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Background: A defined bacterial mixture could be a safer alternative to faecal microbiota transplantation (FMT)., Aims: To compare the efficacy of a 12-strain mixture termed rectal bacteriotherapy with either FMT or vancomycin for recurrent Clostridioides difficile infection (CDI) in an open-label 3-arm randomised controlled trial., Methods: We screened all individuals positive for C difficile from May 2017 to March 2019. Persons with laboratory-confirmed recurrent CDI were included. Before FMT and rectal bacteriotherapy, we pre-treated with vancomycin for 7-14 days. Rectal bacteriotherapy was applied by enema on three consecutive days and FMT by enema once with possible repetition for two to three infusions within 14 days. The vancomycin group was treated for 14 days with additional five weeks of tapering for multiple recurrences. The primary outcome was clinical cure within 90 days. A secondary outcome was 180-day all-cause mortality., Results: Participants in the FMT group (n = 34) were cured more often than participants receiving vancomycin (n = 31), 76% vs 45% (OR 3.9 (1.4-11.4), P < 0.01) or rectal bacteriotherapy (n = 31), 76% vs 52% (OR 3.0 (1.1-8.8), P = 0.04). Rectal bacteriotherapy and vancomycin performed similarly (P = 0.61). The mortality rate was 6% in the FMT group, 13% in the bacteriotherapy group and 23% in the vancomycin group. FMT tended to reduce mortality compared with vancomycin, OR 0.2 (0.04-1.12), P = 0.07., Conclusions: Rectal bacteriotherapy appears as effective as vancomycin but less effective than 1-3 FMTs. FMT by enema with 1-3 infusions is superior to vancomycin for treating recurrent C difficile infections and might reduce mortality., (© 2021 John Wiley & Sons Ltd.)

We compared the transverse and longitudinal approaches to ultrasound-guided identification of the cricothyroid membrane, to determine which was faster and more successful. Forty-two anaesthetists received a one-hour structured training programme consisting of e-learning, a lecture and hands-on training, and then applied both techniques in a randomised, cross-over sequence to obese females with body mass index 39.0 - 43.9 kg.m(-2) . The mean (SD) time to identify the cricothyroid membrane was 24.0 (12.4) s using the transverse technique compared with 37.6 (17.9) s for the longitudinal technique (p = 0.0003). Successful identification of the cricothyroid membrane was achieved by 38 (90%) anaesthetists using either technique. All anaesthetists were successful in identifying the cricothyroid membrane with at least one of the techniques. We advocate the learning and application of these two techniques for identification of the cricothyroid membrane before starting anaesthesia in difficult patients, especially when anatomical landmarks are impalpable. Further use in emergency situations is feasible, if clinicians have experience and the ultrasound machine is readily available., (© 2016 The Association of Anaesthetists of Great Britain and Ireland.)

Background: Videolaryngoscopes with sharp angulated blades improve the view of the vocal cords but this does not necessarily result in higher success rates of intubation The aim of this study was to evaluate the efficacy of using Boedeker intubation forceps in conjunction with McGrath Series 5 Videolaryngoscope (MVL) in patients with predictors for difficult intubation., Methods: The study was conducted at the Department of Anaesthesia, Copenhagen University Hospital from September to December 2013. Patients with one or more predictors of difficult intubation scheduled for general anaesthesia were assessed for eligibility. Patients were intubated using Boedeker intubation forceps and MVL. The primary endpoint was time to intubation. The secondary endpoints were intubation success rate, number of intubation attempts, intubation conditions and post-operative hoarseness., Results: Thirty-three patients were assessed for eligibility, and 25 patients were included in the study with a median SARI score of 3 (IQR 3-4). Twenty-two (88%, 95% confidence interval [74-100%]) of the patients were successfully intubated by the method with a median time to intubation of 115 s (IQR 78-247). Steering and advancement of the tube were reported as acceptable in 21 (84%) and 22 cases (88%), respectively, and excellent in 10 cases (45%) for both measures. Ten cases (40%) were intubated on the first attempt. There were three cases (12%) of failed intubation; in these cases, successful intubation was obtained by using a styletted tube., Conclusion(s): Most patients with anticipated difficult intubation can be successfully intubated with Boedeker intubation forceps and MVL. However, endotracheal tube placement failed in 3/25 patients despite a good laryngeal view., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Clostridium difficile infection is one of the most common nosocomial infections. Among other alternatives to standard treatment with vancomycin for recurrent infection are faecal microbiota transplantation and rectal bacteriotherapy with a fixed mixture of intestinal bacterial strains isolated from faeces of healthy persons to mimic a theoretical normal microflora. Developed by Dr. Tvede and Dr. Rask-Madsen, the latter method has been in use for selected patients during the last 25 years in Denmark. In this study we reviewed the medical records of patients treated with rectal bacteriotherapy for relapsing C. difficile in Denmark, 2000-2012. The primary end point was recurrent diarrhoea within 30 days after treatment. A total of 55 patients were included in this case series. Thirty-five patients (64%) had no recurrence within 30 days of bacteriotherapy. Patients with recurrence tended to be older (75.8 years vs. 61.3 years; p 0.26), and more often have preexisting gastrointestinal illness and longer duration of time from the first CDI to bacteriotherapy (221.6 days vs. 175.3 days; p 0.18). Treatment success was 80% in the subgroup of patients with no known gastrointestinal illness and first C. difficile episode less than 6 months before bacteriotherapy. The most common adverse events were abdominal pain (10.9%) and worsening diarrhoea (4.3%). One patient was hospitalized 10 days after treatment with appendicitis, fever, and Escherichia coli bacteremia. The results from this study indicate that rectal bacteriotherapy is a viable alternative to faecal microbiota transplantation in patients with relapsing C. difficile-associated diarrhoea., (Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Polyacrylamide hydrogel has in the last decade gained popularity as an injectable filler for facial augmentation due to its features of non-toxicity, biocompatibility, safety profile, and immediate effect. However, as all types of injections carry the risk of infection and since the polyacrylamide hydrogel is a non-degradable implant, the possibility of bacterial biofilm formation exists. Theoretically, the risk of infection and subsequent biofilm formation can be avoided by using prophylactic antibiotic treatment prior to the time of injection., Method: This retrospective study of outcomes following polyacrylamide hydrogel injections includes 657 subjects from one centre, which had facial injections from 2001 and 2011. Until 2007 prophylactic antibiotics were not given prior to treatment, but in September 2007 a single oral dose of azithromycin (Zitromax) and moxifloxacin (Avelox) was introduced as prophylactic antibiotics. A total of 496 subjects were injected before 2007 without antibiotic prophylactic treatment, and 161 subjects received these two antibiotics prior to treatment from September 2007., Results: The prophylactic antibiotics (azithromycin and moxifloxacin) significantly reduced the incidence of clinical signs of inflammation/infections from 7 to 2% (P=0.03)., Conclusion: Even though the incidence of inflammation/infections following injection of polyacrylamide hydrogel is relatively low, it may be reduced further by using prophylactic antibiotic treatment. Based on our experience, we recommend prophylactic antibiotics to patients who have facial augmentation with polyacrylamide hydrogel in order to avoid infection and risk of biofilm formation due to contamination during injection with naturally occurring micro flora from skin and lips.

Injection of soft tissue fillers plays an important role in facial reconstruction and esthetic treatments such as cosmetic surgery for lip augmentation and wrinkle smoothening. Adverse events are an increasing problem, and recently, it has been suggested that bacteria are the cause of a vast fraction these. We developed a novel mouse model and evaluated hyaluronic acid gel, calcium hydroxyl apatite microspheres, and polyacrylamide hydrogel for their potential for sustaining bacterial infections and their possible treatments. We were able to culture Pseudomonas aeruginosa, Staphylococcus epidermidis, and Probionibacterium acnes in all three gels. When contaminated gels were left for 7 days in a mouse model, we found sustainment of bacterial infection with the permanent gel, less with the semi-permanent gel, and no growth within the temporary gel. Evaluation of treatment strategies showed that once the bacteria had settled (into biofilms) within the gels, even successive treatments with high concentrations of relevant antibiotics were not effective. Our data substantiate bacteria as a cause of adverse reactions reported when using tissue fillers, and the sustainability of these infections appears to depend on longevity of the gel. Most importantly, the infections are resistant to antibiotics once established but can be prevented using prophylactic antibiotics., (© 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.)

Background: Recurrent Clostridium difficile infection (CDI) is a significant problem due to its increased incidence and severity. Failure rates for standard antibiotic therapies are high. In our hospital, faecal microbiota transplantation (FMT), or instillation of a culture mixture of known enteric bacteria in saline as rectal bacteriotherapy (RBT), has long been used as 'rescue therapy' in patients with recurrent disease, in whom repeated courses of standard antibiotic treatment have failed. We wanted to evaluate the effectiveness of FMT and RBT for recurrent CDI., Methods: The records of 31 patients treated with either FMT or RBT for recurrent CDI were reviewed retrospectively. FMT was based on faecal donation by a close relative and RBT on a defined saline mixture of 10 individually cultured enteric bacterial strains originally isolated from healthy persons. Both types of instillation were carried out through a rectal catheter. FMT (500 ml) was given as 1 installation. RBT (200 ml) was given as 2 or 3 installations with an interval of 2 days between courses. Treatment success was defined as a sustained loss of symptoms and discontinuation of diarrhoea within 3 days., Results: Of 31 patients, 23 (74%) responded successfully to the treatment: 16 of 23 (70%) receiving FMT and 7 of 8 (88%) receiving RBT., Conclusion: We found FMT to be effective in patients with recurrent CDI. RBT based on a predefined bacterial suspension was as effective as or better than FMT based on faecal donation; however, multiple installations may be needed.

New gene sequencing-based techniques and the large worldwide sequencing capacity have introduced a new era within the field of gut microbiota. Animal and human studies have shown that obesity and type 2 diabetes are associated with changes in the composition of the gut microbiota and that prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gut microbiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism.

Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) is a promising and fast method for identifying fungi and bacteria directly from positive blood cultures. Various pre-treatment methods for MALDI-TOF MS identification have been reported for this purpose. In-house results for identification of bacterial colonies by MALDI-TOF MS using a cut-off score of 1.5 did not reduce the diagnostic accuracy compared with the recommended cut-off score of 1.8. A 3-month consecutive study of positive blood cultures was carried out in our laboratory to evaluate whether the Sepsityper™ Kit (Bruker Daltonics) with Biotyper 2.0 software could be used as a fast diagnostic tool for bacteria and fungi and whether a 1.5 cut-off score could improve species identification compared with the recommended score of 1.8. Two hundred and fifty-six positive blood vials from 210 patients and 19 blood vials spiked with fungi were examined. Using the cut-off score of 1.8, 81% Gram-negative bacteria were identified to the species level compared to 84% using a cut-off score of 1.5. For Gram-positive bacteria 44% were identified to the species level with a cut-off of 1.8 compared to 55% with the value of 1.5. The overall identification rate was 63% (cut-off 1.5) and 54% (cut-off 1.8). Seventy-seven per cent of fungal species were identified with both log scores. MALDI-TOF MS was in this study found to be a powerful tool in fast diagnosis of Gram-negative bacteria and fungi and to a lesser degree of Gram positives. Using 1.5 as cut-off score increased the diagnosis for both Gram-positives and -negatives bacteria., (© 2013 APMIS. Published by John Wiley & Sons Ltd.)

Background: This was a retrospective study analyzing the mortality and incidence of Aspergillus infection and invasive disease, comparing patients given voriconazole for 3 months following transplantation to patients not given prophylaxis., Methods: All consecutive patients (n = 147) transplanted at Copenhagen University Hospital, Rigshospitalet from 2002 to 2006 were included in the study; the study period included the 2 years before the initiation of fungal prophylaxis (88 patients) and the 2 years after (59 patients). Eight patients transplanted in this period were excluded leaving 139 patients in the study., Results: No effect of voriconazole on the incidence of Aspergillus infection (colonization, or superficial or invasive infection) or on the time from transplantation to the first sign of infection was seen when the 2 groups of patients were compared. The cumulated incidence of infection was 45% without and 49% with prophylaxis, and in both groups approximately half of the infections occurred in the first 3 months, the time during which prophylaxis was given. There were significantly more cystic fibrosis (CF) patients among the Aspergillus-infected patients compared to other diagnoses, and the effect of prophylaxis was the same as in non-CF patients. There was a significantly lower mortality in the voriconazole-treated group compared to the non-prophylaxis group, but in an isolated analysis of Aspergillus-infected patients this difference no longer existed; hence, the difference in mortality must be attributable to a time effect and not to voriconazole prophylaxis., Conclusions: Routine use of voriconazole treatment for prophylaxis against Aspergillus infection in lung transplant recipients does not appear to be warranted.

Background: Intubation using a flexible optical scope (FOS) is a cornerstone technique for managing the predicted and unpredicted difficult airway. The term FOS covers both fibre-optic scopes and videoscopes. The total costs of using flexible scopes for intubation are unknown. The recent introduction of a disposable flexible scope for intubation merits closer scrutiny of the total costs associated with both modalities., Methods: The costs incurred during intubations using FOSs at a large anaesthesia department were identified, and a series of intubations using a disposable scope were analyzed for comparison. Recognized health-economic methodology was applied., Results: During a 1-year period, 360 FOS intubations were performed. In this clinical setting, the average cost of an intubation using a reusable FOS was €177.7. When using the disposable Ambu(®) aScope (Ambu A/S, Ballerup, Denmark), the cost was €204.4. The break-even point, i.e. the number of intubations per month where the cost of using disposable and non-disposable equipment is identical, was 22.5/month. A subgroup analysis looking solely at intubations performed with flexible videoscopes revealed that the cost per intubation was equal for disposable and reusable videoscopes., Conclusion: At our institution, the total cost of an intubation is greater when using disposable compared with reusable equipment (€204.4 vs. €177.7). If video equipment with an external monitor is considered mandatory, the expenses are of equal magnitude. The cost analysis is particularly sensitive to the actual number of flexible optic intubations performed; with fewer intubations, the total cost will begin to favour disposable equipment., (© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.)

We conducted a retrospective epidemiologic study of catheter related bloodstream infections (CRBSI) in patients receiving long-term home parenteral nutrition (HPN) from January 2002 to December 2005. Our results showed that coagulase negative staphylococci (CoNS) were the most prevalent pathogens (44.7% of all CRBSI episodes), followed by Enterobacteriaceae (33.2%). Prevalence for candidemia and Enterococcus bacteremia was relatively high (14.4% and 10.8%, respectively). Cefuroxime resistance was observed in 65.4% CoNS and 31.5% Enterobacteriaceae. Based on the results from the study, a new empiric antimicrobial treatment regiment was suggested.

Enterococcus species are common in nosocomial bloodstream infections and their incidence is rising. Although well recognized in several serious bacterial infections, the influence of appropriate antimicrobial therapy in enterococcal bacteraemia has not been fully settled. The aim of the study was to determine whether administration of inappropriate antibiotics in enterococcal bacteraemia is an independent risk factor for mortality, among other known and suspected risk factors. We conducted a cohort study of E. faecalis/faecium bacteraemia during a 3-year period at a single tertiary care hospital in Denmark. Patients with growth of non-enterococcus co-pathogens apart from the enterococcal bacteraemia were also included, as were patients with repeated enterococcal bacteraemia. Time to appropriate antimicrobial therapy was counted from the first episode. Appropriate antibiotic therapy was defined as any therapy with documented clinical effect, in vitro activity and a minimum treatment length of 6 days. Multivariate regression models were built to determine the independent risk factors for mortality. We included 196 patients with enterococcal bacteraemia. Appropriate antibiotics for at least 6 days were administered in 146 of these (74%). Thirty-day mortality was 26%. Multivariate logistic regression identified independent predictors of 30-day all-cause mortality: appropriate antimicrobial therapy for ≥ 6 days (odds ratio for mortality 0.33, 0.14-0.79), ICU admission (4.2, 1.7-10), thrombocytopenia (3.9, 1.6-9.3), chronic liver failure (3.3, 1.1-10) and age ≥ 60 years (2.2, 0.99-5.0). Antibiotics not appropriately covering enterococci are frequently administered empirically in suspected bloodstream infections. Inappropriate antibiotic therapy was an independent risk factor for mortality in enterococcal bacteraemia., (© 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.)

A total of 65 toxigenic Clostridium difficile strains isolated from patients with antibiotic-associated diarrhea were tested for susceptibility to avilamycin, flavomycin, monensin, and salinomycin. Except for flavomycin the substances showed in vitro efficacy comparable to reports of the currently most commonly used drugs for treatment of C. difficile. This indicates that these old compounds may be useful for the treatment of C. difficile infections in man and perhaps for other bacterial causes of diarrhea., (© Mary Ann Liebert, Inc.)

A case of infective endocarditis caused by Abiotrophia defectiva is presented. The use of MALDI-TOF mass spectrometry as a rapid and accurate diagnostic tool in infective endocarditis is discussed.

Objective: In this prospective study we investigated the role of plasma levels of soluble urokinase plasminogen activator receptor (suPAR) in children with urinary tract infection., Material and Methods: We measured the levels of plasma suPAR during admission in 42 children with suspected acute pyelonephritis and compared the results to acute DMSA scintigraphy., Results: The mean level of plasma suPAR at admission was significantly elevated in children with renal involvement (7.3 ng/ml) assessed by the DMSA scintigraphy compared to children without renal involvement (4.4 ng/ml, P = 0.010). The positive predictive value of suPAR seems high, since all patients without renal involvement had low suPAR values. During treatment the mean level of plasma suPAR decreased., Conclusion: We conclude that plasma suPAR could be of clinical use for the diagnosis of acute pyelonephritis and that high levels of plasma suPAR might reflect the level of renal involvement and could therefore be a new indicator for renal scarring.

It has become evident that aggregation or biofilm formation is an important survival mechanism for bacteria in almost any environment. In this review, we summarize recent visualizations of bacterial aggregates in several chronic infections (chronic otitis media, cystic fibrosis, infection due to permanent tissue fillers and chronic wounds) both as to distribution (such as where in the wound bed) and organization (monospecies or multispecies microcolonies). We correlate these biofilm observations to observations of commensal biofilms (dental and intestine) and biofilms in natural ecosystems (soil). The observations of the chronic biofilm infections point toward a trend of low bacterial diversity and sovereign monospecies biofilm aggregates even though the infection in which they reside are multispecies. In contrast to this, commensal and natural biofilm aggregates contain multiple species that are believed to coexist, interact and form biofilms with high bacterial and niche diversity. We discuss these differences from both the diagnostic and the scientific point of view.

Background: This study investigated whether intraoperative use of a cell saver reduces the systemic inflammatory response after coronary operations using cardiopulmonary bypass (CPB)., Methods: The study randomized 29 patients, 15 to cell saving of pericardial suction blood and residual blood in the CPB circuit after perfusion (cell saver group) vs 14 who received direct retransfusion of the suction blood and the CPB circuit blood (control group). Outcome measures were plasma concentrations of the inflammatory markers interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha, soluble tumor necrosis factor receptors I and II, and procalcitonin at 6, 24, and 72 hours postoperatively., Results: At 6 hours postoperatively, the cell saver group displayed significantly reduced plasma levels of IL-6 and IL-8 (p < 0.05). A reduction in IL-10 was also found (p = 0.05), along with nonsignificant reductions in the remaining markers. At 24 and 72 hours, significant differences between groups no longer existed. In the cell saver group, the suction blood and CPB circuit blood were cleared for tumor necrosis factor receptors (p < 0.005), and IL-6, IL-8, IL-10, and procalcitonin were significantly reduced (p < 0.05). Median intraoperative blood loss was 250 mL in the cell saver group vs 475 mL (p < 0.02). Immediately postoperatively the hemoglobin level was higher in the cell saver group (p < 0.03). Transfusion requirements were similar., Conclusions: The cell saver reduced the systemic levels of the proinflammatory markers IL-6 and IL-8 at 6 hours after CPB. The role of the anti-inflammatory molecules IL-10 and soluble tumor necrosis factor receptors is undefined in this setting., (Copyright (c) 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Necrotizing fasciitis (NF) is an acute soft-tissue infection, associated with a high mortality and morbidity. To reduce the mortality, an early diagnosis and treatment is essential. Our study aims to identify the number of patients, the microorganisms involved, and NF treatment outcomes among patients admitted to our unit., Material and Methods: This retrospective cohort study enrolled 85 patients admitted to the multidisciplinary, tertiary Intensive Care Unit, Abdominal Center, Rigshospitalet, Denmark in 2005-2007. All received the same protocolled treatment of intensive care, extensive surgical débridements, broad-spectrum antibiotics, intravenous immunoglobulin and hyperbaric oxygen., Results: The microbiological analyses of specimens demonstrated that 51% were positive for polymicrobial infection, 40% for a single pathogen, 74% of these caused by beta-hemolytic streptococci, and 9% of the analyses were inconclusive. Of the patients, 91% required treatment in a respirator, 67.5% presented with septic shock and 25.3% developed acute renal failure needing dialysis. Intensive care unit mortality was 6% and 30-day mortality was 9.5%. Expected mortality based on SAPS II and APACHE II scoring was 38%. Our patients had a significantly higher body mass index than other patients admitted to the unit., Conclusion: NF is a complex disease, often associated with multi-organ failure. A protocolled treatment plan with close cooperation between the intensive care, clinical microbiology, medical and surgical specialties seems to reduce mortality considerably in this vulnerable group of patients.

Bacterial biofilms on long-term catheters are a major source of infection. Exposure to ultraviolet C (UVC - 265 nm) light was shown in an earlier study to reduce the number of bacteria substantially on ex vivo treated urinary patient catheters. Very large doses (long treatment times) should, however, be applied to obtain 99.9% disinfection rates. The major reason was that besides cells the mature biofilm contained absorbing and scattering particulates, which made the biofilm opaque. The potential of UVC light emitting diodes (LED) for disinfection purposes in catheter-like tubes contaminated with biofilm was investigated. It was shown that UVC light propagation was possible through both Teflon and catheter tubes (silicone). The disinfection efficiency of the diodes was demonstrated on tubes contaminated artificially with a Pseudomonas aeruginosa biofilm. The tubes were connected to a flow system and biofilms were produced during a 3 day period. Tubes in lengths of 10 (Teflon, silicone) and 20 cm (Teflon) were contaminated. Tubes for control and for UVC treatment were contaminated in parallel. Biofilms were sampled from the total inner surface of the tubes. Colony counts on the control samples were in the range of 5 x 10(5)-1.3 x 10(9) CFU ml(-1), with disinfection rates in the range 96-100%. The applied UVC doses corresponded to treatment times between 15 and 300 min. Disinfection (100%) was obtained in 10 cm Teflon tubes exposed for 30 min (detection limit <5 CFU ml(-1)). The same result was obtained for a 20 cm Teflon tube exposed for 300 min. The disinfection rate was 96% for the 20 cm tube if the dose was reduced to 30 min. A disinfection rate of 99.99% was observed for a 10 cm peritoneal dialysis catheter tube (silicone) exposed for 300 min. Differences between the tubes were dependent on the differences in length and the type of the material. The UVC light was transmitted six times more efficiently in Teflon than in silicone tubes of equal length (10 cm). The germicidal effect to obtain a 99.99% killing rate for the biofilm ( approximately 78 J m(-2)) is comparable to that for the planktonic bacterium. It is concluded that there is potential for LED UVC light sources if they are used for disinfection of thin biofilms.

In hyperbaric medicine, blinded trials are remarkably few, making results susceptible to criticism. The scopes of the present study are to present a method for a double-blinded randomized clinical study and evaluate the validity of the method in a hyperbaric setting. Twenty-two healthy volunteers with no diving experience were included. The volunteers were randomized either to a "therapeutic pressure" group (15 msw, 253 kPa) or to a "placebo" group (2 msw, 120 kPa). The two profiles were made equal regarding noise, temperature and ventilation. The volunteers were asked whether they had been exposed to placebo or therapeutic pressure. They were asked to present their certainness of the answer on a visual analogue scale (VAS). Fisher's exact test calculates a probability of P = 0,328, which indicates that the volunteers have no valid opinion as to whether they were exposed to 15 msw or to 2 msw. It is found that it is possible to perform a blinded treatment on healthy volunteers with no prior diving experience.

The incidence of Clostridium difficile-associated infections is increasing, but it remains to be defined whether any change in the seroprevalence of C. difficile has also occurred. In a population-based study of the general adult population, 734 subjects, aged 15-69 years, were examined on two occasions 8 years apart (1990 and 1998) for the presence of antibodies against C. difficile in serum. The overall seroprevalence of C. difficile increased significantly from 19% in 1990 to 27% in 1998 (P<0.0001). The seroprevalence increased with increasing age in both 1990 and 1998, but the increase was about four times higher in 1998 than in 1990. In conclusion, the observed increase in seroprevalence suggests a higher exposure to C. difficile in the general Danish adult population.

Bacterial biofilms on permanent catheters are the major sources of infection. Exposure to ultraviolet-C (UVC) light has been proposed as a method for disinfecting the inner surface of catheters. Specification of a UVC-based device for in vivo disinfection is based on the knowledge of the required doses to kill catheter biofilm. Given these doses and the power of available UVC light sources, calculation of the necessary treatment times is then possible. To determine the required doses, contaminated urinary catheters were used as test samples and UVC treated in vitro. Patient catheters (n = 67) were collected and cut into segments of equal size and treated with various UVC doses. After treatment, the biofilm was removed by scraping and quantified by counting colony forming units. Percentage killing rates were determined by calculating ratios between UVC-treated samples and controls (no UVC treatment). Mean killing rates were 89.6% (0.5 min), 98% (2 min), and 99% (60 min). Approximately 99% killing was obtained with a UVC dose of 15 kJ m(-2). This dose, which is about 100 to 1000 times greater than the lethal dose for planktonic cells, is expected to be the maximum dose required to maintain newly inserted catheters free of contamination. The combination of high doses required to kill mature biofilm and the limited effect of current UVC light sources result in a relative long treatment time ( approximately 60 min). If a UVC-based method is to be of practical use for disinfection of catheters in the clinic, repeated preventive treatments should be carried out on newly inserted catheters.

Lung transplant recipients experience a particularly high incidence of Aspergillus infection in comparison with other solid-organ transplantations. This study was conducted to determine the incidence of Aspergillus colonisation and invasive aspergillosis, and the impact on long-term survival associated with Aspergillus infection. A retrospective study of 362 consecutive lung transplant patients from a single national centre who were transplanted 1992-2003 were studied. Twenty-seven patients were excluded due to incomplete or missing files. A total of 105/335 (31%) patients had evidence of Aspergillus infection (colonisation or invasion), including 83 (25%) patients with colonisation and 22 (6%) patients with radiographic or histological evidence of invasive disease. Most of the infections occurred within the first 3 months after transplantation. Cystic fibrosis (CF) patients had higher incidences of colonisation and invasive disease [15 (42%) and 4 (11%) of 36 patients] than non-CF patients [68 (23%) and 18 (6%) of 299 patients] (P = 0.01). Invasive aspergillosis was associated with 58% mortality after 2 years, whereas colonisation was not associated with early increased mortality but was associated with increased mortality after 5 years compared to non-infected patients (P < 0.05). An analysis of demographic factors showed that donor age [OR 1.40 per decade (95% CI 1.10-1.80)], ischaemia time [OR 1.17 per hour increase (95% CI 1.01-1.39)], and use of daclizumab versus polyclonal induction [OR 2.05 (95% CI 1.14-3.75)] were independent risk factors for Aspergillus infection. Invasive aspergillosis was associated with early and high mortality in lung transplant patients. Colonisation with Aspergillus was also associated with a significant increase in mortality after 5 years. CF patients have a higher incidence of Aspergillus infection than non-CF patients.

Background: Urinary tract infection is one of the most common nosocomial infections in hospitalized patients. It is predominantly associated with indwelling urinary catheters., Objective: To determine whether nitrofurazone-impregnated urinary catheters reduce the incidence of catheter-associated bacteriuria and funguria (CABF)., Design: Randomized, double-blind, controlled trial., Setting: Copenhagen Trauma Center, Copenhagen, Denmark., Patients: 212 consecutive adult trauma patients admitted between July 2003 and August 2005. Eligible patients needed a urinary catheter on arrival and were excluded if they were HIV positive, were pregnant, had a primary burn injury, or were receiving steroid treatment or if informed consent was unattainable., Interventions: Nitrofurazone-impregnated or standard silicone catheter throughout the duration of catheterization., Measurements: Catheter-associated bacteriuria and funguria, defined as at least 10(3) colony-forming units/mL, was assessed daily until removal of the catheter, with a prespecified minimum of 24-hour follow-up for the primary analysis. The microbiologist was blinded to study group assignment., Results: 1190 urine cultures were obtained over 1001 catheter-days. Catheter-associated bacteriuria and funguria occurred less frequently in the nitrofurazone catheter group than in the silicone catheter group (7 of 77 [9.1%] vs. 19 of 77 [24.7%]; incidence per 1000 catheter-days, 13.8 vs. 38.6; adjusted risk, 0.31 [95% CI, 0.14 to 0.70]; P = 0.005). Onset of CABF was delayed in the nitrofurazone group (P = 0.01), and nitrofurazone catheters led to fewer instances of new or changed antimicrobial therapy (adjusted risk, 0.27 [CI, 0.10 to 0.69]; P = 0.006)., Limitations: The clinical significance of asymptomatic bacteriuria and funguria is unclear. Data were missing in 27% of patients, and the magnitude of effect of the nitrofurazone catheters varied by assumptions about outcomes in patients who did not complete 24-hour follow-up., Conclusions: Nitrofurazone-impregnated urinary catheters reduced the incidence of CABF in adult trauma patients, reducing the need to change or prescribe new antimicrobial therapy. ClinicalTrials.gov registration number: NCT00192985.

Objective: Crohn's disease (CD) has been associated with low mucosal interleukin (IL)-10 production, but the mechanism behind this deficiency remains unclear. The aim of this study was to investigate IL-10 and interferon (IFN)-gamma production in intestinal CD4+ T cells from CD patients and healthy volunteers (HV) and to examine how this was affected by bacterial products and the presence or absence of autologous dendritic cells., Material and Methods: We cultured intestinal CD4+ T cells from CD patients (n=9) and HV (n=6) and differentiated dendritic cells from their peripheral monocytes. Intestinal T cells were stimulated with Lactobacillus strains or autologous intestinal bacteria in the presence or absence of dendritic cells. IL-10 and IFN-gamma were measured on day 4., Results: When there were autologous dendritic cells present, CD intestinal T cells produced high levels of IFN-gamma (mean 6.4 ng/ml+/-standard error of the mean 1.1 ng/ml) but low levels of IL-10 (0.7 ng/ml+/-0.1 ng/ml). In contrast, HV intestinal T cells produced less IFN-gamma (3.9 ng/ml+/-0.8 ng/ml, p=0.06) and more IL-10 (4.6 ng/ml+/-0.9 ng/ml, p=0.0001) than CD intestinal T cells. Co-culture with Lactobacilli failed to revert this imbalance in CD, but tended to do so in HV. When there were no dendritic cells, CD intestinal T cells responded to autologous bacteria with an increased IFN-gamma production (2.3+/-1.3 ng/ml) compared with HV intestinal T cells (0.3+/-0.2 ng/ml)., Conclusions: Crohn's disease intestinal CD4+ T cells display a pro-inflammatory cytokine profile with impaired production of the regulatory cytokine IL-10. Tolerogenic bacteria (Lactobacilli) failed to restore this regulatory defect.

Introduction: Fever and infections are common complications in children with cancer during chemotherapy. The purpose of this study was to investigate the usefulness of procalcitonin (PCT) in the identification of children with bacteraemia at time of admission with febrile episodes. Furthermore, we compared the usefulness of procalcitonin with that of C-reactive protein (CRP)., Material and Methods: We evaluated 55 febrile episodes in 34 children in treatment for cancer. We found 24 episodes of bacteraemia and 31 episodes with negative blood cultures., Results: The median PCT and CRP levels in children with positive blood cultures were significantly higher compared with children with negative blood cultures. The optimum cut-off level to predict bacteraemia was 1 mg/l for PCT and 50 mg/l for CRP. In distinguishing between febrile episodes with and without bacteraemia, PCT was found to have higher positive predictive value and similar negative predictive value as compared to CRP at the optimum cut-off level., Conclusion: These results show the potential usefulness of PCT as an early indicator for bacteraemia in febrile children with cancer and furthermore indicate that PCT may be more sensitive than CRP in the assessment of the cause of fever in these children.

Introduction: Accurate and timely diagnosis of community-acquired bacterial infections in patients with systemic inflammation remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival. We therefore compared the diagnostic characteristics of novel and routinely used biomarkers of sepsis alone and in combination., Methods: This prospective cohort study included patients with systemic inflammatory response syndrome who were suspected of having community-acquired infections. It was conducted in a medical emergency department and department of infectious diseases at a university hospital. A multiplex immunoassay measuring soluble urokinase-type plasminogen activator (suPAR) and soluble triggering receptor expressed on myeloid cells (sTREM)-1 and macrophage migration inhibitory factor (MIF) was used in parallel with standard measurements of C-reactive protein (CRP), procalcitonin (PCT), and neutrophils. Two composite markers were constructed - one including a linear combination of the three best performing markers and another including all six - and the area under the receiver operating characteristic curve (AUC) was used to compare their performance and those of the individual markers., Results: A total of 151 patients were eligible for analysis. Of these, 96 had bacterial infections. The AUCs for detection of a bacterial cause of inflammation were 0.50 (95% confidence interval [CI] 0.40 to 0.60) for suPAR, 0.61 (95% CI 0.52 to 0.71) for sTREM-1, 0.63 (95% CI 0.53 to 0.72) for MIF, 0.72 (95% CI 0.63 to 0.79) for PCT, 0.74 (95% CI 0.66 to 0.81) for neutrophil count, 0.81 (95% CI 0.73 to 0.86) for CRP, 0.84 (95% CI 0.71 to 0.91) for the composite three-marker test, and 0.88 (95% CI 0.81 to 0.92) for the composite six-marker test. The AUC of the six-marker test was significantly greater than that of the single markers., Conclusion: Combining information from several markers improves diagnostic accuracy in detecting bacterial versus nonbacterial causes of inflammation. Measurements of suPAR, sTREM-1 and MIF had limited value as single markers, whereas PCT and CRP exhibited acceptable diagnostic characteristics.

The aim of the study was to evaluate and compare the diagnostic value of sCD163 serum levels with CRP and PCT in meningitis and bacterial infection. An observational cohort study was conducted between February 2001 and February 2005. The study population comprised 55 patients suspected of meningitis on admission to a 27-bed infectious disease department at a Danish university hospital. Biomarker serum levels on admission were measured. Sensitivity and specificity were evaluated at pre-specified cut-off values and overall diagnostic accuracies were compared using receiver-operating characteristic AUCs (areas under curves). Patients were classified by 2 sets of diagnostic criteria into: A) purulent meningitis, serous meningitis or non-meningitis, and B) systemic bacterial infection, local bacterial infection or non-bacterial disease. An elevated serum level of sCD163 was the most specific marker for distinguishing bacterial infection from non-bacterial disease (specificity 0.91; sensitivity 0.47). However, the overall diagnostic accuracy of CRP (AUC =0.91) and PCT (AUC =0.87) were superior (p<0.02 and p<0.06) compared to that of sCD163 (AUC =0.72). For the diagnosis of systemic bacterial infection, the AUC of sCD163 (0.83) did not differ significantly from those of CRP or PCT. All markers had AUCs <0.75 for differentiating between purulent meningitis and other conditions. In conclusion, CRP and PCT had high diagnostic value and were superior as markers of bacterial infection compared to sCD163. However, sCD163 may be helpful in rapid identification of patients with systemic bacterial infection. If used as an adjunct to lumbar puncture, PCT and CRP had very high diagnostic accuracy for distinguishing between bacterial and viral infection in patients with spinal fluid pleocytosis. However, none of the markers was useful as an independent tool for the clinical diagnosis of patients with purulent meningitis.

Objective: To investigate day-by-day changes in procalcitonin and maximum obtained levels as predictors of mortality in critically ill patients., Design: Prospective observational cohort study., Setting: : Multidisciplinary intensive care unit at Rigshospitalet, Copenhagen University Hospital, a tertiary reference hospital in Denmark., Patients: Four hundred seventy-two patients with diverse comorbidity and age admitted to this intensive care unit., Interventions: Equal in all patient groups: antimicrobial treatment adjusted according to the procalcitonin level., Measurements and Main Results: Daily procalcitonin measurements were carried out during the study period as well as measurements of white blood cell count and C-reactive protein and registration of comorbidity. The primary end point was all-cause mortality in a 90-day follow-up period. Secondary end points were mortality during the stay in the intensive care unit and in a 30-day follow-up period. A total of 3,642 procalcitonin measurements were evaluated in 472 critically ill patients. We found that a high maximum procalcitonin level and a procalcitonin increase for 1 day were independent predictors of 90-day all-cause mortality in the multivariate Cox regression analysis model. C-reactive protein and leukocyte increases did not show these qualities. The adjusted hazard ratio for procalcitonin increase for 1 day was 1.8 (95% confidence interval 1.3-2.7). The relative risk for mortality in the intensive care unit for patients with an increasing procalcitonin was as follows: after 1 day increase, 1.8 (95% confidence interval 1.4-2.4); after 2 days increase, 2.2 (95% confidence interval 1.6-3.0); and after 3 days increase: 2.8 (95% confidence interval 2.0-3.8)., Conclusions: A high maximum procalcitonin level and a procalcitonin increase for 1 day are early independent predictors of all-cause mortality in a 90-day follow-up period after intensive care unit admission. Mortality risk increases for every day that procalcitonin increases. Levels or increases of C-reactive protein and white blood cell count do not seem to predict mortality.

Background: Catheter-associated urinary tract infection is the most common nosocomial infection in clinical settings. For bacteria ascending to the bladder the most common route is the extraluminal, but the intraluminal route also plays a role. For this reason, we compared two urinary closed system bags (CSB), one with a double and the other with a single non-return valve (NRV), in a laboratory setting in order to establish their ability to prevent or delay the ascent of bacteria from the drainage bag to the bladder., Patients and Methods: The tests were performed in two microbiological laboratories (Copenhagen (C), Denmark and Freiburg (F), Germany). These were blinded to each other. A urinary tract model using artificial urine was set up. Two sets of ten drainage bags each with a double NRV (CSB A), and two sets of ten drainage bags each with a single NRV (CSB B) were inoculated with Escherichia coli (F: ATCC 25922; C: clinical strain). Daily samples were taken from two drainage ports on each system - one above the NRV (Port I), the other above the top of the artificial bladder (Port II). Time till E. coli was detected at the drainage ports (time to positivity) was measured. Colonization of the 'bladder' was defined as time to positivity at Port II., Results: No significant differences in time to positivity at Port I (median 9.0, range: 6-12 for CSB B vs median 9.5 days, range: 6-13 for CSB A) were observed between the two systems. However, substantial differences were seen between the two systems in time to positivity at Port II: Port II on the bladder model using CSB B became positive after a median of 14.0 days (range: 10-22), whereas Port II of the model using CSB A only became positive after 21.5 days (range: 13-24). This amounts to a highly significant difference of 7.5 days (p = 0.0001) in the mean., Conclusion: Under laboratory conditions, colonization of the 'bladder' was significantly delayed when the CSB with a double NRV was used in comparison to the results obtained from the single NRV-system. Clinical trials should be conducted to investigate whether the urinary CSB with the double NRV has the ability to prevent (or to delay the onset of) catheter-associated urinary tract infection.

We describe a case of pseudomembraneous colitis (PMC) caused by a toxin A- B+ strain of Clostridium difficile (CD). In Denmark only a few laboratories investigate for toxin production, and if they do, the toxin A enzyme immunoassay (EIA) is the test generally used when testing for CD. This toxin A negative but toxin B positive strain thus remains undetectable. If CD-associated diarrhea is clinically suspected and tests for toxin A are negative, infection with a toxin A- B+ strain should be considered. Further diagnostic tests such as cellular cytotoxicity assays or toxin A/B EIA should be performed. The standard treatment of PMC in severely ill patients should be vancomycin, administered orally.

Objective: To compare two hydrophilic-coated (SpeediCath and LoFric and one uncoated gel-lubricated catheter (InCare Advance Plus) concerning withdrawal friction force and urethral micro trauma., Methods: 49 healthy male volunteers participated in this prospective, randomised, blinded, crossover study of three different bladder catheters. The withdrawal friction force was measured, and urine analysis of blood, nitrite and leucocytes, microbiological analysis of urine cultures and subjective evaluation of the catheters were performed., Results: 40 participants completed the study and were included in the analysis. SpeediCath exerted a significantly lower mean withdrawal friction force and work than the gel-lubricated uncoated catheter, whereas LoFric exerted a significantly higher mean friction force than both of the other catheters. The hydrophilic catheters caused less microscopic haematuria and less pain than the gel-lubricated uncoated catheter. Furthermore, 93% of the participants preferred the hydrophilic catheters., Conclusion: Hydrophilic-coated catheters perform better than uncoated catheters with regard to haematuria and preference. SpeediCath, but not LoFric, exerts less withdrawal friction force than InCare Advance Plus.

A functioning tunnelled central venous catheter (CVC) is a crucial device for patients with haematological malignancies receiving high-dose intravenous chemotherapy. Despite the advantages, CVC infections are a major cause of sepsis and prolonged hospital stay. This study investigated the impact of patient education regarding provision of their own catheter care on the frequency of CVC-related infections (CRIs) and was conducted at a specialized haematological unit at the University Hospital of Copenhagen Rigshospitalet. From May to September 2002, 82 patients fitted with tunnelled double-lumen Hickman catheters were randomized consecutively. The intervention group (42 participants) received individualized training and supervision by a clinical nurse specialist, with the aim of becoming independently responsible for their own catheter care. The control group (40 participants) followed the standard CVC procedures carried out by nurses inside and outside the central hospital. A significant reduction in CRIs was found in the intervention group, with a >50% reduction in the incidence rate of CRIs. We conclude that systematic individualized, supervised patient education is able to reduce catheter-related infections.

Objective: The purpose of this study was to determine the effect of hyperbaric oxygenation (HBO) on postural stability in healthy volunteers. The study was performed in accordance with treatment protocols for divers' decompression sickness and carbon monoxide poisoning., Methods: Twenty-one healthy male divers, aged 31 +/- 6.88 years (mean +/- SD), were tested with quantitative Romberg's test before and after HBO (90 min in a pressure chamber at an ambient pressure of 253 kPa, approximately 15 m of sea water, breathing pure oxygen). The quantitative Romberg's test is a calculation of the average sway for 50 s., Results: No difference was found between sway before and after the HBO (P < 0.05), i.e. we were unable to show that the results of quantitative Romberg's test are affected by HBO. Thus, the quantitative Romberg's test may be a valuable tool in evaluating patients with decompressions sickness, carbon monoxide intoxication and other neurological diseases normally treated with HBO.

Background: The purpose of the study was to investigate the frequency, morbidity and cause of acute gastroenteritis in children attending day-care centers in Denmark., Methods: Children with acute diarrhea (> or =2 consecutive loose stools in 24 hours, with duration of < or =7 days), recruited from 19 day-care centers, were included. Gastroenteritis viruses, group A rotavirus, sapoviruses, noroviruses and astroviruses were detected with reverse transcription-polymerase chain reaction assays. In addition, stool specimens were cultured for bacterial pathogens. Children who were brought to the clinic with acute diarrhea underwent a medical evaluation, including an estimation of dehydration., Results: Two hundred seven children (median age, 20.1 months; range, 9-44 months) were enrolled. During the 6-month study period, 98 diarrheal episodes in 95 children were reported. Of these, 48 were reported retrospectively in telephone interviews. The incidence of acute diarrheal episodes was 0.08 episode per child per month. A viral etiologic agent was identified in 69% of cases. Rotaviruses were identified in 17 cases (40%), sapoviruses in 8 (19%) and astroviruses in 3 (7%). One patient had a coinfection with rotavirus and astrovirus. Campylobacter jejuni was detected in 2 patients and Clostridium difficile was found in 5 patients, all coinfected with a virus. In clinical assessments, 9 patients (18%) showed signs of dehydration and were given oral rehydration solution; 6 of these were hospitalized., Conclusions: Acute diarrhea among children attending day-care centers was common in wintertime. Rotaviruses were, expectedly, the most common causative agents, but sapoviruses were second to rotaviruses as etiologic agents in this population.

The aim of this study was to present the first set of comprehensive data on fungemia in Denmark including the distribution of species and range of susceptibility to major antifungal compounds based on a seminational surveillance study initiated in 2003. The catchment area of the participating hospitals had a population of 2.8 million, or 53% of the Danish population. A total of 303 episodes of fungemia were registered (annual rate, 11 of 100,000 people or 0.49 of 1,000 hospital discharges). Candida species accounted for 97.4% of the fungal pathogens. C. albicans was the predominant species (63%), but the proportion varied from 57% to 72% among participating departments of clinical microbiology. C. glabrata was the second most frequent species (20%; range, 8% to 32%). C. krusei was a rare isolate (3%) and occurred only at two of the participating hospitals. Retrospective data retrieved from the Danish laboratory systems documented a continuous increase of candidemia cases since the early 1990s. For the 272 susceptibility-tested isolates, MICs of amphotericin B and caspofungin were within the limits expected for the species or genus. However, decreased azole susceptibility, defined as a fluconazole MIC of >8 microg/ml and/or itraconazole MIC of >0.125 microg/ml, was detected for 11 Candida isolates that were neither C. glabrata nor C. krusei. Including intrinsically resistant fungi, we detected decreased susceptibility to fluconazole and/or itraconazole in 87 (32%) current Danish bloodstream fungal isolates. We showed a continuous increase of fungemia in Denmark and an annual rate in 2003 to 2004 higher than in most other countries. The proportion of bloodstream fungal isolates with reduced susceptibility to fluconazole and/or itraconazole was also notably high.

Objective: To conduct a survey of the methods used in clinical microbiology laboratories in Europe to diagnose infection with Clostridium difficile., Methods: A questionnaire was devised and sent to a co-ordinating member of the Study Group in each of eight European countries. This co-ordinator was in charge of forwarding the questionnaire to hospital laboratories arbitrarily selected. The number of laboratories in each country was determined on the basis of one laboratory for 10,000 beds of hospitalization. This questionnaire covered different aspects pertaining to Clostridium difficile associated to diarrhea (CDAD) diagnosis such as circumstances of request, criteria used for undertaking C. difficile investigations, methods used for the diagnosis, etc., Results: A total of 212 questionnaires were completed and submitted for analysis: 87.7% of laboratories reported routinely performing C. difficile diagnostic tests. Methods used included toxin detection (93%), culture (55%), and glutamate dehydrogenase (GDH) detection (5.9%). Among the laboratories detecting toxins, different enzyme immunoassays (EIA) and cytotoxicity assays were used in 79% and 17.3% of cases, respectively. Among the different strategies reported, 4.8% were considered suboptimal for the diagnosis of C. difficile infections, but marked discrepancies could be observed between countries. The overall incidence (median) of CDAD was estimated at 1.1 for 1,000 patient admissions., Conclusion: The results of this study suggest marked discrepancies between laboratories and also between countries regarding the criteria by which C. difficile is investigated for, and the methods and the strategies that are used for the diagnosis of C. difficile. These discrepancies could be explained by the lack of clear guidelines for C. difficile diagnosis in each country, and by the importance that physicians attach to C. difficile. Precise guidelines for C. difficile diagnosis would be the first step to make possible accurate comparison of the incidence and the epidemiology of CDAD from one hospital to another or from one country to another.

Background: Seropositivity to food-borne and orofecal microorganisms (hepatitis A virus, Helicobacter pylori, and Toxoplasma gondii ), which are considered to be markers of poor hygiene, has been reported to be associated with a lower prevalence of atopy. In contrast, colonization of the gut with Clostridium difficile, a potential intestinal bacterial pathogen, in early childhood may be associated with a higher prevalence of atopy., Objective: The objective of this study was to investigate the association between atopy and exposure to 2 groups of food-borne and orofecal microorganisms: (1) markers of a poor hygiene and (2) intestinal bacterial pathogens., Methods: A cross-sectional population-based study of 15- to 69-year-olds living in Copenhagen, Denmark, was carried out in 1990 to 1991. Atopy was defined as a positive test result for specific IgE to at least 1 of 6 inhalant allergens. Exposure to microorganisms was assessed as IgG seropositivity to microorganisms., Results: Seropositivity to 2 or 3 markers of poor hygiene (hepatitis A virus, H pylori, and T gondii ) was associated with a lower prevalence of atopy (adjusted odds ratio, 0.5; 95% CI, 0.3 to 0.8). In contrast, seropositivity to 2 or 3 intestinal bacterial pathogens (C difficile, Campylobacter jejuni, and Yersinia enterocolitica ) was associated with a higher prevalence of atopy (adjusted odds ratio, 1.7; 95% CI, 1.2 to 2.6)., Conclusion: Exposure to markers of poor hygiene was associated with a lower prevalence of atopy, whereas exposure to intestinal bacterial pathogens was associated with a higher prevalence of atopy. These findings raise the hypothesis that different groups of food-borne and orofecal microorganisms may have different effects on the risk of atopy.

A new design for estimating the distribution of time to pregnancy is proposed and investigated. The design is based on recording current durations in a cross-sectional sample of women, leading to statistical problems similar to estimating renewal time distributions from backward recurrence times. Non-parametric estimation is studied in some detail and a parametric approach is indicated. The results are illustrated on Monte Carlo simulations and on data from a recent European collaborative study. The role and applicability of this approach is discussed.