共查询到20条相似文献，搜索用时 46 毫秒
1.
Eric Lawitz Mohamed Bidair Thomas Marbury Christopher T. Jones Avantika Barve Baldur Magnusson David T. Barkan Ursula Bodendorf Kathryn Bracken Erica Canino Darlene Chen Kristina Dabovic Tycho Heimbach Marjorie Ison Catherine L. Jones Steven J. Kovacs Jay P. Lakshman Bin Li Richard A. Colvin 《Clinical therapeutics》2018,40(9):1567-1581.e4
Purpose
Infection with hepatitis C virus is the leading cause of infectious disease mortality in the United States. BZF961 is a novel small molecule inhibitor of the hepatitis C virus NS3-4A protease. Here we present the results of a randomized, double-blinded, placebo-controlled, multicentered study in treatment-naïve patients with chronic hepatitis C virus genotype-1 infection.Methods
Patients were enrolled sequentially in 2 parts and treated for 3days. BZF961 was administered as monotherapy (500mg BID for 3 days) or in combination with the cytochrome P450 3A4 inhibitor ritonavir to boost its exposure (BZF961 10, 20, or 50mg QD or BID).Findings
BZF961 was safe and well tolerated in the patients studied with no serious adverse events. There were no appreciable differences in adverse events among patients who received BZF961, BZF961 with ritonavir, or placebo. There was a significant, clinically meaningful reduction in viral load from baseline in patients treated either with BZF961 500mg every 12hours alone or BZF961 50mg every 12hours in combination with ritonavir. Activity against the hepatitis C virus of the lower-dose regimens was apparent but more modest. There were no relevant changes from baseline viral loads in placebo-treated patients.Implications
Coadministration of ritonavir with BZF961 boosted BZF961 exposure (including Cmin, which is the clinically relevant parameter associated with antiviral activity) in a therapeutic range with less variability compared with BZF961 alone. For strategic reasons, BZF961 is no longer under development. 相似文献2.
Kwadwo A. Yeboah Amy Allspaw Akram Al-Makki Brian M. Shepler 《Clinical therapeutics》2018,40(9):1592-1595
Purpose
Several antihypertensive medications have been associated with various forms of sexual dysfunction. We present a case report of a premenopausal patient with hydralazine-associated amenorrhea.Methods
The Naranjo adverse drug reaction probability scale was used to assess causality. We also performed a literature search on PubMed to find publications that report hydralazine-associated amenorrhea.Results
The Naranjo scale generated a score of 6, suggesting a probable relationship between amenorrhea and hydralazine therapy. No publications associating hydralazine with amenorrhea were identified.Implications
A probable relationship exists between hydralazine and the development of amenorrhea. 相似文献3.
Purpose
Respiratory syncytial virus (RSV) and influenza are important viral pathogens worldwide. Children, in particular, bear considerable burdens of morbidity and mortality associated with these viruses. There are limited therapeutic options for children infected with RSV or influenza. This review focuses on therapeutics for RSV and influenza that are currently under clinical investigation.Methods
This study used a systematic approach to identify prospective therapeutics in clinical trials and briefly reviewed those that are currently available for use in adults and children.Findings
Overall, we found 14 investigational drugs currently in clinical trials for RSV and 20 investigation drugs currently in clinical trials for influenza. These candidates range in development from Phase I to Phase III clinical trials.Implications
Both RSV and influenza are targets for active therapeutic research, and promising candidates for both viruses are currently in clinical development. 相似文献4.
Xiaojiao Li Hong Chen Junqi Niu Guiling Chen Gong Shen Benedetta Massetto Diana M. Brainard Xiaoxue Zhu Hong Zhang Yanhua Ding 《Clinical therapeutics》2018,40(9):1556-1566
Purpose
The purpose of this study was to investigate the safety, tolerability, and pharmacokinetic profile of sofosbuvir and its metabolites after a single dose of sofosbuvir 400mg and once daily dosing of sofosbuvir 400mg for 7days in healthy Chinese subjects.Methods
This Phase I, open-label, single- and multiple-dose study enrolled 14 Chinese subjects aged 18 to 45years with an approximately even distribution of healthy male (n?=?9) and nonpregnant, nonlactating female subjects (n?=?5). Subjects received a single oral dose of sofosbuvir 400mg (one tablet) (morning, fasted conditions; single-dose treatment). After a 3-day washout, subjects received oral sofosbuvir 400mg (one tablet) (morning, fasted) for 7days (multiple dose treatment).Findings
No significant accumulation of sofosbuvir, GS-566500, or GS-331007 was observed. Steady state of the major metabolite GS-331007 was achieved after 4days of consecutive dosing with sofosbuvir 400mg once daily. Sofosbuvir was generally well tolerated.Implications
Overall, this study supports the further evaluation of sofosbuvir 400mg in the Chinese population. The pharmacokinetic properties of sofosbuvir, GS-556500, and GS-311007 were found to be broadly similar in healthy Chinese subjects compared with non-Chinese subjects in previous sofosbuvir studies. ChinaDrugTrials.org.cn identifier: CTR20150249. 相似文献5.
Background
Advanced Practice Registered Nurses (APRNs) provide access to cost-effective, high quality care. APRNs are underutilized in states that restrict their practice. Removing restrictions could expand access to quality health care, cost-effectively relieve the physician shortage, and contribute economically.Purpose
This study forecasts the health system and economic impacts of reducing practice restrictions for Florida APRNs.Methods
The analysis utilized a number of data sources and IMPLAN software and estimated changes in APRN supply given less restrictive practice laws, and consequential health system and economic benefits.Findings
Between 2013 and 2025 APRN full time equivalents could increase an additional 11% with less restrictive practice regulations. This could eliminate or reduce the shortage of different types of physicians. Health care cost-savings could be $50 to $493 per resident. There would be a number of general economic benefits.Discussion
A number of health system and economic benefits would ensue from less restrictive APRN regulation. 相似文献6.
Mami Uchida Hitoshi Kawazoe Shingo Takatori Hiroyuki Namba Ryuji Uozumi Akihiro Tanaka Hiromu Kawasaki Hiroaki Araki 《Clinical therapeutics》2018,40(7):1214-1222.e1
Purpose
Oxaliplatin-induced peripheral neuropathy has remained an unresolved issue in clinical practice. Our previous study hypothesized that inhibition of the renin-angiotensin system (RAS) may produce a preventive effect on oxaliplatin-induced neuropathy. The aim of this study was to clarify whether RAS inhibitors prevent oxaliplatin-induced peripheral neuropathy.Methods
This study retrospectively analyzed data from cancer patients who had received chemotherapy including oxaliplatin and were treated with or without RAS inhibitors. This retrospective observational study was conducted at Ehime University Hospital using electronic medical records from May 2009 to December 2016. The primary end point was the incidence of severe peripheral neuropathy during or after oxaliplatin treatment, according to the Common Terminology Criteria for Adverse Events, version 4.0. A multivariate Cox proportional hazards model analysis was used to identify risk factors.Findings
A total of 150 patients were included in the study. The estimated incidence of peripheral neuropathy was 36.9% and 91.7% in the RAS inhibitor group and the non–RAS inhibitor group, respectively. The multivariate analysis using a Cox proportional hazards model showed that the RAS inhibitor group was slightly associated with a decreased risk of neurotoxicity (adjusted hazard ratio, 0.42 [95% CI, 0.18–0.99]; P?=?0.048).Implications
The present findings suggest that RAS inhibitors have the ability to prevent oxaliplatin-induced peripheral neuropathy. 相似文献7.
Su-jin Rhee Howard Lee Li Young Ahn Kyoung Soo Lim Kyung-Sang Yu 《Clinical therapeutics》2018,40(10):1720-1728.e2
Purpose
Pregabalin and thioctic acid are likely to be used concomitantly for the treatment of painful diabetic neuropathy. In this study, the pharmacokinetic interaction between pregabalin and thioctic acid was investigated at steady state.Methods
A randomized, open-label, 6-sequence, 3-period, 3-treatment crossover study was conducted in 42 healthy male volunteers. The volunteers randomly received pregabalin 300 mg BID for 6 times, thioctic acid 600 mg once daily for 3 times, or the combination of pregabalin and thioctic acid. Serial blood samples were collected up to 24 hours after the last dosing in each period. Pharmacokinetic parameters were calculated by using noncompartmental analysis methods.Findings
The mean concentration–time curves were similar between each drug alone and in combination with the other drug. The 90% CIs of the geometric mean ratios with and without the co-administered drug for Cmax at steady state and AUC during the dosing interval were well within the conventional bioequivalence range of 0.8 to 1.25, except for Cmax at steady state for thioctic acid, which barely exceeded only the lower bound (0.78–1.15). Co-administered pregabalin and thioctic acid was well tolerated.Implications
Repeatedly administered pregabalin and thioctic acid do not interact pharmacokinetically. This study suggests that the combination of pregabalin and thioctic acid can safely be administered concomitantly without dose adjustment. ClinicalTrials.gov identifier: NCT01808300. 相似文献8.
Background
Pragmatic dissemination and implementation (D&I) research approaches can benefit patient care because they emphasize real-world settings and populations. Nurse scientists have an opportunity to reduce the gap between science and practice by using pragmatic D&I research and sustainability strategies.Purpose
This article discusses pragmatic models, methods, and measures used in D&I research and their relevance for nursing research and enhancing population health.Methods
Summary of pragmatic D&I models and related methods for designing a pragmatic studies. We discuss the RE-AIM framework and the PRECIS-2 planning aid and figure in detail. A case study is provided and application to nursing research is discussed.Discussion
Successful translation of pragmatic D&I research demands an approach that addresses external validity, and customization at multiple levels including the patient, clinician, and setting. Context is critically important, and it is never too early to design for dissemination.Conclusions
Pragmatic D&I approaches are needed to speed research translation, reduce avoidable waste of funding, improve clinical care, and enhance population health. Pragmatic D&I research is an area of tremendous opportunity for the nursing science community. 相似文献9.
Purpose
This commentary discusses the therapeutic and economic potentials of regenerative medicine (RM) by addressing how the reprioritization of resources in drug development may alleviate unmet medical need across many diseases, but especially cardiovascular diseases (CVDs) and musculoskeletal diseases (MSDs), the leading causes of mortality and morbidity, respectively, in the United States.Methods
Data and perspectives represented in this commentary were obtained through an online literature search, public press releases from federal agencies and companies, online opinion pieces, published journal articles, and consulting agency reports; however, there were limitations to the available data because of the breadth and novelty of the therapeutic modalities involved.Findings
Currently, the misallocation of resources within the therapeutic areas of CVDs and MSDs are possibly contributing to low approval rates, high cost of drug treatments, and consequently, disease burden. With a 2025 global market estimate of US $50.5 billion, RM is expected to become a major player in the pharmaceutical industry, with a potential to change the treatment paradigm and lessen disease burden across multiple disease areas, most notably in CVDs and MSDs.Implications
While the public sector appears to be doing its fair share by funding basic research and revamping regulatory regimes to address the vagaries of RM as a rapidly emerging novel technology, the support framework necessary for transforming the field from a promising concept to available therapy requires levels of resource allocation and marketing support that only the private sector can provide. 相似文献10.
Purpose
This review article focuses on preventing vertical transmission of hepatitis B virus (HBV) among pregnant women living in sub-Saharan Africa (SSA), where disease is endemic and the estimated maternal HBV seroprevalence is >8%. Available interventions that have been studied in low- and middle-income countries are compared in terms of efficacy and effectiveness in clinical practice. Global disease-elimination targets, barriers to HBV-prevention efforts, and critical research gaps are discussed.Methods
A PubMed literature search in February 2018 identified relevant studies of interventions to reduce or prevent the transmission of HBV during pregnancy or in the peripartum period. Studies that focused on interventions that are currently available or could be made available in SSA were included. Trials conducted in SSA and other low-income countries were prioritized, although studies of interventions in middle- and high-income countries were included.Findings
Among 127 studies and reports included in the review, 60 included data from SSA. The most cost-effective intervention to reduce HBV infection rates in SSA is timely birth-dose vaccination followed by completion of the 3-dose infant-vaccination series. The identification and treatment of pregnant women with elevated HBV viral load to further reduce the risk for vertical transmission in SSA show promise, but efficacy and tolerability trials in Africa are lacking.Implications
Scale-up of currently available tools is required to reach HBV disease-elimination goals in SSA. Many countries in SSA are in the process of rolling out national birth-dose vaccination campaigns; this roll out provides an opportunity to evaluate and improve processes in order to expand coverage. Early antenatal care, promotion of facility deliveries, and increased awareness of HBV prevention are also key components of prevention success. Future studies in SSA should identity an HBV-prevention package that is effective, well tolerated, and feasible and can be administered in the antenatal clinic and tailored to vertical-transmission risk. 相似文献11.
Background
Nurses are among the many U.S. health professionals engaged in international learning or service experiences and often travel to low-resource countries lacking guidance for ethical practice, respect for host partners, or collaborative work in different health systems.Purpose
The aim of this study is to develop evidence-based principles or guidelines for ethical global health nursing practice.Methods
A three-round Delphi study was conducted. Global health nurse experts participated in Round 1 focus group, followed by nurses with global health expertise ranking global health nursing statements in Rounds 2 and 3.Discussion
Findings led to 10 Ethical Principles for Global Health Nursing Practice and 30 statements for Ethical Guidelines in Global Health Nursing. These Ten principles address beneficence, nonmaleficence, dignity, respect, autonomy, social justice, and professional practice. The 30 guidelines offer more specific actions nurses must consider when working in global settings. 相似文献12.
13.
Purpose
The objective of this review was to summarize the recent literature describing the current burden of disease due to herpesviruses in the antiviral and transplant era; describe mechanisms of action of antiviral agents and the development of resistance; summarize the literature of recent antiviral agents brought to market as well as agents under development; and to present literature on future strategies for herpesvirus therapeutics.Methods
An extensive search of the medical literature related to antiherpesviral therapy was conducted to compose this narrative review. Literature searches were performed via PubMed and ultimately 137 articles were included as most relevant to the scope of this article.Findings
Herpesviruses are a family of DNA viruses that are ubiquitous throughout human populations and share the feature of establishing lifelong infections in a latent phase with the potential of periodic reactivation. With the exception of herpes simplex virus, varicella zoster virus, and Epstein-Barr virus, which have a significant disease burden in individuals with normal immune function, the morbidity and mortality of the remaining viruses are primarily associated with the immunocompromised host. Over the last half-century, several agents have been tested in large randomized, placebo-controlled trials that have resulted in safe and effective antiviral agents for the treatment of many of these infections.Implications
With increasing use of antiherpesviral agents for extended periods, particularly in immunocompromised hosts, the emergence of resistant viruses has necessitated the development of newer agents with novel targets and better side-effect profiles. 相似文献14.
15.
Purpose
This article focuses on 10 case studies of companies/organizations that are part of the current innovation ecosystem of regenerative medicine (RM) in the United Kingdom. It analyzes the actors, linkages, and influences that will determine the future shape of the RM industry sector and its capacity to live up to its initial expectations.Methods
Using the case study approach, purposive sampling was used to get 18 interview respondents from 10 RM companies/organizations in the United Kingdom. We used semistructured interviews for data gathering and thematic analysis for identifying gaps in the RM value chain (ie, the range of activities required for bringing a product from conception to market and end-use) and the influences of the innovation ecosystem on the evolving RM business models.Findings
RM promises to address currently unmet health care needs by restoring the normal form and function of cells, tissues, and organs. The innovations emerging to support the progress of RM to satisfy these important health care markets will disrupt the business models of incumbent industry sectors, particularly pharmaceuticals. Companies involved in this area must develop innovative business models and value chains and negotiate the complex influences of the innovation ecosystem, including regulatory systems and standards, financial support systems, and new market dynamics.Implications
This article highlights the needs for more systemic analyses of the needs of potentially disruptive innovations, in RM and more widely, and for policymakers to give greater attention to these insights in planning regulatory and other supporting initiatives, with the promotion of innovation in mind. 相似文献16.
Purpose
Morphine ARER is a novel oral, abuse-deterrent, extended-release (ER) formulation of morphine sulfate with physical and chemical properties that deter misuse and abuse by nonoral routes of administration. Here we evaluate the relative bioavailability of morphine ARER and extended-release morphine.Methods
This single-dose, 2-treatment, 2-period, 2-sequence, randomized crossover study in healthy adult subjects compared the relative bioavailability of morphine ARER 100 mg to that of ER morphine 100 mg in the fasted condition. At 12 and 1.5 hours before dosing and 12 hours after dosing, all subjects received a 50-mg oral naltrexone tablet to minimize opioid-related side effects. Pharmacokinetic parameters including the AUC0–t, AUC0–∞, and Cmax of morphine and its metabolite morphine-6-glucuronide (M6G) were determined at various times up to 48 hours postdose. The bioequivalence of morphine ARER and ER morphine was determined using an ANOVA of the least-squares mean values of morphine and M6G bioavailability.Findings
Forty-nine subjects completed the study. Both morphine ARER and ER morphine exhibited peak plasma morphine and M6G concentrations of ～30 ng/mL and ～200 ng/mL, respectively, at 3 hours postdose. The 90% CIs of the ln-transformed values of morphine AUC0–t, AUC0–∞, and Cmax were within the 80% to 125% range for bioequivalence. M6G values also indicated bioequivalence of morphine ARER and ER morphine. The most common adverse events were nausea and somnolence.Implications
These data show that, in these subjects, morphine ARER was bioequivalent to ER morphine, a treatment for pain with well-established efficacy and safety profiles. 相似文献17.
Purpose
Fenfluramine is being developed as a low-dose adjunctive treatment for seizures in patients with Dravet syndrome and other epileptic encephalopathies, including Lennox-Gastaut syndrome. Most patients with Dravet syndrome receive multiple antiepileptic drugs, making it challenging for caregivers to track correct administration times. The present Phase I study was conducted to determine the effect of food on the pharmacokinetic properties of fenfluramine.Methods
Healthy nonsmoking subjects aged 18 to 50 years were enrolled in an open-label, crossover, Phase I pharmacokinetic and safety profile study and received 2 single 0.8-mg/kg doses of ZX008 (fenfluramine hydrochloride oral solution), 1 after a 10-hour overnight fast and the other 30 minutes after the start of consumption of a high-fat breakfast, in a randomly assigned order. A washout period of at least 9 days separated the 2 treatment periods. Venous blood samples were taken before each dose and periodically for 72 hours after each dose for determination of concentrations of fenfluramine and its active metabolite norfenfluramine. Plasma pharmacokinetic parameters were estimated for each subject by noncompartmental analysis.Findings
In the 13 subjects completing both treatment periods, food had no effect on the rate or extent of absorption and bioavailability of fenfluramine as assessed by fed vs fasted adjusted geometric mean observed plasma Cmax (59.1 vs 56.7 ng/mL; NS) and AUC0–∞ (1640 vs 1600 ng?·?h/mL; NS). Additionally, there was no impact of food on systemic exposure of norfenfluramine. Seven subjects reported at least 1 treatment-emergent adverse event; all treatment-emergent adverse events were mild in severity.Implications
The bioequivalence and tolerability of single 0.8-mg/kg oral doses of ZX008 in the fed and fasted states support ZX008 administration without regard to meals. 相似文献18.
Robert Wilson Emily Jarvis Mickael Montembault J. Nicole Hamblin Edith M. Hessel Anthony Cahn 《Clinical therapeutics》2018,40(8):1410-1417
Purpose
Novel therapies to treat chronic obstructive pulmonary disease are highly desirable. The safety, tolerability, and pharmacokinetic (PK) parameters of nemiralisib, a phosphoinositide 3-kinase δ inhibitor, administered via the Ellipta dry powder inhaler (GlaxoSmithKline, Research Triangle Park, North Carolina) was evaluated, including an assessment of oral bioavailability.Methods
This single-center, 3-part, placebo-controlled trial in 22 healthy subjects evaluated single (100 and 200 μg) and repeat (200 μg for 10 days) doses of inhaled nemiralisib in parts A (n?=?12) and B (n?=?12) (double-blind) and single doses of inhaled nemiralisib (200 µg) with and without charcoal block in Part C (n?=?6) (open-label, 2-period, crossover). There was a minimum 14-day washout period between dosing days.Findings
21 subjects completed the study, mean age was similar in the three parts (A: 49 years; B: 44 years; C: 55 years). After single doses of nemiralisib, observed plasma Cmax dropped rapidly, followed by a slower elimination phase. Near-dose proportionality was observed: mean (95% CI) plasma Cmax and AUC0–24 values were 174.3 pg/mL (96.9–313.3) and 694.6 pg·h/mL (503.5–958.2) for 100 μg and 398.9 pg/mL (318.3–500.1) and 1699.6 pg·h/mL (1273.3–2268.7) for 200 μg, respectively. Repeat dosing for 10 days showed exposures ～2- to 4-fold higher than on the single dose (peak, trough, and AUC0–24 levels), achieving steady-state by day 6. Mean AUC0–24 was 2193.6 pg·h/mL and 1645.3 pg·h/mL in the absence/presence of charcoal. Two non–drug-related adverse events were observed; neither was serious or resulted in withdrawal.Implications
Inhalation of nemiralisib was well tolerated in these healthy subjects. Plasma pharmacokinetic variables were well defined, and charcoal block data indicate that ～23% of the total systemic exposure after inhalation from Ellipta was attributable to orally absorbed drug. ClinicalTrials.gov identifier: NCT02691325. 相似文献19.
Peter Ong Giancarlo Pirozzolo Anastasios Athanasiadis Udo Sechtem 《Clinical therapeutics》2018,40(9):1584-1590
Purpose
Coronary spasm is frequently found in patients with angina and unobstructed coronaries. The pathophysiology is incompletely understood, although sex differences have been described. Often a positive family history (PFH) is encountered. We assessed the relationship between sex, coronary spasm, and a PFH for cardiovascular disease.Methods
This single-center observational study recruited 415 stable angina patients with unobstructed coronaries (no stenosis >50%) between 2008 and 2011 (mean [SD] age, 62 [10] years; 38% men). Patients were referred for angiography because of signs and symptoms of myocardial ischemia. Intracoronary acetylcholine (ACh) testing was performed in all patients according to a standardized protocol. Risk factor assessment included hypertension, hypercholesterolemia, diabetes, smoking, and a PFH. The latter was defined as a first-degree relative with myocardial infarction or stroke. Statistical analysis involved comparison of categorical and continuous variables. Multivariable analysis aimed at identifying predictors for a pathologic ACh testing, microvascular spasm, and a PFH.Findings
Epicardial spasm was found in 33% of patients and microvascular spasm in 30% of patients. A pathologic ACh test was more frequent in women than in men (72% vs 49%; P < 0.0005). A PFH was found in 55% of patients with significantly more women than men (61% vs 45%; P?=?0.001). Among patients with epicardial spasm, women had a PFH significantly more often than men (66% vs 43%; P?=?0.006). The latter difference was not found when comparing women and men with microvascular spasm.Implications
There is a female preponderance among patients with angina and unobstructed coronaries. ACh testing enables detection of coronary spasm. Epicardial spasm in women is associated with a PFH. 相似文献20.
Jean Ferrières Katherine Gorcyca Şerban R. Iorga David Ansell Dylan L. Steen 《Clinical therapeutics》2018,40(9):1484-1495.e22