共查询到20条相似文献，搜索用时 31 毫秒
1.
Tomohiro Kusawake Donna Kowalski Akitsugu Takada Kota Kato Masataka Katashima James J. Keirns Michaelene Lewand Kenneth C. Lasseter Thomas C. Marbury Richard A. Preston 《Advances in therapy》2017,34(12):2612-2624
Introduction
Amenamevir (ASP2151) is a nonnucleoside human herpesvirus helicase-primase inhibitor that was approved in Japan for the treatment of herpes zoster (shingles) in 2017. This article reports the results of two clinical trials that investigated the effects of renal and hepatic impairment on the pharmacokinetics of amenamevir.Methods
These studies were phase 1, open-label, single-dose (oral 400 mg), parallel-group studies evaluating the pharmacokinetics, safety, and tolerability of amenamevir in healthy participants and participants with moderate hepatic impairment and mild, moderate, and severe renal impairment.Results
In the hepatic impairment study, the pharmacokinetic profile of amenamevir in participants with moderate hepatic impairment was generally similar to that of participants with normal hepatic function. In the renal impairment study, the area under the amenamevir concentration versus time curve from the time of dosing up to the time of the last sample with extrapolation to infinity of the terminal phase was increased by 78.1% in participants with severe renal impairment. There was a positive relationship between creatinine clearance and oral and renal clearance for amenamevir in the renal impairment study. In both studies, amenamevir was safe and well tolerated.Conclusion
The findings of the hepatic impairment study indicate that no dosing adjustment is required in patients with moderate hepatic impairment. In the renal impairment study, systemic amenamevir exposure was increased by renal impairment. However, it is unlikely that renal impairment will have a significant effect on the safety of amenamevir given that in previous pharmacokinetic and safety studies in healthy individuals amenamevir was safe and well tolerated after a single dose (5–2400 mg, fasted condition) and repeated doses for 7 days (300 or 600 mg, fed condition), and the amount of amenamevir exposure in the renal impairment study was covered by those studies. These findings suggest that amenamevir does not require dosage reduction in accordance with the creatinine clearanceFunding
Astellas Pharma.2.
Yuichiro Yamada Yasuo Terauchi Hirotaka Watada Yasuhiko Nakatsuka Kazuhito Shiosakai Takuo Washio Takashi Taguchi 《Advances in therapy》2018,35(3):367-381
Introduction
G protein-coupled receptor 119 (GPR119) is a promising target for the treatment of type 2 diabetes mellitus (T2DM), as both insulin and glucagon-like peptide-1 secretion can be promoted with a single drug. We compared the efficacy and safety of the GPR119 agonist DS-8500a with placebo and sitagliptin 50 mg in Japanese patients with T2DM.Methods
This randomized, double-blind, parallel-group comparison study was conducted in Japan (trial registration NCT02628392, JapicCTI-153068). Eligible patients aged ≥ 20 years with T2DM and hemoglobin A1c (HbA1c) ≥ 7.0% and < 10.0% were randomized to receive placebo, DS-8500a (25, 50, or 75 mg), or sitagliptin 50 mg once daily for 12 weeks. The primary efficacy endpoint was change in HbA1c from baseline to week 12. Secondary endpoints included change in fasting plasma glucose (FPG), glucose AUC0–3h during a meal tolerance test, 2-hour postprandial glucose (2hr-PPG), and changes in lipid parameters (total, low-density lipoprotein (LDL-) and high-density lipoprotein (HDL-) cholesterol, and triglycerides) at week 12. Safety endpoints included adverse events, hypoglycemia, and clinical/laboratory variables.Results
DS-8500a demonstrated dose-dependent HbA1c lowering compared with placebo at week 12: change from baseline ? 0.23% (p = 0.0173), ? 0.37% (p = 0.0001), and ? 0.44% (p < 0.0001) in the 25-mg, 50-mg, and 75-mg groups, respectively. At 50- and 75-mg doses, DS-8500a significantly lowered FPG, glucose AUC0–3h, and 2hr-PPG compared with placebo. The glucose-lowering effect was maintained up to 12 weeks. DS-8500a did not lower any of the above parameters to a greater extent than sitagliptin. Compared with placebo and sitagliptin, DS-8500a 50 and 75 mg significantly reduced total cholesterol, LDL-cholesterol, and triglycerides, and significantly increased HDL-cholesterol. All DS-8500a doses were well tolerated. Two cases of clinically relevant drug-related hypoglycemia occurred in the DS-8500a 50-mg group.Conclusion
DS-8500a was well tolerated and demonstrated significant glucose-lowering effects and favorable changes in lipid profiles up to 12 weeks in Japanese patients with T2DM.Funding
Daiichi Sankyo Co. Ltd.3.
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.4.
Background
Disseminated intravascular coagulation (DIC) is associated with high mortality in patients with sepsis. Several studies reporting that recombinant human soluble thrombomodulin (rhTM) reduced mortality in sepsis patients. This retrospective cohort study aimed to evaluate the efficacy of rhTM for patients with mild coagulopathy compared with those with severe coagulopathy.Methods
We evaluated about 90-day mortality and SOFA score. SOFA score was also evaluated for the following components: respiratory, cardiovascular, hepatic, renal and coagulation.Results
All 69 patients were diagnosed with sepsis, fulfilled Japanese Association for Acute Medicine criteria for DIC, and were treated with rhTM. Patients were assigned to either the mild coagulopathy group (did not fulfill the International Society on Thrombosis and Haemostasis overt DIC criteria) or the severe coagulopathy group (fulfilled overt DIC criteria). The 90-day mortality was significant lower in severe coagulopathy group than mild coagulopathy group (P?=?0.029). Although the SOFA scores did not decrease in the mild coagulopathy group, SOFA scores decreased significantly in the severe coagulopathy group. Furthermore the respiratory component of the SOFA score significant decreased in severe coagulopathy group compared with mild coagulopathy group.Conclusions
rhTM administration may reduce mortality by improving organ dysfunction especially for respiratory in septic patients with severe coagulopathy.5.
Camilla Bock Jens Drachmann Bukh Maj Vinberg Ulrik Gether Lars Vedel Kessing 《Clin Pract Epidemiol Ment Health》2009,5(1):4
Objective
To validate the ICD-10 diagnosis of a single depressive episode as used in daily clinical psychiatric practice and as recorded in the Danish Psychiatric Central Research Register.Methods
Patients discharged with a diagnosis of a single depressive episode were consecutively sampled from the register and diagnosed according to an interview using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN).Results
A total of 75.4% of 399 patients with a register diagnosis of a single depressive episode also got this diagnosis according to the SCAN interview (82.8% for severe type of a single depression, 76.0% for moderate type of a single depression and 65.2% for mild type of a single depression).Conclusion
The ICD-10 diagnosis of a single depressive episode can be used in daily clinical practice with sufficient precision. The validity of the diagnosis is highest for severe and moderate type of depression and decreases for mild depression.6.
7.
Background
Pain, restriction of mobility and cognitive impairment are often present in old age and intensify each other.Objectives
Is there a relationship between mobility, pain, cognitive capacity, diagnoses and number of prescribed medication for residents of nursing homes?Methods
Subgroup analysis of the baseline data from an intervention study for optimization of the medication safety of 120 nursing home residents.Results
Pain was presumed in 77.8% of the residents. Persons with cognitive impairment were more frequently affected. The results of the observational and self-reported pain assessment in cognitively impaired patients did not agree for two-thirds of the cases. A correlation between prevalence of pain, pain intensity and mobility could only be shown for persons without cognitive impairment. Half of the persons were unable to walk; 80% of the residents with analgesics as a permanent medication were more restricted in their mobility.Conclusions
Cognitive impairment is associated with pain and reduced mobility, whereby self-rated pain did not concur with the observational pain assessment for two-thirds of the residents with cognitive impairment. This illustrates the difficulty of observational pain assessment.8.
Lin Ma Ping Li Jianping Tang Yifeng Guo Chunping Shen Jing Chang Nabil Kerrouche 《Advances in therapy》2017,34(12):2601-2611
Introduction
Delaying or preventing flares is important in atopic dermatitis (AD) management. The objective of the study was to evaluate whether using a ceramide-containing moisturizer in addition to a body wash during latent AD can delay flares.Methods
This was a randomized, investigator-blinded, parallel-group, controlled study among Chinese children with a history of mild to moderate AD, within 1 week of successful treatment with a topical corticosteroid. Subjects were randomized to receive moisturizer twice daily and body wash once daily, or body wash alone once daily for 12 weeks. The primary efficacy endpoint was time to flare [necessitating medical therapy and/or Investigator Global Assessment (IGA) > 1 (at least mild AD)]. Other efficacy endpoints were AD characteristics and emollient effects. The patient-reported outcome comprised satisfaction at week 12. The safety endpoint was incidence of undesirable events.Results
A total of 64 subjects aged 2–12 years were randomized. Median time to flare was delayed by nearly 2 months for moisturizer/body wash compared to body wash alone (89 vs. 27 days, respectively). A significantly earlier onset of action in terms of fewer flares favoring moisturizer was found at week 4 (31 vs. 59%, respectively, p = 0.022), and after 12 weeks, fewer flares occurred (50 vs. 72%). At week 12 for flare-free subjects, nearly half in both groups had clear IGA, and an emollient effect in terms of less dryness or burning was more marked for moisturizer/body wash. Both products led to high patient satisfaction and were well tolerated.Conclusion
A regimen incorporating a moisturizer plus body wash delayed AD flares by nearly 2 months compared to body wash alone, and yielded high patient satisfaction.Funding
Galderma R&D.Trial Registration
ClinicalTrials.gov identifier, NCT02589392.9.
Introduction
This study compared the efficacy and safety of two mesalazine formulations in the treatment of Chinese patients with mildly to moderately active ulcerative colitis (UC).Methods
In this multicenter, single-blind, randomized controlled study of 251 patients with active UC conducted from November 2010 to January 2012, subjects were randomized to treatment with mesalazine modified-release tablets (MR group, n = 123) or enteric-coated tablets (EC group, n = 128) at 800 mg three-times daily for 8 weeks. The primary efficacy measure was the decrease in UC Disease Activity Index (UCDAI) at final evaluation. If the 95% confidence interval (CI) lower limit of the difference of the decrease in UCDAI between groups was over ?1.0, mesalazine modified-release tablets were considered non-inferior to mesalazine enteric-coated tablets. The change in UCDAI in patients with mild and moderate (UCDAI 3–5 and 6–8 at enrollment, respectively) UC was analyzed. Secondary efficacy measures were remission and efficacy rates. Incidences of adverse drug reactions (ADRs) were calculated.Results
The decreases in UCDAI at final evaluation were 2.84 and 2.56 in the MR and EC groups, respectively, with a difference of 0.27 between groups (95% CI ?0.34, 0.88). The remission rates were 48.33% (58/120) and 55.65% (69/124), and the efficacy rates were 63.33% (76/120) and 66.94% (83/124) in the MR and EC groups, respectively (all P > 0.05). In patients with mild UC, the decreases in UCDAI were 2.16 and 2.05 in the MR and EC groups, respectively, while in patients with moderate UC they were 3.49 and 3.03, respectively (all P > 0.05). The incidences of ADRs in the MR and EC groups were 6.61% (8/121) and 10.24% (13/127), respectively (P > 0.05). No serious ADRs were reported during the study.Conclusion
Mesalazine modified-release tablets are non-inferior to enteric-coated tablets and are an effective and safe treatment option in Chinese patients with mildly to moderately active UC.Trial registration
ClinicalTrials.gov identifier: NCT01257386.Funding
Tillotts Pharma AG.10.
Objective
To compare the safety and estimate the response profile of olanzapine, a second-generation antipsychotic, to haloperidol in the treatment of delirium in the critical care setting.Design
Prospective randomized trialSetting
Tertiary care university affiliated critical care unit.Patients
All admissions to a medical and surgical intensive care unit with a diagnosis of delirium.Interventions
Patients were randomized to receive either enteral olanzapine or haloperidol.Measurements
Patient’s delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium.Main results
Delirium Index decreased over time in both groups, as did the administered dose of benzodiazepines. Clinical improvement was similar in both treatment arms. No side effects were noted in the olanzapine group, whereas the use of haloperidol was associated with extrapyramidal side effects.Conclusions
Olanzapine is a safe alternative to haloperidol in delirious critical care patients, and may be of particular interest in patients in whom haloperidol is contraindicated.11.
Objective
Imbalance of the renal medullary oxygen supply/demand relationship can cause hypoxic medullary damage and ischaemic acute renal failure (ARF). The use of mannitol for prophylaxis/treatment of clinical ischaemic ARF is controversial and the effect of mannitol on renal oxygenation in man has not yet been investigated. We evaluated the effects of mannitol on renal oxygen consumption (RVO2), renal blood flow (RBF) and glomerular filtration rate (GFR) in postoperative patients.Design
Prospective interventional study.Setting
University hospital cardiothoracic ICU.Patients
Ten uncomplicated mechanically ventilated and sedated postcardiac surgery patients with preoperatively normal renal function.Interventions
Mannitol infusion (225 mg/kg + 75 mg/kg/h) and combined mannitol and furosemide infusion (0.25 mg/kg + 0.25 mg/kg/h).Measurements and results
Systemic haemodynamics were evaluated by a pulmonary artery catheter. RBF and GFR were measured by the renal vein thermodilution technique and by renal extraction of 51Cr–EDTA, respectively. Mannitol increased urine flow (60%), GFR (20%) and filtration fraction (FF) (20%) with no change in RBF. This was accompanied by an increase in renal sodium reabsorption (18%), RVO2 (19%) and renal oxygen extraction (21%). When combined with mannitol, furosemide normalised sodium reabsorption, RVO2, renal oxygen extraction with no change in RBF, while GFR and FF were still elevated compared to control.Conclusions
In patients with normal renal function, mannitol increases GFR, which increases tubular sodium load, sodium reabsorption and RVO2 after cardiac surgery. The lack of effect on RBF, indicates that mannitol impairs the renal oxygen supply/demand relationship. Furosemide normalised renal oxygenation when combined with mannitol.12.
Background
There is little published guideline or evidence on treating bipolar affective disorder in patients with renal failure having haemodialysis.Case
We present two patients with bipolar affective disorder with renal failure having haemodialysis. We used lorazepam in one patient to manage the immediate risk of non-engagement with dialysis. Risperidone was added in the second patient for managing psychotic symptoms. Valproate was started as a mood stabiliser and titrated upwards for long-term management of the illness.Conclusion
We discuss the similarities in the two cases and the care plan we used to manage them.13.
Aims
Create an educational program in chronic pain (EPCP).Material and methods
We used a four-step process to create the EPCP tailored to patient’s needs.Results
Five groups of patients can benefit from the program annually. Based on their own assessment, patients stated that their knowledge of chronic pain improved between 2.8 to 24%. The satisfaction with the EPCP was 8.67/10.Conclusion
Our EPCP helps patients gain and maintain the skills they need to best manage their lives with a chronic pain.14.
15.
Fredrik Nyberg Laura Horne Robert Morlock Javier Nuevo Chris Storgard Lalitha Aiyer Dionne M. Hines Xavier Ansolabehere Pierre Chevalier 《Advances in therapy》2016,33(7):1180-1198
Introduction
Patients with gout have numerous comorbidities. We aimed to estimate the prevalence and incidence rates of renal and cardiovascular morbidities in trial-aligned patients with established gout in Germany (DE), the United Kingdom (UK), the United States (US), and France (FR).Methods
This longitudinal cohort study used retrospective data from IMS Disease Analyzer? (DE, FR), Clinical Practice Research Datalink–Hospital Episode Statistics (UK), and IMS’ PharMetrics Plus database linked with outpatient laboratory results (US). Included patients were ≥18 years at index date (January 1, 2010; all dates +1 year for FR), with continuous enrollment during the pre-index year, had “prevalent established gout” determined by data in the pre-index year, and ≥1 documented visit after index date; additional inclusion/exclusion criteria were aligned with recent gout clinical trials. Look-back for comorbidity prevalence extended to January 1, 2003 (US: January 1, 2009). Follow-up for incidence extended from index date to at most March 26, 2013 (FR: May 31, 2014). Events of interest were identified by diagnostic codes and/or laboratory data.Results
The trial-aligned cohorts included 35,118 (DE), 24,607 (UK), 121,591 (US), and 17,338 (FR) patients. Among renal conditions, baseline diagnosis of chronic kidney disease/renal failure was most prevalent in the UK followed by DE; abnormal serum creatinine was most prevalent in the UK. Hypertension was the most prevalent cardiovascular diagnosis in all countries, followed by ischemic heart disease (IHD) and myocardial infarction. Incidence rates (per 100 patient-years) for new/worsening renal impairment ranged from 1.67 (DE) to 4.34 (US) and for nephrolithiasis diagnosis from 0.31 (FR) to 3.79 (US). The incidence rates for hypertension diagnosis were highest among cardiovascular-related events, ranging from 3.23 (UK) to 20.27 (US), followed by IHD.Conclusions
Patients with established gout such as those included in gout trials have a high burden of established morbidity and new diagnoses of morbid events. Consideration of comorbidities, which greatly exacerbate disease burden, is important in gout management.Funding
AstraZeneca.16.
Introduction
The objective of this prospective, multicenter, parallel-group, non-interventional clinical trial (NIT) was to characterize the effectiveness of a treatment with the phytomedicines ELOM-080 and BNO 1016 in patients with acute rhinosinusitis (ARS).Methods
A total of 228 patients suffering from ARS took part in this NIT and were treated for a maximum of 14 days with either BNO 1016 or ELOM-080. Focus was on improvement of rhinosinusitis-associated pain/discomfort and nasal congestion in real-life conditions of primary care setting, as assessed by numeric and verbal rating scale, and five-point Likert scale.Results
The course of the key ARS symptom facial pain demonstrated a faster recovery in patients with ELOM-080, when compared to BNO 1016. ELOM-080 tended to be superior for several ancillary criteria and induced significantly higher patient satisfaction with regard to the improvement of feeling of general illness. Physicians assessed both products to be very effective and well tolerated. Adverse drug reactions classified as gastrointestinal disorders occurred in both groups to a comparable extent.Conclusion
This trial demonstrated comparable effectiveness of a therapy of ARS with the phytomedicines ELOM-080 and BNO 1016, although the treatment with ELOM-080 resulted in a more rapid and more complete recovery in ARS key symptoms and tended to be superior for several ancillary criteria. Both treatments were well tolerated.Trial registration number
NIS-6471.Funding
G. Pohl-Boskamp GmbH & Co. KG.17.
Anna I. Guerdjikova Brandon Walsh Kevin Shan Amy E. Halseth Eduardo Dunayevich Susan L. McElroy 《Advances in therapy》2017,34(10):2307-2315
Introduction
Binge eating disorder (BED) is associated with obesity and major depressive disorder (MDD). Naltrexone extended-release (ER)/bupropion ER (NB) is approved as an adjunct to diet and physical activity for chronic weight management. In a prospectively designed 24-week open-label, single-arm, single-site trial of 25 women with MDD and overweight/obesity, NB reduced weight and depressive symptoms.Methods
This post hoc analysis investigated the relationship between change in self-reported binge eating behavior (evaluated with the Binge Eating Scale [BES]) and changes in weight, control of eating, and depressive symptoms.Results
At baseline, 91% of subjects had moderate or severe BES scores, suggesting BED. BES scores were significantly improved from week 4, and by week 24, 83% reported “little or no problem.” Improvement in BES scores correlated with improvement in depressive symptoms and control of eating.Conclusion
NB may be effective in reducing binge eating symptoms associated with MDD and overweight/obesity. Evaluation of NB in BED appears warranted.Funding
Orexigen Therapeutics, Inc.18.
Rachel McDonald Keyue Ding Edward Chow Ralph M. Meyer Abdenour Nabid Pierre Chabot Genevieve Coulombe Shahida Ahmed Joda Kuk Rashid Dar Aamer Mahmud Alysa Fairchild Carolyn F. Wilson Jackson S. Y. Wu Kristopher Dennis Carlo DeAngelis Rebecca K. S. Wong Liting Zhu Michael Brundage 《Supportive care in cancer》2016,24(12):4871-4878
Purpose
Previous studies have determined optimal cut points (CPs) for the classification of pain severity as mild, moderate, or severe using only the Brief Pain Inventory (BPI) or the BPI in conjunction with a quality of life (QOL) tool. The purpose of our study was to determine the optimal CPs based on correlation with only QOL outcomes.Methods
We conducted an analysis of 298 patients treated with radiation therapy for painful bone metastases on a phase III randomized trial. Prior to treatment, patients provided their worst pain score on a scale of 0 (no pain) to 10 (worst possible pain), as well as completed the European Organization of Cancer Research and Treatment (EORTC) QOL Questionnaire Bone Metastases module (QLQ-BM22) and the EORTC QOL Questionnaire Core-15 Palliative (QLQ-C15-PAL). Optimal CPs were determined to be those that yielded the largest F ratio for the between category effect on each subscale of the QLQ-BM22 and QLQ-C15-PAL using the multivariate analysis of variance (MANOVA).Results
The two largest F ratios for Wilk’s λ, Pillai’s Trace, and Hotelling’s Trace were for CPs 5,6 and 5,7. Combining both, the optimal CPs to differentiate between mild, moderate, and severe pain were 5 and 7. Pain scores of 1–5, 6, and 7–10 were classified as mild, moderate, and severe, respectively. Patients with severe pain experienced greater functional interference and poorer QOL when compared to those with mild pain.Conclusion
Our results suggest that, based on the impact of pain on QOL measures, pain scores should be classified as follows: 1–5 as mild pain, 6 as moderate pain, and 7–10 as severe pain. Optimal CPs vary depending on the type of outcome measurement used.19.
Maneesh Gupta 《Clin Pract Epidemiol Ment Health》2007,3(1):12
Background
Quetiapine causes less prolactin elevation and/or galactorrhoea than other atypical antipsychotics.Case Presentation
Ms AB had galactorrhoea and raised prolactin levels at only 100 mg of quetiapine daily.Conclusion
Low dose quetiapine can also cause galactorrhoea.20.
Anton Petrov Natalia Perekhvatova Maxim Skulachev Linda Stein George Ousler 《Advances in therapy》2016,33(1):96-115