Characteristics of children aged 2-17 years undergoing anaesthesia in Danish hospitals 2005-2015: a national observational study.

Provision of paediatric anaesthesia requires careful consideration of the child's cognitive state, unique body composition and physiology. In an observational cohort study, we describe the population characteristics and conduct of anaesthesia in children aged 2-17 years from 1 January 2005 to 31 December 2015. Children were identified from the Danish Anaesthesia Database. We recorded the following variables: age; sex; comorbidities; indications for anaesthesia; practice of anaesthesia; and complications. Results are presented for two age groups: 2-5 and 6-17 years. In total, 32,840 (61% male) children aged 2-5 years received 50,484 anaesthesia episodes and 91,418 (54% male) children aged 6-17 years received 141,082 anaesthesia episodes. The younger children, compared with the older children, were more frequently anaesthetised at a university hospital (50% vs. 36%) and for non-surgical procedures (24% vs. 8%). For both age groups, general anaesthesia was the primary choice of anaesthesia regardless of the reason for anaesthesia. For surgery, general anaesthesia using inhalational agents in addition to intravenous agents or alone was more frequently used in younger children (49% vs. 15%), whereas older children commonly received total intravenous anaesthesia (50% vs. 83%). Regional anaesthesia was infrequently utilised. Complications occurred in 3.3% of anaesthesia episodes among 2-5 year olds compared with 3.7% of anaesthesia episodes among children aged 6-17 years. In conclusion, we found younger children (aged 2-5), compared with older children (aged 6-17) were more frequently anaesthetised for non-surgical reasons, at a university hospital and using inhalational agents. Complications were rare.

Characteristics of children less than 2 years of age undergoing anaesthesia in Denmark 2005-2015: a national observational study.

There are few data available that describe the current anaesthetic management of children. We have analysed anaesthetic practice and peri-operative complications for children in Denmark aged less than two years. We conducted a population-based observational cohort study using the Danish Anaesthesia Database to identify children who received anaesthesia in hospital from 1 January 2005 until 31 December 2015. Data were combined with that from the Danish National Patient Registry and the Danish Civil Registration System. Age, sex, height, weight, ASA physical status, days in hospital before anaesthesia, number of anaesthetics per child, indications for anaesthesia, methods of anaesthesia, airway management and complications were all recorded. A total of 17,436 children (64% of whom were male) received 27,653 anaesthetics during the study period. In 58% of cases, the child had an ASA physical status score of 1. Thirty-seven percent had a previous anaesthetic episode. Seventy-nine percent were anaesthetised at a university hospital. The indications for anaesthesia were surgery (70%), diagnostic radiology (16%), non-surgical care (11%) and other indications (3%). General anaesthesia combining intravenous and inhalational agents was the most common approach for surgery (68%) and diagnostic radiology (47%). For non-surgical care, general anaesthesia using inhalational agents was the most common method (42%). Neuraxial blocks were used infrequently. The most common regional anaesthetic nerve block was an infraclavicular brachial plexus block (11%). Peri-operative complications occurred in 1.71% of cases. A large proportion of anaesthetics were conducted in children with comorbidities. Non-surgical indications for anaesthesia were frequent and peri-operative complications were rare.

Helicopter vs. ground transportation of patients bound for primary percutaneous coronary intervention.

BACKGROUND: Implementation of the first Danish helicopter emergency medical service (HEMS) was associated with reduced time from first medical contact to treatment at a specialized centre for patients with suspected ST elevation myocardial infarction (STEMI). We aimed to investigate effects of HEMS on mortality and labour market affiliation in patients admitted for primary percutaneous coronary intervention (PCI). METHODS: In this prospective observational study, we included patients with suspected STEMI within the region covered by the HEMS from January 1, 2010, to April 30, 2013, transported by either HEMS or ground emergency medical services (GEMS) to the regional PCI centre. The primary outcome was 30-day mortality. RESULTS: Among the 384 HEMS and 1220 GEMS patients, time from diagnostic ECG to PCI centre arrival was lower with HEMS (median 71 min vs. 78 min with GEMS; P = 0.004). Thirty-day mortality was 5.0% and 6.2%, respectively (adjusted OR = 0.82, 95% CI 0.44-1.51, P = 0.52. Involuntary early retirement rates were 0.62 (HEMS) and 0.94 (GEMS) per 100 PYR (adjusted IRR = 0.68, 0.15-3.23, P = 0.63). The proportion of patients on social transfer payments longer than half of the follow-up time was 22.1% (HEMS) vs. 21.2% (adjusted OR = 1.10, 0.64-1.90, P = 0.73). CONCLUSION: In an observational study of patients with suspected STEMI in eastern Denmark, no significant beneficial effect of helicopter transport could be detected on mortality, premature labour market exit or work ability. Only a study with random allocation to one system vs. another, along with a large sample size, will allow determination of superiority of helicopter transport.

Do we need retarded delivery of bone growth factors in facial bone repair? An experimental study in rats.

The aim of the present study was to evaluate the effect of different dosages of retarded vs. rapid release of bone morphogenic protein 2 (BMP2) at different recipient sites. Porous composite poly(D,L-lactic acid) (PDLLA)/CaCO3 scaffolds were loaded with three different dosages of rhBMP2 (24 µg, 48 µg and 96 µg) and implanted, together with blank controls, both into non-healing defects of the mandibles and into the gluteal muscles of 24 adult male Wistar rats. After 26 weeks, bone formation and expression of bone specific markers [alkaline phosphatase (AP) and Runx2] were evaluated by histomorphometry and immunohistochemistry. Results showed that the mode of delivery had no quantitative effect on bone formation in mandibular sites. Expression of AP and Runx2 showed significant differences among the three dosage groups. There were significant correlations between the expression of both AP and Runx2 as well as the extent of bone formation, with both retarded and rapid release of rhBMP2. In ectopic sites, retarded release significantly enhanced bone formation in the low and medium dosage groups, compared to rapid release. Expression of AP was significantly higher and Runx2 significantly lower in ectopic sites, compared to mandibular sites. Significant correlations between the expression of bone specific markers and bone formation occurred only in the retarded delivery groups, but not in the rapid release groups. Within the limitations of the experimental model, it was concluded that retarded delivery of BMP2 was effective, preferably in sites with low or non-existing pristine osteogenic activity. Expression of bone specific markers indicated that osteogenic pathways might be different in mandibular vs. ectopic sites.

Quality of life following trauma before and after implementation of a physician-staffed helicopter.

BACKGROUND: Implementation of a physician-staffed helicopter emergency medical service (PS-HEMS) in Denmark was associated with lower 30-day mortality in severely injured trauma patients and less time on social subsidy. However, the reduced 30-day mortality in severely injured patients might be at the expense of a worse functional outcome and quality of life (QoL) in those who survive. The aim of this study was to investigate the effect of a physician-staffed helicopter on long-term QoL in trauma patients. METHODS: Prospective, observational study including trauma patients who survived at least 3 years after injury. A 5-month period prior to PS-HEMS implementation was compared with the first 12 months after PS-HEMS implementation. QoL was assessed 4.5 years after trauma by the SF-36 questionnaire. Primary endpoint was the Physical Component Summary score. RESULTS: Of the 1994 patients assessed by a trauma team, 1521 were eligible for inclusion in the study. Of these, 566 (37%) gave consent to participate and received a questionnaire by mail, and 402 (71%) of them returned the questionnaire (n = 114 before PS-HEMS; n = 288 after PS-HEMS implementation). Older patients, women and patients with trauma in the after PS-HEMS period were more likely to return the questionnaire. No significant association between QoL and period (before vs. after PS-HEMS) was found; the Physical Component Summary scores were 50.0 and 50.9 in the before and after PS-HEMS periods, respectively (P = 0.47). We also found no difference on multivariable analysis with adjustment for sex, age and injury severity score. CONCLUSION: No significant difference in QoL among trauma patients was found after implementation of a PS-HEMS.

Risk factors for reintervention after surgery for perforated gastroduodenal ulcer.

BACKGROUND: Perforated gastroduodenal ulcer carries a high mortality rate. Need for reintervention after surgical repair is associated with worse outcome, but knowledge on risk factors for reintervention is limited. The aim was to identify prognostic risk factors for reintervention after perforated gastroduodenal ulcer in a nationwide cohort. METHODS: All patients treated surgically for perforated gastroduodenal ulcer in Denmark between 2003 and 2014 were included using data from the Danish Clinical Register of Emergency Surgery. Potential risk factors for reintervention were assessed, and their crude and adjusted associations calculated by the competing risks subdistribution hazards approach. RESULTS: A total of 4086 patients underwent surgery for perforated gastroduodenal ulcer during the study interval. Median age was 71·1 (i.q.r. 59·6-81·0) years and the overall 90-day mortality rate was 30·8 per cent (1258 of 4086). Independent risk factors for reintervention were: male sex (adjusted hazard ratio (HR) 1·46, 95 per cent c.i. 1·20 to 1·78), in-hospital perforation (adjusted HR 1·36, 1·11 to 1·68), high BMI (adjusted HR 1·49, 1·10 to 2·01), high ASA physical status grade (adjusted HR 1·54, 1·23 to 1·94), shock on admission (adjusted HR 1·40, 1·13 to 1·74), surgical delay (adjusted HR 1·07, 1·02 to 1·14) and other co-morbidity (adjusted HR 1·24, 1·02 to 1·51). Preadmission use of steroids (adjusted HR 0·59, 0·41 to 0·84) and age above 70 years (adjusted HR 0·72, 0·59 to 0·89) were associated with a reduced risk of reoperation. CONCLUSION: Obese men with coexisting diseases and high disease severity who have surgery for gastroduodenal perforation are at increased risk of reoperation.

Continuous delivery of rhBMP2 and rhVEGF165 at a certain ratio enhances bone formation in mandibular defects over the delivery of rhBMP2 alone--An experimental study in rats.

The aim of the present study was to test the hypothesis that different amounts of vascular endothelial growth factor and bone morphogenic protein differentially affect bone formation when applied for repair of non-healing defects in the rat mandible. Porous composite PDLLA/CaCO3 carriers were fabricated as slow release carriers and loaded with rhBMP2 and rhVEGF165 in 10 different dosage combinations using gas foaming with supercritical carbon dioxide. They were implanted in non-healing defects of the mandibles of 132 adult Wistar rats with additional lateral augmentation. Bone formation was assessed both radiographically (bone volume) and by histomorphometry (bone density). The use of carriers with a ratio of delivery of VEGF/BMP between 0.7 and 1.2 was significantly related to the occurrence of significant increases in radiographic bone volume and/or histologic bone density compared to the use of carriers with a ratio of delivery of ≤ 0.5 when all intervals and all outcome parameters were considered. Moreover, simultaneous delivery at this ratio helped to "save" rhBMP2 as both bone volume and bone density after 13 weeks were reached/surpassed using half the dosage required for rhBMP2 alone. It is concluded, that the combined delivery of rhVEGF165 and rhBMP2 for repair of critical size mandibular defects can significantly enhance volume and density of bone formation over delivery of rhBMP2 alone. It appears from the present results that continuous simultaneous delivery of rhVEGF165 and rhBMP2 at a ratio of approximately 1 is favourable for the enhancement of bone formation.

Anaesthesia care with and without tracheal intubation during emergency endoscopy for peptic ulcer bleeding: a population-based cohort study.

BACKGROUND: Emergency upper gastrointestinal bleeding is a common condition with high mortality. Most patients undergo oesophagogastroduodenoscopy (OGD), but no universally agreed approach exists to the type of airway management required during the procedure. We aimed to compare anaesthesia care with tracheal intubation (TI group) and without airway instrumentation (monitored anaesthesia care, MAC group) during emergency OGD. METHODS: This was a prospective, nationwide, population-based cohort study during 2006-13. Emergency OGDs performed under anaesthesia care were included. End points were 90 day mortality (primary) and length of stay in hospital (secondary). Associations between exposure and outcomes were assessed in logistic and linear regression models, adjusted for the following potential confounders: shock at admission, level of anaesthetic expertise present, ASA score, Charlson comorbidity index score, BMI, age, sex, alcohol use, referral origin (home or in-hospital), Forrest classification, ulcer localization, and postoperative care. RESULTS: The study group comprised 3580 patients under anaesthesia care: 2101 (59%) for the TI group and 1479 (41%) for the MAC group. During the first 90 days after OGD, 18.9% in the TI group and 18.4% in the MAC group died, crude odds ratio=1.03 [95% confidence interval (CI)=0.87-1.23, P=0.701], adjusted odds ratio=0.95 (95% CI=0.79-1.15, P=0.590). Patients in the TI group stayed slightly longer in hospital [mean 8.16 (95% CI=7.63-8.60) vs 7.63 days (95%=CI 6.92-8.33), P=0.108 in adjusted analysis]. CONCLUSIONS: In this large population-based cohort study, anaesthesia care with TI was not different from anaesthesia care without airway instrumentation in patients undergoing emergency OGD in terms of 90 day mortality and length of hospital stay.

The effectiveness of pneumococcal polysaccharide vaccination in HIV-infected adults: a systematic review.

OBJECTIVE: The effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV-23) in preventing pneumococcal disease in HIV-infected people is a subject of debate. We reviewed the clinical evidence for recommending PPV-23 for use in HIV-infected patients. METHODS: A systematic search of peer-reviewed publications (EMBASE, the Cochrane Library, and PubMed/BioMed Central), the Internet and grey literature was conducted. Three hundred and eighteen documents were reviewed. Studies reporting risk estimates for all-cause pneumonia, all-pneumococcal disease, and/or invasive pneumococcal disease after PPV-23 immunization in HIV-infected adults were included. RESULTS: We identified one randomized trial and 15 observational studies. While the randomized trial found a 60% increased risk of all-cause pneumonia among vaccinees, 11 of the 15 observational studies found various degrees of disease protection associated with PPV-23 immunization. However, most studies suffered from limited confounder control in their multivariate analyses, despite study data suggesting substantial differences between the characteristics of exposed and unexposed individuals. CONCLUSIONS: The current clinical evidence provides only moderate support for PPV-23 immunization of HIV-infected adults. More data are needed on the efficacy of newer conjugated pneumococcal vaccines, which may be more immunogenic and could potentially replace PPV-23 in the future.

Characterization of particulate matter size distributions and indoor concentrations from kerosene and diesel lamps.

UNLABELLED: Over one-quarter of the world's population relies on fuel-based lighting. Kerosene lamps are often located in close proximity to users, potentially increasing the risk for respiratory illnesses and lung cancer. Particulate matter concentrations resulting from cook stoves have been extensively studied in the literature. However, characterization of particulate concentrations from fuel-based lighting has received minimal attention. This research demonstrates that vendors who use a single simple wick lamp in high-air-exchange market kiosks will likely be exposed to PM(2.5) concentrations that are an order of magnitude greater than ambient health guidelines. Using a hurricane lamp will reduce exposure to PM(2.5) and PM(10) concentrations by an order of magnitude compared to using a simple wick lamp. Vendors using a single hurricane or pressure lamp may not exceed health standards or guidelines for PM(2.5) and PM(10), but will be exposed to elevated 0.02-0.3 µm particle concentrations. Vendors who change from fuel-based lighting to electric lighting technology for enhanced illumination will likely gain the ancillary health benefit of reduced particulate matter exposure. Vendors exposed only to ambient and fuel-based lighting particulate matter would see over an 80% reduction in inhaled PM(2.5) mass if they switched from a simple wick lamp to an electric lighting technology. PRACTICAL IMPLICATIONS: Changing lighting technologies to achieve increased efficiency and energy service levels can provide ancillary health benefits. The cheapest, crudest kerosene lamps emit the largest amounts of PM(2.5). Improving affordability and access to better lighting options (hurricane or pressure lamps and lighting using grid or off-grid electricity) can deliver health benefits for a large fraction of the world's population, while reducing the economic and environmental burden of the current fuel-based lighting technologies.

Monocyte chemotactic and activating factor (MCAF/MCP-1) has an autoinductive effect in monocytes, a process regulated by IL-10.

MCAF (MCP-1) a member of the chemokine-beta-family known to be chemotactic for monocytes is believed to play a significant role in several inflammatory processes, both immuno-pathological disorders, such as atherosclerosis, psoriasis, chronic inflammatory diseases of the liver and lungs, and during the normal immune response against microorganisms. This chemokine is produced spontaneously by monocytes, and in the present article we also demonstrate that MCAF induces its own production in monocytes. The methods used are two dimensional SDS-PAGE gel electrophoresis. Western-blotting and ELISA quantification of supernatant from monocyte cultures stimulated with MCAF (1, 10, 100 ng ml). Also, we found that this process is regulated by IL-10 (100 ng ml). Our results suggest that monocytes migrating to a site of inflammation due to the local production of the chemokine MCAF/MCP-1 further enhance the focal accumulation of monocytes by producing and releasing bioactive MCAF MCP-1.

IL-8 induces T cell chemotaxis, suppresses IL-4, and up-regulates IL-8 production by CD4+ T cells.

Interleukin-8 (IL-8), a neutrophil-activating cytokine, also activates certain T cell functions such as chemotaxis. We additionally find (n = 6) that recombinant (rIL-8; 1-100 ng/ml), when added to 24 h culture of human CD4+ T cells, suppressed the spontaneous production of IL-4 (50-85%). Steady state production of Il-4 was typically around 30 pg/ml, determined by use of a solid- phase immunoabsorbant assay. De novo synthesis of IL-4 from CD4+ T cells cultured for 3 days was also evaluated by use of detection of [35S]methionine incorporation, as visualized by autoradiography of 2-D gels, and showed that IL-8 suppressed IL-4 production. This suppression of IL-4 production was confirmed in the cytosol fraction by use of Western blotting. The effect of IL-8 (100 ng/ml) was comparable to that of 10 ng/ml recombinant interferon-gamma, both strongly suppressing IL-4 production. The regulatory effect of IL-8 on IL-4 production was also indicated by the fact that addition of a neutralizing monoclonal anti-IL-8 antibody (WS.4) enhanced the spontaneous IL-4 production when added to the culture of CD4+ T cells, thereby probably inactivating the effect of IL-8 originating from the cultured T cells. Also, we observed that IL-4 mRNA expression was down-regulated when the CD4+ T cells were cultured for 12 h in the presence of 100 ng/ml IL-8. The suppression of IL-4 mRNA expression could be prevented by adding anti-IL-8 (20 microgram/ml) or IL-10 (100 ng/ml) l h before adding rIL-8. Thus, IL-8 may be an important regulator of CD4+ T cell-derived IL-4, thereby possibly regulating the balance between humoral and cellular T cell-dependent responses.

Interleukin-8 in cerebrospinal fluid from patients with septic and aseptic meningitis.

Using a monoclonal antibody enzyme immunoassay, the concentration of interleukin-8 (IL-8) in cerebrospinal fluid (CSF) from 52 patients suspected of having meningitis was studied. The CSF IL-8 concentration was significantly higher in septic meningitis of known and unknown etiology than in aseptic meningitis and significantly higher in aseptic meningitis than in patients without meningitis. The CSF levels of IL-8 correlated with the levels of tumor necrosis factor-alpha, leukocyte count, neutrophil count, protein level, CSF/blood glucose ratio, and the number of days patients were hospitalized. The IL-8 values used to distinguish septic from aseptic meningitis, at a cut-off point of 3.00 micrograms/l, showed a sensitivity of 81%, a specificity of 92%, and a positive predictive value of 96%. The results suggest that determining IL-8 levels may be useful in the differential diagnosis of meningitis.

Interleukin-8 induces its own production in CD4+ T lymphocytes: a process regulated by interleukin 10.

The neutrophil and T cell chemotactic factor interleukin 8 (IL-8) is believed to play a pathophysiological role in the development of various inflammatory disorders. So far no other effects of IL-8 on T cells have been observed. We observed that purified CD4+ T cells in particular, but also CD8+ T cells, spontaneously synthesize IL-8 mRNA and secrete IL-8 protein. The culture supernatants of CD4+ T cells contained T cell chemotactic activity as well as IL-8 protein. In addition, we confirmed the ability of CD4+ T cells to produce IL-8 by double immunofluorescence staining and by the demonstration of IL-8 mRNA expression. Further, IL-8 induced its own production in CD4+ T cells, while its synthesis by CD8+ T cells was low and not always auto-stimulatory. Both the spontaneous, as well as the IL-8 induced IL-8 production, could be inhibited in the presence of human interleukin 10 (100 ng/ml). This observation suggests that IL-10 plays a homeostatic role in regulating the IL-8 circuit in CD4+ T cells.