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1.
Hrvoje Barić Veljko Đorđević Ivan Cerovečki Vladimir Trkulja 《Advances in therapy》2018,35(3):261-288
Introduction
The objective was to evaluate efficacy/safety of complementary and alternative medicine (CAM) methods for generalized anxiety disorder (GAD) based on randomized controlled trials in adults.Methods
Data sources. Six electronic databases (“generalized anxiety (disorder)” and “randomized trial”) and reference lists of identified publications were searched to March 2017. Study selection. Eligibility: full-text publications (English, German language); CAM versus conventional treatment, placebo/sham or no treatment; GAD diagnosed according to standard criteria; and a validated scale for disease severity. Of the 6693 screened records, 32 were included (18 on biologically-based therapies, exclusively herbal preparations; eight on manipulative and body-based therapies; and three on alternative medical systems and three on mind–body therapies). Data extraction. Cochrane Collaboration methodology was used for quality assessment and data extraction.Results
Direct comparisons of Kava Kava (Piper methysticum) extracts to placebo (4 quality trials, n = 233) were highly heterogeneous. Network meta-regression reduced heterogeneity and suggested a modest Kava effect [end-of-treatment Hamilton Anxiety scale score difference adjusted for baseline scores and trial duration: ? 3.24 (95% CI ? 6.65, 0.17; P = 0.059), Kava Kava 4 arms, n = 139; placebo 5 arms, n = 359]. Lavender (Lavandula angustifolia) extract (1 quality trial, 10 weeks, n = 523) and a combination of extracts of C. oxycantha, E. californica and magnesium (1 quality trial, 12 weeks, n = 264) were superior to placebo and balneotherapy was superior to paroxetine (1 quality trial, 8 weeks, n = 237) indicating efficacy. All other trials were small and/or of modest/low quality and/or lacked assay sensitivity. Safety reporting was poor.Conclusion
Evidence about efficacy/safety of most CAM methods in GAD is limited. Apparent efficacy of certain herbal preparations and body-based therapies requires further confirmation.2.
Arrigo F. G. Cicero Federica Fogacci Marilisa Bove Maddalena Veronesi Manfredi Rizzo Marina Giovannini Claudio Borghi 《Advances in therapy》2017,34(8):1966-1975
Introduction
There is a growing interest in nutraceuticals improving cardiovascular risk factor levels and related organ damage.Methods
This double-blind, placebo-controlled randomized clinical trial aims to compare the effect of a combined nutraceutical containing red yeast rice (10 mg), phytosterols (800 mg), and l-tyrosol (5 mg) on lipid profile, blood pressure, endothelial function, and arterial stiffness in a group of 60 patients with polygenic hypercholesterolemia resistant to Mediterranean diet.Results
After 8 weeks of treatment, when compared to the placebo group, the active treated patients experienced a more favorable percentage change in total cholesterol (?16.3% vs 9.9%, P < 0.001 always), LDL-C (?23.4% vs ?13.2%, P < 0.001 always), and hepatic steatosis index (?2.8%, P < 0.01 vs ?1.8%, P < 0.05). Moreover, ALT (?27.7%, P < 0.001), AST (?13.8%, P = 0.004), and serum uric acid (?12.3%, P = 0.005) were reduced by the tested nutraceutical compound both compared to randomization and to placebo, which did not affect these parameters (P < 0.01 for all). Regarding the hemodynamic parameters, there was a decrease of systolic blood pressure (?5.6%) with the active treatment not observed with placebo (P < 0.05 vs baseline and placebo) and endothelial reactivity improved, too (?13.2%, P < 0.001 vs baseline). Consequently, the estimated 10-year cardiovascular risk score improved by 1.19% (SE 0.4%) (P = 0.01) in the nutraceutical-treated patients.Conclusion
The tested nutraceutical association is able to improve the positive effects of a Mediterranean diet on a large number of CV risk factors and consequently of the estimated CV risk.Trial registration
ClinicalTrials.gov identifier NCT02492464.Funding
IBSA Farmaceutici.3.
David J. W. Knight Dale Gardiner Amanda Banks Susan E. Snape Vivienne C. Weston Stig Bengmark Keith J. Girling 《Intensive care medicine》2009,35(5):854-861
Objective
To investigate the effect of enteral Synbiotic 2000 FORTE® (a mixture of lactic acid bacteria and fibre) on the incidence of ventilator associated pneumonia (VAP) in critically ill patients.Design
Prospective, randomised, double blind, placebo controlled trial.Setting
Tertiary referral centre, general Adult Intensive Care Unit (ICU).Patients and participants
259 enterally fed patients requiring mechanical ventilation for 48 h or more were enrolled.Intervention
All patients were enterally fed as per a standard protocol and randomly assigned to receive either synbiotic 2000 FORTE® (twice a day) or a cellulose-based placebo for a maximum of 28 days.Measurements and results
Treatment group (n = 130) was well matched with placebo group (n = 129) for age (mean 49.5 and 50 years, respectively) and APACHE II score (median 17 for both). Oropharyngeal microbial flora and colonisation rates were unaffected by synbiotics. The overall incidence of VAP was lower than anticipated (11.2%) and no statistical difference was demonstrated between groups receiving synbiotic and placebo in the incidence of VAP (9 and 13%, P = 0.42), VAP rate per 1,000 ventilator days (13 and 14.6, P = 0.91) or hospital mortality (27 and 33%, P = 0.39), respectively.Conclusions
Enteral administration of Synbiotic 2000 FORTE® has no statistically significant impact on the incidence of VAP in critically ill patients.4.
Background
DepoFoam® bupivacaine (Pacira Pharmaceuticals, Inc., San Diego, CA, USA), an extended-release liposomal bupivacaine-based analgesic, was compared with placebo for the prevention of pain after bunionectomy in a randomized, multicenter, double-blind phase 3 clinical study.Methods
Patients received placebo (n=96) or DepoFoam bupivacaine 120 mg (n=97) via wound infiltration prior to closure. Pain intensity was assessed using a numeric rating scale (NRS) from time 0 through to 72 hours postsurgically. The primary efficacy measure was area under the curve (AUC) of NRS scores through 24 hours. Other efficacy measures included AUC of NRS at other time points, proportion of patients who were pain-free, time to first opioid use, and total postsurgical consumption of supplemental opioid medication. Adverse events were also assessed.Results
The AUC for NRS scores was significantly less in patients treated with DepoFoam bupivacaine versus patients receiving placebo at 24 hours (P=0.0005) and 36 hours (P<0.0229). More patients treated with DepoFoam bupivacaine avoided use of opioid rescue medication during the first 24 hours (7.2% vs. 1%; P<0.0404) and were pain-free (NRS ≤1) at 2, 4, 8, and 48 hours. Median time-to-first-opioid use was delayed in favor of DepoFoam bupivacaine (4.3 vs. 7.2 hours; P<0.0001). Fewer adverse events were reported by patients treated with DepoFoam bupivacaine (59.8%) versus placebo (67.7%).Conclusions
DepoFoam bupivacaine, a long-acting local analgesic, provided extended pain relief and decreased opioid use after bunionectomy, compared with placebo.5.
Ippei Ikushima Lene Jensen Anne Flint Tomoyuki Nishida Jeppe Zacho Shin Irie 《Advances in therapy》2018,35(4):531-544
Introduction
Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects.Methods
In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC0–168h)].Results
Steady-state exposure of semaglutide was similar for both populations: AUC0–168h estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (Cmax) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC0–168h ERR 1.11; Cmax ERR 1.14). Dose-dependent increases in AUC0–168h and Cmax occurred in both populations. Accumulation was as expected, based on the half-life (t1/2, ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified.Conclusions
The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects.Funding
Novo Nordisk A/S, Denmark.Trial registration
ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550.6.
Jiaywei Tsauo Moon-Won Yoo Ho-Young Song Dae Wook Hwang Jung-Hoon Park Min-Hee Ryu Song Cheol Kim Jeong Hoon Lee Kee Don Choi Jin Hyoung Kim Do Hoon Kim 《Abdominal imaging》2016,41(11):2233-2240
Purpose
To compare the outcomes of partially covered self-expandable metallic stent (SEMS) placement with surgical gastrojejunostomy (GJ) in patients with gastroduodenal obstruction caused by pancreatic cancer.Methods
The medical records of 107 patients with gastroduodenal obstruction caused by pancreatic cancer who underwent fluoroscopic partially covered SEMS placement (n = 75) or surgical GJ (n = 32) at our institution were reviewed.Results
The technical (100% vs. 100%; P > 0.999) and clinical (98.7% vs. 96.9%; P = 0.511) success rates were similar between the SEMS and GJ group. The mean gastric outlet obstruction scoring system score was higher in the SEMS group at 1 week after treatment (2.3 ± 0.5 vs. 1.2 ± 0.4; P < 0.001) but was similar between the two groups at 1 month (2.7 ± 0.5 vs. 2.8 ± 0.5; P = 0.242). The median hospital stay was shorter in the SEMS group than in the GJ group (7 vs. 14 days; P < 0.001). The overall complication (22.7% vs. 28.1%; P = 0.547) and reintervention (21.3% vs. 25.0%; P = 0.677) rates were similar between the two groups. The median patency (99 vs. 138 days; P = 0.102) and survival (106 vs. 140 days; P = 0.245) were also similar between the two groups.Conclusion
The outcomes of partially covered SEMS placement seem to be more favorable than surgical GJ in patients with gastroduodenal obstruction caused by pancreatic cancer.7.
Mustapha Tehfe Scot Dowden Hagen Kennecke Robert El-Maraghi Bernard Lesperance Felix Couture Richard Letourneau Helen Liu Alfredo Romano 《Advances in therapy》2016,33(5):747-759
Introduction
The phase III MPACT trial in patients with metastatic pancreatic cancer (MPC) demonstrated superior efficacy of nab-paclitaxel (nab-P) plus gemcitabine (Gem) compared with Gem monotherapy, including the primary endpoint of overall survival (OS; median 8.7 vs. 6.6 months; hazard ratio [HR] 0.72; P < 0.001). A significant treatment difference favoring nab-P + Gem over Gem was observed for OS in patients treated in North America. The majority of patients were from the US (88%) with only 12% from Canada. Healthcare systems and treatment patterns are different between the 2 countries, and there is limited published information on outcomes of Canadian patients treated with first-line nab-P + Gem. This analysis evaluated efficacy and safety outcomes in Canadian patients in the MPACT trial.Methods
Treatment-naive patients with MPC (N = 861) received either nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 every 4 weeks or Gem 1000 mg/m2 weekly for the first 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle ≥2).Results
The MPACT trial enrolled 63 patients in Canada. Baseline characteristics were well balanced and comparable with those of the intent-to-treat population. Both OS (median 11.9 vs. 7.1 months; HR 0.76; P = 0.373) and progression-free survival (median 7.2 vs. 5.2 months; HR 0.65; P = 0.224) were numerically longer and overall response rate (27% vs. 17%; P = 0.312) was numerically higher with nab-P + Gem vs. Gem. The most common grade ≥3 adverse events with nab-P + Gem vs. Gem were neutropenia (22% vs. 10%), fatigue (34% vs. 33%), and neuropathy (25% vs. 0%).Conclusion
This subanalysis confirmed that nab-P + Gem is an efficacious treatment option and has a manageable safety profile in patients with MPC treated in Canada.Trial registration
ClinicalTrials.gov identifier, NCT00844649.Funding
Celgene Corporation, Summit, NJ, USA.8.
Henrik Svedsater June Roberts Chloe Patel Jake Macey Emma Hilton Lisa Bradshaw 《Advances in therapy》2017,34(6):1466-1481
Introduction
The impact of asthma and chronic obstructive pulmonary disease (COPD) on individuals’ lives may be substantial, yet clinical practice often focuses only on symptoms. We aimed to better understand the perspective of asthma or COPD patients and to identify condition-related burden, life impact, priorities, unmet needs, and treatment goals.Methods
Individuals aged at least 18 years with asthma or COPD were identified by a recruitment panel via clinical referrals, support groups, consumer networks, and a patient database. Interviews were carried out individually (by telephone) or in focus groups (with no more than five participants per group). A semi-structured interview guide was used with prespecified topics, informed by a literature review, that were considered impactful in asthma or COPD (symptoms and daily-life impact, satisfaction with current treatment, important aspects of treatment, adherence, and ideal treatment).Results
Overall, 72 people participated in focus groups/individual interviews (asthma n = 18/n = 21; COPD n = 15/n = 18). “Shortness of breath” was the most frequently reported symptom; however, participants discussed the life impact of their condition more than symptoms alone. Reported physical impacts included the inability to sleep and socialize, while emotional impacts included “embarrassment, stigma, and/or self-consciousness”, “fear and/or panic”, and “sadness, anxiety, and/or depression”. Coping mechanisms for normal activities included continuing at reduced pace and avoidance. Treatment preferences centered on resolving impacts; improved sleep, “speed of action”, and “length of relief” were the most frequently reported ideal treatment factors.Conclusion
Patients with asthma or COPD experience substantial quality of life limitations and tend to focus on these in their expressions of concern, rather than symptoms per se. Life impacts of these conditions may have implications beyond those commonly appreciated in routine practice; these considerations will be applied to a future discrete choice experiment survey.Funding
GSK funded study (H0-15-15502/204821).9.
Takuji Iyama Tomoaki Takata Masahiko Koda Satoko Fukuda Shotaro Hoi Yukari Mae Takeaki Fukui Chishio Munemura Hajime Isomoto 《Journal of Medical Ultrasonics》2018,45(4):571-576
Purpose
To investigate the association of renal elasticity to microscopic findings of nephron hypertrophy and nephrosclerosis.Methods
Patients who underwent renal biopsy were enrolled. Renal elasticity was measured by acoustic radiation force impulse, and nephron size (glomerular volume, non-sclerotic glomerular density, and mean profile tubular area) and nephrosclerosis (globally sclerotic glomeruli and interstitial fibrosis) were estimated. Nephron hypertrophy was indicated by larger glomerular volume, larger tubular area, and lower non-sclerotic glomerular density. Nephrosclerosis was indicated by a higher percentage of globally sclerotic glomeruli and higher severity of fibrosis.Results
Renal elasticity was negatively correlated with glomerular volume (r = ? 0.480, P = 0.024) and mean tubular area (r = ? 0.469, P = 0.028), but it was not correlated with non-sclerotic glomerular density (r = 0.205, P = 0.359), percentage of globally sclerotic glomeruli (r = 0.057, P = 0.800), and severity of fibrosis (r = 0.014, P = 0.950). In a multiple linear regression analysis, glomerular volume and mean tubular area were independently associated with renal elasticity (std β = ? 0.454, P = 0.015 and std β = ? 0.577, P = 0.007, respectively).Conclusion
Renal elasticity was correlated with microstructural findings of nephron hypertrophy. Measuring renal elasticity could help in detecting kidney disease.10.
Saori Ogawa Fuminori Moriyasu Keiko Yoshida Hisashi Oshiro Mayumi Kojima Takatomo Sano Yoshihiro Furuichi Yoshiyuki Kobayashi Ikuo Nakamura Katsutoshi Sugimoto 《Journal of Medical Ultrasonics》2016,43(3):355-360
Purpose
The aim of the present study was to investigate two methods of determining liver stiffness in rats with various degrees of non-alcoholic steatohepatitis induced by a methionine- and choline-deficient (MCD) diet by comparing each finding with reference to histopathological liver findings.Methods
Twenty male Wister rats were fed an MCD diet for up to 32 weeks, and four were fed a normal diet. Ultrasound-based shear wave elastography (SWE) and mechanical compression testing using an Instron Universal Testing machine were performed on each rat at designated time points. After each examination, liver histopathology was analyzed to evaluate the degrees of steatosis, inflammation, and fibrosis based on non-alcoholic fatty liver disease (NAFLD) activity score, and each finding was compared with reference to liver histopathologic findings.Results
Median liver stiffness values measured using SWE showed a stepwise increase with increasing histological inflammation score (P = 0.002), hepatic fibrosis stage (P = 0.029), ballooning score (P = 0.012), and steatosis grade (P = 0.030). Median liver stiffness measured using an Instron machine showed a stepwise increase only with increasing histological fibrosis stage (P = 0.033).Conclusions
Degree of liver stiffness measured by SWE and the Instron machine differed. SWE reflected mainly inflammation, whereas Instron machine-derived values primarily reflected fibrosis. This is the main source of discrepancies between measurements made with these two modalities.11.
Carlo Cattaneo Jaime Kulisevsky Viviana Tubazio Paola Castellani 《Advances in therapy》2018,35(4):515-522
Introduction
Chronic pain is an important yet overlooked non-motor symptom of Parkinson’s disease (PD), caused by an imbalance of the dopaminergic and glutamatergic systems. Safinamide has a multimodal mechanism of action, dopaminergic (reversible MAO-B inhibition) and non-dopaminergic (modulation of the abnormal glutamate release), that might be beneficial for both motor and non-motor symptoms.Objectives
To investigate the long-term (2-year) efficacy of safinamide on PD chronic pain and to confirm the positive effects observed after 6 months of treatment.Methods
This is a post hoc analysis of the data from the 2-year study 018, focused on the reduction of concomitant pain treatments and on the scores of pain-related items of the Parkinson’s disease quality of life questionnaire (PDQ-39).Results
Safinamide, compared with placebo, significantly improved the PDQ-39 items 37 (“painful cramps or spasm,” p?=?0.0074) and 39 (“unpleasantly hot or cold,” p?=?0.0209) and significantly reduced the number of concomitant pain treatments by 26.2% (p?=?0.005). A significantly greater proportion of patients in the safinamide group was not using pain drugs after 2 years of treatment (p?=?0.0478).Conclusions
The positive effects of safinamide on PD chronic pain were maintained in the long term. Further investigations are desirable to confirm their clinical relevance.Funding
Zambon SpA.12.
Hans-Jonas Meyer Stefan Schob Benno Münch Clara Frydrychowicz Nikita Garnov Ulf Quäschling Karl-Titus Hoffmann Alexey Surov 《Molecular imaging and biology》2018,20(2):318-323
Purpose
Previously, some reports mentioned that magnetic resonance imaging (MRI) can predict histopathological features in primary CNS lymphoma (PCNSL). The reported data analyzed diffusion-weighted imaging findings. The aim of this study was to investigate possible associations between histopathological findings, such as tumor cellularity, nucleic areas and proliferation index Ki-67, and signal intensity on T1-weighted and T2-weighted images in PCNSL.Procedures
For this study, 18 patients with PCNSL were retrospectively investigated by histogram analysis on precontrast and postcontrast T1-weighted and fluid-attenuated inversion recovery (FLAIR) images. For every patient, histopathology parameters, nucleic count, total nucleic area, and average nucleic area, as well as Ki-67 index, were estimated.Results
Correlation analysis identified several statistically significant associations. Skewness derived from precontrast T1-weighted images correlated with Ki-67 index (p = ? 0.55, P = 0.028). Furthermore, entropy derived from precontrast T1-weighted images correlated with average nucleic area (p = 0.53, P = 0.04). Several parameters from postcontrast T1-weighted images correlated with nucleic count: maximum signal intensity (p = 0.59, P = 0.017), P75 (p = 0.56, P = 0.02), and P90 (p = 0.52, P = 0.04) as well as SD (p = 0.58, P = 0.02). Maximum signal intensity derived from FLAIR sequence correlated with nucleic count (p = 0.50, P = 0.03).Conclusion
Histogram-derived parameters of conventional MRI sequences can reflect different histopathological features in PSNCL.13.
Todd Schwedt Uwe Reuter Stewart Tepper Messoud Ashina David Kudrow Gregor Broessner Guy P. Boudreau Peter McAllister Thuy Vu Feng Zhang Sunfa Cheng Hernan Picard Shihua Wen Joseph Kahn Jan Klatt Daniel Mikol 《The journal of headache and pain》2018,19(1):92
Background
Subcutaneous erenumab reduced monthly migraine days and increased the likelihood of achieving a?≥?50% reduction at all monthly assessment points tested in 2 pivotal trials in episodic migraine (EM) and chronic migraine (CM). Early efficacy of migraine preventive medications is an important treatment characteristic to patients. Delays in achievement of efficacy can result in failed adherence. The objective of these post-hoc analyses were to evaluate efficacy in the first 4 weeks after initial subcutaneous administration of erenumab 70 mg, erenumab 140 mg, or placebo.Methods
There is no generally accepted methodology to measure onset of action for migraine preventive medications. We used a comprehensive approach with data from both studies to evaluate change from baseline in weekly migraine days (WMD), achievement of ≥?50% reduction in WMD, and proportion of patients experiencing migraine measured on a daily basis. The 7-day moving averages were overlaid with observed data.Results
In both studies (EM: N?=?955; CM: N?=?667), there was evidence of onset of efficacy of erenumab vs. placebo during the first week of treatment, which in some cases reached nominal significance. For EM the changes in WMD were (least squares mean [LSM] [95% CI]): placebo, ??0.1 (??0.3, 0.0); erenumab 70 mg, ??0.3 (??0.5, ??0.2) p?=?0.130; erenumab 140 mg, ??0.6 (??0.7, ??0.4) p?<?0.001. For CM the changes were: placebo, ??0.5 (??0.8, ??0.3); erenumab 70 mg, ??0.9 (??1.2, ??0.7) p?=?0.047; erenumab 140 mg, ??0.8 (??1.1, ??0.5) p?=?0.18. Achievement of ≥?50% reduction in WMD was observed as early as Week 1 (adjusted OR [95% CI] erenumab vs placebo) in EM: erenumab 70 mg, 1.3 (1.0, 1.9) p?=?0.097; erenumab 140 mg, 2.0 (1.4, 2.7) p?<?0.001. A similar outcome was observed for CM: erenumab 70 mg, 1.8 (1.1, 2.8) p?=?0.011; erenumab 140 mg, 1.9 (1.2, 2.9) p?=?0.009. Seven-day moving averages of observed data showed each treatment arm differed from placebo by Week 1 (OR [95% CI]): in EM Day 3 for erenumab 140 mg, 0.7 (0.5, 1.0) p?=?0.031 and at Day 7 for 70 mg, 0.6 (0.4, 0.8) p?=?0.002; in CM: Day 6 for erenumab 70 mg, 0.6 (0.4, 0.9) p?=?0.022 and at Day 7 for 140 mg, 0.7 (0.4, 1.0); p?=?0.038.Conclusion
Erenumab showed early onset of efficacy with separation from placebo within the first week of treatment in both chronic and episodic migraine patients.14.
Yoshishige Samukawa Hirohisa Omiya Hirotaka Watase Kazunari Nozaki Soichi Sakai Rimei Nishimura 《Advances in therapy》2016,33(7):1215-1230
Introduction
In our previous study investigating effects of luseogliflozin, a sodium–glucose cotransporter 2 inhibitor, on 24-h glycemic variability by continuous glucose monitoring (CGM), luseogliflozin elicited parallel downward shifts in fasting and postprandial glucose levels. However, further review of individual patients’ data revealed that postprandial hyperglycemia was not reduced in some patients, while preprandial glucose was ameliorated in most patients. Therefore, we divided patients into two groups according to their postprandial glucose responses and conducted a post hoc subanalyses to elucidate which factors contributed to the differential effects of luseogliflozin.Methods
Thirty-four Japanese type 2 diabetic patients in our previous randomized, double-blind, placebo-controlled, crossover study with 7-day luseogliflozin administration were divided into postprandial glucose responders (PGR, n = 23, ameliorated peak glucose) and postprandial glucose non-responders (PGNR; n = 11, non-ameliorated peak glucose). Baseline characteristics, variations in CGM-measured 24-h glucose levels, and other pharmacodynamic variabilities were compared.Results
Baseline characteristics did not differ significantly between groups. Placebo-subtracted peak glucose was significantly lowered in PGR and significantly increased in PGNR (?43.8 and 17.9 mg/dL; both p < 0.05). Luseogliflozin significantly lowered “lowest glucose” (defined as the lowest level measured throughout a 24-h period) similarly in PGR and PGNR (?19.2 and ?24.0 mg/dL; both p < 0.05), significantly reduced the mean amplitude of glucose excursions in PGR (?15.50 mg/dL; p < 0.05), and increased the area under the curve for plasma glucagon over 24 h in PGNR (median difference vs. placebo: 240 pg/mL h; p < 0.05). Luseogliflozin increased urinary glucose excretion (UGE) and decreased serum insulin by similar magnitudes in both groups.Conclusions
Luseogliflozin diminished glucose fluctuations in most patients by lowering peak glucose to a greater extent than lowest glucose. Luseogliflozin may also lower lowest glucose in patients whose peak glucose was not ameliorated despite increasing UGE. The glucagon increase in PGNR might explain its hypoglycemic effect on postprandial glucose.Funding
Taisho Pharmaceutical Co., Ltd, Tokyo, Japan.Trial Registration
JapicCTI-142548.15.
Ralph Kickuth Hanno Hoppe Bettina Saar Daniel Inderbitzin Jürgen Triller Susanne Raessler Jürgen Gschossmann 《Abdominal imaging》2016,41(9):1782-1792
Purpose
To evaluate the efficacy of superselective transcatheter arterial embolization (TAE) in the treatment of acute peripancreatic bleeding complications.Methods
During a 9-year period, 44 patients with acute bleeding of the peripancreatic arteries underwent TAE in our institution. Thirty-eight patients were treated using microcatheters and 6 patients with a diagnostic catheter. Embolic agents included coils (n = 38), polyvinyl alcohol (PVA) particles (n = 2), isobutyl cyanoacrylate (n = 2), coils plus PVA particles (n = 1), and coils plus isobutyl cyanoacrylate (n = 1). Outcome measures included technical success, clinical success, and the rate of complications.Results
Identified bleeding sources included gastroduodenal artery (n = 14), splenic artery (n = 9), pancreaticoduodenal artery (n = 6), common hepatic artery (n = 5), superior mesenteric artery branches (n = 4), proper hepatic artery (n = 3), and dorsal/transverse pancreatic artery (n = 3). Technical success with effective control of active bleeding was achieved in 41/44 patients (93 %). Clinical success attributed to TAE alone was documented in 40/44 patients (91 %). The rate of major complications was 2 % including death in one patient.Conclusions
Superselective TAE allows effective, minimally invasive control of acute peripancreatic bleeding complications with a low rate of therapeutically relevant complications.16.
Introduction
The aim of this study was to determine the ultrastructural effects of doxorubicin (Adriblastina®; Pharmacia and Upjohn, Milan, Italy), paclitaxel (Taxol®; BMS, Princeton, NJ), Cremophor® EL (a diluent of paclitaxel) and doxorubicin/paclitaxel combinations on normal lung tissues.Methods
In the experimental protocol, 50 Wistar albino rats were used, divided into five different groups: the control group (n=10), the doxorubicin group (1 mg/kg) (n=10), the paclitaxel group (2 mg/kg) (n=10), the Cremophor EL group (150 mg/kg) (n=10) and the paclitaxel/doxorubicin group (2 mg/kg+ 1 mg/kg) (n=10). The drugs were administered weekly to rats via intraperitoneal injections for 14 weeks. After 3 weeks of observation, the rats were killed with thiopental sodium (30 mg/kg) and their left median lung tissues were removed and examined with a Carl Zeiss EM 900 transmission electron microscope.Results
Our experiments showed doxorubicin to cause an increase in collagen fibre content of the alveolar wall, and paclitaxel to cause degenerations in cellular organelles. In the group in which the two agents were administered together, both effects were observed, although the effects of paclitaxel were seen to be dominant. Ultrastructural appearance was similar in the Cremophor EL group compared to the control group.Conclusion
It was detected that doxorubicin and paclitaxel caused ultrastructural degenerations in normal lung tissues and Cremophor EL seemed to be unaccountable for these degenerations.17.
Mai Shibusawa Ryohei Nakayama Yuko Okanami Yumi Kashikura Nao Imai Takashi Nakamura Hiroko Kimura Masako Yamashita Noriko Hanamura Tomoko Ogawa 《Journal of Medical Ultrasonics》2016,43(3):387-394
Purpose
The purpose of this study was to evaluate the usefulness of a computer-aided diagnosis (CAD) scheme for improving the performance of clinicians to diagnose non-mass lesions appearing as hypoechoic areas on breast ultrasonographic images.Methods
The database included 97 ultrasonographic images with hypoechoic areas: 48 benign cases [benign lesion with benign mammary tissue or fibrocystic disease (n = 20), fibroadenoma (n = 11), and intraductal papilloma (n = 17)] and 49 malignant cases [ductal carcinoma in situ (n = 17) and invasive ductal carcinoma (n = 32)]. Seven clinicians, three expert breast surgeons, and four general surgeons participated in the observer study. They were asked their confidence level concerning the possibility of malignancy in all 97 cases with and without the use of the CAD scheme. Receiver operating characteristic (ROC) analysis was performed to evaluate the usefulness of the CAD scheme.Results
The areas under the ROC curve (AUC) improved for all observers when they used the CAD scheme and increased from 0.649 to 0.783 (P = 0.0167). Notably, the AUC for the general surgeon group increased from 0.625 to 0.793 (P = 0.045).Conclusions
This study showed that the performance of clinicians to diagnose non-mass lesions appearing as hypoechoic areas on breast ultrasonographic images was improved by the use of a CAD scheme.18.
Michael Schiff Joe Koo Erik Jin Eric Schiller Ashley Day Rebecca Stevens Christina Laskar 《Advances in therapy》2016,33(2):199-213
Introduction
The purpose of the present study was to determine whether the abatacept autoinjector can be used by the intended population without patterns of preventable use errors, and is acceptable when assessed against key user needs.Methods
Two independently conducted simulated-use studies, with no active drug administered, quantified use errors and evaluated the abatacept autoinjector and competitor devices on key attributes (comfort, control, ease of use, confidence of dose) and overall acceptability. Autoinjector preference was also assessed. Participants were patients with rheumatoid arthritis, caregivers, and healthcare professionals (HCPs). Participants were informed that a new rheumatoid arthritis autoinjector was being tested but were blinded to the intended drug and sponsor identity.Results
In the formative (pre-validation) study (n = 54), two high-priority use errors occurred, both of which resulted from protocol non-compliance rather than mental confusion or physical limitations. In the summative (validation) study (n = 99), one high-priority use error occurred; this was deemed a simulated-use study artifact as participant behavior was guided by actual experience associated with the feel of drug delivery into the skin rather than by protocol, so no mitigation steps were considered necessary. Across user groups, average scores were consistently high for the pre-defined key attributes. Overall acceptability scores (7-point scale) were significantly higher for the abatacept versus competitor autoinjectors—formative study: patients 6.7 vs 5.2 (P = 0.0001), caregivers 7.0 vs 4.6 (P = 0.0093), HCPs 6.8 vs 5.1 (P = 0.0020); summative study: patients 6.5 vs 5.9 (P = 0.0404), caregivers 6.8 vs 5.8 (P = 0.0047), HCPs 6.8 vs 5.1 (P = 0.0002). The abatacept autoinjector was preferred to competitor devices: patients 85.7% vs 14.3% (P = 0.00002), caregivers 84.2% vs 15.8% (P = 0.00443), HCPs 95.0% vs 5.0% (P = 0.00004). Positive experiences with the abatacept autoinjector were attributed to the rubberized grip, device size, visualization of dose progression, button ergonomics, and ease of use.Conclusion
The abatacept autoinjector demonstrated usability without patterns of preventable use errors, and with high acceptability ratings across all key attributes assessed. Preference over competitor autoinjectors was due to device ergonomics, visualization of dose progression, confidence of dose delivery, and overall ease of use.Funding
Bristol-Myers Squibb.19.
Purpose
To retrospectively investigate the utility of diffusion-weighted imaging (DWI) for predicting clinical outcome after concurrent chemoradiotherapy (CCRT) in uterine cervical cancer.Materials and methods
Seventy-four consecutive patients with biopsy-proven cervical cancer who received CCRT underwent DWI at 3T. All patients had MR examinations before therapy (preTx) and at 4 weeks of initiating therapy (midTx). At each point, ADC (apparent diffusion coefficient) was measured in the tumors and ADC change between preTx and midTx were also calculated. For predicting tumor recurrence, MR variables and clinical variables were evaluated and the results were compared.Results
During a mean follow-up of 32.1 months, tumor recurrence developed in 15 (20%) patients: local recurrence (n = 7), distant metastasis (n = 5), and both (n = 3). MidTx tumor ADCs and tumor ADC changes between preTx and midTx were significantly different between the recurrence and non-recurrence groups (P < 0.05), while preTx tumor ADCs were not significantly different between the groups (P = 0.892). Univariate analysis revealed that histologic type, stage, preTx tumor size and volume, and tumor ADC change were significantly related to tumor recurrence (all P < 0.05). However, on multivariate analysis, tumor ADC changes [hazard ratio (HR) 0.886; 95% confidence interval (CI) 0.836–0.940; P = 0.001] and histological type (HR 6.063; 95% CI 1.404–26.187; P = 0.016) were the significant independent predictors of tumor recurrence.Conclusion
Tumor ADC changes between preTx and midTx might be a useful biomarker for the prediction of cervical cancer recurrence after CCRT.20.
Juan Zeng Chun-Ting Wang Fu-Shen Zhang Feng Qi Shi-Fu Wang Shuang Ma Tie-Jun Wu Hui Tian Zhao-Tao Tian Shu-Liu Zhang Yan Qu Lu-Yi Liu Yuan-Zhong Li Song Cui He-Ling Zhao Quan-Sheng Du Zhuang Ma Chun-Hua Li Yun Li Min Si Yu-Feng Chu Mei Meng Hong-Sheng Ren Ji-Cheng Zhang Jin-Jiao Jiang Min Ding Yu-Ping Wang 《Intensive care medicine》2016,42(6):1018-1028