Low-dose oral corticosteroids in asthma associates with increased morbidity and mortality.

BACKGROUND: Long-term oral corticosteroid (OCS) treatment for severe asthma is known to cause significant adverse effects, but knowledge on effects of lower exposures in general asthma populations is limited. We aimed to explore this in a nationwide Danish asthma population. METHODS: Users of asthma medication aged 18-45 years were identified in the Danish nationwide registers during 1999-2018 and followed prospectively in an open-cohort design. Incident OCS users were matched 1:4 to nonusers by propensity scores with replacement. Associations between OCS use and incident comorbidities were examined by Cox regression. Mortality rates, causes of death and rates of unscheduled hospital visits were assessed. RESULTS: OCS users (n=30 352) had, compared with nonusers (n=121 408), an increased risk of all outcomes with evident dose-response relationships starting at cumulative doses of ≤500 mg (prednisolone-equivalent). Hazard ratios ranged from 1.24 (95% CI 1.18-1.30) for fractures to 8.53 (95% CI 3.97-18.33) for adrenal insufficiency. Depression/anxiety had the highest incidence rate difference at 4.3 (95% CI 3.6-5.0) per 1000 person-years. Asthma-specific mortality rates were generally low at 0.15 (95% CI 0.11-0.20) and 0.04 (95% CI 0.02-0.06) per 1000 person-years for OCS users and nonusers, respectively. Mortality rates and unscheduled hospital visits increased with increasing OCS exposure. CONCLUSION: The study findings should be interpreted with their observational nature in mind. However, we found that even at low cumulative exposure, OCS use in asthma management was associated with increased risk of comorbidities, mortality and unscheduled hospital visits. Effective strategies for optimising asthma control and reducing OCS use are pivotal in asthma management.

Association between gabapentinoids and oedema treated with loop diuretics: A pooled sequence symmetry analysis from the USA and Denmark.

AIMS: To assess the gabapentinoid-oedema-loop diuretic prescribing cascade in adults using large administrative health care databases from the USA and Denmark. METHODS: This study used a sequence symmetry analysis to assess loop diuretic initiation before and after the initiation of gabapentinoids among patients aged 20 years or older without heart failure or chronic kidney disease. Data from MarketScan Commercial and Medicare Supplemental Claims databases (2005 to 2019) and Danish National Prescription Register (2005 to 2018) were analyzed. Use of loop diuretics associated with initiation of selective norepinephrine reuptake inhibitors (SNRI) was used as a negative control. We assessed the pooled temporality of loop diuretic initiation relative to gabapentinoid or SNRI initiation across the 2 countries. Secular trend-adjusted sequence ratios (aSRs) with 95% confidence intervals (CIs) were calculated using data from 90 days before and after initiation of gabapentinoids. Pooled ratio of aSRs were calculated by comparing gabapentinoids to SNRIs. RESULTS: Among the 1 511 493 gabapentinoid initiators (Denmark [n = 338 941]; USA [n = 1 172 552]), 20 139 patients had a new loop diuretic prescription 90 days before or after gabapentinoid initiation, resulting in a pooled aSR of 1.33 (95% CI 1.06-1.67). The pooled aSR for the negative control (i.e., SNRI) was 0.84 (95% CI 0.75-0.94), which resulted in a pooled ratio of aSRs of 1.58 (95% CI 1.23-2.04). Pooled estimated incidence of the gabapentinoid-loop diuretic prescribing cascade was 8.14 (95% CI, 1.92-34.49) events per 1000 patient-years. CONCLUSION: We identified evidence of the gabapentinoid-oedema-loop diuretic prescribing cascade in 2 countries.

Use of dipeptidyl peptidase-4 inhibitors and risk of splanchnic vein thrombosis: A Danish nationwide new-user active comparator cohort study.

Use of dipeptidyl peptidase-4 (DPP-4) inhibitors, on the basis of spontaneous adverse event reports, has recently been suspected of causing splanchnic vein thrombosis. Here, we report the results of a population-based new-user active comparator cohort study addressing this hypothesis, comparing DPP-4 inhibitor initiators (n = 75 042) with initiators of glucagon-like-peptide-1 receptor agonists (GLP-1RAs) or sodium-glucose co-transporter-2 (SGLT2) inhibitors (n = 38 718). We estimated the hazard ratio (HR) associating DPP-4 inhibitor use with risk of splanchnic vein thrombosis using Cox regression. In a crude analysis, the incidence rate of splanchnic vein thrombosis was 0.22/1000 person-years among DPP-4 inhibitor initiators, compared to 0.17 among GLP-1RA/SGLT2 inhibitor initiators, corresponding to an unadjusted absolute incidence rate difference of 0.05 (95% confidence interval [CI] -0.04 to 0.14) and an HR of 1.29 (95% CI 0.78 to 2.15). Adjusting for potential confounders using stabilized inverse probability of treatment weighing, we obtained an absolute incidence rate difference of 0.03/1000 person-years (95% CI -0.07 to 0.14) and an HR of 1.18 (95% CI 0.62 to 2.26). No evidence of increased risk of splanchnic vein thrombosis was found in supplementary analyses, including an absence of any dose-response patterns. As such, we found no association between DPP-4 inhibitor use and splanchnic vein thrombosis risk.

Efficacy of bronchial thermoplasty in patients with severe asthma.

Objective: To investigate the efficacy and safety of bronchial thermoplasty (BT) in clinical practice in adults with severe, refractory asthma.Methods: Prospective, single-center, open, observational study comprising patients with uncontrolled asthma (asthma control questionnaire (ACQ) >1.5) and/or frequent exacerbations despite treatment with at least high dose inhaled corticosteroids plus a second controller. Efficacy outcomes was change from baseline 4, 8, 12 and 24 months in FEV1, FVC and FEV1/FVC ratio, asthma control questionnaire (ACQ) score and asthma quality of life score (mini-AQLQ). Results are presented as median with interquartile ranges (IQR). The following were recorded as adverse events: Un-scheduled health care contacts, rescue courses of oral corticosteroid (OCS) and/or antibiotics for exacerbation for exacerbations/respiratory tract infections (RTI).Results: Six-teen patients were enrolled (nine males, median age 50 years; 14 followed for 24 months). Compared to baseline, an improvement in FEV1, FVC, FEV1/FVC ratio, mini-AQLQ and ACQ was observed, i.e.FEV1 (IQR) 1.98 L (1.65-2.45) vs. 2.45 L (2.09-2.93) (p = 0.006), FVC (IQR) 3.23 L (2.76-4.05) vs. 3.75 L (3.22-4.36) (p = 0.041), FEV1/FVC 0.60 (IQR: 0.55-0.70) vs. 0.66 (IQR: 0.63-0.71) (p = 0.016), mini-AQLQ 4.0 (IQR: 3.2-4.9) vs. 5.6 (IQR 4.5-6.5) (p = 0.008, and ACQ 2.9 (IQR: 2.1-3.7) versus 1.5 (IQR 1.0-2.4) (p = 0.004). On the other hand, an increase was observed in unscheduled visits (p = 0.005), as well as use of OCS and antibiotics (p = 0.009 and p = 0.003, respectively).Conclusion: BT in adults with severe asthma improved ACQ, mini-AQLQ and lung function, but resulted in an increased frequency of unscheduled doctor-visits and rescue courses of OCS and antibiotics.

Sodium-glucose cotransporter-2 inhibitors and the risk of gout: A Danish population based cohort study and symmetry analysis.

PURPOSE: Sodium-glucose cotransporter-2 inhibitors (SGLT2-I) are frequently used in type 2 diabetes and have recently been associated with lower rates of gout compared to glucagon-like peptide-1 receptor agonists (GLP1-RA). Our objective was to assess the association between SGLT2-I initiation and gout using a cohort study design and a symmetry analysis. METHODS: Using the Danish nationwide health registries, we conducted an active comparator, new user cohort study comparing the 3-year risk of gout among SGLT2-I users with propensity score matched GLP1-RA users. Individuals were followed according to the intention-to-treat, and incidence rate differences (IRD) and hazard ratios (HR) were obtained. To address unmeasured confounding that is stable over time, a corresponding symmetry analysis was performed. RESULTS: 11 047 pairs of SGLT2-I and GLP1-RA users were identified, contributing 42 201 person-years of follow-up. The incidence rate of gout was 4.1 and 7.0 events per 1000 person years among SGLT2-I and GLP1-RA users, yielding an IRD of -3.0 (95% confidence interval: -4.4 to -1.5) and HR of 0.58 (0.44 to 0.75). In the symmetry analysis, 80 individuals initiated SGLT2-Is prior to gout; 118 patients initiated treatment after gout. The trend adjusted SR was 0.63 (0.47 to 0.84) and the active comparator adjusted estimate was 0.67 (0.44 to 0.86). CONCLUSIONS: Initiation of SGLT2-Is was associated with a markedly decreased risk of gout compared to initiation of GLP1-RAs. The findings are comparable to prior studies addressing this association.

Intended and unintended changes in length of stay following reconfiguration of emergency care departments.

BACKGROUND: The Danish health-care system has witnessed noticeable changes in the acute hospital care organization. The reconfiguration includes closing hospitals, centralizing acute care functions and investing in new buildings and equipment. OBJECTIVE: To examine the impact on the length of stay (LOS) and the proportion of overnight stays for hospitalized acute care patients. METHODS: This nationwide interrupted time series examined trend changes in LOS and overnight stay. Admissions were stratified based on admission time (weekdays/weekends and time of day), age and the level of co-morbidity. RESULTS: In 2007-2016, the global average LOS declined 2.9% per year (adjusted time ratio [CI (confidence interval) 95%] 0.971 [0.970-0.971]). The reconfiguration was overall not associated with change in trend of LOS (time ratio [CI 95%] 1.001 [1.000-1.002]). When admissions were stratified for either weekdays or weekends, the reconfiguration was associated with reduction of the underlying downward trend for weekdays (time ratio [CI 95%] 1.004 [1.003-1.005]) and increased downward trend for weekend admissions (time ratio [CI 95%] 0.996 [0.094-0.098]). Admissions at night were associated with a 0.7% trend change in LOS (time ratio [CI 95%] 0.993 [0.991-0.996]). The reconfiguration was not associated with trend changes for overnight stays. CONCLUSION: The nationwide reconfiguration of acute hospital care was overall not associated with change in trend for the registered LOS and no change in trend for overnight stays. However, the results varied according to hospitalization time, where admissions during weekends and nights after the reconfiguration were associated with shortened LOS.

Selective serotonin reuptake inhibitors and the risk of restless legs syndrome: a symmetry analysis.

PURPOSE: Largely based on case series, several drugs have been implicated in drug-induced restless legs syndrome (RLS) including selective serotonin reuptake inhibitors (SSRI). We aimed to assess the association between initiation of SSRIs and RLS in a self-controlled design. METHODS: We conducted a symmetry analysis, including Danish adults who filled in their first prescription of an SSRI in the period of 1997-2017 and initiated an RLS drug (quinine, ropinirole, pramipexole or rotigotine) 1 year prior to or after this date. A symmetrical distribution of prescriptions before and after SSRI initiation is expected if there is no association between SSRI and RLS (a sequence ratio (SR) of 1.0). The symmetry analysis design is robust to confounders that are stable over time. Subgroup analyses were conducted, restricting the population on sex, age, selected diagnoses and concurrent medication. RESULTS: A total of 10,875 patients filled in their first-ever prescription of both an SSRI and an RLS drug within a 1-year interval; 5341 patients filled their prescription of SSRI prior to their prescription of an RLS drug, and 5534 patients redeemed their prescriptions in the opposite order (SR 0.97, 95% CI 0.93-1.00). Restricting the outcome to dopamine agonist initiation revealed a slightly increased sequence ratio (SR 1.34, 95% CI 1.24-1.46), which was reduced when adjusting for trends in prescription (adjusted SR 1.21, 95% CI 1.12-1.32). Restricting the outcome to quinine initiation showed no association. CONCLUSION: We found no association between the initiation of an SSRI and the development of RLS assessed by the prescription of an RLS drug.

Lung Ultrasound in the Assessment of Pulmonary Complications After Lung Transplantation.

INTRODUCTION: Lung ultrasound (LUS) has a high diagnostic accuracy for identifying frequent conditions in the post-operative phase after lung transplantation (LTx). This study aimed to investigate the feasibility and clinical ability of LUS to identify pulmonary complications such as pleural effusions and pneumonias in the early postoperative phase after LTx. METHODS: A prospective cohort study of lung transplant recipients who consecutively underwent single LTx (SLTx) or double LTx (DLTx) at the National Lung Transplantation Center in Denmark from May 1 to October 31, 2015 was conducted. LUS was performed at four time points corresponding to post-transplant day 3, and weeks 2, 6, and 12 (LUS #1-4) to detect and monitor variation in pathological LUS findings over time. Concurrent with LUS #4, a high-resolution computed tomography examination of the thorax (HRCT) was also performed. RESULTS: 14 patients (1 SLTx/13 DLTx, 7 (50 %) women, mean age: 50.4 years) who had undergone the four prespecified LUS examinations were included. Pleural effusion was the most common condition and most pronounced at post-LTx week 2. Findings consistent with pneumonia increased during week 2 and subsequently decreased. Corresponding to LUS #1, 2, 3, and 4, pleural effusion occurred in 85.7 %, 92.9 %, 85.7 %, and 78.6 %, and pneumonia in 21.4 %, 28.6 %, 14.3 %, and 14.3 %, respectively. HRCT findings at post-LTx week 12 were predominantly presented by unspecific ground glass opacities. CONCLUSION: In a post-LTx setting, LUS represents a clinical novelty as a feasible diagnostic and monitoring tool to identify pathological pulmonary complications in the early post-operative phase.

Discontinuation of therapy among COPD patients who experience an improvement in exacerbation status.

PURPOSE: A subset of patients with chronic obstructive pulmonary disease (COPD) experience a decrease in exacerbation frequency, leading to a diminished need for treatment with inhaled corticosteroids (ICS). We investigated prescribing and discontinuation patterns of long-acting bronchodilators and ICS in COPD patients according to exacerbation frequency. METHODS: Using the nationwide Danish health registries, we conducted a drug utilization study among patients who had at least two exacerbations or one hospitalization due to an exacerbation during 2011-2012. This study population was stratified according to consistency of exacerbation occurrence after 12, 24, 36, and 48 months of follow-up and the groups were described according to use of ICS, long-acting ß2-agonists (LABA), and long-acting anticholinergics (LAMA), and combinations thereof. RESULTS: We identified 29,010 COPD exacerbators during 2011-2012. Upon inclusion, 70% received ICS-containing regimens, in combination with LABA (23%) or both LABA and LAMA (41%). The proportion of prevalent users of ICS-containing regimens decreased to 56% during follow-up among exacerbation-free individuals, while it increased to 86% in individuals who experienced at least one exacerbation annually. Persistence to ICS-containing regimens was 58% after 4 years in individuals without exacerbations compared to 74% among those with annual exacerbations. Similar patterns were observed for triple therapy which was the most extensively used drug combination regardless of consistency of exacerbation occurrence. CONCLUSIONS: The extensive use of ICS and the relatively high persistence to ICS-containing regimens in individuals who had a decrease in exacerbation occurrence highlight a need for the development and implementation of de-escalation strategies in clinical practice.

Treatment with montelukast and antidepressive medication-a symmetry analysis.

PURPOSE: Leukotriene receptor antagonists are used in asthma and rhinitis treatment. Pharmacovigilance data have suggested an association between montelukast and depression, but the association has not been established in controlled study designs. We described the association between initiation of montelukast and depression, using prescriptions of antidepressants as a surrogate marker, and assessed whether the association was related to the underlying asthma disease. METHODS: We performed a symmetry analysis, with a study period from January 1, 2000 to December 31, 2016, using 3 nationwide Danish registers. We included all adults, who filled their first prescription of montelukast and antidepressants within an interval of 1 year. In the absence of an association between montelukast and antidepressant use, a symmetrical distribution of prescriptions is expected before and after montelukast initiation (ie, a sequence ratio [rc ] of 1.0). We subcategorized the subjects after the severity of underlying asthma disease. RESULTS: In total, 4450 subjects filled their first prescriptions of both montelukast and antidepressants within a 1-year interval: 2434 redeemed their first prescription of montelukast before antidepressants, and 2016 redeemed the medications in the opposite order (rc 1.21 [95% CI 1.14-1.28]). We found rc above unity in groups with long-acting asthma treatment, but no increase in antidepressant prescription, when stratifying by the asthma severity. CONCLUSION: We found a weak association between the use of montelukast and the risk of being prescribed an antidepressant, unlikely to be of clinical relevance. Stratified analyses suggest that this association may relate to asthma, rather than to montelukast.

CURB-65 Score is Equal to NEWS for Identifying Mortality Risk of Pneumonia Patients: An Observational Study.

IMPORTANCE: The CURB-65 score is widely implemented as a prediction tool for identifying patients with community-acquired pneumonia (cap) at increased risk of 30-day mortality. However, since most ingredients of CURB-65 are used as general prediction tools, it is likely that other prediction tools, e.g. the British National Early Warning Score (NEWS), could be as good as CURB-65 at predicting the fate of CAP patients. OBJECTIVE: To determine whether NEWS is better than CURB-65 at predicting 30-day mortality of CAP patients. DESIGN: This was a single-centre, 6-month observational study using patients' vital signs and demographic information registered upon admission, survival status extracted from the Danish Civil Registration System after discharge and blood test results extracted from a local database. SETTING: The study was conducted in the medical admission unit (MAU) at the Hospital of South West Jutland, a regional teaching hospital in Denmark. PARTICIPANTS: The participants consisted of 570 CAP patients, 291 female and 279 male, median age 74 (20-102) years. RESULTS: The CURB-65 score had a discriminatory power of 0.728 (0.667-0.789) and NEWS 0.710 (0.645-0.775), both with good calibration and no statistical significant difference. CONCLUSION: CURB-65 was not demonstrated to be significantly statistically better than NEWS at identifying CAP patients at risk of 30-day mortality.

Montelukast use-a 19-year nationwide drug utilisation study.

PURPOSE: Montelukast is a leukotriene receptor antagonist used in asthma and rhinitis treatment. Despite being marketed nearly two decades ago, little is known about its utilisation pattern. METHODS: Using the Danish National Prescription Registry, we identified subjects filling a montelukast prescription between 1998 and 2017. Using descriptive statistics, we reported the development in incidence, and prevalence, as well as a measure of treatment duration, and concomitant use of asthma- or anti-allergic therapy. RESULTS: We identified 147,247 individuals filling 1,327,489 montelukast prescriptions. A total of 54,349 users (37%) filled only one montelukast prescription. The prevalence increased from 0.9/1000 persons in 1998 to 3.3/1000 persons in 2016. The rate of new users reached its maximum of 2.1/1000 person-years in 2009. Among new montelukast users, 28% were still users after 1 year. Among all montelukast initiators, 60% filled at least one prescription of short-acting beta-2-agonists (SABA) up to a year prior to montelukast initiation, and 49% filled a prescription of inhaled corticosteroids (ICS). Only 0.8% (n = 1148) of all individuals initiated montelukast without a redeemed prescription of short- or long-term inhalation therapy, systemic antihistamines, or nasal topical anti-allergic treatment. CONCLUSIONS: The usage of montelukast has increased over threefold since its market entry in 1998, mainly driven by an increased number of prevalent users. The majority of individuals who initiated montelukast filled a prescription of SABA up to a year prior to montelukast initiation, whereas almost half filled a prescription of ICS.

Antimicrobial resistance in the Bacteroides fragilis group in faecal samples from patients receiving broad-spectrum antibiotics.

Members of the Bacteroides fragilis group are opportunistic pathogens and cause severe infections including bacteraemia. As increased levels of antimicrobial resistance in B. fragilis group bacteria can be detected years after administration of specific antibiotics, monitoring antimicrobial susceptibility in the gut microbiota could be important. The objectives of this study were to 1) investigate the distribution of species and the occurrence of reduced antimicrobial susceptibility in the B. fragilis group from patients treated at departments with a high level of antibiotic use, 2) to determine the prevalence of the carbapenem resistance gene cfiA in B. fragilis in this patient group, and 3) to determine the association between previous antibiotic treatment and reduced susceptibility to clindamycin, meropenem, metronidazole, and piperacillin-tazobactam. Consecutive faecal samples (n = 197) were collected from patients at the departments of haematology, oncology, and infectious diseases at Odense University Hospital, Denmark. Three colonies from each sample were identified by Matrix Assisted Lazer Desorption Ionization Time of Flight Mass Spectrometry and isolates were screened for resistance to clindamycin, meropenem, metronidazole, and piperacillin-tazobactam. B. fragilis isolates were tested for the cfiA metallo-beta-lactamase gene. Fisher's Exact test was used to test for correlation between antimicrobial exposure and reduced susceptibility. A total of 359 isolates were tested for reduced susceptibility. Of these 28%, 5%, <1%, and 11% were intermediate susceptible or resistant to clindamycin, meropenem, metronidazole, and piperacillin-tazobactam respectively. Three metronidazole resistant Bacteroides spp. were isolated. The proportion of B. fragilis belonging to division II (cfiA+) was 5.3%. Previous exposure to meropenem was associated with reduced susceptibility to meropenem (p= 0.001). In conclusion, antimicrobial resistance is prevalent and the distribution of species appears to be affected in the B. fragilis group from patients receiving broad-spectrum antibiotics, with meropenem exposure being associated with meropenem resistance.

Incidence rate of community-acquired sepsis among hospitalized acute medical patients-a population-based survey.

OBJECTIVE: Sepsis is a frequent cause of admission, but incidence rates based on administrative data have previously produced large differences in estimates. The aim of the study was to estimate the incidence of community-acquired sepsis based on patients' symptoms and clinical findings at arrival to the hospital. DESIGN: Population-based survey. SETTING: Medical emergency department from September 1, 2010, to August 31, 2011. PATIENTS: All patients were manually reviewed using a structured protocol in order to identify the presence of infection. Vital signs and laboratory values were collected to define the presence of systemic inflammatory response syndrome and organ dysfunction. MEASUREMENTS AND MAIN RESULTS: Incidence rate of sepsis of any severity. Among 8,358 admissions to the medical emergency department, 1,713 patients presented with an incident admission of sepsis of any severity, median age 72 years (5-95%; range, 26-91 yr), 793 (46.3%) were men, 728 (42.5%) presented with a Charlson comorbidity index greater than 2,621 (36.3%) were admitted with sepsis, 1,071 (62.5%) with severe sepsis, and 21 (1.2%) with septic shock. Incidence rate was 731/100,000 person-years at risk (95% CI, 697-767) in patients with sepsis of any severity, 265/100,000 person-years at risk (95% CI, 245-287) in patients with sepsis, 457/100,000 person-years at risk (95% CI, 430-485) in patients with severe sepsis, and 9/100,000 person-years at risk (95% CI, 6-14) in patients with septic shock. CONCLUSIONS: Based on symptoms and clinical findings at arrival, incidence rates of patients admitted to a medical emergency department with sepsis and severe sepsis are more frequent than previously reported based on discharge diagnoses.

The potential drug-drug interaction between proton pump inhibitors and warfarin.

BACKGROUND: Proton pump inhibitors (PPIs) have been suggested to increase the effect of warfarin, and clinical guidelines recommend careful monitoring of international normalized ratio (INR) when initiating PPI among warfarin users. However, this drug-drug interaction is sparsely investigated in a clinical setting. The aim was to assess whether initiation of PPI treatment among users of warfarin leads to increased INR values. METHODS: The study was an observational self-controlled study from 1998 to 2012 leveraging data on INR measurements on patients treated with warfarin from primary care and outpatient clinics and their use of prescription drugs. Data were analyzed in 2015. We assessed INR, warfarin dose, and dose/INR ratio before and after initiating PPI treatment using the paired student's t-test. RESULTS: We identified 305 warfarin users initiating treatment with PPIs. The median age was 71 years (interquartile range 63-78 years), and 64% were men. The mean INR in the 70 days prior to PPI initiation was 2.6 (95%CI 2.5-2.8) and 2.6 (95%CI 2.5-2.7) in the period 1-3 weeks after PPI initiation (p = 0.67). Further, neither mean warfarin dose nor the dose/INR ratios were significantly different before and after PPI initiation. Sensitivity analyses revealed no differences among individual PPIs. CONCLUSIONS: We found no evidence of a clinically meaningful drug-drug interaction between PPIs and warfarin in a Northern European patient population of unselected patients from an everyday outpatient and primary care clinical setting. Thus, we do not support the recommendation to "cautiously monitor" users of warfarin initiating PPI treatment.

Time to initial antibiotic administration, and short-term mortality among patients admitted with community-acquired severe infections with and without the presence of systemic inflammatory response syndrome: a follow-up study.

BACKGROUND: The prognosis for patients with severe infection is related to early treatment, including early administration of antibiotics. The study aim was to compare the short-term mortality among patients admitted with severe infection with and without systemic inflammatory response syndrome (SIRS) at arrival, and to ascertain whether the presence of SIRS might affect the timing of antibiotic administration. METHODS: In this retrospective follow-up study, we included all adult patients (≥15 years) presenting to a medical emergency department in the period between September 2010 and August 2011 with a first-time admission of community-acquired severe infection (infection with evidence of organ dysfunction), with and without SIRS at arrival. The presence of SIRS was defined as two or more of the criteria according to the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) definitions. Cases were identified by manual chart review using predefined criteria of infection. Data on vital signs, laboratory values and antibiotic treatment were obtained electronically. RESULTS: We included 1169 patients with infection and organ dysfunction, treated with antibiotics within 24 h after arrival (median age 76.1 years (IQR 63.1-83.5), 567 (48.5%) men). In all, 886 (75.8%) presented with SIRS, and 283 (24.2%) presented without SIRS. Median time to antibiotics was 4.6 h (IQR 2.9-7.0) in patients with SIRS and 6.7 h (IQR 4.5-10.3) in patients without SIRS (p<0.0001). Thirty-day mortality in patients with and without SIRS was 18.4% (95% CI 15.9% to 21.1%) and 16.6% (95% CI 12.5% to 21.5%), respectively. CONCLUSIONS: SIRS was absent in one-quarter of patients admitted with severe infection. The 'door-to-antibiotics' time was significantly shorter for patients with SIRS compared with patients without SIRS, but no difference was found in 30-day mortality.

Network of doctors for multimorbidity and diabetes - the NOMAD intervention: protocol for feasibility trial of multidisciplinary team conferences for people with diabetes and multimorbidity.

BACKGROUND: The prevalence of diabetes and coexisting multimorbidity rises worldwide. Treatment of this patient group can be complex. Providing an evidence-based, coherent, and patient-centred treatment of patients with multimorbidity poses a challenge in healthcare systems, which are typically designed to deliver disease-specific care. We propose an intervention comprising multidisciplinary team conferences (MDTs) to address this issue. The MDT consists of medical specialists in five different specialities meeting to discuss multimorbid diabetes patients. This protocol describes a feasibility test of MDTs designed to coordinate care and improve quality of life for people with diabetes and multimorbidity. METHODS: A mixed-methods one-arm feasibility test of the MDT. Feasibility will be assessed through prospectively collected data. We will explore patient perspectives through patient-reported outcomes (PROs) and assess the feasibility of electronic questionnaires. Feasibility outcomes are recruitment, PRO completion, technical difficulties, impact of MDT, and doctor preparation time. During 17 months, up to 112 participants will be recruited. We will report results narratively and by the use of descriptive statistics. The collected data will form the basis for a future large-scale randomised trial. DISCUSSION: A multidisciplinary approach focusing on better management of diabetic patients suffering from multimorbidity may improve functional status, quality of life, and health outcomes. Multimorbidity and diabetes are highly prevalent in our healthcare system, but we lack a solid evidence-based approach to patient-centred care for these patients. This study represents the initial steps towards building such evidence. The concept can be efficiency tested in a randomised setting, if found feasible to intervention providers and receivers. If not, we will have gained experience on how to manage diabetes and multimorbidity as well as organisational aspects, which together may generate hypotheses for research on how to handle multimorbidity in the future. ADMINISTRATIVE INFORMATION: Protocol version: 01 TRIAL REGISTRATION: NCT05913726 - registration date: 21 June 2023.

Mortality before and after reconfiguration of the Danish hospital-based emergency healthcare system: a nationwide interrupted time series analysis.

OBJECTIVES: The study aimed to investigate how the 'natural experiment' of reconfiguring the emergency healthcare system in Denmark affected in-hospital and 30-day mortality on a national level. The reconfiguration included the centralisation of hospitals and the establishment of emergency departments with specialists present around the clock. DESIGN: Hospital-based cohort study. SETTING: All public hospitals in Denmark. PARTICIPANTS: Patients with an unplanned contact from 1 January 2007 until 31 December 2016. INTERVENTIONS: Stepped-wedge reconfiguration of the Danish emergency healthcare system. MAIN OUTCOME MEASURES: We determined the adjusted ORs for in-hospital mortality and HRs for 30-day mortality using logistic and Cox regression analysis adjusted for sex, age, Charlson Comorbidity Index, income, education, mandatory referral and the changes in the out of hours system in the Capital Region. The main outcomes were stratified by the time of arrival. We performed subgroup analyses on selected diagnoses: myocardial infarction, stroke, pneumonia, aortic aneurysm, bowel perforation, hip fracture and major trauma. RESULTS: We included 11 367 655 unplanned hospital contacts. The adjusted OR for overall in-hospital mortality after reconfiguration of the emergency healthcare system was 0.998 (95% CI 0.968 to 1.010; p=0.285), and the adjusted OR for 30-day mortality was 1.004 (95% CI 1.000 to 1.008; p=0.045)). Subgroup analyses showed some possible benefits of the reconfiguration such as a reduction in-hospital and 30-day mortality for myocardial infarction, stroke, aortic aneurysm and major trauma. CONCLUSIONS: The Danish emergency care reconfiguration programme was not associated with an improvement in overall in-hospital mortality trends and was associated with a slight slowing of prior improvements in 30-day mortality trends.

Variation in daytime general practice services and association with out-of-hours use for older patients: protocol for a Danish cohort study.

INTRODUCTION: Out-of-hours primary care services cannot provide the same continuity and coordination of care as general practice. Thus, patients with high risk of complex care trajectories should, when possible, be treated by the general practitioner during daytime opening hours. This study aims to analyse the variation among general practices in the frequencies of daytime services for persons aged ≥75 years and how it relates to the patients' use of out-of-hours services. METHODS AND ANALYSIS: Register-based cohort study of all Danish citizens aged ≥75 years, of whom >98% are listed with a general practice. Using Poisson regression, we will estimate each practice's excess variation in delivered daytime services compared with the expected based on the characteristics of its listed patients. Delivered daytime services will be analysed overall and separately for face-to-face, phone, email, home visit and preventive services. The association with the use of out-of-hours services will be analysed by Poisson regression. ETHICS AND DISSEMINATION: Complying with European data protection rules, the legal services at University of Southern Denmark (Research & Innovation Organisation) approved the data processing activities regarding this project (journal number 11.593). According to section 14.2 of the Act on Research Ethics Review of Health Research Projects, because the study is based solely on register data, approval from the ethics committee and informed consent are not required. Results from the study will be disseminated as publications in peer-reviewed scientific journals and at international conferences.