Anaesthesia praCtice for Caesarean dElivery Snapshot Study (ACCESS): Protocol and baseline characteristics of registered centres.

BACKGROUND: Specific guidelines to manage caesarean delivery anaesthesia are lacking. A European multicentre study, ACCESS investigates caesarean delivery anaesthesia management in European centres. In order to identify ACCESS participating centres, a registration survey was created. OBJECTIVE: The aim of the current report is to describe the characteristics of ACCESS study participating centres, the rationale for the ACCESS study and the study methodology. DESIGN AND SETTING: The ACCESS study is a European multicentre cross-sectional study to describe anaesthesia management for caesarean delivery (CD) using a snapshot (2-week) design. The ACCESS registration survey gathered: contact details for National Coordinators (NC); Lead Investigators (LI) per centre; centre annual CD volume; expected no. of CD during 2-week snapshot window; centre practice information; data collection language. The ACCESS registration survey was launched July 2022 (Google Forms, Google Inc., Mountain View, CA, USA) and distributed through personal connections, national and international societies, social media networks, during Euroanaesthesia 2023, through the European Society of Anaesthesiology and Intensive Care newsletter. RESULTS: The ACCESS registration survey identified Lead Investigators for 418 centres, in 32 countries, representing an anticipated number of 15,073 CD cases over the planned 12-month study period. A median (range) of 20 (2 to 400) CD cases are anticipated per centre during the 2-week snapshot window. Most 366/418 (87.6%) centres are small, ≤2000 annual CD cases, 42 are medium 2000-5000 cases and 10 are large, ≥5000 annual CD cases. Registered centres reported in 134 (32.0%) centres that anaesthesia for caesarean delivery is performed mostly by a specialist obstetric anaesthesiologist. CONCLUSION: The ACCESS registration survey revealed variability in volume and CD practice as well as training-levels and staffing among European countries. The ACCESS study (https://www.access-study.org/) aims to generate practice data to guide CD anaesthetic management strategies.

Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial.

BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. RESULTS: Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. CONCLUSIONS: We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.

Development of knowledge tests for multi-disciplinary emergency training: a review and an example.

BACKGROUND: The literature is sparse on written test development in a post-graduate multi-disciplinary setting. Developing and evaluating knowledge tests for use in multi-disciplinary post-graduate training is challenging. The objective of this study was to describe the process of developing and evaluating a multiple-choice question (MCQ) test for use in a multi-disciplinary training program in obstetric-anesthesia emergencies. METHODS: A multi-disciplinary working committee with 12 members representing six professional healthcare groups and another 28 participants were involved. Recurrent revisions of the MCQ items were undertaken followed by a statistical analysis. The MCQ items were developed stepwise, including decisions on aims and content, followed by testing for face and content validity, construct validity, item-total correlation, and reliability. RESULTS: To obtain acceptable content validity, 40 out of originally 50 items were included in the final MCQ test. The MCQ test was able to distinguish between levels of competence, and good construct validity was indicated by a significant difference in the mean score between consultants and first-year trainees, as well as between first-year trainees and medical and midwifery students. Evaluation of the item-total correlation analysis in the 40 items set revealed that 11 items needed re-evaluation, four of which addressed content issues in local clinical guidelines. A Cronbach's alpha of 0.83 for reliability was found, which is acceptable. CONCLUSION: Content and construct validity and reliability were acceptable. The presented template for the development of this MCQ test could be useful to others when developing knowledge tests and may enhance the overall quality of test development.

Characterisation of invasive group B streptococci from adults in Denmark 1999 to 2004.

The aim of this study was to characterise the group B streptococci (GBS) isolates causing severe invasive infections in patients >15 years of age in Denmark from 1999 to 2004. A total of 411 invasive GBS isolates were phenotypically characterised by the capsular polysaccharide (CPS) serotype and protein Calpha, Cbeta and R4. The incidence of invasive GBS disease ranged from 2.2 to 3.2 per 100,000 adults in the study period, being highest among adults over 65 years of age. Diabetes was observed in 15% of the cases, 12% had alcohol abuse and 7% had cancer. Of all isolates, 77% were CPS serotypes Ia, Ib, III or V. The surface proteins Calpha or R4 were detected as the only protein in 57% of the GBS isolates. Cbeta was detected in 12% of the isolates, but always in combination with either Calpha or both Calpha and R4. The incidence of invasive GBS infections continued to increase in Denmark from 1999 to 2004. In that period, the overall case fatality was 14%. The most prevalent CPS serotypes were serotypes III, Ia, V and Ib. The most prevalent surface protein was R4 when testing for R4, Calpha and Cbeta. There was no clear relation between the GBS phenotype and infections with fatal outcome.

Rectangular solid domains in ceramide-cholesterol monolayers - 2D crystals.

Very small rectangular domains were observed by atomic force microscopy in binary monolayers of synthetic ceramides and cholesterol. When the cholesterol content is increased the domains are bigger although the rectangular shape is retained. The almost perfect shape of the domains indicates two-dimensional single ceramide crystals. Lipid domains in monolayers of this particular shape and size have to our knowledge not been reported in the literature previously.

Invasive group A, B, C and G streptococcal infections in Denmark 1999-2002: epidemiological and clinical aspects.

Group A streptococci (GAS) have been described frequently as an emerging cause of severe invasive infections in population-based surveillance studies, whereas the descriptions of group B, C and G streptococci (GBS, GCS and GGS) have been less frequent. Enhanced surveillance for invasive GAS, GBS, GCS and GGS was performed in Denmark in 1999-2002. A detailed questionnaire was completed for 1237 (98%) of 1260 invasive infections. GAS infections dominated (40%), followed by GGS (32%), GBS (23%) and GCS (6%). Most (74%) patients had predisposing factors, and there were no significant differences between the four serogroups when comparing the prevalence of cancer, diabetes mellitus, chronic heart or lung diseases, immunodeficiency or alcohol abuse. The overall case fatality rate at day 30 was 21%, increasing significantly to 59% for patients with streptococcal toxic shock syndrome (STSS). STSS was significantly more frequent in GAS patients (10%) than in GCS (4%), GBS (2%) and GGS (2%) patients. Regression analyses showed that, despite a younger median age among GAS patients, the probability of developing septic shock and mortality was significantly higher among GAS patients than among GBS and GGS patients. These analyses showed no significant differences between GAS and GCS infections. Invasive infections caused by GAS, GBS, GCS and GGS are still a major challenge for clinicians. Continued epidemiological and microbiological surveillance is important to assess the development of these infections and to improve preventative strategies.

Evaluation of gastrointestinal symptoms as primary sign of severe invasive group A streptococcal infections.

BACKGROUND & OBJECTIVES: Severe invasive infections caused by group A Streptococcus (GAS) are often associated with shock and organ failure. We describe epidemiological and disease related data from the national surveillance of invasive GAS infection in Denmark in addition to three fatal cases that occurred in Denmark in 2002 with gastrointestinal (GI) symptoms as the dominating preliminary signs. METHODS: As the National Streptococcal Reference Centre The Streptococcus Unit, Statens Serum Institut (SSI) receives the vast majority of the invasive GAS isolates from patients admitted to all the hospitals in Denmark. The isolates were T-typed by slide agglutination test emm-squencing and pulsed field gel electrophoresis (PFGE) were also performed. RESULTS: During January 2002 three patients died at home and GAS were found at autopsy. Cases 1 (12 yr) and 3 (25 yr) had been ill for less than two days with nausea, diarrhoea and vomiting. Case 2 (25 yr) had the same symptoms for two weeks. None of the three had any underlying diseases. The GAS isolates from cases 1 and 2 were T-type 3-13-B3264, emm89 and SpeA-, SpeC-. The third isolate was Ttype 1, emm1 and SpeA+, SpeC-. PFGE could not discriminate between the two isolates with T-type 3-13-B3264. The PFGE patterns of the three isolates were similar to those identified from GAS isolated elsewhere in Denmark at different times and from non-fatal cases. In 1999-2002, SSI received 409 isolates from patients with invasive GAS infection, and the mortality rate was 18 per cent. In 40 patients the primary symptoms were gastrointestinal, and in 30 per cent of these the outcome was fatal. INTERPRETATION & CONCLUSION: The various early clinical manifestations of severe GAS infections are still a major challenge for clinicians because of the importance of a fast and appropriate diagnosis and immediate start of treatment.

The skin barrier from a lipid perspective.

This contribution summarises the results from a number of investigations undertaken in the spirit of the Domain Mosaic Model proposed by Forslind in 1994. Atomic Force Microscopy (AFM) studies on the two-dimensional phase behaviour of some stratum corneum lipids revealed phase separation of the lipids in the typical case and the ability of cholesterol to reduce the line tension between phases. A theoretical model was developed describing the response of an oriented stack of polar lipid bilayers in the presence of a gradient in water chemical potential (water solution to humid air). The gradient gives rise to an inhomogeneous water swelling, and presumably to a liquid crystal-to-gel transition in the lamellar region closest to humid air. Skin penetration enhancers such as Azone and oleic acid cause phase transformations in lipid bilayer systems which may be relevant in the context of skin permeation.

Output of bilirubin and pancreatic enzymes in response to different liquid test meals in man.

The output of bilirubin and pancreatic enzymes was determined after ingestion of three different liquid test meals in man. Doubling the amount of protein in a composite meal was followed by a delivery of more protein per time unit to the intestine and by a higher output of bilirubin and enzymes than was recorded after a similar meal containing less protein. The ingestion of a 15% glucose solution awoke a considerable output of bilirubin and enzymes during the first hour, thereafter it was low and decreasing. The differences in enzyme and bilirubin output corresponded to differences in quality and quantity of the emptied food components.

Relation between body weight and the gastric and intestinal handling of an oral caloric load.

The gastric and intestinal handling of a standard liquid 300-ml meal (0.89 kcal/ml) was examined in 10 healthy, non-obese subjects by a quantitative multiple-indicator dilution technique. Such a meal contains about one-tenth of the daily energy requirements. The heavier the subject the more energy was transferred from the stomach to the intestine during the first 80 minutes after taking the meal. A high body weight was also associated with a rapid transit through the proximal 70 cm of intestine and the passing of a substantial part of the meal calories to the lower intestine. These circumstances favour a fast incorporation of fed calories. In subjects with lower body weights eneryg was delivered more slowly from the stomach. The absorbed an equal amount of energy in the proximal intestine as did the heavier subjects, but during the longer transit times. The percentage absorption in the investigated segment was therefore higher.

Output of bile and pancreatic enzymes after test meals with different fat content. Influence of body weight on pancreatic enzyme composition.

The output of bile and pancreatic enzymes after two mixed meals with different fat content was studied in 16 healthy volunteers of normal body-weight. A quantitative multiple indicator dilution method was used. The delivery of more fat per time to the duodenum after the fat rich compared to the low fat meal was followed by the emptying of more bile but did not significantly increase the pancreatic response. The ratio between amylase and lipase was constant throughout the course of a single experiment but differed between the subjects. The ratio decreased with an increasing body weight, indicating a relative dominance of amylase over lipase in the lighter and the reverse in the heavy subjects. The same correlation was found when results from a previously reported series with a glucose containing mixed meal were reexamined. It is proposed that long time dietary differences might influence the enzyme composition of the postprandial pancreatic secretion.

[Duovac 300--udder health and milking routines. A field experiment (author's transl)]. / Duovac 300, jurhelse og melkingsrutiner. Resultater av feltforsøk.

The effect on udder health and milking routine of two Alfa Laval milking units, the Duovac 300 with a normal (380 mm Hg) and a low (250 mm Hg) vacuum phase and the standard HP 100 unit with only the normal (380 mm Hg) vacuum phase, was investigated on six dairy farms. A total of 197 cows were involved in the study. Each herd was divided into two groups which were as similar as possible in terms of age, stage of parturition and milk yield. One group was milked with the Duovac unit, while the other was milked with the HP 100 units for a test period of 100 days. No differences in cell counts from the cow samples, the presence of subclinical mastitis or clinical condition of the teats were observed between the two test groups. The total milking machine time for the Duovac units was longer than for the HP 100 units. However, the time spent in the normal vacuum phase (380 mm Hg) for the Duovac units was shorter than the total milking machine time for the HP 100 units (380 mm Hg). The Duovac units had the shortest machine stripping time, but the "waiting time" for the milkers (the time between the various operations) was longer. These time studies showed that the number of cows milked per hour by one man using four or five Duovac units was equal to or greater than the number of cows milked per hour by one man using three HP 100 units. It was recommended that no more than three HP 100 units be managed by one man.

Effects of 16,16 dimethyl prostaglandin E2 on food-stimulated pancreatic secretion and output of bile in man.

The effect of 140 microgram 16,16 dimethyl prostaglandin E2 on food-stimulated pancreatic and biliary response has been studied in 7 healthy subjects, using a multiple indicator dilution technique. Intragastic administration of the methyl analogue decreased significantly the pancreatic and the biliary response, despite an enhanced gastric emptying rate of the test meal.

Jejunitis with malaborption. A quantitative study of the gastric and intestinal handling of a meal during malabsorption and after recovery.

The gastric and intestinal response to a standard meal was examined with a quantitative multiple indicator dilution technique in a patient with jejunitis and malabsorption. Examinations were made during and after recovery from disease. The malabsorptive state was associated with a marked delay of the gastric emptying paralleled by a low gastric secretion rate. Despite the low delivery rate from the stomach, large fluid volumes passed at the investigated level 70 cm distal to the pyloric sphincter. This was due to a reduced absorption of nutrients and water during a rapid transit of the proximal intestine and to persistently high pancreatic and intestinal secretion rates. A comparison with data from the healthy experiment suggests that the strong gastric inhibition during malabsorption works as an effective compensation for the decreased absorptive capacity after the second hour from meal intake and onwards.

Invasive group B streptococcal disease in infants: a 19-year nationwide study. Serotype distribution, incidence and recurrent infection.

During the period 1984-2002, 472 cases of invasive group B streptococcal (GBS) disease in infants aged 0-90 days in Denmark were registered. The overall incidence was 0.4/1000 live births. Most infants (73%) had early-onset GBS infection with 53% registered within the first day. Serotype III predominated (59%) with other serotypes as follows: Ia (16%), Ib (8%), NT (7%), II (6%), other serotypes (5%). Recurrence of GBS infection was registered in six infants, and the interval with no antibiotic therapy varied from 2 to 39 days. The serotypes of the isolates obtained from first and second episodes were identical (serotype III in five, and serotype Ia in one infant). Paired isolates were indistinguishable by PFGE and antibiotic susceptibility testing. Invasive GBS infections in infants are still a problem in Denmark, and recurrent infections are registered in 1% of these infants.

Structural, neuronal, and functional adaptive changes in atrophic rat ileum.

BACKGROUND: Inactivity of the gut leads to atrophic changes of which little is known. AIMS: To investigate structural, neuronal, and functional changes occurring in bypassed rat ileum. METHODS: Morphometry was used to characterise the atrophic changes. The numbers of enteric neurones, their expression of neurotransmitters, and the presence of interstitial cells of Cajal were studied using immunocytochemistry and in situ hybridisation. Motor activity was studied in vitro. RESULTS: Adaptive changes in bypassed ileum include atrophy and remodelling of the gut wall. The total numbers of submucous and myenteric neurones per unit length increased one and four weeks after bypass but were identical to sham operated intestine 10 weeks after bypass. Neurones expressing vasoactive intestinal peptide, neuropeptide Y, or pituitary adenylate cyclase activating peptide decreased gradually in number in bypassed ileum. Nitric oxide synthase expressing neurones were increased, particularly in the myenteric ganglia. No change in the frequency and distribution of interstitial cells of Cajal was noted. The contractile response elicited by electrical stimulation of sham operated ileum consisted of a fast cholinergic twitch followed by a slower non-adrenergic, non-cholinergic contraction. In the bypassed ileum an identical biphasic contraction was elicited; however, the entire response was non-adrenergic, non-cholinergic. The relaxatory response to electrical stimulation in sham operated ileum was nitric oxide mediated; after bypass it was non-nitrergic. CONCLUSIONS: Notable atrophic changes were seen in the rat ileum after bypass. The enteric nervous system reacted with neuronal cell death and plasticity in terms of release and expression of neurotransmitters.

A RAPD-PCR method for large-scale typing of Bacillus cereus.

A robust RAPD-PCR procedure for large-scale typing of Bacillus cereus was developed. It is based on a simple DNA preparation, involving only freezing and boiling of cells in water with active carbon. By using a computerized system for data collection and processing, an efficient system for handling RAPD patterns for large-scale investigations was achieved. The procedure was highly discriminatory for Bacillus cereus strains and was found to give reproducible classification of RAPD fingerprints for five reference strains.