of allergic rhinitis was a positive serum specific IgE (≥0.35) and self-reported nasal symptoms retrieved from two general health examination studies conducted in Danish adults (18-69 years) during 2006 to 2008 (n = 3416) and 2012 to 2015 (n = 7237). The secondary gold standard of allergic rhinitis was self-reported physician diagnosis. We calculated sensitivity, specificity, positive predictive value (PPV), negative predictive value, and corresponding 95% confidence intervals (95% CI) for each register-based algorithm in the two time periods. RESULTS: Sensitivity (≤0.40) was low for all algorithms irrespective of definition of allergic rhinitis (gold standard) or time period. The highest PPVs were obtained for algorithms requiring both antihistamines and intranasal corticosteroids; yielding a PPV of 0.69 (0.62-0.75) and a corresponding sensitivity of 0.10 (0.09-0.12) for the primary gold standard of allergic rhinitis in 2012 to 2015. CONCLUSION: Algorithms based on both antihistamines and intranasal corticosteroids yielded the highest PPVs. However, the PPVs were still moderate and came at the expense of low sensitivity when applying the strict primary gold standard (sIgE and nasal symptom).

Alterations of monocyte NF-κB p65/RelA signaling in a cohort of older medical patients, age-matched controls, and healthy young adults.

BACKGROUND: Altered monocyte NF-κB signaling is a possible cause of inflammaging and driver of aging, however, evidence from human aging studies is sparse. We assessed monocyte NF-κB signaling across different aging trajectories by comparing healthy older adults to older adults with a recent emergency department (ED) admission and to young adults. METHODS: We used data from: 52 older (≥65 years) Patients collected upon ED admission and at follow-up 30-days after discharge; 52 age- and sex-matched Older Controls without recent hospitalization; and 60 healthy Young Controls (20-35 years). Using flow cytometry, we assessed basal NF-κB phosphorylation (pNF-κB p65/RelA; Ser529) and induction of pNF-κB following stimulation with LPS or TNF-α in monocytes. We assessed frailty (FI-OutRef), physical and cognitive function, and plasma levels of IL-6, IL-18, TNF-α, and soluble urokinase plasminogen activator receptor. RESULTS: Patients at follow-up were frailer, had higher levels of inflammatory markers and decreased physical and cognitive function than Older Controls. Patients at follow-up had higher basal pNF-κB levels than Older Controls (median fluorescence intensity (MFI): 125, IQR: 105-153 vs. MFI: 80, IQR: 71-90, p < 0.0001), and reduced pNF-κB induction in response to LPS (mean pNF-κB MFI fold change calculated as the log10 ratio of LPS-stimulation to the PBS-control: 0.10, 95% CI: 0.08 to 0.12 vs. 0.13, 95% CI: 0.10 to 0.15, p = 0.05) and TNF-α stimulation (0.02, 95% CI: - 0.00 to 0.05 vs. 0.10, 95% CI: 0.08 to 0.12, p < 0.0001). Older Controls had higher levels of inflammatory markers than Young Controls, but basal pNF-κB MFI did not differ between Older and Young Controls (MFI: 81, IQR: 70-86; p = 0.72). Older Controls had reduced pNF-κB induction in response to LPS and TNF-α compared to Young Controls (LPS: 0.40, 95% CI: 0.35 to 0.44, p < 0.0001; and TNF-α: 0.33, 95% CI: 0.27 to 0.40, p < 0.0001). In Older Controls, basal pNF-κB MFI was associated with FI-OutRef (p = 0.02). CONCLUSIONS: Increased basal pNF-κB activity in monocytes could be involved in the processes of frailty and accelerated aging. Furthermore, we show that monocyte NF-κB activation upon stimulation was impaired in frail older adults, which could result in reduced immune responses and vaccine effectiveness.

Characterization of burning mouth syndrome profiles based on response to a local anaesthetic lozenge.

OBJECTIVE: Burning mouth syndrome (BMS) is a chronic oral pain condition with unknown aetiology but assumed to involve peripheral/central neuropathological and immune-mediated inflammatory factors. We aimed at characterizing inflammatory and neurogenic profiles and oral symptomatology of patients with BMS based on response to a local anaesthetic lozenge. METHODS: Patients with BMS were divided into an Effect (n = 13), No effect (n = 8) or Unspecified (n = 2) group according to their response to a local anaesthetic lozenge on oral pain. Inflammation was assessed in blood plasma and saliva by analyses of IL-6, IL-8, IL-17A, IL-23 and TNF-α levels. The degree of inflammation and distribution of oestrogen receptor, NGF, NGF-receptor, TRPV-1 and IL-17F in buccal mucosal tissue were investigated by immunohistochemistry. RESULTS: Immunoreactivity to the oestrogen receptor was most intense in the Effect group, whereas the No effect group tended to have higher plasma levels of the pro-inflammatory cytokines. CONCLUSIONS: Our findings indicate that the response to treatment with local anaesthesia enables subgrouping of patients with BMS according to the potential pathogenic mechanisms. Effect of local anaesthesia indicates a peripheral neuropathology involving lack of oestrogen and upregulation of oestrogen receptors, and no effect indicates a systemic inflammation-induced mechanism leading to increased levels of plasma cytokines.

Post-hospital medical respite care for homeless people in Denmark: a randomized controlled trial and cost-utility analysis.

BACKGROUND: Being homeless entails higher mortality, morbidity, and prevalence of psychiatric diseases. This leads to more frequent and expensive use of health care services. Medical respite care enables an opportunity to recuperate after a hospitalization and has shown a positive effect on readmissions, but little is known about the cost-effectiveness of medical respite care for homeless people discharged from acute hospitalization. Therefore, the aim of the present study was to investigate the cost-effectiveness of a 2-week stay in post-hospital medical respite care. METHODS: A randomized controlled trial and cost-utility analysis, from a societal perspective, was conducted between April 2014 and March 2016. Homeless people aged > 18 years with an acute admission were included from 10 different hospitals in the Capital Region of Denmark. The intervention group (n = 53) was offered a 2-week medical respite care stay at a Red Cross facility and the control group (n = 43) was discharged without any extra help (usual care), but with the opportunity to seek help in shelters and from street nurses and doctors in the municipalities. The primary outcome was the difference in health care costs 3 months following inclusion in the study. Secondary outcomes were change in health-related quality of life and health care costs 6 months following inclusion in the study. Data were collected through Danish registries, financial management systems in the municipalities and at the Red Cross, and by using the EQ-5D questionnaire. RESULTS: After 3 and 6 months, the intervention group had €4761 (p = 0.10) and €8515 (p = 0.04) lower costs than the control group, respectively. Crude costs at 3 months were €8448 and €13,553 for the intervention and control group respectively. The higher costs in the control group were mainly related to acute admissions. Both groups had minor quality-adjusted life year gains. CONCLUSIONS: This is the first randomized controlled trial to investigate the cost-effectiveness of a 2-week medical respite care stay for homeless people after hospitalization. The study showed that the intervention is cost-effective. Furthermore, this study illustrates that it is possible to perform research with satisfying follow-up with a target group that is hard to reach. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02649595.

Efficacy of Supervised Pelvic Floor Muscle Training and Biofeedback vs Attention-Control Treatment in Adults With Fecal Incontinence.

BACKGROUND & AIMS: Pelvic floor muscle training (PFMT) in combination with conservative treatment is recommended as first-line treatment for patients with fecal incontinence, although its efficacy is unclear. We investigated whether supervised PFMT in combination with conservative treatment is superior to attention-control massage treatment and conservative treatment in adults with fecal incontinence. METHODS: We performed a randomized, controlled, superiority trial of patients with fecal incontinence at a tertiary care center at a public hospital in Denmark. Ninety-eight adults with fecal incontinence were randomly assigned to groups that received supervised PFMT and biofeedback plus conservative treatment or attention-control treatment plus conservative treatment. The primary outcome was rating of symptom changes, after 16 weeks, based on scores from the Patient Global Impression of Improvement scale. Secondary outcomes were changes in the Vaizey incontinence score (Vaizey Score), Fecal Incontinence Severity Index, and Fecal Incontinence Quality of Life Scale. RESULTS: In the intention-to-treat analysis, participants in the PFMT group were significantly more likely to report improvement in incontinence symptoms based on Patient Global Impression of Improvement scale scores (unadjusted odds ratio, 5.16; 95% CI, 2.18-12.19; P = .0002). The PFMT group had a larger reduction in the mean Vaizey Score (reduction, -1.83 points; 95% CI, -3.57 to -0.08; P = .04). There were no significant differences in condition-specific quality of life. In the per-protocol analyses, the superiority of PFMT was increased. No adverse events were reported. CONCLUSIONS: This randomized controlled trial of adults with fecal incontinence provides support for a superior effect of supervised PFMT in combination with conservative treatment compared with attention-control massage treatment and conservative treatment. We found that participants who received supervised PFMT had 5-fold higher odds of reporting improvements in fecal incontinence symptoms and had a larger mean reduction of incontinence severity based on the Vaizey Score compared with attention control massage treatment. Clinicaltrials.gov no: NCT01705535.

Use of prescription drugs in the older adult population-a nationwide pharmacoepidemiological study.

PURPOSE: Multi-morbidity and polypharmacy are common among older people. It is essential to provide a better understanding of the complexity of prescription drug use among older adults to optimise rational pharmacotherapy. Population-based utilisation data in this age group is limited. Using the Danish nationwide health registries, we aimed to characterise drug use among Danish individuals ≥ 60 years. METHODS: This is a descriptive population-based study assessing drug prescription patterns in 2015 in the full Danish population aged ≥ 60 years. The use of specific therapeutic subgroups and chemical subgroups and its dependence on age were described using descriptive statistics. Profiles of drug combination patterns were evaluated using latent class analysis. RESULTS: We included 1,424,775 residents (median age 70 years, 53% women). Of all the older adults, 89% filled at least one prescription during 2015. The median number of drug groups used was five per person. The most used single drug groups were paracetamol and analogues (34%), statins (33%) and platelet aggregation inhibitors (24%). Eighteen drug profiles with different drug combination patterns were identified. One drug profile with expected use of zero drugs and 11 drug profiles expected to receive more than five different therapeutic subgroup drugs were identified. CONCLUSION: The use of drugs is extensive both at the population level and increasing with age at an individual level. Separating the population into different homogenous groups related to drug use resulted in 18 different drug profiles, of which 11 drug profiles received on average more than five different therapeutic subgroup drugs.

Histological and Molecular Adipose Tissue Changes Are Related to Metabolic Syndrome Rather Than Lipodystrophy in Human Immunodeficiency Virus-Infected Patients: A Cross-Sectional Study.

Background: In human immunodeficiency virus (HIV)-infected patients on combination antiretroviral therapy (cART), lipodystrophy shares many similarities with metabolic syndrome, but only metabolic syndrome has objective classification criteria. We examined adipose tissue changes related to lipodystrophy and metabolic syndrome to clarify whether it may be acceptable to focus diagnosis on metabolic syndrome rather than lipodystrophy. Methods: This is a cross-sectional study of 60 HIV-infected men on cART and 15 healthy men. We evaluated lipodystrophy (clinical assessment) and metabolic syndrome (JIS-2009). We compared adipocyte size, leukocyte infiltration, and gene expression in abdominal subcutaneous adipose tissue biopsies of patients with and without lipodystrophy and with and without metabolic syndrome. Results: Lipodystrophy was only associated with increased macrophage infiltration (P = .04) and adiponectin messenger ribonucleic acid ([mRNA] P = .008), whereas metabolic syndrome was associated with larger adipocytes (P < .0001), decreased expression of genes related to adipogenesis and adipocyte function (P values between <.0001 and .08), increased leptin mRNA (P = .04), and a trend towards increased expression of inflammatory genes (P values between .08 and .6). Conclusions: Metabolic syndrome rather than lipodystrophy was associated with major unfavorable abdominal subcutaneous adipose tissue changes. In a clinical setting, it may be more relevant to focus on metabolic syndrome diagnosis in HIV-infected patients on cART with regards to adipose tissue dysfunction and risk of cardiometabolic complications.