Impact of tricuspid regurgitation on survival in patients with chronic heart failure: unexpected findings of a long-term observational study.

AIMS: Tricuspid regurgitation (TR) is common in patients with chronic heart failure (CHF) but its prognostic impact is unclear. METHODS AND RESULTS: A total of 576 consecutive patients with CHF were prospectively included. The impact of moderate and severe (significant) TR on the combined endpoint death/heart transplantation/left ventricular-assist device implantation was assessed. Patients were followed for 5.8 ± 4.2 (maximum 14.4) years. Kaplan-Meier analysis showed a worse outcome of patients with significant TR (P < 0.0001). By multivariable analysis, amino terminal pro B-type natriuretic peptide (NT-proBNP) (P = 0.0028), systolic left ventricular function (LVF) (P = 0.0014), serum sodium, NYHA functional class, systolic blood pressure, right atrial size (all P = 0.0001), but not TR were significantly related with the outcome. However, as soon as the strong interaction between TR and LVF was included in the model, significant TR determined outcome as well (P = 0.0059). Therefore, in a second analysis patients were stratified for LVF. In patients with mildly or moderately impaired LVF, TR was significantly related with the outcome (HR: 1.368, CI: 1.070-1.748, P = 0.0125), whereas in patients with severely depressed LVF it was not (P = 0.1401). As a proof of concept, we additionally stratified patients according to serum NT-proBNP concentrations. In patients with NT-proBNP concentrations below the median (≤ 280 fmol/mL), TR was related with the outcome (HR: 2.512, CI: 1.127-5.597, P = 0.0242) but it was not in patients with NT-proBNP concentrations above the median (P = 0.3935). CONCLUSION: The prognostic impact of TR depends on the severity of CHF. While TR was significantly related with excess mortality in mild to moderate CHF, it provided no additive value in advanced disease when compared with established risk factors.

Antipsychotics for acute and chronic pain in adults.

BACKGROUND: This is an updated version of the original Cochrane review published in Issue 4, 2008. The role of antipsychotics as adjuvant analgesics is a subject of longstanding controversy. Neuroleptanalgesia (that is a state of quiescence, altered awareness, and analgesia produced by a combination of taking an opioid analgesic and an antipsychotic), an established term for the management of acute pain, was shown to negatively influence disease course and total mortality in unstable angina patients. Nevertheless, antipsychotics are used to treat chronic pain (for example chronic headache, fibromyalgia and diabetic neuropathia). With atypical antipsychotics, a new class of antipsychotics, both fewer extrapyramidal side effects and additional benefits may be available. OBJECTIVES: To assess the analgesic efficacy and adverse effects of antipsychotics in acute or chronic pain in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, and EMBASE in October 2011 and January 2013. SELECTION CRITERIA: Randomised controlled trials (RCTs) of adults prescribed any dose of an oral antipsychotic for acute or chronic pain, where subjective pain assessment was described as either the primary or a secondary outcome, were included in this review. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent review authors, and results were compared for differences. Discrepancies were resolved by discussion. All trials were quality scored according to the methods set out in section six of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: A total of 770 participants were involved in the 11 included studies. Data from five included randomised double-blind studies showed beneficial effects of antipsychotics in the treatment of acute and chronic pain. Quantitative analysis of these studies showed a significant reduction of mean pain intensity after administration of the antipsychotic compared to placebo or another active compound, weighted mean difference (WMD) -1.78 (95% CI -2.71 to -0.85) for the continuous data; and relative risk (RR) 0.43 (95% CI 0.25 to 0.73), number needed to treat to benefit (NNT) 2.6 for the dichotomous data. Nevertheless, the test for heterogeneity was significant for both the continuous data (P = 0.0007) and the dichotomous data (P = 0.04). Obviously this makes the calculated NNT less reliable and caution is warranted when interpreting these results.The most frequently reported adverse effects were extrapyramidal (that is involuntary movements, parkinsonism and akathisia) and sedating effects. AUTHORS' CONCLUSIONS: The recent search found five new studies which were all excluded, so the review remains the same as previously.Antipsychotics might be used as an add-on therapy in the treatment of painful conditions. Nevertheless, extrapyramidal and sedating side effects have to be considered before using antipsychotics for treating painful conditions.Results for antipsychotics in the treatment of different painful conditions are mixed and most sample sizes in the reviewed RCTs are small. Further studies on atypical antipsychotics in larger double-blind placebo-controlled studies that include standardised pain assessment and documentation are warranted.

Effectiveness of averaging strategies to reduce variance in retinal nerve fibre layer thickness measurements using spectral-domain optical coherence tomography.

BACKGROUND: Automated detection of subtle changes in peripapillary retinal nerve fibre layer thickness (RNFLT) over time using optical coherence tomography (OCT) is limited by inherent image quality before layer segmentation, stabilization of the scan on the peripapillary retina and its precise placement on repeated scans. The present study evaluates image quality and reproducibility of spectral domain (SD)-OCT comparing different rates of automatic real-time tracking (ART). METHODS: Peripapillary RNFLT was measured in 40 healthy eyes on six different days using SD-OCT with an eye-tracking system. Image brightness of OCT with unaveraged single frame B-scans was compared to images using ART of 16 B-scans and 100 averaged frames. Short-term and day-to-day reproducibility was evaluated by calculation of intraindividual coefficients of variation (CV) and intraclass correlation coefficients (ICC) for single measurements as well as for seven repeated measurements per study day. RESULTS: Image brightness, short-term reproducibility, and day-to-day reproducibility were significantly improved using ART of 100 frames compared to one and 16 frames. Short-term CV was reduced from 0.94 ± 0.31 % and 0.91 ± 0.54 % in scans of one and 16 frames to 0.56 ± 0.42 % in scans of 100 averaged frames (P ≤ 0.003 each). Day-to-day CV was reduced from 0.98 ± 0.86 % and 0.78 ± 0.56 % to 0.53 ± 0.43 % (P ≤ 0.022 each). The range of ICC was 0.94 to 0.99. Sample size calculations for detecting changes of RNFLT over time in the range of 2 to 5 µm were performed based on intraindividual variability. CONCLUSION: Image quality and reproducibility of mean peripapillary RNFLT measurements using SD-OCT is improved by averaging OCT images with eye-tracking compared to unaveraged single frame images. Further improvement is achieved by increasing the amount of frames per measurement, and by averaging values of repeated measurements per session. These strategies may allow a more accurate evaluation of RNFLT reduction in clinical trials observing optic nerve degeneration.

Beta 2 microglobulin and the risk for cardiovascular events in patients with asymptomatic carotid atherosclerosis.

BACKGROUND AND PURPOSE: Atherosclerosis is a chronic inflammatory disease. Ongoing inflammation is associated with elevated levels of beta 2 microglobulin (B2M). We investigated B2M levels in a large cohort of patients with carotid atherosclerosis for the occurrence of major adverse cardiovascular events. METHODS: One thousand five of 1286 consecutive, neurologically asymptomatic patients with carotid atherosclerosis were followed for a median of 3 years (interquartile range, 2.5 to 3.5) for the occurrence of major adverse cardiovascular events, a composite of myocardial infarction, percutaneous coronary intervention, coronary bypass graft, stroke, and death. RESULTS: We recorded 359 major cardiovascular events in 271 (27%) patients. B2M was significantly associated with the occurrence of major adverse cardiovascular events. With increasing quartiles of B2M, the adjusted hazard ratios were 1.19 (95% CI, 0.81 to 1.73), 1.51 (95% CI, 1.05 to 2.18), and 1.88 (95% CI, 1.26 to 2.79) compared with the lowest quartile, respectively (P<0.001). Adjusted hazard ratios for the occurrence of death, myocardial infarction, and stroke for increasing quartiles of B2M were 1.25 (95% CI, 0.92 to 1.70), 1.52 (95% CI, 1.12 to 2.06), and 1.62 (95% CI, 1.16 to 2.67) compared with the lowest quartile, respectively (P<0.001). Through statistical estimation of improvement in risk stratification, addition of B2M to baseline risk factors improved the risk stratification for major cardiovascular events, at least as much as high-sensitivity C-reactive protein or even better. CONCLUSIONS: B2M was independently and significantly associated with adverse cardiovascular outcome in patients with prevalent asymptomatic carotid atherosclerosis.

Improved outcome in patients with chronic myelogenous leukemia after allogeneic hematopoietic stem cell transplantation over the past 25 years: a single-center experience.

Although imatinib has become standard first-line therapy in chronic myelogenous leukemia (CML), allogeneic hematopoietic stem cell transplantation (HSCT) is still considered to be an important treatment alternative for patients with drug resistance or advanced disease. We retrospectively analyzed 175 adult CML patients who underwent HSCT at our institution between 1983 and 2007, with the aim to compare outcomes in patient subgroups and to identify prognostic variables. The median follow-up was 65 months. The probability of overall survival (OS) for all patients was 62%, with a significant improvement seen in the imatinib-era (2001-2007) compared to previous time periods (P <.05). Furthermore, a significantly better outcome for patients with chronic phase CML compared to patients with accelerated or blast phase could be observed (P < .05). Cumulative incidence (CI) of treatment-related mortality (TRM) was 9.7% at 100 days and 1 year after HSCT. CI of relapse was 5% at 1 year and 7.5% at 3 years after HSCT. Post-HSCT outcome was not influenced by pretreatment therapy with imatinib, donor type, or a conditioning regimen with total body irradiation (TBI). These data confirm earlier observations and suggest that allogeneic HSCT is still an important treatment option for high-risk patients with CML, and should thus remain an integral component in current and future treatment algorithms.

Previous tubal ectopic pregnancy raises the incidence of repeated ectopic pregnancies in in vitro fertilization-embryo transfer patients.

PURPOSE: To investigate the incidence of Tubal Ectopic Pregnancies (TEP) in IVF-ET patients with respect to the status of the fallopian tubes after a previous TEP. MATERIAL AND METHODS: This retrospective study compares patients undergoing 481 IVF-ET cycles after conservatively or surgically treated TEP(s) with a Control Group (idiopathic or male factor for IVF-ET indication). Medical reports of surgery and/or hysterosalpingograms prior to the IVF cycles classified the status of the fallopian tubes. RESULTS: 12 TEPs (8.95%/Pregnancies (PR)) occurred in the Study Group. In the Control Group one TEP (0.75%/PR; p < 0.001) was found. Smoking increased the probability of TEPs (p = 0.0028) and of pathological pregnancies (abortion, biochemical and ectopic PR; (p = 0.0411)). For statistic evolution logistic regression (PROC GENMOD) and a repeated measure model were applied. CONCLUSION: Women with a previous TEP should be informed about the significantly increased risk for a further TEP in IVF-ET treatment, especially if they are smoking.

Systemic pressure does not directly affect pressure gradient and valve area estimates in aortic stenosis in vitro.

AIMS: Hypertension is a frequent finding in patients with aortic stenosis (AS). However, controversial data about the influence of systemic blood pressure on the quantification of AS have been published. METHODS AND RESULTS: Various models of AS (plates and biological valves) were studied in an in vitro circuit. Valve areas were calculated with the Doppler continuity equation and the Gorlin formula. Systolic systemic pressures were increased from 80 to 200 mmHg while flow rates were maintained constant. In addition, a computational fluid dynamics (CFD) model was constructed to test the effect of systemic pressures on pressure gradient and valve area estimates. When systemic pressure was raised, pressure gradients as well as valve areas did not change (mean difference 3.4 +/- 1.8 mmHg, range 0.4-6.8 mmHg; mean difference 0.01 +/- 0.03 cm(2), range -0.02 to 0.05 cm(2)). By multivariable analysis, neither valve area nor pressure gradient were independently affected by systemic pressure. In addition, CFD analysis revealed no effect of systemic pressure on pressure gradient and valve area. CONCLUSION: Our results suggest that blood pressure itself does not directly affect pressure gradients and valve area estimates in AS. Thus, when observed in vivo, these changes are most likely due to afterload-related variations of ejection fraction and, therefore, flow rate.

Quality of ECG monitoring with a miniature ECG recorder.

BACKGROUND: Long-term monitoring of patients at risk of arrhythmias would benefit from a miniaturized device. This study evaluated the quality of electrocardiogram (ECG) signals recorded by a miniaturized ECG recorder. METHODS: ECG data were concurrently recorded with an investigational device (Philips Medical Systems, Seattle, WA, USA) and a Holter recorder from patients with cardiac-related symptoms at the emergency department of a tertiary care university hospital. The device was attached in one of four locations (L1: below left clavicle, L2: midsternal, L3: below left breast, L4: left anterior axillary line in 5th intercostal space). Selected ECG strips were analyzed for atrial activity, QRS width, and basic rhythm by two physicians. Patients were divided into groups based on their number of strips (A 2-5, B 6-9, C 10-21) for descriptive presentation of the data. For statistical analyses, nonlinear mixed-effects models were used. RESULTS: In 90 patients, 574 pairs of strips were analyzed. In L1 (n = 37), agreement between the device and the Holter recorder on presence of P wave was 58-80% in groups A-C and in L2 (n = 28):94-98%, L3 (n = 12):30-72%, and L4 (n = 13):0-70%; on PR interval in L1:58-80%, L2:94-98%, L3:30-62%, and L4:0-70%; on rhythm in L1:56-79%, L2:94-98%, L3:30-62%, and L4:0-70%; on QRS width in L1:86-100%, L2:88-98%, L3:100%, and L4:96-100%. The agreement of L2 in the parameters P wave, PR interval, and rhythm diagnosis was better than in the other locations (P < 0.01). CONCLUSIONS: A miniature ECG monitor provided accurate assessment of atrial beats and rhythm diagnosis at a midsternal location and of QRS width at all locations.

Antipsychotics for acute and chronic pain in adults.

BACKGROUND: The role of antipsychotics as adjuvant analgesics is a subject of longstanding controversy. Neuroleptanalgesia (i.e. a state of quiescence, altered awareness, and analgesia produced by a combination of taking an opioid analgesic and an antipsychotic), an established term for the management of acute pain, was shown to negatively influence disease course and total mortality in unstable angina patients. Nevertheless, antipsychotics are used to treat chronic pain (e.g. chronic headache, fibromyalgia and diabetic neuropathia). With atypical antipsychotics, a new class of antipsychotics, fewer extrapyramidal side effects and additional benefits may be available. OBJECTIVES: Assess analgesic efficacy and adverse effects of antipsychotics in acute or chronic pain. SEARCH STRATEGY: Cochrane Pain, Palliative & Supportive Care Register, CENTRAL, MEDLINE, PsycINFO, and EMBASE searched in October 2007. SELECTION CRITERIA: Randomised controlled trials (RCTs) of adults prescribed any dose of oral antipsychotics for acute or chronic pain, describing subjective pain assessment as either the primary or a secondary outcome, were included in this review. DATA COLLECTION AND ANALYSIS: Data was extracted by two independent review authors, and results were compared for differences. Discrepancies were resolved by discussion. All trials were quality scored according to the methods set out in section six of the Cochrane Handbook. MAIN RESULTS: A total of 770 participants were involved in the eleven included studies. Data from five included randomised double-blind studies showed beneficial effects of antipsychotics in the treatment of acute and chronic pain. Quantitative analysis of these studies showed a significant reduction of mean pain intensity after administration of the antipsychotic compared to placebo or another active compound: Weighted Mean Difference (WMD) -1.78 (95% CI -2.71 to -0.85) for the continuous data and Relative Risk (RR) 0.43 (95% CI 0.25 to 0.73), number-needed-to-treat-to-benefit (NNT) 2.6 for the dichotomous data. Nevertheless, the test for heterogeneity was significant for the continuous data (P = 0.0007) and the dichotomous data (P = 0.04). The most frequently reported adverse effects were extrapyramidal (i.e. involuntary movements, parkinsonism and akathisia) and sedating effects. AUTHORS' CONCLUSIONS: Antipsychotics might be used as an add-on therapy in the treatment of painful conditions. Nevertheless, extrapyramidal and sedating side effects have to be considered before using antipsychotics for treating painful conditions.Results for antipsychotics in the treatment of different painful conditions are mixed and most sample sizes in the reviewed RCTs are small. Further studies on atypical antipsychotics in larger double-blind placebo-controlled studies including standardised pain assessment/documentation are warranted.

On the applicability of secondary dentin formation to radiological age estimation in young adults.

The literature provides linear regression formulas for dental age estimation that is based on radiological two-dimensional measurements of the pulp size. The aim of the present study was to explore whether the previously presented regression formulas could lead to statistically sound results and to appropriate repeatability when applied to young individuals. Orthopantomograms (OPGs) of 44 Austrian individuals, aged between 13 and 24 years, were selected at random. In accordance with the reported method, six teeth on each OPG were chosen to carry out the measurements. Statistical analysis was performed in order to assess the difference between the estimated and the true chronological age. The regression formulas reported by Kvaal et al. (1995) led to a consistent underestimation; the regression formulas reported by Paewinsky et al. (2005) resulted in a constant overestimation of age. The statistical analysis of intraobserver and interobserver variation revealed a variation width below 2%, respectively.

Length bias correction in one-day cross-sectional assessments - The nutritionDay study.

BACKGROUND & AIMS: A major problem occurring in cross-sectional studies is sampling bias. Length of hospital stay (LOS) differs strongly between patients and causes a length bias as patients with longer LOS are more likely to be included and are therefore overrepresented in this type of study. To adjust for the length bias higher weights are allocated to patients with shorter LOS. We determined the effect of length-bias adjustment in two independent populations. METHODS: Length-bias correction is applied to the data of the nutritionDay project, a one-day multinational cross-sectional audit capturing data on disease and nutrition of patients admitted to hospital wards with right-censoring after 30 days follow-up. We applied the weighting method for estimating the distribution function of patient baseline variables based on the method of non-parametric maximum likelihood. Results are validated using data from all patients admitted to the General Hospital of Vienna between 2005 and 2009, where the distribution of LOS can be assumed to be known. Additionally, a simplified calculation scheme for estimating the adjusted distribution function of LOS is demonstrated on a small patient example. RESULTS AND CONCLUSION: The crude median (lower quartile; upper quartile) LOS in the cross-sectional sample was 14 (8; 24) and decreased to 7 (4; 12) when adjusted. Hence, adjustment for length bias in cross-sectional studies is essential to get appropriate estimates.

The Patient- And Nutrition-Derived Outcome Risk Assessment Score (PANDORA): Development of a Simple Predictive Risk Score for 30-Day In-Hospital Mortality Based on Demographics, Clinical Observation, and Nutrition.

OBJECTIVE: To develop a simple scoring system to predict 30 day in-hospital mortality of in-patients excluding those from intensive care units based on easily obtainable demographic, disease and nutrition related patient data. METHODS: Score development with general estimation equation methodology and model selection by P-value thresholding based on a cross-sectional sample of 52 risk indicators with 123 item classes collected with questionnaires and stored in an multilingual online database. SETTING: Worldwide prospective cross-sectional cohort with 30 day in-hospital mortality from the nutritionDay 2006-2009 and an external validation sample from 2012. RESULTS: We included 43894 patients from 2480 units in 32 countries. 1631(3.72%) patients died within 30 days in hospital. The Patient- And Nutrition-Derived Outcome Risk Assessment (PANDORA) score predicts 30-day hospital mortality based on 7 indicators with 31 item classes on a scale from 0 to 75 points. The indicators are age (0 to 17 points), nutrient intake on nutritionDay (0 to 12 points), mobility (0 to 11 points), fluid status (0 to 10 points), BMI (0 to 9 points), cancer (9 points) and main patient group (0 to 7 points). An appropriate model fit has been achieved. The area under the receiver operating characteristic curve for mortality prediction was 0.82 in the development sample and 0.79 in the external validation sample. CONCLUSIONS: The PANDORA score is a simple, robust scoring system for a general population of hospitalised patients to be used for risk stratification and benchmarking.

Interface pressure at different degrees of backrest elevation with various types of pressure-redistribution surfaces.

BACKGROUND: Increased elevation of the head of the bed is linked to a higher risk for sacral pressure ulcers. A semirecumbent position of at least 30° is recommended for the prevention of ventilator-associated pneumonia in patients treated with mechanical ventilation. Therefore, prevention of pressure ulcers and prevention of pneumonia seem to demand contradictory, possibly incompatible, positioning. OBJECTIVES: To measure pressure at the interface between sacral skin and the supporting surface in healthy volunteers at different degrees of upright position with different types of mattresses. METHODS: An open, prospective, randomized crossover trial was conducted with 20 healthy volunteers. Interface pressure was measured by using a pressure mapping device with the participant in a supine position at 0, 10°, 30°, and 45° elevation and in the reverse Trendelenburg position at 10° and 30°. Four types of mattresses were examined: 2 different foam mattresses and 2 air suspension beds, 1 of the latter with low-air-loss technology. RESULTS: Peak sacral interface pressures increased significantly only at 45° of backrest elevation (P < .001). A mattress system with low-air-loss technology significantly reduced peak interface pressures at all angles (P < .001). The reverse Trendelenburg position led to lower peak pressures for all positions (P = .01). CONCLUSIONS: Backrest elevation up to 30° might be a compromise between the seemingly incompatible demands of skin integrity and the prevention of ventilator-associated pneumonia. The reverse Trendelenburg position and a mattress system with low-air-loss technology could be additional useful tools to help prevent skin breakdown at the sacrum.

Size matters! Impact of age, sex, height, and weight on the normal heart size.

BACKGROUND: Therapeutic decisions in cardiology are determined frequently by cardiac chamber size. To decide whether cardiac dimensions are still in the normal range, reliable reference values are needed. However, published reference values mostly refer to historical cohorts using motion-mode measurements and have not been adjusted for sex or age. The impact of body size was only vaguely addressed. The importance of such adjustments is illustrated by studies, which show that smaller individuals and women are at risk of delayed treatment and impaired outcome when currently used reference values are applied. The aim of the present study was to assess the impact of body size, sex, and age on the normal heart size. METHODS AND RESULTS: We prospectively studied 622 individuals (52.7% women; 17-91 years; 143-200 cm; 32-240 kg) without cardiac disease by standard transthoracic echocardiography. Multivariable linear regression analyses of the impact of sex, age, height, and weight on cardiac chamber size were performed. By multivariable regression analysis (n=500), all 4 variables independently influenced cardiac chamber size. The validity of cardiac dimensions predicted by the regression model was tested prospectively in a validation cohort (n=122). A calculator is proposed that estimates cardiac dimensions on the basis of the regression analysis. CONCLUSIONS: Sex, height, weight, and age significantly affect the normal heart size. These parameters need to be considered when cutoff values indicating the need for treatment or even surgery are established.

Predictors of outcome of non-ischemic mitral valve surgery.

BACKGROUND: Data on the risk stratification of patients undergoing mitral valve (MV) surgery for non-ischemic mitral disease are sparse. The present study seeks to define them in a contemporary cohort. METHODS: 193 consecutive patients referred to non-ischemic MV surgery were prospectively studied. Baseline characteristics and the type of surgery were analyzed with regard to operative and late mortality as well as functional outcome. RESULTS: 129 patients underwent MV replacement and 64 MV repair. MV replacement patients presented with more symptoms (p = 0.010), higher EuroSCORE (6.1 versus 5.6; p=0.009), more frequently underwent additional valve surgery (7.8 versus 0%; p = 0.003) and were more frequently female (p=0.048). Operative mortality was 3.1%, two thirds of operative deaths had additional surgery of the tricuspid valve (p = 0.019). Patients were followed for 5.2 ± 2.7 years. 1-, 3-, 5- and 7-year survival rates were 93-, 91-, 82-, and 79% in MV replacement patients versus 100-, 98-, 96-, and 89% in patients with MV repair (p = 0.015). However, by multivariate logistic regression, overall mortality was determined by additional surgery of the tricuspid valve (p = 0.0103), multivessel coronary disease (p = 0.026), and age (p<0.0001), but not by the type of surgery (p=0.066). Furthermore, the type of surgery did not influence functional outcome (p = 0.515). CONCLUSIONS: Apart from age and coronary artery disease the need for additional tricuspid valve surgery significantly determines the outcome of non-ischemic MV surgery. The type of operation appears less important when the need for additional valve surgery and co-morbidities like coronary artery disease are taken into consideration.

Endogenous erythroid colony formation in chronic myeloid leukemia: a recurrent finding associated with persistent minimal residual disease under imatinib.

In vitro endogenous erythroid colony (EEC) formation is a common finding in BCR-ABL-negative myeloproliferative neoplasms. The aim of the present study was to determine the prevalence and the clinical significance of EEC growth in chronic myeloid leukemia (CML). Results of clonogeneic progenitor cell assays from 52 patients with newly diagnosed CML were correlated with disease characteristics at presentation and molecular response to imatinib. EECs (median 7 per dish, range 1-39) were detectable in 16 patients (31%). The proportion of patients with a high-risk Sokal score was lower in the EEC group (7% vs. 30%, respectively). The cumulative incidence of achieving a major molecular response after 2 years of imatinib was similar for both groups. However, patients with EECs were less likely to achieve a more profound decline of BCR-ABL transcripts. After 6 years of imatinib, the cumulative probability [95% CI] of reaching a ≥4 log reduction of BCR-ABL was 48% [16%; 92%] for patients of the EEC group and 84% [63%; 97%] for patients of the No EEC group. The probability [95% CI] of achieving a >4.5 log reduction of BCR-ABL after 7 years was 13% [2%; 61%] for patients with EECs and 52% [30%; 78%] for patients without EECs. In vitro EECs disappeared after achievement of a major molecular response in all evaluable patients. The data indicate that EEC formation is a recurrent finding in patients with CML which deserves further attention as a possible biomarker predicting the degree of molecular response to imatinib.

Renal function and long-term mortality in patients with asymptomatic carotid atherosclerosis.

Renal dysfunction is a risk factor for mortality in patients with atherosclerosis. Estimated glomerular filtration rate (eGFR), cystatin C (CysC) and beta-2-microglobulin (B2M) are measures of renal function. It remains unclear, which of these parameters is the strongest predictor of outcome in patients with atherosclerosis. All-cause and cardiovascular mortality were prospectively investigated in 1,065 consecutive patients with asymptomatic carotid atherosclerosis. During a median follow-up of 6.3 years 275 patients died (25.8%), including 182 (66.2%) from cardiovascular causes. Estimated GFR, CysC and B2M were all significantly and independently associated with mortality. Inclusion of the renal parameters CysC and B2M but not of eGFR into a model with established cardiovascular risk factors improved the C-statistics significantly (p=0.0035 and 0.036, respectively; p=0.182 for eGFR). The net reclassification improvement (NRI) was 32.4% (p<0.0001) for CysC, 29% (p<0.0001) for B2M, and 16.5% (p=0.019) for eGFR. The integrated discrimination improvement (IDI) was 0.014 (p=0.0009) for CysC and 0.011 (p=0.005) for B2M while it was not significant for eGFR. Results were consistent for various subgroups with different extent of atherosclerosis. In summary, CysC and B2M were found to be independent predictors for mortality and had superior predictive value compared to eGFR in patients with asymptomatic carotid atherosclerosis. The clinical importance of these findings has to be validated in larger studies with a community-based approach.

Prognostic value of serial B-type natriuretic peptide measurement in asymptomatic organic mitral regurgitation.

AIMS: Optimal timing of surgery is crucial in mitral regurgitation (MR) to avoid excess mortality and morbidity. The role of brain-type natriuretic peptide (BNP) in this setting remains controversial. We evaluated the value of serial BNP measurements for early prediction of deterioration in asymptomatic MR. METHODS AND RESULTS: Eighty-seven consecutive asymptomatic patients with severe organic MR, normal left ventricular (LV) function (ejection fraction ≥ 60%, end-systolic diameter index < 26 mm/m²), systolic pulmonary artery pressure (sPAP) <50 mmHg, and no atrial fibrillation underwent clinical assessment, echocardiography, and measurement of BNP and N-terminal pro-BNP (NT-proBNP) at 6-month intervals. The primary endpoint was the development of symptoms and/or LV dysfunction. The secondary endpoint was the occurrence of atrial fibrillation or sPAP ≥ 50 mmHg. Over a mean follow-up of 786 ± 454 days, 20 patients reached the primary endpoint and 5, the secondary endpoint. By univariate analysis, age, BNP, NT-proBNP, and sPAP were significant predictors of reaching the primary endpoint during the 6 months following testing, whereas LV function and dimensions were not. By multivariate analysis, only BNP (P = 0.03) and sPAP (P = 0.04) remained independent predictors. When secondary endpoints were additionally considered, results remained unchanged. Receiver operator curve analysis yielded AUC-values of 0.90, 0.84, and 0.80 for BNP, NT-proBNP, and sPAP, but 0.60 and 0.57 for left ventricular ejection fraction and end-systolic diameter. The negative predictive value for normal neurohormone levels and sPAP was high (98-100%). A BNP of 145 pg/mL had a positive predictive value of 36%. CONCLUSION: Brain natriuretic peptide and NT-proBNP independently predict outcome in asymptomatic MR. Serial measurements may help to improve timing of surgery. Low plasma levels with their high negative predictive values appear to be particularly helpful by identifying low-risk individuals.

Antipsychotics for acute and chronic pain in adults.

CONTEXT: The role of antipsychotics as adjuvant analgesics is a subject of long-standing controversy. Antipsychotics have been used to treat chronic pain (e.g., chronic headache, fibromyalgia, and painful diabetic neuropathy). With atypical antipsychotics, a new class of antipsychotics, with fewer extrapyramidal side effects and additional benefits, may be available. OBJECTIVES: This review aimed to assess analgesic efficacy and adverse effects of antipsychotics in acute or chronic pain. METHODS: Randomized controlled trials of adults prescribed any dose of oral antipsychotics for acute or chronic pain, describing subjective pain assessment as either the primary or a secondary outcome, were included in this review. RESULTS: We included 11 studies involving a total number of 770 participants. Data from five randomized, double-blind studies showed beneficial effects of antipsychotics in the treatment of acute and chronic pain. Because of the clinical heterogeneity of painful conditions studied and significant statistical heterogeneity, the intended meta-analysis was omitted. The most frequently reported adverse effects were extrapyramidal (i.e., involuntary movements, parkinsonism, and akathisia) and sedating effects. CONCLUSION: Because of limitations in the available evidence, further research is needed to understand whether antipsychotics are effective for acute or chronic pain or specific pain conditions.

Evaluation of the decontamination efficacy of new and reprocessed microfiber cleaning cloth compared with other commonly used cleaning cloths in the hospital.

BACKGROUND: The aim of this study was to investigate the decontamination capacity of 4 different types of cleaning cloths (microfiber cleaning cloth, cotton cloth, sponge cloth, and disposable paper towels) commonly used in hospital in their ability to reduce microbial loads from a surface used dry or wet in new condition. All of the cloths except disposable paper towels were also compared after 10 and 20 times of reprocessing, respectively, at 90 degrees C for 5 minutes in a washing machine. METHODS: Staphylococcus aureus (ATCC 6538) and Escherichia coli (ATCC 8739) were used as test organisms. Test organisms were then added to a test soil (6% bovine serum albumin and 0.6% sheep erythrocytes) resulting in a controlled concentration of 5 x 10(7) colony-forming units per milliliter in the final test suspension. Standardized tiles measuring 5 x 5 cm were used as test surface. RESULTS: Microfiber cloths showed the best results when being used in new condition. However, after multiple reprocessing, cotton cloth showed the best overall efficacy. CONCLUSION: We therefore suggest that the choice of the cleaning utilities should be based on their decontamination efficacy after several reprocessings and recommend the establishment of strict and well-defined cleaning and disinfection protocols.