Proton pump inhibitors and diarrhoea related to Clostridium difficile infection in hospitalised patients: a case-control study.

The incidence and disease severity of Clostridium difficile infection are rising. There is increasing evidence of a potential association between proton-pump inhibitors (PPI) and C. difficile infection. We performed a case-control study to examine the relationship between PPI and polymerase chain reaction (PCR)-proven C. difficile infection in 137 hospitalised patients in a tertiary hospital in Western Australia. Only antibiotic exposure within 3 months prior to onset of diarrhoea was associated with PCR-proven C. difficile infection (odds ratio 5.97, 95% confidence interval 2.40-14.8, P= 0.001). A restricted analysis on those who had exposure to antibiotics within 3 months before the onset of diarrhoea did not change the negative association between PPI exposure and PCR-proven C. difficile infection. Long-term PPI usage and intensity of PPI exposure prior to onset of diarrhoea were not significantly associated with C. difficile infection.

Assessment of nociceptin/orphanin FQ and micro-opioid receptor mRNA in the human right atrium.

BACKGROUND: The expression of micro (mu: MOP) and nociceptin/orphanin FQ (NOP) receptors in the human myocardium is controversial. In this polymerase chain reaction (PCR)-based study using human right atrial biopsies, we have (i) probed for mRNA encoding NOP receptor and its endogenous peptide precursor, ppN/OFQ, and mRNA encoding MOP and (ii) attempted to correlate expression with cardiac function. METHODS: mRNA encoding MOP, NOP, and the precursor for NOP (ppN/OFQ) was assessed by quantitative real-time PCR (Q-PCR) using validated TaqMan primers and compared with a housekeeper (glyceraldehyde-3-phosphate dehydrogenase, GAPDH). Q-PCR data are expressed as the difference in cycle threshold (DeltaC(t)=C(tGene of interest)-C(tGAPDH): high value, low expression) and patients were grouped according to left ventricular ejection fraction (LVEF). RESULTS: Forty patients were recruited; NOP, MOP, and ppN/OFQ mRNA were measured in 38, 29, and 10 patients, respectively. DeltaC(t) (median and range) values for NOP and MOP were 10.9 (7.8-13.7) and 16.0 (12.3-18.9), respectively, representing low expression of MOP and approximately 34-fold more NOP. MOP mRNA was not detected in seven samples and with DeltaC(t) values of approximately 20, ppN/OFQ was considered absent. When patients were grouped into normal (>50%) and impaired (<50%) LVEF, there was no difference between the groups for either NOP or MOP. In some patients, intraoperative LVEF was estimated using transoesophageal echocardiography, and there was no correlation with either NOP or MOP. CONCLUSIONS: The human right atrium of patients with coronary artery disease and heart failure expresses mRNA encoding NOP and possibly low levels of MOP. This does not correlate with degree of cardiac dysfunction. In addition, the atrium does not express ppN/OFQ mRNA.

Urotensin II receptor expression in human right atrium and aorta: effects of ischaemic heart disease.

BACKGROUND: Urotensin II (UII) and its receptor UT are involved in control of the cardiovascular system and are implicated in heart failure. We measured UT expression by quantitative PCR (Q-PCR) in atrial and aortic tissue, and plasma UII while simultaneously assessing cardiac function in 40 patients undergoing coronary artery bypass surgery. METHODS: RNA extracted from atrial and aortic samples was probed with specific Q-PCR UT and housekeeper (glyceraldehyde-3-phosphate dehydrogenase, GAPDH) TaqMan primers. Plasma UII was measured using radioimmunoassay. Left ventricular ejection fraction (LVEF) was measured using preoperative trans-thoracic echocardiography and ventriculography, and intraoperatively using transoesophageal echocardiography. Q-PCR data are expressed as difference in cycle threshold (DeltaC(t)=C(tUT)-C(tGAPDH): high number indicates low expression). RESULTS: There was no difference in DeltaC(t) in either atrium or aorta between patients with normal (LVEF >50%) or those with impaired (LVEF <50%) preoperative systolic function. There was a weak negative correlation (r(2)=0.245, P=0.031) between intraoperative LVEF and DeltaC(t) in 19 patients possibly indicating down-regulation of UT with worsening LVEF. Atria expressed significantly more UT than aorta (P=0.011). In the absence of non-diseased controls, plasma UII was higher than a historical control group. CONCLUSIONS: This is the first study to simultaneously measure UT (mRNA), UII, and cardiovascular function. Collectively, these pilot data may suggest a down-regulation of UT within the right atrium of patients with heart failure.

Comparison of central venous and external jugular venous pressures during repair of proximal femoral fracture.

BACKGROUND: External jugular venous pressure (EJVP) is a close estimate of central venous pressure (CVP) in patients undergoing mechanical ventilation in the supine position, but the effects of spontaneous respiration and posture on this relationship are not known. In this study, we compared CVP with EJVP measurements in 36 patients undergoing repair of proximal femoral fracture breathing spontaneously in the supine or lateral positions. METHODS: A standard general anaesthetic was administered with patients breathing spontaneously via a laryngeal mask airway and i.v. fluids administered according to an algorithm guided by CVP measurements. CVP and EJVP catheters were placed on the right side of the neck where possible. RESULTS: In the supine position, 185 paired measurements of CVP and EJVP and 79 in the lateral position were recorded by a blinded observer during surgery. In the supine position, the mean difference between CVP and EJVP was -0.3 mm Hg (limits of agreement -2.6 to +1.9 mm Hg, 95% confidence intervals for both upper and lower limits of agreement, respectively, were -2.9 to -2.2 and +1.6 to +2.2 mm Hg). In the lateral position, the mean difference was -1.2 mm Hg (limits of agreement -5.8 to +3.8 mm Hg, 95% confidence intervals -6.8 to -4.5 and +2.7 to +4.9 mm Hg). CONCLUSIONS: These data suggest that EJVP is an acceptable estimate of CVP in the supine position. Agreement was poor in the lateral position but was stronger for estimates of trend rather than absolute values. This could be explained by the direct effects of posture.

Reliance on prothrombin time ratios causes significant errors in anticoagulation therapy.

BACKGROUND: The intensity of warfarin anticoagulation in the United States may be inappropriate if the international normalized ratio (INR) is not used, or if the international sensitivity index (ISI) of the thromboplastin is outside the range of 2.2 to 2.6. METHODS: Fifty-three hospital laboratories provided data on the sensitivity of their thromboplastin and whether they reported INR values. Additional data on thromboplastin sensitivity were obtained from 140 laboratories involved in the Stroke Prevention in Atrial Fibrillation study. The three major manufacturers of thromboplastin confirmed the range of thromboplastin sensitivity reported by the laboratories. RESULTS: Of 53 laboratories surveyed, 16 (30%) could not provide ISI data and only 11 (21%) reported INR results. Unlabeled thromboplastin was being used by 20% to 24% of laboratories, and only 8% to 20% were using thromboplastins with an ISI of 2.2 to 2.6. At the time the three manufacturers were contacted, they reported marketing thromboplastins with ISI values from 1.2 to 2.8, but none of the thromboplastins at that time had ISI values between 2.2 and 2.6. CONCLUSION: Warfarin therapy in the United States is managed inappropriately because most laboratories do not report INRs and the variability in thromboplastin sensitivity produces misleading prothrombin time ratio results. Additionally, recent research may require reexamination if INR or ISI data were not provided.

Cardioembolic stroke.

Approximately 15% of ischemic strokes are the result of an embolism from a cardiac source. Patients with nonvalvular atrial fibrillation, acute myocardial infarction, ventricular aneurysm, rheumatic heart disease, prosthetic heart valves and other less common cardiac disorders are at an increased risk for cardioembolic stroke. Clinicians must distinguish cardioembolic from atherosclerotic strokes to provide unique management for each patient. The nurse plays a dynamic role in diagnosis, education and treatment of patients at risk or who have had a stroke from a cardiac source. Knowledge of the pathophysiologic mechanisms and treatment options is essential for the nurse to adequately manage patient care.

Concentration-dependent effect of hypocalcaemia on mortality of patients with critical bleeding requiring massive transfusion: a cohort study.

Mortality of patients with critical bleeding requiring massive transfusion is high. Although hypothermia, acidosis and coagulopathy have been well described as important determinants of mortality in patients with critical bleeding requiring massive transfusion, the risk factors and outcome associated with hypocalcaemia in these patients remain uncertain. This cohort study assessed the relationship between the lowest ionised calcium concentration during the 24-hour period of critical bleeding and the hospital mortality of 352 consecutive patients, while adjusting for diagnosis, acidosis, coagulation results, transfusion requirements and use of recombinant factor VIIa. Hypocalcaemia was common (mean concentrations 0.77 mmol/l, SD 0.19) and had a linear; concentration-dependent relationship with mortality (odds ratio [OR] 1.25 per 0.1 mmol/l decrement, 95% confidence interval [CI]: 1.04 to 1.52; P = 0.02). Hypocalcaemia accounted for 12.5% of the variability and was more important than the lowest fibrinogen concentrations (10.8%), acidosis (7.9%) and lowest platelet counts (7.7%) in predicting hospital mortality. The amount of fresh frozen plasma transfused (OR 1.09 per unit, 95% CI: 1.02 to 1.17; P = 0.02) and acidosis (OR 1.45 per 0.1 decrement, 95% CI: 1.19 to 1.72; P = 0.01) were associated with the occurrence of severe hypocalcaemia (< 0.8 mmol/l). In conclusion, ionised calcium concentrations had an inverse concentration-dependent relationship with mortality of patients with critical bleeding requiring massive transfusion. Both acidosis and the amount of fresh frozen plasma transfused were the main risk factors for severe hypocalcaemia. Further research is needed to determine whether preventing ionised hypocalcaemia can reduce mortality of patients with critical bleeding requiring massive transfusion.