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Antibody-based CD47 blockade aims to activate macrophage phagocytosis of tumor cells. However, macrophages possess a high degree of phenotype heterogeneity that likely influences phagocytic capacity. In murine models, proinflammatory (M1) activation increases macrophage phagocytosis of tumor cells, but in human models, results have been conflicting. Here, we investigated the effects of proinflammatory polarization on the phagocytic response of human monocyte-derived macrophages in an in vitro model. Using both flow cytometry-based and fluorescence live-cell imaging-based phagocytosis assays, we observed that mouse monoclonal anti-CD47 antibody (B6H12) induced monocyte-derived macrophage phagocytosis of cancer cells in vitro. Proinflammatory (M1) macrophage polarization with IFN-γ+LPS resulted in a severe reduction in phagocytic response to CD47 blockade. This reduction coincided with increased expression of the antiphagocytic membrane proteins LILRB1 and Siglec-10 but was not rescued by combination blockade of the corresponding ligands. However, matrix metalloproteinase inhibitors (TAPI-0 or GM6001) partly restored response to CD47 blockade in a dose-dependent manner. In summary, these data suggest that proinflammatory (M1) activation reduces phagocytic response to CD47 blockade in human monocyte-derived macrophages., (© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.)

Background: Preliminary evidence shows promising treatment outcomes at short-term follow-up for intensive posttraumatic stress disorder (PTSD) treatment, but long-term follow-up studies are sparse. This study is a sequel to a previous pilot study and open trial, set out to investigate treatment outcomes at 12-month follow-up for outpatients completing an 8-day intensive treatment for PTSD., Methods: All patients were diagnosed with PTSD and had multiple previous psychotherapy attempts (M = 3.1). Patients were assessed at pre-treatment, post-treatment, 3- and 12-month follow-up. Of 35 treated patients, 32 (91.4%) attended the long-term follow-up assessment. The treatment programme combined prolonged exposure therapy, eye movement desensitization and reprocessing, and physical activity., Results: The effect sizes indicated large reductions in symptoms of PTSD, depression, anxiety, interpersonal problems, and well-being. Changes in functioning showed a small-medium effect. Results were stable across the follow-up period. The treatment response rates showed that 46-60% of patients achieved recovery with respect to PTSD symptoms, and that 44-48% no longer met diagnostic criteria for PTSD., Conclusions: Time-limited and concentrated outpatient treatment for PTSD can yield large and enduring positive outcomes. Controlled trials are needed to establish relative efficacy., Trial Registration: The study was registered in Current Research Information System In Norway (Cristin). Cristin-project-ID: 654,790. Date of registration: 18.03.2019., (© 2024. The Author(s).)

Background: Intensive outpatient treatment could be a promising option for patients with post-traumatic stress disorder (PTSD). Objective: The aim of the study was to test the effectiveness of an eight-day (two-week) intensive treatment for PTSD within a public health care setting (open trial design). Method: Eighty-nine patients were offered the choice between intensive treatment and spaced individual treatment, of which 34 (38.2%) chose the intensive format. Patients were assessed with self-report batteries and interviews at pre-treatment, start of treatment, post-treatment and three-month follow-up. Each day consisted of individual Prolonged Exposure therapy, Eye Movement Desensitization and Reprocessing therapy, group psychoeducation, and physical activity. Therapists rotated between patients. Results: Between 55 and 62% of the patients showed a clinically significant change (recovery) in symptoms of PTSD, and the effect sizes were large ( d  = 1.38-1.52). Patients also showed reduction in symptoms of depression and anxiety, along with improved well-being and interpersonal functioning. Changes in social and work functioning were more ambiguous. There were no dropouts, attendance was high, and patients were highly satisfied with the treatment. Conclusions: The intensive programme was an attractive and effective treatment option for patients with PTSD., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: To summarize the available literature on long-term-development of children exposed to benzodiazepines in utero, through a systematic review., Information Sources: We conducted a systematic literature search of PubMed, PsycINFO and embase (1/9-2020 to 3/9-2020)., Eligibility Criteria: We included original studies with children older than one year prenatally exposed to BZ's and Z-hypnotics with outcomes regarding all psychological-, social-, motor- and neurodevelopmental disorders or disturbances of the children. Studies without a BZ-unexposed comparison group were excluded. Studies with only a single-dose exposure, conference abstracts, case reports and case series were excluded., Risk of Bias: The intern validity of the included studies was assessed with the Newcastle Ottawa Scale tool (NOS)., Included Studies: 13 cohort studies were included in this systematic review., Synthesis of Results: The outcomes investigated were internalizing and externalizing problems, language, hearing and communication skills, neurological outcomes and motor function, behavioral and emotional problems, social skills, intellect and academic achievements, psychiatric diagnoses and overall development. We found some evidence of higher risk of developing internalizing problems, impaired gross motor skills, lower academic achievements and increased ADHD-traits among children exposed to benzodiazepines in utero., Conclusion: Prenatal exposure to benzodiazepines were associated with 4 developmental outcomes indicating an impaired long-term-development of the offspring. However, results were contradicting, and it cannot be ruled out, that findings might be due to bias. Furthermore, it remains uncertain if the results are of clinical relevance and whether developmental problems persist in later childhood. This study revealed a clear need for further research in the subject., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Intensive treatments have shown encouraging results in the treatment of several psychological disorders, including post-traumatic stress disorder (PTSD). However, qualitative studies on patient experiences with intensive treatment for PTSD remain scarce., Objective: The aim of this study was to explore patient experiences with an intensive, outpatient treatment for PTSD and to discover important factors behind treatment feasibility., Method: Eight participants were recruited from two groups of patients having completed the intensive treatment programme. Semi-structured qualitative interviews were conducted, and data sets were analysed using thematic analysis., Results: The main result indicated that patients experienced the treatment as very demanding, but still worth the effort in terms of reducing symptoms. The intensity was valued as useful. Participants emphasized the sense of unity with other participants as well as physical activity as important factors for completion of the treatment programme. The rotation of therapists was also highlighted as important for treatment efficacy., Conclusions: This study provides insights into what the patients experienced and emphasized as important aspects of treatment and essential factors for completing treatment. The main conclusions were that all of the patients evaluated the treatment as demanding, but the reward of reduced symptoms made it worthwhile. The high frequency of therapy sessions and the therapist rotation were reported to counteract avoidance and increase the patients' commitment to therapy. Physical activity and unity in the group were highlighted as essential for treatment feasibility., Highlights: • High treatment intensity enabled increased focus and adherence, and reduced avoidance.  Therapist rotation led to heightened intensity and new learning experiences.• Physical activity and sense of unity through group elements were reported as important factors for treatment feasibility., Competing Interests: No potential conflict of interest was reported by the authors., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: The third dose of diphtheria-tetanus-pertussis vaccine (DTP3) is used to monitor immunization programs. DTP has been associated with higher female mortality., Methods: We updated previous literature searches for DTP studies of mortality by sex. We examined the female/male (F/M) mortality rate ratio (MRR) with increasing number of doses of DTP and for subsequent doses of measles vaccine (MV) after DTP and of DTP after MV., Results: Eight studies had information on both DTP1 and DTP3. The F/M MRR was 1.17 (95% confidence interval [CI], .88-1.57) after DTP1 and increased to 1.66 (95% CI, 1.32-2.09) after DTP3. Following receipt of MV, the F/M MRR declined to 0.63 (95% CI, .42-.96). In 11 studies the F/M MRR increased to 1.73 (95% CI, 1.33-2.27) when DTP-containing vaccine was administered after MV., Conclusions: F/M MRR increased with increasing doses of DTP. After MV, girls had lower mortality than boys. With DTP after MV, mortality increased again for girls relative to boys. No bias can explain these changes in F/M MRR. DTP does not improve male survival substantially in situations with herd immunity to pertussis and higher F/M MRR after DTP may therefore reflects an absolute increase in female mortality., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Goal-directed therapy (GDT) is increasingly used in abdominal surgery. Whether crystalloids can exert the same effect as colloid, and how this may affect perfusion, is still unclear. The effect of GDT on the systemic oxygen delivery index (sDO2I) and the mesenteric oxygen delivery index (mDO2I) can be quantified by measuring cardiac index and flow in the superior mesenteric artery, respectively., Objective: The aim of this study was to test the hypothesis that intra-operative GDT with bolus human albumin 5% is superior to GDT with bolus ringer acetate in maintaining sDO2I and mDO2I in elective major upper gastrointestinal cancer surgery., Design: Randomised controlled double blinded trial., Setting: Odense University Hospital, Denmark, from May 2014 to June 2015., Patients: A total of 89 adults scheduled for elective major upper gastrointestinal cancer surgery were randomised and data from 60 were analysed., Exclusion Criteria: contraindications for using the LiDCOplus system, known allergy to albumin, pre-operative renal failure, pancreatic cancer and pre-operative down staging using chemotherapy and/or radiation therapy, pregnancy., Interventions: Patients were randomised to intra-operative GDT with either bolus human albumin or ringer acetate 250 ml, guided by pulse pressure variation and stroke volume., Main Outcome Measures: Changes in sDO2I and mDO2I. Secondary outcomes were changes in other haemodynamic variables, fluid balance, blood transfusions, fluid-related complications and length of stay (LOS) in ICU and hospital., Results: Median [IQR] sDO2I was 522 [420 to 665] ml min m in the ringer acetate group and 490 [363 to 676] ml min m in the human albumin group, P = 0.36. Median [IQR] mDO2I was 12.1 [5.8 to 28.7] ml min m in the ringer acetate group and 17.0 [7.6 to 27.5] ml min m in the human albumin group, P = 0.17. Other haemodynamic comparisons did not differ significantly. More trial fluid was administered in the ringer acetate group. We found no significant difference in transfusions, complications or LOS., Conclusion: Bolus human albumin 5% was not superior to bolus ringer acetate in maintaining systemic or mesenteric oxygen delivery in elective major upper gastrointestinal cancer surgery, despite the administration of larger volumes of trial fluid in the ringer acetate group. No significant difference was seen in fluid-related complications or LOS., Trial Registration: https://eudract.ema.europa.eu/ Identifier: 2013-002217-36.

Introduction: Intravenous lidocaine has been shown to have analgesic effects leading to a reduced post-operative opiate need, but this effect is still debated in various surgical populations. We investigated whether this effect could be demonstrated in robot-assisted colorectal surgery., Methods: A total of 60 adult patients undergoing robot-assisted colorectal surgery were randomly assigned to two groups in this prospective, double-blinded trial. The lidocaine group was treated with intravenous lidocaine. Treatment was initiated before induction of anaesthesia with a bolus of 1.5 mg/kg and immediately followed by infusion of 1.5 mg/kg/h continued until 2 h after end of surgery. The control group received placebo treatment with an equal volume and a dosing of 0.9% saline. The follow-up period was 72 h., Results: No significant difference between groups in the median cumulated morphine consumption at 24 and 72 h was observed. Nor were there any differences in pain score, use of antiemetics, time until flatus and/or defecation or length of hospital stay., Conclusions: In this randomised, double-blinded, prospective study using intravenous lidocaine versus 0.9% saline in robot-assisted colorectal surgery, we found no significant difference in post-operative cumulated morphine consumption at 24 or at 72 h., Funding: The study received funding from DASAIMs Forskningsinitiativ (2016) and DASAIMs Smerteforskningspris (2016)., Trial Registration: The trial is registered with EudraCT (2014-003466-25) and ClinicalTrials.gov (ID: NCT03044808)., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are ligand-gated ion channels that mediate the majority of fast excitatory neurotransmission in the central nervous system. Despite recent advances in structural studies of AMPARs, information about the specific conformational changes that underlie receptor function is lacking. Here, we used single and dual insertion of GFP variants at various positions in AMPAR subunits to enable measurements of conformational changes using fluorescence resonance energy transfer (FRET) in live cells. We produced dual CFP/YFP-tagged GluA2 subunit constructs that had normal activity and displayed intrareceptor FRET. We used fluorescence lifetime imaging microscopy (FLIM) in live HEK293 cells to determine distinct steady-state FRET efficiencies in the presence of different ligands, suggesting a dynamic picture of the resting state. Patch-clamp fluorometry of the double- and single-insert constructs showed that both the intracellular C-terminal domain (CTD) and the loop region between the M1 and M2 helices move during activation and the CTD is detached from the membrane. Our time-resolved measurements revealed unexpectedly complex fluorescence changes within these intracellular domains, providing clues as to how posttranslational modifications and receptor function interact.

Objectives: An association between infection and arterial thromboembolic events (ATE) has been suggested. Here we examined the risk of myocardial infarction (MI), stroke and other ATE after Staphylococcus aureus bacteremia (SAB)., Methods: Danish register-based nation-wide observational cohort study between 1995 and 2008 with matched control subjects from the general population., Results: Within a year, 278 of 15,669 SAB patients and 2570 of 156,690 controls developed MI, stroke or another ATE. The incidence rates among SAB patients were highest within the first 30 days and decreased over a year. The adjusted relative risk of MI, stroke and other ATE during the first 30 days after SAB in patients compared to controls were 2.2 (95% CI: 1.6-3.1), 5.5 (95% CI: 3.8-8.3) and 15.5 (95% CI: 6.9-35), respectively. Compared to controls, the increased adjusted relative risk persisted for 30 days for MI, 180 days for stroke and one year for other ATE. Increasing age, hypertension, atrial flutter/fibrillation, prior ATE and endocarditis in SAB patients were associated with an increased risk of ATE., Conclusions: SAB was associated with a short-term increased risk of ATE that persisted longer dependent on type of event. Studies are warranted to investigate treatment strategies to diminish ATE after SAB., (Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Polyamine toxins from spiders and wasps are potent open-channel blockers of ionotropic glutamate (iGlu) receptors. It is well-established that secondary amino groups in the polyamine moiety of these toxins are key to both selectivity and potency at iGlu receptors, still some native spider polyamine toxins comprise both N-methyl and N-hydroxy functionalities. Here, we investigate the effect of both N-methylation and N-hydroxylation of spider polyamine toxins by the synthesis and biological evaluation of the naturally occurring N-methylated argiopinines and pseudoargiopinines I and II, N-hydroxylated Agel-489 and Agel-505, as well as N-methylated analogues of the NMDA and AMPA iGlu receptor subtype selective antagonists ArgTX-93 and ArgTX-48. Efficient synthetic strategies for the synthesis of target compounds were developed, and evaluation of biological activity at AMPA and NMDA receptors identified highly potent and in some cases very selective ligands.

Objectives: Recent evidence suggests that there is an association between infection and venous thromboembolism (VTE). Here, we examined the risk of VTE after Staphylococcus aureus bacteraemia (SAB) compared to the risk in control subjects., Design and Setting: Register-based nationwide observational cohort study of hospitalized patients and matched control subjects from the general population in Denmark between 1995 and 2008., Results: Amongst 15 669 SAB cases and 156 690 controls, 182 and 511, respectively, experienced VTE within 1 year. The overall incidence rate (IR) of VTE amongst cases was highest within the first 30 days [IR of deep vein thrombosis (DVT), 39.3 (95% confidence interval (CI) 28.9-53.4)/1000 person-years (PYs); IR of pulmonary embolism (PE), 16.3 (95% CI 10.1-26.2)/1000 PYs]. IRs of DVT were particularly increased amongst cases with a previous diagnosis of VTE, community-acquired infection, a history of injection drug use and in younger age groups. The overall hazard ratio of VTE for cases compared to controls declined from 15.6 (95% CI 10.3-23.5) in the first 30 days after SAB to 4.5 (95% CI 3.2-6.2) from 181 to 365 days after infection. The increased risk of VTE amongst SAB patients persisted after excluding cases with identified VTE risk factors., Conclusions: There was a particularly high risk of VTE during the first month following an episode of SAB. The risk declined over time, but remained at a threefold increased level compared to control subjects, suggesting that there are shared risk factors for SAB and VTE. Patients with SAB and well-documented risk factors for VTE may benefit from thromboprophylaxis., (© 2013 The Association for the Publication of the Journal of Internal Medicine.)

Background: To investigate the correlation between CYP3A4/5 activity and clarithromycin metabolism, and between CYP3A activity and CYP3A genotype., Methods: This is an open-label, prospective pharmacokinetic study evaluating CYP3A activity using The Erythromycin Breath Test. Eight blood samples were collected within 12h after clarithromycin 500 mg was administered orally. The clarithromycin concentrations were measured by liquid chromatography-tandem mass spectrometry. AUC, Tmax and Cmax were calculated. Selected Single Nucleotide polymorphisms in CYP3A4/5 genes were assessed by PCR and single base extension., Results: Twenty-one chronically infected patients were included. An 8-fold variation in the CYP3A4 activity, 10-fold variation in AUC for clarithromycin (median 881 μg/mL × min), and a 16-fold variation in Cmax for clarithromycin (median 3.4 μg/mL) were found. A linear correlation between the CYP3A4-activity and clarithromycin metabolism was demonstrated (P < 0.05)., Conclusion: The large variation in the clarithromycin pharmacokinetics in cystic fibrosis patients may cause treatment failure. The Erythromycin Breath Test could be valuable in identifying cystic fibrosis patients in risk of treatment failure/drug toxicity., (© 2013.)

Background: Data on risk factors and rates of reinfection associated with Staphylococcus aureus bacteraemia (SAB) are sparse., Methods: We conducted a nationwide cohort study of cases of SAB diagnosed between 1995 and 2008. Reinfection was defined as an episode of SAB more than 90 days after the initial episode of SAB. Comorbidity was evaluated by the Charlson Comorbidity Index (CCI). Cox proportional hazards modelling was used to estimate hazard rates (HR)., Results: Of 10,891 eligible patients, 774 (7.1%) experienced reinfection a median of 458 days (range 90-5021 days) after their primary SAB episode corresponding to a reinfection rate of 1459 (95% confidence interval (CI): 1357-1562) per 100,000 personyears. In multivariate analysis, sex, origin, a vascular or peritoneal device, endocarditis and comorbidity were associated with reinfection. The association was more than two-fold higher among patients in dialysis and for patients with severe comorbidity (CCI ≥ 2). HIV infection (Hazard ratio (HR) 6.18, 95% CI: 4.17-9.16), renal disease (HR 3.92, 95% CI: 3.22-4.78), diabetes with complications (HR 2.11, 95% CI: 1.69-2.62), diabetes without complications (HR 1.61, 95% CI: 1.34-1.93), mild (HR: 1.94, 95% CI: 1.36-2.76) and severe liver disease (HR 2.08, 95% CI: 1.08-4.03), peptic ulcer (HR 1.33, 95% CI: 1.03-1.72), and paraplegia (HR 2.15, 95% CI: 1.02-4.54) were each associated with an increased risk of reinfection., Conclusions: Patients with previous SAB have a 60-fold higher risk of SAB compared to the general population. Patients with HIV infection, renal disease, diabetes, liver disease, peptic ulcer and paraplegia had the highest rates of reinfection., (Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: The treatment of peptic ulcer bleeding (PUB) is complex, and mortality remains high. We present results from a nationwide initiative to monitor and improve the quality of care (QOC) in PUB., Methods: All Danish hospitals treating PUB patients between 2004 and 2011 prospectively registered demographic, clinical, and prognostic data. QOC was evaluated using eight process and outcome indicators, including time to initial endoscopy, hemostasis obtainment, proportion undergoing surgery, rebleeding risks, and 30-day mortality., Results: A total of 13,498 PUB patients (median age 74 years) were included, of which one-quarter were in-hospital bleeders. Preadmission use of anticoagulants, multiple coexisting diseases, and the American Society of Anesthesiologists scores increased between 2004 and 2011. Considerable improvements were observed for most QOC indicators over time. Endoscopic treatment was successful with primary hemostasis achieved in more patients (94% in 2010-2011 vs. 89% in 2004-2006, relative risk (RR) 1.06 (95% confidence intervals 1.04-1.08)), endoscopy delay for hemodynamically unstable patients decreased during this period (43% vs. 34% had endoscopy within 6 h, RR 1.33 (1.10-1.61)), and fewer patients underwent open surgery (4% vs. 6%, RR 0.72 (0.59-0.87)). After controlling for time changes in prognostic factors, rebleeding rates improved (13% vs. 18%, adjusted RR 0.77 (0.66-0.91)). Crude 30-day mortality was unchanged (11% vs. 11%), whereas adjusted mortality decreased nonsignificantly over time (adjusted RR 0.89 (0.78-1.00))., Conclusions: QOC in PUB has improved substantially in Denmark, but the 30-day mortality remains high. Future initiatives to improve outcomes may include earlier endoscopy, having fully trained endoscopists on call, and increased focus on managing coexisting disease.

Background: Magnetic resonance imaging (MRI) of children is generally performed under sedation or with general anaesthesia (GA), but the ideal regimen has not been found. The aim of this study was to see if propofol-remifentanil would be a suitable alternative for the maintenance of anaesthesia in this category of patients., Patients and Methods: Children aged 1-10 years, American Society of Anesthesiologists physical status 1-2 were included. After induction with thiopental or sevoflurane, the children were randomised to maintenance of anaesthesia with an infusion of propofol and remifentanil (group PR) (56 μg/kg/min of propofol and 0.06 μg/kg/min of remifentanil) or with sevoflurane 1.3 MAC (group S). A binasal catheter was placed in group PR and a laryngeal mask airway in group S. The children breathed spontaneously. The Paediatric Anaesthesia Emergence Delirium (PAED) score (primary end point), the number of movements during MRI, and the length of stay in the recovery room (secondary endpoints) were recorded., Results: Sixty children were included in each group. A lower level of emergence delirium (measured as a lower PAED score) was found in group PR compared with group S, and the children in group PR were discharged earlier from the recovery room than the children in group S. However, 15 children in group PR vs. 0 in group S moved during the scan (P < 0.001)., Conclusion: The PR infusion ensured a satisfactory stay in the recovery room, but additional boluses were necessary during the MRI. Sevoflurane was reliable during the MRI, but emergence delirium was a concern., (© 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Drosophila embryonic dorsal vessel (DV) morphogenesis is a highly stereotyped process that involves the migration and morphogenesis of 52 pairs of cardioblasts (CBs) in order to form a linear tube. This process requires spatiotemporally-regulated localization of signaling and adhesive proteins in order to coordinate the formation of a central lumen while maintaining simultaneous adhesion between CBs. Previous studies have shown that the Slit/Roundabout and Netrin/Unc5 repulsive signaling pathways facilitate site-specific loss of adhesion between contralateral CBs in order to form a luminal space. However, the concomitant mechanism by which attraction initiates CB outgrowth and discrete localization of adhesive proteins remains poorly understood. Here we provide genetic evidence that Netrin signals through DCC (Deleted in Colorectal Carcinoma)/UNC-40/Frazzled (Fra) to mediate CB outgrowth and attachment and that this function occurs prior to and independently of Netrin/UNC-5 signaling. fra mRNA is expressed in the CBs prior to and during DV morphogenesis. Loss-of-fra-function results in significant defects in cell shape and alignment between contralateral CB rows. In addition, CB outgrowth and attachment is impaired in both fra loss- and gain-of-function mutants. Deletion of both Netrin genes (NetA and NetB) results in CB attachment phenotypes similar to fra mutants. Similar defects are also seen when both fra and unc5 are deleted. Finally we show that Fra accumulates at dorsal and ventral leading edges of paired CBs, and this localization is dependent upon Netrin. We propose that while repulsive guidance mechanisms contribute to lumen formation by preventing luminal domains from coming together, site-specific Netrin/Frazzled signaling mediates CB attachment., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Mortality and morbidity are considerable after treatment for perforated peptic ulcer (PPU). Since 2003, a Danish nationwide quality-of-care (QOC) improvement initiative has focused on reducing preoperative delay, and improving perioperative monitoring and care for patients with PPU. The present study reports the results of this initiative., Methods: This was a nationwide cohort study based on prospectively collected data, involving all hospitals caring for patients with PPU in Denmark. Details of patients treated surgically for PPU between September 2004 and August 2011 were reported to the Danish Clinical Register of Emergency Surgery. Changes in baseline patient characteristics and in seven QOC indicators are presented, including relative risks (RRs) for achievement of the indicators., Results: The study included 2989 patients. An increasing number fulfilled the following four QOC indicators in 2010-2011 compared with the first 2 years of monitoring: preoperative delay no more than 6 h (59·0 versus 54·0 per cent; P = 0·030), daily monitoring of bodyweight (48·0 versus 29·0 per cent; P < 0·001), daily monitoring of fluid balance (79·0 versus 74·0 per cent; P = 0·010) and daily monitoring of vital signs (80·0 versus 68·0 per cent; P < 0·001). A lower proportion of patients had discontinuation of routine prophylactic antibiotics (82·0 versus 90·0 per cent; P < 0·001). Adjusted 30-day mortality decreased non-significantly from 2005-2006 to 2010-2011 (adjusted RR 0·87, 95 per cent confidence interval 0·76 to 1·00), whereas the rate of reoperative surgery remained unchanged (adjusted RR 0·98, 0·78 to 1·23)., Conclusion: This nationwide quality improvement initiative was associated with reduced preoperative delay and improved perioperative monitoring in patients with PPU. A non-significant improvement was seen in 30-day mortality., (Copyright © 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Objective: Validation of a salutogenic theory for return to work (RTW) and an associated program process theory., Methods: A longitudinal non-randomized one-year trial study design was used with a two-year follow-up and with comparison to a reference group. Changes in attitudes and active behaviour in the intervention group and at the workplace were supported by cognitive and behavioural approaches., Participants: The intervention group included 118 unskilled Danish public employees and privately employed house-cleaners on sick leave due to musculoskeletal and/or common mental illnesses., Results: Significant improvements of work ability index and perceived health (SF36 subgroups) were reported. A significantly higher RTW and a shorter sick leave than in the reference group also emerged. Positive predictors of RTW were keeping the pre-sick-leave job and improving work ability index and physical impairment/role physical. Decline in self-efficacy was a negative predictor., Conclusions: Support for the theory and associated program process theory was found. The intervention seemed to influence RTW and the employees' attitudes, behaviour and health by affecting comprehensibility, meaningfulness and manageability. Sustainable RTW emerged from a synergism of support from the work place and improved personal resources, especially such as concern mental health. The approach is consistent with integrating health promotion in RTW.

Objective: Presentation of a salutogenic theory of return to work (RTW)., Participants: The study group include 118 unskilled Danish public employees and privately employed house-cleaners on sick leave due to musculoskeletal and/or common mental illnesses., Methods: Theory of RTW is discussed from a theoretical and empirical viewpoint, using baseline-data from an intervention study in a longitudinal, non-randomized study design with follow-up after one year., Results: High work ability, strong social support from colleagues and over-commitment are the most important prognostic factors for RTW. An active coping style, high self-efficacy and Sense of Coherence (SOC) are found to increase RTW and high hostility and over-commitment to decrease RTW. Besides health elements in work ability are SOC, self-efficacy, social support and physical activity. Work ability and active coping mediate positive associations between RTW and health, and a negative association with stress., Conclusions: Work ability seems to express the intention to work decisive for RTW, reflecting the interpretation of the work/health situation based on comprehensibility, meaningfulness and manageability. It is influenced by the personal view of life, attitudes and interaction with the workplace. An ecological theory, integrating health promotion is proposed. A later paper will present the intervention study and further validation of the theory.

Background: The objective of this study was to assess temporal changes in incidence and short term mortality of Staphylococcus aureus bacteraemia (SAB) from 1995 through 2008., Methods: The study was conducted as a nation-wide observational cohort study with matched population controls. The setting was hospitalized patients in Denmark 1995-2008. Uni- and multivariate analyses were used to analyze the hazard of death within 30 days from SAB., Results: A total of 16 330 cases of SAB were identified: 57% were hospital-associated (HA), 31% were community-acquired (CA) and 13% were of undetermined acquisition. The overall adjusted incidence rate remained stable at 23 per 100 000 population but the proportion of SAB cases older than 75 years increased significantly. Comorbidity in the cohort as measured by Charlson comorbidity index (CCI) score and alcohol-related diagnoses increased over the study period. In contrast, among the population controls the CCI remained stable and alcohol-related diagnoses increased slightly. For HA SAB crude 30-day mortality decreased from 27.8% to 21.8% (22% reduction) whereas the change for CA SAB was small (26.5% to 25.8%). By multivariate Cox regression, age, female sex, time period, CCI score and alcohol-related diagnoses were associated with increased mortality regardless of mode of acquisition., Conclusions: Throughout a 14-year period the overall incidence of SAB remained stable while the overall short term prognosis continued to improve despite increased age and accumulation of comorbidity in the cohort. However, age and comorbidity were strong prognostic indicators for short term mortality.

Due to a low cardiovascular complication rate even in patients with shock, etomidate is often used for intubation. Etomidate inhibits the steroid synthesis. A single bolus injection of etomidate has so far been considered to be safe. However, new investigations have shown that even a single bolus dose of etomidate inhibits the steroid synthesis and is associated with increased mortality in patients with septic shock.

AUF1 is an AU-rich element (ARE)-binding protein that recruits translation initiation factors, molecular chaperones, and mRNA degradation enzymes to the ARE for mRNA destruction. We recently found chaperone Hsp27 to be an AUF1-associated ARE-binding protein required for tumor necrosis factor alpha (TNF-α) mRNA degradation in monocytes. Hsp27 is a multifunctional protein that participates in ubiquitination of proteins for their degradation by proteasomes. A variety of extracellular stimuli promote Hsp27 phosphorylation on three serine residues--Ser(15), Ser(78), and Ser(82)-by a number of kinases, including the mitogen-activated protein (MAP) pathway kinases p38 and MK2. Activating either kinase stabilizes ARE mRNAs. Likewise, ectopic expression of phosphomimetic mutant forms of Hsp27 stabilizes reporter ARE mRNAs. Here, we continued to examine the contributions of Hsp27 to mRNA degradation. As AUF1 is ubiquitinated and degraded by proteasomes, we addressed the hypothesis that Hsp27 phosphorylation controls AUF1 levels to modulate ARE mRNA degradation. Indeed, selected phosphomimetic mutants of Hsp27 promote proteolysis of AUF1 in a proteasome-dependent fashion and render ARE mRNAs more stable. Our results suggest that the p38 MAP kinase (MAPK)-MK2-Hsp27 signaling axis may target AUF1 destruction by proteasomes, thereby promoting ARE mRNA stabilization.

Emergency patients need special considerations and the number and severity of complications from general anaesthesia can be higher than during scheduled procedures. Guidelines are therefore needed. The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine appointed a working group to develop guidelines based on literature searches to assess evidence, and a consensus meeting was held. Consensus opinion was used in the many topics where high-grade evidence was unavailable. The recommendations include the following: anaesthesia for emergency patients should be given by, or under very close supervision by, experienced anaesthesiologists. Problems with the airway and the circulation must be anticipated. The risk of aspiration must be judged for each patient. Pre-operative gastric emptying is rarely indicated. For pre-oxygenation, either tidal volume breathing for 3 min or eight deep breaths over 60 s and oxygen flow 10 l/min should be used. Pre-oxygenation in the obese patients should be performed in the head-up position. The use of cricoid pressure is not considered mandatory, but can be used on individual judgement. The hypnotic drug has a minor influence on intubation conditions, and should be chosen on other grounds. Ketamine should be considered in haemodynamically compromised patients. Opioids may be used to reduce the stress response following intubation. For optimal intubation conditions, succinylcholine 1-1.5 mg/kg is preferred. Outside the operation room, rapid sequence intubation is also considered the safest method. For all patients, precautions to avoid aspiration and other complications must also be considered at the end of anaesthesia.

Objective: The overall mortality for patients undergoing surgery for perforated peptic ulcer has increased despite improvements in perioperative monitoring and treatment. The objective of this study was to identify and describe perioperative risk factors in order to identify ways of optimizing the treatment and to improve the outcome of patients with perforated peptic ulcer., Material and Methods: Three hundred and ninety-eight patients undergoing emergency surgery in four university hospitals in Denmark were included in the study. Information regarding the pre-, intra- and postoperative phases were recorded retrospectively from medical records. Data were analysed using multiple logistic regression analysis. The primary end-point was 30-day mortality., Results: The 30-day mortality rate was 27%. The following variables were independently associated with death within 30 days of surgery: ASA (American Society of Anaesthesiologists) class, age, shock upon admission, preoperative metabolic acidosis, elevated concentration of creatinine upon admission, subnormal concentration of albumin upon admission and insufficient postoperative nutrition., Conclusions: Thus, preoperative metabolic acidosis, renal insufficiency upon admission and insufficient postoperative nutrition have been added to the list of independent risk factors for death within 30 days of surgery in patients with peptic ulcer perforation. Finding that shock upon admission, reduced albumin blood levels upon admission, renal insufficiency upon admission and preoperative metabolic acidosis are independently related to 30-day mortality could indicate that patients with peptic ulcer perforation are septic upon admission, and thus might benefit from a perioperative care protocol with early source control and early goal-directed therapy according to The Surviving Sepsis Campaign. This hypothesis should be addressed in future studies.

Background: Staphylococcus aureus is known to be a leading cause of bacteremia in childhood, and is associated with severe morbidity and increased mortality. To determine developments in incidence and mortality rates, as well as risk factors associated with outcome, we analyzed data from 1971 through 2000., Methods: Nationwide registration of S. aureus bacteremia (SAB) among children and adolescents from birth to 20 years of age was performed. Data on age, sex, source of bacteremia, comorbidity and outcome were extracted from discharge records. Rates were population adjusted and risk factors for death were assessed by multivariate logistic regression analysis., Results: During the 30-year study period, 2648 cases of SAB were reported. Incidence increased from 4.6 to 8.4 cases per 100,000 population and case-mortality rates decreased from 19.6% to 2.5% (P = 0.0001). Incidence in the infant age group (<1 year) were 10- to 17-fold greater compared with that in the other age strata and mortality rate was twice as high. Hospital-acquired infections dominated the infant group, accounting for 73.9%-91.0% versus 39.2%-50.5% in the other age groups. By multivariate analysis, pulmonary infection and endocarditis for all age groups, comorbidity for the older than 1 year, and hospital-acquired infections for the oldest group were independently associated with an increased risk of death., Conclusions: Mortality rates associated with SAB decreased significantly in the past 3 decades, possibly because of new and improved treatment modalities. However, incidence rates have increased significantly in the same period, underscoring that S. aureus remains an important invasive pathogen.

Most soluble lysosomal proteins carry Man6P (mannose 6-phosphate), a specific carbohydrate marker that enables their binding to cellular MPRs (Man6P receptors) and their subsequent targeting towards the lysosome. This characteristic was exploited to identify novel soluble lysosomal proteins by proteomic analysis of Man6P proteins purified from a human cell line. Among the proteins identified during the course of the latter study [Journet, Chapel, Kieffer, Roux and Garin (2002) Proteomics, 2, 1026-1040], some had not been previously described as lysosomal proteins. We focused on a protein detected at 76 kDa by SDS/PAGE. We named this protein 'p76' and it appeared later in the NCBI protein database as the 'hypothetical protein LOC196463'. In the present paper, we describe the identification of p76 by MS and we analyse several of its biochemical characteristics. The presence of Man6P sugars was confirmed by an MPR overlay experiment, which showed the direct and Man6P-dependent interaction between p76 and the MPR. The presence of six N-glycosylation sites was validated by progressive peptide-N-glycosidase F deglycosylation. Experiments using N- and C-termini directed anti-p76 antibodies provided insights into p76 maturation. Most importantly, we were able to demonstrate the lysosomal localization of this protein, which was initially suggested by its Man6P tags, by both immunofluorescence and sub-cellular fractionation of mouse liver homogenates.

Staphylococcus aureus is a leading cause of bacteraemia. This study analysed temporal trends from 18,702 adult cases of S. aureus bacteraemia in Denmark between 1981 and 2000. After stratification for mode of acquisition, 57% of cases were hospital-acquired (HA), 28% were community-acquired (CA) and 15% were of undetermined acquisition (UA). Incidence rates increased from 18.2 to 30.5 cases/100,000 population. Annual rates increased by 6.4% for CA, by 2.2% for HA and by 3.6% for UA cases, respectively. Case-mortality associated with HA bacteraemia decreased from 36.2% to 20.7% (43% rate reduction, p 0.0001), compared with a decrease from 34.5% to 26.5% (23% rate reduction, p 0.0001) for CA bacteraemia. Following multivariate analysis, age, pneumonia, endocarditis and chronic illness were associated with increased mortality, regardless of the mode of acquisition. Overall, mortality associated with S. aureus bacteraemia declined significantly between 1981 and 2000, but incidence rates doubled, so that the total number of deaths increased. These data emphasise the public health importance of S. aureus bacteraemia and the need for further preventive measures and improved care in order to reduce incidence rates and improve outcomes.

Background: Haematogenous Staphylococcus aureus meningitis is rare but associated with high mortality. Knowledge about the disease is still limited. The objective of this study was to evaluate demographic and clinical prognostic features of bacteraemic S. aureus meningitis., Methods: Nationwide surveillance in Denmark from 1991 to 2000 with clinical and bacteriological data. Risks of death were estimated by Cox proportional hazards regression analysis., Results: Among 12480 cases of S. aureus bacteraemia/sepsis, we identified 96 cases of non-surgical bacteraemic S. aureus meningitis (0.8%). Incidence rates were 0.24 (95% confidence interval [CI], 0.18 to 0.30)/100,000 population between 1991-1995 and 0.13 (CI, 0.08 to 0.17)/100,000 population between 1996-2000. Mortality was 56%. After adjustment, only co morbidity (hazard ratio [HR], 3.45; CI, 1.15 to 10.30) and critical illness (Pitt score > or = 4) (HR, 2.14; CI, 1.09 to 4.19) remained independent predictors of mortality., Conclusion: The incidence, but not mortality of bacteraemic S. aureus meningitis decreased during the study period. Co morbidity and critical illness were independent predictors of a poor outcome.

Staphylococcus aureus bacteremia (SAB) is still associated with a high mortality, and knowledge on risk factors and the clinical and the therapeutic aspects of SAB is still limited. This thesis focuses on the clinical aspects of SAB and its metastatic infections. In a study of all patients with bacteremia in Copenhagen County October 1992 through April 1993 (study I) we emphasized previous findings, that S. aureus is one of the most frequent pathogens in bacteremia, and in a case control study also in Copenhagen County 1994-95 (study II) we demonstrated, that not only an inserted central venous catheter and nasal S. aureus carriage but also hyponatremia and anemia are important risk factors for hospital-acquired SAB (study II). Studies on the treatment of SAB have pointed out, that the eradication of a primary is important, but there are only limited clinical studies dealing with antibiotic treatment. By logistic regression analysis, we were able to demonstrate that focus eradication is essential, but also that treatment with dicloxacillin 1 g x 4 or 2 g x 3 are superior to 1 g x 3 (studie III), indicating that the time for serum concentration above the Minimal Inhibitory Concentration (MIC) for the bacteria plays a role in the outcome of SAB treatment. S. aureus osteomyelitis secondary to SAB is frequently observed. No other countries, however, have a centralized registration, which make it possible to evaluate a large number of these patients. Since 1960, The Staphylococcal Laboratory, Statens Serum Institut in Copenhagen, has registrated selected clinical informations from nearly all patients with positive blood cultures of S. aureus. Based on this registration, we were able to show an increased number of S. aureus osteomyelitis among older patients and a decreased number of S. aureus osteomyelitis of femur and tibia among younger infants in the period 1980-90 (study IV). By reviewing the records of a large number of patients with vertebral S. aureus osteomyelitis, we could evaluate important aspects in the diagnosis and treatment of these patients (study V). We illustrated, that symptoms and laboratory findings were relatively unspecific, and CT-scanning or bone scintigraphy were absolutely necessary for the diagnosis (study V). The relatively high number of patients in the study allowed us to evaluate different treatment regimens, and we found, that treatment with penicillinase-stable penicillins four grams daily for at least eight weeks was necessary (study V). S. aureus meningitis is relatively uncommon and most often a neurosurgical infection based on the presence of a catheter. Meningitis secondary to SAB is relatively rare. The nationwide registration on Statens Serum Institut enabled us to study a large number of patients with special emphasis on clinical, outcome and treatment (study VI). We found, that these patients often were older people with chronic underlying diseases, the infection developed as a community-acquired infection, and the patients also had an unknown focus of infection. Furthermore, these patients often had other secondary manifestations such as endocarditis or osteomyelitis and an extremely high mortality (study VI). Finally, I believe that our studies will contribute to reduce the incidence of SAB and improve the diagnosis and treatment of SAB in the future.

Staphylococcus aureus bacteraemia increases in frequency, and it is still a life-threatening disease. In recent years, some interesting studies such as the need for focus identification and the focus eradication have been performed. The aim of this review is to present an up-to-date assessment of the current challenges in the management of S. aureus bacteraemia in order to improve the outcome.

Background: Staphylococcus aureus bacteremia is still a serious problem, and the optimal treatment is under debate. Only a few studies concerning treatment are available., Methods: The study population was all patients with a positive blood culture result for S aureus in Copenhagen County, Denmark, from May 1994 through April 1996. Of 278 patients with S aureus bacteremia, 186 were evaluated according to outcome in a prospective, observational follow-up study. The time above the minimum inhibitory concentration was estimated for dicloxacillin sodium for each treatment regimen and evaluated by logistic regression along with other potential risk factors., Results: The following variables were statistically associated with death: the presence of an uneradicated focus (odds ratio [OR], 6.7; 95% confidence interval [CI], 2.1-21.0); the presence of septic shock (OR, 3.7; 95% CI, 1.5-9.1); the total daily dose of penicillinase-stable penicillin less than 4 g (OR, 3.7; 95% CI, 1.3-11.1); and age 60 years or older (OR, 2.4; 95% CI, 1.1-5.3). The following variables were significantly associated with recurrence: the total daily dose of penicillinase-stable penicillin less than 3 g (OR, 3.9; 95% CI, 1.6-10.0) and the presence of a secondary focus (OR, 3.2; 95% CI, 1.3-7.7). Among 155 patients with observation time longer than duration of treatment, this factor (duration of treatment, <14 days) was significantly related to mortality (OR, 0.84; 95% CI, 0.76-0.94)., Conclusions: Focus eradication and the dosing of penicillinase-stable penicillin are important to the outcome of S aureus bacteremia. We recommend treatment with at least 1 g of penicillinase-stable penicillins 4 times daily for longer than 14 days.

In order to evaluate the composition of active constituents in phytopharmaceutical preparations, valid analytical methods are required. For the determination of the active terpene constituents of Ginkgo biloba (the ginkgolides and bilobalide), a liquid chromatography-mass spectrometry (LC-MS) method has been developed using atmospheric pressure chemical ionisation (APCI) in the negative ion mode. This detection mode was found to be much more sensitive and selective compared to UV; indeed the ginkgo terpene trilactones lack strong UV chromophores and flavonoids interfere with their UV detection. LC-APCI/MS detection allowed a considerable reduction in analysis time when compared to LC-UV, because LC resolution was only needed between the pair of isomers ginkgolide B and ginkgolide J. All compounds were selectively detected by single ion monitoring of their specific deprotonated molecules [M-H]-. The samples were directly injected without pre-purification, and a fast gradient was applied, reducing the total time of analysis to 14 min. With this method, the ginkgo terpene trilactones were detected on-line in the picogram range. Several commercial ginkgo preparations on the Swiss market were analysed, and the ginkgolide and bilobalide contents were evaluated using the method described.

The separation of the lipophilic compounds in extracts of Hypericum perforatum L. is demonstrated in a non-aqueous capillary electrophoresis system with reversed electro-osmotic flow. Solvent mixtures of methanol, dimethylsulfoxide and N-methylformamide were used for the electrophoresis media, with addition of ammonium acetate and sodium acetate as electrolytes. The flow was reversed by the addition of the polycation hexadimethrine bromide, and thus negative voltage was applied. The method shows baseline separation between the four hypericins-protopseudohypericin, pseudohypericin, protohypericin and hypericin-whereas total baseline separation between the two hyperforins-hyperforin and adhyperforin-was not achieved. Using a fused-silica capillary (30 cm x 25 microm ID) and a voltage of -25 kV the analysis time of the hypericins and hyperforins was obtainable within 3 min. Application of the method with a fused-silica capillary of a larger internal diameter (48.5 cm x 50 microm ID) and a voltage of -20 kV resulted in analysis times of 8 min, but also lower limits of detection. The maximal attainable voltage was applied in both cases. Simultaneous separation of the flavonoids-although less efficient-may also be achieved. The technique of non-aqueous capillary electrophoresis with reversed electro-osmotic flow provides a very fast technique to evaluate the composition of hypericins and hyperforins in extracts of Hypericum perforatum L.

Objective: To study the possibility of reporting results of identification and susceptibility testing of Gram-negative bacilli the same day as bacteremia is detected by using direct inoculation from positive blood cultures (Bactec 9240) into VITEK GNI+ and GNS-GA cards., Methods: All blood cultures with Gram-negative enteric bacillus-like morphology on microscopy found to be positive on workdays between 15 June 1999 and 29 February 2000 were included. Identification and susceptibility testing were done by three methods: the direct method using a suspension made by differential centrifugation of positive blood culture broth for inoculation of the VITEK cards; the standard method using an inoculum made from an overnight culture on a solid media; and the routine method (reference method) using conventional testing., Results: Of 169 isolates, the direct method resulted in 75% correct identifications, 9% misidentifications and 17% non-identifications. All misidentified isolates were Escherichia coli, of which 80% were reported as Salmonella arizonae. Five biochemical tests yielded most of the aberrant results; correcting the citrate and malonate reactions in most cases led to correct identification by the VITEK database. Despite a negative H2S reaction, 11 E. coli isolates were reported as S. arizonae. Two-thirds (69%) of identifications were reported within 6 h, and 95% of these were correct. The direct susceptibility testing method was assessable for 140 isolates. Correct results were found in 99% of isolate-antimicrobial combinations, and 85% were reported within 6 h., Conclusion: The direct VITEK method could correctly report identifications and susceptibility patterns within 6 h, making same-day reporting possible for almost two-thirds (63%) of bacteremic episodes with Gram-negative bacilli. These results could probably be improved by modification of the identification algorithms of the VITEK software.

The present paper describe investigations which demonstrate that hyperforin is not the only phloroglucinol derivative in extracts of the medicinal plant Hypericum perforatum L., which possess a biological activity. Hyperforin was the major lipophilic constituent in two different extracts, whereas the amount of adhyperforin was approximately 10 times lower. Adhyperforin, like hyperforin, is a potent inhibitor of the uptake of dopamine, serotonin and noradrenaline. Neither hyperforin nor adhyperforin inhibited binding of the cocaine analogue, [3H]WIN 35,428 to the dopamine transporter. However, the known antidepressives imipramine, nomifensine and fluoxetine all inhibited binding of [3H]WIN 35,428, indicating that hyperforin and adhyperforin do not bind to the same site on the dopamine transporter as these compounds. Furthermore, hyperforin and adhyperforin did not prevent dopamine binding, but inhibited dopamine translocation. Our studies further support recent reports suggesting that the effect of hyperforin on uptake of monoamines is probably not caused by a direct effect of hyperforin on known sites on the transporters.

Moraxella canis was isolated from an infected foot ulcer in a patient suffering from diabetes mellitus with neuropathy. Bacteriological findings and 16S rDNA data are presented.

Background: Staphylococcus aureus bacteremia (SAB) acquired in hospitals continues to be a frequent and serious complication to hospitalization, and no previous case-control studies dealing with risk factors of this severe disease are available., Methods: Based on a 1-year prospective analysis, the data from all patients with hospital-acquired SAB admitted to 4 hospitals in Copenhagen County, Denmark, from May 1, 1994, through April 30, 1995, were evaluated. Eighty-five patients with hospital-acquired SAB were matched to 85 control patients with a similar primary diagnosis at admission (matched controls). Of these, 62 patients with hospital-acquired SAB were compared with 118 other patients with a similar time of admission, who were randomly selected with no clinical evidence of SAB (unmatched controls)., Results: The incidence of hospital-acquired SAB was 0.71 per 1000 hospital admissions. The presence of a central venous catheter (odds ratio, 6.9; 95% confidence interval [CI], 2.8-17.0), anemia (odds ratio, 3.3; 95% CI, 1.4-7.6), and hyponatremia (odds ratio, 3.3; 95% CI, 1.5-7.0) was significantly associated with hospital-acquired SAB in a conditional and a usual logistic regression analysis. Nasal carriage was not an independent risk factor, but nasal carriers among patients in surgery (odds ratio, 4.0; 95% CI, 1.3-13.0) had a significantly higher risk for hospital-acquired SAB compared with matched and unmatched controls. The presence of hospital-acquired SAB increased the mortality rate 2.4-fold (95% CI, 1.1-5.2)., Conclusions: The presence of a central venous catheter is an important risk factor, and hyponatremia and anemia are associated with the development of hospital-acquired SAB. Furthermore, hospital-acquired SAB in itself increases mortality.

Background: The incidence of hematogenous Staphylococcus aureus osteomyelitis of the vertebral column is rapidly increasing and few studies dealing with the diagnosis, treatment, and outcome of this severe disease are available., Methods: Based on a nationwide registration, the clinical and bacteriological data were reviewed from 133 cases with a positive blood culture for S aureus and symptoms of vertebral osteomyelitis in Denmark for the period 1980 to 1990., Results: The 133 cases of vertebral S aureus osteomyelitis reviewed were mainly community-acquired infections (82%) in older patients (median age, 65 years) and often occurred with underlying diseases. Both symptoms and laboratory values were relatively unspecific. Bone scan methods proved to be more optimal for diagnosis of vertebral S aureus osteomyelitis in the early stages compared with conventional radiography that proved a lack of consistency in the formative stages. The infection was mostly (70%) localized in the lower part of the column. The recurrence rate and rate of therapeutic failure depended on the duration and dosage of penicillinase-stable penicillins, respectively. Patients treated with fusidic acid in addition to penicillinase-stable penicillins had a significantly lower recurrence rate. Based on these findings, we recommend treatment with penicillinase-stable penicillins and fusidic acid for a total of 8 weeks, with a daily dosage of penicillinase-stable penicillins higher than 4 g., Conclusions: The diagnosis of vertebral S aureus osteomyelitis based on clinical findings is difficult to ascertain. Bone scans are necessary because radiographic methods do not detect disease as early. Treatment with penicillinase-stable penicillins, at least 4 g/d for at least 8 weeks, is recommended.

Background: Opioid receptors have been demonstrated on peripheral afferent nerves throughout the body. The aim of the present study was to compare the effects of intravenous and intraperitoneal administration of morphine with regard to pain, postoperative morphine requirement, and recovery after major abdominal surgery, and to describe the pharmacokinetics of intraperitoneal morphine in humans., Methods: In a double-blind manner, 30 patients scheduled for major abdominal surgery were randomized to either 50 mg of morphine intravenously (i.v.) or 50 mg of morphine intraperitoneally (i.p.) before operation. Pain was measured on a visual analogue scale and morphine requirements were registered for 3 days. Recovery was measured as time to oral intake of food, time to flatulence and days in hospital. Plasma morphine, morphine-3-glucuronide, and morphine-6-glucuronide concentrations were determined during the first 4 h after morphine administration., Results: During the first postoperative hours there was less pain at rest (P = 0.02) and on coughing (P = 0.004) in the intravenous group. The requirement of additional morphine (P = 0.016) was lower in the intravenous group during the first postoperative day. No major differences in recovery were seen. The plasma concentrations of morphine measured as area under the curve (AUC) during the first 4 h were similar, but the intravenous group showed significantly higher concentrations of the active metabolite morphine-6-glucuronide, (P = 0.016), indicating a difference in pharmacokinetics after intraperitoneal compared to intravenous administration of morphine., Conclusion: Intraperitoneal administration of 50 mg of morphine before major abdominal surgery is less efficient in reducing pain and postoperative morphine requirements than the same amount of morphine given intravenously.

From 1980 to 1990, 309 cases of haematogenous osteomyelitis were identified in Denmark. Haematogenous osteomyelitis of the vertebral column increased significantly (P < 0.01) from the first to the second half of the period due to an increased number of patients > 50 years of age with community-acquired infection. Vertebral osteomyelitis differed significantly from osteomyelitis of other bones in accordance to age distribution (median 66 vs. 16 years), male/female ratio (75/71 vs. 105/ 58) and patients with diabetes (13% vs. 6%). We found a higher risk of haematogenous osteomyelitis in patients > 50 years of age and among patients with community-acquired infection. The highest incidence (5%) of vertebral osteomyelitis in Staphylococcus aureus bacteraemia in this age group was found in cases without an identified portal of entry. The highest incidence (34%) of osteomyelitis of other bones was found in community-acquired cases in the age group 1-20 years and without an identified portal of entry. The present study discusses reasons for the continued increase of vertebral osteomyelitis among adults and describes incidence rates and major risk factors for developing haematogenous osteomyelitis among patients with S. aureus bacteraemia. We suggest that the localization of haematogenous S. aureus osteomyelitis is connected with the presence of red bone marrow.

During a 6-month period, 892 positive blood cultures were detected in the Copenhagen County hospitals. 302 (34%) were regarded as contaminations, and of the remaining cases 419 (71%) were community-acquired and 171 (29%) hospital-acquired, giving incidence rates of 6.8/1,000 admissions and 2.8/1,000 admissions, respectively. Both frequency and rate of hospital-acquired bacteremia were lower compared to most other studies. E. coli was more commonly found in community-acquired infections, while coagulase-negative staphylococci were the organisms most often considered as a contaminant. The main causative organisms in hospital-acquired infections were S. aureus (n = 37) and E. coli (n = 34). The proportion of polymicrobial bacteremias in this study was lower compared to most other studies (8%). E. coli from hospital-acquired infections were resistant to ampicillin in 42% of cases, but other Enterobacteriaceae showed higher percentage of resistance to beta-lactam antibiotics. S. aureus was penicillin-resistant in 92% of cases, but no methicillin-resistant strains were isolated. The frequency of antibiotic resistance was low compared to reports from other countries. A total of 136 hospital-acquired cases were followed prospectively. 61% of the patients were male and 46% were > or = 60 years of age. Most patients had predisposing diseases, 90% had foreign body and/or recent surgery performed, and 74 (54%) had an intraveneous catheter. The portal of entry was known in 132 (97%) of the cases, the most common being the urinary tract (42%), followed by an intravenous catheter (30%). The prevalence of urinary tract catheters gave an increased number of cases with E. coli bacteremia. The mortality was 16%.

Sixty patients, ASA I-III, presenting for elective colonic surgery were studied to assess the stability of blood pressure and heart rate during anaesthesia with three equally potent anaesthetic techniques. Patients in group I (n = 20) received thiopentone induction, isoflurane and nitrous oxide; patients in group II (n = 20) received total intravenous anaesthesia with propofol; and patients in group III (n = 20) received intravenous propofol supplemented with nitrous oxide. Fentanyl and vecuronium were used in all three groups. The depth of anaesthesia was judged on clinical signs of adequate anaesthesia. Episodes of bradycardia (heart rate < 50 beats min-1), tachycardia (heart rate > 90 beats min-1), hypotension (mean arterial pressure > or = 30% below pre-operative blood pressure) or hypertension (mean arterial pressure > 30%, or systolic blood pressure > 15 mmHg, above pre-operative value) were recorded when lasting > 5 min. Any use of ephedrine or glycopyrrolate given to correct hypotension or bradycardia was documented: In group II, significantly more patients were given ephedrine (P < 0.01) to treat hypotension. The drug was administered after intubation but before skin incision in the majority of cases (9/11). Glycopyrrolate was given to significantly more patients in group III (P < 0.025) to treat bradycardia, and in 21 of a total of 34 patients given glycopyrrolate it was administered before surgery. With the use of these additional drugs, there were no differences in the number of patients with 5 min episodes of hypotension, hypertension, tachycardia or bradycardia.(ABSTRACT TRUNCATED AT 250 WORDS)