Premature Discontinuation of Randomized Trials in Critical and Emergency Care: A Retrospective Cohort Study.

OBJECTIVES Randomized clinical trials that enroll patients in critical or emergency care (acute care) setting are challenging because of narrow time windows for recruitment and the inability of many patients to provide informed consent. To assess the extent that recruitment challenges lead to randomized clinical trial discontinuation, we compared the discontinuation of acute care and nonacute care randomized clinical trials. DESIGN Retrospective cohort of 894 randomized clinical trials approved by six institutional review boards in Switzerland, Germany, and Canada between 2000 and 2003. SETTING Randomized clinical trials involving patients in an acute or nonacute care setting. SUBJECTS AND INTERVENTIONS We recorded trial characteristics, self-reported trial discontinuation, and self-reported reasons for discontinuation from protocols, corresponding publications, institutional review board files, and a survey of investigators. MEASUREMENTS AND MAIN RESULTS Of 894 randomized clinical trials, 64 (7%) were acute care randomized clinical trials (29 critical care and 35 emergency care). Compared with the 830 nonacute care randomized clinical trials, acute care randomized clinical trials were more frequently discontinued (28 of 64, 44% vs 221 of 830, 27%; p = 0.004). Slow recruitment was the most frequent reason for discontinuation, both in acute care (13 of 64, 20%) and in nonacute care randomized clinical trials (7 of 64, 11%). Logistic regression analyses suggested the acute care setting as an independent risk factor for randomized clinical trial discontinuation specifically as a result of slow recruitment (odds ratio, 4.00; 95% CI, 1.72-9.31) after adjusting for other established risk factors, including nonindustry sponsorship and small sample size. CONCLUSIONS Acute care randomized clinical trials are more vulnerable to premature discontinuation than nonacute care randomized clinical trials and have an approximately four-fold higher risk of discontinuation due to slow recruitment. These results highlight the need for strategies to reliably prevent and resolve slow patient recruitment in randomized clinical trials conducted in the critical and emergency care setting.

Comparative dendritic cell biology of veterinary mammals.

Dendritic cells (DC) have a main function in innate immunity in that they sense infections and environmental antigens at the skin and mucosal surfaces and thereby critically influence decisions about immune activation or tolerance. As professional antigen-presenting cells, they are essential for induction of adaptive immune responses. Consequently, knowledge on this cell type is required to understand the immune systems of veterinary mammals, including cattle, sheep, pigs, dogs, cats, and horses. Recent ontogenic studies define bona fide DC as an independent lineage of hematopoietic cells originating from a common precursor. Distinct transcription factors control the development into the two subsets of classical DC and plasmacytoid DC. These DC subsets express a distinguishable transcriptome, which differs from that of monocyte-derived DC. Using a comparative approach based on phenotype and function, this review attempts to classify DC of veterinary mammals and to describe important knowledge gaps.

Calcium Disorders in the Emergency Department: Independent Risk Factors for Mortality.

BACKGROUND Calcium disorders are common in both intensive care units and in patients with chronic kidney disease and are associated with increased morbidity and mortality. It is unknown whether calcium abnormalities in unselected emergency department admissions have an impact on in-hospital mortality. METHODS This cross-sectional analysis included all admissions to the Emergency Department at the Inselspital Bern, Switzerland from 2010 to 2011. For hyper- and hypocalcaemic patients with a Mann-Whitney U-test, the differences between subgroups divided by age, length of hospital stay, creatinine, sodium, chloride, phosphate, potassium and magnesium were compared. Associations between calcium disorders and 28-day in-hospital mortality were assessed using the Cox proportional hazard regression model. RESULTS 8,270 patients with calcium measurements were included in our study. Overall 264 (3.2%) patients died. 150 patients (6.13%) with hypocalcaemia and 7 patients with hypercalcaemia (6.19%) died, in contrast to 104 normocalcaemic patients (1.82%). In univariate analysis, calcium serum levels were associated with sex, mortality and pre-existing diuretic therapy (all p<0.05). In multivariate Cox regression analysis, hypocalcaemia and hypercalcaemia were independent risk factors for mortality (HR 2.00 and HR 1.88, respectively; both p<0.01). CONCLUSION Both hypocalcaemia and hypercalcaemia are associated with increased 28-day in-hospital mortality in unselected emergency department admissions.

Primary Hyperventilation in the Emergency Department: A First Overview.

BACKGROUND Primary hyperventilation is defined as a state of alveolar ventilation in excess of metabolic requirements, leading to decreased arterial partial pressure of carbon dioxide. The primary aim of this study was to characterise patients diagnosed with primary hyperventilation in the ED. METHODS Our retrospective cohort study comprised adult (≥16 years) patients admitted to our ED between 1 January 2006 and 31 December 2012 with the primary diagnosis of primary (=psychogenic) hyperventilation. RESULTS A total of 616 patients were eligible for study. Participants were predominantely female (341 [55.4%] female versus 275 [44.6%] male respectively, p <0.01). The mean age was 36.5 years (SD 15.52, range 16-85). Patients in their twenties were the most common age group (181, 29.4%), followed by patients in their thirties (121, 19.6%). Most patients presented at out-of-office hours (331 [53.7%]. The most common symptom was fear (586, 95.1%), followed by paraesthesia (379, 61.5%) and dizziness (306, 49.7%). Almost a third (187, 30.4%) of our patients had previously experienced an episode of hyperventilation and half (311, 50.5%) of patients had a psychiatric co-morbidity. CONCLUSION Hyperventilation is a diagnostic chimera with a wide spectrum of symptoms. Patients predominantly are of young age, female sex and often have psychiatric comorbidities. The severity of symptoms accompanied with primary hyperventilation most often needs further work-up to rule out other diagnosis in a mostly young population. In the future, further prospective multicentre studies are needed to evaluate and establish clear diagnostic criteria for primary hyperventilation and possible screening instruments.

Trends and characteristics of attendance at the emergency department of a Swiss university hospital: 2002-2012.

BACKGROUND The numbers of people attending emergency departments (EDs) at hospitals are increasing. We aimed to analyse trends in ED attendance at a Swiss university hospital between 2002 and 2012, focussing on age-related differences and hospital admission criteria. METHODS We used hospital administrative data for all patients aged ≥16 years who attended the ED (n=298,306) at this university hospital between 1 January 2002, and 31 December 2012. We descriptively analysed the numbers of ED visits according to the admission year and stratified by age (≥65 vs <65 years). RESULTS People attending the ED were on average 46.6 years old (standard deviation 20 years, maximum range 16‒99 years). The annual number of ED attendances grew by n=6,639 (27.6%) from 24,080 in 2002 to 30,719 in 2012. In the subgroup of patients aged ≥65 the relative increase was 42.3%, which is significantly higher (Pearson's χ2=350.046, df=10; p=0.000) than the relative increase of 23.4% among patients<65 years. The subgroup of patients≥65 years attended the ED more often because of diseases (n=56,307; 85%) than accidents (n=9,844; 14.9%). This subgroup (patients≥65 years) was also more often admitted to hospital (Pearson's χ2=23,377.190; df=1; p=0.000) than patients<65 years. CONCLUSIONS ED attendance of patients≥65 years increased in absolute and relative terms. The study findings suggest that staff of this ED may want to assess the needs of patients≥65 years and, if necessary, adjust the services (e.g., adapted triage scales, adapted geriatric screenings, and adapted hospital admission criteria).

Spine radiography in the evaluation of back and neck pain in an orthopaedic emergency clinic

BACKGROUND AND OBJECTIVES Despite the recommendations of national and international societies for the treatment of patients with acute neck and back pain, still too many radiologic examinations were performed. The purpose of this study was to analyze and optimize diagnostics and treatment of patients with acute back pain. METHODS The medical records of 484 patients presented to the emergency clinic with acute neck or back pain were analyzed for clinical history, physical examination, radiographic findings and therapy. RESULTS Radiographs of the lumbar, cervical, or thoracic spine were performed in 338 cases (70%). Radiographs were normal in 142 patients (42%) and degenerative changes were identified in 123 patients (36%). Only 2 patients (0.4%) had radiographic findings that had direct therapeutic relevance: 1 patient with metastatic disease and 1 patient with posttraumatic C1-C2 instability. For most patients without sensorimotor deficits and absent specific indications for radiography (“red flags”), therapy was not affected by the results of radiography. CONCLUSIONS Plain radiography of the spine was unnecessary in most patients initially evaluated with non-specific acute back pain and does not improve the clinical outcome. The implementation of national and international guidelines is a slow process, but helps to reduce costs and to protect patients from unnecessary ionizing radiation exposure.

Biomarker-guided personalised emergency medicine for all - hope for another hype?

Polymorbid patients, diverse diagnostic and therapeutic options, more complex hospital structures, financial incentives, benchmarking, as well as perceptional and societal changes put pressure on medical doctors, specifically if medical errors surface. This is particularly true for the emergency department setting, where patients face delayed or erroneous initial diagnostic or therapeutic measures and costly hospital stays due to sub-optimal triage. A "biomarker" is any laboratory tool with the potential better to detect and characterise diseases, to simplify complex clinical algorithms and to improve clinical problem solving in routine care. They must be embedded in clinical algorithms to complement and not replace basic medical skills. Unselected ordering of laboratory tests and shortcomings in test performance and interpretation contribute to diagnostic errors. Test results may be ambiguous with false positive or false negative results and generate unnecessary harm and costs. Laboratory tests should only be ordered, if results have clinical consequences. In studies, we must move beyond the observational reporting and meta-analysing of diagnostic accuracies for biomarkers. Instead, specific cut-off ranges should be proposed and intervention studies conducted to prove outcome relevant impacts on patient care. The focus of this review is to exemplify the appropriate use of selected laboratory tests in the emergency setting for which randomised-controlled intervention studies have proven clinical benefit. Herein, we focus on initial patient triage and allocation of treatment opportunities in patients with cardiorespiratory diseases in the emergency department. The following five biomarkers will be discussed: proadrenomedullin for prognostic triage assessment and site-of-care decisions, cardiac troponin for acute myocardial infarction, natriuretic peptides for acute heart failure, D-dimers for venous thromboembolism, C-reactive protein as a marker of inflammation, and procalcitonin for antibiotic stewardship in infections of the respiratory tract and sepsis. For these markers we provide an overview on physiopathology, historical evolution of evidence, strengths and limitations for a rational implementation into clinical algorithms. We critically discuss results from key intervention trials that led to their use in clinical routine and potential future indications. The rational for the use of all these biomarkers, first, tackle diagnostic ambiguity and consecutive defensive medicine, second, delayed and sub-optimal therapeutic decisions, and third, prognostic uncertainty with misguided triage and site-of-care decisions all contributing to the waste of our limited health care resources. A multifaceted approach for a more targeted management of medical patients from emergency admission to discharge including biomarkers, will translate into better resource use, shorter length of hospital stay, reduced overall costs, improved patients satisfaction and outcomes in terms of mortality and re-hospitalisation. Hopefully, the concepts outlined in this review will help the reader to improve their diagnostic skills and become more parsimonious laboratory test requesters.

Repatriations and 28-day mortality of ill and injured travellers: 12 years of experience in a Swiss emergency department

QUESTIONS UNDER STUDY Many persons are travelling all over the world; the elderly with pre-existing diseases also travel to places with less developed health systems. Reportedly, fewer than 0.5% of all travellers need repatriation. We aimed to analyse and examine people who are injured or ill while abroad, where they travelled to and by what means they were repatriated. METHODS Retrospective cross-sectional study with adult patients repatriated to a single level 1 trauma centre in Switzerland (2000-2011). RESULTS A total of 372 patients were repatriated, with an increasing trend per year. Of these, 67% were male; the median age was 56 years. Forty-nine percent sustained an injury, and 13% had surgical and 38% medical pathologies. Patients with medical conditions were older than those with injuries or surgical emergencies (p <0.001). Seventy-three percent were repatriated from Europe. For repatriation from Africa trauma was slightly more frequent (53%, n = 17) than illnesses, whereas for most other countries illnesses and trauma were equally distributed. Injured patients had a median Injury Severity Score of 8. The majority of illnesses involved the nervous system (38%), mainly stroke. Forty-five percent were repatriated by Swiss Air Ambulance, 26% by ground ambulance, 18% by scheduled flights with or without medical assistance and two patients injured near the Swiss boarder by helicopter. The 28-day mortality was 4%. CONCLUSIONS The numbers of travellers repatriated increased from 2000 to 2011. About half were due to illnesses and half due to injuries. The largest group were elderly Swiss nationals repatriated from European countries. As mortality is relatively high, special consideration to this group of patients is warranted.

If hunters end up in the emergency room: a retrospective analysis of hunting injuries in a swiss emergency department.

Aim. to characterize the mechanisms, patterns, and outcomes of nonfatal hunting-related injuries in patients presenting to Bern University Hospital, Switzerland, and compare these to reports of hunting injuries worldwide. Methods. patients presenting with hunting-related injuries to the Emergency Department at Bern University hospital from 2000 to 2014 were identified by retrospectively searching the department database using the keyword "hunt." Each case was analyzed in terms of the patient age and gender, the mechanism and pattern of injury, and management and patient follow-up. Results. 19 patients were identified. 16 were male with a mean age of 50 years (range: 16-74). Mechanisms of injury included firearm-related injuries, falls, and knife wounds. The most common patterns of injury were head injuries (7), followed by injuries to the upper (5) or lower limb (5) and trunk (2). Over half of the patients were admitted, and nine required emergency surgery. Conclusion. Nonfatal hunting accidents in Bern, Switzerland, are largely caused by firearms and falls and tend to occur in male hunters with a mean age of 50 years. The most common patterns of injury are orthopedic and head injuries, often requiring surgery. These findings are consistent with international studies of nonfatal hunting accidents.

Emergency management of ischemic stroke in children.

OPINION STATEMENT Children who present with acute neurological symptoms suggestive of a stroke need immediate clinical assessment and urgent neuroimaging to confirm diagnosis. Magnetic resonance imaging (MRI) is the investigation of first choice due to limited sensitivity of computed tomography (CT) for detection of ischaemia. Acute monitoring should include monitoring of blood pressure and body temperature, and neurological observations. Surveillance in a paediatric high dependency or intensive care unit and neurosurgical consultation are mandatory in children with large infarcts at risk of developing malignant oedema or haemorrhagic transformation. Thrombolysis and/or endovascular treatment, whilst not currently approved for use in children, may be considered when stroke diagnosis is confirmed within 4.5 to 6 h, provided there are no contraindications on standard adult criteria. Standard treatment consists of aspirin, but anticoagulation therapy is frequently prescribed in stroke due to cardiac disease and extracranial dissection. Steroids and immunosuppression have a definite place in children with proven vasculitis, but their role in focal arteriopathies is less clear. Decompressive craniotomy should be considered in children with deteriorating consciousness or signs of raised intracranial pressure.

A case-control study to estimate the effects of acute clinical infection with the Schmallenberg virus on milk yield, fertility and veterinary costs in Swiss dairy herds.

Schmallenberg virus (SBV) was first detected in Switzerland in July 2012 and many Swiss dairy farmers reported acute clinical signs in dairy cattle during the spread of the virus until December 2012. The objectives of the present study were to investigate the effects of an acute infection with SBV on milk yield, fertility and veterinary costs in dairy farms with clinical signs of SBV infection (case farms), and to compare those farms to a matched control group of dairy farms in which cattle did not show clinical signs of SBV infection. Herd size was significantly (p<0.001) larger in case farms (33 cows, n=77) than in control farms (25 cows, n=84). Within case herds, 14.8% (median) of the cows showed acute clinical signs. Managers from case farms indicated to have observed a higher abortion rate during the year with SBV (6.5%) than in the previous year (3.7%). Analysis of fertility parameters based on veterinary bills and data from the breeding associations showed no significant differences between case and control farms. The general veterinary costs per cow from July to December 2012 were significantly higher (p=0.02) in case (CHF 19.80; EUR 16.50) than in control farms (CHF 15.90; EUR 13.25). No differences in milk yield were found between groups, but there was a significant decrease in milk production in case farms in the second half year in 2012 compared to the same period in 2011 (p<0.001) and 2013 (p=0.009). The average daily milk yield per cow (both groups together) was +0.73kg higher (p=0.03) in the second half year 2011 and +0.52kg (p=0.12) in the second half year 2013 compared to the same half year 2012. Fifty-seven percent of the cows with acute clinical signs (n=461) were treated by a veterinarian. The average calculated loss after SBV infection for a standardized farm was CHF 1606 (EUR 1338), which can be considered as low at the national level, but the losses were subject to great fluctuations between farms, so that individual farms could have very high losses (>CHF 10,000, EUR 8333).