Klaus Larsen

Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study

IntroductionAccurate 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.MethodsThis 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.ResultsA 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.ConclusionCombining 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.Trial registrationNCT 00389337

Predicting mortality in patients with systemic inflammatory response syndrome: an evaluation of two prognostic models, two soluble receptors, and a macrophage migration inhibitory factor

Better outcomes in patients suspected of community-acquired infections requires the optimal and timely assessment of disease severity at the point of first contact with the health care system, which is typically in the emergency department. This study was conducted using a previously described, prospectively collected cohort of patients with systemic inflammatory response syndrome (SIRS) that were admitted to an emergency department and a department of infectious diseases at a university hospital. Plasma samples were collected and disease severity scores calculated upon admission. A multiplex immunoassay and a newly developed enzyme-linked immunosorbent assay (ELISA)-based assay were used to measure the soluble urokinase-type plasminogen activator receptor, soluble triggering receptor expressed on myeloid cells-1, and macrophage migration inhibitory factor. The area under the receiver operating characteristic (ROC) curve for the prediction of 30- and 180-day mortality was used to compare the performance of the markers and the models. A total of 151 patients were eligible for analysis. Of these, nine died before day 30 and 19 died before day 180 post-admission. Admission-soluble urokinase-type plasminogen activator receptor levels were significantly higher in both day 30 and day 180 non-survivors. There was a non-significant trend towards higher macrophage migration inhibitory factor concentrations in day 30 non-survivors. Soluble triggering receptor expressed on myeloid cells-1 levels were significantly lower in non-survivors at both time points. The simplified acute physiology score II (SAPS II) and sequential organ failure assessment (SOFA) scores were significantly higher in non-survivors at both time points, indicating that these models intended for use in intensive care units might also be useful in an emergency department setting.

Functional Oral Intake and Time to Reach Unrestricted Dieting for Patients With Traumatic Brain Injury

OBJECTIVESnTo investigate the status of functional oral intake for patients with severe traumatic brain injury (TBI) and time to return to unrestricted dieting; and to investigate whether severity of brain injury is a predictor for unrestricted dieting.nnnDESIGNnObservational retrospective cohort study.nnnSETTINGnSubacute rehabilitation department, university hospital.nnnPARTICIPANTSnPatients age 16 to 65 years (N=173) with severe TBI (posttraumatic amnesia from 7d to >6 mo) admitted over a 5-year period. Patients are transferred to the brain injury unit as soon as they ventilate spontaneously.nnnINTERVENTIONnFacial oral tract therapy.nnnMAIN OUTCOME MEASUREnUnrestricted dieting assessed by the Functional Oral Intake Scale (FOIS).nnnRESULTSnWe found that 93% of all patients had problems with functional oral intake at admission. Within 126 days of rehabilitation, 64% recovered to unrestricted dieting before discharge. The chance of returning to total oral diet depends on the severity of the brain injury and can be predicted by Glasgow Coma Scale (GCS; measured the day after cessation of sedation; Wald chi(2)=42.78, P<.01), Rancho Los Amigos Scale (RLAS) level (Wald chi(2)=11.84, P=.01), FIM instrument (Wald chi(2)=44.40, P<.01), and FOIS score at admission (Wald chi(2)=82.93, P<.01).nnnCONCLUSIONSnImpairment in functional oral intake was found to be very common for patients with severe TBI admitted to a subacute rehabilitation department. For those who recovered during hospital rehabilitation, return to unrestricted dieting happened within 126 days of rehabilitation. The chance of returning to unrestricted dieting depends on the severity of the brain injury and can be predicted by GCS score, RLAS level, FIM score, and functional oral intake at admission. These results are important when planning rehabilitation, giving information to patients and relatives, and designing efficacy studies of facial oral tract therapy, which are highly recommended.

The Association of Functional Oral Intake and Pneumonia in Patients With Severe Traumatic Brain Injury

OBJECTIVESnTo investigate the incidence and onset time of pneumonia for patients with severe traumatic brain injury (TBI) in the early phase of rehabilitation and to identify parameters associated with the risk of pneumonia.nnnDESIGNnObservational retrospective cohort study.nnnSETTINGnSubacute rehabilitation department in a university hospital in Denmark.nnnPARTICIPANTSnPatients (N=173) aged 16 to 65 years with severe TBI who were admitted during a 5-year period. Patients are transferred to the brain injury unit as soon as they ventilate spontaneously.nnnINTERVENTIONSnNot applicable.nnnMAIN OUTCOME MEASUREnPneumonia.nnnRESULTSnTwenty-seven percent of the patients admitted to the brain injury unit were in treatment for pneumonia; pneumonia developed in 12% of the patients during rehabilitation; the condition occurred within 19 days of admission in all but 1 patient. Of these patients, 81% received nothing by mouth. Three factors identified patients at highest risk of pneumonia: Glasgow Coma Scale score less than 9 (1 day after cessation of sedation); Rancho Los Amigos Scale score less than 3 (on admission); and no oral intake on admission. Having a tracheotomy tube and/or feeding tube was also associated with a higher occurrence of pneumonia.nnnCONCLUSIONSnAmong patients with severe TBI, 27% had pneumonia at transfer from the intensive care unit. Pneumonia developed in only 12% of the participants during rehabilitation. Patients with a low level of consciousness and patients with a tracheotomy tube or feeding tube had a higher likelihood of pneumonia.

Continued Significant Effect of Physical Training as Treatment for Overuse Injury 8- to 12-Year Outcome of a Randomized Clinical Trial

Background: The treatment of exercise-related injuries is often a problem, and recurrent injuries are common. Two recent systematic reviews found only one high-quality paper on the treatment of long-standing groin pain. In this randomized clinical trial, a training program including strength training resulted in a return of 79% of the athletes to the previous level of sport without any groin pain. The long-term effect of this exercise program was evaluated. Hypothesis: The effect of the exercise program for adductor-related groin pain is long lasting. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Forty-seven (80%) of the 59 original participants of the study agreed to participate in this 8- to 12-year follow-up. They were all interviewed and examined using a standardized and reproducible protocol, identical to the one used in the original trial. The investigating physician (P.N.) was not involved in the original study and was unaware of the original treatment allocation. Results: A significant effect of the active training treatment still existed for the whole group (P = .047) and even more for the subgroup of 39 (83%) soccer players (P = .012). No significant differences were found regarding age, present sports activity, reasons for activity reduction, or time to follow-up. Conclusion: The beneficial short-term effect of the exercise program used in the primary randomized clinical trial for treating long-standing adductor-related groin pain in athletes was found to be lasting, both for the whole group and even more for the large subgroup of soccer players. This is the first time an exercise treatment for overuse injuries to the musculoskeletal system has been shown to have a long-lasting effect (8-12 years).

Alcohol Withdrawal Syndrome: Symptom-Triggered versus Fixed-Schedule Treatment in an Outpatient Setting

AIMSnTo investigate whether, in the treatment with chlordiazepoxide for outpatient alcohol withdrawal, there are advantages of symptom-triggered self-medication over a fixed-schedule regimen.nnnMETHODSnA randomized controlled trial in outpatient clinics for people suffering from alcohol dependence (AD) and alcohol-related problems; 165 adult patients in an outpatient setting in a specialized alcohol treatment unit were randomized 1:1 to either a symptom-triggered self-medication or tapered dose, using chlordiazepoxide. Alcohol withdrawal symptoms, amount of medication, duration of symptoms, time to relapse and patient satisfaction were measured. Patients assessed their symptoms using the Short Alcohol Withdrawal Scale (SAWS). Patient satisfaction was monitored by the Diabetes Treatment Satisfaction Questionnaire. We used the Well-Being Index and the European addiction severity index for the 1-year follow-up.nnnRESULTSnWe found no differences in the quantity of medication consumed, time to relapse, well being or treatment satisfaction.nnnCONCLUSIONnSymptom-triggered self-medication was as safe as fixed-schedule medication in treating outpatients with AD and mild to moderate symptoms of AWS. The SAWS is a powerful monitoring tool, because it is brief and permits the subject to log the withdrawal symptoms.

A prospective study evaluating the presence of Rickettsia in Danish patients with sarcoidosis

Rickettsia helvetica has previously been proposed as an aetiological agent in sarcoidosis. The purpose of the present study was to detect possible signs of Rickettsia infection in a Danish population of patients with sarcoidosis. Twenty-six patients with newly diagnosed sarcoidosis were prospectively enrolled in the study. The diagnosis was confirmed by biopsy in 18 and by clinical characteristics in 8 patients; 11 patients with different non-sarcoid lung diseases were recruited as controls. We obtained information regarding tick exposure and sarcoid disease manifestations by a structured interview. Evidence of rickettsial infection was assessed by an immunofluorescence assay testing for antibodies towards Rickettsia as well as specific real-time polymerase chain reaction (PCR) on lung biopsy specimens. We performed fluorescent in situ hybridization (FISH) on the biopsies to detect rickettsial and eubacterial rRNA. One sarcoidosis patient had serum rickettsial IgG antibodies above the chosen cut-off level. We found no positive rickettsial PCR or FISH analyses in any of the biopsy specimens. One sarcoid patient sample and 1 control sample contained unidentified bacteria. There was no difference in the reported frequency of tick bite between patients and controls. In conclusion, we found no evidence of Rickettsia being involved in the pathogenesis of sarcoidosis in Denmark.

Circadian Variation in QT Dispersion Determined from a 12-Lead Holter Recording: A Methodological Study of an Age- and Sex-Stratified Group of Healthy Subjects

Background: QT dispersion is considered to reflect inhomogeneity of myocardial repolarization.

Does the MOSES Study Provide Sufficient Evidence for Eprosartan Against Nitrendipine

To the Editor:nnWe read the article by Dr Schrader et al1 with great interest. Their conclusion, “MOSES does reveal protective effects of Eprosartan over Nitrendipine,” hinges entirely on the analysis of the primary end point, which includes recurrent events (cardiovascular and cerebrovascular events, and all-cause mortality) for the patients. Statistical analysis of recurrent events is …