Reinhold Muller

Origin of the Amphibian Chytrid Fungus

Histologic evidence indicates southern Africa as the origin of the amphibian chytrid fungus.

Early discharge using single cardiac troponin and copeptin testing in patients with suspected acute coronary syndrome (ACS): a randomized, controlled clinical process study

Abstract Aims This randomized controlled trial (RCT) evaluated whether a process with single combined testing of copeptin and troponin at admission in patients with low-to-intermediate risk and suspected acute coronary syndrome (ACS) does not lead to a higher proportion of major adverse cardiac events (MACE) than the current standard process (non-inferiority design). Methods and results A total of 902 patients were randomly assigned to either standard care or the copeptin group where patients with negative troponin and copeptin values at admission were eligible for discharge after final clinical assessment. The proportion of MACE (death, survived sudden cardiac death, acute myocardial infarction (AMI), re-hospitalization for ACS, acute unplanned percutaneous coronary intervention, coronary artery bypass grafting, or documented life threatening arrhythmias) was assessed after 30 days. Intention to treat analysis showed a MACE proportion of 5.17% [95% confidence intervals (CI) 3.30–7.65%; 23/445] in the standard group and 5.19% (95% CI 3.32–7.69%; 23/443) in the copeptin group. In the per protocol analysis, the MACE proportion was 5.34% (95% CI 3.38–7.97%) in the standard group, and 3.01% (95% CI 1.51–5.33%) in the copeptin group. These results were also corroborated by sensitivity analyses. In the copeptin group, discharged copeptin negative patients had an event rate of 0.6% (2/362). Conclusion After clinical work-up and single combined testing of troponin and copeptin to rule-out AMI, early discharge of low- to intermediate risk patients with suspected ACS seems to be safe and has the potential to shorten length of stay in the ED. However, our results need to be confirmed in larger clinical trials or registries, before a clinical directive can be propagated.

Chronic spinal pain syndromes: A clinical pilot trial comparing acupuncture, a nonsteroidal anti-inflammatory drug, and spinal manipulation

OBJECTIVE To compare needle acupuncture, medication (tenoxicam with ranitidine), and spinal manipulation for managing chronic (>13 weeks duration) spinal pain syndromes. DESIGN Prospective, randomized, independently assessed preintervention and postintervention clinical pilot trial. SETTING Specialized spinal pain syndrome out-patient unit at Townsville General Hospital, Queensland, Australia. SUBJECTS Seventy-seven patients (without contraindication to manipulation or medication) were recruited. INTERVENTIONS One of three separate, clearly defined intervention protocols: needle acupuncture, nonsteroidal anti-inflammatory medication, or chiropractic spinal manipulation. MAIN OUTCOME MEASURES Main outcome measures were changes (4 weeks vs. initial visit) in the scores of the (1) Oswestry Back Pain Disability Index, (2) Neck Disability Index, and (3) three visual analogue scales of local pain intensity. RESULTS Randomization was successful. After a median intervention period of 30 days, spinal manipulation was the only intervention that achieved statistically significant improvements (all expressed as percentages of the original scores) with (1) a reduction of 30.7% on the Oswestry scale, (2) an improvement of 25% on the neck disability index, and (3) reductions on the visual analogue scale of 50% for low back pain, 46% for upper back pain, and 33% for neck pain (all P<.001). Neither of the other interventions showed any significant improvement on any of the outcome measures. CONCLUSIONS The consistency of the results provides, in spite of several discussed shortcomings of this pilot study, evidence that in patients with chronic spinal pain syndromes spinal manipulation, if not contraindicated, results in greater improvement than acupuncture and medicine.

Chief complaints in medical emergencies: do they relate to underlying disease and outcome? The Charité Emergency Medicine Study (CHARITEM)

Objectives To evaluate the relationship between chief complaints and their underlying diseases and outcome in medical emergency departments (EDs). Methods All 34 333 patients who attended two of the EDs of the Charité Berlin over a 1-year period were included in the analysis. Data were retrieved from the hospital information system. For study purposes, the chief complaint (chest pain, dyspnoea, abdominal pain, headache or ‘none of these symptoms’) was prospectively documented in an electronic file by the ED-physician. Documentation was mandatory. Results The majority of patients (66%) presented with ‘none of these symptoms’, 11.5% with chest pain, 11.1% with abdominal pain and 7.4% with dyspnoea. In total, 39.4% of all patients were admitted to the hospital. The leading diagnosis was acute coronary syndrome (50.7%) for chest pain in-patients and chronic obstructive pulmonary disease (16.5%) and heart failure (16.1%) for in-patients with dyspnoea. The causes of abdominal pain in in-patients were of diverse gastrointestinal origin (47.2%). In-hospital mortality of in-patients was 4.7%. Patients with chest pain had significantly lower in-hospital mortality (0.9%) than patients with dyspnoea (9.4%) and abdominal pain (5.1%). Conclusion The majority of emergency patients lack diagnosis-specific symptoms. Chief complaints help preselect patients but must not be mistaken as disease specific. Mortality largely differs depending on the chief complaint. In chest pain patients, standardized processes may be one factor that explains the low mortality in this group.

Suburethral slingplasty evaluation study in North Queensland, Australia: The SUSPEND trial

Objective:  To compare the safety and efficacy of three types of suburethral slings for the treatment of urodynamic stress incontinence.

Logistic regression and CART in the analysis of multimarker studies

BACKGROUND The rapid development of new biomarkers increasingly motivates multimarker studies to assess/compare the value of different markers for risk stratification or diagnostic prediction. Analysis of these studies is usually governed by logistic regression (LR) which is however often applied quite uncritically resulting in unclear or even deceptive results. METHODS AND DATA This methodological review is intended for the practical medical researcher and critically discusses in non-technical terms where possible LR models and CART (classification and regression trees) as analytical approaches for multimarker studies. Some in practice often neglected but vital aspects for a valid application and interpretation of LR models are presented and the basic principles of building and interpreting a CART tree are demonstrated. All approaches are applied to original data of a multimarker study which aimed to assess and compare the value of different laboratory parameters to predict the need for intensive care treatment in unselected emergency room patients. CONCLUSIONS When applied prudently, both LR and CART are suitable for the analysis of multimarker studies. For a valid interpretation of LR it is especially important that the format of the model fits the study design. In general LR and CART will identify very similar sets of significant markers. While LR models generally focus more on the relative statistical significance of the assessed markers, CART results emphasise the absolute effects; results come as observed risk groups. Thus the complementary use of both techniques seems to be a promising approach to perform the difficult task of analysing and interpreting the results of multimarker studies.

Evaluation of the diagnostic and prognostic value of plasma D-dimer for abdominal aortic aneurysm

AIMS A number of biomarkers have been associated with abdominal aortic aneurysm (AAA), but there has been no assessment of how such markers along with clinical risk factors can be used to stratify the risk of AAA presence and its progression. The aims of this study were to assess the diagnostic, prognostic, and risk stratification potential of plasma D-dimer for AAA presence and growth. METHODS AND RESULTS We included 1260 subjects (337 with AAA) recruited from a population screening study and 132 (41 with AAA) from a referral clinic. A total of 299 of the population group were followed by repeat ultrasound imaging for a median of 5.5 years to monitor AAA growth. The diagnostic and prognostic potential of plasma D-dimer was assessed by multivariate regression (adjusting for other AAA risk factors), receiver operator characteristic, and classification and regression tree (CART) analyses. In both groups, the dominant risk factor for AAA was D-dimer; thus in the population group, cut-off values of > 400 and > 900 ng/mL had adjusted odds ratios of 12.1 (95% CI 7.1-20.5) and 24.7 (95% CI 13.7-44.6), respectively. In both groups, CART analyses confirmed the dominating role of plasma D-dimer in defining extreme risk-groups with AAA prevalence as disparate as 3 and 82%. Average yearly AAA growth was positively and significantly associated with D-dimer which was able to predict growth as disparate as 0.4 and 2.5 mm/year. CONCLUSION This study suggests that plasma D-dimer can play a role in the diagnosis and prognosis of AAA.

Predictors of the prevalence of bacterial STI among young disadvantaged Indigenous people in north Queensland, Australia.

Objective: To identify sexually transmitted infections in rural and remote Indigenous communities in north eastern Australia and examine factors that may influence prevalence. Methods: A cross sectional survey of 26 Aboriginal and Torres Strait Islander communities in northern Queensland was carried out. 3313 people (2862 Indigenous) aged 15 years and over resident in participating communities during the period March 1998 to December 2000. The main outcome measures were community and population prevalence of chlamydia and gonorrhoea and independently associated risk factors. Results: A total of 238 cases of chlamydia, 66 cases of gonorrhoea, and 37 cases of co-infection were detected among Indigenous participants. Prevalence of chlamydia and/or gonorrhoea ranged from 23.0% among 15–19 year olds to 3.5% among those 40 years and older. In the adjusted analysis younger age, female sex, lower socioeconomic status, the use of alcohol and tobacco, and the structure of community health services were independently associated with a higher prevalence of bacterial STI. Conclusion: This study highlights the need for improved STI control in north Queensland Indigenous communities through strategies to improve the reach and accessibility of primary healthcare services.

Neonatal outcome of gastroschisis and exomphalos: A 10-year review

Objective: To study neonatal outcomes associated with gastroschisis and exomphalos in a regional neonatal unit.

Lipoprotein-associated phospholipase A2 for early risk stratification in patients with suspected acute coronary syndrome: a multi-marker approach: the North Wuerttemberg and Berlin Infarction Study-II (NOBIS-II).

AimsNumerous markers have been identified as useful predictors of major adverse cardiac events (MACE) in patients with suspected acute coronary syndrome (ACS). However, only little is known about the relative benefit of the single markers in risk stratification and the best combination for optimising prognostic power.The aim of the present study was to define the role of the emerging cardiovascular risk marker lipoprotein-associated phospholipase A2 (Lp-PLA2) in a multi-marker approach in combination with troponin I (TnI), NT-proBNP, high sensitivity (hs)CRP, and D-dimer in patients with ACS.Methods and resultsA total of 429 consecutive patients (age 60.5±14.1 years, 60.6% male) who were admitted to the emergency room with suspected ACS were analysed in the study. Biochemical markers were measured by immunoassay techniques. All patients underwent point-of-care TnI testing and early coronary angiography if appropriate, in accordance with the current guidelines. Classification and regression trees (CART) and logistic regression techniques were employed to determine the relative predictive power of markers for the primary end-point defined as any of the following events within 42 days after admission: death, non-fatal myocardial infarction, unstable AP requiring admission, admission for decompensated heart failure or shock, percutaneous coronary intervention, coronary artery bypass grafting, life threatening arrhythmias or resuscitation. The incidence of the primary end-point was 13.1%, suggesting a mild to moderate risk population. The best overall risk stratification was obtained using NT-proBNP at a cut-off of 5000 pg/mL (incidence of 40% versus 10.3%, relative risk (RR) 3.9 (95% CI 2.4–6.3)). In the remaining lower risk group with an incidence of 10.3%, further separation was performed using TnI (cut-off 0.14 µg/L; RR= 3.1 (95% CI 1.7–5.5) 23.2% versus 7.5%) and again NT-proBNP (at a cut-off of 140 ng/L) in patients with negative TnI (RR=3.2 (95% CI 1.3–7.9), 11.7% versus 3.6%). A final significant stratification in patients with moderately elevated NT-proBNP levels was achieved using Lp-PLA2 at a cut-off of 210 µg/L) (17.9% versus 6.9%; RR=2.6 (95% CI 1.1–6.6)). None of the clinical or ECG variables of the TIMI (Thrombolysis In Myocardial Infarction) risk score provided comparable clinically relevant information for risk stratification.ConclusionsIn the setting of stateof- the-art coronary care for patients with suspected ACS in the emergency room, NT-proBNP, troponin I, and Lp-PLA2 are effective independent markers for risk stratification that proved to be superior to the TIMI risk score. Lp-PLA2 turned out to be a more effective risk marker than hsCRP in these patients.