Crossover Comparison Research Articles

Effects of Motor Imagery on Cognitive Function and Prefrontal Cortex Activity in Normal Adults Evaluated by NIRS.

Recent near-infrared spectroscopy (NIRS) studies demonstrated that physical exercise enhances working memory (WM) performance and prefrontal cortex (PFC) activity during WM tasks in normal adults. Interestingly, the effects of rehabilitation (i.e. physiotherapy) on post-stroke patients could be enhanced by motor imagery (MI), an active process during which the specified action is reproduced within WM without any actual physical movement. However, it is not known whether MI can enhance cognitive function and associated brain activity. To clarify these issues, we evaluated the effect of MI on WM performance and PFC activity during WM tasks in normal adults, employing NIRS. We studied 10 healthy adults. The present study was a crossover comparison test; the MI training and control condition (rest) were applied to the subjects at random. The Time Up and Go method was used for MI training: the subject sat on a chair and conducted MI for 3 min, three times. Neuronal activity (oxyhemoglobin concentration) in the bilateral PFC was measured using 2-CH NIRS during WM tasks. We found that MI improved the behavioral performance of WM compared with the control (p < 0.01). NIRS revealed that MI enhanced PFC activity induced by the WM task compared with the control task (p < 0.01). These results suggest that MI can improve cognitive function and increase associated PFC activity in normal adults.

Deep brain stimulation of the posterior subthalamic area and the thalamus in patients with essential tremor: study protocol for a randomized controlled pilot trial.

BackgroundDeep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is effective in medication refractory essential tremor (ET). In recent years, evidence has accumulated that the region ventral to the VIM, the posterior subthalamic area (PSA), might be an equally or even more effective target for electrode implantation. However, this evidence is primarily based on case series, cross-sectional observations, and retrospective data.Methods/designA prospective crossover pilot study investigating the effects of PSA stimulation in medication refractory ET patients was designed. In this study, bilateral electrodes are implanted such that at least one of the electrode contacts is located in the PSA and VIM, respectively. This implantation approach allows (1) a prospective double-blind investigation of the effects of PSA stimulation compared to baseline, as well as (2) a crossover comparison between VIM and PSA stimulation with respect to tremor suppression and side effect profiles.DiscussionThe results of this double-blinded, prospective study will allow a better understanding of the effects and side effects of PSA compared to VIM-DBS in patients with ET.Trial registrationGerman Clinical Trials Register: DRKS00004235. Registered on 4 July 2012.

A Randomized Crossover Comparison of Team-based Learning and Lecture Format on Learning Outcomes

Objective. To compare learning outcomes and student confidence between team-based learning (TBL) and lecture. Methods. A crossover study was conducted with 30 students divided into two sections. Each section was taught six therapeutic topics (three TBL and three lecture). There were two assessments of 24 questions each. A survey (Likert scale) assessing student confidence and attitudes was administered at the end. Results. A significantly higher overall examination score was observed for TBL as compared to lecture. Students were more confident in providing therapeutic recommendations following TBL. Higher survey scores favoring TBL were also seen related to critical-thinking skills and therapeutic knowledge. Conclusion. Learning outcomes and student confidence in performing higher-order tasks were significantly higher with TBL. The findings of this novel crossover type design showed that TBL is an effective pedagogy.

Cross-Over Efficiency Comparison of Different Tidal Automated Peritoneal Dialysis Schedules

This study compares 5 different tidal automated peritoneal dialysis (APD) prescriptions. Six low-average and 6 high-average transporters performed 3 separate sessions with 5 different schedules: (A) 50% tidal with initial fill volume (FV) 2 liters, (B) 50% tidal with 2.2 liters initial FV, (C) 2.2 liters initial FV with 70% tidal, (D) as in B, with one complete renewal of the initial FV at midsession, (E) 2.2 liters FV with breakpoint modality. Urea, creatinine and phosphate peritoneal clearances, sodium removal and ultrafiltration (UF) were compared using analysis of variance. Compared to treatment A, all the tested alternative schedules were associated with 10% significantly higher urea clearance; B, D and E, but not C, were associated with 10% higher creatinine clearance. Phosphate clearance was significantly higher with D, while sodium removal was larger with both C and D. UF was lower with A and E in high average transporters. Manipulation of the main prescriptive parameters of tidal APD has significant impact on its efficiency.

Randomized Crossover Comparison of Injection Site Pain with 40mg/0.4 or 0.8mL Formulations of Adalimumab in Patients with Rheumatoid Arthritis.

IntroductionAdalimumab, an anti-tumor necrosis factor antibody, is currently available in a 40 mg/0.8 mL formulation. The objective of this analysis was to evaluate injection site-related pain, safety, and tolerability of a 40 mg/0.4 mL formulation of adalimumab that had fewer excipients, a smaller volume, and a delivery presentation with a smaller gauge needle, versus the current 40 mg/0.8 mL formulation in patients with rheumatoid arthritis (RA).MethodsTwo identically designed, phase 2, randomized, single-blind, two-period crossover studies were conducted in Belgium and the Czech Republic (Study 1) and Australia, Canada, and Germany (Study 2). In both studies, adults with RA [biologic-naive or current users of 40 mg/0.8 mL adalimumab with an average injection site-related pain rating ≥3 cm on a visual analog scale (VAS; 0–10 cm)] were randomized to receive 40 mg/0.8 mL or 40 mg/0.4 mL adalimumab at visit 1. After 1–2 weeks (depending on patient medication schedule), patients received the other formulation at visit 2. A pain VAS [McGill Pain Questionnaire (MPQ-SF)] and the Draize scale were evaluated immediately after injection and 15 min postinjection. The primary endpoint was immediate pain after injection.Results64 and 61 patients were randomized in Studies 1 and 2, respectively. Both studies found a clinically relevant and statistically significant lower immediate pain after injection for the 40 mg/0.4 mL versus the 40 mg/0.8 mL formulation. The mean difference on the VAS for the pooled data (−2.48 cm) was also clinically relevant. Most other endpoints in both studies favored the 40 mg/0.4 mL formulation, and its tolerability and safety profile were consistent with 40 mg/0.8 mL adalimumab.ConclusionA 40 mg/0.4 mL adalimumab formulation was well tolerated and associated with less injection site-related pain than the 40 mg/0.8 mL adalimumab formulation.Trial registrationClinicalTrials.gov identifier, NCT01561313 and NCT01502423.FundingAbbVie.Electronic supplementary materialThe online version of this article (doi:10.1007/s40744-016-0041-3) contains supplementary material, which is available to authorized users.

Tidal Estimation from TOPEX/Poseidon, Jason Primary, and Interleaved Missions in the Bohai, Yellow, and East China Seas

ABSTRACT Cheng, Y.; Xu, Q., and Zhang, Y., 2016. Tidal estimation from TOPEX/Poseidon, Jason primary, and interleaved missions in the Bohai, Yellow, and East China seas. In this study, response analysis of 18 years of TOPEX/Poseidon–Jason-1–Jason-2 (T/P-Jason) primary mission and 4 years of TOPEX–Jason-1 (TOPEX-Jason) interleaved mission along-track data is performed to derive four principal tidal constituents (M2, S2, K1, and O1) in the Bohai, Yellow, and East China seas (BYE). The intercomparison at crossover points and comparison with the ground truth show that the combination of T/P-Jason primary with TOPEX-Jason interleaved mission data are suitable for estimating the four principal tidal constituents in the regions. Three data sets of harmonic constants determined from tide-gauge records are used to investigate the impacts of TOPEX-Jason interleaved mission data on tidal constituent estimation over the BYE regions. The accuracy of estimated tidal constituents using 18 years of T/P-Jason data is slig...

Evaluation of quality of life using a tablet PC-based survey in cancer patients treated with radiotherapy: a multi-institutional prospective randomized crossover comparison of paper and tablet PC-based questionnaires (KROG 12–01)

This study compared a tablet PC questionnaire with a paper method for reliability and patient preferences in the acquisition of patient-reported outcomes (PROs) for patients treated with radiotherapy. By comparing the two modes of PRO administration, we aimed to evaluate the adequacy of using tablet PC questionnaires in future clinical use. Patients were randomized in a crossover study design using two different methods for PRO entry. A group of 89 patients answered a paper questionnaire followed by the tablet PC version, whereas 89 patients in another group completed the tablet PC questionnaire followed by the paper version. Surveys were performed four times per patient throughout the course of the radiotherapy. The Korean versions of the M.D. Anderson Symptom Inventory (MDASI-K) and the Brief Fatigue Inventory (BFI-K) were used. The primary endpoint of our current study was an assessment of patient preference for the survey method. The proportions of patients preferring each mode of questionnaire were evaluated. The proportion of patients who preferred the tablet PC version, paper form, or who had no preference was 52.2, 22.1, and 25.7%, respectively. More than half of the patients preferred the tablet PC to the paper version in all four surveys. Age, gender, educational status, prior experience of using a tablet PC, and the order of paper to tablet PC administration did not impact patient preferences. Inter-class correlation coefficients (ICCs) between the modes were 0.92 for MDASI-K and 0.94 for BFI-K and ranged from 0.91 to 0.96 on both instruments during the four surveys. A tablet PC-based PRO is an acceptable and reliable method compared with paper-based data collection for Korean patients receiving radiotherapy.

Do mask aperture bars of extraglottic airway devices prevent prolapse of epiglottis causing airway obstruction? A randomized crossover trial in anesthetized adult patients

Study objectiveThe study objective is to determine whether extraglottic airway devices (EADs) with or without mask aperture bars (MABs) result in similar anatomical positions in patients undergoing surgery. DesignProspective, randomized, crossover comparison of four extraglottic airway devices. SettingOperating theatre at a large teaching hospital. PatientsEighty consenting patients scheduled to undergo surgery with general anesthesia. InterventionsPatients were randomly allocated to receive anesthesia with one of four tested EADs. Two versions of each EAD were inserted in random order; one with and one without MABs. Measurements and main resultsEndoscopic evaluation did not demonstrate any difference between the EADs with or without MABs. Contact between MABs and arytenoids (n=15) and herniation of arytenoids (n=7) was restricted to the Cobra-group patients. In nine patients the epiglottis made contact with a MAB, although this contact was very limited and often unilateral. ConclusionThis study demonstrated that the anatomical position of the four tested single-use EADs is similar with or without mask aperture bars. We therefore question whether MABs have a protective role in prevention of airway occlusion and whether MABs are essential components. In the overall majority of EADs with MABs, the latter did not prevent contact with the epiglottis. Contact and herniation of the laryngeal structures are seen more frequently when more than two MABs are present.

A randomised cross-over comparison of the transverse and longitudinal techniques for ultrasound-guided identification of the cricothyroid membrane in morbidly obese subjects

We compared the transverse and longitudinal approaches to ultrasound-guided identification of the cricothyroid membrane, to determine which was faster and more successful. Forty-two anaesthetists received a one-hour structured training programme consisting of e-learning, a lecture and hands-on training, and then applied both techniques in a randomised, cross-over sequence to obese females with body mass index 39.0 - 43.9 kg.m(-2) . The mean (SD) time to identify the cricothyroid membrane was 24.0 (12.4) s using the transverse technique compared with 37.6 (17.9) s for the longitudinal technique (p = 0.0003). Successful identification of the cricothyroid membrane was achieved by 38 (90%) anaesthetists using either technique. All anaesthetists were successful in identifying the cricothyroid membrane with at least one of the techniques. We advocate the learning and application of these two techniques for identification of the cricothyroid membrane before starting anaesthesia in difficult patients, especially when anatomical landmarks are impalpable. Further use in emergency situations is feasible, if clinicians have experience and the ultrasound machine is readily available.

Long-acting Insulin Analogs Effect on gh/igf Axis of Children with Type 1 Diabetes: a Randomized, Open-label, Two-period, Cross-over Trial.

Growth hormone (GH) secretion is increased in pre-pubertal children with type 1 diabetes and GH excess produces insulin resistance. Early-morning insulinopenia contributes to lower insulin-like growth factor (IGF-I) levels and to GH hypersecretion. To evaluate differences in GH/IGF-I axis of pre-pubertal children with type 1 diabetes treated with glargine or detemir as long-acting insulin analogues, which was the main outcome measure, and to compare insulin effects in obtaining good metabolic control. Children with type 1 diabetes. This was a 32-week, randomized, open-label, two-period, cross-over comparison between bedtime glargine and twice-daily detemir insulin, involving pre-pubertal children in care at a diabetes pediatric centre. After a 8-week-run-in period subjects were randomized to bedtime glargine or twice-daily detemir insulin administration. After a 12-week period treatments were inverted and continued for additional 12 weeks. Overall, 15 pre-pubertal children (53.3% males, mean age 8.6±1.5 years, duration of diabetes 4.2±1.5 years) completed the study. Groups did not differ for GH/IGF axis and HbA1c levels. Treatment with glargine was associated with lower fasting glucose values than treatment with detemir (8.1±1.5 vs. 8.2±1.7 mmol/L, p=0.01). Incidence rate of hypoglycemia was not different between insulin treatments (IRR=1.18, 95%CI 1.00-1.38; p=0.07). Detemir treatment was associated with a higher increase in body weight (p=0.008) and height (p=0.02) when compared with glargine. Detemir and glargine not show significant differential effects on the GH/IGFI axis. The greater weight gain and height associated with detemir treatment, apparently not related to the level of pubertal growth, deserve further investigation.

Topical Nasal Anesthesia in Flexible Bronchoscopy--A Cross-Over Comparison between Two Devices.

IntroductionTopical airway anesthesia is known to improve tolerance and patient satisfaction during flexible bronchoscopy (FB). Lidocaine is commonly used, delivered as an atomized spray. The current study assesses safety and patient satisfaction for nasal anesthesia of a new atomization device during outpatient bronchoscopy in lung transplant recipients.MethodsUsing a prospective, non-blinded, cross-over design, patients enrolled between 01-10-2014 and 24-11-2014 received 2% lidocaine using the standard reusable nasal atomizer (CRNA). Those enrolled between 25-11-2014 and 30-01-2015, received a disposable intranasal mucosal atomization device (DIMAD). After each procedure, the treating physician, their assistant and the patient independently rated side-effects and satisfaction, basing their responses on visual analogue scales (VAS). At their next scheduled bronchoscopy during the study period, patients then received the alternative atomizer. Written consent was obtained prior to the first bronchoscopy, and the study approved by the institutional ethics committee.ResultsOf the 252 patients enrolled between 01-10-2014 and 30-01-2015, 80 (32%) received both atomizers. Physicians reported better efficacy (p = 0.001) and fewer side effects (p< = 0.001) for DIMAD in patients exposed to both procedures. Among patients with one visit, physicians and their assistants reported improved efficacy (p = 0.018, p = 0.002) and fewer side effects (p< = 0.001, p = 0.029) for the disposable atomizer, whereas patients reported no difference in efficacy or side effects (p = 0.72 and p = 0.20). No severe adverse events were noted. The cost of the reusable device was 4.08€ per procedure, compared to 3.70€ for the disposable device.DiscussionTopical nasal anesthesia via a disposable intranasal mucosal atomization device (DIMAD) offers comparable safety and patient comfort, compared to conventional reusable nasal atomizers (CRNA) in lung transplant recipients. Procedural costs were reduced by 0.34€ per procedure.Trial Registrationclinicaltrials.gov NCT02237651

Comparison of Two Different Sprint Interval Training Work-to-Rest Ratios on Acute Inflammatory Responses.

BackgroundThe study aims to compare how work-to-rest ratio (W:R) influences insulin sensitivity (Si) and inflammatory responses following one session of sprint interval training (SIT).MethodsThirteen men and two women completed a cross-over comparison of two SIT interventions—Tabata (TAB), 10 × 20-s sprints/10-s rest, and Wingate (WIN), 5 × 30-s sprints with 270-s rest. IL-6, IL-10, and TNF-α were assessed at baseline, immediately following, and 1 h after SIT, as well as prior to the 24-h post-exercise oral glucose tolerance tests (OGTTs).ResultsParticipants were 23.8 (±3.5) years old and 180.0 (±10.2) cm tall, weighed 78.5 (13.0) kg, and had 16.9 (±6.5) % body fat, with a mean VO2Peak of 42.0 (±7.9) ml kg−1 min−1. There were no differences in total work (kJ) between TAB (64.7 ± 12.0) and WIN (68.0 ± 15.0). Mean (±95 % CI) Si 24 h changed −2.8 (−5.1, −0.5) from baseline after TAB and −3.9 (−6.9, −0.9) after WIN. Cytokines were measured in pg ml−1 and expressed as mean change (±95 % CI). IL-6 increased significantly immediately following SIT for TAB 0.70 (0.23, 1.17), and WIN 1.11 (0.60, 1.62), and remained elevated 1 h post SIT for TAB 1.10 (0.37, 1.83), and WIN 0.95 (0.26, 1.65). IL-10 showed a significant positive change immediately following exercise for TAB 1.53 (0.77, 2.29) and WIN 1.59 (0.58, 2.59). TNF-α also increased immediately both TAB 3.26 (1.57, 4.96) and WIN 3.05 (0.56, 5.54) and was directly proportional to IL-10 (r = 0.64, p < 0.0001).ConclusionsW:R did not alter either the inflammatory or metabolic response following SIT nor does SIT improve 24-h Si, despite increased levels of IL-10.

Randomized Crossover Comparison of Personalized MPC and PID Control Algorithms for the Artificial Pancreas.

To evaluate two widely used control algorithms for an artificial pancreas (AP) under nonideal but comparable clinical conditions. After a pilot safety and feasibility study (n = 10), closed-loop control (CLC) was evaluated in a randomized, crossover trial of 20 additional adults with type 1 diabetes. Personalized model predictive control (MPC) and proportional integral derivative (PID) algorithms were compared in supervised 27.5-h CLC sessions. Challenges included overnight control after a 65-g dinner, response to a 50-g breakfast, and response to an unannounced 65-g lunch. Boluses of announced dinner and breakfast meals were given at mealtime. The primary outcome was time in glucose range 70-180 mg/dL. Mean time in range 70-180 mg/dL was greater for MPC than for PID (74.4 vs. 63.7%, P = 0.020). Mean glucose was also lower for MPC than PID during the entire trial duration (138 vs. 160 mg/dL, P = 0.012) and 5 h after the unannounced 65-g meal (181 vs. 220 mg/dL, P = 0.019). There was no significant difference in time with glucose <70 mg/dL throughout the trial period. This first comprehensive study to compare MPC and PID control for the AP indicates that MPC performed particularly well, achieving nearly 75% time in the target range, including the unannounced meal. Although both forms of CLC provided safe and effective glucose management, MPC performed as well or better than PID in all metrics.

Prospective Randomized and Crossover Comparison of Two Apheresis Machines for Peripheral Blood Stem and Progenitor Cell Collection: A Multicenter Study

Peripheral blood stem and progenitor cell (PBSPC) collection imposes apheresis-related risks including thrombocytopenia, hypocalcemia and thromboembolism in donors for PBSPC transplantation. Efficient PBSC collection with fewer apheresis risks and less contamination in the collected products is crucial and we have shown some distinct characteristics among apheresis devices (Transfusion, 2003, 2007 and 2014). A recently introduced apheresis device for PBSPC collections, Spectra-Optia, has not yet established supremacy in safety and efficiency over other established previous apparatuses/programs. To compare the Optia with the widely used automated program for a former apheresis machine, Spectra-Auto (Software version 6.1), we for the first time carried out a prospective randomized multicenter and crossover study for a total of 233 apheresis done from November 2013 to May 2015 in adult (≥18 years) and G-CSF-given patients/donors. The device for the first-day apheresis was randomly assigned, and a total of 152, consisting of 47 for autologous (auto-) patients and 105 for allogeneic (allo-) donors, were studied (1st-day analysis). Among them, the 81 subjects who required the second-day apheresis to collect more cells, the second-day apheresis was performed with the other machine than the one used in the first day, and apheresis collections for 2 consecutive days using both machines were compared by a paired-t test (crossover analysis). In the both devices, apheresis was performed based on the manufacturer's protocols, with 12:1 to 15:1 ratios of whole blood to acid citrate dextrose without heparin. There was no difference between the Optia (n = 74) and the Spectra-Auto (n = 78) in the pre-apheresis parameters including age, sex, circulating blood volume (CBV), and peripheral complete blood counts (CBCs). In the crossover comparison, age, sex and CBV were technically same and CBCs were similar between the two machines (n = 81 in each). The Spectra-Auto processed larger volumes compared with the Optia [P = .02 (1st-day analysis) and .08 (crossover analysis)], although run time was similar with the two devices [P = .57 (1st-day) and .52 (crossover)]. Mild apheresis-related reactions occurred in both machines with similar frequencies of reactions, and volumes of ACD used were not different between them. Volumes of harvested products were greater in the Optia compared with the Spectra-Auto [158 vs. 95 mL, P < .01 (1st-day) and 137 vs. 86 mL, P < .01 (crossover)]. Yields of mononuclear cells [P = .27 (1st-day) and .22 (crossover)] and CD34+ cells [P = .10 (1st-day) and .19 (crossover)] were not different between them. However, regardless of program, pre-apheresis peripheral CD34+ cell counts strongly correlated with the number of CD34+ cells collected, and collection efficiencies of CD34+ cells were significantly higher in the Optia compared with the Spectra-Auto [82.2% vs. 66.3%, P < .01 (1st-day) and 80.5% vs. 63.1%, P < .01 (crossover)]. The products collected using the Optia contained more contaminating red blood cells [64 vs. 36 x 106 cells, P < .01 (1st-day) and 56 vs. 33 x 106 cells, P < .01 (crossover)], compared with the Spectra-Auto, without corresponding anemia. Only in crossover analysis, there was a trend that contaminated platelets were higher with the Optia compared with the Spectra-Auto (154 vs. 127 x 109 cells, P = .06). In conclusion, the Optia is tolerable, and has no significant inferiority in the yield or adverse events in apheresis collection of PBSPCs compared with Spectra-Auto. This trial was registered at http://www.umin.ac.jp/ctr/index.htm as #UMIN000012095. DisclosuresOhto:Terumo BCT: Research Funding.

Pharmacokinetic (PK) Comparison of Two Fibrinogen Concentrates in Patients with Congenital Fibrinogen Deficiency: Final Analysis

IntroductionPatients with congenital afibrinogenaemia and hypofibrinogenaemia, experience frequent severe bleeding episodes starting at birth or early childhood. Bleeding may occur after a minor trauma or a small surgical intervention, into the skin, mucosa, muscles, gastrointestinal tract, or the brain. Therapeutic substitution with human fibrinogen concentrate can correct the haemostatic defect and arrest the bleeding in patients with these fibrinogen deficiencies. Octafibrin is a plasma derived, highly purified, lyophilized, fibrinogen concentrate, which has been double virus safeguarded using two dedicated virus inactivation/removal steps. In this study, the (PK) profile of this new concentrate is compared to a commercially available product.MethodsThis study was a prospective, randomized, open-label, multinational, crossover PK comparison of Octafibrin to an existing marketed product (Haemocomplettan¨ P/RiaSTAPTM) in adult and adolescent afibrinogenemic patients, including comparison of a surrogate efficacy endpoint Maximum Clot Firmness (MCF) measured by ROTEM¨. Patients were randomized to either product and received a single dose of 70mg/kg b.w. and blood samples were collected over 14 days followed by an observational period up to 45 days. Afibrinogenemia was confirmed by baseline fibrinogen activity plasma level of < 0.20. All fibrinogen and MCF testing was performed in a central lab using validated methods. Primary objective was to show bioequivalence between both products based on the Normalized Area Under the Curve (AUCnorm).ResultsTwenty two adult and adolescent patients were included in the final analysis. Mean AUCnorm) for Octafibrin was 1.62, and for the marketed concentrate 1.35 (hákgág/L/mg) and mean clearance 0.67 and 0.82 mL/h/kg, respectively. Both showed a statistically significant differences between the groups (see figure and table below). Other PK parameter were comparable between the products. Comparable haemostatic efficacy of the two products was demonstrated based on their ability to significantly increase MCF from baseline. There were no reports of adverse events (AE) related to the infusion of this novel concentrate.ConclusionsIn conclusion, this study showed a statistically significantly higher AUCnorm and lower clearance for Octafibrin compared to the comparator. Other PK parameters were in general comparable. Change in MCF compared to baseline as a surrogate efficacy parameter, was similar to that of the licensed comparator used in this study, and there was no related AE or SAE for Octafibrin after single-dose administration.TableRatios of Octafibrin Relative to Haemocomplettan¨ P/RiaSTAPTM for AUC and AUCnorm (PK Population, N=22)Fibrinogen activityParameter ratioMean90% CI ofmean ratiop-valueAUC1.34(1.23, 1.41)<0.0001AUCnorm1.21(1.25, 1.44)0.0002 [Display omitted] DisclosuresRoss:Octapharma: Other: Investigator. Rangarajan:Octapharma: Other: Investigator. Karimi:Octapharma: Other: Investigator. Schwartz:Octapharma: Employment. Knaub:Octapharma: Employment. Peyvandi:LFB, Kedrion, Novonordisk, Bayer, Roche, CSL Behring.: Consultancy, Honoraria, Research Funding; Octapharma: Other: Investigator.

Chrysanthemum flower oil inhibits diet-induced serum uric acid elevation in adult male subjects

This randomised, double-blind, cross-over comparison study investigated the effect of chrysanthemum flower oil (CFO) on diet-induced serum uric acid elevation (DUE). Twenty Japanese male subjects (aged 30–60 years) were randomly divided into two groups. During Period I, one group received the purine-loading food followed by the placebo, and the other received CFO instead of placebo. During Period II, after a wash-out period, the test was repeated and the subjects crossed over to the alternate treatment. Blood was collected at 0, 60, 120, 180 and 240 min after purine loading to measure serum uric acid (sUA) level. Urine was collected from 0 to 120 min. All 20 subjects completed the study, but one subject, with suspected occult blood in his urine at the time of screening and a particularly large difference in urine volume between Periods I and II, was excluded from the efficacy analysis population. In the efficacy analysis population, CFO did not suppress DUE in subjects with baseline sUA between 5.5 and 8.0 mg/dl. However, stratification analysis revealed a statistically significant reduction in DUE by CFO in subjects with baseline sUA ≥7.1 mg/dl. The area under the concentration curve from 0 to 240 min tended to decrease in the same population. For safety analysis, all 20 subjects were evaluated. One patient who developed mild cold symptoms recovered quickly with the symptoms disappearing. No clinically important adverse events were observed. It was concluded that CFO is effective in reducing DUE in Japanese male subjects.

The Benefits of High Relaxivity for Brain Tumor Imaging: Results of a Multicenter Intraindividual Crossover Comparison of Gadobenate Dimeglumine with Gadoterate Meglumine (The BENEFIT Study).

Gadobenate dimeglumine (MultiHance) has higher r1 relaxivity than gadoterate meglumine (Dotarem) which may permit the use of lower doses for MR imaging applications. Our aim was to compare 0.1- and 0.05-mmol/kg body weight gadobenate with 0.1-mmol/kg body weight gadoterate for MR imaging assessment of brain tumors. We performed crossover, intraindividual comparison of 0.1-mmol/kg gadobenate with 0.1-mmol/kg gadoterate (Arm 1) and 0.05-mmol/kg gadobenate with 0.1-mmol/kg gadoterate (Arm 2). Adult patients with suspected or known brain tumors were randomized to Arm 1 (70 patients) or Arm 2 (107 patients) and underwent 2 identical examinations at 1.5 T. The agents were injected in randomized-sequence order, and the 2 examinations were separated by 2-14 days. MR imaging scanners, imaging sequences (T1-weighted spin-echo and T1-weighted high-resolution gradient-echo), and acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images for diagnostic information (degree of definition of lesion extent, lesion border delineation, visualization of lesion internal morphology, contrast enhancement) and quantitatively for percentage lesion enhancement and lesion-to-background ratio. Safety assessments were performed. In Arm 1, a highly significant superiority (P < .002) of 0.1-mmol/kg gadobenate was demonstrated by all readers for all end points. In Arm 2, no significant differences (P > .1) were observed for any reader and any end point, with the exception of percentage enhancement for reader 2 (P < .05) in favor of 0.05-mmol/kg gadobenate. Study agent-related adverse events were reported by 2/169 (1.2%) patients after gadobenate and by 5/175 (2.9%) patients after gadoterate. Significantly superior morphologic information and contrast enhancement are demonstrated on brain MR imaging with 0.1-mmol/kg gadobenate compared with 0.1-mmol/kg gadoterate. No meaningful differences were recorded between 0.05-mmol/kg gadobenate and 0.1-mmol/kg gadoterate.

240 A randomized, double-blind, multicentre, multinational crossover comparison of the pancreatic enzyme product (PEP) APT-1008 (ZENPEP®) to KREON® in the treatment of exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF) in patients ≥12 years of age

Objectives An investigational PEP (APT-1008, to be marketed in Europe as ENZEPI®) was compared to KREON® in the treatment of EPI associated with CF. Methods This was a randomized, double-blind, active-controlled, 2-arm crossover, multinational, multicentre study comparing APT-1008 (APT) to KREON in the treatment of EPI in patients ≥12 years of age with CF. Patients were stabilized on their current PEP treatment during screening followed by randomization to APT or KREON for 28 days; then switched without washout to the opposite treatment with the same treatment schedule. The primary efficacy endpoint was the coefficient of fat absorption over 72 hours (CFA-72h) at the end of each period. Secondary endpoints included the coefficient of nitrogen absorption over 72 hours, clinical signs and symptoms of EPI, and quality of life. Safety assessments included adverse events (AE), laboratory tests and vital signs. Results 96 patients were randomized into 2 treatment sequences (APT/KREON or KREON/APT) with 83 completers comprising the efficacy population. APT demonstrated both non-inferiority and equivalence to KREON in fat absorption (LS mean CFA-72h: APT 84.08% [SE 1.109] vs. KREON 85.33% [SE 1.109]). Efficacy results of APT and KREON were generally similar for the secondary endpoints. The most frequent AEs were gastrointestinal, in 8.7% and 11.1% of patients on APT and KREON, respectively; no treatment-related serious AEs occurred. APT demonstrated safety and tolerability similar to KREON. Conclusions This study demonstrated that APT has comparable efficacy and safety to KREON in the treatment of adolescents and adult patients with EPI associated with CF.

Intravenous dexketoprofen induces less injection pain than racemic ketoprofen

Ketoprofen has high analgesic efficacy against inflammatory and nociceptive pain. Additionally, when ketoprofen is administered in conjunction with an opioid during pain management, it prevents the development of opioid-induced hyperalgesia. The main limitation for racemic ketoprofen IV administration is venous irritation. Dexketoprofen is the active enantiomer of racemic ketoprofen and has a similar analgesic efficacy in a dose proportion of 1:2, but it causes fewer adverse effects than racemic ketoprofen. It has been claimed that dexketoprofen may cause less frequent and less severe injection pain than racemic ketoprofen. In this study, we compared the injection pain of IV administered racemic ketoprofen and dexketoprofen in elective surgical patients. The ethics committee of our institution approved this randomized, double-blinded, two-treatment, two-period, crossover clinical comparison of ketoprofen and dexketoprofen. A total of 221ASA I-III adult patients, aged 20-75years, were initially IV administered either 0·5mg/kg racemic ketoprofen followed 2h later with 0·25mg/kg dexketoprofen (group 1) or vice versa (group 2). Both compounds were diluted in 20mL of normal saline and were injected over 6min. Patients reported injection pain on an 11-point numerical rating scale (NRS) (0=no pain, 10=most pain). Significantly less injection pain was reported after dexketoprofen administration. A total of 201 of 209 patients reported pain during racemic ketoprofen injection, and 157 of 210 patients reported pain during dexketoprofen injection, respectively. Moderate or severe pain was reported by 90 (41%) patients during racemic ketoprofen administration and by 43 (20%) during dexketoprofen injection (P=0·001). The mean of injection pain during racemic ketoprofen injection was 4·2 (SD 2·5) and was 2·5 (2·4) during dexketoprofen injection (P=0·001). No serious or unexpected adverse events were reported. Dexketoprofen causes significantly less injection pain than racemic ketoprofen; therefore, it may be a more suitable IV non-steroidal anti-inflammatory than the racemate.

His-bundle pacing versus biventricular pacing in cardiac resynchronization therapy patients: A crossover design comparison.

Cardiac resynchronization therapy (CRT) typically is attempted with biventricular pacing (BiVP). One-third of patients are nonresponders. His-bundle pacing (HBP) has been evaluated as an alternative means of effecting CRT because it generates truly physiologic ventricular activation, as evidenced in part by the morphologic identity between normally conducted and paced QRS complexes. The purpose of this study was to assess the feasibility of, and clinical response to, permanent HBP as an alternative to BiVP in CRT-indicated patients. Patients were implanted with a right atrial pacing lead, defibrillation lead, left ventricular (LV) lead via the coronary sinus, and HBP lead. His and LV leads were plugged into the LV port via a Y-adapter. After successful implant, patients were randomized in single patient-blinded fashion to either HBP or BiVP. After 6 months, patients were crossed over to the other pacing modality and followed for another 6 months. Quality-of-life assessments, echocardiographic measurements, New York Heart Association classification, and 6-minute hall walk test were obtained at baseline and at each 6-month follow-up. Twenty-nine patients were enrolled; 21 (72%) demonstrated electrical resynchronization (QRS narrowing) at implant. Twelve patients completed the crossover analysis at 1 year. Clinical outcomes (quality of life, New York Heart Association functional class, 6-minute hall walk test, LV ejection fraction) were significantly improved for both pacing modes compared with baseline measures. In this crossover comparison between HBP and BiVP, HBP was found to effect an equivalent CRT response. QRS narrowing was observed in 21 of 29 patients, suggesting this approach may be feasible in more patients with left bundle branch block than previously assumed.