Decision aid and cost compensation influence uptake of PSA-based early detection without affecting decisional conflict: a cluster randomised trial.

International guidelines recommend to inform men about the benefits and harms of prostate specific antigen (PSA) based early detection of prostate cancer. This study investigates the influence of a transactional decision aid (DA) or cost compensation (CC) for a PSA test on the decisional behaviour of men. Prospective, cluster-randomised trial to compare two interventions in a 2 × 2 factorial design: DA versus counselling as usual, and CC versus noCC for PSA-testing. 90 cluster-randomised physicians in the administrative district of Muenster, Germany recruited 962 participants aged 55-69 yrs. in 2018. Primary endpoint: the influence of the DA and CC on the decisional conflict. Secondary endpoints: factors which altered the involvement of the men regarding their decision to take a PSA-test. The primary endpoint was analysed by a multivariate regression model. The choice to take the PSA test was increased by CC and reduced by the DA, the latter also reduced PSA uptake in men who were offered CC. The DA led to an increase of the median knowledge about early detection, changed willingness to perform a PSA test without increasing the level of shared decision, giving participants a stronger feeling of having made the decision by themselves. The DA did not alter the decisional conflict, as it was very low in all study groups. DA reduced and CC increased the PSA uptake. The DA seemed to have a greater impact on the participants than CC, as it led to fewer PSA tests even if CC was granted.Trial registration: German Clinical Trial Register (Deutsches Register Klinischer Studien DRKS00007687). Registered: 06/05/2015. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00007687 .

Bypass Grafting vs Endovascular Therapy in Patients With Non-Dialysis-Dependent Chronic Kidney Disease and Chronic Limb-Threatening Ischemia (CRITISCH Registry).

Purpose: To report the outcomes of bypass grafting (BG) vs endovascular therapy (EVT) in patients with non-dialysis-dependent chronic kidney disease (CKD) and chronic limb-threatening ischemia (CLTI). Materials and Methods: The CRITISCH Registry is a prospective, national, interdisciplinary, multicenter registry evaluating the current practice of all available treatment options in 1200 consecutive CLTI patients. For the purposes of this analysis, only the 337 patients with non-dialysis-dependent CKD treated by either BG (n=86; median 78 years, 48 men) or EVT (n=251; median age 80 years, 135 men) were analyzed. The primary composite outcome was amputation-free survival (AFS); secondary outcomes were overall survival (OS) and amputation-free time (AFT). All outcomes were evaluated in Cox proportional hazards models; the results are reported as the hazard ratio (HR) and 95% confidence interval (CI). Results: The Cox regression analysis revealed a significantly greater hazard of amputation or death after BG (HR 1.78, 95% CI 1.05 to 3.03, p=0.028). The models for AFT and overall survival also suggested a higher hazard for BG, but the differences were not significant (AFT: HR 1.66, 95% CI 0.78 to 3.53, p=0.188; OS: HR 1.41, 95% CI 0.80 to 2.47, p=0.348). The absence of runoff vessels (HR 1.73, 95% CI 1.15 to 2.60, p=0.008) was associated with a decreased AFS. The likelihood of amputation was higher in male patients (HR 2.21, 95% CI 1.10 to 4.45, p=0.027) and was associated with a lack of runoff vessels (HR 1.95, 95% CI 0.96 to 3.95, p=0.065) and myocardial infarction (HR 3.74, 95% CI 1.23 to 11.35, p=0.020). Death was more likely in patients without runoff vessels (HR 1.76, 95% CI 1.11 to 2.80, p=0.016) and those with a higher risk score (HR 1.73, 95% CI 1.03 to 2.91, p=0.038). Conclusion: This analysis suggested that BG was associated with poorer AFS than EVT in patients with non-dialysis-dependent CKD and CLTI. Male sex, previous myocardial infarction, and the absence of runoff vessels were additionally identified as predictors of poorer outcomes.

Procedure related risk of premature delivery and fetal growth reduction following amniocentesis, transcervical and transabdominal chorionic villus sampling: a retrospective study.

Background The aim of this study was to compare transabdominal and transcervical chorionic villus sampling (CVS) as well as amniocentesis (AC) with respect to their rates of premature delivery and fetal growth restriction. Methods We retrospectively evaluated the mentioned procedures of invasive prenatal testing performed in a single center between 2001 and 2016. Seven hundred and ninety-nine cases of AC and 719 cases of CVS were included, of which 400 were performed transvaginally. Only singleton pregnancies with a normal karyotype and delivery after 24 + 0 weeks of gestation were included. Fetal growth restriction was defined as birth weight below the 10th percentile. Premature delivery was defined as delivery before 37 + 0 weeks of gestation. Data were compared to a control group without an invasive procedure. Results The frequency of premature delivery was 8.5% after transabdominal CVS, 6.3% after transcervical CVS and 10.5% after AC as compared to 10.8% in the control group. The frequency of fetal growth restriction was 8.2% after transabdominal CVS 6.8% after transcervical CVS and 8.4% after AC as compared to 9.7% in the control group. Conclusion Our study supports that the three different methods of invasive prenatal testing do not lead to a higher risk of either premature delivery or fetal growth restriction when compared to controls. We found no difference in risk profile among the three techniques.

Normative Yo-Yo Intermittent Recovery Level 1 and Yo-Yo Intermittent Endurance Level 1 test values of boys aged 9-16years.

OBJECTIVES: To provide age- and sex-specific reference values of Yo-Yo tests in children and adolescents. DESIGN: Systematic review. METHODS: A literature search for articles on Yo-Yo Intermittent (YYI) tests was performed in MEDLINE, SPORTDiscus, Web of Science and Google Scholar. Original reports on healthy children/adolescents 6-16years of age were eligible. For each test, age- and sex-related reference values were calculated using global means and percentiles. RESULTS: Ninety-two studies (7398 participants) fulfilled the eligibility criteria. The YYI tests most frequently used were the Yo-Yo Intermittent Recovery Level 1 test (YYIR1, 57.8%), Yo-Yo Intermittent Endurance Level 1 test (YYIE1, 14.7%), Yo-Yo Intermittent Recovery Level 1 Children's test (YYIR1C, 12.7%), Yo-Yo Intermittent Endurance Level 2 test (YYIE2, 8.8%) and the Yo-Yo Intermittent Recovery Level 2 test (YYIR2, 5.9%). Of these, 71.6% reported test results of boys, 17.6% reported mixed test results and 10.8% reported test results of girls. Smoothed centile curves for the YYIR1 and YYIE1 over the entire age range were generated for boys, revealing constantly increasing performance with increasing age. CONCLUSIONS: YYI tests values differ with respect to age and sex. In boys, development of YYIR1 and YYIE1 test values (6-16years of age) was different, suggesting better applicability of the YYIR1 test for boys >13years of age. The results may be used to rate YYI test performance for continuous screening and to identify children with low physical fitness. Since limited data was available of females, further research on YYI tests is needed with respect to sex-specific results.

Development and Prospective Randomized Evaluation of a Decision Aid for Prostate-specific Antigen-based Early Detection of Prostate Cancer in Men Aged Between 55 and 69Yr: The PSAInForm Trial.

For men interested in early detection of prostate cancer, the potential impact on decisional conflict of a decision aid with or without cost compensation for the prostate-specific antigen test will be investigated.

Aprepitant in Anti-histamine-refractory Chronic Nodular Prurigo: A Multicentre, Randomized, Double-blind, Placebo-controlled, Cross-over, Phase-II trial (APREPRU).

The aim of this multicentre, randomized, double-blind, placebo-controlled, cross-over, phase-II study was to determine the antipruritic effect of aprepitant vs. placebo in 58 patients with anti-histamine-refractory chronic pruritus in chronic nodular prurigo. Patients were randomized to receive either first oral aprepitant 80 mg/day or placebo for 4 weeks. Following a 2-week wash-out phase, the patients were crossed-over to receive the other treatment for 4 weeks. Primary efficacy criterion was the intra-individual difference between mean itch intensity (visual analogue scale) at baseline compared with the end of treatment period. Prurigo lesions, pruritus course, quality of life, patient benefits, and safety were secondary parameters. No significant differences were found between aprepitant treatment and placebo for any of the parameters investigated. Under the experimental conditions of the study, aprepitant, 80 mg daily for 4 weeks, did not have an antipruritic effect in patients with chronic prurigo. (DRKS00005594; EudraCT Number: 2013-001601-85).

Improve hip fracture outcome in the elderly patient (iHOPE): a study protocol for a pragmatic, multicentre randomised controlled trial to test the efficacy of spinal versus general anaesthesia.

INTRODUCTION: Hip fracture surgery is associated with high in-hospital and 30-day mortality rates and serious adverse patient outcomes. Evidence from randomised controlled trials regarding effectiveness of spinal versus general anaesthesia on patient-centred outcomes after hip fracture surgery is sparse. METHODS AND ANALYSIS: The iHOPE study is a pragmatic national, multicentre, randomised controlled, open-label clinical trial with a two-arm parallel group design. In total, 1032 patients with hip fracture (>65 years) will be randomised in an intended 1:1 allocation ratio to receive spinal anaesthesia (n=516) or general anaesthesia (n=516). Outcome assessment will occur in a blinded manner after hospital discharge and inhospital. The primary endpoint will be assessed by telephone interview and comprises the time to the first occurring event of the binary composite outcome of all-cause mortality or new-onset serious cardiac and pulmonary complications within 30 postoperative days. In-hospital secondary endpoints, assessed via in-person interviews and medical record review, include mortality, perioperative adverse events, delirium, satisfaction, walking independently, length of hospital stay and discharge destination. Telephone interviews will be performed for long-term endpoints (all-cause mortality, independence in walking, chronic pain, ability to return home cognitive function and overall health and disability) at postoperative day 30±3, 180±45 and 365±60. ETHICS AND DISSEMINATION: iHOPE has been approved by the leading Ethics Committee of the Medical Faculty of the RWTH Aachen University on 14 March 2018 (EK 022/18). Approval from all other involved local Ethical Committees was subsequently requested and obtained. Study started in April 2018 with a total recruitment period of 24 months. iHOPE will be disseminated via presentations at national and international scientific meetings or conferences and publication in peer-reviewed international scientific journals. TRIAL REGISTRATION NUMBER: DRKS00013644; Pre-results.

Frequency of atrial thrombus formation in patients with atrial fibrillation under treatment with non-vitamin K oral anticoagulants in comparison to vitamin K antagonists: a systematic review and meta-analysis.

BACKGROUND: To assess the frequency of left atrium/left atrial appendage (LA/LAA) thrombus under treatment with non-vitamin K oral anticoagulants (NOACs) in comparison with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (AF). METHODS: PubMed, Web of Science™, EMBASE and the Cochrane Library databases were searched for studies comparing NOACs with VKAs in AF patients who underwent diagnostic transoesophageal echocardiography (TEE). RESULTS: A total of four trials were considered eligible and were included in the meta-analysis. Four RCTs comprising n = 2397 AF patients (NOACs: n = 1412, VKAs: n = 985) were included in the meta-analysis. The frequency of LA/LAA thrombus formation under treatment with NOACs was similar to VKAs [odds ratio (OR) 1.14, 95% confidence intervals (95% CIs) 0.97-1.65, p = 0.48]. Both treatment groups revealed an approximately 5% frequency of thrombus formation, although a precise calculation is not possible due to Simpson paradox. Indications of heterogeneity between the included trials were not found (χ2 test p = 0.99, I2 = 0%). CONCLUSIONS: The findings of this meta-analysis suggest that NOACs are similar to VKAs regarding the frequency of LA/LAA thrombus in patients with AF. An unknown number of patients in the original studies did not receive sufficient anticoagulation for at least 3 weeks prior to TEE examination, and therefore the present results should be interpreted with caution. Systematic review registration- http://www.crd.york.ac.uk/PROSPERO . Unique identifier: PROSPERO CRD42017059293.

The Yo-Yo Intermittent Tests: A Systematic Review and Structured Compendium of Test Results.

Background: Although Yo-Yo intermittent tests are frequently used in a variety of sports and research studies to determine physical fitness, no structured reference exists for comparison and rating of test results. This systematic review of the most common Yo-Yo tests aimed to provide reference values for test results by statistical aggregation of published data. Methods: A systematic literature search for articles published until August 2017 was performed in MEDLINE, Web of Science, SPORTDiscus and Google Scholar. Original reports on healthy females and males ≥16 years were eligible for the analysis. Sub-maximal test versions and the Yo-Yo Intermittent Recovery Level 1 Children's test (YYIR1C) were not included. Results: 248 studies with 9,440 participants were included in the structured analysis. The Yo-Yo test types most frequently used were the Yo-Yo Intermittent Recovery Level 1 (YYIR1, 57.7%), the Yo-Yo Intermittent Recovery Level 2 (YYIR2, 28.0%), the Yo-Yo Intermittent Endurance Level 2 (YYIE2, 11.4%), and the Yo-Yo Intermittent Endurance Level 1 (YYIE1, 2.9%) test. For each separate test, reference values (global means and percentiles) for sports at different levels and both genders were calculated. Conclusions: Our analysis provides evidence that Yo-Yo intermittent tests reference values differ with respect to the type and level of sport performed.The presented results may be used by practitioners, trainers and athletes to rate Yo-Yo intermittent test performance levels and monitor training effects.

One-Year Results of First-Line Treatment Strategies in Patients With Critical Limb Ischemia (CRITISCH Registry).

PURPOSE: To examine the outcomes of all first-line strategies for the treatment of critical limb ischemia (CLI), identify factors that influenced the treatment choice, and determine the risk of amputation or death after each treatment. METHODS: CRITISCH ( ClinicalTrials.gov identifier NCT01877252) is a multicenter, national, prospective registry evaluating all available treatment strategies applied in 1200 consecutive CLI patients in 27 vascular centers in Germany. The recruitment started in January 2013 and was completed in September 2014. Treatment options were endovascular revascularization (642, 53.5%), bypass surgery (284, 23.7%), femoral artery patchplasty (126, 10.5%) with or without concomitant peripheral intervention, conservative treatment (118, 9.8%), and primary major amputation (30, 2.5%). The primary endpoint of this study was amputation-free survival (AFS). The Society of Vascular Surgery's suggested objective performance goal (OPG) for AFS (71%) was used as the effectiveness criterion. Multivariable regression methods were employed to identify variables that influenced the treatment selection and AFS after each treatment; results are presented as the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: The 12-month AFS estimates following endovascular therapy, bypass grafting, femoral patchplasty, and conservative treatment were 75%, 72%, 73%, and 72%, respectively. Factors influencing treatment choice were age, chronic kidney disease (CKD), diabetes, smoking, prior vascular procedures in the index leg, TransAtlantic Inter-Society Consensus II C/D lesions, and absence of runoff vessels. Cox regression analysis identified CKD (HR 2.07, 95% CI 1.26 to 3.41, p=0.004), the use of a prosthetic bypass conduit (HR 1.97, 95% CI 1.23 to 3.14, p=0.004), and previous vascular intervention in the index limb (HR 1.52, 95% CI 0.94 to 2.43, p=0.085) as independent risk factors for diminished AFS after bypass surgery. CKD (HR 1.47, 95% CI 1.09 to 1.99, p=0.012) and Rutherford category 6 (HR 1.81, 95% CI 1.30 to 2.52, p<0.001) compromised the performance of endovascular revascularization. CONCLUSION: CRITISCH registry data revealed that all first-line treatment strategies selected and indicated by the treating physicians met the suggested OPGs. CKD was an important determinant of patient prognosis after treatment regardless of the revascularization method.

Foetal thymus size in pregnancies after assisted reproductive technologies.

PURPOSE: The aim of our study was to compare thymus sizes in foetuses conceived using assisted reproductive technologies (ART) to those conceived naturally (control group). METHODS: Sonographic foetal thymus size was assessed retrospectively in 162 pregnancies conceived using ART and in 774 pregnancies conceived naturally. The anteroposterior thymic and the intrathoracic mediastinal diameter were measured to calculate the thymic-thoracic ratio (TT-ratio). The ART cases were subdivided into two groups: (1) intracytoplasmic sperm injection (ICSI; n = 109) and (2) in vitro fertilisation (IVF; n = 53). RESULTS: The TT-ratio was smaller in pregnancies conceived using ART (p < 0.001). In both ART subgroups (ICSI and IVF), the TT-ratio was lower compared to the control group (p < 0.001). However, no difference between the two subgroups could be detected (p = 0.203). CONCLUSIONS: Our data show reduced thymus size in foetuses conceived using ART compared to controls. These findings indicate that the use of ART may lead to certain deviations in organogenesis.

Assessment of the Fetal Cerebral Artery: Importance of Doppler Preset Settings.

OBJECTIVES: The Doppler assessment of the middle cerebral artery (MCA) has a central role in the monitoring of high-risk pregnancies. The objective of this study was to investigate the importance of Doppler preset settings for measurement of the peak systolic velocity (PSV) and pulsatility index (PI) of the MCA. METHODS: The PI and PSV of the MCA were determined prospectively in 350 healthy fetuses between 19 and 42 weeks of pregnancy. The first measurement of the MCA (MCA.S) was performed with the conventional settings and the second (MCA.O) with an optimized setting of the maximum achievable frame rate. For the MCA.O measurement, the width of the B-mode image and the color Doppler window were adjusted as narrowly as possible. In addition, the MCA was shown in optimized high-definition zoom. Resulting values were compared with commonly used reference values. RESULTS: The PSV and PI values and frame rates of the MCA.O setting were noticeably greater than those of the MCA.S setting (P < .001 for all). For both settings, the PSV and PI values were increased compared to common reference values. CONCLUSIONS: The assessment of the MCA with the optimized Doppler default setting yielded increased PSV and PI values compared to the commonly used measurement technique. Moreover, the resulting median curves differed from the established median reference curves. Therefore, an updated standardization for measuring the MCA should be set out, and current reference values should be adjusted.

Direct determination of carbapenem-resistant Enterobacteriaceae and Pseudomonas aeruginosa from positive blood cultures using laser scattering technology.

Delays in appropriate antimicrobial treatment contribute to increased mortality of septic patients. We aimed to develop a methodology for detection of carbapenem resistance in Gram-negative bacteria directly from positive blood cultures (BCs). Initially, meropenem-resistant Enterobacteriaceae (n = 13) and Pseudomonas aeruginosa (n = 32) isolates as well as the same numbers of meropenem-susceptible isolates were used to establish the detection of carbapenem resistance from agar cultures. Growth-based phenotypic detection of meropenem resistance was performed by a laser scattering (LS) method using a BacterioScan™216R instrument. A subset of the strain collection consisting of meropenem-susceptible and -resistant isolates (each comprising seven P. aeruginosa and three Klebsiella pneumoniae) was used for determination of carbapenem resistance directly from positive BCs. Lysis/centrifugation and filtration/dilution methods were investigated for processing of positive BCs. Four different statistical approaches to discriminate between susceptible and resistant bacteria in real-time were applied and were compared regarding their sensitivity and specificity. After 3 h and 4 h of incubation, respectively, detection of carbapenem resistance in Enterobacteriaceae (sensitivity, 100%; specificity, 100%) and P. aeruginosa (sensitivity, 100%; specificity, ≥90%) agar cultures was attainable. Detection of carbapenem resistance directly from positive BCs was achievable with 100% sensitivity and 100% specificity after 4 h and 5 h, respectively, applying lysis/centrifugation and filtration/dilution methods. In conclusion, LS technology combined with lysis/centrifugation and appropriate statistical real-time analyses represents a promising option for rapid detection of carbapenem resistance in Gram-negative rods directly from positive BCs.

Predicting ROSC in out-of-hospital cardiac arrest using expiratory carbon dioxide concentration: Is trend-detection instead of absolute threshold values the key?

AIM: Guidelines recommend detecting return of spontaneous circulation (ROSC) by a rising concentration of carbon dioxide in the exhalation air. As CO2 is influenced by numerous factors, no absolute cut-off values of CO2 to detect ROSC are agreed on so far. As trends in CO2 might be less affected by influencing factors, we investigated an approach which is based on detecting CO2-trends in real-time. METHODS: We conducted a retrospective case-control study on 169 CO2 time series from out of hospital cardiac arrests resuscitated by Muenster City Ambulance-Service, Germany. A recently developed statistical method for real-time trend-detection (SCARM) was applied to each time series. For each series, the percentage of time points with detected positive and negative trends was determined. RESULTS: ROSC time series had larger percentages of positive trends than No-ROSC time series (p=0.003). The median percentage of positive trends was 15% in the ROSC time series (IQR: 5% to 23%) and 7% in the No-ROSC time series (IQR: 3% to 14%). A receiver operating characteristic (ROC) analysis yielded an optimal threshold of 13% to differentiate between ROSC and No-ROSC cases with a specificity of 58.4% and sensitivity of 73.9%; the area under the curve was 63.5%. CONCLUSION: Patients with ROSC differed from patients without ROSC as to the percentage of detected CO2 trends, indicating the potential of our real-time trend-detection approach. Since the study was designed as a proof of principle and its calculated specificity and sensitivity are low, more research is required to implement CO2-trend-detection into clinical use.

Association between statin therapy and amputation-free survival in patients with critical limb ischemia in the CRITISCH registry.

OBJECTIVE: Secondary prevention in patients with critical limb ischemia (CLI) is crucial for the reduction of cardiovascular morbidity and mortality. Nonetheless, current recommendations are extrapolated from other high-risk populations because of the lack of CLI-dedicated trials. The aim of this explorative study was to evaluate the association of statin therapy with the outcomes of CLI patients. METHODS: The First-Line Treatments in Patients With Critical Limb Ischemia (CRITISCH) registry is a prospective multicenter registry analyzing the effectiveness of all available treatment strategies in 1200 CLI patients. For the purposes of this analysis, patients were divided into two groups based on statin administration. Treatment crossovers and nonadherent patients were excluded from analysis. The primary composite end point of this study was the amputation-free survival (AFS). Major adverse cardiovascular and cerebral events (MACCEs), time to death, and time to major amputation were also analyzed. RESULTS: Statin therapy was applied in 445 individuals (37%), 371 (31%) patients received no statins, and 384 subjects were excluded from analysis (treatment crossovers). Patients receiving statins were more likely to be younger (P < .001) and to have a history of coronary heart disease (P < .001) or previous intervention at index limb (P < .001). Patients receiving statin therapy had a lower hazard regarding AFS (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.34-0.63; P < .001) and death (HR, 0.40; 95% CI, 0.24-0.66; P < .001) as well as lower odds of MACCE (odds ratio, 0.41; 95% CI, 0.23-0.69; P = .001). However, statin therapy was not associated with reduced amputation rates (HR, 1.02; 95% CI, 0.67-1.56; P = .922). Statin effect on AFS was consistent among diabetics (HR, 0.47; 95% CI, 0.31-0.70; P < .001), patients with chronic kidney disease (HR, 0.53; 95% CI, 0.32-0.87; P = .012), and patients older than 75 years (HR, 0.40; 95% CI, 0.26-0.60; P < .001). Statin administration was also associated with an improved AFS in patients with antiplatelet medication (HR, 0.64; 95% CI, 0.41-0.99; P = .049) and without antiplatelet medication (HR, 0.26; 95% CI, 0.12-0.57; P = .001) and after both endovascular therapy (HR, 0.51; 95% CI, 0.34-0.76; P = .001) and bypass revascularization (HR, 0.38; 95% CI, 0.21-0.68; P = .001). CONCLUSIONS: Statin therapy in CLI patients is associated with an increased AFS and lower rates of mortality and MACCEs without improving, however, the salvage rates of the affected limb.

Rapid Phenotypic Detection of Microbial Resistance in Gram-Positive Bacteria by a Real-Time Laser Scattering Method.

We developed a methodology for antimicrobial susceptibility testing (AST) based on the BacterioScanTM216R laser scattering technology, using methicillin resistance in Staphylococcus aureus and vancomycin resistance in enterococci as exemplar for important resistance phenotypes. Fifty methicillin-resistant (MRSA) and 50 methicillin-susceptible (MSSA) S. aureus, as well as 50 vancomycin-resistant enterococci (VRE) and 50 vancomycin-susceptible enterococci (VSE) isolates were used for the study. Optimal test conditions were derived by investigating the effects of inoculum size, medium, incubation temperature and broth filtration. We proposed four different statistical approaches for rapid discrimination between resistant and susceptible bacteria. The statistical approach based on raw measurements of bacterial concentrations delivered sensitivity of 100% and specificity of 94% for discrimination between MRSA and MSSA already after 3 hours of incubation. Categorical agreement of ≥90% was achieved after 140 min with this approach. Differentiation between VRE and VSE was possible with 98% sensitivity and 92% specificity after 3 hours, using a sophisticated statistical approach based on concentration slopes derived from the raw concentration measurements. This approach provided categorical agreement of ≥90% after 165 min. The sensitivity and specificity estimates were confirmed by leave-one-out cross validation. In conclusion, the phenotypic AST methods developed in this study are promising for rapid detection of MRSA and VRE. The development and application of this technology would allow early detection of the resistant pathogens, thus facilitating swift change to the targeted antimicrobial treatment as well as timely initiation of appropriate infection control measures. Further studies are warranted to validate this approach for the detection of other resistance phenotypes, including direct testing from clinical specimens.

Predictors of hearing recovery in patients with severe sudden sensorineural hearing loss.

BACKGROUND: Sudden sensorineural hearing loss (SSHL) is a disease, which severely affects the patient's social and relational life. The underlying pathomechanisms have not been finally clarified yet and outcome is not predictable. METHODS: We conducted a retrospective study in order to identify parameters that influence hearing recovery. The data base contains results of basic otoneurological tests and clinical parameters of 198 patients with idiopathic SSHL of at least 60 dB in at least four frequencies, diagnosed and treated at the University Hospital of Münster, Germany, between 1999 and 2015. Hearing recovery was measured by pure tone audiometry. RESULTS: Multivariate linear and logistic regression analyses indicate that the chance as well as the magnitude of hearing recovery is higher for patients with normal caloric testing than for patients with pathological caloric testing. However, for the subgroup of patients who attained a hearing recovery, the caloric testing result was not found to influence the magnitude. Instead, the magnitude was noticeably lower for patients within this subgroup who had a previous hearing loss. Furthermore, we found indications that the magnitude is higher for men than for women and that receiving a high-dose steroid therapy is associated with a higher chance and magnitude of a hearing recovery. CONCLUSIONS: We conclude that SSHL associated with disorders of the vestibular system or previous hearing loss represent special sub-entities of SSHL that may be caused by unique pathophysiological mechanisms and are associated with worse outcome. Furthermore, our data support the importance of elevated dosage of steroids in SSHL therapy.

Endovascular Therapy Versus Bypass Surgery as First-Line Treatment Strategies for Critical Limb Ischemia: Results of the Interim Analysis of the CRITISCH Registry.

OBJECTIVES: The most effective first-line treatment between endovascular therapy and bypass surgery for patients with critical limb ischemia (CLI) is still not well defined. The primary aim of the interim analysis of CRITISCH (Registry of First-Line Treatments in Patients With Critical Limb Ischemia) was to compare both treatment options in a prospective confirmatory manner. BACKGROUND: Only 1 randomized controlled trial between endovascular therapy and bypass surgery has been published yet. Several retrospective studies showed comparable outcomes between the 2 treatment strategies, but in the majority of them, current endovascular technologies have not been included. METHODS: Between January 2013 and September 2014, 1,200 CLI patients (Rutherford 4 to 6) from 27 vascular centers were enrolled. The selection of the first-line treatment was left completely to the discretion of the responsible physician. The primary composite endpoint was amputation-free survival (AFS), that is, time to major amputation and/or death from any cause. A pre-specified interim analysis aimed at showing noninferiority of the endovascular therapy versus bypass surgery as to the hazard ratio (HR) of AFS (noninferiority bound = 1.33; interim α = 0.0058). Time-to-event analyses of major amputation, death, and the composite endpoint of reintervention and/or above-ankle amputation were also conducted. RESULTS: Endovascular therapy was applied to 642 (54%) and bypass surgery to 284 (24%) patients. Median follow-up time was 12 months in both groups. One-year AFS was 75% and 72%, respectively. The noninferiority of endovascular therapy versus bypass surgery for AFS was confirmed (HR: 0.91; upper bound of 1-sided (1 - 0.0058) confidence interval [CI]: 1.29; p = 0.003). An impact of the treatment strategy on time until death (HR: 1.14; 95% CI: 0.80 to 1.63; p = 0.453), major amputation (HR: 0.86; 95% CI:0.56 to 1.30; p = 0.463), and reintervention and/or above-ankle amputation (HR: 0.89; 95% CI: 0.70 to 1.14; p = 0.348) was not observed. CONCLUSIONS: The interim analysis confirmed that when physicians are free to individualize therapy to CLI patients, the endovascular-first approach achieved a noninferior AFS rate compared with bypass surgery. (Registry of First-Line Treatments in Patients With Critical Limb Ischemia [CRITISCH]; NCT01877252).

Pharmacokinetic and pharmacodynamic study of doxorubicin in children with cancer: results of a "European Pediatric Oncology Off-patents Medicines Consortium" trial.

PURPOSE: Doxorubicin is a key component in many pediatric oncology treatment regimens; still pharmacology data on which current dosing regimens are based are very limited. METHODS: We conducted a multinational pharmacokinetic study investigating age dependency of doxorubicin metabolism and elimination in children with cancer. One hundred and one patients treated with doxorubicin according to a cancer-specific national or European therapeutic trial were recruited. Doses of doxorubicin ranged from 10.4 to 57.7 mg/m2. Blood samples for measurement of doxorubicin and its metabolite doxorubicinol were collected after two administrations, with five samples collected in children <3 years and eight in children ≥3 years. A population pharmacokinetic approach was used for analysis, including pharmacogenetic covariates. Natriuretic peptides and cardiac troponins were measured to evaluate their role as early indicators of cardiotoxicity. RESULTS: Age dependence of doxorubicin clearance was demonstrated, with children less than 3 years having a statistically significant lower clearance (21.1 ± 5.8 l/h/m2) than older children (26.6 ± 6.7 l/h/m2) (p = 0.0004) after correcting for body surface area. No effect of the investigated genetic polymorphisms on the pharmacokinetics could be observed. Although natriuretic peptides were transiently elevated after each doxorubicin administration and troponin levels increased with increasing doxorubicin exposure, only limited correlation could be observed between their blood levels and doxorubicin pharmacokinetics. CONCLUSION: In the European framework of funding and regulatory support, an add-on study to existing therapeutic trials was developed. The pediatric need concerning missing PK data could be addressed with limited burden for the patients. Empirically used dose adaptations for infants were generally found to be justified based on our PK analyses.

Incidence of left atrial abnormalities under treatment with dabigatran, rivaroxaban, and vitamin K antagonists.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran or rivaroxaban are alternatives to vitamin K antagonists (VKAs) for prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) and atrial flutter (AFL). Incidences of risk factors for left atrium (LA) and left atrial appendage (LAA) thrombus formation, such as dense spontaneous echo contrast (SEC), low LAA velocity (LAAV) <20 cm/s under treatment with dabigatran and rivaroxaban in comparison with VKAs are unknown. METHODS: We studied 306 patients with AF (94 %) and AFL (6 %) undergoing transesophageal echocardiography. Patients received VKAs (n = 138), dabigatran (n = 68), or rivaroxaban (n = 100) for at least 3 weeks prior to investigation. Time in therapeutic range was 67 % for VKA. Mean CHADS2 score and CHA2DS2-VASc score were 1.3 and 2.5, respectively. Left atrial abnormality was defined as either dense SEC, low LAAV <20 cm/s, or thrombus. RESULTS: Any LA abnormality occurred in 9, 3, and 5 % of patients receiving VKA, dabigatran, and rivaroxaban, respectively. The most frequent abnormality was LAA thrombus (VKA: 4 %, dabigatran: 0 %, rivaroxaban: 2 %) and low LAAV of less than 20 cm/s (VKA: 4 %, dabigatran: 1 %, rivaroxaban: 1 %), followed by dense SEC (VKA: 2 %, dabigatran: 1 %, rivaroxaban: 2 %). Results of uni- and multivariate analyses revealed a numerically lower but not significantly different frequency of any LA abnormality under dabigatran (OR 0.4, 95 % Cl 0.08 - 1.88, p = 0.25) and rivaroxaban (OR 0.65, 95 % Cl 0.22 - 1.98, p = 0.45) compared to VKA. CONCLUSION: With respect to the incidence of LA abnormalities, dabigatran and rivaroxaban are not inferior to VKA.