Validation of the PAC-SYM questionnaire for opioid-induced constipation in patients with chronic low back pain.

Background The Patient Assessment of Constipation Symptoms (PAC‐SYM) questionnaire is a 12‐item self‐report instrument divided into abdominal, rectal and stool domains. Aims This study aimed to (1) evaluate the psychometric properties of PAC‐SYM in assessing the symptoms and severity of opioid‐induced constipation; (2) test for differences in opioid‐induced constipation between Durogesic® fentanyl transdermal reservoir (TDF) and oral sustained‐release morphine (SRM) in patients with chronic low back pain (CLBP). Methods In a 13‐month, open‐label, parallel‐group study, 680 patients were randomised to receive either TDF (n = 338) or SRM (n = 342) for CLBP. Assessments were recorded at Visit 1 (baseline), Visit 5 (Day 29) and Visit 17 (Month 13). Concurrent validity, clinical validity and responsiveness of PAC‐SYM were determined based on patients' confirmation of constipation (CC) scores. Differences in PAC‐SYM scores between treatment groups were also evaluated. Results The study included 677 patients, of whom 638 were opioid‐naïve. Mean PAC‐SYM scores for constipated patients were substantially higher than for non‐constipated patients, demonstrating good clinical validity for PAC‐SYM. The PAC‐SYM could detect changes in bowel function over the treatment period, indicating responsiveness. Homogeneity of each symptom domain exceeded Cronbach's α coefficient of 0.70, suggesting good internal consistency and reliability. Changes in mean PAC‐SYM scores from baseline to Visit 5 and Visit 17 were significantly lower for the TDF group than for the SRM group, indicating that the TDF group experienced less severe constipation. Conclusion PAC‐SYM is a reliable, valid and responsive measure of the presence and severity of opioid‐induced constipation symptoms.     

Comparison of pharmaceutical removal in two membrane bioreactors with/without powdered activated carbon addition

The present study investigates the removal of six selected pharmaceuticals from municipal wastewater in two membrane bioreactors (MBRs) with and without powdered activated carbon (PAC) addition. Two approaches were carried out for obtaining different carbon dosages related to the influent: (1) with a fixed solids retention time (SRT) and varying PAC concentrations; (2) with varying SRTs and a fixed PAC concentration. The results reveal that a PAC dosage related to influent of 21 mg L⁻¹ and SRT of 20 d are optimal. The first approach achieved a better removal performance than the second. The removal of amidotrizoic acid (up to 46%), bezafibrate (>92%) and iopromide (around 85%) were mainly caused by biological process, but were also enhanced by PAC addition. Efficient removal (>95%) of sulfamethoxazole, carbamazepine and diclofenac were highly dependent on the PAC dosage. However, carbamazepine shows re-metabolization properties during biological processing. Decreasing the SRT as done in the second approach, not only increased the PAC amount, but also decreased the mass of activated sludge and reduced the capability to degrade complex organic matter. Consequently, biodegradability and adsorbability played decisive roles in the removal of each compound.

The present study investigates the removal of six selected pharmaceuticals from municipal wastewater in two membrane bioreactors (MBRs) with and without powdered activated carbon (PAC) addition.     

In vitro cell quality of buffy coat platelets in additive solution treated with pathogen reduction technology

BACKGROUND: Pathogen reduction technologies (PRTs) may induce storage lesion in platelet (PLT) concentrates. To investigate this, buffy coat PLTs (BCPs) in PLT additive solution (AS; SSP+) with or without Mirasol PRT (CaridianBCT Biotechnologies) were assessed by quality control tests and four‐color flow cytometry. STUDY DESIGN AND METHODS: In vitro comparison of PRT and control pooled‐and‐split BCPs after 2, 3, 6, 7, and 8 days of storage was made. PLT concentration, count per unit, swirl, metabolism, activation (CD62P, PAC1, CD42b/GPIb, CD63, CD40L/CD154, CD40, annexin V), and microparticle, sCD40L, and sCD62P release were evaluated. RESULTS: PRT induced a minor initial PLT loss (Day 2 [mean ± SD], 302 × 10⁹ ± 44 × 10⁹ PLTs/unit vs. 325 × 10⁹ ± 46 × 10⁹ PLTs/unit; p < 0.001) but the decline was comparable to control BCP. Swirling was comparable and declined with similar rates in PRT‐treated and control BCPs during storage. PRT enhanced PLT metabolism and activation, evidenced by lower pH₂₂; increased glucose consumption and lactate production rates (p < 0.01); early increases in CD62P‐, PAC1‐, CD63‐, CD40L‐, CD40‐, and annexin V–positive PLTs; reduced GPIb expression; and enhanced release of PLT‐derived MPs and sCD40L (all p < 0.05). CD62P and PAC1 expression changed with different kinetics during storage and varying GPIb expression was displayed within the CD62P/PAC1‐positive PLT subsets. CONCLUSION: PRT treatment of BCP in AS induced a minor initial PLT loss and enhanced metabolism and PLT activation. The clinical relevance for PLT function in vivo of these findings will be investigated in a clinical trial.     

Hemiazygous Coil Placement for High‐Defibrillation Thresholds in a Patient with a Right‐Sided Implantable Cardioverter Defibrillator

A 41‐year‐old man underwent implantation of a right‐sided implantable cardioverter defibrillator after removal of an infected left‐sided system. Defibrillation threshold (DFT) testing on the right‐sided system failed to convert ventricular fibrillation at maximum device output (35 J) compared with a DFT of less than 15 J on the previous left‐sided system. A single‐coil lead was selectively placed into the hemiazygous vein, which courses leftward of the spine in a posterior‐anterior projection, resulting in an improved shocking vector and reduction in DFTs to less than 25 J. (PACE 2012; 35:e10–e12)     

Application of Enteromorpha polysaccharides as a new coagulant aid to remove silver nanoparticles: role of dosage sequence and solution pH

Silver nanoparticles (AgNPs) in surface water cause a serious threat to the health of humans and aquatic organisms. However, it is difficult to remove AgNPs completely since they could adsorb onto the surface of humic acid (HA) and meanwhile release Ag⁺ into water. In this paper, Enteromorpha polysaccharides (Ep) were applied as a coagulant aid with polyaluminum chloride (PAC) to solve this problem. The influences of Ep dosage, dosing sequence and solution pH on the coagulation efficiency, kinetics and removal mechanism of AgNPs were discussed systematically. Results showed that when Ep was applied, AgNPs could be removed effectively due to charge neutralization of PAC hydrolysate and the bridging-sweeping role of Ep gel network. When Ep was added 30 s after PAC dosing, the coagulation efficiency was about 10–20% higher than that of the reverse order. Under this condition, flocs sizes achieved 450 μm when the solution pH was 6.0, which is much larger than that using Ep–PAC. Additionally, Ep showed an ability to promote the re-aggregation of broken flocs, and AgNP–HA flocs exhibited larger sizes, better shear resistance, higher recovery ability and denser structure at pH 6.0. Factorial analysis results indicated that PAC dosage had the greatest impact on HA and AgNP removal, while Ag⁺ removal is more sensitive to Ep dosage.

Silver nanoparticles (AgNPs) could be removed effectively due to bridging-sweep role of Enteromorpha polysaccharides (Ep), and flocs exhibited larger sizes, better shear resistance, higher recovery ability and denser structure when Ep was added.     

Commentary: Trzeciak S et al. (2006). Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department

Early goal‐directed therapy (EGDT) has been shown to decrease mortality in patients with severe sepsis and septic shock. Consensus guidelines now advocate EGDT for the first 6 h of sepsis resuscitation. However, EGDT has not yet been widely adopted in practice. A need for effective collaboration between emergency medicine and critical care medicine services has been identified as an obstacle to implementation. We aimed to determine if EGDT end‐points could reliably be achieved in real‐world clinical practice. EGDT was implemented as a collaborative emergency medicine/critical care quality improvement initiative. EGDT include the following: intravenous (IV) fluids (IVF) targeting central venous pressure ≥8 mmHg, vasopressors targeting mean arterial pressure ≥65 mmHg, and (if necessary) packed RBCs (PRBCs) and/or dobutamine targeting central venous oxygen saturation ≥70%. A retrospective analysis was performed of emergency department (ED) patients with persistent sepsis‐induced hypotension (systolic blood pressure <90 mmHg despite 1.5 L of IVF) treated with EGDT during the first year of the initiative. Primary outcome measures included successful achievement of EGDT end‐points and time to achievement. A secondary analysis was performed, comparing EGDT cases to historical control cases (non‐protocolized control subjects without invasive monitoring). All end‐points were achieved in 20 of 22 cases (91%). The median time to reach end‐point was ≤6 h. In the secondary analysis, patients (n = 38; EGDT, n = 22; pre‐EGDT, n = 16) had similar age, do‐not‐resuscitate status, severity scores, hypotension duration and vasopressor requirement (p = not significant). In the ED, EGDT used more IVF and included PRBC/dobutamine utilization, without any effect on the overall use of these therapies through the first 24 h in the ICU. EGDT was associated with decreased intensive care unit pulmonary artery catheter (PAC) utilization (9.1% versus 43.7%, p = 0.01). With effective emergency medicine/critical care collaboration, we demonstrate that EGDT end‐points can reliably be achieved in real‐world sepsis resuscitation. ED‐based EGDT appears to decrease ICU PAC utilization. Abstract reprinted from the Chest volume 129, Trzeciak et al., ‘Translating research to clinical practice: a 1–year experience with implementing early goal‐directed therapy for septic shock in the emergency department.’, pages 225–232. © 2006, with permission from Blackwell Publishing Ltd.     

Electrocardiographic activity before onset of postoperative atrial fibrillation in cardiac surgery patients

Background: Electrocardiographic (ECG) characteristics were analyzed in postoperative cardiac surgery patients in an attempt to predict development of new‐onset postoperative atrial fibrillation (AF). Methods: Nineteen ECG characteristics were analyzed using computer‐based algorithms. The parameters were retrospectively analyzed from ECG signals recorded in postoperative cardiac surgery patients while they were in the cardiovascular intensive care unit (CVICU) at our institution. ECG data from 99 patients (of whom 43 developed postoperative AF) were analyzed. A bootstrap variable selection procedure was applied to select the most important ECG parameters, and a multivariable logistic regression model was developed to classify patients who did and did not develop AF. Results: Premature atrial activity (PAC) was greater in AF patients (P < 0.01). Certain heart rate variability (HRV) and turbulence parameters also differed in patients who did and did not develop AF. In contrast, P‐wave morphology was similar in patients with and without AF. Receiver operating curve (ROC) analysis applied to the model produced a C‐statistic of 0.904. The model thus correctly classified AF patients with more than a 90% sensitivity and a 70% specificity. Conclusion: Among the 19 ECG parameters analyzed, PAC activity, frequency‐domain HRV, and heart rate turbulence parameters were the best discriminators for postoperative AF.     

Expression of EMMPRIN (CD147) on circulating platelets in vivo

Summary. Background and Objectives: EMMPRIN (CD147) is a matrix metalloproteinase inducer present on leukocytes and recently identified on platelets in vitro. We examined platelet CD147 expression in vivo and in correlation with markers of platelet activation and coronary artery disease (CAD). Patients/Methods: This prospective observational study involved 70 subjects (55 patients with CAD and 15 controls). Platelet CD62P expression, PAC‐1 expression, platelet–leukocyte aggregates and CD147 (both platelet and leukocyte) expression were assessed by flow cytometry, and soluble CD62P expression was assessed by enzyme‐linked immunosorbent assay. A full blood count and high‐sensitivity C‐reactive protein test were performed. Results: CD147 was expressed on 20.45% ± 1.63% (mean ± standard error of the mean) of circulating platelets, whereas CD62P and PAC‐1 were expressed on 0.87% ± 0.12% and 0.90% ± 0.27% of platelets, respectively. Platelet CD147 expression correlated with CD62P expression (r = 0.359, P = 0.002), PAC‐1 expression (r = 0.428, P < 0.001), leukocyte CD147 expression (monocyte, r = 0.416, P = 0.001; granulocyte, r = 0.434, P < 0.001), C‐reactive protein level and neutrophil/lymphocyte ratio (NLR). CAD patients had significantly higher CD147 mean fluorescence intensity than controls on circulating platelets (2.41 ± 0.14 vs. 2.87 ± 0.09, P = 0.014), monocytes (8.57 ± 1.20 vs. 12.3 ± 0.57, P = 0.006) and granulocytes (4.30 ± 0.65 vs. 6.50 ± 0.34, P = 0.005). Age adjustment eliminated the association between platelet CD147 expression and CAD, but the association between leukocyte CD147 expression and CAD persisted. According to multivariate analysis, the independent predictors of platelet CD147 expression were monocyte CD147 expression, NLR and age. Conclusions: Platelet CD147 expression is evident in vivo and correlates moderately with traditional platelet activation markers and leukocyte CD147 expression. Platelet CD147 expression shows a stronger association with age, and leukocyte CD147 expression a stronger association with clinical CAD, suggesting differences in the regulation of platelet and leukocyte CD147 expression in vivo.     

Failure of the active-fixation mechanism during removal of active-fixation pacing leads

Background: Active‐fixation pacing leads are being widely employed due to their theoretical advantages when compared with traditional passive‐fixation leads: easy fixation and reposition, possible deployment in alternative pacing sites, lower rates of dislodgment, and chronic removability. However, the behavior of the active‐fixation mechanism during lead removal has not been yet systematically studied and may have important clinical implications. Objective: To evaluate if the active‐fixation mechanism was still working properly in pacing leads that were removed due to different causes. Methods: Thirty‐one consecutive patients undergoing active‐fixation lead removal (40 leads) were studied. Before lead removal, the helix was retracted using the appropriate tool, and fluoroscopy signs were evaluated. After removal, the helix status was examined, and the active‐fixation mechanism was once again retested when possible. Results: In nine of 40 leads (22.5%), the helix remained extended after lead removal in spite of having applied the number of rotations recommended by the manufacturer with the clip‐on tool. There was no linear relationship between lead longevity and the presence of an extended helix after lead removal. However, failure of the active‐fixation mechanism was more frequent among leads implanted <1 year before versus >1 year before (OR 6.8, 95% CI 1.1–42.7, P = 0.043). In 38% of patients with failure of the active‐fixation mechanism, a previous lead reposition had been attempted before lead removal due to significant pacing threshold rise. Conclusions: In our series, the active‐fixation mechanism failed in up to 22.5% of explanted leads. This may have important clinical implications during active‐fixation lead removal and reposition. 2011; 34:1217–1224)     

Fabrication of a novel high-performance leather waste-based composite retention aid

In this study, a novel biomass composite retention aid was developed by using collagen hydrolysate (CH) extracted from collagen waste as the starting material, glutaraldehyde as the organic crosslinking agent and polymeric aluminum chloride (PAC) as the inorganic modifying agent. The as-prepared retention aids were characterized by gel chromatography, hydrodynamic diameter, zeta potential, transmission electron microscope (TEM), ultraviolet-visible adsorption spectra (UV-Vis), Fourier infrared spectrometer (FT-IR), and X-ray photoelectron spectroscopy (XPS). The results indicated that glutaraldehyde increased the molecular size of CH (i.e., CCH) through the crosslinking reaction between the aldehyde group of glutaraldehyde and the primary amine group of CH. Subsequently, the PAC further increased cationic charge density and molecular size of CCH (i.e., PAC–CCH) by the coordination interaction and self-assembly, thereby endowing PAC–CCH with better charge neutralization and bridging flocculation abilities. Compared to CH, CCH and PAC, the PAC–CCH exhibited excellent retention and drainage performances, and the best retention rate was greater than 85% at the dosage of 0.6 wt%. Our experimental results suggest that collagen wastes have a great potential to produce novel high-performance retention aids.

A novel biomass composite retention aid was developed by using collagen hydrolysate extracted from collagen waste as starting material, glutaraldehyde as organic crosslinking agent and polymeric aluminum chloride as inorganic modifying agent.     

Metabolic and anti-inflammatory benefits of eccentric endurance exercise - a pilot study

Background Eccentric endurance exercise (e.g. hiking downwards) is less strenuous than concentric exercise (e.g. hiking upwards) but its potential to reduce cardiovascular risk is unknown. Materials and methods We randomly allocated 45 healthy sedentary individuals (16 men and 29 women, mean age 48 years) to one of two groups, one beginning with two months of hiking upwards, the other with two months of hiking downwards the same route, with a crossover for a further two months. For the opposite way, a cable car was used where compliance was recorded electronically. The difference in altitude was 540 metres; the distance was covered three to five times a week. Fasting and postprandial metabolic profiles were obtained at baseline and after the two month periods of eccentric and concentric exercise, respectively. Results Forty‐two of the 45 participants completed the study; the compliance rate was therefore 93%. Compared with baseline, eccentric exercise lowered total cholesterol (by 4·1%; P = 0·026), low‐density lipoprotein (LDL) cholesterol (by 8·4%, P = 0·001), Apolipoprotein B/Apolipoprotein A1 ratio (by 10·9%, P < 0·001), homeostasis model assessment of insulin resistance scores (by 26·2%, P = 0·017) and C‐reactive protein (by 30·0%; P = 0·007); the magnitude of these changes was comparable to that of concentric exercise. Eccentric exercise improved glucose tolerance (by 6·2%, P = 0·023), whereas concentric exercise improved triglyceride tolerance (by 14·9%, P = 0·022). Conclusions Eccentric endurance exercise is a promising new exercise modality with favourable metabolic and anti‐inflammatory effects and is well applicable to sedentary individuals.     

Evaluation oF FactORs ImpacTing CLinical Outcome and Cost EffectiveneSS of the S-ICD: design and rationale of the EFFORTLESS S-ICD Registry

Background: Leads in and on the heart of the transvenous implantable cardioverter defibrillator (ICD) form the Achilles’ heel of this system due to potential for peri‐ and postimplant complications. The S‐ICD is a newer generation of the ICD that does not require leads on the heart or in the vasculature. We present the rationale and study design of the Evaluation oF FactORs ImpacTing CLinical Outcome and Cost EffectiveneSS of the S‐ICD (EFFORTLESS S‐ICD) Registry which was designed to evaluate the long‐term performance of the S‐ICD including patient quality of life and long‐term resource utilization. Methods: The Registry is an observational, nonrandomized, standard of care evaluation to be conducted at approximately 50 investigational centers in Europe and New Zealand where the S‐ICD is approved for use and distribution. Clinical Registry endpoints include perioperative (30 days postimplant) complication‐free rate, 360‐day complication‐free rate, and percentage of inappropriate shocks for atrial fibrillation and supraventricular ventricular tachyarrhythmia. Other endpoints include patient‐reported outcomes (e.g., quality of life) and hospital personnel implant and follow‐up experience with the S‐ICD system. Conclusions: Results from EFFORTLESS will build on and expand the initial published experience with the S‐ICD, which demonstrated that the device successfully and consistently detects and treats episodes of sustained ventricular tachyarrhythmias. The Registry will also evaluate the patients’ perspective of how it is to live with an S‐ICD as compared to a contemporary transvenous system and track the experience of implanting physicians and personnel performing patient follow‐up with a completely subcutaneous system. (PACE 2012; 1–6)     

The impact of humic acid on metaldehyde adsorption onto powdered activated carbon in aqueous solution

Metaldehyde has been detected in surface water and drinking water in the UK, exceeding the EU and UK standard of 0.1 μg L⁻¹. The presence of natural organic matter (NOM) is considered to affect the removal efficiency of metaldehyde using traditional treatment methods such as adsorption by granular activated carbon. This paper selected humic acid (HA) to represent NOM and investigated the single and binary adsorption systems of metaldehyde and HA by powdered activated carbon (PAC). Metaldehyde was effectively removed by PAC in both systems. Since the percentage removal of metaldehyde was only 3% lower in the binary adsorption system, HA was therefore not considered as a significant compound competing with metaldehyde for adsorption sites on PAC. An adsorption equilibrium study and kinetic study for metaldehyde in a single system suggested that the Langmuir isotherm and the pseudo-second order kinetic model were more suitable in this case than the Freundlich isotherm and the pseudo-first order kinetic model. The two models revealed that the maximum adsorption capacity (q_m) of metaldehyde by PAC was 28.3 mg g⁻¹ and the adsorption rate (k₂) was 0.16 g mg⁻¹ min⁻¹. The effect of pH of metaldehyde solution was also investigated in a single system. Higher percentage removal of metaldehyde was found under alkaline conditions. In contrast to metaldehyde, HA was not effectively and efficiently removed by PAC in both systems, even with higher PAC dosages and longer contact times. Hence, the microporous and mesoporous PAC was suitable for removing metaldehyde even in the binary system.

Powdered activated carbon with abundant micropores and mesopores can effectively remove metaldehyde from aqueous solution in the presence of humic acid.     

Cloning and paratope analysis of an antibody fragment, a rational approach for the design of a PAI-1 inhibitor

Summary. This study reports the cloning, characterization and paratope analysis of the plasminogen activator inhibitor‐1 (PAI‐1) neutralizing single‐chain variable fragment 56A7C10 (scFv‐56A7C10). ScFv‐56A7C10‐wt exhibits a similar affinity (K_A = 1.01 ± 0.3 × 10⁹ m ^?1) and PAI‐1 inhibitory capacity (90 ± 6% PAI‐1 inhibition at a 16‐fold molar excess and IC₅₀ = 44 ± 14 ng mL^?1) as MA‐56A7C10 (K_A = 1.43 ± 0.4 × 10⁹ m ^?1, 90 ± 2% PAI‐1 inhibition at a 16‐fold molar excess and IC₅₀ = 122 ± 26 ng mL^?1). Subsequently, alanine scanning of the six complementarity determining regions (CDRs) was performed and the scFv‐56A7C10‐mutants (n = 26) were analyzed for their PAI‐1 binding and PAI‐1 inhibitory properties. Mutation of the residues Y32 and V33 in the CDR1 of the heavy chain (HCDR1) and the residues R98, H99, W100 or F100a (HCDR3) resulted in reduced PAI‐1 inhibitory capacities (IC₅₀ ≥ 418 ng mL^?1), confirmed by reduced affinities (14‐, 17‐, 7‐, 9‐ and 16‐fold reduced, respectively, vs. scFv‐56A7C10‐wt). In the light chain, mutation of the residues W50 (LCDR2), H91, Y92, D93, or W96 (LCDR3) resulted in reduced PAI‐1 inhibitory properties (IC₅₀ ≥ 160 ng mL^?1) and decreased affinities (i.e. 4‐, 9‐, 3‐, 3‐ and 2‐fold reduced affinity, respectively, vs. scFv‐56A7C10‐wt). Furthermore, an overlapping peptide scan confirmed the importance of the HCDR3 region. These data, combined with a three‐dimensional model of scFv‐56A7C10, reveal the molecular and structural properties of the paratope and contribute to the rational design of PAI‐1 neutralizing compounds.     

P47Inherited Familial Thrombocytopenia due to an Autosomal Dominant Mutation in the Cytoplasmic Domain of Platelet β3‐Integrin that is Associated with the Expression of Activation‐Dependent Epitopes

Background Glanzmann's Thrombasthenia (GT) and Bernard Soulier Syndrome (BSS) are the two most common inherited forms of thrombasthenia. They are caused by alterations in expression or function of integrin alphaIIb/β3 or glycoprotein (GP) Ib/IX/V respectively. We identified an individual with chronic mild macrothrombocytopenia (range 59–100 × 10⁹ L^?1) but no overt bleeding diathesis. The propositus was found to have atypical binding of monoclonal antibodies (mAb) to β3 integrin and increased expression of GPIbVIX. Methods and Results The exons and flanking intronic sequences of ITGB3, ITGA2B GPIBA, GPIBB, GP9 and GP5 genes were sequenced. Heterozygous, non‐synonymous single nucleotide polymorphisms (SNP) were identified in the ITGB3 and the GPIBA genes. These result in the substitution of Histidine for Aspartate at residue 723 (D723H) in ITGB3 and Leucine for Proline at residue 69 (P69L) in GPIBA. Asp723 in ITGB3 is known to form a critical salt‐bridge with ITGA2B and charge reversal at residue 723 causes constitutive activation of the integrin in vitro. In agreement with this, mutant alphaIIb/β3‐His723 expressing CHO cell lines showed an increased expression of activation dependent epitopes relative to wild‐type as measured by mAb PAC‐1 binding. Increased PAC‐1 binding was also observed on resting platelets of affected individuals compared with non‐affected family members. Further investigation of three generations of the propositus’ family identified several individuals with both SNPs each of whom had an identical platelet phenotype. However, in the one family member identified who carried the GPIBA mutation alone, normal platelet size and count were observed suggesting that the ITGB3 D723H substitution is the causative mutation. Genotyping a panel of 1127 unrelated controls for the two SNPs identified five individuals with the GPIBA mutation and none with the ITGB3 mutation. Conclusions We report a novel autosomal dominant cause of a mild form of macrothrombocytopenia caused by a D723H substitution in the beta3 integrin. We postulate that the low platelet count is due to increased consumption of platelets due to enhanced levels of surface expressed, activated GPIIbIIIa.     

Nurse-determined assessment of cardiac output. Comparing a non-invasive cardiac output device and pulmonary artery catheter: A prospective observational study

Background

The accurate measurement of Cardiac output (CO) is vital in guiding the treatment of critically ill patients. Invasive or minimally invasive measurement of CO is not without inherent risks to the patient. Skilled Intensive Care Unit (ICU) nursing staff are in an ideal position to assess changes in CO following therapeutic measures. The USCOM (Ultrasonic Cardiac Output Monitor) device is a non-invasive CO monitor whose clinical utility and ease of use requires testing.

Objectives

To compare cardiac output measurement using a non-invasive ultrasonic device (USCOM) operated by a non-echocardiograhically trained ICU Registered Nurse (RN), with the conventional pulmonary artery catheter (PAC) using both thermodilution and Fick methods.

Design

Prospective observational study.

Setting and participants

Between April 2006 and March 2007, we evaluated 30 spontaneously breathing patients requiring PAC for assessment of heart failure and/or pulmonary hypertension at a tertiary level cardiothoracic hospital.

Methods

SCOM CO was compared with thermodilution measurements via PAC and CO estimated using a modified Fick equation. This catheter was inserted by a medical officer, and all USCOM measurements by a senior ICU nurse. Mean values, bias and precision, and mean percentage difference between measures were determined to compare methods. The Intra-Class Correlation statistic was also used to assess agreement. The USCOM time to measure was recorded to assess the learning curve for USCOM use performed by an ICU RN and a line of best fit demonstrated to describe the operator learning curve.

Results

In 24 of 30 (80%) patients studied, CO measures were obtained. In 6 of 30 (20%) patients, an adequate USCOM signal was not achieved. The mean difference (±standard deviation) between USCOM and PAC, USCOM and Fick, and Fick and PAC CO were small, −0.34 ± 0.52 L/min, −0.33 ± 0.90 L/min and −0.25 ± 0.63 L/min respectively across a range of outputs from 2.6 L/min to 7.2 L/min. The percent limits of agreement (LOA) for all measures were −34.6% to 17.8% for USCOM and PAC, −49.8% to 34.1% for USCOM and Fick and −36.4% to 23.7% for PAC and Fick. Signal acquisition time reduced on average by 0.6 min per measure to less than 10 min at the end of the study.

Conclusions

In 80% of our cohort, USCOM, PAC and Fick measures of CO all showed clinically acceptable agreement and the learning curve for operation of the non-invasive USCOM device by an ICU RN was found to be satisfactorily short. Further work is required in patients receiving positive pressure ventilation.     

Qualitative and quantitative evaluation for morphological changes of the splenic artery in autoimmune pancreatitis: novel imaging findings for differentiation from pancreatic adenocarcinoma

Purpose

To determine whether morphological changes can occur in the splenic artery (SPA) of autoimmune pancreatitis (AIP) cases, and if present, to compare them with those in pancreatic adenocarcinoma (PAC) to clarify any arterial morphological differences between AIP and PAC.

Methods

A total of 101 AIP cases were included in this study. The presence or absence of morphological change in the SPA was assessed, using arterial phase axial computed tomography images. Subsequently, imaging parameters (imaging pattern, capsule-like rim, other organ involvement, splenic vein [SPV] stenosis, and SPA calcification) were compared between cases with and without morphological changes. Additionally, comparison analyses (visual SPA assessment and % minimal lumen diameter [MLD] stenosis) among normal pancreas, PAC, and AIP groups were performed using early arterial phase (EAP) reconstructed images.

Results

In 25 (24.8%) AIP cases, marginal irregularities of the SPA were present. The presence of the capsule-like rim and SPV stenosis were significantly associated with the arterial morphological changes. All cases with morphological changes had a capsule-like rim. Visual assessment using EAP reconstructed images revealed irregularities of the SPA in 9 of 38 AIP cases (23.7%); however, arterial narrowing was not detected in any cases. % MLD stenosis in AIP group was significantly lower than that in PAC group (p < 0.0001).

Conclusions

Although approximately one-quarter of AIP cases potentially demonstrate marginal irregularity in the SPA when it is surrounded by an apparent capsule-like rim, arterial luminal narrowing rarely occurs in contrast to PAC. These arterial findings can help to distinguish AIP from PAC.

     

Development of a single-tube PCR-pyrosequencing method for the simultaneous and rapid detection of four variant alleles of CYP2C9 gene polymorphism

Background and Objective: CYP2C9 is a polymorphic enzyme that has been reported to metabolize several clinically useful drugs such as warfarin, phenytoin and non‐steroidal anti‐inflammatory drugs. We designed a rapid single‐tube multiplex assay to detect four variant alleles of the CYP2C9 in a single polymerase chain reaction (PCR) and a single pyrosequencing reaction. Methods: A multiplex PCR was designed to amplify two fragments simultaneously, one containing 430C>T (CYP2C9*2) polymorphism and other containing 1075A>C (CYP2C9*3), 1076T>C (CYP2C9*4) and 1080C>G (CYP2C9*5) polymorphisms. Results: Four variants of the CYP2C9 gene could be simultaneously detected using only two varieties of pyrosequencing primers in a single‐tube. The success rate for the four SNPs (*2, *3,*4 and *5) was high. Genotypes obtained by the multiplex reaction were 100% concordant with genotypes obtained using direct DNA sequencing (n = 96). The analysis time was halved, compared with existing simplex pyrosequencing. The system allowed high‐throughput analysis of over 384 samples per hour. Discussion: Our method reduces running cost and halves analysis time, compared to simplex pyrosequencing. Another advantage of this method is that it analyses and determines multiple bases around the polymorphic site thereby reducing the possibility of scoring a truncated PCR product.     

The effectiveness of an osteoporosis prevention education programme for women in Hong Kong: a randomized controlled trial

Aims. The purpose of this study was to evaluate whether a nurse‐initiated education programme on four specific osteoporosis‐prevention related behaviours leads to their adoption or positive attitude changes compared with women who did not participate in this programme. Research method. The design was a randomized controlled design and the setting was a local private beauty clinic. Outcome measures. Pre‐, post‐ and follow‐up education data compared attitudes and consumption frequency before and after the education programme. Results. The results showed significant increases in the reported follow‐up for each behaviour: consumption of soya foods (mean = 4·3, SD = 0·5), milk (mean = 4·2, SD = 0·8), more exercise (mean = 4·3, SD = 0·5) and vitamin D/exposure to sunlight (mean = 4·2, SD = 0·9) for subjects in the case group compared with control group subjects (soya foods: mean = 3·3, SD = 0·9, P < 0·001; milk: mean = 3·0, SD = 0·9, P < 0·001; more exercise: mean = 3·4, SD = 1·0, P = 0·003; vitamin D/sunlight: mean = 2·7, SD = 0·9, P < 0·00). Most of the participants either disagreed (n = 11, 55·0%) or strongly disagreed (n = 9, 45·0%) that there was not enough information provided in the education programme to motivate them to change. On the satisfaction score, they rated the nurse's performance as either satisfactory (n = 11, 55·0%) or very satisfactory (n = 9, 45·0%) on presentation and ability to answer their questions and either satisfactory (n = 12, 60·0%) or very satisfactory (n = 8, 40·0%) on ability to describe each behaviour clearly. Conclusion. A targeted education programme conducted with Hong Kong women resulted in significantly increased consumption of calcium including soya‐based foods, milk and vitamin D. According to the reported attitudinal and behavioural intentions, participants’ positive feedback suggests that women who participated in this educational programme were motivated to make changes and benefited from the support of this nurse‐initiated education programme. Relevance to clinical practice. Osteoporosis was a serious health concern that most commonly affected women. As indicated by the results of this study, this educational programme can act as simple but effective nursing intervention to promote women's attitudinal and behavioural intentions towards osteoporosis‐prevention.     

Continuous cardiac index monitoring: A prospective observational study of agreement between a pulmonary artery catheter and a calibrated minimally invasive technique

IntroductionContinuous cardiac index (CCI) monitoring can provide information to assist in hemodynamic support. However, pulmonary artery catheters (PAC) pose logistic challenges in acute care settings. We hypothesized that CCI measured with a calibrated minimally invasive technique (LiDCO/PulseCO, UK) would have good agreement with the PAC.MethodsWe performed a prospective observational study in post-operative cardiac surgery patients. All patients had a PAC with CCI monitoring capability. We connected the LiDCO apparatus to a radial artery line and performed a one-time calibration with a lithium dilution indicator. In order to test the least invasive method possible, we used a peripheral intravenous (IV) line for indicator delivery rather than the conventional central line technique. We recorded paired PAC/LiDCO-PulseCO CCI measurements every minute for 3 h. We blinded investigators and clinicians to minimally invasive data with an opaque shield over the monitor. We assessed agreement with Bland-Altman analysis.ResultsWe obtained 1485 paired measurements in 8 subjects. The mean CI was 2.9 L/min/m². By Bland-Altman plot, PAC and LiDCO measurements showed minimal bias (?0.01), but the 95% limits of agreement (±2SD) of ± 1.3 L/min/m² were relatively wide with respect to the mean.ConclusionsThis calibrated minimally invasive (i.e. radial arterial line and peripheral IV) technique demonstrated low bias compared with CCI measured by PAC. However, the relatively wide confidence limits indicate that differences in the two measurements could still be clinically significant.