Patients' perspectives on point-of-care diagnostics and treatment by emergency medical technicians in acute COPD exacerbations: A qualitative study.

BACKGROUND: In Denmark emergency medical technicians transport patients with acute COPD exacerbations to the nearest emergency department. From a clinical and economic perspective, this transport and assessment at the hospital may be inconvenient if the patient is immediately discharged from the emergency department. We established an emergency technical technicians point-of-care diagnostics and treatment program of patients with COPD with use of ultrasound and blood analysis. Patients' perspectives on treatment at home and sense of security are important to qualify clinical practice at home with patients with acute exacerbation. AIM AND OBJECTIVES: To explore patient's and relatives' experience of treatment at home during emergency calls due to COPD in exacerbation and to investigate their attitude to avoid hospitalization as well as experience of stress during point-of-care diagnostics in their own home. METHOD: A qualitative study comprising semi-structured interviews with 16 patients carried out from April 1st, 2019 to March 31st, 2020 in Denmark. Data was analysed inspired by Malteruds' text condensation and informed by Critical Psychology with first person perspective focusing on the patient's views on point-of-care diagnostics and treatment of their COPD in acute exacerbation. RESULTS: The interviews revealed that in order to ensure an experience of quality in the assessment and treatment of patients in their own homes, it was important that the ambulance staff showed great safety and experience in the use of the technical equipment and treatment of dyspnea. It was also of importance that the patients felt confident that their general practitioner followed up on the home treatment initiated. CONCLUSION: Patients' perspectives showed that point-of-care diagnostics and treatment of acute COPD in exacerbation was considered a qualitative offer by the patients and their relatives. At the same time, it was crucial that the emergency medical technicians showed experience and safety in handling shortness of breath as well as the technical equipment. TRIAL REGISTRATION: Approved by the Danish Data Protection Agency Project-ID: 20/24845.

Point-of-care ultrasound of the heart and lungs in patients with respiratory failure: a pragmatic randomized controlled multicenter trial.

BACKGROUND: Point-of-care ultrasound is a focus oriented tool for differentiating among cardiopulmonary diseases. Its value in the hands of emergency physicians, with various ultrasound experience, remains uncertain. We tested the hypothesis that, in emergency department patients with signs of respiratory failure, a point-of-care cardiopulmonary ultrasound along with standard clinical examination, performed by emergency physicians with various ultrasound experience would increase the proportion of patients with presumptive diagnoses in agreement with final diagnoses at four hours after admission compared to standard clinical examination alone. METHODS: In this prospective multicenter superiority trial in Danish emergency departments we randomly assigned patients presenting with acute signs of respiratory failure to intervention or control in a 1:1 ratio by block randomization. Patients received point-of-care cardiopulmonary ultrasound examination within four hours from admission. Ultrasound results were unblinded for the treating emergency physician in the intervention group. Final diagnoses and treatment were determined by blinded review of the medical record after the patients´ discharge. RESULTS: From October 9, 2015 to April 5, 2017, we randomized 218 patients and included 211 in the final analyses. At four hours we found; no change in the proportion of patients with presumptive diagnoses in agreement with final diagnoses; intervention 79·25% (95% CI 70·3-86·0), control 77·1% (95% CI 68·0-84·3), an increased proportion of appropriate treatment prescribed; intervention 79·3% (95% CI 70·3-86·0), control 65·7% (95% CI 56·0-74·3) and of patients who spent less than 1 day in hospital; intervention n = 42 (39·6%, 25·8 38·4), control n = 25 (23·8%, 16·5-33·0). No adverse events were reported. CONCLUSIONS: Focused cardiopulmonary ultrasound added to standard clinical examination in patients with signs of respiratory failure had no impact on the diagnostic accuracy, but significantly increased the proportion of appropriate treatment prescribed and the proportion of patients who spent less than 1 day in hospital. TRIAL REGISTRATION: https://clinicaltrials.gov/ , number NCT02550184 .

A change from high-flow to titrated oxygen therapy in the prehospital setting is associated with lower mortality in COPD patients with acute exacerbations: an observational cohort study.

BACKGROUND: The aim of this study was to investigate 30-day mortality for COPD patients treated by ambulances in the period before and after implementation of a pre-hospital oxygen protocol. METHODS: Prehospital High-flow oxygen was used from April to September 2012 and titrated oxygen from April to September 2013. Primary outcome was 30-day mortality. RESULTS: 707 patients were included; 209 in the high-flow group and 498 in the titration group. Of these, 56 and 132 arrived with acute exacerbation (AE). Overall 30-day mortality was 11.5% vs. 9.4% (p=0.41), respectively. For patients with AE, it was 19.6% vs. 4.6% (p=0.001). CONCLUSION: Change of treatment protocol is associated with a lower 30-day mortality for patients registered with acute exacerbation, but not for all COPD patients.

C-reactive protein and albumin kinetics before community-acquired bloodstream infections - a Danish population-based cohort study.

Early changes in biomarker levels probably occur before bloodstream infection (BSI) is diagnosed. However, this issue has not been fully addressed. We aimed at evaluating the kinetics of C-reactive protein (CRP) and plasma albumin (PA) in the 30 days before community-acquired (CA) BSI diagnosis. From a population-based BSI database we identified 658 patients with at least one measurement of CRP or PA from day -30 (D-30) through day -1 (D-1) before the day of CA-BSI (D0) and a measurement of the same biomarker at D0 or D1. Amongst these, 502 had both CRP and PA measurements which fitted these criteria. CRP and PA concentrations began to change inversely some days before CA-BSI diagnosis, CRP increasing by day -3.1 and PA decreasing by day -1.3. From D-30 to D-4, CRP kinetics (expressed as slopes - rate of concentration change per day) was -1.5 mg/l/day. From D-3 to D1, the CRP slope increased to 36.3 mg/l/day. For albumin, the slope between D-30 to D-2 was 0.1 g/l/day and changed to -1.8 g/l/day between D-1 and D1. We showed that biomarker levels begin to change some days before the CA-BSI diagnosis, CRP 3.1 days and PA 1.3 days before.

Optimal measuring point for ST deviation in chest pain patients with possible acute coronary syndrome.

INTRODUCTION: In the ECG, significant ST elevation or depression according to specific amplitude criteria can be indicative of acute coronary syndrome (ACS). Guidelines state that the ST amplitude should be measured at the J point, but data to support that this is the optimal measuring point for ACS detection is lacking. We evaluated the impact of different measuring points for ST deviation on the diagnostic accuracy for ACS in unselected emergency department (ED) chest pain patients. MATERIAL AND METHODS: We included 14,148 adult patients with acute chest pain and an ECG recorded at a Swedish ED between 2010 and 2014. ST deviation was measured at the J point (STJ) and at 20, 40, 60 and 80 ms after the J point. A discharge diagnosis of ACS or not at the index visit was noted in all patients. RESULTS: In total, 1489 (10.5%) patients had ACS. ST amplitude criteria at STJ had a sensitivity of 28% and a specificity of 92% for ACS. With these criteria, the highest positive and negative predictive values for ACS were obtained near the J point, but the optimal point varied with ST deviation, age group and sex. The overall best measuring points were STJ and ST20. CONCLUSIONS: This study indicates that the diagnostic accuracy of the ECG criteria for ACS is very low in ED chest pain patients, and that the optimal measuring point for the ST amplitude in the detection of ACS differs between ST elevation and depression, and between patient subgroups.

Detection of meticillin-resistant Staphylococcus aureus and carbapenemase-producing Enterobacteriaceae in Danish emergency departments - evaluation of national screening guidelines.

BACKGROUND: Multi-resistant bacteria (MRB) are an emerging problem. Early identification of patients colonized with MRB is mandatory to avoid in-hospital transmission and to target antibiotic treatment. Since most patients pass through specialized emergency departments (EDs), these departments are crucial in early identification. The Danish National Board of Health (DNBH) has developed exposure-based targeted screening tools to identify and isolate carriers of meticillin-resistant Staphylococcus aureus (MRSA) and carbapenemase-producing Enterobacteriaceae (CPE). AIM: To assess the national screening tools for detection of MRSA and CPE carriage in a cohort of acute patients. The objectives were to investigate: (i) if the colonized patients were detected; and (ii) if the colonized patients were isolated. METHODS: This was a multi-centre cross-sectional survey of adults visiting EDs. The patients answered the DNBH questions, and swabs were taken from the nose, throat and rectum. The collected samples were examined for MRSA and CPE. Screening performances were calculated. FINDINGS: Of the 5117 included patients, 16 were colonized with MRSA and four were colonized with CPE. The MRSA screening tool had sensitivity of 50% [95% confidence interval (CI) 25-75%] for carrier detection and 25% (95% CI 7-52%) for carrier isolation. The CPE screening tool had sensitivity of 25% (95% CI 1-81%) and none of the CPE carriers were isolated. CONCLUSION: The national screening tools were of limited use as the majority of MRSA and CPE carriers passed unidentified through the EDs, and many patients were isolated unnecessarily.

Diagnostic value of whole-body-focused ultrasonography in high-acuity patients in the emergency department: a prospective single-center cross-sectional study.

BACKGROUND: A fast and diagnostic accurate tool to assess the unselected category of high-acuity patients, in whom the underlying pathology is not always obvious, is needed in the emergency departments (ED). We aim to describe the feasibility, validity and diagnostic yield of a routine whole-body-focused ultrasonography (wbf-us) in an unselected group of high-acuity ED patients. METHODS: In a prospective observational study, a convenience sample of ED patients (≥ 18 years) with a high-acuity score or systolic blood pressure < 100 mmHg received a routine wbf-us of the heart, lungs, abdomen and deep veins by two non-expert sonographers. Final diagnosis was established by experienced auditors. Investigators were blinded to the patients' medical history and emergency physicians and auditors were blinded to the investigators assessments. Diagnostic accuracy was assessed by comparing the investigators' ultrasonography findings to a structured double-blinded clinical audit of patient files. RESULTS: We included 171 patients, initiated a whole-body-focused ultrasonography examination (wbf-us) in 160 and completed it in 128 patients with an average time of a full examination of 28 min. We found pathology in 65/171 (38%) of the patients whose most frequent symptoms upon arrival were cardiopulmonary. Among the patients who received wbf-us, we found the majority of pathology by wbf-us of the lungs (n = 50, 31%), the heart (n = 26, 16%), few in the abdomen (n = 5, 3%) and none in the deep veins. The overall sensitivity was 50-100%, specificity 84-94%, positive predictive value 11-44% and negative predictive value 94-100%. CONCLUSION: Focused cardiopulmonary ultrasonography might be considered for routine use in high-acuity ED patients with cardiopulmonary symptoms whereas focused ultrasonography of the abdomen and deep veins performed by non-expert sonographers only seems indicated in selected patients. Trial registration Danish Data Protection Agency (ID 13/12076). Committee on Biomedical Research Ethics for the Region of Southern Denmark (ID S-20130047).

Hypoalbuminaemia as a marker of trans-capillary leakage in community-acquired bacteraemia patients.

Community-acquired bacteraemia patients (n = 2472), Denmark, 2000-2008. Albumin, C-reactive protein (CRP) and haemoglobin (Hb) measured 2000-2010. We assessed daily mean levels of albumin, CRP and Hb from 30 days before to 30 days after bacteraemia and correlations between albumin vs. CRP and albumin vs. Hb. In linear regression models, we evaluated the contribution of CRP, Hb, chronic and acute variables to the albumin level variations. The mean albumin level (33.6 g/l) was steady before day 1, declined to 29.3 g/l on day 1 with little increase afterward. The mean CRP increased from day -5, peaked on day 1 and declined thereafter. The mean Hb level was fairly constant during days -30/30. Albumin was inversely (R range, - 0.18/-0.47, P < 10-4) correlated with the CRP level and positively (R = 0.17-0.46, P < 10-4) correlated with the HB level. In most models, CRP was the first variable that contributed to the albumin variations, 34-70% of the full model. The sudden decrease of albumin levels, without sudden fluctuations of CRP or Hb, indicated that hypoalbuminaemia was a marker of trans-capillary leakage.

Patterns of anaphylaxis after diagnostic workup: A follow-up study of 226 patients with suspected anaphylaxis.

BACKGROUND: Most published studies on anaphylaxis are retrospective or register based. Data on subsequent diagnostic workup are sparse. We aimed to characterize patients seen with suspected anaphylaxis at the emergency care setting (ECS), after subsequent diagnostic workup at our Allergy Center (AC). METHODS: Prospective study including patients from the ECS, Odense University Hospital, during May 2013-April 2014. Possible anaphylaxis cases were daily identified based on a broad search profile including history and symptoms in patient records, diagnostic codes and pharmacological treatments. At the AC, all patients were evaluated according to international guidelines. RESULTS: Among 226 patients with suspected anaphylaxis, the diagnosis was confirmed in 124 (54.9%) after diagnostic workup; 118 of the 124 fulfilled WAO/EAACI criteria of anaphylaxis at the ECS, while six were found among 46 patients with clinical suspicion but not fulfilling the WAO/EAACI criteria at the ECS. The estimated incidence rate of anaphylaxis was 26 cases per 100 000 person-years and the one-year period prevalence was 0.04%. The most common elicitor was drugs (41.1%) followed by venom (27.4%) and food (20.6%). In 13 patients (10.5%), no elicitor could be identified. Mastocytosis was diagnosed in 7.7% of adult patients and was significantly associated with severe anaphylaxis. Atopic diseases were significantly associated only with food-induced anaphylaxis. Cofactors were present in 58.1% and were significantly associated with severe anaphylaxis. CONCLUSION: A broad search profile in the ECS and subsequent diagnostic workup is important for identification and classification of patients with anaphylaxis. Evaluation of comorbidities and cofactors is important.

Termination of pre-hospital resuscitation by anaesthesiologists - causes and consequences. A retrospective study.

AIM: Differentiating between a newly deceased patient and the lifeless patient in whom immediate resuscitation is required may be facilitated by a pre-hospital anaesthesiologist. The purpose of our study was to investigate to what extent and why the pre-hospital anaesthesiologist pronounced life extinct in situations where an emergency medical technician (EMT) would have been required to resuscitate. METHODS: All lifeless patients seen pre-hospitally by the anaesthesiologist-manned Mobile Emergency Care Unit in Odense, Denmark, from 2010 to 2014 were retrospectively studied. RESULTS: Of 17 035 contacts, 1275 patients were lifeless without reliable signs of death. In 642 of these patients (3.8%) resuscitation was initiated (median age 68 years). The remaining 633 patients (3.7%) were declared dead at the scene without any resuscitation attempt (median age 77 years). These latter patients would have been attempted resuscitated, had the anaesthesiologist not been present. In 54.5% of cases where documentation was available in the patient records, reasons for not resuscitating these patients included time elapsed from incident to contact with physician, 'overall assessment', chronic disease, or do-not-resuscitate order. CONCLUSION: In one patient in 30, the MECU refrained from futile resuscitation in cases where legislation required an EMT to initiate resuscitation. This practice reduced unethical attempts of resuscitation, reduced unnecessary emergency ambulance transports, and reduced the work load of the hospital resuscitation teams for one unnecessary alarm every third day. Differentiating between lifeless patients and dead patients not exhibiting reliable signs of death, however, is a complex task which is only sparsely documented.

Focused ultrasound examination of the chest on patients admitted with acute signs of respiratory problems: a study protocol for a pragmatic randomised controlled multicentre trial.

INTRODUCTION: Patients with acute respiratory problems poses a diagnostic challenge because similar symptoms can be caused by various pathological conditions. Focused ultrasound examination (f-US) of the heart and lungs has proven to increase the diagnostic accuracy in these patients. In this protocol of a randomised multicentre trial, we study the effect of f-US of the heart and lungs in patients with respiratory problems performed by emergency physicians (EP) as soon as the patient arrives to the emergency department (ED). The primary outcome is the number of patients with a correct presumptive diagnosis at 4 hours from admission. METHODS AND ANALYSIS: This is a semiblinded randomised prospective study. 288 patients will be included and randomised into the control or intervention group. All patients receive a standard diagnostic evaluation by the EP to assess the primary presumptive diagnosis. Investigators are EP, with varying degrees of experience in f-US, who perform an f-US of the heart and lungs in patients in both treatment arms. f-US results in the intervention group are non-blinded to the treating EP to be included in the assessment of the 4-hour presumptive diagnosis. As standard for correct diagnosis, we perform a blinded journal audit after discharge. As primary analysis, we use the intention-to-treat analysis. CONCLUSIONS: This study is the first multicentre trial in EDs to investigate whether f-US, in the hands of the EP, increases the proportion of correct diagnosis at 4 hours after arrival when performed on patients with respiratory problems. ETHICS AND DISSEMINATION: This trial is conducted in accordance with the Helsinki II Declaration and approved by the Danish Data Protection Agency and the Committee on Biomedical Research Ethics for the Region of Southern Denmark. Results will be published in accordance with the CONSORT statement in a peer-reviewed scientific journal regardless of the outcome. TRIAL REGISTRATION NUMBER: NCT02550184; Pre-results.

Hospitalized acute patients with fever and severe infection have lower mortality than patients with hypo- or normothermia: a follow-up study.

OBJECTIVES: Severe infection is a frequent cause of admission to an acute medical unit (AMU). However, not all infected patients present with fever. The aim was to assess differences in 30-day mortality among patients hospitalized with community-acquired severe infection presenting with hypothermia, normothermia or fever. METHODS: A retrospective single-center follow-up at an AMU from August 1, 2009 to August 31, 2011. Patients were included the first time they presented with severe infection within the study period. Temperature was categorized into hypothermia (<36.0ºC), normothermia (36.0ºC-38.0ºC) and fever (>38.0ºC). Severe infection was defined as a discharge diagnosis indicating infection combined with organ failure within the first 24 h after arrival. Multivariable Cox regression analysis was computed to assess the association between temperature and 30-day mortality. RESULTS: A total of 2128 patients with severe infection were included. 3.0% (N = 64) were hypothermic, 57.1% (N = 1216) normothermic and 39.9% (N = 848) had fever at arrival. Crude 30-day mortality was 16.1% (N = 342, 95%CI 14.5-17.7%); 37.5% (N = 24, 95% CI 25.7-50.5%) for hypothermic patients, 18.3% (N = 223, 95%CI 16.2-20.6%) for normothermic patients and 11.2% (N = 95, 95%CI 9.2-13.5%) for patients with fever. Compared to normothermic patients, the adjusted hazard ratio of 30-day mortality among hypothermic patients was 1.62 (95%CI 1.06-2.49) and 0.74 (95%CI 0.58-0.94) among patients with fever. CONCLUSIONS: Over half of the patients admitted to an AMU with severe infection were normothermic at arrival. Hypothermia was associated with an increased risk of short-term mortality, whereas patients with fever were associated with a lower risk compared to those with normothermia.

Readmissions of medical patients: an external validation of two existing prediction scores.

BACKGROUND: Hospital readmissions are increasingly used as a quality indicator with a belief that they are a marker of poor care and have led to financial penalties in UK and USA. Risk scoring systems, such as LACE and HOSPITAL, have been proposed as tools for identifying patients at high risk of readmission but have not been validated in international populations. AIM: To perform an external independent validation of the HOSPITAL and LACE scores. DESIGN: An unplanned secondary cohort study. METHODS: Patients admitted to the medical admission unit at the Hospital of South West Jutland (10/2008-2/2009; 2/2010-5/2010) and the Odense University Hospital (6/2009-8/2011) were analysed. Validation of the scores using 30 day readmissions as the endpoint was performed. RESULTS: A total of 19 277 patients fulfilled the inclusion criteria. Median age was 67 (range 18-107) years and 8977 (46.6%) were female. The LACE score had a discriminatory power of 0.648 with poor calibration and the HOSPITAL score had a discriminatory power of 0.661 with poor calibration. The HOSPITAL score was significantly better than the LACE score for identifying patients at risk of 30 day readmission (P < 0.001). The discriminatory power of both scores decreased with increasing age. CONCLUSION: Readmissions are a complex phenomenon with not only medical conditions contributing but also system, cultural and environmental factors exerting a significant influence. It is possible that the heterogeneity of the population and health care systems may prohibit the creation of a simple prediction tool that can be used internationally.

Decreasing incidence rates of bacteremia: a 9-year population-based study.

BACKGROUND: Numerous studies have shown that the incidence rate of bacteremia has been increasing over time. However, few studies have distinguished between community-acquired, healthcare-associated and nosocomial bacteremia. METHODS: We conducted a population-based study among adults with first-time bacteremia in Funen County, Denmark, during 2000-2008 (N = 7786). We reported mean and annual incidence rates (per 100,000 person-years), overall and by place of acquisition. Trends were estimated using a Poisson regression model. RESULTS: The overall incidence rate was 215.7, including 99.0 for community-acquired, 50.0 for healthcare-associated and 66.7 for nosocomial bacteremia. During 2000-2008, the overall incidence rate decreased by 23.3% from 254.1 to 198.8 (3.3% annually, p < .001), the incidence rate of community-acquired bacteremia decreased by 25.6% from 119.0 to 93.8 (3.7% annually, p < .001) and the incidence rate of nosocomial bacteremia decreased by 28.9% from 82.2 to 56.0 (4.2% annually, p < .001). The incidence rate of healthcare-associated bacteremia remained stable. The most common microorganisms were Escherichia coli (28.3%), Staphylococcus aureus (12.3%), coagulase-negative staphylococci (10.0%) and Streptococcus pneumoniae (9.1%). Regardless of place of acquisition, the proportion of bacteremias caused by enterococci increased (p < .05) and the proportion caused by coagulase-negative staphylococci decreased (p < .05). CONCLUSIONS: The incidence rates of community-acquired and nosocomial bacteremia decreased substantially over time.

Effectiveness of offering healthy labelled meals in improving the nutritional quality of lunch meals eaten in a worksite canteen.

Healthier meal selections at restaurants and canteens are often limited and not actively promoted. In this Danish study the effectiveness of a healthy labelling certification program in improving dietary intake and influencing edible plate waste was evaluated in a quasi-experimental study design. Employees from an intervention worksite canteen and a matched control canteen were included in the study at baseline (February 2012), after completing the certification process (end-point) and six month from end-point (follow-up) (total n=270). In order to estimate nutrient composition of the consumed lunch meals and plate waste a validated digital photographic method was used combining estimation of food intake with food nutrient composition data. Food satisfaction was rated by participants using a questionnaire. Several significant positive nutritional effects were observed at the intervention canteen including a mean decrease in energy density in the consumed meals from 561kJ/100g at baseline to 368 and 407kJ/100g at end-point and follow-up, respectively (P<0.001). No significant changes were seen with regard to food satisfaction and plate waste. In the control canteen no positive nutritional effects were observed. The results of the study highlight the potential of using healthy labelling certification programs as a possible driver for increasing both the availability and awareness of healthy meal choices, thereby improving dietary intake when eating out.

Bacteremia with Streptococcus pneumoniae: sepsis and other risk factors for 30-day mortality--a hospital-based cohort study.

We conducted a hospital-based cohort study among adult patients with first-time Streptococcus pneumoniae bacteremia (SPB) from 2000 through 2008. Patients were identified in a population-based bacteremia database and followed up for mortality through the Danish Civil Registration System (CRS). The aim of the study was to determine the focal diagnosis of SPB, the severity of sepsis at presentation, demographics and comorbidity characteristics of the patients, and to determine the 30-day mortality rate and factors related to mortality. We identified 481 patients, of which 238 were males. The mean age of the patients was 65 years. The focal diagnosis of the SPB was pneumonia in 381 (79 %) patients, followed in frequency by meningitis in 33 (7 %) patients. Of the 481 patients, 390 (81 %) had community-acquired SPB. Of these, 23 (6 %) did not have sepsis, 132 (34 %) had sepsis, 224 (57 %) had severe sepsis, and 11 (3 %) were in septic shock. Overall, the 30-day mortality was 16 %. Mortality increased with the severity of sepsis. There was no association between the focal diagnosis of SPB or the number of diagnoses and mortality. Nosocomial infection, male sex, increasing age, and increasing comorbidity were all associated with an increased 30-day mortality rate.

Re-prescribing of causative drugs in persons discharged after serious drug-induced upper gastrointestinal bleeding.

BACKGROUND: Several drug classes are known to be associated with serious upper gastrointestinal bleeding (UGIB), among others NSAID, low-dose acetylsalicylic acid (ASA), vitamin K antagonists (VKA), clopidogrel and selective serotonin reuptake inhibitors (SSRIs). There are few data on how and to what extent these drugs are reintroduced in patients who have been discharged after a bleeding episode related to any of them. AIM: To assess if physicians re-prescribed potential causative drugs after an episode of UGIB and to explore whether drugs with antihaemostatic action (DAHA) are re-prescribed without a gastro-protective agent. METHODS: By use of the Kaplan-Meyer method, we estimated the time from UGIB to re-prescribing for 3652 cases who were all admitted to hospital with a diagnosis of serious upper gastrointestinal bleeding from 1995 to 2006. Data on drug exposure were retrieved from a Danish prescription database, a recent study on drug-related UGIB, and The National Board of Health in Denmark. RESULTS: One-year rates of re-prescribing after UGIB were; 82%, 25%, 43%, 68%, 55%, 71% for SSRIs, NSAID, low-dose ASA, VKA, clopidogrel and dipyridamol, respectively. However, re-prescribing rates without proton pump inhibitors (PPIs) were markedly lower 25%, 3%, 5%, 1%, 17% and 6%, respectively. Non-users of DAHA had a prevalence of PPI use of about 30% a few months after an UGIB. CONCLUSIONS: Drugs with antihaemostatic action are re-prescribed to a large extent after an episode of upper gastrointestinal bleeding, but usually covered by PPIs. This use of PPI is specific for users of drugs with antihaemostatic action.

Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder.

1-[2-(2,4-Dimethylphenyl-sulfanyl)-phenyl]-piperazine (Lu AA21004) is a human (h) serotonin (5-HT)(3A) receptor antagonist (K(i) = 3.7 nM), h5-HT(7) receptor antagonist (K(i) = 19 nM), h5-HT(1B) receptor partial agonist (K(i) = 33 nM), h5-HT(1A) receptor agonist (K(i) = 15 nM), and a human 5-HT transporter (SERT) inhibitor (K(i) = 1.6 nM) (J Med Chem 54:3206-3221, 2011). Here, we confirm that Lu AA21004 is a partial h5-HT(1B) receptor agonist [EC(50) = 460 nM, intrinsic activity = 22%] using a whole-cell cAMP-based assay and demonstrate that Lu AA21004 is a rat (r) 5-HT(7) receptor antagonist (K(i) = 200 nM and IC(50) = 2080 nM). In vivo, Lu AA21004 occupies the r5-HT(1B) receptor and rSERT (ED(50) = 3.2 and 0.4 mg/kg, respectively) after subcutaneous administration and is a 5-HT(3) receptor antagonist in the Bezold-Jarisch reflex assay (ED(50) = 0.11 mg/kg s.c.). In rat microdialysis experiments, Lu AA21004 (2.5-10.0 mg/kg s.c.) increased extracellular 5-HT, dopamine, and noradrenaline in the medial prefrontal cortex and ventral hippocampus. Lu AA21004 (5 mg/kg per day for 3 days; minipump subcutaneously), corresponding to 41% rSERT occupancy, significantly increased extracellular 5-HT in the ventral hippocampus. Furthermore, the 5-HT(3) receptor antagonist, ondansetron, potentiated the increase in extracellular levels of 5-HT induced by citalopram. Lu AA21004 has antidepressant- and anxiolytic-like effects in the rat forced swim (Flinders Sensitive Line) and social interaction and conditioned fear tests (minimal effective doses: 7.8, 2.0, and 3.9 mg/kg). In conclusion, Lu AA21004 mediates its pharmacological effects via two pharmacological modalities: SERT inhibition and 5-HT receptor modulation. In vivo, this results in enhanced release of several neurotransmitters and antidepressant- and anxiolytic-like profiles at doses for which targets in addition to the SERT are occupied. The multimodal activity profile of Lu AA21004 is distinct from that of current antidepressants.

There is an association between selective serotonin reuptake inhibitor use and uncomplicated peptic ulcers: a population-based case-control study.

BACKGROUND: Persons who use serotonin reuptake inhibitors (SSRIs) seem to be at increased risk of having serious upper gastrointestinal bleeding. In vitro studies have shown that SSRIs inhibit platelet aggregation. It remains unknown if SSRIs have a direct ulcerogenic effect. AIM: To investigate if there is a possible association between use of SSRIs and uncomplicated peptic ulcers. METHODS: A population-based case-control study was conducted in the county of Funen, Denmark, using local prescription database and patient register. The 4862 cases all had a first diagnosis of uncomplicated peptic ulcers from 1995 to 2009. Controls (n = 19 448), matched for age and gender, were selected by risk-set sampling. RESULTS: The adjusted odds ratios (OR) of uncomplicated peptic ulcers among current, recent and past users of SSRIs were 1.50 (95% CI 1.18-1.90), 1.56 (95% CI 0.98-2.49) and 1.32 (95% CI 1.08-1.61). There was no association with tricyclic antidepressants [OR 0.94 (95% CI 0.65-1.35)]. The adjusted OR for the SSRI-uncomplicated peptic ulcers association was 0.76 (95% CI 0.46-1.25) among users of proton pump inhibitors. CONCLUSIONS: Use of SSRI is associated with uncomplicated peptic ulcers, possibly by some effect on the healing process. We cannot exclude some effects of residual confounding or bias by frequent physician contact.

Comparison of buffet and à la carte serving at worksite canteens on nutrient intake and fruit and vegetable consumption.

OBJECTIVE: To evaluate the nutritional composition of worksite canteen lunches and to examine the impact of two meal serving systems on employee intake, i.e. buffet style with a fixed price for a varied number of dishes and à la carte style with a separate price for each item on the menu. DESIGN: Laboratory technicians observed employees' food selection and collected identical dishes. Food items were weighed separately to calculate the content of fruit and vegetables. The content of protein, fat and ash of each dish was chemically analysed and the carbohydrate and energy content calculated. SETTING: Fifteen randomly chosen worksite canteens in Denmark: eight canteens serving buffet style and seven canteens with an à la carte line. SUBJECTS: one hundred and eighty randomly chosen employees having lunch at the worksite canteens. RESULTS: The average percentage energy from fat was 37 +/- 12 among men and 33 +/- 12 among women. No association was found between the meal serving system and energy intake or macronutrient composition. Eating at canteens serving buffet style, on the other hand, was associated with an increased intake of fruit and vegetables, on average 76 g, and a lower energy density of the food for both genders. CONCLUSION: The results highlight the possibilities of promoting healthy food choices in the catering sector and the need to identify models of healthy catering practice. Serving buffet style appears to be a promising strategy in order to increase fruit and vegetable consumption in food served away from home.