Observational study of need for thrombolytic therapy and incidence of bacteremia using taurolidine-citrate-heparin, taurolidine-citrate and heparin catheter locks in patients treated with hemodialysis.

Catheter-related blood stream infections may be reduced by interdialytic locking with Taurolidine, a nontoxic antimicrobial agent. A formulation of 1.35% Taurolidine in 4% citrate (TC) is associated with a greater need for thrombolysis to maintain catheter patency than 5000 U/ml heparin. Our aim was to determine whether addition of 500 Units/ml of heparin to TC reduces the need for thrombolysis. TCH (1.35% taurolidine, 4% citrate and 500 U/ml heparin) was compared to TC and Heparin 5000 U/ml using retrospective data. Hundred and six adult hemodialysis patients with internal jugular tunnelled intravascular catheters using TCH were compared with 34 patients using TC and 34 patients using heparin 5000 U/ml respectively. Outcomes were time to first use of thrombolysis and bacteremia rates.TCH reduced the need for thrombolysis compared to TC (hazard ratio, 0.2; 95%CI: 0.06, 0.5; p < 0.001) and was not significantly different from heparin 5000 U/ml (hazard ratio, 1.4; 95%CI: 0.5, 3.9; p = 0.5). The bacteremia rates from all causes were 1.33, 1.22 and 3.25 per 1000 catheter- days (p < 0.001) in the TCH, TC and heparin groups respectively. Addition of 500 U/ml heparin to TC reduces the need for thrombolysis without increasing bacteremia and may achieve patency comparable to heparin 5000 U/ml.

Phosphorylated α-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson's disease.

Parkinson's disease (PD) is characterized by the presence of Lewy bodies containing phosphorylated and aggregated α-synuclein (α-syn). α-Syn is present in human body fluids, including blood plasma, and is a potential biomarker for PD. Immunoassays for total and oligomeric forms of both normal and phosphorylated (at Ser-129) α-syn have been used to assay plasma samples from a longitudinal cohort of 32 patients with PD (sampled at mo 0, 1, 2, 3), as well as single plasma samples from a group of 30 healthy control participants. The levels of α-syn in plasma varied greatly between individuals, but were remarkably consistent over time within the same individual with PD. The mean level of phospho-α-syn was found to be higher (P=0.053) in the PD samples than the controls, whereas this was not the case for total α-syn (P=0.244), oligo-α-syn (P=0.221), or oligo-phospho-α-syn (P=0.181). Immunoblots of plasma revealed bands (at 21, 24, and 50-60 kDa) corresponding to phosphorylated α-syn. Thus, phosphorylated α-syn can be detected in blood plasma and shows more promise as a diagnostic marker than the nonphosphorylated protein. Longitudinal studies undertaken over a more extended time period will be required to determine whether α-syn can act as a marker of disease progression.

Diagnostic efficacy of activated partial thromboplastin time waveform and procalcitonin analysis in pediatric meningococcal sepsis.

OBJECTIVE: A biphasic activated partial thromboplastin time waveform predicts sepsis and disseminated intravascular coagulation in adults. This has not been previously investigated in children. Our aim is to ascertain whether there are changes in the activated partial thromboplastin time waveform in children with meningococcal disease and to compare its diagnostic use with procalcitonin. SETTING: Alder Hey Children's National Health Service Foundation Trust, Liverpool, UK. PATIENTS: Thirty-six children admitted to the hospital for the treatment of suspected meningococcal disease had activated partial thromboplastin time waveform and procalcitonin analysis performed at admission. The light transmittance level at 18 secs was used to quantitate the waveform. Severity of disease was assessed using the Glasgow Meningococcal Septicaemia Prognostic Score, Pediatric Risk of Mortality III score, and the Pediatric Logistic Organ Dysfunction score. MEASUREMENTS AND MAIN RESULTS: Twenty-four children had proven meningococcal disease, 12 had a presumed viral illness, and 20 control subjects were recruited. Transmittance level at 18 secs was lower in children with meningococcal disease and those with a viral illness (p < .0001) and control subjects (p < .0005). Sensitivity and specificity was 0.91 and 0.96 for transmittance level at 18 secs and 0.92 and 1 for procalcitonin in identifying meningococcal disease. There was a significant difference in procalcitonin between children with meningococcal disease and those with a viral illness and control subjects (p < .0005). A negative correlation was found between transmittance level at 18 secs and length of hospital stay (p < .0001), C-reactive protein (p < .0001), procalcitonin (p < .0001), Glasgow Meningococcal Septicaemia Prognostic Score (p < .01), Pediatric Risk of Mortality III score (p < .0001), and Pediatric Logistic Organ Dysfunction score score (p < .0001). CONCLUSION: The activated partial thromboplastin time waveform is abnormal in children with meningococcal disease and may be a useful adjunct in the diagnosis and management of sepsis in children.

On the operational characteristics of the Benjamini and Hochberg False Discovery Rate procedure.

Multiple testing procedures are commonly used in gene expression studies for the detection of differential expression, where typically thousands of genes are measured over at least two experimental conditions. Given the need for powerful testing procedures, and the attendant danger of false positives in multiple testing, the False Discovery Rate (FDR) controlling procedure of Benjamini and Hochberg (1995) has become a popular tool. When simultaneously testing hypotheses, suppose that R rejections are made, of which Fp are false positives. The Benjamini and Hochberg procedure ensures that the expectation of Fp/R is bounded above by some pre-specified proportion. In practice, the procedure is applied to a single experiment. In this paper we investigate the across-experiment variability of the proportion Fp/R as a function of three experimental parameters. The operational characteristics of the procedure when applied to dependent hypotheses are also considered.