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1.
Susanne V. Fleig Bettina Weger Hermann Haller Florian P. Limbourg 《Advances in therapy》2018,35(3):353-366
Introduction
We conducted a prospective, non-interventional, multicenter study to examine the effect of a fixed-dose combination of perindopril/amlodipine in patients with arterial hypertension.Methods
Patients who were previously untreated or required a change in medication were treated with a fixed combination of perindopril/amlodipine (3.5/2.5 or 7.0/5.0 mg) for 12 weeks. Changes in office, home and ambulatory blood pressure (BP) were recorded. Adherence was assessed by the Hill-Bone medication adherence scale.Results
Overall, 1814 patients (mean age 60.0 ± 13.4 years) were included in 614 German practices, and data of 1770 patients were analyzed. At study entry, 97.7% of patients received perindopril/amlodipine at a daily dose of 3.5 mg/2.5 mg, and 47.9% of patients remained on this dose during the study period. Treatment with perindopril/amlodipine decreased mean office BP from 163.7/95.4 to 133.6/80.3 mmHg (p < 0.0001), resulting in a hypertension control rate of 69.1%. Blood pressure control was comparable in previously untreated and treated patients (70.3 vs. 68.1%), and in younger and older patients (70.6 < 65 vs. 66.3% ≥ 65 years). Ambulatory BP measurements were available in a subgroup of patients (n = 167), and mean 24 h ambulatory BP decreased from 150.6 ± 12.6/88.9 ± 8.8 to 132.4 ± 11.9/79.4 ± 8.5 mmHg (p < 0.0001). Furthermore, the proportion of patients with severe hypertension European Society of Hypertension/European Society of Cardiology (ESH/ESC) grade II or III decreased from 64.4 to 3.9%, and patients with pre-existing isolated systolic hypertension (n = 284) converted to normal BP in 67.6% of cases. Nearly half of the patients (47.2%) were perfectly adherent during the study. In previously treated patients, the percentage of patients with perfect adherence increased from 20.6% prior to study to 43.5% at final visit (p < 0.0001). Adverse drug reactions were documented for 4.9% of patients.Conclusion
A fixed-dose combination of perindopril/amlodipine shows significant blood pressure reduction and improvement in medication adherence in a primary care setting.Trial Registration
ISRCTN26323538.Funding
Servier Deutschland GmbH.2.
Introduction
Long-term therapy with a combination of perindopril and amlodipine has shown a beneficial effect on the morbidity and mortality of patients with stable coronary artery disease (SCAD) and hypertension. On the basis of the antiproliferative, antithrombotic, and antiatherogenic effects of the active substances, we initiated data collection to examine the short-term cardioprotective effect of perindopril/amlodipine fixed-dose combination therapy in this patient group. The aim of this study was to evaluate the effect of perindopril/amlodipine fixed-dose combination on the Canadian Cardiovascular Society (CCS) class and exercise capacity of patients with SCAD in everyday medical practice.Methods
This was a multicenter, prospective, observational, non-interventional, open-label, 6-month clinical study. Patients attended four visits (inclusion, and at months 1, 3, and 6), and clinical information was collected [risk factors, comorbidities, blood pressure (BP), and heart rate measured at the physician’s office, drug treatment, CCS class, adverse events, optional laboratory blood tests, and exercise electrocardiography (ECG)].Results
This study included 3472 patients. The mean office systolic BP/diastolic BP decreased from 157.5 ± 12.9/92.9 ± 8.6 to 130.3 ± 8.3/79.8 ± 6.1 mmHg (P < 0.0001). During the 6-month study period, a favorable change in CCS grading was observed following treatment with fixed-dose combination perindopril/amlodipine: CCS I, from 42.6% to 71.4%; CCS II, from 46.4% to 26.5%; CCS III, from 10.2% to 2.0%; and CCS IV, from 0.8% to 0.1% (all P < 0.0001). In those patients who had exercise ECG at inclusion and the end of month 6 (n = 197) the mean performance, measured in watts, increased from 88.9 ± 37.9 to 110.5 ± 38.4 W (+24.4%; P < 0.001) and from 7.86 ± 2.95 to 8.78 ± 2.92 metabolic equivalent of task (MET) (+11.7%; P < 0.001). No serious adverse events were reported and the treatment was found to have a positive impact on patients’ metabolic profiles.Conclusion
The fixed-dose combination of perindopril and amlodipine improved the CCS class and exercise capacity in patients with SCAD after 6 months of treatment. The fixed-dose combination of perindopril and amlodipine can have favorable effects on the cardiovascular system, not only by its BP-lowering effect and its effect on vascular resistance but also through its direct cardiovascular protective effects.Funding
Egis Pharmaceuticals.Trial registration
21938-1/2011-EKU (698/PI/11.)3.
Alberto Mazza Salvatore Lenti Laura Schiavon Antonella Paola Sacco Fabio Dell’Avvocata Gianluca Rigatelli Emilio Ramazzina 《Advances in therapy》2017,34(4):975-985
Introduction
Blood pressure (BP) control is the main clinical goal in the management of hypertensive patients; however, BP in most of these patients remains uncontrolled, despite the widespread availability of antihypertensive drugs as free-combination therapy. This study compared the efficacy of a fixed-dose triple combination (FDTC) of antihypertensive drugs with that of a free combination of three antihypertensives in patients with uncontrolled hypertension.Methods
Ninety-two patients (mean age 60.8 ± 12.1, 58.0% male) with uncontrolled essential hypertension (office systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg) previously treated with a renin–angiotensin–aldosterone system (RAAS) inhibitor plus hydrochlorothiazide were switched to once-daily FDTC therapy with perindopril/indapamide/amlodipine (5–10/1.25–2.5/5–10 mg). Patients were age- and sex-matched with a control group of hypertensive patients receiving free-combination therapy with three drugs including a RAAS inhibitor, a diuretic, and a calcium channel blocker. Office BP and 24-h ambulatory BP monitoring (ABPM) were evaluated at baseline and after 1 and 4 months.Results
Significant reductions in ambulatory 24-h, daytime, and nighttime systolic BP, and pulse pressure (PP) were found in the FDTC group relative to reductions seen with free-combination therapy, after the first month only of follow-up. Target BP values (mean 24-h ambulatory systolic/diastolic BP < 130/80 mmHg) were reached by more recipients of FDTC than free-combination therapy (64.8% vs. 46.9%, p < 0.05) at month 4 of follow-up, despite reductions in 24-h ABPM values from baseline being similar in both groups at this time point.Conclusion
FDTC of perindopril/indapamide/amlodipine was effective at reducing SBP and PP in previously treated patients with uncontrolled hypertension, and well tolerated, providing support for clinicians in choosing a fixed-dose triple combination over the free-combination of a RAAS inhibitor, a diuretic, and a calcium antagonist.4.
Introduction
In everyday medical practice, physicians often need to manage patients whose blood pressure is not well controlled. Those with a history of cerebrovascular disease are a high-risk group in need of rapid blood pressure control.Methods
The PICASSO study was a real-life, observational trial involving 9257 inadequately treated hypertensive patients who were switched from previous therapy to the fixed-dose combination of perindopril 10 mg/indapamide 2.5 mg (PI) for 3 months. A subanalysis of data of 1117 hypertensive patients who met the clinical criteria of previous stroke or transient ischemic attack was performed. Twenty-four hour ambulatory blood pressure measurements (ABPMs) were also done in a small group of patients (n:38).Results
At baseline, mean systolic/diastolic blood pressure (SBP/DBP) was 161.5?±?15.2/93.1?±?9.9 mmHg. After 1 month with the fixed dose of PI, average office SBP/DBP decreased to 140.0?±?11.9/83.5?±?7.7 mmHg. After 3 months, SBP/DBP had dropped to 132.9?±?9.8/80.0?±?6.2 mmHg, by 28.6?±?15.5/13.1?±?10.0 mmHg (p?<?0.001). Blood pressure control rate (<?140/90 mmHg) was 67.3% after 3 months. When data were stratified by baseline blood pressure, decreases in SBP/DBP were statistically significant in patients with all grades (1–3) of hypertension. In patients previously treated with an angiotensin-converting enzyme inhibitor?±?hydrochlorothiazide (n?=?677), blood pressure decreased by 29.8?±?15.5/13.3?±?10.2 mmHg (p?<?0.001). Decreases in 24-h ABPM values were also significant (n?=?38). Treatment was well tolerated; only a few adverse events were recorded.Conclusion
This study suggests that fixed combination perindopril 10 mg/indapamide 2.5 mg is an effective and well-tolerated treatment for patients with a history of stroke or transient ischemic attack.Funding
EGIS Pharmaceuticals Plc.5.
Guido Grassi Gino Seravalle Gianmaria Brambilla Raffaella Dell’Oro Fosca Quarti Trevano Francesco Fici Luc van Bortel Giuseppe Mancia 《Advances in therapy》2016,33(12):2173-2187
Introduction
The present study was aimed at comparing the antihypertensive efficacy, tolerability, and side effects profile of nebivolol/hydrochlorothiazide (NH) vs irbesartan/hydrochlorothiazide (IH) combination in elderly patients with isolated systolic hypertension (ISH).Methods
124 ISH patients aged 69.1 ± 5.1 years (mean ± SD) were enrolled by 13 general practitioners in Netherlands and Belgium and randomized in a double-blind fashion to receive either NH (5/12.5 mg day, n = 62) or IH (150/12.5 mg day, n = 62) for a 12-week period. The primary efficacy endpoint of the study was the comparison of the two combinations in terms of sitting office systolic blood pressure (BP) reduction after 12 weeks of treatment. In addition ambulatory BP, 24-h BP variability, tolerability, and safety profile were also investigated.Results
122 patients were included in the intention-to-treat analysis. After 12 weeks of treatment the reduction of systolic BP with NH was significantly greater than IH (?25.8 ± 12 vs ?21.2 ± 14 mm Hg, P < 0.03). Diastolic BP reduction was significantly greater with NH after 4 and 8 weeks of treatment but similar at the end of the study (or after 12 weeks). In contrast, the magnitude of the 24-h, daytime, and nighttime systolic and diastolic BP reduction was almost similar in the two groups, while heart rate reduction induced by NH was significantly (P < 0.001) greater during the 24-h, daytime, and nighttime period than that induced by IH. NH caused a reduction in 24-h BP variability significantly greater than IH (standard deviation ?4.4 ± 2.7 vs ?2.2 ± 5.1 mm Hg, P < 0.02, variation coefficient ?2.0 ± 2.6 vs ?0.3 ± 3.4%, P < 0.01). Both treatment regimens were well tolerated.Conclusions
These data provide evidence that NH reduces office BP more than IH but has similar effects on 24-h BP. NH reduces 24-h systolic and diastolic BP variability more than IH, suggesting a greater protective effect on a variable known to adversely affect prognosis.Trial Registration
EU clinical Trials Register identifier, 2010-023104-28.Funding
Menarini International Operations Luxembourg.6.
Silvia Natoli Marzia Lazzari Roberta Carpenedo Elisa Palombo Maria Beatrice Silvi Massimo Mammucari Mario Dauri 《Advances in therapy》2016,33(6):1025-1032
Introduction
Oxycodone is one of the most commonly used opioid analgesics in the clinical management of pain. The present retrospective analysis aimed to determine the dose of oxycodone that could achieve effective control of moderate pain when combined with a fixed dose of acetaminophen, and the time required to reach a clinically relevant reduction in intensity of pain.Methods
Data of patients treated with a combination of oxycodone (5, 10, and 20 mg) and acetaminophen (325 mg) were evaluated for gender, current disease condition, basal pain intensity, total daily dose, days of controlled pain at the initial low dose, and pain intensity after treatment using a numeric pain rating scale.Results
Data from a total of 491 patients were assessed; of these 93.5% of patients experienced persistent non-cancer pain and had an average baseline pain score of 5.68 ± 1.35. For the overall population, the pain score was reduced to 2.49 ± 1.71 with a mean dose of 8.68 ± 4.96 mg oxycodone after 21.60 ± 6.12 days of treatment with the combination. Almost 97% of the patients who reported relief of pain received 1.61 ± 0.67 doses of oxycodone 5 mg combined with 325 mg of acetaminophen.Conclusion
A low-dose combination of oxycodone with acetaminophen can be effective in the management of moderate pain and may help in reducing the treatment-associated adverse reactions and drug dependence.Funding
Sponsorship for article processing charges was provided by Molteni Farmaceutici, Florence, Italy.7.
Heringlake M Handke U Hanke T Eberhardt F Schumacher J Gehring H Heinze H 《Intensive care medicine》2007,33(12):2168-2172
Objective
The modified algorithm for the non-invasive determination of cardiac output (CO) by electrical bioimpedance—electrical velocimetry (EV®)—has been reported to give reliable results in comparison with echocardiography and pulmonary arterial thermodilution (PA-TD) in patients either before or after cardiac surgery. The present study was designed to determine whether EV®-CO measurements reflect intraindividual changes in CO during cardiac surgery.Design
Prospective, observational study.Setting
Operating room (OR) and intensive care unit (ICU) of a university hospital.Patients
Twenty-nine patients undergoing elective cardiac surgery.Interventions
None.Measurements
CO was determined simultaneously by PA-TD and EV® after induction of anesthesia (t1) and 4.9?±?3.5?h after ICU admission (t2).Results
TD-CO was 3.9?±?1.4 and 5.4?±?1.1 l/min at t1 and t2 (?p?0.0001). EV®-CO was 4.3?±?1.1 and 4.9?±?1.5 l/min at t1 and t2 (?p?=?0.013). Bland–Altman analysis showed a bias of ?0.4 l/min and 0.4 l/min and a precision of 3.2 and 3.6 l/min (34.3% and 67.4%) at t1 and t2, respectively. Analysis of the individual pre- to postoperative changes in CO with both methods revealed bidirectional changes in n?=?12 patients and unidirectional changes with a difference greater than 50% and less than 50% in n?=?9 and n?=?8 patients, respectively.Conclusions
The disagreement between PA-TD and EV®-CO measurements after anesthesia induction and after ICU admission, as well as the fact that thoracic bioimpedance did not adequately reflect pre- to postoperative changes in CO, questions the reliability of EV®-CO measurements in cardiac surgery patients and contrasts sharply with previous studies.8.
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.9.
Shiro Mizoue Koji Nitta Motohiro Shirakashi Akiyoshi Nitta Shigeki Yamabayashi Tairo Kimura Toshihiko Ueda Ryuji Takeda Shun Matsumoto Keiji Yoshikawa 《Advances in therapy》2017,34(6):1438-1448
Introduction
This study compared the efficacy and safety of adjunctive brimonidine tartrate 0.1% ophthalmic solution (brimonidine) and timolol maleate 0.5% ophthalmic solution (timolol) in prostaglandin analogue (PGA)-treated normal-tension glaucoma (NTG), assessing the non-inferiority of brimonidine in terms of intraocular pressure (IOP) reduction.Methods
In this multicenter, randomized, investigator-masked, parallel-group, clinical study, adjunctive brimonidine or timolol was administered twice daily for 12 weeks in eyes with NTG that had been treated with PGA for at least 90 days and required additional treatment despite an IOP of 16 mmHg or less. IOP was measured on at least three visits before add-on therapy (mean baseline IOP), and at weeks 4, 8, and 12 after adjunctive administration. Systolic/diastolic blood pressure, pulse rate, and adverse events (AEs) were recorded at each visit.Results
A total of 152 individuals were enrolled and 128 (84.2%) were eligible for efficacy analyses. IOP in both groups at each visit decreased significantly from baseline (P < 0.001). However, the difference in the change from baseline IOP at week 12 between the brimonidine (?1.05 ± 1.81 mmHg) and timolol (?1.41 ± 1.40 mmHg) groups was 0.36 mmHg (95% confidence interval [CI] [?0.21, 0.92]), which exceeded the value of the non-inferiority margin (0.75 mmHg). Baseline systolic/diastolic blood pressure decreased significantly in both groups at certain visits (P < 0.05), while baseline pulse rates decreased significantly in the timolol group (P < 0.001), with no significant differences in the brimonidine group. AE-related treatment discontinuation occurred in 2/71 (2.8%) and 2/75 (2.7%) patients in the brimonidine and timolol groups, respectively.Conclusion
This study demonstrated an add-on effect of brimonidine to PGAs, although non-inferiority of brimonidine to timolol as adjunctive therapy in PGA-treated NTG in terms of IOP reduction was not observed. Brimonidine was associated with no adverse effects on pulse rate.Funding
Senju Pharmaceutical Co., Ltd.Trial registration
UMIN Clinical Trials Registry identifier, UMIN000014810.10.
Maria?Glezer 《Advances in therapy》2018,35(7):1103-1113
Introduction
Trimetazidine (TMZ) has been shown to reduce angina symptoms and to increase exercise capacity in randomized clinical trials, but more extensive data would be useful to assess its effects in real-world clinical practice and in patients with different durations of disease.Methods
CHOICE-2 was a Russian, multicenter, 6-month, open-label, prospective observational study that assessed the effect of adding TMZ modified release 35 mg bid to antianginal treatment in a real-world setting. The present analysis of CHOICE-2 results explored the effects of adding TMZ to background antianginal therapies with regard to the duration of stable angina.Results
A total of 741 patients with known durations of disease were divided into four groups according to stable angina pectoris (AP) duration, ranging from less than 1 year to more than 9 years. Addition of TMZ led to a significant decrease in the frequency of angina attacks and in the use of short-acting nitrates in all groups. In patients with recently diagnosed angina (AP duration < 1 year), the average number of angina attacks per week decreased significantly from 3.75 ± 4.63 to 0.67 ± 1.51 and in those with advanced disease (AP duration > 9 years) from 5.63 ± 5.24 to 1.32 ± 2.07. Angina-free walking distance also improved significantly. Addition of TMZ also improved patient well-being. Results were achieved rapidly (within 2 weeks), were maintained over 6 months, and were obtained in all patient groups regardless of angina duration.Conclusion
TMZ added to other antianginal therapies proved to be effective for reducing angina attacks and short-acting nitrate use, increasing angina-free walking distance, and improving patient well-being in a real-life setting, irrespective of angina duration, including patients with recently diagnosed angina. This provides an opportunity for intensification of treatment early on in the disease process, with the aim of decreasing angina burden and improving patient quality of life.Funding
Servier.Trial Registration
ISRCTN identifier ISRCTN65209863.Plain Language Summary
Plain language summary available for this article.11.
Introduction
To present short-term safety and efficacy data of men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) treated with Aquablation.Methods
Men with LUTs secondary to BPH (60–150 cc) underwent Aquablation treatment from February 2016 to December 2017 across 17 investigational sites in the USA from two contemporary investigational device exemption (IDE) studies called WATER (NCT02505919) and WATER II (NCT03123250).Results
One hundred seven males with mean age of 67.3?±?6.5 years were treated with Aquablation; mean prostate volume was 99.4?±?24.1 cc. The pooled results show that large prostates have an average procedure time of less than 36 min and discharge on average 1.6?±?1 days. The IPSS decreased by 16.7?±?8.1 points at 3 months and Qmax increased by 11.2?±?12.4 ml/s. The Clavien-Dindo (CD) grade 2 or higher event rate at 3 months was 29%. A non-hierarchical breakdown for CD events yielded 18% grade 2 and 19% grade 3 or higher.Conclusion
Men with LUTS secondary to BPH (60–150 cc) in a pooled analysis were treated safely and effectively with Aquablation up to 3 months postoperatively.Trial Registration
ClinicalTrials.gov identifiers, NCT02505919 and NCT03123250.Funding
PROCEPT BioRobotics.12.
Elena A. Zheleznykh Yulia A. Danilogorskaya Elena V. Privalova Yury N. Belenkov Anastasia A. Schendrygina Irina S. Chekneva Nikolay A. Pavlov Mikhail I. Tishman 《Advances in therapy》2018,35(10):1698-1712
Introduction
The objective of this study was to assess the impact of a single-pill combination (SPC) of perindopril/indapamide (PER/IND) at full doses (10/2.5 mg) on endothelial and cognitive function as a clinical intermediate marker of vascular improvement.Methods
This open-label, uncontrolled, observational study enrolled 30 patients (20 females and 10 males) with grade II–III uncontrolled arterial hypertension (SBP/DBP ≥ 160/100 mmHg) and no evidence of cerebrovascular disease. All patients underwent assessment of macro- and microvascular endothelial function parameters at baseline and after 12 months of treatment with SPC PER/IND using photoplethysmography and video capillaroscopy. Cognitive function was assessed using the Montreal Cognitive Assessment scale (MoCA).Results
All patients (mean age 60.06 ± 10.19 years) were at high risk for cardiovascular events: mean body mass index (BMI) 31.2 ± 3.9 kg/m2, 33% diagnosed with coronary artery disease angina class I, 30% with impaired glucose tolerance, and 7% with type 2 diabetes. Impaired endothelial function was observed at the both micro- and macrovascular levels. Endothelial function parameters improved after 12-month treatment with SPC PER/IND with an increase in occlusion index from 1.4 to 1.8 (P < 0.00005) and phase shift from 5.0 to 10.8 (P < 0.00001); all values achieved levels in the normal range. Resting capillary network density (CND) increased from 44.8 to 52 cap/mm2 (P < 0.00007), and CND after a venous occlusion test increased from 55 to 61 cap/mm2 (P < 0.006). Signs of cognitive impairment were present at baseline with a mean MoCA score of 23 (normal cognitive function score ≥ 26), but improved after 12-month treatment with a mean MoCA score of 27 (P< 0.0001). Treatment was well tolerated.Conclusion
SPC PER/IND at full doses for 12 months improves endothelial function, structural and functional parameters of the microcirculation, as well as cognitive function in patients with arterial hypertension at high cardiovascular risk.Funding
Les Laboratoires Servier.13.
Sven De Bruycker Christel Vangestel Tim Van den Wyngaert Leonie wyffels An Wouters Patrick Pauwels Steven Staelens Sigrid Stroobants 《Molecular imaging and biology》2016,18(4):606-616
Purpose
The purpose of this study was to characterize imaging biomarkers for the potential benefit of hypoxia-inducible factor-1 (HIF-1)α inhibition (by PX-12) during 5-fluorouracil (5-FU) chemotherapy in the treatment of colorectal cancer (CRC).Procedures
Therapy response to 5-FU?±?PX-12 was assessed with baseline [18F]fluoromisonidazole ([18F]FMISO) and longitudinal 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) positron emission computed tomography (μPET/CT) in CRC xenograft model (n?=?36) during breathing of a hypoxic (10 % O2) or normoxic (21 % O2) atmosphere. Ex vivo, immunohistochemistry was performed.Results
Baseline [18F]FMISO uptake and relative tumor volume (RTV) 2 days after 5-FU or 5-FU?+?PX-12 administration correlated significantly (p?≤?0.01). Under hypoxic breathing conditions, [18F]FDG uptake (?53.1?±?8.4 %) and Ki67 expression (?16 %) decreased and RTV stagnated in the 5-FU?+?PX-12 treatment group, but not in 5-FU alone-treated tumors. Under normoxic breathing, [18F]FDG uptake (?23.5?±?15.2 % and ?72.8?±?7.1 %) and Ki67 expression (?5 % and ?19 %) decreased and RTV stagnated in both the 5-FU and the combination treatment group, respectively.Conclusion
Baseline [18F]FMISO μPET may predict the beneficial effect of HIF-1α inhibition during 5-FU chemotherapy in CRC.14.
Hideaki Jinnouchi Kazunari Nozaki Hirotaka Watase Hirohisa Omiya Soichi Sakai Yoshishige Samukawa 《Advances in therapy》2016,33(3):460-479
Introduction
We investigated the impact of reduced renal function on 24-h glucose variability in Japanese patients with type 2 diabetes mellitus (T2DM) treated with luseogliflozin.Methods
In this double-blind, placebo-controlled, crossover study, 37 Japanese patients with T2DM [glycated hemoglobin (HbA1c) 7.0–10.0%] and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2 were randomized into two groups in which patients first received luseogliflozin then placebo, or vice versa, for 7 days each. Twenty-four-hour glucose variability was measured on day 7 in each period and was compared among patients divided into three groups according to their baseline eGFR (mL/min/1.73 m2): normal (≥90; n = 13; normal group), normal-to-mildly reduced renal function (≥75 to <90; n = 12; normal–mild group), and mild-to-moderately reduced renal function (<75; n = 9; mild–moderate group).Results
The mean [95% confidence interval (CI)] placebo-subtracted 24-h cumulative urinary glucose excretion (g) was 82.1 (72.7, 91.5), 82.5 (73.4, 91.5), and 62.2 (51.2, 73.3); the placebo-subtracted 24-h mean glucose concentration (mg/dL) was ?24.39 (?32.53, ?16.26), ?28.28 (?39.35, ?17.22), and ?11.53 (?23.93, 0.86); and the placebo-subtracted peak postprandial glucose (mg/dL) was ?26.9 (?46.9, ?6.9), ?38.1 (?59.6, ?16.6), and 1.5 (?25.5, 28.4) in the normal, normal–mild, and mild–moderate groups, respectively. The mean lowest glucose concentrations (placebo vs. luseogliflozin, mg/dL) decreased to similar levels in the normal (115.4 vs. 93.4), normal–mild (121.0 vs. 97.9), and mild–moderate (104.0 vs. 91.1) groups.Conclusion
This post hoc subanalysis revealed that although mild-to-moderately reduced renal function attenuated the glucose-lowering effects of luseogliflozin on peak postprandial glucose, it did not attenuate the effects of luseogliflozin on fasting glucose. These findings may explain the smaller increase in urinary glucose excretion in these patients relative to patients with normal renal function or normal-to-moderately reduced renal function. Further studies may be needed to examine these findings in large populations of patients with T2DM and reduced renal function.Trial registration
JapicCTI-142548.Funding
Taisho Pharmaceutical Co., Ltd.15.
Jiun-Cheng Hsu Po-Han Chen Kuo-Chin Huang Yao-Hung Tsai Wei-Hsiu Hsu 《Journal of Medical Ultrasonics》2017,44(4):297-303
Purpose
The gray-level histogram of ultrasound is a promising tool for scanning the hypoechogenic appearance of supraspinatus tendinopathy, and the aim of this study was to test the hypothesis that the gray-level value of the supraspinatus tendon in the painful shoulder has a lower value on B-mode images even though in different ultrasound devices.Methods
Sixty-seven patients who had unilateral shoulder pain with rotator cuff tendinopathy underwent bilateral shoulder ultrasonography, and we compared the mean gray-level values of painful shoulders and contralateral shoulders without any pain in each patient using two ultrasound devices. The echogenicity ratio (symptomatic/asymptomatic side) of two ultrasound devices was compared.Results
A significant difference existed between the symptomatic shoulder and contralateral asymptomatic shoulder (p < 0.001) on the mean gray-level value measurements of each device. The symptomatic-to-asymptomatic tendon echogenicity ratio of device A was 0.919 ± 0.090 in the transverse plane and 0.937 ± 0.081 in the longitudinal plane, and the echogenicity ratio of device B was 0.899 ± 0.113 in the transverse plane and 0.940 ± 0.113 in the longitudinal plane.Conclusions
The decline of the mean gray-level value and the echogenicity ratio of the supraspinatus tendon in the painful shoulder may be utilized as a useful sonographic reference of unilateral rotator cuff lesions.Level of evidence
Diagnostic level III.16.
Syed Imran Ayaz Craig M. Sharkey Gregory M. Kwiatkowski Suprat Saely Wilson Reba S. John Rosa Tolomello Arushi Mahajan Scott Millis Phillip D. Levy 《International journal of emergency medicine》2016,9(1):28
Background
Afterload reduction with bolus enalaprilat is used by some for management of acute hypertensive heart failure (HF) but existing data on the safety and effectiveness of this practice are limited. The purpose of this study was to evaluate the clinical effects of bolus enalaprilat when administered to patients with acute hypertensive heart failure.Findings
We performed an IRB-approved retrospective cohort study of patients who presented to the emergency department of a large urban academic hospital. Patients were identified by pharmacy record and included if they received enalaprilat intravenous (IV) bolus in the setting of acute hypertensive HF. A total of 103 patients were included. Patients were hypertensive on presentation (systolic blood pressure [SBP]?=?195.2 [SD?±?32.3]?mmHg) with significantly elevated mean NT-proBNP levels (3797.8 [SD?±?6523.2]?pg/ml). The mean dose of enalaprilat was 1.3 [SD?±?0.7]?mg, with most patients (76.7%) receiving a single 1.25 mg bolus. By 3 h postenalaprilat, SBP had decreased substantially (?30.5 mmHg) with only 2 patients (1.9%) developing hypotension. Renal function was unaffected, with no significant change in serum creatinine by 72 h. In the 30 days post-admission, patients spent an average of 23 [SD?±?7.5]?days alive and out of hospital.Conclusions
In this retrospective cohort of acute hypertensive HF patients, bolus IV enalaprilat resulted in a substantial reduction in systolic BP without adverse effect.17.
Luc Martinez Alfred Penfornis Jean-Francois Gautier Eveline Eschwège Guillaume Charpentier Amira Bouzidi Pierre Gourdy 《Advances in therapy》2017,34(3):674-685
Introduction
The objective of this subgroup analysis is to investigate the effectiveness of liraglutide in people with type 2 diabetes (T2D) treated within the primary care physician (PCP) and specialist care settings.Methods
EVIDENCE is a prospective, observational study of 3152 adults with T2D recently starting or about to start liraglutide treatment in France. We followed patients in the PCP and specialist settings for 2 years to evaluate the effectiveness of liraglutide in glycemic control and body weight reduction. Furthermore, we evaluated the changes in combined antihyperglycemic treatments, the reasons for prescribing liraglutide, patient satisfaction, and safety of liraglutide in these two treatment settings.Results
After 2 years of follow-up, 477 out of 1209 (39.0%) of PCP and 297 out of 1398 (21.2%) of specialist-treated patients still used liraglutide and maintained the glycated hemoglobin (HbA1c) target of <7.0%. Significant reductions from baseline were observed in both PCP- and specialist-treated cohorts in mean HbA1c (?1.22% and ?0.8%, respectively), fasting plasma glucose (FPG) concentration (?39 and ?23 mg/dL), body weight (?4.4 and ?3.8 kg), and body mass index (BMI) (?1.5 and ?1.4 kg/m2), all p < 0.0001. Reductions in HbA1c and FPG were significantly greater among PCP- compared with specialist-treated patients, p < 0.0001 for both. Patient treatment satisfaction was also significantly increased in both cohorts. Reported gastrointestinal adverse events were less frequent among PCP-treated patients compared with specialist-treated patients (4.5% vs. 16.1%).Conclusion
Despite differences in demography and clinical characteristics of patients treated for T2D in PCP and specialty care, greater reduction in HbA1c and increased glycemic control durability were observed with liraglutide in primary care, compared with specialist care. These data suggest that liraglutide treatment could benefit patients in primary care by delaying the need for further treatment intensification.Trial Registration
ClinicalTrials.gov identifier, NCT01226966.Funding
Novo Nordisk A/S.18.
Sabina Stumpf Heike Jaeger Tilmann Graeter Suemeyra Oeztuerk Julian Schmidberger Mark Martin Haenle Wolfgang Kratzer The Elasto-Study Group Ulm 《Abdominal imaging》2016,41(7):1310-1316
Purpose
A variety of elastographic techniques have been developed to facilitate the non-invasive assessment of tissue properties. The goal of the study was to examine the influence of gender, age, BMI, alcohol consumption, and smoking in healthy volunteers.Methods
Of the 263 participants who met all the study inclusion criteria, 234 had successful measurements. The examination was performed with the Siemens Acuson S3000 (Siemens Healthcare, Erlangen, Germany), using the 6C1 curved array transducer with the virtual touch tissue quantification (VTQ) method.Results
The values determined with the curved array in the head of the pancreas were 1.44 ± 0.39 m/s for women and 1.19 ± 0.29 m/s for men; in the body, the results were 1.49 ± 0.37 m/s for women and 1.26 ± 0.30 m/s for men; in the tail, the corresponding values were 1.29 ± 0.36 m/s for women and 1.05 ± 0.30 m/s for men. Comparison of gender showed that men have significantly lower mean values than women. There were significantly higher values in all parts of the organ with the increasing age of the participants (p < 0.0001). For BMI, there was a significant correlation with the values only when considering the BMI in continuous form. Alcohol consumption and smoking did not have any significant effects.Conclusions
ARFI-VTQ is qualified for use on pancreatic tissue. Further studies are required to examine the influence of other factors in larger populations.19.
Frerichs I Schiffmann H Oehler R Dudykevych T Hahn G Hinz J Hellige G 《Intensive care medicine》2003,29(5):787-794
Objective
The aim of our study was to determine the effect of the irregular spontaneous breathing pattern and posture on the spatial distribution of ventilation in neonates free from respiratory disease by the non-invasive imaging method of electrical impedance tomography (EIT). Scanning of spontaneously breathing neonates is the prerequisite for later routine application of EIT in babies with lung pathology undergoing ventilator therapy.Design
Prospective study.Setting
Neonatal intensive care unit at a university hospital.Patients
Twelve pre-term and term neonates (mean age: 23 days; mean body weight: 2,465 g; mean gestational age: 34 weeks; mean birth weight: 2,040 g).Interventions
Change in body position in the sequence: supine, right lateral, prone, supine.Measurements and results
EIT measurements were performed using the Göttingen GoeMF I system. EIT scans of regional lung ventilation showing the distribution of respired air in the chest cross-section were generated during phases of rapid tidal breathing and deep breaths. During tidal breathing, 54.5±8.3%, 55.2±10.5%, 59.9±8.4% and 54.2±8.5% of inspired air (mean values ± SD) were directed into the right lung in the supine, right lateral, prone and repeated supine postures respectively. During deep inspirations, the right lung ventilation accounted for 52.6±7.9%, 68.5±8.5%, 55.4±8.2% and 50.5±6.6% of total ventilation respectively.Conclusion
The study identified the significant effect of breathing pattern and posture on the spatial distribution of lung ventilation in spontaneously breathing neonates. The results demonstrate that changes in regional ventilation can easily be determined by EIT and bode well for the future use of this method in paediatric intensive care.20.
Maisch S Boehm SH Weismann D Reissmann H Beckmann M Fuellekrug B Meyer A Schulte Am Esch J 《Intensive care medicine》2007,33(5):912-916