Study design and setting
We conducted a prospective, observational, multicentre study of adults acutely admitted to two university-affiliated hospital organizations in Southern Denmark (study period from the 1st April 2015 to the 31st August 2016) and Northern Germany (study period from the 15th November 2015 to the 31st July 2016). The hospital in Southern Denmark (Hospital of Southern Jutland) included two EDs, the hospital in Northern Germany included two hospitals, St. Franziskus Hospital and Diakonissenkrankenhaus in Flensburg.
Although the study sites were in two different countries, they were located in the same geographical region, with less than 50 km distance between the sites.
Use of isolation procedures
The attending physicians made the decision on whether admitted patients required isolation procedures according to their individual judgement, whether they suspected Norovirus or C. difficile infections or not. This judgement was based on their general knowledge and experience with the diseases, as no national guidelines or local instructions existed concerning when to suspect these infections.
Inclusion and exclusion criteria
We identified eligible patients by reviewing patients who were admitted to participating EDs during weekdays (Monday to Friday). Using electronic patient logistic systems, the participating EDs in Denmark were screened twice daily for eligible patients. At the Danish sites, the electronic patient logistic systems require that physicians specify a chief complaint. We reviewed patients with the following chief complaints: (i) “diarrhoea and/or vomit of presumed infectious genesis” or (ii) “abdominal pain” with the additional note “under observation for acute appendicitis”. We included this latter group as a previous study found that such patients are frequently discharged with a diagnosis of GE [2]. Fever is also a predefined chief complaint, but not used to identify patients with gastroenteritis in our setting.
We included patients over 18 years who met the standard definition of GE, namely: an acute onset of three or more loose stools or any vomiting in 24 h, excluding patients with (a) cancer of the bowel, irritable bowel syndrome, Crohn’s disease, ulcerative colitis, cystic fibrosis, coeliac disease, or other chronic illness characterized by symptoms of diarrhoea or vomiting, or (b) for whom symptoms were assumed to be due to drugs, alcohol, or pregnancy [13]. Furthermore we excluded patients who had an ileostomy or colostomy (stool counts are inaccurate), patients who were unable to communicate in Danish or German, and patients who were unable or unwilling to provide consent.
Once a patient was identified in the electronic patient logistic systems, the nurse caring for the patient was contacted by a member of the study team to clarify if the patient met inclusion criteria. If they did then a member of the research team visited the patient to obtain informed consent and conduct a bedside interview.
The German sites did not register patients in a readily accessible registration system. Instead, these sites were called by phone once daily to screen for possible study participants. All nurses in the participating EDs received general information on the project.
The research team consisted of three study nurses and the first author. The study nurses were native language speakers according to the county where they worked. Members of the research team instructed the nurses who were providing patient care to obtain and send three faecal samples (one for each of the examinations for Norovirus, C. difficile and enteropathogenic bacteria) from a single bowel movement. A standardized method for collecting stool samples was used in the participating hospitals. Samples were collected in a sterile specimen container, immediately refrigerated, and then transported to the microbiological department at Soenderborg Hospital, where they were analysed for Norovirus and C. difficile (PCR analysis by BD Max, Becton Dickinson, New Jersey, USA). All stool samples were tested for C. difficile Toxin B, and if positive were further analysed for the presence of the binary toxin. The analyses for enteropathogenic bacteria, by culturing stool specimens on agar plates, were done in local microbiology departments.
Variables/ data sources
A standardized electronic questionnaire was used to obtain demographic data (patient identification number, date of admission, age, sex, medication, and comorbidities) and potential risk factors for infection. The questionnaire was available in German and Danish and the translation was conducted by native speakers of both languages. The questionnaire had been validated in a previous project [2]. The questionnaire was completed by research team members. Obtaining informed consent and interviewing the patient were performed in the same way in the Danish and German sites apart for the respectively spoken languages. Information on vital signs and isolation regimes was obtained from each patient’s medical file. Information on medications and comorbidities was self-reported.
We collected information on symptoms (duration of diarrhoea, number episodes of bowel movements on the day of symptom onset and number of episodes of vomiting on the day of symptom onset, faecal characteristics, and the presence of abdominal pain), vital signs including temperature, travel history, the recent use of drugs (including antibiotics), and infectious contacts, travel in the 2 months prior to the admission and current use of medications, recent use of antibiotics was defined as taking antibiotics on the day of admission, whereas the previous use of antibiotics was classified based on whether patients had completed an antibiotic treatment in the week prior to admission, in the month prior to admission, or in the 2 months prior to admission. In case of long term antibiotic use, the date of completing the cure was relevant. Data for “appearance of another patient in the ED with a positive sample for Norovirus or C. difficile within the last week” was generated using information contained in the study database.
The following three outcome variables were recorded: results of the faecal samples analyses for Norovirus, for C. difficile, and for enteropathogenic bacteria (Salmonella species, Campylobacter species, Yersinia species, and Shigella species).
Study size
In a previous study from the Hospital of Southern Jutland returned 64% of the patients discharged with a gastroenteritis diagnosis a faecal sample, of which 20% were positive for Norovirus or C. difficile [2].
Analysing with logistic regression methods requires a minimum 50 patients and an additional 10 cases per analysed variable [14]. Since for practical reasons we limited patient enrolment to weekdays (excluding holidays), we expected to identify no more than 25 positive stool samples during a one-year study period at the two Danish sites. We therefore established study duration of 18 months in the Danish sites and 6 months in the German sites hospital, with an aim to have at least 50 cases in total. We predefined, in case of less than 50 cases, only a univariate analysis would be reported.
Statistical methods
Questionnaires and laboratory results were collected electronically, stored according to the requirements of the Danish Data Protection Agency, and then merged and analysed in cooperation with a statistician. Data analysis was performed with Stata statistical software, version 14.2 (Stata Corp, College Station, Texas, USA). Continuous variables were described with median and interquartile range. Categorical variables were presented as absolute numbers and proportions. Independent risk factors were identified by logistic regression analysis and expressed in Odd Ratios (OR). t. Variables were treated as missing if clinical data or the results of faecal samples were unavailable. The OR for Norovirus and C. difficile were calculated separately, since these infections have distinct risk factors.
