Diagnostic performance of high-sensitive troponin T in patients with renal insufficiency

In the present study, we wanted to (1) evaluate whether high-sensitive troponin T levels correlate with the grade of renal insufficiency and (2) test the accuracy of high-sensitive troponin T determination in patients with renal insufficiency for diagnosis of acute myocardial infarction (AMI). In this cross-sectional analysis, all patients who received serial measurements of high-sensitive troponin T from August 1, 2010, to October 31, 2012, at the Department of Emergency Medicine were included. We analyzed data on baseline characteristics, reason for referral, medication, cardiovascular risk factors, and outcome in terms of presence of AMI along with laboratory data (high-sensitive troponin T, creatinine). A total of 1,514 patients (67% male, aged 65 ± 16 years) were included, of which 382 patients (25%) had moderate to severe renal insufficiency and significantly higher levels of high-sensitive troponin T on admission (0.028 vs 0.009, p <0.0001). In patients without AMI, high-sensitive troponin T correlated inversely with the estimated glomerular filtration rate (R = -0.12, p <0.0001). Overall, sensitivity of an elevated high-sensitive troponin for diagnosis of AMI was 0.64 (0.56 to 0.71) and the specificity was 0.48 (0.45 to 0.51). The area under the curve of the receiver operating characteristic for all patients was 0.613 (standard error [SE] 0.023), whereas it was 0.741 (SE 0.029) for patients with a Modification of Diet in Renal Disease estimated glomerular filtration rate >60 ml/min presenting with acute chest pain or dyspnea and 0.535 (SE 0.056) for patients with moderate to severe renal insufficiency presenting with acute chest pain or dyspnea. In conclusion, the diagnostic accuracy for presence of AMI of a baseline measurement of high-sensitive troponin in patients with renal insufficiency was poor and resembles tossing a coin.

Next-generation sequencing of HIV-1 RNA genomes: determination of error rates and minimizing artificial recombination.

Next-generation sequencing (NGS) is a valuable tool for the detection and quantification of HIV-1 variants in vivo. However, these technologies require detailed characterization and control of artificially induced errors to be applicable for accurate haplotype reconstruction. To investigate the occurrence of substitutions, insertions, and deletions at the individual steps of RT-PCR and NGS, 454 pyrosequencing was performed on amplified and non-amplified HIV-1 genomes. Artificial recombination was explored by mixing five different HIV-1 clonal strains (5-virus-mix) and applying different RT-PCR conditions followed by 454 pyrosequencing. Error rates ranged from 0.04-0.66% and were similar in amplified and non-amplified samples. Discrepancies were observed between forward and reverse reads, indicating that most errors were introduced during the pyrosequencing step. Using the 5-virus-mix, non-optimized, standard RT-PCR conditions introduced artificial recombinants in a fraction of at least 30% of the reads that subsequently led to an underestimation of true haplotype frequencies. We minimized the fraction of recombinants down to 0.9-2.6% by optimized, artifact-reducing RT-PCR conditions. This approach enabled correct haplotype reconstruction and frequency estimations consistent with reference data obtained by single genome amplification. RT-PCR conditions are crucial for correct frequency estimation and analysis of haplotypes in heterogeneous virus populations. We developed an RT-PCR procedure to generate NGS data useful for reliable haplotype reconstruction and quantification.

A randomised double-blind, cross-over trial of 4-aminopyridine for downbeat nystagmus--effects on slowphase eye velocity, postural stability, locomotion and symptoms

Objective The effects of 4-aminopyridine (4-AP) on downbeat nystagmus (DBN) were analysed in terms of slow-phase velocity (SPV), stance, locomotion, visual acuity (VA), patient satisfaction and side effects using standardised questionnaires. Methods Twenty-seven patients with DBN received 5 mg 4-AP four times a day or placebo for 3 days and 10 mg 4-AP four times a day or placebo for 4 days. Recordings were done before the first, 60 min after the first and 60 min after the last drug administration. Results SPV decreased from 2.42 deg/s at baseline to 1.38 deg/s with 5 mg 4-AP and to 2.03 deg/s with 10 mg 4-AP (p<0.05; post hoc: 5 mg 4-AP: p=0.04). The rate of responders was 57%. Increasing age correlated with a 4-AP-related decrease in SPV (p<0.05). Patients improved in the ‘get-up-and-go test’ with 4-AP (p<0.001; post hoc: 5 mg: p=0.025; 10 mg: p<0.001). Tandem-walk time (both p<0.01) and tandem-walk error (4-AP: p=0.054; placebo: p=0.059) improved under 4-AP and placebo. Posturography showed that some patients improved with the 5 mg 4-AP dose, particularly older patients. Near VA increased from 0.59 at baseline to 0.66 with 5 mg 4-AP (p<0.05). Patients with idiopathic DBN had the greatest benefit from 4-AP. There were no differences between 4-AP and placebo regarding patient satisfaction and side effects. Conclusions 4-AP reduced SPV of DBN, improved near VA and some locomotor parameters. 4-AP is a useful medication for DBN syndrome, older patients in particular benefit from the effects of 5 mg 4-AP on nystagmus and postural stability.

Driving ability, mental illness and psychotropic medication in the elderly

Fitness to drive in elderly drivers is most commonly discussed with a focus on cognitive impairment. Therefore, this article is focussing on mental illness and the use of psychotropic drugs in elderly drivers, which can both interfere with fitness to drive. Based on a detailed literature review and on clinical judgement, we propose signposts and "red flags" to judge the individual risks. Health professionals dealing with elderly patients should in particular be aware of the dangers related to cumulative risks and need to inform the patients appropriately. For medico-legal reasons the information provided to patients must be written down in the medical record. Individual counselling is important as fitness to drive is a complex topic.

High Incorrect Use of the Standard Error of the Mean (SEM) in Original Articles in Three Cardiovascular Journals Evaluated for 2012.

RATIONALE In biomedical journals authors sometimes use the standard error of the mean (SEM) for data description, which has been called inappropriate or incorrect. OBJECTIVE To assess the frequency of incorrect use of SEM in articles in three selected cardiovascular journals. METHODS AND RESULTS All original journal articles published in 2012 in Cardiovascular Research, Circulation: Heart Failure and Circulation Research were assessed by two assessors for inappropriate use of SEM when providing descriptive information of empirical data. We also assessed whether the authors state in the methods section that the SEM will be used for data description. Of 441 articles included in this survey, 64% (282 articles) contained at least one instance of incorrect use of the SEM, with two journals having a prevalence above 70% and "Circulation: Heart Failure" having the lowest value (27%). In 81% of articles with incorrect use of SEM, the authors had explicitly stated that they use the SEM for data description and in 89% SEM bars were also used instead of 95% confidence intervals. Basic science studies had a 7.4-fold higher level of inappropriate SEM use (74%) than clinical studies (10%). LIMITATIONS The selection of the three cardiovascular journals was based on a subjective initial impression of observing inappropriate SEM use. The observed results are not representative for all cardiovascular journals. CONCLUSION In three selected cardiovascular journals we found a high level of inappropriate SEM use and explicit methods statements to use it for data description, especially in basic science studies. To improve on this situation, these and other journals should provide clear instructions to authors on how to report descriptive information of empirical data.

In the aftermath of medical error : Caring for patients, family, and the healthcare workers involved

Medical errors, in particular those resulting in harm, pose a serious situation for patients ("first victims") and the healthcare workers involved ("second victims") and can have long-lasting and distressing consequences. To prevent a second traumatization, appropriate and empathic interaction with all persons involved is essential besides error analysis. Patients share a nearly universal, broad preference for a complete disclosure of incidents, regardless of age, gender, or education. This includes the personal, timely and unambiguous disclosure of the adverse event, information relating to the event, its causes and consequences, and an apology and sincere expression of regret. While the majority of healthcare professionals generally support and honest and open disclosure of adverse events, they also face various barriers which impede the disclosure (e.g., fear of legal consequences). Despite its essential importance, disclosure of adverse events in practice occurs in ways that are rarely acceptable to patients and their families. The staff involved often experiences acute distress and an intense emotional response to the event, which may become chronic and increase the risk of depression, burnout and post-traumatic stress disorders. Communication with peers is vital for people to be able to cope constructively and protectively with harmful errors. Survey studies among healthcare workers show, however, that they often do not receive sufficient individual and institutional support. Healthcare organizations should prepare for medical errors and harmful events and implement a communication plan and a support system that covers the requirements and different needs of patients and the staff involved.